Science.gov

Sample records for act regulations decisions

  1. The Equal Access Act: Recent Court Decisions.

    ERIC Educational Resources Information Center

    Bjorklun, Eugene C.

    1989-01-01

    Examines court decisions which led to the passage of the Equal Access Act of 1984. Although the act was designed to clarify the issue over the legality of permitting religious clubs to meet on school property, it may have created more confusion. Concludes that the Supreme Court may have to decide the issue. (SLM)

  2. Language and Legal Speech Acts: Decisions.

    ERIC Educational Resources Information Center

    Kevelson, Roberta

    The first part of this essay argues specifically that legal speech acts are not statements but question/answer constructions. The focus in this section is on the underlying interrogative structure of the legal decision. The second part of the paper touches on significant topics related to the concept of legal speech acts, including the philosophic…

  3. Advance decisions and the Mental Capacity Act.

    PubMed

    Halliday, Samantha

    This article considers the requirements set out in the Mental Capacity Act 2005 for valid advance decisions. The Act recognizes that an adult with capacity may refuse treatment, including life-sustaining treatment, in advance of losing capacity. If that advance decision is valid and applicable, it will bind health-care professionals, taking effect as if the patient had contemporaneously refused the treatment. However, in cases where the advance decision does not relate to treatment for a progressive disease, it will be extremely difficult for the patient to meet the dual specificity requirement - specifying the treatment to be refused and the circumstances in which that refusal should operate. Moreover, while a patient may explicitly revoke an advance decision while she retains the capacity to do so, the continuing validity of an advance decision may be called into question by the patient implicitly revoking her advance refusal or by a change of circumstance. This article concludes that the key to enabling patients to exercise precedent autonomy will be full and frank discussion of the scope and intentions underlying advance decisions between patients and their health-care professionals. PMID:19525915

  4. 76 FR 40367 - Federal Acquisition Regulation; Information Collection; Buy American Act-Construction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... Regulation; Information Collection; Buy American Act--Construction AGENCY: Department of Defense (DOD... previously approved information collection requirement concerning the Buy American Act--Construction..., American Act--Construction (Grimberg Decision), by any of the following methods: ] Regulations.gov :...

  5. 75 FR 63703 - Privacy Act of 1974; Privacy Act Regulation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-18

    ...The Board of Governors of the Federal Reserve System (Board) is issuing a final rule to amend its regulation implementing the Privacy Act of 1974 (Privacy Act). The primary changes concern the waiver of copying fees charged to current and former Board employees, and applicants for Board employment, for access to their records under the Privacy Act; the amendment of special procedures for the......

  6. 75 FR 37287 - Privacy Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-29

    ... April 19, 2010 (75 FR 20298) for a public comment period to end on June 18, 2010. This rule amends the... criminal law enforcement duties. (2) From subsection (c)(4) and (d) because notification would alert a... regulations implementing the Privacy Act of 1974 (Privacy Act), Public Law 93-579, 5 U.S.C. 552a. This...

  7. 77 FR 15368 - Clean Water Act; Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-15

    ... AGENCY Clean Water Act; Availability of List Decisions AGENCY: Environmental Protection Agency (EPA... availability of the Environmental Protection Agency's (EPA) proposed decision identifying water quality limited segments and associated pollutants in Oregon to be listed pursuant to section 303(d)(2) of the Clean...

  8. 78 FR 20912 - Clean Water Act: Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-08

    ... AGENCY Clean Water Act: Availability of List Decisions AGENCY: Environmental Protection Agency (EPA). ACTION: Notice and initial request for public input. SUMMARY: The Clean Water Act requires that States... existing technology-based pollution controls are not stringent enough to attain or maintain State...

  9. 78 FR 45925 - Clean Water Act: Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-30

    ... AGENCY Clean Water Act: Availability of List Decisions AGENCY: Environmental Protection Agency (EPA... waterbodies were added by EPA because the applicable numeric water quality standards marine criterion for... 303(d) List can be obtained at EPA Region 6's Web site at...

  10. 77 FR 54909 - Clean Water Act: Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    ... AGENCY Clean Water Act: Availability of List Decisions AGENCY: Environmental Protection Agency (EPA... certain water quality limited waters and the associated pollutant to be listed pursuant to the Clean Water... technology-based pollution controls are not stringent enough to attain or maintain State water...

  11. 78 FR 27233 - Clean Water Act: Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-09

    ... decree, or settlement agreement required EPA to take action on a list in 2000 (65 FR 17170). Consistent... AGENCY Clean Water Act: Availability of List Decisions AGENCY: Environmental Protection Agency (EPA... identifying water quality limited segments and associated pollutants in Louisiana to be listed pursuant...

  12. To Act or Not to Act: Endocannabinoid/Dopamine Interactions in Decision-Making

    PubMed Central

    Hernandez, Giovanni; Cheer, Joseph F.

    2015-01-01

    Decision-making is an ethologically adaptive construct that is impaired in multiple psychiatric disorders. Activity within the mesocorticolimbic dopamine system has been traditionally associated with decision-making. The endocannabinoid system through its actions on inhibitory and excitatory synapses modulates dopamine activity and decision-making. The aim of this brief review is to present a synopsis of available data obtained when the endocannabinoid system is manipulated and dopamine activity recorded. To this end, we review research using different behavioral paradigms to provide further insight into how this ubiquitous signaling system biases dopamine-related behaviors to regulate decision-making. PMID:26733830

  13. 8 CFR 103.9 - Availability of decisions and interpretive material under the Freedom of Information Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Availability of decisions and interpretive material under the Freedom of Information Act. 103.9 Section 103.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS POWERS AND DUTIES; AVAILABILITY OF RECORDS § 103.9 Availability of decisions and interpretive...

  14. The French Space Operations Act: Technical Regulations

    NASA Astrophysics Data System (ADS)

    Lazare, B.

    2013-12-01

    The French Space Operations Act (FSOA) [1] stipulates that one of the National Technical Regulations' prime objectives is to protect people, property, public health and the environment. Compliance with these Technical Regulations has been mandatory since 10 December, 2010 for space operations by French space operators and for space operations conducted on French territory. The space safety requirements and regulations governing procedures are based on national and international best practices and experience. A critical design review of the space system and procedures shall be carried out by applicant space operators, in order to verify compliance with the Technical Regulations. An independent technical assessment of the operation is delegated to CNES. The principles applied when drafting the Technical Regulations are as follows: requirements must, as far as possible, establish the rules according to the objective to be obtained, rather than how it is to be achieved; requirements must give preference to international standards recognised as being state of the art; requirements must take previous experience into account. The Technical Regulations are divided into three sections covering requirements common to the launch, control and return of a space object. A special section will cover specific rules to be applied at the Guiana Space Centre. The main topics addressed by the Technical Regulations are: operator safety management system; study of risks to people, property, public health and the Earth's environment; impact study on the outer space environment: space debris generated by the operation; planetary protection. The first version of the Technical Regulations [2], issued in March 2011, is dedicated to unmanned space systems.

  15. 48 CFR 1480.102 - Buy Indian Act acquisition regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Buy Indian Act acquisition... INDIAN AFFAIRS SUPPLEMENT ACQUISITIONS UNDER THE BUY INDIAN ACT General 1480.102 Buy Indian Act... the Buy Indian Act. (b) This part is under the direct oversight and control of the Chief...

  16. 75 FR 48955 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice of arbitration panel decision under the Randolph- Sheppard Act. SUMMARY: The Department of Education (Department) gives notice that on July 17, 2009, an arbitration panel rendered a decision in the matter of...

  17. 76 FR 6604 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-07

    ... Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice of arbitration panel decision under the Randolph- Sheppard Act. SUMMARY: The Department of Education (Department) gives notice that on September 28, 2010, an arbitration panel rendered a decision in the matter of...

  18. 76 FR 43676 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice of arbitration panel decision under the Randolph- Sheppard Act. SUMMARY: The Department of Education (Department) gives notice that on March 18, 2011, an arbitration panel rendered a decision in the matter of Sam...

  19. NASA Principal Center for Review of Clean Air Act Regulations

    NASA Technical Reports Server (NTRS)

    Clark-Ingram, Marceia; Munafo, Paul M. (Technical Monitor)

    2002-01-01

    The Clean Air Act (CAA) regulations have greatly impacted materials and processes utilized in the manufacture of aerospace hardware. Code JE/ NASA's Environmental Management Division at NASA Headquarters recognized the need for a formal, Agency-wide review process of CAA regulations. Marshall Space Flight Center (MSFC) was selected as the 'Principal Center for Review of Clean Air Act Regulations'. This presentation describes the centralized support provided by MSFC for the management and leadership of NASA's CAA regulation review process.

  20. 75 FR 35686 - Community Reinvestment Act Regulation Hearings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... TREASURY Office of Thrift Supervision 12 CFR Part 563e Community Reinvestment Act Regulation Hearings... financial institution's performance under the Community Reinvestment Act (CRA). The purpose of the hearings... better serve the goals of the Community Reinvestment Act. The hearings will be held in:...

  1. 48 CFR 1480.102 - Buy Indian Act acquisition regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Buy Indian Act acquisition... INDIAN AFFAIRS SUPPLEMENT ACQUISITIONS UNDER THE BUY INDIAN ACT Subpart 1480.1 General 1480.102 Buy... in implementing the Buy Indian Act. (b) This part is under the direct oversight and control of...

  2. 13 CFR 108.30 - Amendments to Act and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Amendments to Act and regulations. 108.30 Section 108.30 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Introduction to Part 108 § 108.30 Amendments to Act and regulations. A...

  3. 13 CFR 107.30 - Amendments to Act and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Amendments to Act and regulations. 107.30 Section 107.30 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES Introduction to Part 107 § 107.30 Amendments to Act and regulations. A Licensee shall...

  4. 75 FR 20298 - Privacy Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-19

    ...,'' pursuant to the Privacy Act, as amended (74 FR 60302, Nov. 20, 2009). The Board received no comments on... amendment procedures for this record system. Ivan J. Flores, Paralegal Specialist, Recovery...

  5. 77 FR 75521 - Community Reinvestment Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-21

    ... 1, 2005. 70 FR 44256 (Aug. 2, 2005). As explained in the SUPPLEMENTARY INFORMATION section of these... Home Mortgage Disclosure Act (HMDA). 70 FR 12148 (Mar. 11, 2005). See 12 U.S.C. 2808; 12 CFR 203.2(e)(1... the other federal banking agencies in its CRA rule set forth at 12 CFR part 563e. 72 FR 13429 (Mar....

  6. 75 FR 78932 - Federal Seed Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-17

    ...--Zea mays L. subsp. mays'', ``Crambe--Crambe abyssinica R.E. Fr.'', ``Crotalaria, slenderleaf... Federalism implications. Background The FSA, Title II (7 U.S.C. 1571-1575) regulates agricultural...

  7. 78 FR 32595 - Revision of Freedom of Information Act Regulation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-31

    ...This proposed rule would amend HUD's regulations implementing the Freedom of Information Act (FOIA). HUD is proposing these amendments to update and streamline HUD's current FOIA regulation. This proposed rule would update HUD's regulations to reflect statutory changes to FOIA, current HUD organizational structure, and current HUD policies and practices with respect to FOIA. Finally, the rule......

  8. 78 FR 79283 - Community Reinvestment Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... CRA purposes by the OCC, Board, and FDIC on August 2, 2005, effective September 1, 2005. 70 FR 44256... Act (HMDA). 70 FR 12148 (Mar. 11, 2005). See 12 U.S.C. 2808; 12 CFR 203.2(e)(1). On March 22, 2007... other federal banking agencies in its CRA rule previously set forth at 12 CFR 563e. 72 FR 13429 (Mar....

  9. 76 FR 79529 - Community Reinvestment Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-22

    ... adopted for CRA purposes by the OCC, Board, and FDIC on August 2, 2005, effective September 1, 2005. 70 FR... Disclosure Act (HMDA). 70 FR 12148 (Mar. 22, 2007). See 12 U.S.C. 2808; 12 CFR 203.2(e)(1). On March 22, 2007... federal banking agencies in its CRA rule set forth at 12 CFR 563e. 72 FR 13429. Pursuant to the...

  10. 76 FR 21871 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice of arbitration panel decision under the Randolph- Sheppard Act. SUMMARY: The Department of Education...

  11. 76 FR 21872 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice of arbitration panel decision under the Randolph- Sheppard Act. SUMMARY: The Department of Education...

  12. 76 FR 2890 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-18

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice of arbitration panel decision under the Randolph- Sheppard Act. SUMMARY: The Department of Education...

  13. 75 FR 52735 - Clean Water Act Section 303(d): Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ... AGENCY Clean Water Act Section 303(d): Availability of List Decisions AGENCY: Environmental Protection... EPA's decision identifying 12 water quality limited waterbodies and associated pollutants in South Dakota to be listed pursuant to the Clean Water Act Section 303(d)(2), and requests public...

  14. 78 FR 46555 - Privacy Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ... File ] System--Interior, FWS-20 (48 FR 54719, December 6, 1983); Bureau of Land Management Criminal... proposing to amend its regulations to exempt certain records in the Incident Management, Analysis and... Management, Analysis and Reporting System (IMARS) system of records. IMARS is an incident management...

  15. 75 FR 36270 - Appraisal Subcommittee; Appraiser Regulation; Privacy Act Implementation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-25

    ... From the Federal Register Online via the Government Publishing Office FEDERAL FINANCIAL INSTITUTIONS EXAMINATION COUNCIL 12 CFR Part 1102 Appraisal Subcommittee; Appraiser Regulation; Privacy Act Implementation AGENCY: Appraisal Subcommittee of the Federal Financial Institutions Examination...

  16. 77 FR 56592 - Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ... Office of the Secretary 43 CFR Part 2 RIN 1093-AA15 Freedom of Information Act Regulations AGENCY: Office... Department follows in processing records under the Freedom of Information Act (``FOIA''). The revisions clarify and update procedures for requesting information from the Department and procedures that...

  17. 75 FR 68783 - Clean Water Act Section 303(d): Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ... AGENCY Clean Water Act Section 303(d): Availability of List Decisions AGENCY: Environmental Protection... pursuant to Clean Water Act section 303(d)(2), and requests public comment. Section 303(d)(2) requires that...) of the Clean Water Act (CWA) requires that each State identify those waters for which...

  18. 77 FR 27770 - Clean Water Act Section 303(d): Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... AGENCY Clean Water Act Section 303(d): Availability of List Decisions AGENCY: Environmental Protection... pursuant to the Clean Water Act Section 303(d)(2), and requests public comment. Section 303(d)(2) requires...-6237 or jensen.kris@epa.gov . SUPPLEMENTARY INFORMATION: Section 303(d) of the Clean Water Act...

  19. 76 FR 20664 - Clean Water Act Section 303(d): Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... AGENCY Clean Water Act Section 303(d): Availability of List Decisions AGENCY: Environmental Protection... pursuant to Clean Water Act Section 303(d), and request for public comment. Section 303(d) requires that...: Diane Smith at (214) 665-2145. ] SUPPLEMENTARY INFORMATION: Section 303(d) of the Clean Water Act...

  20. 78 FR 6216 - Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... corrections to the final rule published on December 31, 2012 (77 FR 76898). The regulation revises the... publication on December 31, 2012, of the final rule that was the subject of FR Doc. 2012-31117, is corrected... Office of the Secretary 43 CFR Part 2 RIN 1093-AA15 Freedom of Information Act Regulations AGENCY:...

  1. 77 FR 75362 - Government in the Sunshine Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-20

    ... From the Federal Register Online via the Government Publishing Office EQUAL EMPLOYMENT OPPORTUNITY COMMISSION 29 CFR Part 1612 Government in the Sunshine Act Regulations CFR Correction 0 In Title 29 of the Code of Federal Regulations, Parts 900 to 1899, revised as of July 1, 2012, on page 266, in Sec....

  2. 7 CFR 4290.30 - Amendments to Act and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4290.30 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Introduction to Part 4290 § 4290.30 Amendments to Act and regulations. A RBIC is subject to...

  3. 76 FR 15236 - Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-21

    ... Information Fee Schedule and Guidelines published by the Office of Management and Budget at 52 FR 10012 (Mar... Information Act (FOIA). The regulations are being revised to update and streamline the language of several... revisions to the Department's regulations under the FOIA to update and streamline the language of...

  4. 75 FR 22320 - Regulations Implementing the Freedom of Information Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-28

    ... HEALTH REVIEW COMMISSION 29 CFR Part 2201 Regulations Implementing the Freedom of Information Act AGENCY: Occupational Safety and Health Review Commission. ACTION: Notice of proposed rulemaking. SUMMARY: The Occupational Safety and Health Review Commission (OSHRC) is proposing to revise its regulations...

  5. 76 FR 62061 - Clean Water Act Section 303(d): Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-06

    ... Register at 76 FR 20664-20665 providing the public the opportunity to review its decision to partially... AGENCY Clean Water Act Section 303(d): Availability of List Decisions AGENCY: Environmental Protection... added by EPA because the applicable numeric water quality standards marine criterion for...

  6. 77 FR 2279 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice of decision. SUMMARY: The Department of Education (Department) gives notice that on September 18, 2010,...

  7. 77 FR 4288 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice of... arbitration panel rendered a decision in the matter of the Oregon Commission for the Blind v. United States... the Blind. FOR FURTHER INFORMATION CONTACT: You can obtain a copy of the full text of the...

  8. Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF

    PubMed Central

    Maeda, Takahiro; Merghoub, Taha; Hobbs, Robin M.; Dong, Lin; Maeda, Manami; Zakrzewski, Johannes; van den Brink, Marcel R. M.; Zelent, Arthur; Shigematsu, Hirokazu; Akashi, Koichi; Teruya-Feldstein, Julie; Cattoretti, Giorgio; Pandolfi, Pier Paolo

    2010-01-01

    Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that the proto-oncogene LRF plays an essential role in the B versus T lymphoid cell fate decision. We demonstrate that LRF is key for instructing early lymphoid progenitors to develop into B lineage cells by repressing T cell-instructive signals produced by the cell fate signal protein, Notch. We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of B versus T lineage fate decision. PMID:17495164

  9. Decision making and effort in the self-regulation of hypertension: testing two competing theories.

    PubMed

    Taylor, Stephanie D; Bagozzi, Richard P; Gaither, Caroline A

    2005-11-01

    We compare the ability of two social psychological models to explain self-regulation decisions to control hypertension by 208 patients at a hospital clinic: the theory of planned behaviour (TPB) and the model of goal-directed behaviour (MGB). The sample was drawn from patients at a large research hospital in North America. The findings show that the MGB not only explains significantly more variance in decision making than the TPB, but it provides an account for how reasons for acting become integrated and transformed into intentions to act, which the TPB does not address. The MGB does this in part by introducing the variable, desire, as an essential mediator between reasons for acting and intentions. The MGB also incorporates the effects of anticipated emotions on decision making, which are forms of forward-looking counterfactual thinking with respect to goals. In addition, the present study reconceptualized instrumental behaviour to encompass how hard one tries to act in the senses of (1) devoting time to planning with respect to reducing/maintaining blood pressure, (2) expending mental/physical energy to reduce/maintain blood pressure, (3) maintaining will power to reduce/maintain blood pressure, and (4) sustaining self-discipline (e.g. in overcoming obstacles) to reduce/maintain blood pressure. Key differences, as well as commonalities, in decision making are pointed-out between men and women and between people whose goal is to reduce versus maintain blood pressure. PMID:16238862

  10. 77 FR 20020 - Clean Water Act Section 303(d): Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-03

    ... AGENCY Clean Water Act Section 303(d): Availability of List Decisions AGENCY: Environmental Protection.... SUPPLEMENTARY INFORMATION: Section 303(d) of the Clean Water Act (CWA) requires that each state identify those... numeric water quality standards marine criterion for dissolved oxygen was not attained in these...

  11. 75 FR 71431 - Clean Water Act Section 303(d): Availability of List Decisions Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-23

    ... AGENCY Clean Water Act Section 303(d): Availability of List Decisions Correction AGENCY: Environmental... Register notice that published on November 9, 2010 at 75 FR 68783 announcing the availability of EPA... pursuant to Clean Water Act section 303(d)(2), and requests public comment. This announcement corrects...

  12. 76 FR 74057 - Clean Water Act Section 303(d): Availability of List Decisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-30

    ... AGENCY Clean Water Act Section 303(d): Availability of List Decisions AGENCY: Environmental Protection... action identifying water quality limited segments and associated pollutants in Louisiana to be listed pursuant to Clean Water Act Section 303(d), and request for public comment. Section 303(d) requires...

  13. Regulation of dietary choice by the decision-making circuitry

    PubMed Central

    Rangel, Antonio

    2014-01-01

    To advance our understanding of how the brain makes food decisions, it is essential to combine knowledge from two fields that have not yet been well integrated: the neuro-computational basis of decision-making and the homeostatic regulators of feeding. This Review integrates these two literatures from a neuro-computational perspective, with an emphasis in describing the variables computed by different neural systems and how they affect dietary choice. We highlight what is unique about feeding decisions, the mechanisms through which metabolic and endocrine factors affect the decision-making circuitry, why making healthy food choices is difficult for many people, and key processes at work in the obesity epidemic. PMID:24270272

  14. 75 FR 41370 - Regulations Implementing the Freedom of Information Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-16

    ... amended. 75 FR 22320, Apr. 28, 2010. Interested persons were afforded an opportunity to participate in the... HEALTH REVIEW COMMISSION 29 CFR Part 2201 Regulations Implementing the Freedom of Information Act AGENCY: Occupational Safety and Health Review Commission. ACTION: Final rule. SUMMARY: The Occupational Safety...

  15. 76 FR 59071 - Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... follows: Authority: 50 U.S.C. 401-442; 50 U.S.C. 403a-403v; 5 U.S.C. 552; Executive Order 13392, 70 FR... From the Federal Register Online via the Government Publishing Office CENTRAL INTELLIGENCE AGENCY 32 CFR Part 1900 Freedom of Information Act Regulations AGENCY: Central Intelligence Agency....

  16. 78 FR 50351 - Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ... compliance with, among others, the Comprehensive Plan, principals of good planning and urban design, and...; ] NATIONAL CAPITAL PLANNING COMMISSION 1 CFR Part 456 Freedom of Information Act Regulations AGENCY: National Capital Planning Commission. ACTION: Notice of Proposed Rulemaking. SUMMARY: The National Capital...

  17. 76 FR 45403 - Bank Secrecy Act Regulations-Definitions and Other Regulations Relating to Prepaid Access

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-29

    ... regulations. See 75 FR 65806 (October 26, 2010) (Transfer and Reorganization of Bank Secrecy Act Regulations... Relating to Money Services Businesses, 74 FR 22129 (May 12, 2009), was issued before the Chapter X Final...), (c). \\16\\ 75 FR 36589. B. Prior Regulation of Stored Value In 1999, when FinCEN issued its final...

  18. NASA's Principal Center for Review of Clean Air Act Regulations

    NASA Technical Reports Server (NTRS)

    Clark-Ingram, Marceia

    2003-01-01

    Marshall Space Flight Center (MSFC) was selected as the Principal Center for review of Clean Air Act (CAA) regulations. The CAA Principal Center is tasked to: 1) Provide centralized support to NASA/HDQ Code JE for the management and leadership of NASA's CAA regulation review process; 2) Identify potential impact from proposed CAA regulations to NASA program hardware and supporting facilities. The Shuttle Environmental Assurance Initiative, one of the responsibilities of the NASA CAA Working Group (WG), is described in part of this viewgraph presentation.

  19. Shared Decision Aids: Increasing Patient Acceptance of Long-Acting Reversible Contraception

    PubMed Central

    George, Tracy P.; DeCristofaro, Claire; Dumas, Bonnie P.; Murphy, Pamela F.

    2015-01-01

    Unintended pregnancies are an important public health issue. Long-acting reversible contraceptive methods (LARCs) are reliable, safe, highly effective methods for most women; however they are underutilized in the United States. Shared decision aids were added to usual care in five public health family planning clinics in the Southeastern United States, staffed by advance practice nurses and registered nurses. All five sites showed an increase in the use of LARCs during the time period that shared decision aids were used (results statistically significant to p < 0.001). It is important for women to make informed choices about contraception, and shared decision aids can be utilized to support this decision making. This resource has been adopted for statewide use in all public health clinics, and implications for practice suggest that the use of shared decision aids is an effective method to support informed patient decision making and acceptance of LARC methods of contraception. PMID:27417757

  20. Medical loss ratio regulation under the Affordable Care Act.

    PubMed

    Harrington, Scott E

    2013-01-01

    The minimum medical loss ratio (MLR) regulations in the Affordable Care Act guarantee that a specific percentage of health insurance premiums is spent on medical care and specified activities to improve health care quality. This paper analyzes the regulations' potential unintended consequences and incentive effects, including: higher medical costs and premiums for some insurers; less innovation to align consumer, provider, and health plan incentives, less consumer choice and increased market concentration; and the risk that insurers will pay rebates if claim costs are lower than projected when premiums are established, despite the regulations' permitted "credibility adjustments." The paper discusses modifications and alternatives to the MLR regulations to help achieve their stated goals with less potential for adverse effects. PMID:23720876

  1. Balancing act creating the right regulation for coal combustion waste

    SciTech Connect

    Manuel, J.

    2009-11-15

    The December 2008 collapse of a coal ash pond in Tennessee threw safe management of coal combustion waste (CCW) into the spotlight. Millions of tons of CCW are produced in the United States each year, and a large percentage of that is recycled. The US Environmental Protection Agency is pursuing a host of initiatives that could directly or indirectly affect the disposition of CCW. States, too, are taking a look at how they regulate CCW. Among the options is the possibility of regulating CCW under the Resource Conservation and Recovery Act, a move that could have far-reaching implications for both the recycling and the disposal of this waste.

  2. 77 FR 74347 - Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-14

    ... Information Act (FOIA) (U.S.C. 552) in the Federal Register. See 77 FR 42673, July 20, 2012. CIGIE provided..., Regulatory Planning and Review, 58 FR 51735. This regulation has not been reviewed by the Office of.... Authority: Pub. L. 110-409, 122 Stat. 4302; 5 U.S.C. App; E.O. 12600, 52 FR 23781, 3 CFR, 1987 Comp., p....

  3. 76 FR 43585 - Bank Secrecy Act Regulations; Definitions and Other Regulations Relating to Money Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ...The Financial Crimes Enforcement Network (``FinCEN''), a bureau of the Department of the Treasury (``Treasury''), is revising the regulations implementing the Bank Secrecy Act (``BSA'') regarding money services businesses (``MSBs'') to clarify which entities are covered by the definitions. The changes more clearly delineate the scope of entities regulated as MSBs, so that determining which......

  4. 77 FR 13311 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-06

    ... Blind, Case no. R-S/08-8. FOR FURTHER INFORMATION CONTACT: You can obtain a copy of the full text of the... fair hearing. A hearing was held and the administrative law judge (ALJ) recommended that Complainant's... Arbitration Panel Decision Under the Randolph-Sheppard Act AGENCY: Department of Education. ACTION: Notice...

  5. Mechanics Regulates Fate Decisions of Human Embryonic Stem Cells

    PubMed Central

    Sun, Yubing; Villa-Diaz, Luis G.; Lam, Raymond H. W.; Chen, Weiqiang; Krebsbach, Paul H.; Fu, Jianping

    2012-01-01

    Research on human embryonic stem cells (hESCs) has attracted much attention given their great potential for tissue regenerative therapy and fundamental developmental biology studies. Yet, there is still limited understanding of how mechanical signals in the local cellular microenvironment of hESCs regulate their fate decisions. Here, we applied a microfabricated micromechanical platform to investigate the mechanoresponsive behaviors of hESCs. We demonstrated that hESCs are mechanosensitive, and they could increase their cytoskeleton contractility with matrix rigidity. Furthermore, rigid substrates supported maintenance of pluripotency of hESCs. Matrix mechanics-mediated cytoskeleton contractility might be functionally correlated with E-cadherin expressions in cell-cell contacts and thus involved in fate decisions of hESCs. Our results highlighted the important functional link between matrix rigidity, cellular mechanics, and pluripotency of hESCs and provided a novel approach to characterize and understand mechanotransduction and its involvement in hESC function. PMID:22615930

  6. Evaluation of the ACT intervention to improve nurses' cardiac triage decisions.

    PubMed

    Arslanian-Engoren, Cynthia; Hagerty, Bonnie; Eagle, Kim A

    2010-10-01

    Emergency department (ED) nurses are in a key position to initiate life-saving recommendations for myocardial infarction, which include a physician-read electrocardiogram (ECG) within 10 min of ED arrival. Using a quasi-experimental, one-group pretest-posttest design, the authors evaluated the preliminary effectiveness of the Aid to Cardiac Triage (ACT) intervention to improve ED nurses' cardiac triage decisions. Charts of all women who received an ED ECG 3 months before ( n = 171) and after (n = 184) the intervention and who were at least 18 years of age were reviewed. A 1-hr educational session was conducted to improve nurses' (n = 23) cardiac triage decisions. Postintervention, the proportion of women receiving an ECG within 10 min of ED arrival improved, as did the odds of women receiving a timely ECG. Preliminary evaluation of the ACT intervention indicates its effectiveness at improving ED nurses' cardiac triage decisions and obtaining a 10-min physician-read ECG. PMID:20634399

  7. 77 FR 55271 - Truth in Lending Act (Regulation Z); Loan Originator Compensation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-07

    ...The Bureau of Consumer Financial Protection is publishing for public comment a proposed rule amending Regulation Z (Truth in Lending) to implement amendments to the Truth in Lending Act (TILA) made by the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act). The proposal would implement statutory changes made by the Dodd- Frank Act to Regulation Z's current loan......

  8. Making decisions about decision-making: conscience, regulation, and the law.

    PubMed

    Miola, José

    2015-01-01

    The exercise of conscience can have far reaching effects. Poor behaviour can be fatal, as it has occurred in various medical scandals over the years. This article takes a wide definition of conscience as its starting point, and argues that the decision-making processes open to society--legal regulation and professional regulation--can serve to limit the options available to an individual and thus her ability to exercise her conscience. The article charts the law's changing attitude to legal intervention, which now seeks to limit the use of conscience by individuals, and addresses concerns that this may serve to 'de-moralise' medicine. It also examines the reasons for this legal change of approach. PMID:25910908

  9. 7 CFR 800.7 - Information about the Service, Act, and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Information about the Service, Act, and regulations... AGRICULTURE GENERAL REGULATIONS Administration § 800.7 Information about the Service, Act, and regulations. Information about the Grain Inspection, Packers and Stockyards Administration, Service, Act,...

  10. Regulations Under the Americans With Disabilities Act; Genetic Information Nondiscrimination Act. Final rule.

    PubMed

    2016-05-17

    The Equal Employment Opportunity Commission (EEOC or Commission) is issuing its final rule to amend the regulations and interpretive guidance implementing Title I of the Americans with Disabilities Act (ADA) to provide guidance on the extent to which employers may use incentives to encourage employees to participate in wellness programs that ask them to respond to disability-related inquiries and/or undergo medical examinations. This rule applies to all wellness programs that include disability-related inquiries and/or medical examinations whether they are offered only to employees enrolled in an employer-sponsored group health plan, offered to all employees regardless of whether they are enrolled in such a plan, or offered as a benefit of employment by employers that do not sponsor a group health plan or group health insurance. Published elsewhere in this issue of the Federal Register, the EEOC also issued a final rule to amend the regulations implementing Title II of the Genetic Information Nondiscrimination Act (GINA) that addresses the extent to which employers may offer incentives for an employee's spouse to participate in a wellness program. PMID:27192736

  11. 75 FR 1408 - Notice of Availability of the Record of Decision for the Lincoln County Land Act Groundwater...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ...The Bureau of Land Management (BLM) announces the availability of the Record of Decision (ROD) for the Lincoln County Land Act Groundwater Development and Utility Right-of-Way (ROW) Project (the project). The BLM Ely District Manager signed the ROD on January 8, 2010, which constitutes the final decision of the BLM and makes the decision effective...

  12. Adaptive Equilibrium Regulation: A Balancing Act in Two Timescales

    PubMed Central

    Boker, Steven M.

    2015-01-01

    An equilibrium involves a balancing of forces. Just as one maintains upright posture in standing or walking, many self-regulatory and interpersonal behaviors can be framed as a balancing act between an ever changing environment and within-person processes. The emerging balance between person and environment, the equilibria, are dynamic and adaptive in response to development and learning. A distinction is made between equilibrium achieved solely due to a short timescale balancing of forces and a longer timescale preferred equilibrium which we define as a state towards which the system slowly adapts. Together, these are developed into a framework that this article calls Adaptive Equilibrium Regulation (ÆR), which separates a regulatory process into two timescales: a faster regulation that automatically balances forces and a slower timescale adaptation process that reconfigures the fast regulation so as to move the system towards its preferred equilibrium when an environmental force persists over the longer timescale. This way of thinking leads to novel models for the interplay between multiple timescales of behavior, learning, and development. PMID:27066197

  13. Polypurine/polypyrimidine sequences as cis-acting transcriptional regulators.

    PubMed

    Brahmachari, S K; Sarkar, P S; Raghavan, S; Narayan, M; Maiti, A K

    1997-04-29

    Genome sequence information has generated increasing evidence for the claim that repetitive DNA sequences present within and around genes could play a important role in the regulation of gene expression. Polypurine/polypyrimidine sequences [poly(Pu/Py)] have been observed in the vicinity of promoters and within the transcribed regions of many genes. To understand whether such sequences influence the level of gene expression, we constructed several prokaryotic and eukaryotic expression vectors incorporating poly(Pu/Py) repeats both within and upstream of a reporter gene, lacZ (encoding beta-galactosidase), and studied its expression in vivo. We find that, in contrast to the situation in Escherichia coli, the presence of poly(Pu/Py) sequences within the gene does not significantly inhibit gene expression in mammalian cells. On the other hand, the presence of such sequences upstream of lacZ leads to a several-fold reduction of gene expression in mammalian cells. Similar down-regulation was observed when a structural cassette containing poly(Pu/Py) sequences upstream of lacZ was integrated into yeast chromosome V. Sequence analysis of the nine totally sequenced yeast chromosomes shows that a large number of such sequences occur upstream of ORFs. On the basis of our experimental results and DNA sequence analysis, we propose that these sequences can function as cis-acting transcriptional regulators. PMID:9185844

  14. 77 FR 43081 - Federal Acquisition Regulation; Information Collection; Buy American Act-Free Trade Agreements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

    ... Regulation; Information Collection; Buy American Act--Free Trade Agreements--Israeli Trade Act Certificate... previously approved information collection requirement concerning the Buy American Act--Free Trade Agreements..., Buy American Act--Free Trade Agreements--Israeli Trade Act Certificate, by any of the...

  15. Revisiting advance decision making under the Mental Capacity Act 2005: a tale of mixed messages.

    PubMed

    Heywood, Rob

    2015-01-01

    Whilst most of the existing literature relating to advance decisions has focused on philosophical questions, this article reflects on the significant legal developments that have occurred since the introduction of the Mental Capacity Act 2005. The article provides a critique of the controversial issues which have emerged within contemporary case law. The focus of the discussion centres on capacity, the interpretation of the safeguards, and the bias towards preservation of life. PMID:25016383

  16. The NEPA mandate and federal regulation of the natural gas industry. [NEPA (National Environmental Policy Act)

    SciTech Connect

    Hoecker, J.J.

    1992-01-01

    Utility regulators increasingly take responsibility for the [open quotes]extemalities[close quotes] associated with their decisions, meaning the economic and social costs related to rate decisions or other kinds of authorizations. Yet, when Congress adopted the National Environmental Policy Act of 1969 (NEPA), it intervened to ensure protection of the natural environment, not from abuses by the citizenry but from the activities of the federal government itself. Comprised of action forcing procedures, NEPA was designed to infuse the decisional processes of federal agencies with a broad awareness of the environmental consequences of their actions. NEPA encourages decisionmakers to counterbalance the organic statutory and political missions of their departments or agencies with a sensitivity to the ecological consequences of their directives and authorizations. This paper examines how the requirements of NEPA have fared in the environment of classical public utility regulation at the Federal Energy Regulatory Commission. Commission proceedings did not evidence any widely held opinion that economic regulation of the gas industry is hostile to the NEPA process.

  17. STENOFOLIA acts as a repressor in regulating leaf blade outgrowth

    PubMed Central

    Lin, Hao; Niu, Lifang; Tadege, Million

    2013-01-01

    We recently reported that the Medicago WOX gene, STENOFOLIA (STF), acts as a transcriptional repressor in regulating leaf blade outgrowth. By using the Nicotiana sylvestris bladeless lam1 mutant as a genetic tool, we showed that the WUS-box, which is conserved among WUS clade WOX genes, is partly responsible for the repressive activity of STF. All members of the modern/WUS clade genes (WUS, WOX1-WOX7) in Arabidopsis that contain intact WUS-box can substitute for STF/LAM1 function while the intermediate and ancient clade members including WOX9,WOX11 and WOX13 cannot, due to lack of the intact WUS-box. Taken together, our results reveal a conserved repression mechanism playing a central role in cell proliferation conferred to the evolutionarily dynamic WOX gene family with acquisition of a repressor domain. PMID:23603965

  18. Prostaglandin E2 Regulates Liver versus Pancreas Cell Fate Decisions and Endodermal Outgrowth

    PubMed Central

    Nissim, Sahar; Sherwood, Richard I.; Wucherpfennig, Julia; Saunders, Diane; Harris, James M.; Esain, Virginie; Carroll, Kelli J.; Frechette, Gregory M.; Kim, Andrew J.; Hwang, Katie L.; Cutting, Claire C.; Elledge, Susanna; North, Trista E.; Goessling, Wolfram

    2014-01-01

    SUMMARY The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here, we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver-versus-pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell fate decisions and outgrowth of the embryonic endodermal anlagen. PMID:24530296

  19. 77 FR 57199 - 2012 Real Estate Settlement Procedures Act (Regulation X) Mortgage Servicing Proposal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-17

    ...The Bureau of Consumer Financial Protection (the Bureau) is proposing to amend Regulation X, which implements the Real Estate Settlement Procedures Act of 1974 (RESPA) and the official interpretation of the regulation. The proposed amendments implement the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act) provisions regarding mortgage loan servicing. Specifically, this......

  20. 78 FR 11279 - Loan Originator Compensation Requirements Under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ...The Bureau of Consumer Financial Protection (Bureau) is amending Regulation Z to implement amendments to the Truth in Lending Act (TILA) made by the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act). The final rule implements requirements and restrictions imposed by the Dodd-Frank Act concerning loan originator compensation; qualifications of, and registration or......

  1. 7 CFR 868.10 - Information about the Service, Act, and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Information about the Service, Act, and regulations. 868.10 Section 868.10 Agriculture Regulations of the Department of Agriculture (Continued) GRAIN... § 868.10 Information about the Service, Act, and regulations. Information about the Service,...

  2. 76 FR 24027 - Federal Acquisition Regulation; Information Collection; Buy American Act Certificate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-29

    ... Regulation; Information Collection; Buy American Act Certificate AGENCY: Department of Defense (DOD), General... previously approved information collection requirement concerning the Buy American Act certificate. Public... Comment'' screen. Please include your name, company name (if any), and ``Information Collection...

  3. Homeostatic Regulation of Memory Systems and Adaptive Decisions

    PubMed Central

    Mizumori, Sheri JY; Jo, Yong Sang

    2013-01-01

    While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The “multiple memory systems of the brain” have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result

  4. 76 FR 78977 - Real Estate Settlement Procedures Act (Regulation X)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... this rule. See 76 FR 43569 (July 21, 2011). \\11\\ Section 1066 of the Dodd-Frank Act grants the...-Frank Act In developing the interim final rule, the Bureau has conducted an analysis of potential... the described analyses and consultations. Although not required by the interim final rule,...

  5. 60 FR 8812 - Real Estate Settlement Procedures Act (Regulation X); Escrow Accounting Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    1995-02-15

    ... 24 CFR Part 3500 Real Estate Settlement Procedures Act (Regulation X); Escrow Accounting Procedures...-Federal Housing Commissioner 24 CFR Part 3500 RIN 2502-AF77 Real Estate Settlement Procedures Act... of the Real Estate Settlement Procedures Act. Subsequent to the publication of that rule,...

  6. 76 FR 68690 - Rules and Regulations Under the Textile Fiber Products Identification Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-07

    ... Wool Products Labeling Act, and the Fur Products Labeling Act: Final Rule, 63 FR 7508 (Feb. 13, 1998). \\2\\ Federal Trade Commission: Miscellaneous Rules: Final Rule, 63 FR 71582 (Dec. 29, 1998). \\3... and Regulations Under the Wool Products Labeling Act of 1939, Final Rule, 65 FR 75154 (Dec. 1,...

  7. 22 CFR 91.1 - Answering inquiries regarding tariff acts and customs regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Answering inquiries regarding tariff acts and... IMPORT CONTROLS § 91.1 Answering inquiries regarding tariff acts and customs regulations. In replying to inquiries received from exporters, travelers, or other interested parties, concerning tariff acts or...

  8. 20 CFR 626.3 - Purpose, scope, and applicability of the Job Training Partnership Act regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Purpose, scope, and applicability of the Job... ADMINISTRATION, DEPARTMENT OF LABOR INTRODUCTION TO THE REGULATIONS UNDER THE JOB TRAINING PARTNERSHIP ACT § 626.3 Purpose, scope, and applicability of the Job Training Partnership Act regulations. (a) Parts...

  9. 20 CFR 626.3 - Purpose, scope, and applicability of the Job Training Partnership Act regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Purpose, scope, and applicability of the Job Training Partnership Act regulations. 626.3 Section 626.3 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR INTRODUCTION TO THE REGULATIONS UNDER THE JOB TRAINING PARTNERSHIP ACT § 626.3 Purpose, scope, and...

  10. 20 CFR 626.3 - Purpose, scope, and applicability of the Job Training Partnership Act regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Purpose, scope, and applicability of the Job... ADMINISTRATION, DEPARTMENT OF LABOR INTRODUCTION TO THE REGULATIONS UNDER THE JOB TRAINING PARTNERSHIP ACT § 626.3 Purpose, scope, and applicability of the Job Training Partnership Act regulations. (a) Parts...

  11. 14 CFR 374.3 - Compliance with the Consumer Credit Protection Act and regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Compliance with the Consumer Credit Protection Act and regulations. 374.3 Section 374.3 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS IMPLEMENTATION OF THE CONSUMER CREDIT PROTECTION ACT WITH RESPECT TO AIR CARRIERS...

  12. 29 CFR 1903.2 - Posting of notice; availability of the Act, regulations and applicable standards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Posting of notice; availability of the Act, regulations and... § 1903.2 Posting of notice; availability of the Act, regulations and applicable standards. (a)(1) Each... large type, generally not less than 36 pt. (b) Establishment means a single physical location...

  13. 78 FR 29263 - Rules andRegulations Under the Textile Fiber Products Identification Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-20

    ... Under the Textile Fiber Products Identification Act, 76 FR 68690 (Nov. 7, 2011). This Notice of Proposed...--Rules and Regulations Under the Textile Fiber Products Identification Act, 24 FR 4480, 4485 (June 2... Rulemaking, 50 FR 15100 at 15101 (Apr. 15, 1985). This Notice compared the Customs regulations in 19 CFR...

  14. 75 FR 50718 - Regulations Implementing the Longshore and Harbor Workers' Compensation Act: Recreational Vessels

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-17

    ...This document contains proposed regulations implementing amendments to the Longshore and Harbor Workers' Compensation Act (LHWCA) by the American Recovery and Reinvestment Act of 2009 (ARRA), relating to the exclusion of certain recreational-vessel workers from the LHWCA's definition of ``employee.'' These regulations would clarify both the definition of ``recreational vessel'' and those......

  15. 77 FR 29982 - Federal Acquisition Regulation; Submission for OMB Review; Davis Bacon Act-Price Adjustment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-21

    ... (actual method). A notice was published in the Federal Register at 77 FR 13328, on March 6, 2012. No... Regulation; Submission for OMB Review; Davis Bacon Act-Price Adjustment (Actual Method) AGENCY: Department of... Bacon Act-Price Adjustment (Actual Method), by any of the following methods: Regulations.gov :...

  16. 78 FR 4725 - Escrow Requirements Under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-22

    ...The Bureau of Consumer Financial Protection (Bureau) is publishing a final rule that amends Regulation Z (Truth in Lending) to implement certain amendments to the Truth in Lending Act made by the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act). Regulation Z currently requires creditors to establish escrow accounts for higher-priced mortgage loans secured by a first......

  17. 77 FR 57043 - Regulations Under the Fur Products Labeling Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-17

    ... Labeling Act (``TFLA''), and, on its own initiative, deleting unnecessary requirements. \\1\\ 76 FR 13550..., most recently in 1967.\\17\\ \\16\\ 15 U.S.C. 69e(b). \\17\\ 32 FR 6023 (Apr. 15, 1967). C. TFLA In 2010....ftc.gov/opa/2011/07/regreview.shtm . \\24\\ 76 FR 13550. \\25\\ The comments, along with a transcript...

  18. 77 FR 66539 - Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ... electronic records and automated searches along with paper records and manual searches. In addition, FMCS's... twenty cents per page, while document search and review charges will increase to $4.00 per each quarter... revisions read as follows: Sec. 1401.36 Freedom of Information Act fee schedules. (a) * * * (2) Search...

  19. The Equal Access Act: Policy and Regulations for Implementation.

    ERIC Educational Resources Information Center

    Jones, H. Lawrence; Martin, James

    The Equal Access Act of 1984 was drafted to implement access for religious clubs to public secondary schools, but with constitutionally protected safeguards to preclude entanglement of church and state. A number of challenges were made on the constitutional grounds of excessive entanglement of church and state, as well as what the definition of…

  20. 77 FR 50390 - Equal Credit Opportunity Act (Regulation B)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-21

    ... from the Bureau's rulemaking authority by section 1029 of the Dodd-Frank Act). 76 FR 79442 (Dec. 21... burdens on industry. Thus, many of the rulemakings listed above involve issues that extend across two or... Bureau planned to conduct qualitative testing with industry participants as well as consumers. Each...

  1. Gonadotropins regulate ovarian germ cell mitosis/meiosis decision in the embryonic chicken.

    PubMed

    He, Bin; Mi, Yuling; Zhang, Caiqiao

    2013-05-01

    Gonadotropins are required for gametogenesis but in embryonic gonads this mechanism is not well understood. Here we use chicken embryos to investigate the mechanism that gonadotropins regulate the ovarian germ cell mitosis/meiosis decision. Treatment with follicle-stimulating hormone (FSH) delayed germ cell meiosis entry and promoted their proliferation. This action was blocked by an aromatase inhibitor. Treatment with luteinizing hormone (LH) accelerated germ cell meiosis entry and promoted transcription of 3βHSDII to increase progesterone (P4) production. In the cultured ovaries, P4 triggered meiotic initiation in germ cells. MiR181a, which acts to downregulate the NR6A1 transcript to inhibit the meiotic initiation, was upregulated by FSH and downregulated by LH. Collectively, gonadotropins regulate germ cells mitosis and meiotic initiation through steroid hormones and a miR181a-mediated pathway. In particularly, FSH delays germ cell meiosis entry and promotes cell proliferation via estrogen while LH accelerates the meiotic initiation via elevated P4 production. PMID:23422072

  2. 25 CFR 101.10 - Federal Reserve Regulation Z and Fair Credit Reporting Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... subject to the provisions of Federal Reserve Regulation Z (Truth In Lending, 12 CFR part 226; Pub. L. 91... 25 Indians 1 2012-04-01 2011-04-01 true Federal Reserve Regulation Z and Fair Credit Reporting Act... ACTIVITIES LOANS TO INDIANS FROM THE REVOLVING LOAN FUND § 101.10 Federal Reserve Regulation Z and...

  3. The Final Regulations to the Carl D. Perkins Vocational and Applied Technology Education Act of 1990.

    ERIC Educational Resources Information Center

    American Vocational Association, Alexandria, VA.

    This publication presents the final regulations to the Carl D. Perkins Vocational and Applied Technology Education Act of 1990. The first section is an analysis of the regulations. This analysis compares the proposed regulations to the final version and explains the differences between the two and the potential impact on program administration.…

  4. Enhancing Decision-Making in STSE Education by Inducing Reflection and Self-Regulated Learning

    NASA Astrophysics Data System (ADS)

    Gresch, Helge; Hasselhorn, Marcus; Bögeholz, Susanne

    2015-12-01

    Thoughtful decision-making to resolve socioscientific issues is central to science, technology, society, and environment (STSE) education. One approach for attaining this goal involves fostering students' decision-making processes. Thus, the present study explores whether the application of decision-making strategies, combined with reflections on the decision-making processes of others, enhances decision-making competence. In addition, this study examines whether this process is supported by elements of self-regulated learning, i.e., self-reflection regarding one's own performance and the setting of goals for subsequent tasks. A computer-based training program which involves the resolution of socioscientific issues related to sustainable development was developed in two versions: with and without elements of self-regulated learning. Its effects on decision-making competence were analyzed using a pre test-post test follow-up control-group design (N = 242 high school students). Decision-making competence was assessed using an open-ended questionnaire that focused on three facets: consideration of advantages and disadvantages, metadecision aspects, and reflection on the decision-making processes of others. The findings suggest that students in both training groups incorporated aspects of metadecision into their statements more often than students in the control group. Furthermore, both training groups were more successful in reflecting on the decision-making processes of others. The students who received additional training in self-regulated learning showed greater benefits in terms of metadecision aspects and reflection, and these effects remained significant two months later. Overall, our findings demonstrate that the application of decision-making strategies, combined with reflections on the decision-making process and elements of self-regulated learning, is a fruitful approach in STSE education.

  5. 77 FR 76898 - Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ... Federal Register (77 FR 56592) and requested comments over a 60-day period ending on November 13, 2012... regulations must be based on the best available science and that the rulemaking process must allow for public.... Finally, the revisions include current cost figures to be used in calculating and charging fees...

  6. Auxin acts independently of DELLA proteins in regulating gibberellin levels.

    PubMed

    Reid, James B; Davidson, Sandra E; Ross, John J

    2011-03-01

    Shoot elongation is a vital process for plant development and productivity, in both ecological and economic contexts. Auxin and bioactive gibberellins (GAs), such as GA1, play critical roles in the control of elongation, along with environmental and endogenous factors, including other hormones such as the brassinosteroids. The effect of auxins, such as indole-3-acetic acid (IAA), is at least in part mediated by its effect on GA metabolism, since auxin up-regulates biosynthesis genes such as GA 3-oxidase and GA 20-oxidase and down regulates GA catabolism genes such as GA 2-oxidases, leading to elevated levels of bioactive GA 1. In our recent paper, we have provided evidence that this action of IAA is largely independent of DELLA proteins, the negative regulators of GA action, since the auxin effects are still present in the DELLA-deficient la cry-s genotype of pea. This was a crucial issue to resolve, since like auxin, the DELLAs also promote GA 1 synthesis and inhibit its deactivation. DELLAs are deactivated by GA, and thereby mediate a feedback system by which bioactive GA regulates its own level. However, our recent results, in themselves, do not show the generality of the auxin-GA relationship across species and phylogenetic groups or across different tissue types and responses. Further, they do not touch on the ecological benefits of the auxin-GA interaction. These issues are discussed below as well as the need for the development of suitable experimental systems to allow this process to be examined. PMID:21358281

  7. TRF2 acts as a transcriptional regulator in tumor angiogenesis

    PubMed Central

    Maï, Mounir El; Wagner, Kay-Dietrich; Michiels, Jean-François; Gilson, Eric; Wagner, Nicole

    2015-01-01

    We recently showed that telomeric repeat-binding factor 2 (TRF2) regulates gene expression to promote angiogenesis. We found that TRF2 is highly expressed in tumor vessels and transcriptionally activates platelet-derived growth factor receptor β to promote endothelial cell angiogenic properties independently of its function in telomere protection. This work identifies TRF2 as a promising dual target for cancer therapy. PMID:27308469

  8. Modelling Dynamic Decision Making with the ACT-R Cognitive Architecture

    NASA Astrophysics Data System (ADS)

    Peebles, David; Banks, Adrian

    2010-12-01

    This paper describes a model of dynamic decision making in the Dynamic Stocks and Flows (DSF) task, developed using the ACT-R cognitive architecture. This task is a simple simulation of a water tank in which the water level must be kept constant whilst the inflow and outflow changes at varying rates. The basic functions of the model are based around three steps. Firstly, the model predicts the water level in the next cycle by adding the current water level to the predicted net inflow of water. Secondly, based on this projection, the net outflow of the water is adjusted to bring the water level back to the target. Thirdly, the predicted net inflow of water is adjusted to improve its accuracy in the future. If the prediction has overestimated net inflow then it is reduced, if it has underestimated net inflow it is increased. The model was entered into a model comparison competition—the Dynamic Stocks and Flows Challenge—to model human performance on four conditions of the DSF task and then subject the model to testing on five unseen transfer conditions. The model reproduced the main features of the development data reasonably well but did not reproduce human performance well under the transfer conditions. This suggests that the principles underlying human performance across the different conditions differ considerably despite their apparent similarity. Further lessons for the future development of our model and model comparison challenges are considered.

  9. Act quickly, decide later: long-latency visual processing underlies perceptual decisions but not reflexive behavior.

    PubMed

    Jolij, Jacob; Scholte, H Steven; van Gaal, Simon; Hodgson, Timothy L; Lamme, Victor A F

    2011-12-01

    Humans largely guide their behavior by their visual representation of the world. Recent studies have shown that visual information can trigger behavior within 150 msec, suggesting that visually guided responses to external events, in fact, precede conscious awareness of those events. However, is such a view correct? By using a texture discrimination task, we show that the brain relies on long-latency visual processing in order to guide perceptual decisions. Decreasing stimulus saliency leads to selective changes in long-latency visually evoked potential components reflecting scene segmentation. These latency changes are accompanied by almost equal changes in simple RTs and points of subjective simultaneity. Furthermore, we find a strong correlation between individual RTs and the latencies of scene segmentation related components in the visually evoked potentials, showing that the processes underlying these late brain potentials are critical in triggering a response. However, using the same texture stimuli in an antisaccade task, we found that reflexive, but erroneous, prosaccades, but not antisaccades, can be triggered by earlier visual processes. In other words: The brain can act quickly, but decides late. Differences between our study and earlier findings suggesting that action precedes conscious awareness can be explained by assuming that task demands determine whether a fast and unconscious, or a slower and conscious, representation is used to initiate a visually guided response. PMID:21557644

  10. Clinical decision support for imaging in the era of the Patient Protection and Affordable Care Act.

    PubMed

    Zafar, Hanna M; Mills, Angela M; Khorasani, Ramin; Langlotz, Curtis P

    2012-12-01

    Imaging clinical decision support (CDS) systems provide evidence for or against imaging procedures ordered within a computerized physician order entry system at the time of the image order. Depending on the pertinent clinical history provided by the ordering clinician, CDS systems can optimize imaging by educating providers on appropriate image order entry and by alerting providers to the results of prior, potentially relevant imaging procedures, thereby reducing redundant imaging. The American Recovery and Reinvestment Act (ARRA) has expedited the adoption of computerized physician order entry and CDS systems in health care through the creation of financial incentives and penalties to promote the "meaningful use" of health IT. Meaningful use represents the latest logical next step in a long chain of legislation promoting the areas of appropriate imaging utilization, accurate reporting, and IT. It is uncertain if large-scale implementation of imaging CDS will lead to improved health care quality, as seen in smaller settings, or to improved patient outcomes. However, imaging CDS enables the correlation of existing imaging evidence with outcome measures, including morbidity, mortality, and short-term imaging-relevant management outcomes (eg, biopsy, chemotherapy). The purposes of this article are to review the legislative sequence relevant to imaging CDS and to give guidance to radiology practices focused on quality and financial performance improvement during this time of accelerating regulatory change. PMID:23206649

  11. Brightening up: the effect of the Physician Payment Sunshine Act on existing regulation of pharmaceutical marketing.

    PubMed

    Gorlach, Igor; Pham-Kanter, Genevieve

    2013-01-01

    With the passage of the Physician Payment Sunshine Act as part of the federal health care reform law, pharmaceutical manufacturers are now required to disclose a wide range of payments made by manufacturers to physicians. We review current state regulation of pharmaceutical marketing and consider how the federal sunshine provision will affect existing marketing regulation. We analyze the legal and practical implications of the Physician Payment Sunshine Act. PMID:23581674

  12. 20 CFR 626.2 - Format of the Job Training Partnership Act regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., including complaint processing and compliance reviews, will be governed by the provisions of 29 CFR part 34... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Format of the Job Training Partnership Act... LABOR INTRODUCTION TO THE REGULATIONS UNDER THE JOB TRAINING PARTNERSHIP ACT § 626.2 Format of the...

  13. 20 CFR 626.4 - Table of contents for the Job Training Partnership Act regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the Job Training Partnership Act, 20 CFR parts 626-638 and 1005, 1 is as follows: 1 Part 1005 was... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Table of contents for the Job Training..., DEPARTMENT OF LABOR INTRODUCTION TO THE REGULATIONS UNDER THE JOB TRAINING PARTNERSHIP ACT § 626.4 Table...

  14. 20 CFR 626.2 - Format of the Job Training Partnership Act regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., including complaint processing and compliance reviews, will be governed by the provisions of 29 CFR part 34... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Format of the Job Training Partnership Act... LABOR INTRODUCTION TO THE REGULATIONS UNDER THE JOB TRAINING PARTNERSHIP ACT § 626.2 Format of the...

  15. 20 CFR 626.4 - Table of contents for the Job Training Partnership Act regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the Job Training Partnership Act, 20 CFR parts 626-638 and 1005, 1 is as follows: 1 Part 1005 was... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Table of contents for the Job Training..., DEPARTMENT OF LABOR INTRODUCTION TO THE REGULATIONS UNDER THE JOB TRAINING PARTNERSHIP ACT § 626.4 Table...

  16. The Fair Labor Standards Act and the Child Care Industry--What Regulations Apply.

    ERIC Educational Resources Information Center

    Lee, Elisa

    1996-01-01

    Discusses how the federal Fair Labor Standard Act (FLSA) affects the wages and work hours of child care employees and how FLSA interacts with analogous state laws. Examines how child care centers can determine whether FLSA regulations apply to them, existing exemptions to the current act, minimum wage and overtime, whether training time is working…

  17. 77 FR 13328 - Federal Acquisition Regulation; Information Collection; Davis Bacon Act-Price Adjustment (Actual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-06

    ... Regulation; Information Collection; Davis Bacon Act--Price Adjustment (Actual Method) AGENCY: Department of... (actual method). Public comments are particularly invited on: Whether this collection of information is... comments identified by Information Collection 9000- 0154, Davis Bacon Act--Price Adjustment (Actual...

  18. Social and ecological regulation of a decision-making circuit.

    PubMed

    Neumeister, H; Whitaker, K W; Hofmann, H A; Preuss, T

    2010-12-01

    Ecological context, sensory inputs, and the internal physiological state are all factors that need to be integrated for an animal to make appropriate behavioral decisions. However, these factors have rarely been studied in the same system. In the African cichlid fish Astatotilapia burtoni, males alternate between two phenotypes based on position in a social hierarchy. When dominant (DOM), fish display bright body coloration and a wealth of aggressive and reproductive behavioral patterns that make them conspicuous to predators. Subordinate (SUB) males, on the other hand, decrease predation risk by adopting cryptic coloration and schooling behavior. We therefore hypothesized that DOMs would show enhanced startle-escape responsiveness to compensate for their increased predation risk. Indeed, behavioral responses to sound clicks of various intensities showed a significantly higher mean startle rate in DOMs compared with SUBs. Electrophysiological recordings from the Mauthner cells (M-cells), the neurons triggering startle, were performed in anesthetized animals and showed larger synaptic responses to sound clicks in DOMs, consistent with the behavioral results. In addition, the inhibitory drive mediated by interneurons (passive hyperpolarizing potential [PHP] cells) presynaptic to the M-cell was significantly reduced in DOMs. Taken together, the results suggest that the likelihood for an escape to occur for a given auditory stimulus is higher in DOMs because of a more excitable M-cell. More broadly, this study provides an integrative explanation of an ecological and social trade-off at the level of an identifiable decision-making neural circuit. PMID:20926612

  19. The application of genetic information for regulatory standard setting under the clean air act: a decision-analytic approach.

    PubMed

    Cullen, Alison C; Corrales, Mark A; Kramer, C Bradley; Faustman, Elaine M

    2008-08-01

    In 2002, the U.S. Environmental Protection Agency (EPA) released an "Interim Policy on Genomics," stating a commitment to developing guidance on the inclusion of genetic information in regulatory decision making. This statement was followed in 2004 by a document exploring the potential implications. Genetic information can play a key role in understanding and quantifying human susceptibility, an essential step in many of the risk assessments used to shape policy. For example, the federal Clean Air Act (CAA) requires EPA to set National Ambient Air Quality Standards (NAAQS) for criteria pollutants at levels to protect even sensitive populations from adverse health effects with an adequate margin of safety. Asthmatics are generally regarded as a sensitive population, yet substantial research gaps in understanding genetic susceptibility and disease have hindered quantitative risk analysis. This case study assesses the potential role of genomic information regarding susceptible populations in the NAAQS process for fine particulate matter (PM(2.5)) under the CAA. In this initial assessment, we model the contribution of a single polymorphism to asthma risk and mortality risk; however, multiple polymorphisms and interactions (gene-gene and gene-environment) are known to play key roles in the disease process. We show that the impact of new information about susceptibility on estimates of population risk or average risk derived from large epidemiological studies depends on the circumstances. We also suggest that analysis of a single polymorphism, or other risk factor such as health status, may or may not change estimates of individual risk enough to alter a particular regulatory decision, but this depends on specific characteristics of the decision and risk information. We also show how new information about susceptibility in the context of the NAAQS for PM(2.5) could have a large impact on the estimated distribution of individual risk. This would occur if a group were

  20. Identifying Specific Learning Disabilities: Legislation, Regulation, and Court Decisions

    ERIC Educational Resources Information Center

    Zumeta, Rebecca O.; Zirkel, Perry A.; Danielson, Louis

    2014-01-01

    Specific learning disability (SLD) identification and eligibility practices are evolving and sometimes contentious. This article describes the historical context and current status of the SLD definition, legislation, regulation, and case law related to the identification of students eligible for special education services. The first part traces…

  1. 78 FR 39901 - Amendments to the 2013 Mortgage Rules Under the Equal Credit Opportunity Act (Regulation B), Real...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... Bureau issued Escrow Requirements Under the Truth in Lending Act (Regulation Z), 78 FR 4726 (Jan. 30... Settlement Procedures Act (Regulation X), 78 FR 6856 (Jan. 31, 2013) (2013 HOEPA Final Rule), and Ability to Repay and Qualified Mortgage Standards Under the Truth in Lending Act (Regulation Z), 78 FR 6407...

  2. 14 CFR 374.3 - Compliance with the Consumer Credit Protection Act and regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... credit card practices. (2) The Fair Credit Reporting Act, 15 U.S.C. 1681-1681 setting forth requirements... air carrier and foreign air carrier shall comply with the requirements of Regulation B, 12 CFR part 202, and Regulation Z, 12 CFR part 226, of the Board of Governors of the Federal Reserve Board....

  3. 14 CFR 374.3 - Compliance with the Consumer Credit Protection Act and regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... credit card practices. (2) The Fair Credit Reporting Act, 15 U.S.C. 1681-1681 setting forth requirements... air carrier and foreign air carrier shall comply with the requirements of Regulation B, 12 CFR part 202, and Regulation Z, 12 CFR part 226, of the Board of Governors of the Federal Reserve Board....

  4. 14 CFR 374.3 - Compliance with the Consumer Credit Protection Act and regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... credit card practices. (2) The Fair Credit Reporting Act, 15 U.S.C. 1681-1681 setting forth requirements... air carrier and foreign air carrier shall comply with the requirements of Regulation B, 12 CFR part 202, and Regulation Z, 12 CFR part 226, of the Board of Governors of the Federal Reserve Board....

  5. 40 CFR 261.8 - PCB wastes regulated under Toxic Substance Control Act.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 27 2012-07-01 2012-07-01 false PCB wastes regulated under Toxic... (CONTINUED) SOLID WASTES (CONTINUED) IDENTIFICATION AND LISTING OF HAZARDOUS WASTE General § 261.8 PCB wastes regulated under Toxic Substance Control Act. The disposal of PCB-containing dielectric fluid and...

  6. 40 CFR 261.8 - PCB wastes regulated under Toxic Substance Control Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 27 2013-07-01 2013-07-01 false PCB wastes regulated under Toxic... (CONTINUED) SOLID WASTES (CONTINUED) IDENTIFICATION AND LISTING OF HAZARDOUS WASTE General § 261.8 PCB wastes regulated under Toxic Substance Control Act. The disposal of PCB-containing dielectric fluid and...

  7. 40 CFR 261.8 - PCB wastes regulated under Toxic Substance Control Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 26 2014-07-01 2014-07-01 false PCB wastes regulated under Toxic... (CONTINUED) SOLID WASTES (CONTINUED) IDENTIFICATION AND LISTING OF HAZARDOUS WASTE General § 261.8 PCB wastes regulated under Toxic Substance Control Act. The disposal of PCB-containing dielectric fluid and...

  8. 40 CFR 261.8 - PCB wastes regulated under Toxic Substance Control Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 26 2011-07-01 2011-07-01 false PCB wastes regulated under Toxic... (CONTINUED) SOLID WASTES (CONTINUED) IDENTIFICATION AND LISTING OF HAZARDOUS WASTE General § 261.8 PCB wastes regulated under Toxic Substance Control Act. The disposal of PCB-containing dielectric fluid and...

  9. 75 FR 59609 - Rescission of Regulations Under the Comprehensive Smokeless Tobacco Health Education Act of 1986

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... its smokeless tobacco regulations, 16 CFR Part 307, on November 4, 1986.\\1\\ 51 FR 40015. \\1\\ The... on utilitarian items. 56 FR 11654 (Mar. 20, 1991). II. Basis for Removal of Regulations On June 22... the enactment of the Family Smoking Prevention Act. 75 FR 3665 (Jan. 22, ] 2010). The...

  10. 78 FR 8963 - Update of Existing Privacy Act-NASA Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ... document contains corrections to the final regulations (NASA-2012-0005), which were published in the Federal Register of Thursday, October 4, 2012 (77 FR 60620). The regulations relate to requests to access... SPACE ADMINISTRATION 14 CFR Part 1212 RIN 2700-AD86 Update of Existing Privacy Act--NASA...

  11. GUAM - FACILITIES REGULATED UNDER THE RESOURCE CONVERVATION AND RECOVERY ACT (RCRA)

    EPA Science Inventory

    Points represent facilities that are regulated by the EPA under the Resource Conservation and Recovery Act (RCRA). Facilities regulated under RCRA generate, dispose of, treate or transport hazardous waste. RCRA is a law enacted by Congress in 1976 and amended in 1984 to include ...

  12. NEVADA FACILITIES REGULATED UNDER THE RESOURCE CONVERVATION AND RECOVERY ACT (RCRA)

    EPA Science Inventory

    Points represent facilities that are regulated by the EPA under the Resource Conservation and Recovery Act (RCRA). Facilities regulated under RCRA generate, dispose of, treate or transport hazardous waste. RCRA is a law enacted by Congress in 1976 and amended in 1984 to include ...

  13. 76 FR 24291 - Proposed National Marketing Agreement Regulating Leafy Green Vegetables; Recommended Decision and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-29

    ...This recommended decision proposes the issuance of a marketing agreement (agreement) under the Agricultural Marketing Agreement Act of 1937 to cover the handling of fresh leafy green vegetables in the United States. Leafy green vegetables include lettuce, spinach, cabbage, and similar items. The proposed agreement would authorize the development and implementation of production and handling......

  14. Regulating Emotions during Difficult Multiattribute Decision Making: The Role of Pre-Decisional Coherence Shifting.

    PubMed

    Carpenter, Stephanie M; Yates, J Frank; Preston, Stephanie D; Chen, Lydia

    2016-01-01

    Almost all real-life decisions entail attribute conflict; every serious choice alternative is better than its competitors on some attribute dimensions but worse on others. In pre-decisional "coherence shifting," the decision maker gradually softens that conflict psychologically to the point where one alternative is seen as dominant over its competitors, or nearly so. Specifically, weaknesses of the eventually chosen alternative come to be perceived as less severe and less important while its strengths seem more desirable and significant. The research described here demonstrates that difficult multiattribute decision problems are aversive and that pre-decisional coherence shifting aids individuals in regulating that emotional discomfort. Across three studies, attribute conflict was confirmed to be aversive (Study 1), and skin conductance responses and ratings of decision difficulty both decreased in participants who coherence shifted (Study 2). Coherence shifting was also diminished among decision makers who were depleted of regulatory resources, known to be required for common emotion regulation mechanisms. Further, coherence shifting was shown to be relatively common among people who reported strong suppression tendencies in everyday emotion regulation (Study 3). Overall, the data suggest that, at least in part, coherence shifting serves as a tool that helps decision makers manage the pre-decisional discomfort generated by attribute conflict. Theoretical and practical implications are discussed. PMID:26986752

  15. Regulating Emotions during Difficult Multiattribute Decision Making: The Role of Pre-Decisional Coherence Shifting

    PubMed Central

    Carpenter, Stephanie M.; Yates, J. Frank; Preston, Stephanie D.; Chen, Lydia

    2016-01-01

    Almost all real-life decisions entail attribute conflict; every serious choice alternative is better than its competitors on some attribute dimensions but worse on others. In pre-decisional “coherence shifting,” the decision maker gradually softens that conflict psychologically to the point where one alternative is seen as dominant over its competitors, or nearly so. Specifically, weaknesses of the eventually chosen alternative come to be perceived as less severe and less important while its strengths seem more desirable and significant. The research described here demonstrates that difficult multiattribute decision problems are aversive and that pre-decisional coherence shifting aids individuals in regulating that emotional discomfort. Across three studies, attribute conflict was confirmed to be aversive (Study 1), and skin conductance responses and ratings of decision difficulty both decreased in participants who coherence shifted (Study 2). Coherence shifting was also diminished among decision makers who were depleted of regulatory resources, known to be required for common emotion regulation mechanisms. Further, coherence shifting was shown to be relatively common among people who reported strong suppression tendencies in everyday emotion regulation (Study 3). Overall, the data suggest that, at least in part, coherence shifting serves as a tool that helps decision makers manage the pre-decisional discomfort generated by attribute conflict. Theoretical and practical implications are discussed. PMID:26986752

  16. A Primer on Decision Analysis for Individually Prescribed Instruction. ACT Technical Bulletin No. 17.

    ERIC Educational Resources Information Center

    Davis, Charles E.; And Others

    A coherent system of decision making is described that may be incorporated into an instructional sequence to provide a supplement to the experience-based judgment of the classroom teacher. The elements of this decision process incorporate prior information such as a teacher's past experience, experimental results such as a test score, and…

  17. 29 CFR 1902.41 - Decision.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Decision. 1902.41 Section 1902.41 Labor Regulations... 18(e) of the Act Procedures for 18(e) Determination § 1902.41 Decision. (a) Within a reasonable time... shall publish his decision in the Federal Register. His decision shall state whether or not...

  18. 78 FR 18344 - Federal Acquisition Regulation; Submission for OMB Review; Buy American Act-Free Trade Agreements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... Regulation; Submission for OMB Review; Buy American Act--Free Trade Agreements--Israeli Trade Act Certificate... previously approved information collection requirement concerning the Buy American Act--Free Trade Agreements... comments identified by Information Collection 9000- 0130, Buy American Act--Free Trade......

  19. 25 CFR 162.253 - Will BIA's regulations concerning appeal bonds apply to cancellation decisions involving...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Will BIA's regulations concerning appeal bonds apply to cancellation decisions involving agricultural leases? 162.253 Section 162.253 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER LEASES AND PERMITS Agricultural Leases Lease Enforcement §...

  20. 25 CFR 162.253 - Will BIA's regulations concerning appeal bonds apply to cancellation decisions involving...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Will BIA's regulations concerning appeal bonds apply to cancellation decisions involving agricultural leases? 162.253 Section 162.253 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER LEASES AND PERMITS Agricultural Leases Lease Enforcement §...

  1. Neural mechanisms regulating different forms of risk-related decision-making: Insights from animal models.

    PubMed

    Orsini, Caitlin A; Moorman, David E; Young, Jared W; Setlow, Barry; Floresco, Stan B

    2015-11-01

    Over the past 20 years there has been a growing interest in the neural underpinnings of cost/benefit decision-making. Recent studies with animal models have made considerable advances in our understanding of how different prefrontal, striatal, limbic and monoaminergic circuits interact to promote efficient risk/reward decision-making, and how dysfunction in these circuits underlies aberrant decision-making observed in numerous psychiatric disorders. This review will highlight recent findings from studies exploring these questions using a variety of behavioral assays, as well as molecular, pharmacological, neurophysiological, and translational approaches. We begin with a discussion of how neural systems related to decision subcomponents may interact to generate more complex decisions involving risk and uncertainty. This is followed by an overview of interactions between prefrontal-amygdala-dopamine and habenular circuits in regulating choice between certain and uncertain rewards and how different modes of dopamine transmission may contribute to these processes. These data will be compared with results from other studies investigating the contribution of some of these systems to guiding decision-making related to rewards vs. punishment. Lastly, we provide a brief summary of impairments in risk-related decision-making associated with psychiatric disorders, highlighting recent translational studies in laboratory animals. PMID:26072028

  2. 21 CFR 16.24 - Regulatory hearing required by the act or a regulation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory hearing required by the act or a regulation. 16.24 Section 16.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL REGULATORY HEARING BEFORE THE FOOD AND DRUG ADMINISTRATION Initiation of Proceedings §...

  3. 60 FR 11194 - Real Estate Settlement Procedures Act (Regulation X); Escrow Accounting Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    1995-03-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT Office of the Assistant Secretary for Housing-Federal Housing Commissioner 24 CFR Part 3500 RIN 2502-AF77 Real Estate Settlement Procedures Act (Regulation X); Escrow Accounting...

  4. 75 FR 40754 - Government in the Sunshine Act Regulations of the National Science Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-14

    ... From the Federal Register Online via the Government Publishing Office NATIONAL SCIENCE FOUNDATION 45 CFR Part 614 RIN 3145-AA53 Government in the Sunshine Act Regulations of the National Science Board AGENCY: National Science Board (NSB), National Science Foundation (NSF). ACTION: Direct final...

  5. The National Labor Relations Act and the Regulation of Public Employee Collective Bargaining

    ERIC Educational Resources Information Center

    McCann, Walter; Smiley, Stafford

    1976-01-01

    The arguments for and against federal assumption of the responsibility for regulating the relationship between public employers and public employees are analyzed. It is suggested that the National Labor Relations Act should be extended to include them, thereby imposing upon them a duty to bargain collectively. Available from: the Harvard…

  6. 77 FR 20295 - Regulations To Implement the Equal Employment Provisions of the Americans With Disabilities Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... From the Federal Register Online via the Government Publishing Office ] EQUAL EMPLOYMENT OPPORTUNITY COMMISSION 29 CFR Part 1630 Regulations To Implement the Equal Employment Provisions of the Americans With Disabilities Act, as Amended CFR Correction In Title 29 of the Code of Federal...

  7. 78 FR 70515 - Petition To Promulgate Standards for Bears Under the Animal Welfare Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ...; ] DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Part 3 Petition To Promulgate Standards for Bears Under the Animal Welfare Act Regulations AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice of petition. SUMMARY: We are notifying the public that the Animal and...

  8. 75 FR 24862 - Removing Regulations Implementing the Fish and Wildlife Conservation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-06

    ...'' (59 FR 22951), E.O. 13175, and 512 DM 2. We have determined that there are no potential effects. This... Fish and Wildlife Service 50 CFR Part 83 RIN 1018-AX00 Removing Regulations Implementing the Fish and Wildlife Conservation Act AGENCY: Fish and Wildlife Service, Interior. ACTION: Proposed rule. SUMMARY:...

  9. 75 FR 19241 - Financial Crimes Enforcement Network; Amendment to the Bank Secrecy Act Regulations; Defining...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-14

    ... for Mutual Funds, 67 FR 21117 (April 29, 2002); Customer Identification Programs for Mutual Funds, 68 FR 25131 (May 9, 2003); Amendment to the Bank Secrecy Act Regulations--Requirement That Mutual Funds Report Suspicious Activity, 71 FR 26213 (May 4, 2006); Anti-Money Laundering Programs; Special...

  10. 76 FR 57940 - Revision of Department of Justice Freedom of Information Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-19

    ... NRPM published on March 21, 2011 (76 FR 15236), closed on April 20, 2011. This document reopens the... the Freedom of Information Act. The comment period for that rule closed on April 20, 2011. The... revising its existing regulations under the FOIA. (See 76 FR 15236.) The rule proposed to amend...

  11. 76 FR 35963 - Disclosure of Information; Privacy Act Regulations; Notice and Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ... CORPORATION 12 CFR Parts 309 and 310 RIN 3064-AD83 Disclosure of Information; Privacy Act Regulations; Notice... disclosure of information and the PA, as amended. In taking this action the FDIC's goal is to avoid potential... to correct addresses and other matters that have changed since the FDIC's rules involving...

  12. Impact of Clean Air Act Regulations on Nitrogen Fate and Transport in Neuse River Basin

    EPA Science Inventory

    This study investigated impacts of Clean Air Act Amendment (CAAA) NOx emissions regulations on the fate and transport of nitrogen for two watersheds in the Neuse River Basin, North Carolina, USA from 1990 to 2020. The Soil and Water Assessment Tool (SWAT) and the Community Multi-...

  13. 75 FR 14547 - Tribal Consultation on Draft Buy Indian Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs 48 CFR Chapter 14 RIN 1076-AE95 Tribal Consultation on Draft Buy Indian Act Regulations AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice of tribal consultation...

  14. 14 CFR 374.3 - Compliance with the Consumer Credit Protection Act and regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Compliance with the Consumer Credit... OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS IMPLEMENTATION OF THE CONSUMER CREDIT PROTECTION ACT WITH RESPECT TO AIR CARRIERS AND FOREIGN AIR CARRIERS § 374.3 Compliance with the...

  15. 76 FR 20569 - Horse Protection Act; Petition for Amendments to Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... Animal and Plant Health Inspection Service 9 CFR Part 11 Horse Protection Act; Petition for Amendments to... changes to our horse protection regulations and our current enforcement practices and related policies... are noting, however, that certain requests in the petition lack authority in the Horse Protection...

  16. The Decision Analysis Interview Approach in the Collaborative Management of a Large Regulated Water Course

    NASA Astrophysics Data System (ADS)

    Marttunen, Mika; Hämäläinen, Raimo P.

    2008-12-01

    There are always conflicting goals in the management of large water courses. However, by involving stakeholders actively in the planning and decision-making processes, it is possible to work together toward commonly acceptable solutions. In this article, we describe how we applied interactive multicriteria decision analysis (MCDA) in a collaborative process which aimed at an ecologically, socially, and economically sustainable water course regulation policy. The stakeholders’ opinions about the alternative regulation schemes and the relative importance of their impacts were elicited with the HIPRE software. Altogether, 20 personal interactive decision analysis interviews (DAIs) were carried out with the stakeholders. Our experience suggests that the DAIs can considerably improve the quality and efficiency of the collaborative planning process. By improving communication and understanding of the decision situation in the steering group, the approach helped to develop a consensus solution in a case having strong conflicts of interest. In order to gain the full benefits of the MCDA approach, interactive preference elicitation is vital. It is also essential to integrate the approach tightly into the planning and decision-making process. The project’s home pages are available to the public at http://www.paijanne.hut.fi/ .

  17. The decision analysis interview approach in the collaborative management of a large regulated water course.

    PubMed

    Marttunen, Mika; Hämäläinen, Raimo P

    2008-12-01

    There are always conflicting goals in the management of large water courses. However, by involving stakeholders actively in the planning and decision-making processes, it is possible to work together toward commonly acceptable solutions. In this article, we describe how we applied interactive multicriteria decision analysis (MCDA) in a collaborative process which aimed at an ecologically, socially, and economically sustainable water course regulation policy. The stakeholders' opinions about the alternative regulation schemes and the relative importance of their impacts were elicited with the HIPRE software. Altogether, 20 personal interactive decision analysis interviews (DAIs) were carried out with the stakeholders. Our experience suggests that the DAIs can considerably improve the quality and efficiency of the collaborative planning process. By improving communication and understanding of the decision situation in the steering group, the approach helped to develop a consensus solution in a case having strong conflicts of interest. In order to gain the full benefits of the MCDA approach, interactive preference elicitation is vital. It is also essential to integrate the approach tightly into the planning and decision-making process. The project's home pages are available to the public at http://www.paijanne.hut.fi/. PMID:18830741

  18. Rationing health protection: a proposal to exempt nuisance dust from US Clean Air Act regulations.

    PubMed

    Centner, Terence J; Colson, Gregory

    2013-03-15

    The US House of Representative has passed a bill called the "Farm Dust Regulation Prevention Act" (Dust Act) that would exempt most types of particulate matter (PM) in rural areas from the air quality controls of the US Clean Air Act. The Dust Act would markedly change the country's air quality standards. An examination of the proposed provisions shows that they would exempt non-combustion PM pollutants from mining, smelting, petroleum production, and power generation from existing air quality standards. Persons downwind from pollutants generated in rural areas could be exposed to concentrations of carcinogenic heavy metals, asbestos, and benzene known to adversely affect their health and ecological resources. Existing federal air quality standards based on science would be replaced by a flexible standard that rations health protection. PMID:23376304

  19. 75 FR 48956 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... had violated CBV's right to actively participate in the SLA's administrative decision making..., the money remained in Fund 650. In 2005, because of increased health insurance premiums, CBV... vendors' health insurance plan. The second referendum requested that the SLA transfer the unused...

  20. 75 FR 79352 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ...) gives notice that on July 17, 2009, an arbitration panel rendered a decision in the matter of Jerry Bird... under 20 U.S.C. 107d-1(a), after the Department received a complaint filed by the petitioner, Jerry Bird... affecting the administration of vending facilities on Federal and other property. Background Jerry...

  1. 76 FR 11434 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... panel rendered a decision in the matter of Calvette Brown v. Illinois Department of Human Services... U.S.C. 107d-1(a), after the Department received a complaint filed by the petitioner, Calvette Brown... affecting the administration of vending facilities on Federal and other property. Background Calvette...

  2. Regulating the regulator: Numb acts upstream of p53 to control mammary stem and progenitor cell

    PubMed Central

    Faraldo, Marisa M.

    2015-01-01

    In this issue, Tosoni et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505037) report that cell fate determinant and tumor suppressor Numb imposes asymmetric cell divisions in mammary stem cells by regulating p53. Numb thereby restricts mammary stem cell expansion and controls the proliferation and lineage-specific characteristics of their progeny. PMID:26598611

  3. Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program.

    PubMed

    Khacho, Mireille; Clark, Alysen; Svoboda, Devon S; Azzi, Joelle; MacLaurin, Jason G; Meghaizel, Cynthia; Sesaki, Hiromi; Lagace, Diane C; Germain, Marc; Harper, Mary-Ellen; Park, David S; Slack, Ruth S

    2016-08-01

    Regulated mechanisms of stem cell maintenance are key to preventing stem cell depletion and aging. While mitochondrial morphology plays a fundamental role in tissue development and homeostasis, its role in stem cells remains unknown. Here, we uncover that mitochondrial dynamics regulates stem cell identity, self-renewal, and fate decisions by orchestrating a transcriptional program. Manipulation of mitochondrial structure, through OPA1 or MFN1/2 deletion, impaired neural stem cell (NSC) self-renewal, with consequent age-dependent depletion, neurogenesis defects, and cognitive impairments. Gene expression profiling revealed ectopic expression of the Notch self-renewal inhibitor Botch and premature induction of transcription factors that promote differentiation. Changes in mitochondrial dynamics regulate stem cell fate decisions by driving a physiological reactive oxygen species (ROS)-mediated process, which triggers a dual program to suppress self-renewal and promote differentiation via NRF2-mediated retrograde signaling. These findings reveal mitochondrial dynamics as an upstream regulator of essential mechanisms governing stem cell self-renewal and fate decisions through transcriptional programming. PMID:27237737

  4. Can Contrast Effects Regulate Emotions? A Follow-Up Study of Vital Loss Decisions

    PubMed Central

    Liu, Xianyun; Luo, Jing

    2012-01-01

    Although many studies focus on the how contrast effects can impact cognitive evaluations, the question of whether emotions are regulated by such contrast effects is still the subject of considerable debate, especially in the study of loss-related decisions. To address this gap in the literature, we designed three decision making loss conditions: (i) both losses are trivial (TT), (ii) one loss is trivial and the other loss is vital (TV), or (iii) one loss is trivial and the other loss is routine (TR). In study 1, which compared the difference between the negative emotion ratings in TT and TV, we found that negative emotions were affected by the contrast effects. In study 2, which compared the difference between the importance of trivial options in TT and TV, we found that the contrast effects differentially changed the importance of trivial options in the two conditions, which in turn down-regulated negative emotions. In study 3, the impact of decision difficulty was controlled by predetermining the items to be lost. In this study, we found that, when comparing the differences between the negative emotions of losing trivial options in TV and TR, the contrast effects still modulated the loss-related emotions. We concluded that the contrast effects could down-regulate emotions. To our knowledge, this is the first demonstration that contrast effects can alleviate negative affect in loss-related decision making. This study will enrich and extend the literature on emotion regulation theory, and it will provide a new cost-effective mitigation strategy for regulating negative emotions. PMID:22905170

  5. Can contrast effects regulate emotions? A follow-up study of vital loss decisions.

    PubMed

    Li, Qi; Qi, Yue; Liu, Xianyun; Luo, Jing

    2012-01-01

    Although many studies focus on the how contrast effects can impact cognitive evaluations, the question of whether emotions are regulated by such contrast effects is still the subject of considerable debate, especially in the study of loss-related decisions. To address this gap in the literature, we designed three decision making loss conditions: (i) both losses are trivial (TT), (ii) one loss is trivial and the other loss is vital (TV), or (iii) one loss is trivial and the other loss is routine (TR). In study 1, which compared the difference between the negative emotion ratings in TT and TV, we found that negative emotions were affected by the contrast effects. In study 2, which compared the difference between the importance of trivial options in TT and TV, we found that the contrast effects differentially changed the importance of trivial options in the two conditions, which in turn down-regulated negative emotions. In study 3, the impact of decision difficulty was controlled by predetermining the items to be lost. In this study, we found that, when comparing the differences between the negative emotions of losing trivial options in TV and TR, the contrast effects still modulated the loss-related emotions. We concluded that the contrast effects could down-regulate emotions. To our knowledge, this is the first demonstration that contrast effects can alleviate negative affect in loss-related decision making. This study will enrich and extend the literature on emotion regulation theory, and it will provide a new cost-effective mitigation strategy for regulating negative emotions. PMID:22905170

  6. 21 CFR 1271.10 - Are my HCT/P's regulated solely under section 361 of the PHS Act and the regulations in this part...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Are my HCT/P's regulated solely under section 361..., AND CELLULAR AND TISSUE-BASED PRODUCTS General Provisions § 1271.10 Are my HCT/P's regulated solely.../P is regulated solely under section 361 of the PHS Act and the regulations in this part if it...

  7. Industry invites regulation: the passage of the Pure Food and Drug Act of 1906.

    PubMed Central

    Barkan, I D

    1985-01-01

    Ending its 27-year stranglehold on proposals for federal pure food and drug legislation, Congress passed the Pure Food and Drug Act and its companion bill, the Meat Inspection Act, on June 30, 1906. An unprecedented convergence of consumer, scientific, and industrial support in 1906 prompted such action; most industries even planned for it, hoping regulation would restore the competitiveness of their products on weak foreign and domestic markets. The ways in which these interests converged, and the reasons therefore, suggest a change in their relationships to each other and with the federal government as America headed into the twentieth century. Images p21-a p21-b PMID:3881052

  8. 76 FR 48831 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-09

    ...The Department of Education (Department) gives notice that on May 3, 2010, and April 19, 2011, an arbitration panel rendered decisions in the matter of Art Stevenson v. Oregon Commission for the Blind, Case no. R-S/07-4. This panel was convened by the Department under 20 U.S.C. 107d-1(a), after the Department received a complaint filed by the petitioner, Art...

  9. 75 FR 48954 - Arbitration Panel Decision Under the Randolph-Sheppard Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... Department of Defense, Department of the Air Force, Case no. R-S/07-5. This panel was convened by the Department under 20 U.S.C. 107d-1(b) after the Department received a complaint filed by the petitioner, the..., the issues to be resolved were: (1) The Air Force's alleged failure to comply with the Act by...

  10. The Maharashtra Felling of Trees (Regulation) (Amendment) Act, 1988 (No. 26 of 1989), 5 August 1989.

    PubMed

    1989-01-01

    Among other things, this Act amends the Maharashtra (India) Felling of Trees (Regulation) Act, 1964, to authorize the Tree Officer to order the planting of trees in any land (other than government-designated drought land) that he thinks does not contain an adequate number of trees. Owners and occupiers of the land must comply with the order, after being given a reasonable opportunity to be heard. If they do not comply, they can be charged for expenses incurred in having the trees planted. In 1989 the government of West Bengal enacted The Indian Forest (West Bengal Amendment) Act, 1989 (No. 22 of 1988) (Calcutta Gazette, Extraordinary, Part III, 3 February 1989). This Act increases the punishment for various infractions of the Indian Forest Act, 1927, as applied to West Bengal and inserts new language relating to the power of officers to stop and search vehicles; the ability of the state government to seize contraband and related tools, vehicles, boats, and cattle; and punishment for abetting offenses delineated by the Act. PMID:12344326

  11. 78 FR 45842 - Amendments to the 2013 Mortgage Rules Under the Real Estate Settlement Procedure Act (Regulation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-30

    ... From the Federal Register Online via the Government Publishing Office BUREAU OF CONSUMER FINANCIAL PROTECTION 12 CFR Parts 1024 and 1026 RIN 3170-AA37 Amendments to the 2013 Mortgage Rules Under the Real Estate Settlement Procedure Act (Regulation X) and the Truth in Lending Act (Regulation Z) Correction...

  12. 26 CFR 1.706-2T - Temporary regulations; question and answer under the Tax Reform Act of 1984.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Temporary regulations; question and answer under the Tax Reform Act of 1984. 1.706-2T Section 1.706-2T Internal Revenue INTERNAL REVENUE SERVICE... Partnerships § 1.706-2T Temporary regulations; question and answer under the Tax Reform Act of 1984. Question...

  13. 26 CFR 1.706-2T - Temporary regulations; question and answer under the Tax Reform Act of 1984.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Temporary regulations; question and answer under the Tax Reform Act of 1984. 1.706-2T Section 1.706-2T Internal Revenue INTERNAL REVENUE SERVICE...-2T Temporary regulations; question and answer under the Tax Reform Act of 1984. Question 1:...

  14. 26 CFR 18.0 - Effective date of temporary regulations under the Subchapter S Revision Act of 1982.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Effective date of temporary regulations under the Subchapter S Revision Act of 1982. 18.0 Section 18.0 Internal Revenue INTERNAL REVENUE SERVICE... SUBCHAPTER S REVISION ACT OF 1982 § 18.0 Effective date of temporary regulations under the Subchapter...

  15. 26 CFR 18.0 - Effective date of temporary regulations under the Subchapter S Revision Act of 1982.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Effective date of temporary regulations under the Subchapter S Revision Act of 1982. 18.0 Section 18.0 Internal Revenue INTERNAL REVENUE SERVICE... SUBCHAPTER S REVISION ACT OF 1982 § 18.0 Effective date of temporary regulations under the Subchapter...

  16. 46 CFR 1.03-35 - Appeals from decisions or actions of a recognized classification society acting on behalf of the...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... classification society acting on behalf of the Coast Guard. 1.03-35 Section 1.03-35 Shipping COAST GUARD... recognized classification society acting on behalf of the Coast Guard. (a) Any person directly affected by a decision or action of a recognized classification society performing plan review, tonnage measurement,...

  17. HIPAA Mental Health Parity Act--IRS. Notice of proposed rulemaking by cross-reference to temporary regulations.

    PubMed

    1997-12-22

    Elsewhere in this issue of the Federal Register, the IRS is issuing temporary regulations relating to mental health parity requirements imposed on group health plans. These requirements were added to the Internal Revenue Code by section 1532 of the Taxpayer Relief Act of 1997. The IRS is issuing the temporary regulations at the same time that the Pension and Welfare Benefits Administration of the U.S. Department of Labor and the Health Care Financing Administration of the U.S. Department of Health and Human Services are issuing substantially similar interim final regulations relating to mental health parity requirements added by the Mental Health Parity Act of 1996 to the Employee Retirement Income Security Act of 1974 and the Public Health Service Act. The temporary regulations provide guidance to employers and group health plans relating to the new mental health parity requirements. The text of those temporary regulations also serves as the text of these proposed regulations. PMID:10179306

  18. The decision to exclude agricultural and domestic workers from the 1935 Social Security Act.

    PubMed

    DeWitt, Larry

    2010-01-01

    The Social Security Act of 1935 excluded from coverage about half the workers in the American economy. Among the excluded groups were agricultural and domestic workers-a large percentage of whom were African Americans. This has led some scholars to conclude that policymakers in 1935 deliberately excluded African Americans from the Social Security system because of prevailing racial biases during that period. This article examines both the logic of this thesis and the available empirical evidence on the origins of the coverage exclusions. The author concludes that the racial-bias thesis is both conceptually flawed and unsupported by the existing empirical evidence. The exclusion of agricultural and domestic workers from the early program was due to considerations of administrative feasibility involving tax-collection procedures. The author finds no evidence of any other policy motive involving racial bias. PMID:21261169

  19. Numb is not a critical regulator of Notch-mediated cell fate decisions in the developing chick inner ear

    PubMed Central

    Eddison, Mark; Weber, Sara J.; Ariza-McNaughton, Linda; Lewis, Julian; Daudet, Nicolas

    2015-01-01

    The Notch signaling pathway controls differentiation of hair cells and supporting cells in the vertebrate inner ear. Here, we have investigated whether Numb, a known regulator of Notch activity in Drosophila, is involved in this process in the embryonic chick. The chicken homolog of Numb is expressed throughout the otocyst at early stages of development and is concentrated at the basal pole of the cells. It is asymmetrically allocated at some cell divisions, as in Drosophila, suggesting that it could act as a determinant inherited by one of the two daughter cells and favoring adoption of a hair-cell fate. To test the implication of Numb in hair cell fate decisions and the regulation of Notch signaling, we used different methods to overexpress Numb at different stages of inner ear development. We found that sustained or late Numb overexpression does not promote hair cell differentiation, and Numb does not prevent the reception of Notch signaling. Surprisingly, none of the Numb-overexpressing cells differentiated into hair cells, suggesting that high levels of Numb protein could interfere with intracellular processes essential for hair cell survival. However, when Numb was overexpressed early and more transiently during ear development, no effect on hair cell formation was seen. These results suggest that in the inner ear at least, Numb does not significantly repress Notch activity and that its asymmetric distribution in dividing precursor cells does not govern the choice between hair cell and supporting cell fates. PMID:25814931

  20. Slit/Robo signaling regulates cell fate decisions in the intestinal stem cell lineage of Drosophila

    PubMed Central

    Biteau, Benoît; Jasper, Heinrich

    2014-01-01

    To maintain tissue homeostasis, cell fate decisions within stem cell lineages have to respond to the needs of the tissue. This coordination of lineage choices with regenerative demand remains poorly characterized. Here we identify a signal from enteroendocrine cells (EEs) that controls lineage specification in the Drosophila intestine. We find that EEs secrete Slit, a ligand for the Robo2 receptor in stem cells (ISCs) that limits ISC commitment to the endocrine lineage, establishing negative feedback control of EE regeneration. We further show that this lineage decision is made within ISCs and requires induction of the transcription factor Prospero in ISCs. Our work identifies a new function for the conserved Slit/Robo pathway in the regulation of adult stem cells, establishing negative feedback control of ISC lineage specification as a critical strategy to preserve tissue homeostasis. Our results further amend the current understanding of cell fate commitment within the Drosophila ISC lineage. PMID:24931602

  1. Slit/Robo signaling regulates cell fate decisions in the intestinal stem cell lineage of Drosophila.

    PubMed

    Biteau, Benoît; Jasper, Heinrich

    2014-06-26

    In order to maintain tissue homeostasis, cell fate decisions within stem cell lineages have to respond to the needs of the tissue. This coordination of lineage choices with regenerative demand remains poorly characterized. Here, we identify a signal from enteroendocrine cells (EEs) that controls lineage specification in the Drosophila intestine. We find that EEs secrete Slit, a ligand for the Robo2 receptor in intestinal stem cells (ISCs) that limits ISC commitment to the endocrine lineage, establishing negative feedback control of EE regeneration. Furthermore, we show that this lineage decision is made within ISCs and requires induction of the transcription factor Prospero in ISCs. Our work identifies a function for the conserved Slit/Robo pathway in the regulation of adult stem cells, establishing negative feedback control of ISC lineage specification as a critical strategy to preserve tissue homeostasis. Our results further amend the current understanding of cell fate commitment within the Drosophila ISC lineage. PMID:24931602

  2. 78 FR 44685 - Amendments to the 2013 Mortgage Rules Under the Real Estate Settlement Procedures Act (Regulation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-24

    ... Final Rule), 78 FR 6407 (Jan. 30, 2013). \\2\\ Mortgage Servicing Rules Under the Real Estate Settlement... Final Rules), 78 FR 10695 (Feb. 14, 2013) (Regulation X), 78 FR 10901 (Feb. 14, 2013) (Regulation Z). \\3\\ Amendments to the 2013 Escrows Final Rule under the Truth in Lending Act (Regulation Z), 78 FR 30739 (May...

  3. 78 FR 13298 - Notice of Retrospective Review of the Americans With Disabilities Act Regulations for Over-the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ... Statement in the Federal Register published on April 11, 2000 (65 FR 19477). FOR FURTHER INFORMATION CONTACT... Act Regulations for Over-the-Road Bus Operators; Request for Comments AGENCY: Office of the Secretary...) implementing regulations for over-the-road bus (OTRB) operators. The DOT will review regulations specified...

  4. Revision of Department of Justice Freedom of Information Act and Privacy Act Regulations and Implementation of Electronic Freedom of Information Act Amendments of 1996--DoJ. Proposed Rule.

    PubMed

    1997-08-26

    This document sets forth proposed revision of the Department's regulations under both the Freedom of Information Act (FOIA) and the Privacy Act of 1974. The FOIA and Privacy Act regulations have been streamlined and condensed, in accordance with the principles of the National Performance Reviews. With more "user-friendly" language wherever possible. These revisions also reflect the principles established by President Clinton and Attorney General Reno in their FOIA Policy Memoranda of October 4, 1993. The new statement of discretionary disclosure policy will supercede the existing regulation regarding discretionary access to records of historical interest. Additionally, the regulations have been updated to reflect developments in the case law and to include updated cost figures to be used in calculating and charging fees. These proposed revisions also contain new provisions implementing the Electronic Freedom of Information Act Amendments of 1996. PMID:10169840

  5. Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration

    PubMed Central

    Bernis, Cyril; Swift-Taylor, Beth; Nord, Matthew; Carmona, Sarah; Chook, Yuh Min; Forbes, Douglass J.

    2014-01-01

    The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin β for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin β, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107–160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin β and transportin “global positioning system”or “GPS” pathways that are mechanistically parallel. PMID:24478460

  6. 29 CFR 1905.41 - Summary decision.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 5 2011-07-01 2011-07-01 false Summary decision. 1905.41 Section 1905.41 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR RULES OF... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Summary Decisions § 1905.41 Summary decision. (a) No genuine...

  7. 29 CFR 1905.41 - Summary decision.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Summary decision. 1905.41 Section 1905.41 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR RULES OF... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Summary Decisions § 1905.41 Summary decision. (a) No genuine...

  8. 20 CFR 355.37 - Initial decision.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Initial decision. 355.37 Section 355.37... REGULATIONS UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.37 Initial decision. (a) The ALJ shall issue an initial decision based only on the record, which shall contain findings of fact, conclusions...

  9. 17 CFR 201.56 - Decision.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Decision. 201.56 Section 201... Regulations Pertaining to the Equal Access to Justice Act § 201.56 Decision. The administrative law judge shall issue an initial decision on the application promptly after completion of proceedings on...

  10. Vav1 Regulates Mesenchymal Stem Cell Differentiation Decision Between Adipocyte and Chondrocyte via Sirt1.

    PubMed

    Qu, Peng; Wang, Lizhen; Min, Yongfen; McKennett, Lois; Keller, Jonathan R; Lin, P Charles

    2016-07-01

    Mesenchymal stem cells (MSCs) are multipotent stromal cells residing in the bone marrow. MSCs have the potential to differentiate to adipocytes, chondrocytes, and other types of cells. In this study, we investigated the molecular mechanism that controls MSC cell fate decisions for differentiation. We found that Vav1, a guanine nucleotide exchange factor for Rho GTPase, was highly expressed in MSCs. Interestingly, loss of Vav1 in MSCs led to spontaneous adipogenic but impaired chondrogenic differentiation, and accordingly Vav1 null mice displayed an increase in fat content and a decrease in cartilage. Conversely, ectopic expression of Vav1 in MSCs reversed this phenotype, and led to enhanced MSC differentiation into chondrocyte but retarded adipogenesis. Mechanistically, loss of Vav1 reduced the level of Sirt1, which was responsible for an increase of acetylated PPARγ. As acetylation activates PPARγ, it increased C/EBPα expression and promoted adipogenesis. On the other hand, loss of Vav1 resulted in an increase of acetylated Sox9, a target of Sirt1. As acetylation represses Sox9 activity, it led to a dramatic reduction of collagen 2α1, a key regulator in chondrocyte differentiation. Finally, we found that Vav1 regulates Sirt1 in MSCs through Creb. Together this study reveals a novel function of Vav1 in regulating MSC cell fate decisions for differentiation through Sirt1. Sirt1 deacetylates PPARγ and Sox9, two key mediators that control adipocyte and chondrocyte differentiation. The acetylation status of PPARγ and Sox9 has opposite effects on its activity, thereby controlling cell fate decision. Stem Cells 2016;34:1934-1946. PMID:26990002

  11. The Arabidopsis LYST INTERACTING PROTEIN 5 Acts in Regulating Abscisic Acid Signaling and Drought Response.

    PubMed

    Xia, Zongliang; Huo, Yongjin; Wei, Yangyang; Chen, Qiansi; Xu, Ziwei; Zhang, Wei

    2016-01-01

    Multivesicular bodies (MVBs) are unique endosomes containing vesicles in the lumens and play essential roles in many eukaryotic cellular processes. The Arabidopsis LYST INTERACTING PROTEIN 5 (LIP5), a positive regulator of MVB biogenesis, has critical roles in biotic and abiotic stress responses. However, whether the abscisic acid (ABA) signaling is involved in LIP5-mediated stress response is largely unknown. Here, we report that LIP5 functions in regulating ABA signaling and drought response in Arabidopsis. Analyses of a LIP5 promoter-β-glucuronidase (GUS) construct revealed substantial GUS activity in whole seedlings. The expression of LIP5 was induced by ABA and drought, and overexpression of LIP5 led to ABA hypersensitivity, enhanced stomatal closure, reduced water loss, and, therefore, increased drought tolerance. On the contrary, LIP5 knockdown mutants showed ABA-insensitive phenotypes and reduced drought tolerance; suggesting that LIP5 acts in regulating ABA response. Further analysis using a fluorescent dye revealed that ABA and water stress induced cell endocytosis or vesicle trafficking in a largely LIP5-dependent manner. Furthermore, expression of several drought- or ABA-inducible marker genes was significantly down-regulated in the lip5 mutant seedlings. Collectively, our data suggest that LIP5 positively regulates drought tolerance through ABA-mediated cell signaling. PMID:27313589

  12. The Arabidopsis LYST INTERACTING PROTEIN 5 Acts in Regulating Abscisic Acid Signaling and Drought Response

    PubMed Central

    Xia, Zongliang; Huo, Yongjin; Wei, Yangyang; Chen, Qiansi; Xu, Ziwei; Zhang, Wei

    2016-01-01

    Multivesicular bodies (MVBs) are unique endosomes containing vesicles in the lumens and play essential roles in many eukaryotic cellular processes. The Arabidopsis LYST INTERACTING PROTEIN 5 (LIP5), a positive regulator of MVB biogenesis, has critical roles in biotic and abiotic stress responses. However, whether the abscisic acid (ABA) signaling is involved in LIP5-mediated stress response is largely unknown. Here, we report that LIP5 functions in regulating ABA signaling and drought response in Arabidopsis. Analyses of a LIP5 promoter-β-glucuronidase (GUS) construct revealed substantial GUS activity in whole seedlings. The expression of LIP5 was induced by ABA and drought, and overexpression of LIP5 led to ABA hypersensitivity, enhanced stomatal closure, reduced water loss, and, therefore, increased drought tolerance. On the contrary, LIP5 knockdown mutants showed ABA-insensitive phenotypes and reduced drought tolerance; suggesting that LIP5 acts in regulating ABA response. Further analysis using a fluorescent dye revealed that ABA and water stress induced cell endocytosis or vesicle trafficking in a largely LIP5-dependent manner. Furthermore, expression of several drought- or ABA-inducible marker genes was significantly down-regulated in the lip5 mutant seedlings. Collectively, our data suggest that LIP5 positively regulates drought tolerance through ABA-mediated cell signaling. PMID:27313589

  13. Identification of trans-acting factors regulating SamDC expression in Oryza sativa

    SciTech Connect

    Basu, Supratim; Roychoudhury, Aryadeep; Sengupta, Dibyendu N.

    2014-03-07

    Highlights: • Identification of cis elements responsible for SamDC expression by in silico analysis. • qPCR analysis of SamDC expression to abiotic and biotic stress treatments. • Detection of SamDC regulators using identified cis-elements as probe by EMSA. • Southwestern Blot analysis to predict the size of the trans-acting factors. - Abstract: Abiotic stress affects the growth and productivity of crop plants; to cope with the adverse environmental conditions, plants have developed efficient defense machinery comprising of antioxidants like phenolics and flavonoids, and osmolytes like polyamines. SamDC is a key enzyme in the polyamine biosynthesis pathway in plants. In our present communication we have done in silico analysis of the promoter region of SamDC to look for the presence of different cis-regulatory elements contributing to its expression. Based on the presence of different cis-regulatory elements we completed comparative analysis of SamDC gene expression in rice lamina of IR-29 and Nonabokra by qPCR in response to the abiotic stress treatments of salinity, drought, cold and the biotic stress treatments of ABA and light. Additionally, to explore the role of the cis-regulatory elements in regulating the expression of SamDC gene in plants we comparatively analyzed the binding of rice nuclear proteins prepared from IR-29 and Nonabokra undergoing various stress treatments. The intensity of the complex formed was low and inducible in IR-29 in contrast to Nonabokra. Southwestern blot analysis helped in predicting the size of the trans-acting factors binding to these cis-elements. To our knowledge this is the first report on the comprehensive analysis of SamDC gene expression in rice and identification of the trans-acting factors regulating its expression.

  14. Index of Federal Regulations and Court Cases on the Implementation of Section 504 of the Rehabilitation Act of 1973.

    ERIC Educational Resources Information Center

    California State and Consumer Services Agency, Sacramento. Office of Statewide Compliance Coordination.

    This index is divided into two sections: an Index on Federal Regulations and an Abstracts section of Court Cases and Administrative Decisions. Section 1 provides a topic index and comparison of contents and coverage of 16 federal departments with regulations established as of August 1981. Presented in tabular form, this index shows major topics…

  15. The European "clinical trial" regulation; relationship with the Jardé Act: a Giens workshop.

    PubMed

    Lemaire, François; Marchenay, Brigitte; Chassany, Olivier; Barthélémy, Philippe; Bouzzagou, Mohamed; Comet, Denis; Delval, Cécile; Dubray, Claude; Fouret, Cécile; Frija-Orvoen, Elisabeth; Gambotti, Laetitia; Lamarque, Véronique; d'Orsay, Geneviève; Plattner, Valérie; Sibenaler, Claire; Roux, Jacques; Thoby, Frédérique

    2015-01-01

    In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency. PMID:25679191

  16. Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly.

    PubMed

    Lettice, Laura A; Horikoshi, Taizo; Heaney, Simon J H; van Baren, Marijke J; van der Linde, Herma C; Breedveld, Guido J; Joosse, Marijke; Akarsu, Nurten; Oostra, Ben A; Endo, Naoto; Shibata, Minoru; Suzuki, Mikio; Takahashi, Eiichi; Shinka, Toshikatsu; Nakahori, Yutaka; Ayusawa, Dai; Nakabayashi, Kazuhiko; Scherer, Stephen W; Heutink, Peter; Hill, Robert E; Noji, Sumihare

    2002-05-28

    Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (Ssq). The genetic lesions in both lie within the same respective intron of the LMBR1/Lmbr1 gene, which resides approximately 1 Mb away from Shh. Genetic analysis of Ssq reveals that the Lmbr1 gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of Shh. This regulator is most likely the target for generating PPD mutations in human. PMID:12032320

  17. Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly

    PubMed Central

    Lettice, Laura A.; Horikoshi, Taizo; Heaney, Simon J. H.; van Baren, Marijke J.; van der Linde, Herma C.; Breedveld, Guido J.; Joosse, Marijke; Akarsu, Nurten; Oostra, Ben A.; Endo, Naoto; Shibata, Minoru; Suzuki, Mikio; Takahashi, Eiichi; Shinka, Toshikatsu; Nakahori, Yutaka; Ayusawa, Dai; Nakabayashi, Kazuhiko; Scherer, Stephen W.; Heutink, Peter; Hill, Robert E.; Noji, Sumihare

    2002-01-01

    Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (Ssq). The genetic lesions in both lie within the same respective intron of the LMBR1/Lmbr1 gene, which resides ≈1 Mb away from Shh. Genetic analysis of Ssq reveals that the Lmbr1 gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of Shh. This regulator is most likely the target for generating PPD mutations in human. PMID:12032320

  18. Knowledge of the animal welfare act and animal welfare regulations influences attitudes toward animal research.

    PubMed

    Metzger, Mitchell M

    2015-01-01

    Recent public-opinion polls indicate that Americans have shown a decline in support for animal experimentation, and several reports suggest a relationship between people's knowledge of animal welfare regulations and their attitudes toward animal research. Therefore, this study was designed to assess respondent's knowledge of several provisions in the Animal Welfare Act (AWA) and Animal Welfare Regulations (AWR), and determine whether exposure to elements of this legislation would influence an individual's attitudes toward the use of animals in research. A survey was used to assess knowledge of animal research regulations and attitudes toward animal research from a sample of individuals recruited through Amazon's Mechanical Turk crowdsourcing marketplace. Results from study 1 confirmed the hypothesis that respondents had little knowledge of various federal regulations that govern animal research activities. Data from study 2 revealed that exposure to elements of the AWA and AWR influenced participants' attitudes toward the use of animals in research. These results suggest that providing information to the general public about the AWA and AWR that protect laboratory animals from abuse and neglect may help alleviate concerns about using animals in research settings. PMID:25651094

  19. Knowledge of the Animal Welfare Act and Animal Welfare Regulations Influences Attitudes toward Animal Research

    PubMed Central

    2015-01-01

    Recent public-opinion polls indicate that Americans have shown a decline in support for animal experimentation, and several reports suggest a relationship between people's knowledge of animal welfare regulations and their attitudes toward animal research. Therefore, this study was designed to assess respondent's knowledge of several provisions in the Animal Welfare Act (AWA) and Animal Welfare Regulations (AWR), and determine whether exposure to elements of this legislation would influence an individual's attitudes toward the use of animals in research. A survey was used to assess knowledge of animal research regulations and attitudes toward animal research from a sample of individuals recruited through Amazon's Mechanical Turk crowdsourcing marketplace. Results from study 1 confirmed the hypothesis that respondents had little knowledge of various federal regulations that govern animal research activities. Data from study 2 revealed that exposure to elements of the AWA and AWR influenced participants’ attitudes toward the use of animals in research. These results suggest that providing information to the general public about the AWA and AWR that protect laboratory animals from abuse and neglect may help alleviate concerns about using animals in research settings. PMID:25651094

  20. APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation

    PubMed Central

    Shu, R; Wong, W; Ma, Q H; Yang, Z Z; Zhu, H; Liu, F J; Wang, P; Ma, J; Yan, S; Polo, J M; Bernard, C C A; Stanton, L W; Dawe, G S; Xiao, Z C

    2015-01-01

    Amyloid precursor protein (APP) is best known for its involvement in the pathogenesis of Alzheimer's disease. We have previously demonstrated that APP intracellular domain (AICD) regulates neurogenesis; however, the mechanisms underlying AICD-mediated regulation of neuronal differentiation are not yet fully characterized. Using genome-wide chromatin immunoprecipitation approaches, we found that AICD is specifically recruited to the regulatory regions of several microRNA genes, and acts as a transcriptional regulator for miR-663, miR-3648 and miR-3687 in human neural stem cells. Functional assays show that AICD negatively modulates neuronal differentiation through miR-663, a primate-specific microRNA. Microarray data further demonstrate that miR-663 suppresses the expression of multiple genes implicated in neurogenesis, including FBXL18 and CDK6. Our results indicate that AICD has a novel role in suppression of neuronal differentiation via transcriptional regulation of miR-663 in human neural stem cells. PMID:25695604

  1. The Neuropeptide Allatostatin A Regulates Metabolism and Feeding Decisions in Drosophila.

    PubMed

    Hentze, Julie L; Carlsson, Mikael A; Kondo, Shu; Nässel, Dick R; Rewitz, Kim F

    2015-01-01

    Coordinating metabolism and feeding is important to avoid obesity and metabolic diseases, yet the underlying mechanisms, balancing nutrient intake and metabolic expenditure, are poorly understood. Several mechanisms controlling these processes are conserved in Drosophila, where homeostasis and energy mobilization are regulated by the glucagon-related adipokinetic hormone (AKH) and the Drosophila insulin-like peptides (DILPs). Here, we provide evidence that the Drosophila neuropeptide Allatostatin A (AstA) regulates AKH and DILP signaling. The AstA receptor gene, Dar-2, is expressed in both the insulin and AKH producing cells. Silencing of Dar-2 in these cells results in changes in gene expression and physiology associated with reduced DILP and AKH signaling and animals lacking AstA accumulate high lipid levels. This suggests that AstA is regulating the balance between DILP and AKH, believed to be important for the maintenance of nutrient homeostasis in response to changing ratios of dietary sugar and protein. Furthermore, AstA and Dar-2 are regulated differentially by dietary carbohydrates and protein and AstA-neuronal activity modulates feeding choices between these types of nutrients. Our results suggest that AstA is involved in assigning value to these nutrients to coordinate metabolic and feeding decisions, responses that are important to balance food intake according to metabolic needs. PMID:26123697

  2. TrkB/BDNF Signaling Regulates Photoreceptor Progenitor Cell Fate Decisions

    PubMed Central

    Turner, Brian A.; Sparrow, Janet; Cai, Bolin; Monroe, Julie; Mikawa, Takashi; Hempstead, Barbara L.

    2008-01-01

    Neurotrophins, via activation of Trk receptor tyrosine kinases, serve as mitogens, survival factors and regulators of arborization during retinal development. Brain-derived neurotrophic factor (BDNF) and TrkB regulate neuronal arborization and survival in late retinal development. However, TrkB is expressed during early retinal developmet where its functions are unclear. To assess TrkB/BDNF actions in the early chick retina, replication-incompetent retroviruses were utilized to over-express a dominant negative truncated form of TrkB (trunc TrkB), or BDNF and effects were assessed at E15. Clones expressing trunc TrkB were smaller than controls, and proliferation and apoptosis assays suggest that decreased clone size correlated with increased cell death when BDNF/TrkB signaling was impaired. Analysis of clonal composition revealed that trunc TrkB over-expression decreased photoreceptor numbers (41%) and increased cell numbers in the middle third of the inner nuclear layer (INL) (23%). Conversely, BDNF over-expression increased photoreceptor numbers (25%) and decreased INL numbers (17%). Photoreceptors over-expressing trunc TrkB demonstrated no increase in apoptosis nor abnormalities in lamination suggesting that TrkB activation is not required for photoreceptor cell survival or migration. These studies suggest that TrkB signaling regulates commitment to and/or differentiation of photoreceptor cells from retinal progenitor cells, identifying a novel role for TrkB/BDNF in regulating cell fate decisions. PMID:17005175

  3. 38 CFR 26.7 - VA environmental decision making and documents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... environmental decision making and documents. (a) Relevant environmental documents shall accompany other decision documents as they proceed through the decision-making process. (b) The major decision points for VA actions... observing the provisions of these regulations, VA must act in accordance with CEQ Regulations, 40 CFR...

  4. 38 CFR 26.7 - VA environmental decision making and documents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... environmental decision making and documents. (a) Relevant environmental documents shall accompany other decision documents as they proceed through the decision-making process. (b) The major decision points for VA actions... observing the provisions of these regulations, VA must act in accordance with CEQ Regulations, 40 CFR...

  5. 38 CFR 26.7 - VA environmental decision making and documents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... environmental decision making and documents. (a) Relevant environmental documents shall accompany other decision documents as they proceed through the decision-making process. (b) The major decision points for VA actions... observing the provisions of these regulations, VA must act in accordance with CEQ Regulations, 40 CFR...

  6. 38 CFR 26.7 - VA environmental decision making and documents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... environmental decision making and documents. (a) Relevant environmental documents shall accompany other decision documents as they proceed through the decision-making process. (b) The major decision points for VA actions... observing the provisions of these regulations, VA must act in accordance with CEQ Regulations, 40 CFR...

  7. Identification of trans-acting factors regulating SamDC expression in Oryza sativa.

    PubMed

    Basu, Supratim; Roychoudhury, Aryadeep; Sengupta, Dibyendu N

    2014-03-01

    Abiotic stress affects the growth and productivity of crop plants; to cope with the adverse environmental conditions, plants have developed efficient defense machinery comprising of antioxidants like phenolics and flavonoids, and osmolytes like polyamines. SamDC is a key enzyme in the polyamine biosynthesis pathway in plants. In our present communication we have done in silico analysis of the promoter region of SamDC to look for the presence of different cis-regulatory elements contributing to its expression. Based on the presence of different cis-regulatory elements we completed comparative analysis of SamDC gene expression in rice lamina of IR-29 and Nonabokra by qPCR in response to the abiotic stress treatments of salinity, drought, cold and the biotic stress treatments of ABA and light. Additionally, to explore the role of the cis-regulatory elements in regulating the expression of SamDC gene in plants we comparatively analyzed the binding of rice nuclear proteins prepared from IR-29 and Nonabokra undergoing various stress treatments. The intensity of the complex formed was low and inducible in IR-29 in contrast to Nonabokra. Southwestern blot analysis helped in predicting the size of the trans-acting factors binding to these cis-elements. To our knowledge this is the first report on the comprehensive analysis of SamDC gene expression in rice and identification of the trans-acting factors regulating its expression. PMID:24530223

  8. 75 FR 35338 - Implementation of Regulations Required Under Title XI of the Food, Conservation and Energy Act of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    ...-AB07 Implementation of Regulations Required Under Title XI of the Food, Conservation and Energy Act of... participants regarding compliance. In enacting Title XI of the Food, Conservation and Energy Act of 2008 (Farm..., and its coverage was to encompass the complete chain of commerce and give the Secretary of...

  9. 76 FR 39007 - Native American Graves Protection and Repatriation Act Regulations- Definition of “Indian Tribe”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ... Office of the Secretary of the Interior 43 CFR Part 10 RIN 1024-AD98 Native American Graves Protection... regulations implementing the Native American Graves Protection and Repatriation Act (NAGPRA) removes the... implementation of the Native American Graves Protection and Repatriation Act, including the issuance...

  10. 21 CFR 1271.10 - Are my HCT/P's regulated solely under section 361 of the PHS Act and the regulations in this part...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Are my HCT/P's regulated solely under section 361... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS,...

  11. 21 CFR 1271.10 - Are my HCT/P's regulated solely under section 361 of the PHS Act and the regulations in this part...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Are my HCT/P's regulated solely under section 361... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS,...

  12. MecA Protein Acts as a Negative Regulator of Genetic Competence in Streptococcus mutans

    PubMed Central

    Tian, Xiao-Lin; Dong, Gaofeng; Liu, Tianlei; Gomez, Zubelda A.; Wahl, Astrid; Hols, Pascal

    2013-01-01

    Streptococcus mutans develops competence for genetic transformation through a complex network that receives inputs from at least two signaling peptides, competence-stimulating peptide (CSP) and sigX-inducing peptide (XIP). The key step of competence induction is the transcriptional activation of comX, which encodes an alternative sigma factor, SigX (σX), controlling the expression of late competence genes essential for DNA uptake and recombination. In this study, we provide evidence that MecA acts as a negative regulator in the posttranslational regulation of SigX in S. mutans. Using luxAB transcriptional reporter strains, we demonstrate that MecA represses the expression of late competence genes in S. mutans grown in a complex medium that is subpermissive for competence induction by CSP. The negative regulation of competence by MecA requires the presence of a functional SigX. Accordingly, inactivation of MecA results in a prolonged competence state of S. mutans under this condition. We have also found that the AAA+ protease ClpC displays a similar repressing effect on late competence genes, suggesting that both MecA and ClpC function coordinately to regulate competence in the same regulatory circuit in S. mutans. This suggestion is strongly supported by the results of bacterial two-hybrid assays, which demonstrate that MecA interacts with both SigX and ClpC, forming a ternary SigX-MecA-ClpC complex. Western blot analysis also confirms that inactivation of MecA or ClpC results in the intracellular accumulation of the SigX in S. mutans. Together, our data support the notion that MecA mediates the formation of a ternary SigX-MecA-ClpC complex that sequesters SigX and thereby negatively regulates genetic competence in S. mutans. PMID:24039267

  13. 14-3-3 family members act coordinately to regulate mitotic progression.

    PubMed

    Dalal, Sorab N; Yaffe, Michael B; DeCaprio, James A

    2004-05-01

    The mitosis promoting phosphatase, cdc25C, is a target of both the DNA replication and DNA damage checkpoint pathways. These pathways regulate cdc25C function, in part, by promoting the association of cdc25C with 14-3-3 proteins, which results in the retention of cdc25C in the cytoplasm. To determine which 14-3-3 proteins were required to regulate cdc25C function, we tested the ability of various 14-3-3 family members to form a complex with and negatively regulate cdc25C in human cells. Two 14-3-3 family members, 14-3-3epsilon and 14-3-3gamma specifically formed a complex with cdc25C but not with the 14-3-3 binding defective cdc25C mutant, S216A. In addition, 14-3-3epsilon and 14-3-3gamma inhibited the ability of cdc25C, but not the S216A mutant, to induce premature chromatin condensation (PCC) in U-2OS cells. These results suggested that the reduction in PCC by 14-3-3epsilon and 14-3-3gamma was due to inhibition of cdc25C function. In contrast, 14-3-3sigma was unable to form a complex with cdc25C, but was able to inhibit the ability of both wild type cdc25C and S216A to induce PCC. This suggests that 14-3-3sigma regulates entry into mitosis independently of cdc25C and 14-3-3epsilon and 14-3-3gamma. Thus, specific members of the 14-3-3 family of proteins may act coordinately to maintain the DNA replication checkpoint by regulating the activity of different cell cycle proteins. PMID:15107609

  14. Application of decision-making theory to the regulation of muscular work rate during self-paced competitive endurance activity.

    PubMed

    Renfree, Andrew; Martin, Louise; Micklewright, Dominic; St Clair Gibson, Alan

    2014-02-01

    Successful participation in competitive endurance activities requires continual regulation of muscular work rate in order to maximise physiological performance capacities, meaning that individuals must make numerous decisions with regards to the muscular work rate selected at any point in time. Decisions relating to the setting of appropriate goals and the overall strategic approach to be utilised are made prior to the commencement of an event, whereas tactical decisions are made during the event itself. This review examines current theories of decision-making in an attempt to explain the manner in which regulation of muscular work is achieved during athletic activity. We describe rational and heuristic theories, and relate these to current models of regulatory processes during self-paced exercise in an attempt to explain observations made in both laboratory and competitive environments. Additionally, we use rational and heuristic theories in an attempt to explain the influence of the presence of direct competitors on the quality of the decisions made during these activities. We hypothesise that although both rational and heuristic models can plausibly explain many observed behaviours in competitive endurance activities, the complexity of the environment in which such activities occur would imply that effective rational decision-making is unlikely. However, at present, many proposed models of the regulatory process share similarities with rational models. We suggest enhanced understanding of the decision-making process during self-paced activities is crucial in order to improve the ability to understand regulation of performance and performance outcomes during athletic activity. PMID:24113898

  15. Eya 1 acts as a critical regulator for specifying the metanephric mesenchyme.

    PubMed

    Sajithlal, Gangadharan; Zou, Dan; Silvius, Derek; Xu, Pin-Xian

    2005-08-15

    Although it is well established that the Gdnf-Ret signal transduction pathway initiates metanephric induction, no single regulator has yet been identified to specify the metanephric mesenchyme or blastema within the intermediate mesoderm, the earliest step of metanephric kidney development and the molecular mechanisms controlling Gdnf expression are essentially unknown. Previous studies have shown that a loss of Eya 1 function leads to renal agenesis that is a likely result of failure of metanephric induction. The studies presented here demonstrate that Eya 1 specifies the metanephric blastema within the intermediate mesoderm at the caudal end of the nephrogenic cord. In contrast to its specific roles in metanephric development, Eya 1 appears dispensable for the formation of nephric duct and mesonephric tubules. Using a combination of null and hypomorphic Eya 1 mutants, we now demonstrated that approximately 20% of normal Eya 1 protein level is sufficient for establishing the metanephric blastema and inducing the ureteric bud formation but not for its normal branching. Using Eya 1, Gdnf, Six 1 and Pax 2 mutant mice, we show that Eya 1 probably functions at the top of the genetic hierarchy controlling kidney organogenesis and it acts in combination with Six 1 and Pax 2 to regulate Gdnf expression during UB outgrowth and branching. These findings uncover an essential function for Eya 1 as a critical determination factor in acquiring metanephric fate within the intermediate mesoderm and as a key regulator of Gdnf expression during ureteric induction and branching morphogenesis. PMID:16018995

  16. Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity

    PubMed Central

    Yang, Chao-Shun; Chang, Kung-Yen; Dang, Jason; Rana, Tariq M.

    2016-01-01

    The polycomb repressive complex 1 (PRC1) is a multi-subunit complex that plays critical roles in the epigenetic modulation of gene expression. Here, we show that the PRC1 component polycomb group ring finger 6 (Pcgf6) is required to maintain embryonic stem cell (ESC) identity. In contrast to canonical PRC1, Pcgf6 acts as a positive regulator of transcription and binds predominantly to promoters bearing active chromatin marks. Pcgf6 is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulators Oct4, Sox2, and Nanog. Conversely, Pcgf6 overexpression prevents downregulation of these factors and impairs differentiation. In addition, Pcgf6 enhanced reprogramming in both mouse and human somatic cells. The genomic binding profile of Pcgf6 is highly similar to that of trithorax group proteins, but not of PRC1 or PRC2 complexes, suggesting that Pcgf6 functions atypically in ESCs. Our data reveal novel roles for Pcgf6 in directly regulating Oct4, Nanog, Sox2, and Lin28 expression to maintain ESC identity. PMID:27247273

  17. Epithelial IL-1R2 acts as a homeostatic regulator during remission of ulcerative colitis

    PubMed Central

    Mora-Buch, R; Dotti, I; Planell, N; Calderón-Gómez, E; Jung, P; Masamunt, M C; Llach, J; Ricart, E; Batlle, E; Panés, J; Salas, A

    2016-01-01

    Ulcerative colitis (UC) is a chronic intestinal inflammatory disease that may undergo periods of activity followed by remission. We aimed to identify the endogenous regulatory mechanisms that may promote disease remission. Transcriptional and protein analysis of the intestinal mucosa revealed that the IL-1 decoy receptor, interleukin-1 receptor type 2 (IL1R2), was upregulated in remission compared with active UC and controls. We identified epithelial cells as being responsible for increased IL-1R2 production during remission. Expression of IL1R2 was negatively regulated by Wnt/beta-catenin signals in colonic crypts or epithelial stem cell cultures; accordingly, epithelial stem cells upregulated IL-1R2 upon differentiation. Blocking IL-1R2 in isolated colonic crypt cultures of UC patients in remission and T-cell cultures stimulated with biopsy supernatant from UC patients in remission boosted IL-1β-dependent production of inflammation-related cytokines. Finally, IL1R2 transcription was significantly lower in patients that relapsed during a 1-year follow-up period compared with those in endoscopic remission. Collectively, our results reveal that the IL-1/IL-1R2 axis is differentially regulated in the remitting intestinal mucosa of UC patients. We hypothesize that IL-1R2 in the presence of low concentrations of IL-1β may act locally as a regulator of intestinal homeostasis. PMID:26530134

  18. 78 FR 30296 - Revisions to Oil Pipeline Regulations Pursuant to the Energy Policy Act of 1992; Notice of Annual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Revisions to Oil Pipeline Regulations Pursuant to the Energy Policy Act of 1992; Notice of Annual Change in the Producer Price Index for Finished Goods The Commission's regulations include a methodology for oil...

  19. 77 FR 29997 - Revisions to Oil Pipeline Regulations Pursuant to the Energy Policy Act of 1992; Notice of Annual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Revisions to Oil Pipeline Regulations Pursuant to the Energy Policy Act of 1992; Notice of Annual Change in the Producer Price Index for Finished Goods The Commission's regulations include a methodology for oil...

  20. 76 FR 28966 - Revisions to Oil Pipeline Regulations Pursuant to the Energy Policy Act of 1992; Notice of Annual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Revisions to Oil Pipeline Regulations Pursuant to the Energy Policy Act of 1992; Notice of Annual Change in the Producer Price Index for Finished Goods The Commission's regulations include a methodology for oil...

  1. The decision to germinate is regulated by divergent molecular networks in spores and seeds.

    PubMed

    Vesty, Eleanor F; Saidi, Younousse; Moody, Laura A; Holloway, Daniel; Whitbread, Amy; Needs, Sarah; Choudhary, Anushree; Burns, Bethany; McLeod, Daniel; Bradshaw, Susan J; Bae, Hansol; King, Brian Christopher; Bassel, George W; Simonsen, Henrik Toft; Coates, Juliet C

    2016-08-01

    Dispersal is a key step in land plant life cycles, usually via formation of spores or seeds. Regulation of spore- or seed-germination allows control over the timing of transition from one generation to the next, enabling plant dispersal. A combination of environmental and genetic factors determines when seed germination occurs. Endogenous hormones mediate this decision in response to the environment. Less is known about how spore germination is controlled in earlier-evolving nonseed plants. Here, we present an in-depth analysis of the environmental and hormonal regulation of spore germination in the model bryophyte Physcomitrella patens (Aphanoregma patens). Our data suggest that the environmental signals regulating germination are conserved, but also that downstream hormone integration pathways mediating these responses in seeds were acquired after the evolution of the bryophyte lineage. Moreover, the role of abscisic acid and diterpenes (gibberellins) in germination assumed much greater importance as land plant evolution progressed. We conclude that the endogenous hormone signalling networks mediating germination in response to the environment may have evolved independently in spores and seeds. This paves the way for future research about how the mechanisms of plant dispersal on land evolved. PMID:27257104

  2. Regulating outdoor advertisement boards; employing spatial decision support system to control urban visual pollution

    NASA Astrophysics Data System (ADS)

    Wakil, K.; Hussnain, MQ; Tahir, A.; Naeem, M. A.

    2016-06-01

    Unmanaged placement, size, location, structure and contents of outdoor advertisement boards have resulted in severe urban visual pollution and deterioration of the socio-physical living environment in urban centres of Pakistan. As per the regulatory instruments, the approval decision for a new advertisement installation is supposed to be based on the locational density of existing boards and their proximity or remoteness to certain land- uses. In cities, where regulatory tools for the control of advertisement boards exist, responsible authorities are handicapped in effective implementation due to the absence of geospatial analysis capacity. This study presents the development of a spatial decision support system (SDSS) for regularization of advertisement boards in terms of their location and placement. The knowledge module of the proposed SDSS is based on provisions and restrictions prescribed in regulatory documents. While the user interface allows visualization and scenario evaluation to understand if the new board will affect existing linear density on a particular road and if it violates any buffer restrictions around a particular land use. Technically the structure of the proposed SDSS is a web-based solution which includes open geospatial tools such as OpenGeo Suite, GeoExt, PostgreSQL, and PHP. It uses three key data sets including road network, locations of existing billboards and building parcels with land use information to perform the analysis. Locational suitability has been calculated using pairwise comparison through analytical hierarchy process (AHP) and weighted linear combination (WLC). Our results indicate that open geospatial tools can be helpful in developing an SDSS which can assist solving space related iterative decision challenges on outdoor advertisements. Employing such a system will result in effective implementation of regulations resulting in visual harmony and aesthetic improvement in urban communities.

  3. Acting Decisively: China's Story

    ERIC Educational Resources Information Center

    Kohn, Gerald W.; Harvey, James J.

    2009-01-01

    During a 10-day visit to China last year, 25 American superintendents observed a global giant in pursuit of educational excellence. In this article, two of the travelers reflect on what they learned from their experience and what it could mean for Americans. They saw a profound respect for education and pride in learning. They also found support…

  4. atonal regulates neurite arborization but does not act as a proneural gene in the Drosophila brain

    NASA Technical Reports Server (NTRS)

    Hassan, B. A.; Bermingham, N. A.; He, Y.; Sun, Y.; Jan, Y. N.; Zoghbi, H. Y.; Bellen, H. J.

    2000-01-01

    Drosophila atonal (ato) is the proneural gene of the chordotonal organs (CHOs) in the peripheral nervous system (PNS) and the larval and adult photoreceptor organs. Here, we show that ato is expressed at multiple stages during the development of a lineage of central brain neurons that innervate the optic lobes and are required for eclosion. A novel fate mapping approach shows that ato is expressed in the embryonic precursors of these neurons and that its expression is reactivated in third instar larvae (L3). In contrast to its function in the PNS, ato does not act as a proneural gene in the embryonic brain. Instead, ato performs a novel function, regulating arborization during larval and pupal development by interacting with Notch.

  5. Enhancer of zeste acts as a major developmental regulator of Ciona intestinalis embryogenesis

    PubMed Central

    Le Goff, Emilie; Martinand-Mari, Camille; Martin, Marianne; Feuillard, Jérôme; Boublik, Yvan; Godefroy, Nelly; Mangeat, Paul; Baghdiguian, Stephen; Cavalli, Giacomo

    2015-01-01

    ABSTRACT The paradigm of developmental regulation by Polycomb group (PcG) proteins posits that they maintain silencing outside the spatial expression domains of their target genes, particularly of Hox genes, starting from mid embryogenesis. The Enhancer of zeste [E(z)] PcG protein is the catalytic subunit of the PRC2 complex, which silences its targets via deposition of the H3K27me3 mark. Here, we studied the ascidian Ciona intestinalis counterpart of E(z). Ci-E(z) is detected by immunohistochemistry as soon as the 2- and 4-cell stages as a cytoplasmic form and becomes exclusively nuclear thereafter, whereas the H3K27me3 mark is detected starting from the gastrula stage and later. Morpholino invalidation of Ci-E(z) leads to the total disappearance of both Ci-E(z) protein and its H3K27me3 mark. Ci-E(z) morphants display a severe phenotype. Strikingly, the earliest defects occur at the 4-cell stage with the dysregulation of cell positioning and mitotic impairment. At later stages, Ci-E(z)-deficient embryos are affected by terminal differentiation defects of neural, epidermal and muscle tissues, by the failure to form a notochord and by the absence of caudal nerve. These major phenotypic defects are specifically rescued by injection of a morpholino-resistant Ci-E(z) mRNA, which restores expression of Ci-E(z) protein and re-deposition of the H3K27me3 mark. As observed by qPCR analyses, Ci-E(z) invalidation leads to the early derepression of tissue-specific developmental genes, whereas late-acting developmental genes are generally down-regulated. Altogether, our results suggest that Ci-E(z) plays a major role during embryonic development in Ciona intestinalis by silencing early-acting developmental genes in a Hox-independent manner. PMID:26276097

  6. Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

    PubMed Central

    Wang, Hongyan; Somers, Gregory W.; Bashirullah, Arash; Heberlein, Ulrike; Yu, Fengwei; Chia, William

    2006-01-01

    The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Neural progenitors of the Drosophila post-embryonic brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which divides terminally to produce two differentiating neuronal/glial daughters. Here we show that Aurora-A (AurA) acts as a tumor suppressor by suppressing NB self-renewal and promoting neuronal differentiation. In aurA loss-of-function mutants, supernumerary NBs are produced at the expense of neurons. AurA suppresses tumor formation by asymmetrically localizing atypical protein kinase C (aPKC), an NB proliferation factor. Numb, which also acts as a tumor suppressor in larval brains, is a major downstream target of AurA and aPKC. Notch activity is up-regulated in aurA and numb larval brains, and Notch signaling is necessary and sufficient to promote NB self-renewal and suppress differentiation in larval brains. Our data suggest that AurA, aPKC, Numb, and Notch function in a pathway that involved a series of negative genetic interactions. We have identified a novel mechanism for controlling the balance between self-renewal and neuronal differentiation during the asymmetric division of Drosophila larval NBs. PMID:17182870

  7. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells.

    PubMed

    Trapnell, Cole; Cacchiarelli, Davide; Grimsby, Jonna; Pokharel, Prapti; Li, Shuqiang; Morse, Michael; Lennon, Niall J; Livak, Kenneth J; Mikkelsen, Tarjei S; Rinn, John L

    2014-04-01

    Defining the transcriptional dynamics of a temporal process such as cell differentiation is challenging owing to the high variability in gene expression between individual cells. Time-series gene expression analyses of bulk cells have difficulty distinguishing early and late phases of a transcriptional cascade or identifying rare subpopulations of cells, and single-cell proteomic methods rely on a priori knowledge of key distinguishing markers. Here we describe Monocle, an unsupervised algorithm that increases the temporal resolution of transcriptome dynamics using single-cell RNA-Seq data collected at multiple time points. Applied to the differentiation of primary human myoblasts, Monocle revealed switch-like changes in expression of key regulatory factors, sequential waves of gene regulation, and expression of regulators that were not known to act in differentiation. We validated some of these predicted regulators in a loss-of function screen. Monocle can in principle be used to recover single-cell gene expression kinetics from a wide array of cellular processes, including differentiation, proliferation and oncogenic transformation. PMID:24658644

  8. ABORTED MICROSPORES Acts as a Master Regulator of Pollen Wall Formation in Arabidopsis.

    PubMed

    Xu, Jie; Ding, Zhiwen; Vizcay-Barrena, Gema; Shi, Jianxin; Liang, Wanqi; Yuan, Zheng; Werck-Reichhart, Danièle; Schreiber, Lukas; Wilson, Zoe A; Zhang, Dabing

    2014-04-29

    Mature pollen is covered by durable cell walls, principally composed of sporopollenin, an evolutionary conserved, highly resilient, but not fully characterized, biopolymer of aliphatic and aromatic components. Here, we report that ABORTED MICROSPORES (AMS) acts as a master regulator coordinating pollen wall development and sporopollenin biosynthesis in Arabidopsis thaliana. Genome-wide coexpression analysis revealed 98 candidate genes with specific expression in the anther and 70 that showed reduced expression in ams. Among these 70 members, we showed that AMS can directly regulate 23 genes implicated in callose dissociation, fatty acids elongation, formation of phenolic compounds, and lipidic transport putatively involved in sporopollenin precursor synthesis. Consistently, ams mutants showed defective microspore release, a lack of sporopollenin deposition, and a dramatic reduction in total phenolic compounds and cutin monomers. The functional importance of the AMS pathway was further demonstrated by the observation of impaired pollen wall architecture in plant lines with reduced expression of several AMS targets: the abundant pollen coat protein extracellular lipases (EXL5 and EXL6), and CYP98A8 and CYP98A9, which are enzymes required for the production of phenolic precursors. These findings demonstrate the central role of AMS in coordinating sporopollenin biosynthesis and the secretion of materials for pollen wall patterning. PMID:24781116

  9. PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator

    PubMed Central

    Kim, Yoosik; Lee, Jung Hyun; Park, Jong-Eun; Cho, Jun; Yi, Hyerim; Kim, V. Narry

    2014-01-01

    dsRNA-dependent protein kinase R (PKR) is a ubiquitously expressed enzyme well known for its roles in immune response. Upon binding to viral dsRNA, PKR undergoes autophosphorylation, and the phosphorylated PKR (pPKR) regulates translation and multiple signaling pathways in infected cells. Here, we found that PKR is activated in uninfected cells, specifically during mitosis, by binding to dsRNAs formed by inverted Alu repeats (IRAlus). While PKR and IRAlu-containing RNAs are segregated in the cytosol and nucleus of interphase cells, respectively, they interact during mitosis when nuclear structure is disrupted. Once phosphorylated, PKR suppresses global translation by phosphorylating the α subunit of eukaryotic initiation factor 2 (eIF2α). In addition, pPKR acts as an upstream kinase for c-Jun N-terminal kinase and regulates the levels of multiple mitotic factors such as CYCLINS A and B and POLO-LIKE KINASE 1 and phosphorylation of HISTONE H3. Disruption of PKR activation via RNAi or expression of a transdominant-negative mutant leads to misregulation of the mitotic factors, delay in mitotic progression, and defects in cytokinesis. Our study unveils a novel function of PKR and endogenous dsRNAs as signaling molecules during the mitosis of uninfected cells. PMID:24939934

  10. Gamma-aminobutyric acid acts as a specific virulence regulator in Pseudomonas aeruginosa.

    PubMed

    Dagorn, Audrey; Hillion, Mélanie; Chapalain, Annelise; Lesouhaitier, Olivier; Duclairoir Poc, Cécile; Vieillard, Julien; Chevalier, Sylvie; Taupin, Laure; Le Derf, Franck; Feuilloley, Marc G J

    2013-02-01

    Gamma-aminobutyric acid (GABA) is widespread in the environment and can be used by animal and plants as a communication molecule. Pseudomonas species, in particular fluorescent ones, synthesize GABA and express GABA-binding proteins. In this study, we investigated the effects of GABA on the virulence of Pseudomonas aeruginosa. While exposure to GABA (10 µM) did not modify either the growth kinetics or the motility of the bacterium, its cytotoxicity and virulence were strongly increased. The Caenorhabditis elegans 'fast killing test' model revealed that GABA acts essentially through an increase in diffusible toxin(s). GABA also modulates the biofilm formation activity and adhesion properties of PAO1. GABA has no effect on cell surface polarity, biosurfactant secretion or on the lipopolysaccharide structure. The production of several exo-enzymes, pyoverdin and exotoxin A is not modified by GABA but we observed an increase in cyanogenesis which, by itself, could explain the effect of GABA on P. aeruginosa virulence. This mechanism appears to be regulated by quorum sensing. A proteomic analysis revealed that the effect of GABA on cyanogenesis is correlated with a reduction of oxygen accessibility and an over-expression of oxygen-scavenging proteins. GABA also promotes specific changes in the expression of thermostable and unstable elongation factors Tuf/Ts involved in the interaction of the bacterium with the host proteins. Taken together, these results suggest that GABA is a physiological regulator of P. aeruginosa virulence. PMID:23154974

  11. Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis.

    PubMed

    Prévost, Gaëtan; Jeandel, Lydie; Arabo, Arnaud; Coëffier, Moïse; El Ouahli, Mariama; Picot, Marie; Alexandre, David; Gobet, Françoise; Leprince, Jérôme; Berrahmoune, Hind; Déchelotte, Pierre; Malagon, Maria; Bonner, Caroline; Kerr-Conte, Julie; Chigr, Fatiha; Lefebvre, Hervé; Anouar, Youssef; Chartrel, Nicolas

    2015-08-01

    26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is upregulated in obese animal models, and its orexigenic activity is accentuated in rodents fed a high-fat diet, suggesting that this neuropeptide might play a role in the development and maintenance of the obese status. As obesity is frequently associated with type 2 diabetes, we investigated whether 26RFa may be involved in the regulation of glucose homeostasis. In the current study, we show a moderate positive correlation between plasma 26RFa levels and plasma insulin in patients with diabetes. Plasma 26RFa concentration also increases in response to an oral glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103 are present in human pancreatic β-cells as well as in the gut. In mice, 26RFa attenuates the hyperglycemia induced by a glucose load, potentiates insulin sensitivity, and increases plasma insulin concentrations. Consistent with these data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we show, using in vivo and in vitro approaches, that a glucose load induces a massive secretion of 26RFa by the small intestine. Altogether, the present data indicate that 26RFa acts as an incretin to regulate glucose homeostasis. PMID:25858563

  12. Neuropeptide Y acts in the paraventricular nucleus to suppress sympathetic nerve activity and its baroreflex regulation.

    PubMed

    Cassaglia, Priscila A; Shi, Zhigang; Li, Baoxin; Reis, Wagner L; Clute-Reinig, Nicholas M; Stern, Javier E; Brooks, Virginia L

    2014-04-01

    Neuropeptide Y (NPY), a brain neuromodulator that has been strongly implicated in the regulation of energy balance, also acts centrally to inhibit sympathetic nerve activity (SNA); however, the site and mechanism of action are unknown. In chloralose-anaesthetized female rats, nanoinjection of NPY into the paraventricular nucleus of the hypothalamus (PVN) dose-dependently suppressed lumbar SNA (LSNA) and its baroreflex regulation, and these effects were blocked by prior inhibition of NPY Y1 or Y5 receptors. Moreover, PVN injection of Y1 and Y5 receptor antagonists in otherwise untreated rats increased basal and baroreflex control of LSNA, indicating that endogenous NPY tonically inhibits PVN presympathetic neurons. The sympathoexcitation following blockade of PVN NPY inhibition was eliminated by prior PVN nanoinjection of the melanocortin 3/4 receptor inhibitor SHU9119. Moreover, presympathetic neurons, identified immunohistochemically using cholera toxin b neuronal tract tracing from the rostral ventrolateral medulla (RVLM), express NPY Y1 receptor immunoreactivity, and patch-clamp recordings revealed that both NPY and α-melanocyte-stimulating hormone (α-MSH) inhibit and stimulate, respectively, PVN-RVLM neurons. Collectively, these data suggest that PVN NPY inputs converge with α-MSH to influence presympathetic neurons. Together these results identify endogenous NPY as a novel and potent inhibitory neuromodulator within the PVN that may contribute to changes in SNA that occur in states associated with altered energy balance, such as obesity and pregnancy. PMID:24535439

  13. Cis-acting elements in its 3' UTR mediate post-transcriptional regulation of KRAS.

    PubMed

    Kim, Minlee; Kogan, Nicole; Slack, Frank J

    2016-03-15

    Multiple RNA-binding proteins and non-coding RNAs, such as microRNAs (miRNAs), are involved in post-transcriptional gene regulation through recognition motifs in the 3' untranslated region (UTR) of their target genes. The KRAS gene encodes a key signaling protein, and its messenger RNA (mRNA) contains an exceptionally long 3' UTR; this suggests that it may be subject to a highly complex set of regulatory processes. However, 3' UTR-dependent regulation of KRAS expression has not been explored in detail. Using extensive deletion and mutational analyses combined with luciferase reporter assays, we have identified inhibitory and stabilizing cis-acting regions within the KRAS 3' UTR that may interact with miRNAs and RNA-binding proteins, such as HuR. Particularly, we have identified an AU-rich 49-nt fragment in the KRAS 3' UTR that is required for KRAS 3' UTR reporter repression. This element contains a miR-185 complementary element, and we show that overexpression of miR-185 represses endogenous KRAS mRNA and protein in vitro. In addition, we have identified another 49-nt fragment that is required to promote KRAS 3' UTR reporter expression. These findings indicate that multiple cis-regulatory motifs in the 3' UTR of KRAS finely modulate its expression, and sequence alterations within a binding motif may disrupt the precise functions of trans-regulatory factors, potentially leading to aberrant KRAS expression. PMID:26930719

  14. Flavonoids act as negative regulators of auxin transport in vivo in arabidopsis

    NASA Technical Reports Server (NTRS)

    Brown, D. E.; Rashotte, A. M.; Murphy, A. S.; Normanly, J.; Tague, B. W.; Peer, W. A.; Taiz, L.; Muday, G. K.

    2001-01-01

    Polar transport of the plant hormone auxin controls many aspects of plant growth and development. A number of synthetic compounds have been shown to block the process of auxin transport by inhibition of the auxin efflux carrier complex. These synthetic auxin transport inhibitors may act by mimicking endogenous molecules. Flavonoids, a class of secondary plant metabolic compounds, have been suggested to be auxin transport inhibitors based on their in vitro activity. The hypothesis that flavonoids regulate auxin transport in vivo was tested in Arabidopsis by comparing wild-type (WT) and transparent testa (tt4) plants with a mutation in the gene encoding the first enzyme in flavonoid biosynthesis, chalcone synthase. In a comparison between tt4 and WT plants, phenotypic differences were observed, including three times as many secondary inflorescence stems, reduced plant height, decreased stem diameter, and increased secondary root development. Growth of WT Arabidopsis plants on naringenin, a biosynthetic precursor to those flavonoids with auxin transport inhibitor activity in vitro, leads to a reduction in root growth and gravitropism, similar to the effects of synthetic auxin transport inhibitors. Analyses of auxin transport in the inflorescence and hypocotyl of independent tt4 alleles indicate that auxin transport is elevated in plants with a tt4 mutation. In hypocotyls of tt4, this elevated transport is reversed when flavonoids are synthesized by growth of plants on the flavonoid precursor, naringenin. These results are consistent with a role for flavonoids as endogenous regulators of auxin transport.

  15. Neuropeptide Y acts in the paraventricular nucleus to suppress sympathetic nerve activity and its baroreflex regulation

    PubMed Central

    Cassaglia, Priscila A; Shi, Zhigang; Li, Baoxin; Reis, Wagner L; Clute-Reinig, Nicholas M; Stern, Javier E; Brooks, Virginia L

    2014-01-01

    Neuropeptide Y (NPY), a brain neuromodulator that has been strongly implicated in the regulation of energy balance, also acts centrally to inhibit sympathetic nerve activity (SNA); however, the site and mechanism of action are unknown. In chloralose-anaesthetized female rats, nanoinjection of NPY into the paraventricular nucleus of the hypothalamus (PVN) dose-dependently suppressed lumbar SNA (LSNA) and its baroreflex regulation, and these effects were blocked by prior inhibition of NPY Y1 or Y5 receptors. Moreover, PVN injection of Y1 and Y5 receptor antagonists in otherwise untreated rats increased basal and baroreflex control of LSNA, indicating that endogenous NPY tonically inhibits PVN presympathetic neurons. The sympathoexcitation following blockade of PVN NPY inhibition was eliminated by prior PVN nanoinjection of the melanocortin 3/4 receptor inhibitor SHU9119. Moreover, presympathetic neurons, identified immunohistochemically using cholera toxin b neuronal tract tracing from the rostral ventrolateral medulla (RVLM), express NPY Y1 receptor immunoreactivity, and patch-clamp recordings revealed that both NPY and α–melanocyte-stimulating hormone (α-MSH) inhibit and stimulate, respectively, PVN–RVLM neurons. Collectively, these data suggest that PVN NPY inputs converge with α-MSH to influence presympathetic neurons. Together these results identify endogenous NPY as a novel and potent inhibitory neuromodulator within the PVN that may contribute to changes in SNA that occur in states associated with altered energy balance, such as obesity and pregnancy. PMID:24535439

  16. Flavonoids act as negative regulators of auxin transport in vivo in arabidopsis.

    PubMed

    Brown, D E; Rashotte, A M; Murphy, A S; Normanly, J; Tague, B W; Peer, W A; Taiz, L; Muday, G K

    2001-06-01

    Polar transport of the plant hormone auxin controls many aspects of plant growth and development. A number of synthetic compounds have been shown to block the process of auxin transport by inhibition of the auxin efflux carrier complex. These synthetic auxin transport inhibitors may act by mimicking endogenous molecules. Flavonoids, a class of secondary plant metabolic compounds, have been suggested to be auxin transport inhibitors based on their in vitro activity. The hypothesis that flavonoids regulate auxin transport in vivo was tested in Arabidopsis by comparing wild-type (WT) and transparent testa (tt4) plants with a mutation in the gene encoding the first enzyme in flavonoid biosynthesis, chalcone synthase. In a comparison between tt4 and WT plants, phenotypic differences were observed, including three times as many secondary inflorescence stems, reduced plant height, decreased stem diameter, and increased secondary root development. Growth of WT Arabidopsis plants on naringenin, a biosynthetic precursor to those flavonoids with auxin transport inhibitor activity in vitro, leads to a reduction in root growth and gravitropism, similar to the effects of synthetic auxin transport inhibitors. Analyses of auxin transport in the inflorescence and hypocotyl of independent tt4 alleles indicate that auxin transport is elevated in plants with a tt4 mutation. In hypocotyls of tt4, this elevated transport is reversed when flavonoids are synthesized by growth of plants on the flavonoid precursor, naringenin. These results are consistent with a role for flavonoids as endogenous regulators of auxin transport. PMID:11402184

  17. Decree No. 0784 of 18 April 1989 regulating, in part, Act 21 of 1982 and Act 71 of 1988.

    PubMed

    1989-01-01

    This Colombian Decree regulates certain aspects of the system of family allowances. Among other things, it provides that allowances can be granted in terms of food, clothing, school scholarships, textbooks, drugs, and other substitutes for money. Further provisions of the Decree deal with the definition of persons affiliated to the regime, booklets certifying affiliation, family service subsidies, and financing. PMID:12344547

  18. Allowance trading under the Clean Air Act: Who should regulate, and when?

    SciTech Connect

    Lock, R.

    1993-07-01

    The goal of this paper is to explore how compliance with the Clean Air Act Amendments of 1990 (CAAA), especially Title IV and emission trading under it, will affect the current relationship between state and federal regulation. It is difficult, with the limited experience we have had under Title IV, to be definitive about or to be a very strong advocate of too many policy positions. What may be most helpful at this point is to identify where the difficult issues in state/federal relations might arise; and then to explore ways in which tensions might be either avoided or resolved. One anticipated conclusion is that a traditional regulatory mindset could be very destructive if applied to this new area of oversight without due sensitivity to what Congress is trying to achieve in Title IV. That concern pervaded the early legislative debates; and it persists today. Title IV presents some unique challenges to state regulators and will require some creative solutions and fresh thinking if the goals of Congress are to be realized and the full benefits that allowance trading can offer are to be reaped by electricity consumers. In the ultimate analysis, Title IV amounts to a massive internalization of the external costs imposed on society by acid rain deposition. (This places in serious question the notion of additional externality {open_quotes}adders{close_quotes} for sulfur dioxide (SO{sub 2}) and nitrous oxide (NO{sub x}) at the state level for utility supply planning purposes.) The whole point of Title IV is to give those directly charged with compliance, namely power producers, the maximum flexibility to pursue least-cost compliance solutions. Perhaps the biggest single factor in how well they do this will be how state regulators respond to their compliance and allowance trading initiatives.

  19. Decision-making in product portfolios of pharmaceutical research and development – managing streams of innovation in highly regulated markets

    PubMed Central

    Jekunen, Antti

    2014-01-01

    Decision-making is a core function of any drug development firm. Developing drugs demands a firm to be highly innovative, while at the same time the activity is strictly regulated. Successful drug development offers the right to apply for a long-term patent that confers exclusive marketing rights. This article addresses the issue of what constitutes an adequate portfolio of drugs for a drug development firm and how it might be managed successfully. The paper investigates decision-making in the industry and specifically in the development of oncology drugs from various perspectives: the need for decisions, their timing, decision-making at the project level, the optimal portfolio, tools for portfolio analysis, the evaluation of patents, and finally the importance of the drug portfolio. Drug development decisions as important organizational elements should get more emphasis, and decisions in drug portfolio using modern decision-making methods should be used more widely than what currently happens. Structured, informed decisions would help avoiding late terminations of drugs in Phase III development. An improved research and development pipeline and drug portfolio management are the major elements in the general strategy targeting success. PMID:25364229

  20. Decision-making in product portfolios of pharmaceutical research and development--managing streams of innovation in highly regulated markets.

    PubMed

    Jekunen, Antti

    2014-01-01

    Decision-making is a core function of any drug development firm. Developing drugs demands a firm to be highly innovative, while at the same time the activity is strictly regulated. Successful drug development offers the right to apply for a long-term patent that confers exclusive marketing rights. This article addresses the issue of what constitutes an adequate portfolio of drugs for a drug development firm and how it might be managed successfully. The paper investigates decision-making in the industry and specifically in the development of oncology drugs from various perspectives: the need for decisions, their timing, decision-making at the project level, the optimal portfolio, tools for portfolio analysis, the evaluation of patents, and finally the importance of the drug portfolio. Drug development decisions as important organizational elements should get more emphasis, and decisions in drug portfolio using modern decision-making methods should be used more widely than what currently happens. Structured, informed decisions would help avoiding late terminations of drugs in Phase III development. An improved research and development pipeline and drug portfolio management are the major elements in the general strategy targeting success. PMID:25364229

  1. 77 FR 4498 - Rules and Regulations Under the Wool Products Labeling Act of 1939

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-30

    ... Identification Act, the Wool Products Labeling Act, and the Fur Products Labeling Act: Final Rule, 63 FR 7508...: Miscellaneous Rules: Final Rule, 63 FR 71582 (Dec. 29, 1998). \\7\\ Federal Trade Commission: Rules and... Labeling Act of 1939, Final Rule, 65 FR 75154 (Dec. 1, 2000). \\8\\ The Wool Rules provide that...

  2. Serotonin 2A receptors contribute to the regulation of risk-averse decisions

    PubMed Central

    Macoveanu, Julian; Rowe, James B; Hornboll, Bettina; Elliott, Rebecca; Paulson, Olaf B; Knudsen, Gitte M; Siebner, Hartwig R

    2013-01-01

    Pharmacological studies point to a role of the neurotransmitter serotonin (5-HT) in regulating the preference for risky decisions, yet the functional contribution of specific 5-HT receptors remains to be clarified. We used pharmacological fMRI to investigate the role of the 5-HT2A receptors in processing negative outcomes and regulating risk-averse behavior. During fMRI, twenty healthy volunteers performed a gambling task under two conditions: with or without blocking the 5-HT2A receptors. The volunteers repeatedly chose between small, likely rewards and large, unlikely rewards. Choices were balanced in terms of expected utility and potential loss. Acute blockade of the 5-HT2A receptors with ketanserin made participants more risk-averse. Ketanserin selectively reduced the neural response of the frontopolar cortex to negative outcomes that were caused by low-risk choices and were associated with large missed rewards. In the context of normal 5-HT2A receptor function, ventral striatum displayed a stronger response to low-risk negative outcomes in risk-taking as opposed to risk-averse individuals. This (negative) correlation between the striatal response to low-risk negative outcomes and risk-averse choice behavior was abolished by 5-HT2A receptor blockade. The results provide the first evidence for a critical role of 5-HT2A receptor function in regulating risk-averse behavior. We suggest that the 5-HT2A receptor system facilitates risk-taking behavior by modulating the outcome evaluation of “missed” reward. These results have implications for understanding the neural basis of abnormal risk-taking behavior, for instance in pathological gamblers. PMID:23810974

  3. Users guide to working in and around water: Regulation under British Columbia`s Water Act. Revised edition

    SciTech Connect

    1998-12-01

    This booklet has been published to help understand and comply with the Regulation under the British Columbia Water Act for works and changes in and about a stream. Works carried out under the Regulation are those that do not involve water diversion, may be completed within a short period of time, and have little environmental impact. Examples include installation or removal of culverts or docks, repair of dikes, beaver dam removal, and installation of drain tile outlets. Information is included on definitions of terms, scope of the Regulation, general conditions for projects, specific project requirements, notification requirements, and enforcement. A copy of the Regulation is included.

  4. The differential regulation of human ACT1 isoforms by Hsp90 in IL-17 signaling1

    PubMed Central

    Wu, Ling; Wang, Chenhui; Boisson, Bertrand; Misra, Saurav; Rayman, Patricia; Finke, James H.; Puel, Anne; Casanova, Jean-Laurent; Li, Xiaoxia

    2014-01-01

    IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of autoimmune diseases including psoriasis. ACT1 is an essential adaptor molecule in the IL-17 signaling pathway. A missense single nucleotide polymorphism (rs33980500; SNP-D10N) that resulted in the substitution of an asparagine for an aspartic acid at position 10 of ACT1 (ACT1-D10N) is associated with psoriasis susceptibility. Due to alternative splicing in humans, SNP-D10N encodes two mutated ACT1 proteins, ACT1-D10N and ACT1-D19N. Though both ACT1 isoforms are Hsp90 ‘client’ proteins, the nine additional amino acids in ACT1-D19N provide an additional Hsp90 binding site that is absent in ACT1-D10N. Therefore, while ACT1-D10N is a dead protein that is unable to transduce IL-17 signals for gene expression, ACT1-D19N is fully responsive to IL-17. Intriguingly, the two ACT1 isoforms are differentially expressed in ACT1D10N/D10N fibroblasts and T cells. Fibroblasts express both isoforms equally, enabling ACT1-D19N to compensate for the loss of ACT1-D10N function. ACT1D10N/D10N T cells, however, express predominantly ACT1-D10N. Lacking this compensatory mechanism, ACT1D10N/D10N T cells behave like ACT1-deficient T cells, exhibiting a dysregulated and hyperactive Th17 phenotype with overproduction of IL-22 and IL-17. The hyperactive Th17 response combined with fully responsive fibroblasts likely synergized to contribute to psoriasis susceptibility in SNP-D10N patients. PMID:25024377

  5. The differential regulation of human ACT1 isoforms by Hsp90 in IL-17 signaling.

    PubMed

    Wu, Ling; Wang, Chenhui; Boisson, Bertrand; Misra, Saurav; Rayman, Patricia; Finke, James H; Puel, Anne; Casanova, Jean-Laurent; Li, Xiaoxia

    2014-08-15

    IL-17 is a proinflammatory cytokine implicated in the pathogenesis of autoimmune diseases including psoriasis. ACT1 is an essential adaptor molecule in the IL-17 signaling pathway. A missense single nucleotide polymorphism (rs33980500; SNP-D10N) that resulted in the substitution of an asparagine for an aspartic acid at position 10 of ACT1 (ACT1-D10N) is associated with psoriasis susceptibility. Due to alternative splicing in humans, SNP-D10N encodes two mutated ACT1 proteins, ACT1-D10N and ACT1-D19N. Although both ACT1 isoforms are Hsp90 client proteins, the nine additional amino acids in ACT1-D19N provide an additional Hsp90 binding site that is absent in ACT1-D10N. Therefore, whereas ACT1-D10N is a dead protein that is unable to transduce IL-17 signals for gene expression, ACT1-D19N is fully responsive to IL-17. Intriguingly, the two ACT1 isoforms are differentially expressed in ACT1(D10N/D10N) fibroblasts and T cells. Fibroblasts express both isoforms equally, enabling ACT1-D19N to compensate for the loss of ACT1-D10N function. ACT1(D10N/D10N) T cells, however, express predominantly ACT1-D10N. Lacking this compensatory mechanism, ACT1(D10N/D10N) T cells behave like ACT1-deficient T cells, exhibiting a dysregulated and hyperactive Th17 phenotype with overproduction of IL-22 and IL-17. The hyperactive Th17 response combined with fully responsive fibroblasts likely synergized to contribute to psoriasis susceptibility in SNP-D10N patients. PMID:25024377

  6. Some impacts of the 1990 Clean Air Act and state clean-air regulations on the fertilizer industry

    SciTech Connect

    Breed, C.E.; Kerns, O.S.

    1992-12-01

    The Clean Air Act amendments of 1990 will intensify national efforts to reduce air pollution. They will have major impacts an governmental agencies and on industrial and commercial facilities throughout the country. As with other industries, it is essential for fertilizer dealers and producers to understand how these changes to the Clean Air Act can significantly change the way they do business. This paper is proffered as an overview of ways in which the 1990 amendments to the Clean Air Act may impact the fertilizer industry. The nonattainment, toxics, and permit provisions of the amended act will be three areas of particular concern to the fertilizer industry. Implementation of the new regulatory requirements of this legislation promises to be a long and onerous process for all concerned. However, it appears that state and local regulations may have a much more profound impact on the fertilizer industry than the new Clean Air Act.

  7. Some impacts of the 1990 Clean Air Act and state clean-air regulations on the fertilizer industry

    SciTech Connect

    Breed, C.E.; Kerns, O.S.

    1992-12-31

    The Clean Air Act amendments of 1990 will intensify national efforts to reduce air pollution. They will have major impacts on governmental agencies and on industrial and commercial facilities throughout the country. As with other industries, it is essential for fertilizer dealers and producers to understand how these changes to the Clean Air Act can significantly change the way they do business. This paper is proffered as an overview of ways in which the 1990 amendments to the Clean Air Act may impact the fertilizer industry. The nonattainment, toxics, and permit provisions of the amended act will be three areas of particular concern to the fertilizer industry. Implementation of the new regulatory requirements of this legislation promises to be a long and onerous process for all concerned. However, it appears that state and local regulations may have a much more profound impact on the fertilizer industry than the new Clean Air Act.

  8. Testing decision rules for categorizing species' extinction risk to help develop quantitative listing criteria for the U.S. Endangered Species Act.

    PubMed

    Regan, Tracey J; Taylor, Barbara L; Thompson, Grant G; Cochrane, Jean Fitts; Ralls, Katherine; Runge, Michael C; Merrick, Richard

    2013-08-01

    Lack of guidance for interpreting the definitions of endangered and threatened in the U.S. Endangered Species Act (ESA) has resulted in case-by-case decision making leaving the process vulnerable to being considered arbitrary or capricious. Adopting quantitative decision rules would remedy this but requires the agency to specify the relative urgency concerning extinction events over time, cutoff risk values corresponding to different levels of protection, and the importance given to different types of listing errors. We tested the performance of 3 sets of decision rules that use alternative functions for weighting the relative urgency of future extinction events: a threshold rule set, which uses a decision rule of x% probability of extinction over y years; a concave rule set, where the relative importance of future extinction events declines exponentially over time; and a shoulder rule set that uses a sigmoid shape function, where relative importance declines slowly at first and then more rapidly. We obtained decision cutoffs by interviewing several biologists and then emulated the listing process with simulations that covered a range of extinction risks typical of ESA listing decisions. We evaluated performance of the decision rules under different data quantities and qualities on the basis of the relative importance of misclassification errors. Although there was little difference between the performance of alternative decision rules for correct listings, the distribution of misclassifications differed depending on the function used. Misclassifications for the threshold and concave listing criteria resulted in more overprotection errors, particularly as uncertainty increased, whereas errors for the shoulder listing criteria were more symmetrical. We developed and tested the framework for quantitative decision rules for listing species under the U.S. ESA. If policy values can be agreed on, use of this framework would improve the implementation of the ESA by

  9. Cis-acting elements in its 3′ UTR mediate post-transcriptional regulation of KRAS

    PubMed Central

    Kim, Minlee; Kogan, Nicole; Slack, Frank J.

    2016-01-01

    Multiple RNA-binding proteins and non-coding RNAs, such as microRNAs (miRNAs), are involved in post-transcriptional gene regulation through recognition motifs in the 3′ untranslated region (UTR) of their target genes. The KRAS gene encodes a key signaling protein, and its messenger RNA (mRNA) contains an exceptionally long 3′ UTR; this suggests that it may be subject to a highly complex set of regulatory processes. However, 3′ UTR-dependent regulation of KRAS expression has not been explored in detail. Using extensive deletion and mutational analyses combined with luciferase reporter assays, we have identified inhibitory and stabilizing cis-acting regions within the KRAS 3′ UTR that may interact with miRNAs and RNA-binding proteins, such as HuR. Particularly, we have identified an AU-rich 49-nt fragment in the KRAS 3′ UTR that is required for KRAS 3′ UTR reporter repression. This element contains a miR-185 complementary element, and we show that overexpression of miR-185 represses endogenous KRAS mRNA and protein in vitro. In addition, we have identified another 49-nt fragment that is required to promote KRAS 3′ UTR reporter expression. These findings indicate that multiple cis-regulatory motifs in the 3′ UTR of KRAS finely modulate its expression, and sequence alterations within a binding motif may disrupt the precise functions of trans-regulatory factors, potentially leading to aberrant KRAS expression. PMID:26930719

  10. Alternative 3'UTRs act as scaffolds to regulate membrane protein localization

    PubMed Central

    Berkovits, Binyamin D.; Mayr, Christine

    2015-01-01

    About half of human genes use alternative cleavage and polyadenylation (ApA) to generate mRNA transcripts that differ in the length of their 3' untranslated regions (3'UTRs) while producing the same protein 1–3. Here we show in human cell lines that alternative 3' UTRs differentially regulate the localization of membrane proteins. The long 3'UTR of CD47 enables efficient cell surface expression of CD47 protein, whereas the short 3'UTR primarily localizes CD47 protein to the endoplasmic reticulum. CD47 protein localization occurs post-translationally and independently of RNA localization. In our model of 3' UTR-dependent protein localization, the long 3' UTR of CD47 acts as a scaffold to recruit a protein complex containing the RNA-binding protein HuR (also known as ELAVL1) and SET4 to the site of translation. This facilitates interaction of SET with the newly translated cytoplasmic domains of CD47 and results in subsequent translocation of CD47 to the plasma membrane via activated RAC1 5. We also show that CD47 protein has different functions depending on whether it was generated by the short or long 3'UTR isoforms. Thus, ApA contributes to the functional diversity of the proteome without changing the amino acid sequence. 3' UTR-dependent protein localization has the potential to be a widespread trafficking mechanism for membrane proteins because HuR binds to thousands of mRNAs6–9, and we show that the long 3' UTRs of CD44, ITGA1 and TNFRSF13C, which are bound by HuR, increase surface protein expression compared to their corresponding short 3' UTRs. We propose that during translation the scaffold function of 3' UTRs facilitates binding of proteins to nascent proteins to direct their transport or function—and that this role of 3' UTRs can be regulated by ApA. PMID:25896326

  11. 25 CFR 162.597 - Will BIA appeal bond regulations apply to cancellation decisions involving WSR leases?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Will BIA appeal bond regulations apply to cancellation decisions involving WSR leases? 162.597 Section 162.597 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER LEASES AND PERMITS Wind and Solar Resource Leases Wsr Lease...

  12. 25 CFR 162.597 - Will BIA appeal bond regulations apply to cancellation decisions involving WSR leases?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Will BIA appeal bond regulations apply to cancellation decisions involving WSR leases? 162.597 Section 162.597 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER LEASES AND PERMITS Wind and Solar Resource Leases Wsr Lease...

  13. Impact of Clean Air Act Regulations on Nitrogen Fate and Transport in the Neuse River Basin

    NASA Astrophysics Data System (ADS)

    Gabriel, M. C.; Knightes, C. D.; Dennis, R. L.; Cooter, E. J.

    2012-12-01

    This study investigated impacts of Clean Air Act Amendment (CAAA) NOx emissions regulations on the fate and transport of nitrogen for two watersheds in the Neuse River Basin, North Carolina, USA from 1990 to 2020. The Soil and Water Assessment Tool (SWAT) and the Community Multi-scale Air Quality (CMAQ) modeling system were used. CMAQ simulated atmospheric chemical transport and nitrogen deposition. This data was entered into SWAT which simulated watershed hydrology and water quality. Two cases were investigated: one that incorporates CAAA regulatory emissions controls in CMAQ simulation (with) and a second case that does not (without). SWAT model results forecasted a 70% decrease in inorganic nitrogen discharge from the Little River watershed and a 50% decrease for the Nahunta watershed by 2020 under the emission control (with) scenario. Denitrification and plant nitrogen uptake played important roles in nitrogen discharge from each watershed. The nitrogen discharge response time following a change in atmospheric nitrogen deposition was 4 years for the Nahunta watershed and 2 years for the Little River watershed. The longer response time for Nahunta is primarily due to a higher percentage of soybean land cover (22.5% [Nahunta]; 1.6% [Little River]). Agricultural land covers had varied nitrogen response times to changes in atmospheric deposition, particularly for soybean, hay and corn. The studied watersheds retained >80% of all nitrogen delivered by agriculture fertilization, biological fixation and atmospheric deposition.

  14. 21 CFR 1271.10 - Are my HCT/P's regulated solely under section 361 of the PHS Act and the regulations in this part...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES... objective intent; (3) The manufacture of the HCT/P does not involve the combination of the cells or tissues... not have a systemic effect and is not dependent upon the metabolic activity of living cells for...

  15. 21 CFR 1271.10 - Are my HCT/P's regulated solely under section 361 of the PHS Act and the regulations in this part...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES... objective intent; (3) The manufacture of the HCT/P does not involve the combination of the cells or tissues... not have a systemic effect and is not dependent upon the metabolic activity of living cells for...

  16. Forward genetics identifies Kdf1/1810019J16Rik as an essential regulator of the proliferation-differentiation decision in epidermal progenitor cells

    PubMed Central

    Lee, Sunjin; Kong, Yong; Weatherbee, Scott D.

    2013-01-01

    Cell fate decisions during embryogenesis and adult life govern tissue formation, homeostasis and repair. Two key decisions that must be tightly coordinated are proliferation and differentiation. Overproliferation can lead to hyperplasia or tumor formation while premature differentiation can result in a depletion of proliferating cells and organ failure. Maintaining this balance is especially important in tissues that undergo rapid turnover like skin however, despite recent advances, the genetic mechanisms that balance cell differentiation and proliferation are still unclear. In an unbiased genetic screen to identify genes affecting early development, we identified an essential regulator of the proliferation-differentiation balance in epidermal progenitor cells, the Keratinocyte differentiation factor 1 (Kdf1; 1810019J16Rik) gene. Kdf1 is expressed in epidermal cells from early stages of epidermis formation through adulthood. Specifically, Kdf1 is expressed both in epidermal progenitor cells where it acts to curb the rate of proliferation as well as in their progeny where it is required to block proliferation and promote differentiation. Consequently, Kdf1 mutants display both uncontrolled cell proliferation in the epidermis and failure to develop terminal fates. Our findings reveal a dual role for the novel gene Kdf1 both as a repressive signal for progenitor cell proliferation through its inhibition of p63 and a strong inductive signal for terminal differentiation through its interaction with the cell cycle regulator Stratifin. PMID:24075906

  17. Toward a multi-objective decision support framework to support regulations of unconventional oil and gas development

    NASA Astrophysics Data System (ADS)

    Alongi, M.; Howard, C.; Kasprzyk, J. R.; Ryan, J. N.

    2015-12-01

    Unconventional oil and gas development (UOGD) using hydraulic fracturing and horizontal drilling has recently fostered an unprecedented acceleration in energy development. Regulations seek to protect environmental quality of areas surrounding UOGD, while maintaining economic benefits. One such regulation is a setback distance, which dictates the minimum proximity between an oil and gas well and an object such as a residential or commercial building, property line, or water source. In general, most setback regulations have been strongly politically motivated without a clear scientific basis for understanding the relationship between the setback distance and various performance outcomes. This presentation discusses a new decision support framework for setback regulations, as part of a large NSF-funded sustainability research network (SRN) on UOGD. The goal of the decision support framework is to integrate a wide array of scientific information from the SRN into a coherent framework that can help inform policy regarding UOGD. The decision support framework employs multiobjective evolutionary algorithm (MOEA) optimization coupled with simulation models of air quality and other performance-based outcomes on UOGD. The result of the MOEA optimization runs are quantitative tradeoff curves among different objectives. For example, one such curve could demonstrate air pollution concentrations versus estimates of energy development profits, for different levels of setback distance. Our results will also inform policy-relevant discussions surrounding UOGD such as comparing single- and multi-well pads, as well as regulations on the density of well development over a spatial area.

  18. 31 CFR 501.740 - Decision of Administrative Law Judge.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Decision of Administrative Law Judge... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.740 Decision of Administrative Law Judge. The Administrative Law Judge shall prepare a decision that constitutes his or her final disposition of...

  19. 43 CFR 10010.50 - Implementing the decision.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... POLICY ACT Relationship to Decision-Making § 10010.50 Implementing the decision. The terms “monitoring” and “conditions” in 40 CFR 1505.3 of the CEQ regulations will be interpreted as being relevant to... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Implementing the decision....

  20. 43 CFR 10010.50 - Implementing the decision.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... POLICY ACT Relationship to Decision-Making § 10010.50 Implementing the decision. The terms “monitoring” and “conditions” in 40 CFR 1505.3 of the CEQ regulations will be interpreted as being relevant to... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Implementing the decision....

  1. 43 CFR 10010.50 - Implementing the decision.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... POLICY ACT Relationship to Decision-Making § 10010.50 Implementing the decision. The terms “monitoring” and “conditions” in 40 CFR 1505.3 of the CEQ regulations will be interpreted as being relevant to... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Implementing the decision....

  2. 43 CFR 10010.50 - Implementing the decision.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... POLICY ACT Relationship to Decision-Making § 10010.50 Implementing the decision. The terms “monitoring” and “conditions” in 40 CFR 1505.3 of the CEQ regulations will be interpreted as being relevant to... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Implementing the decision....

  3. 20 CFR 261.7 - Effect of revised decision.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Effect of revised decision. 261.7 Section 261.7 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ADMINISTRATIVE FINALITY § 261.7 Effect of revised decision. A revised decision is binding unless: (a) The...

  4. 45 CFR 1703.201 - Decision to hold meeting.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Decision to hold meeting. 1703.201 Section 1703.201 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL COMMISSION ON LIBRARIES AND INFORMATION SCIENCE GOVERNMENT IN THE SUNSHINE ACT Procedures Governing Decisions About Meetings § 1703.201 Decision to hold meeting....

  5. 29 CFR 102.117 - Freedom of Information Act Regulations: Board materials and formal documents available for public...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 2 2011-07-01 2011-07-01 false Freedom of Information Act Regulations: Board materials and formal documents available for public inspection and copying; requests for described records; time limit for response; appeal from denial of request; fees for document search and duplication; files and records not subject to inspection....

  6. 75 FR 8844 - Financial Crimes Enforcement Network; Amendment to the Bank Secrecy Act Regulations-Reports of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY 31 CFR Part 103 RIN 1506-AB08 Financial Crimes Enforcement Network; Amendment to the Bank Secrecy Act Regulations--Reports of Foreign Financial Accounts AGENCY: Financial Crimes Enforcement Network...

  7. 78 FR 6407 - Ability-to-Repay and Qualified Mortgage Standards Under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... underwriting standards. See 73 FR 44524 (July 30, 2008). The following discussion provides background... rulemaking authority by section 1029 of the Dodd- Frank Act). 76 FR 79768 (Dec. 22, 2011). This rule did not... Regulation Z. See 60 FR 15463 (Mar. 24, 1995). In particular, Sec. 226.32(e)(1) \\42\\ implemented TILA...

  8. 78 FR 23171 - Amendments to the 2013 Escrows Final Rule Under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-18

    ... loans made in ``rural'' or ``underserved'' areas. \\1\\ 78 FR 4726 (Jan. 22, 2013). \\2\\ The other rules...) (2013 ATR Final Rule), 78 FR 6407; High-Cost Mortgages and Homeownership Counseling Amendments to the... Settlement Procedures Act (Regulation X) (2013 HOEPA Final Rule), 78 FR 6855; Disclosure and...

  9. 75 FR 29526 - Revisions to Oil Pipeline Regulations Pursuant to the Energy Policy Act of 1992; Notice of Annual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission 61,161; Docket No. RM93-11-000] Revisions to Oil Pipeline Regulations Pursuant to the Energy Policy Act of 1992; Notice of Annual Change in the Producer Price Index for Finished Goods May 19, 2010. The...

  10. 78 FR 60381 - Amendments to the 2013 Mortgage Rules Under the Equal Credit Opportunity Act (Regulation B), Real...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... February 15, 2013, at 78 FR 11280. FOR FURTHER INFORMATION CONTACT: Whitney Patross, Attorney; Richard... Under the Truth in Lending Act (Regulation Z), 78 FR 4726 (Jan. 22, 2013) (2013 Escrows Final Rule...), 78 FR 6856 (Jan. 31, 2013) (2013 HOEPA Final Rule), and Ability-to-Repay and Qualified...

  11. 9 CFR 331.3 - States designated under paragraph 301(c) of the Act; application of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false States designated under paragraph 301(c) of the Act; application of regulations. 331.3 Section 331.3 Animals and Animal Products FOOD... DESIGNATED STATES AND TERRITORIES; AND FOR DESIGNATION OF ESTABLISHMENTS WHICH ENDANGER PUBLIC HEALTH AND...

  12. 9 CFR 381.222 - States designated under paragraph 5(c) of the Act; application of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false States designated under paragraph 5(c) of the Act; application of regulations. 381.222 Section 381.222 Animals and Animal Products FOOD... Designating Establishments With Operations Which Would Clearly Endanger the Public Health; Disposition...

  13. 78 FR 63408 - Petition To Amend Animal Welfare Act Regulations To Prohibit Public Contact With Big Cats, Bears...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... 5, 2013 (78 FR 47215) is reopened. We will consider all comments that we receive on or before.... SUPPLEMENTARY INFORMATION: On August 5, 2013, we published in the Federal Register (78 FR 47215-47217, Docket No... Animal Welfare Act Regulations To Prohibit Public Contact With Big Cats, Bears, and Nonhuman...

  14. 78 FR 30739 - Amendments to the 2013 Escrows Final Rule under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-23

    .... \\1\\ 78 FR 4726 (Jan. 22, 2013). \\2\\ The other rules include: Ability-to-Repay and Qualified Mortgage Standards under the Truth in Lending Act (Regulation Z) (2013 ATR Final Rule), 78 FR 6407 (Jan. 30, 2013...) (2013 HOEPA Final Rule), 78 FR 6855 (Jan. 31, 2013); Disclosure and Delivery Requirements for Copies...

  15. 75 FR 34271 - Federal Acquisition Regulation; FAR Case 2009-010, American Recovery and Reinvestment Act of 2009...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... Federal Register at 74 FR 14636 on March 31, 2009, with a request for comments by June 1, 2009. The... the Federal Register at 74 FR 14636 on March 31, 2009, is adopted as a final rule with the following... Acquisition Regulation; FAR Case 2009-010, American Recovery and Reinvestment Act of 2009 (the Recovery...

  16. 76 FR 10527 - Regulatory Flexibility Act: Section 610 Review of National Organic Program Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-25

    ... regulations implementing the National Organic Program (NOP) were published December 21, 2000 (65 FR 80548... FR 14827), its schedule to review certain regulations, including the NOP regulations, under criteria... Organic Program Regulations AGENCY: Agricultural Marketing Service, USDA. ACTION: Review and request...

  17. 31 CFR 501.740 - Decision of Administrative Law Judge.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Decision of Administrative Law Judge. 501.740 Section 501.740 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.740 Decision of Administrative Law Judge....

  18. 31 CFR 501.740 - Decision of Administrative Law Judge.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Decision of Administrative Law Judge. 501.740 Section 501.740 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.740 Decision of Administrative Law Judge....

  19. 31 CFR 501.747 - Procedures on remand of decisions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Procedures on remand of decisions. 501.747 Section 501.747 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.747 Procedures on remand of decisions. Either...

  20. 31 CFR 501.740 - Decision of Administrative Law Judge.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Decision of Administrative Law Judge. 501.740 Section 501.740 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.740 Decision of Administrative Law Judge....

  1. 31 CFR 501.747 - Procedures on remand of decisions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Procedures on remand of decisions. 501.747 Section 501.747 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.747 Procedures on remand of decisions. Either...

  2. 31 CFR 501.747 - Procedures on remand of decisions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Procedures on remand of decisions. 501.747 Section 501.747 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.747 Procedures on remand of decisions. Either...

  3. 31 CFR 501.747 - Procedures on remand of decisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Procedures on remand of decisions. 501.747 Section 501.747 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.747 Procedures on remand of decisions. Either...

  4. 31 CFR 501.740 - Decision of Administrative Law Judge.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Decision of Administrative Law Judge. 501.740 Section 501.740 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.740 Decision of Administrative Law Judge....

  5. 31 CFR 501.747 - Procedures on remand of decisions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Procedures on remand of decisions. 501.747 Section 501.747 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... REGULATIONS Trading With the Enemy Act (TWEA) Penalties § 501.747 Procedures on remand of decisions. Either...

  6. 75 FR 74770 - Final Treasury Decision; Comment Request for Regulation Project [127391-07], (TD 9403 Final)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-01

    ... Care Act of 2006. The regulations affect charitable remainder trusts that have UBTI in taxable years... approved by OMB. Type of Review: Extension of a currently approved collection. Affected Public: Businesses...) Whether the collection of information is necessary for the proper performance of the functions of...

  7. Coordination and decision making of regulation, operation, and market activities in power systems

    NASA Astrophysics Data System (ADS)

    Nakashima, Tomoaki

    Electric power has been traditionally supplied to customers at regulated rates by vertically integrated utilities (VIUs), which own generation, transmission, and distribution systems. However, the regulatory authorities of VIUs are promoting competition in their businesses to lower the price of electric energy. Consequently, in new deregulated circumstances, many suppliers and marketers compete in the generation market, and conflict of interest may often occur over transmission. Therefore, a neutral entity, called an independent system operator (ISO), which operates the power system independently, has been established to give market participants nondiscriminatory access to transmission sectors with a natural monopoly, and to facilitate competition in generation sectors. Several types of ISOs are established at present, with their respective regions and authorities. The ISO receives many requests from market participants to transfer power, and must evaluate the feasibility of their requests under the system's condition. In the near future, regulatory authorities may impose various objectives on the ISOs. Then, based on the regulators' policies, the ISO must determine the optimal schedules from feasible solutions, or change the market participants' requests. In a newly developed power market, market participants will conduct their transactions in order to maximize their profit. The most crucial information in conducting power transactions is price and demand. A direct transaction between suppliers and consumers may become attractive because of its stability of price, while in a power exchange market, gaming and speculation of participants may push up electricity prices considerably. To assist the consumers in making effective decisions, suitable methods for forecasting volatile market price are necessary. This research has been approached from three viewpoints: Firstly, from the system operator's point of view, desirable system operation and power market structure

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

    SciTech Connect

    Gaba, J.M.

    1990-12-31

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

  9. 76 FR 78130 - Mortgage Acts and Practices-Advertising (Regulation N); Mortgage Assistance Relief Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... Advance Notice of Proposed Rulemaking: Mortgage Acts and Practices, 74 FR 26118 (June 1, 2009), that.... See 76 FR 43569 (July 21, 2011). The Omnibus Appropriations Act, as amended, authorizes the Bureau to... response to a notice published at 76 FR 75825 (Dec. 5, 2011) concerning its efforts to identify...

  10. 75 FR 12377 - Native American Graves Protection and Repatriation Act Regulations-Disposition of Culturally...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-15

    ... first rules to implement the Act on December 4, 1995 (43 CFR part 10, 60 FR 62158). --We published rules for assessing civil penalties under the Act on April 3, 2003 (43 CFR 10.12, 68 FR 16354). --We....13, 72 FR 13189). --We are publishing this rule today. --We are developing additional rules to...

  11. 78 FR 41835 - Inflation Adjustments to the Price-Anderson Act Financial Protection Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ... consistent with the Plain Writing Act as well as the Presidential Memorandum, ``Plain Language in Government... made the initial changes to the Price-Anderson Act amounts on October 27, 2005 (70 FR 61885), and the first periodic inflation adjustments on September 29, 2008 (73 FR 56451). This final rule makes...

  12. When knowing what to do is not sufficient to make good decisions: deficient use of explicit understanding in remitted patients with histories of suicidal acts.

    PubMed

    Jollant, Fabrice; Guillaume, Sébastien; Jaussent, Isabelle; Bechara, Antoine; Courtet, Philippe

    2013-12-15

    Disadvantageous decision-making has been reported in patients who had attempted suicide and may represent a cognitive risk factor for suicide. Making decisions necessitates both implicit/associative and explicit/analytic processes. Here, we explored explicit mechanisms, and hypothesized that suicide attempters fail to use explicit understanding to make favorable choices. The Iowa Gambling Task (IGT) was used to assess decision-making in 151 non-depressed patients with a history of mood disorder and suicidal act, 81 non-depressed patients with a history of mood disorders but no suicidal act, and 144 healthy individuals. After performing the task, we assessed the explicit understanding of the participants of the contingencies in the task, i.e. which options yielded higher gain or loss. Correct explicit understanding was reported less often in suicide attempters and affective controls than in healthy controls (45.7% and 42.0% vs. 66.0%). Moreover, understanding was associated with better performance in healthy and affective controls, but not in suicide attempters, with no between-group difference among those who did not reach understanding. Patients with histories of suicide attempt, therefore, show a disconnection between what they "know" and what they "do", possibly reflecting underlying impairments in implicit associative processes. These cognitive alterations should be addressed in preventative interventions targeting suicide. PMID:23972765

  13. 25 CFR 101.10 - Federal Reserve Regulation Z and Fair Credit Reporting Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... subject to the provisions of Federal Reserve Regulation Z (Truth In Lending, 12 CFR part 226; Pub. L. 91... 25 Indians 1 2013-04-01 2013-04-01 false Federal Reserve Regulation Z and Fair Credit Reporting... ACTIVITIES LOANS TO INDIANS FROM THE REVOLVING LOAN FUND § 101.10 Federal Reserve Regulation Z and...

  14. 25 CFR 101.10 - Federal Reserve Regulation Z and Fair Credit Reporting Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... subject to the provisions of Federal Reserve Regulation Z (Truth In Lending, 12 CFR part 226; Pub. L. 91... 25 Indians 1 2010-04-01 2010-04-01 false Federal Reserve Regulation Z and Fair Credit Reporting... ACTIVITIES LOANS TO INDIANS FROM THE REVOLVING LOAN FUND § 101.10 Federal Reserve Regulation Z and...

  15. 25 CFR 101.10 - Federal Reserve Regulation Z and Fair Credit Reporting Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... subject to the provisions of Federal Reserve Regulation Z (Truth In Lending, 12 CFR part 226; Pub. L. 91... 25 Indians 1 2014-04-01 2014-04-01 false Federal Reserve Regulation Z and Fair Credit Reporting... ACTIVITIES LOANS TO INDIANS FROM THE REVOLVING LOAN FUND § 101.10 Federal Reserve Regulation Z and...

  16. 25 CFR 101.10 - Federal Reserve Regulation Z and Fair Credit Reporting Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... subject to the provisions of Federal Reserve Regulation Z (Truth In Lending, 12 CFR part 226; Pub. L. 91... 25 Indians 1 2011-04-01 2011-04-01 false Federal Reserve Regulation Z and Fair Credit Reporting... ACTIVITIES LOANS TO INDIANS FROM THE REVOLVING LOAN FUND § 101.10 Federal Reserve Regulation Z and...

  17. GP Supervisors' Experience in Supporting Self-Regulated Learning: A Balancing Act

    ERIC Educational Resources Information Center

    Sagasser, Margaretha H.; Kramer, Anneke W. M.; van Weel, Chris; van der Vleuten, Cees P. M.

    2015-01-01

    Self-regulated learning is essential for professional development and lifelong learning. As self-regulated learning has many inaccuracies, the need to support self-regulated learning has been recommended. Supervisors can provide such support. In a prior study trainees reported on the variation in received supervisor support. This study aims at…

  18. WORKING AND CARING: THE SIMULTANEOUS DECISION OF LABOR FORCE PARTICIPATION AND INFORMAL ELDERLY AND CHILD SUPPORT ACT IVITIES IN MEXICO*

    PubMed Central

    van Gameren, Edwin; Velandia Naranjo, Durfari

    2016-01-01

    We analyze factors determining women’s decisions to participate in the labor market and provide elderly care and nonfinancial support to their (grand)children. We use data from the Mexican Health and Aging Study, a survey of people aged 50 and over, applying a three-equation, reduced-form SUR model. Results suggest that care needs are the driving force behind caregiving activities. Traditional roles also appear to be relevant in the labor force participation decision: women with a closer labor market connection when they were young are more likely to work. Simulations of demographic changes illustrate potential effects for future caregiving and participation rates. PMID:26924883

  19. The Regulation of Medical Computer Software as a “Device” under the Food, Drug, and Cosmetic Act

    PubMed Central

    Brannigan, Vincent

    1986-01-01

    Recent developments in computer software have raised the possibility that federal regulators may claim to control medical computer software as a “device” under the Food, Drug and Cosmetic Act. The purpose of this paper is to analyze the FDCA to determine whether computer software is included in the statutory scheme, examine constitutional arguments relating to computer software, and discuss regulatory principles that should be taken into account when deciding appropriate regulation. This paper is limited to computer program output used by humans in deciding appropriate medical therapy for a patient.

  20. 78 FR 20291 - Fisheries of the United States; Billfish Conservation Act of 2012 Implementing Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ...NMFS issues this advance notice of proposed rulemaking (ANPR) to provide background information and request public comment on potential issues related to the implementation of the Billfish Conservation Act of...

  1. RECOVERY ACT - Methods for Decision under Technological Change Uncertainty and Risk Assessment for Integrated Assessment of Climate Change

    SciTech Connect

    Webster, Mort David

    2015-03-10

    This report presents the final outcomes and products of the project as performed at the Massachusetts Institute of Technology. The research project consists of three main components: methodology development for decision-making under uncertainty, improving the resolution of the electricity sector to improve integrated assessment, and application of these methods to integrated assessment. Results in each area is described in the report.

  2. Regulation of caulimovirus gene expression and the involvement of cis-acting elements on both viral transcripts.

    PubMed

    Scholthof, H B; Wu, F C; Gowda, S; Shepherd, R J

    1992-09-01

    In a further analysis of gene regulation of figwort mosaic virus (FMV), a caulimovirus, we studied transient gene expression with modified viral genomes in Nicotiana edwardsonii cell suspension protoplasts. The results demonstrated that the presence of the promoter for the full-length RNA interferes with expression from the separate downstream promoter for gene VI. In addition, expression of gene VI was inhibited by cis-acting sequences within gene VI itself. Both inhibitory effects could be partially relieved by coelectroporation with a plasmid that produces gene VI protein, demonstrating that expression of gene VI is transactivated by its own product. Subsequent expression studies with partially redundant FMV plasmids containing a reporter gene in frame with gene IV showed that efficient transactivation of CAT expression relies on a cis-acting element inside the downstream gene VI. Insertions of a transcriptional terminator upstream of the cis-acting element for premature termination of transcription showed that the cis-acting region is not a DNA element but is active only as a feature of the RNA transcript. We conclude that the cis-acting element, together with the transacting gene VI product, enhances expression of all major genes, including gene VI, from the polycistronic mRNA and the separate mRNA for gene VI. PMID:1529539

  3. 76 FR 10234 - Amendment to the Bank Secrecy Act Regulations-Reports of Foreign Financial Accounts

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... Regulations (CFR) for BSA regulations. (See 75 FR 65806 (October 26, 2010) (Transfer and Reorganization of... draft of which appeared in the Federal Register as an attachment to the NPRM. \\3\\ See 75 FR 8844... foreign financial institution.\\5\\ \\4\\ 75 FR 8851 (February 26, 2010) (Emphasis added). \\5\\ A revised...

  4. 75 FR 51420 - Removing Regulations Implementing the Fish and Wildlife Conservation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... implementing regulations (50 CFR 83) in the May 6, 2010, Federal Register (75 FR 24862) and invited public... with Native American Tribal Governments'' (59 FR 22951), E.O. 13175, and 512 DM 2. We have determined... Fish and Wildlife Service 50 CFR Part 83 RIN 1018-AX00 Removing Regulations Implementing the Fish...

  5. 76 FR 64049 - Bank Secrecy Act Regulations: Definition of “Monetary Instrument”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... Code of Federal Regulations for the BSA regulations. See 75 FR 65806 (October 26, 2010) (Transfer and... rule could be proposed by creating a regulatory framework and definition of prepaid access. \\10\\ 75 FR... regarding reporting of the international transport of prepaid access, see 75 FR 36593. \\11\\ 76 FR 45403....

  6. The Real Education for Healthy Youth Act: Honest, Age Appropriate Sexual Health Education for Responsible Decision Making. Policy Brief

    ERIC Educational Resources Information Center

    Phillip, Jendayi

    2012-01-01

    The Real Education for Healthy Youth Act (S. 1782/H.R. 3324), introduced in November 2011 by Senator Frank Lautenberg (D-NJ) and Representative Barbara Lee (D-CA), would ensure that federal funding is allocated to comprehensive sexual health education programs that provide young people with the skills and information they need to make informed,…

  7. Educational Decisions about the Culturally and Linguistically Diverse (CLD) Students under the No Child Left Behind (NCLB) Act

    ERIC Educational Resources Information Center

    Shah, Amee P.

    2008-01-01

    Purpose: The present paper is geared to help speech-language pathologists and other members of the school-based teams to become acquainted with the new educational structure and context in schools today as driven by NCLB [No Child Left Behind Act], and thus, be better prepared to meet the needs of CLD [Culturally and Linguistically Diverse]…

  8. The second act. With Obama and the reform law here to stay, big decisions are ahead for healthcare.

    PubMed

    Daly, Rich; Zigmond, Jessica

    2012-11-12

    The re-election of President Barack Obama to a second term and the preservation of a Democratic majority in the Senate removed doubts about the survival of the Patient Protection and Affordable Care Act as the law of the land. PMID:23495400

  9. Twenty Years of the Dietary Supplement Health and Education Act--How Should Dietary Supplements Be Regulated?

    PubMed

    Wallace, Taylor C

    2015-08-01

    The Dietary Supplement Health and Education Act (DSHEA) of 1994 defines the FDA's statutory authority to regulate dietary supplement products in the United States. The dietary supplement industry has rapidly expanded since 1994, presenting an obvious need for "DSHEA 2.0." Current regulations surrounding dietary supplements have been increasingly and reasonably scrutinized, given their widespread use by over one-half of the US population as well as highly publicized safety concerns over the past 20 y. As the market continues to expand and evolve, so too must the laws that protect consumers from potential harm and misleading communication. This article is meant to begin a scientific dialogue on how regulations may be improved to provide both ease of access and safer products to the consumer by focusing on 4 topics: premarket approval, label claims, current Good Manufacturing Practices, and adverse event reporting. PMID:26063064

  10. Fnr (EtrA) acts as a fine-tuning regulator of anaerobic metabolism in Shewanella oneidensis MR-1

    SciTech Connect

    Cruz-Garza, Claribel; Murray, Alison E.; Rodrigues, Jorge L.M.; Gralnick, Jeffrey A.; McCue, Lee Ann; Romine, Margaret F.; Loffler, F. E.; Tiedje, James M.

    2011-03-30

    EtrA in Shewanella oneidensis MR-1, a model organism for study of adaptation to varied redox niches, shares 73.6% and 50.8% amino acid sequence identity with the oxygen-sensing regulators Fnr in E. coli and Anr in Pseudomonas aeruginosa, respectively; however, its regulatory role of anaerobic metabolism in Shewanella spp. is not well understood. The expression of the nap genes, nrfA, cymA and hcp was significantly reduced in etrA deletion mutant EtrA7-1; however, limited anaerobic growth and nitrate reduction occurred, suggesting that multiple regulators control nitrate reduction in this strain. Dimethyl sulfoxide (DMSO) and fumarate reductase gene expression was down regulated at least 2-fold and the EtrA7-1 mutant grew poorly with fumarate and dimethyl sulfoxide (DMSO), suggesting both respiratory pathways are under EtrA control. Transcript analysis further suggested a role of EtrA in prophage activation and down regulation of genes implicated in aerobic metabolism. In contrast to previous studies that attributed a minor regulatory role to EtrA in Shewanella spp., this study demonstrates that EtrA acts as a global transcriptional regulator and confers physiological advantages to strain MR-1 under certain growth conditions. In conjunction with other regulators, EtrA fine-tunes the expression of genes involved in anaerobic metabolism in S. oneidensis strain MR-1.

  11. 75 FR 63425 - Regulations Implementing the Longshore and Harbor Workers' Compensation Act: Recreational Vessels

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... the responsible employer, and that he or she is disabled as a result of the illness. (3) Hearing loss. If the individual claims compensation for hearing loss, the date of injury is the date the individual... and Harbor Workers' Compensation Act: Recreational Vessels, published on August 17, 2010 (75 FR...

  12. 75 FR 46859 - Lacey Act Implementation Plan; Definitions for Exempt and Regulated Articles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... is being phased in, as described in two notices we published in the Federal Register (74 FR 5911-5913 and 74 FR 45415- 45418, Docket No. APHIS-2008-0119). Under the Act, ``Plant'' means: ``Any wild member... an appendix to the Convention on International Trade in Endangered Species of Wild Fauna and...

  13. 76 FR 78483 - S.A.F.E. Mortgage Licensing Act (Regulations G & H)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ... part of the public record and subject to public disclosure. Sensitive personal information, such as... for licensing loan originators that meets the requirements of the S.A.F.E. Act. \\1\\ 75 FR 44656 (July... this rule. See 76 FR 43569 (July 21, 2011). \\6\\ Public Law 111-203, section 1002(14)...

  14. Trans-acting factors regulate the expression of CD44 splice variants.

    PubMed Central

    Konig, H; Moll, J; Ponta, H; Herrlich, P

    1996-01-01

    Variant isoforms of the cell surface glycoprotein CD44 (CD44v) are expressed during development, in selected adult tissues and in certain metastatic tumor cells. CD44v differ from the standard isoform (CD44s) by up to ten additional exon sequences included by alternative splicing. By cell fusion experiments, we have obtained evidence for the existence of cell-type specific trans-acting factors recruiting CD44 variant exon sequences. Stable cell hybrids of CD44s and CD44v expressing cells indicated a dominant mechanism for variant-exon inclusion. In transient interspecies heterokaryons of human keratinocytes and rat fibroblasts, the ability of the keratinocytes to include all variant exon sequences in CD44 was conferred completely on the rat fibroblast nucleus. Fusions of cells with complex CD44 splice patterns do not permit interpretation of splice control by the relative abundance of a single trans-acting factor, but rather by (a) positively acting factor(s) recruiting variant exon sequences in the 3' to 5' direction and additional factors selecting individual exons. Since the pancreatic carcinoma cell line BSp73ASML (in contrast to the cervix carcinoma cell lines SiHa and ME180) could not transfer its specific splice pattern in cell fusions, we conclude that in some tumors, splicing is also controlled by mutation of cis-acting recognition sites. Images PMID:8670907

  15. 78 FR 36693 - Rules and Regulations Under the Fur Products Labeling Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... guaranties annually. \\10\\ 78 FR 29263 (May 20, 2013). In light of the proposed amendments to the Textile... Act, 77 FR 57043 (Sept. 17, 2012). \\8\\ National Retail Federation Comment 00025 at 1-5, available at... Activities; Submission for OMB Review; Comment Request, 7 FR 10744 (Feb. 23, 2012). D. Projected...

  16. 76 FR 63817 - Disclosure of Information; Privacy Act Regulations; Notice and Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-14

    ... supervisory agency, for purposes of Sec. 309.6, to which exempt records could be disclosed.\\1\\ \\1\\ 76 FR 35963.... D. Plain Language Section 722 of the Gramm-Leach-Bliley Act (Pub. L. 106-102, 113 Stat. 1338, 1471), requires the Federal banking agencies to use plain language in all proposed and final rules published...

  17. 75 FR 58389 - Federal Acquisition Regulation; Information Collection; American Recovery and Reinvestment Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... Reporting Requirements for Prime Contractors AGENCY: Department of Defense (DOD), General Services... American Recovery and Reinvestment Act-Reporting Requirements--One Time Reporting Requirements for Prime... for which the burden is imposed on the prime contractor under the FAR requirements include...

  18. 75 FR 58388 - Federal Acquisition Regulation; Information Collection; American Recovery and Reinvestment Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... Reporting for Prime Contractors AGENCY: Department of Defense (DOD), General Services Administration (GSA... Recovery and Reinvestment Act--Quarterly Reporting for Prime Contractors. Public comments are particularly...- mail to ernest.woodson@gsa.gov . ] SUPPLEMENTARY INFORMATION: A. Purpose Quarterly Reporting for...

  19. 20 CFR 626.4 - Table of contents for the Job Training Partnership Act regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the Job Training Partnership Act, 20 CFR parts 626-638 and 1005, 1 is as follows: 1 Part 1005 was...—Center Operations 638.500Orientation program. 694.501Student handbook. 638.502Job Corps basic...

  20. Market effects of environmental regulation: coal, railroads, and the 1990 Clean Air Act

    SciTech Connect

    Busse, M.R.; Keohane, N.O.

    2007-01-01

    Many environmental regulations encourage the use of 'clean' inputs. When the suppliers of such an input have market power, environmental regulation will affect not only the quantity of the input used but also its price. We investigate the effect of the Title IV emissions trading program for sulfur dioxide on the market for low-sulfur coal. We find that the two railroads transporting coal were able to price discriminate on the basis of environmental regulation and geographic location. Delivered prices rose for plants in the trading program relative to other plants, and by more at plants near a low-sulfur coal source.

  1. Dopamine D1 Receptors in the Anterior Cingulate Cortex Regulate Effort-Based Decision Making

    ERIC Educational Resources Information Center

    Schweimer, Judith; Hauber, Wolfgang

    2006-01-01

    The anterior cingulate cortex (ACC) has been implicated in encoding whether or not an action is worth performing in view of the expected benefit and the cost of performing the action. Dopamine input to the ACC may be critical for this form of effort-based decision making; however, the role of distinct ACC dopamine receptors is yet unknown.…

  2. Ethylene acts as a negative regulator of glucose induced lateral root emergence in Arabidopsis.

    PubMed

    Singh, Manjul; Gupta, Aditi; Laxmi, Ashverya

    2015-01-01

    Plants, being sessile organisms, are more exposed to the hazards of constantly changing environmental conditions globally. During the lifetime of a plant, the root system encounters various challenges such as obstacles, pathogens, high salinity, water logging, nutrient scarcity etc. The developmental plasticity of the root system provides brilliant adaptability to plants to counter the changes exerted by both external as well as internal cues and achieve an optimized growth status. Phytohormones are one of the major intrinsic factors regulating all aspects of plant growth and development both independently as well as through complex signal integrations at multiple levels. We have previously shown that glucose (Glc) and brassinosteroid (BR) signalings interact extensively to regulate lateral root (LR) development in Arabidopsis. (1) Auxin efflux as well as influx and downstream signaling components are also involved in Glc-BR regulation of LR emergence. Here, we provide evidence for involvement of ethylene signaling machinery downstream to Glc and BR in regulation of LR emergence. PMID:26236960

  3. 75 FR 3665 - Regulations under the Comprehensive Smokeless Tobacco Health Education Act; Termination of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-22

    ... cars, banners, flags, and other event-related objects. On November 4, 1993 (58 FR 58810), the FTC... Tobacco to Protect Children and Adolescents, 61 FR 44615-618 (Aug. 28, 1996). Those regulations...

  4. Ethylene acts as a negative regulator of glucose induced lateral root emergence in Arabidopsis

    PubMed Central

    Singh, Manjul; Gupta, Aditi; Laxmi, Ashverya

    2015-01-01

    Plants, being sessile organisms, are more exposed to the hazards of constantly changing environmental conditions globally. During the lifetime of a plant, the root system encounters various challenges such as obstacles, pathogens, high salinity, water logging, nutrient scarcity etc. The developmental plasticity of the root system provides brilliant adaptability to plants to counter the changes exerted by both external as well as internal cues and achieve an optimized growth status. Phytohormones are one of the major intrinsic factors regulating all aspects of plant growth and development both independently as well as through complex signal integrations at multiple levels. We have previously shown that glucose (Glc) and brassinosteroid (BR) signalings interact extensively to regulate lateral root (LR) development in Arabidopsis.1 Auxin efflux as well as influx and downstream signaling components are also involved in Glc-BR regulation of LR emergence. Here, we provide evidence for involvement of ethylene signaling machinery downstream to Glc and BR in regulation of LR emergence. PMID:26236960

  5. 75 FR 66699 - Lacey Act Implementation Plan; Definitions for Exempt and Regulated Articles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-29

    ... published in the Federal Register (75 FR 46859-46861, Docket No. APHIS-2009-0018) a proposal to establish... Implementation Plan; Definitions for Exempt and Regulated Articles AGENCY: Animal and Plant Health...

  6. Toward an operational model of decision making, emotional regulation, and mental health impact.

    PubMed

    Collura, Thomas Francis; Zalaquett, Ronald P; Bonnstetter, Carlos Joyce; Chatters, Seria J

    2014-01-01

    Current brain research increasingly reveals the underlying mechanisms and processes of human behavior, cognition, and emotion. In addition to being of interest to a wide range of scientists, educators, and professionals, as well as laypeople, brain-based models are of particular value in a clinical setting. Psychiatrists, psychologists, counselors, and other mental health professionals are in need of operational models that integrate recent findings in the physical, cognitive, and emotional domains, and offer a common language for interdisciplinary understanding and communication. Based on individual traits, predispositions, and responses to stimuli, we can begin to identify emotional and behavioral pathways and mental processing patterns. The purpose of this article is to present a brain-path activation model to understand individual differences in decision making and psychopathology. The first section discusses the role of frontal lobe electroencephalography (EEG) asymmetry, summarizes state- and trait-based models of decision making, and provides a more complex analysis that supplements the traditional simple left-right brain model. Key components of the new model are the introduction of right hemisphere parallel and left hemisphere serial scanning in rendering decisions, and the proposition of pathways that incorporate both past experiences as well as future implications into the decision process. Main attributes of each decision-making mechanism are provided. The second section applies the model within the realm of clinical mental health as a tool to understand specific human behavior and pathology. Applications include general and chronic anxiety, depression, paranoia, risk taking, and the pathways employed when well-functioning operational integration is observed. Finally, specific applications such as meditation and mindfulness are offered to facilitate positive functioning. PMID:25590293

  7. Neuronal correlates of decisions to speak and act: Spontaneous emergence and dynamic topographies in a computational model of frontal and temporal areas.

    PubMed

    Garagnani, Max; Pulvermüller, Friedemann

    2013-10-01

    The neural mechanisms underlying the spontaneous, stimulus-independent emergence of intentions and decisions to act are poorly understood. Using a neurobiologically realistic model of frontal and temporal areas of the brain, we simulated the learning of perception-action circuits for speech and hand-related actions and subsequently observed their spontaneous behaviour. Noise-driven accumulation of reverberant activity in these circuits leads to their spontaneous ignition and partial-to-full activation, which we interpret, respectively, as model correlates of action intention emergence and action decision-and-execution. Importantly, activity emerged first in higher-association prefrontal and temporal cortices, subsequently spreading to secondary and finally primary sensorimotor model-areas, hence reproducing the dynamics of cortical correlates of voluntary action revealed by readiness-potential and verb-generation experiments. This model for the first time explains the cortical origins and topography of endogenous action decisions, and the natural emergence of functional specialisation in the cortex, as mechanistic consequences of neurobiological principles, anatomical structure and sensorimotor experience. PMID:23489583

  8. GP supervisors' experience in supporting self-regulated learning: a balancing act.

    PubMed

    Sagasser, Margaretha H; Kramer, Anneke W M; van Weel, Chris; van der Vleuten, Cees P M

    2015-08-01

    Self-regulated learning is essential for professional development and lifelong learning. As self-regulated learning has many inaccuracies, the need to support self-regulated learning has been recommended. Supervisors can provide such support. In a prior study trainees reported on the variation in received supervisor support. This study aims at exploring supervisors' perspectives. The aim is to explore how supervisors experience self-regulated learning of postgraduate general practitioners (GP) trainees and their role in this, and what helps and hinders them in supervising. In a qualitative study using a phenomenological approach, we interviewed 20 supervisors of first- and third-year postgraduate GP trainees. Supervisors recognised trainee activity in self-regulated learning and adapted their coaching style to trainee needs, occasionally causing conflicting emotions. Supervisors' beliefs regarding their role, trainees' role and the usefulness of educational interventions influenced their support. Supervisors experienced a relation between patient safety, self-regulated learning and trainee capability to learn. Supervisor training was helpful to exchange experience and obtain advice. Supervisors found colleagues helpful in sharing supervision tasks or in calibrating judgments of trainees. Busy practice occasionally hindered the supervisory process. In conclusion, supervisors adapt their coaching to trainees' self-regulated learning, sometimes causing conflicting emotions. Patient safety and entrustment are key aspects of the supervisory process. Supervisors' beliefs about their role and trainees' role influence their support. Supervisor training is important to increase awareness of these beliefs and the influence on their behaviour, and to improve the use of educational instruments. The results align with findings from other (medical) education, thereby illustrating its relevance. PMID:25314934

  9. CoREST acts as a positive regulator of Notch signaling in the follicle cells of Drosophila melanogaster

    PubMed Central

    Domanitskaya, Elena; Schüpbach, Trudi

    2012-01-01

    The Notch signaling pathway plays important roles in a variety of developmental events. The context-dependent activities of positive and negative modulators dramatically increase the diversity of cellular responses to Notch signaling. In a screen for mutations affecting the Drosophila melanogaster follicular epithelium, we isolated a mutation in CoREST that disrupts the Notch-dependent mitotic-to-endocycle switch of follicle cells at stage 6 of oogenesis. We show that Drosophila CoREST positively regulates Notch signaling, acting downstream of the proteolytic cleavage of Notch but upstream of Hindsight activity; the Hindsight gene is a Notch target that coordinates responses in the follicle cells. We show that CoREST genetically interacts with components of the Notch repressor complex, Hairless, C-terminal Binding Protein and Groucho. In addition, we demonstrate that levels of H3K27me3 and H4K16 acetylation are dramatically increased in CoREST mutant follicle cells. Our data indicate that CoREST acts as a positive modulator of the Notch pathway in the follicular epithelium as well as in wing tissue, and suggests a previously unidentified role for CoREST in the regulation of Notch signaling. Given its high degree of conservation among species, CoREST probably also functions as a regulator of Notch-dependent cellular events in other organisms. PMID:22331351

  10. Regulation by consensus: The expanded use of regulatory negotiation under the Clean Air Act

    SciTech Connect

    Claiborne, M.L.

    1996-12-31

    This article discusses the consensus building approach, which stems from the more formal regulatory negotiation process under the Negotiated Rulemaking Act of 1990, for improving air quality. The article uses as examples the joint plan to improve air quality and visibility in the Grand Canyon and 15 other national parks and wilderness areas in the SW USA, and the Southern Appalachian Mountain initiative tackling more complex issues including visibility, ground ozone, acid deposition, etc.

  11. Insulin/IGF-1 and Hypoxia Signaling Act in Concert to Regulate Iron Homeostasis in Caenorhabditis elegans

    PubMed Central

    Ackerman, Daniel; Gems, David

    2012-01-01

    Iron plays an essential role in many biological processes, but also catalyzes the formation of reactive oxygen species (ROS), which can cause molecular damage. Iron homeostasis is therefore a critical determinant of fitness. In Caenorhabditis elegans, insulin/IGF-1 signaling (IIS) promotes growth and reproduction but limits stress resistance and lifespan through inactivation of the DAF-16/FoxO transcription factor (TF). We report that long-lived daf-2 insulin/IGF-1 receptor mutants show a daf-16–dependent increase in expression of ftn-1, which encodes the iron storage protein H-ferritin. To better understand the regulation of iron homeostasis, we performed a TF–limited genetic screen for factors influencing ftn-1 gene expression. The screen identified the heat-shock TF hsf-1, the MAD bHLH TF mdl-1, and the putative histone acetyl transferase ada-2 as activators of ftn-1 expression. It also revealed that the HIFα homolog hif-1 and its binding partner aha-1 (HIFβ) are potent repressors of ftn-1 expression. ftn-1 expression is induced by exposure to iron, and we found that hif-1 was required for this induction. In addition, we found that the prolyl hydroxylase EGL-9, which represses HIF-1 via the von Hippel-Lindau tumor suppressor VHL-1, can also act antagonistically to VHL-1 in regulating ftn-1. This suggests a novel mechanism for HIF target gene regulation by these evolutionarily conserved and clinically important hydroxylases. Our findings imply that the IIS and HIF pathways act together to regulate iron homeostasis in C. elegans. We suggest that IIS/DAF-16 regulation of ftn-1 modulates a trade-off between growth and stress resistance, as elevated iron availability supports growth but also increases ROS production. PMID:22396654

  12. Oct-3/4 regulates stem cell identity and cell fate decisions by modulating Wnt/β-catenin signalling

    PubMed Central

    Abu-Remaileh, Monther; Gerson, Ariela; Farago, Marganit; Nathan, Gili; Alkalay, Irit; Zins Rousso, Sharon; Gur, Michal; Fainsod, Abraham; Bergman, Yehudit

    2010-01-01

    Although the transcriptional regulatory events triggered by Oct-3/4 are well documented, understanding the proteomic networks that mediate the diverse functions of this POU domain homeobox protein remains a major challenge. Here, we present genetic and biochemical studies that suggest an unexpected novel strategy for Oct-3/4-dependent regulation of embryogenesis and cell lineage determination. Our data suggest that Oct-3/4 specifically interacts with nuclear β-catenin and facilitates its proteasomal degradation, resulting in the maintenance of an undifferentiated, early embryonic phenotype both in Xenopus embryos and embryonic stem (ES) cells. Our data also show that Oct-3/4-mediated control of β-catenin stability has an important function in regulating ES cell motility. Down-regulation of Oct-3/4 increases β-catenin protein levels, enhancing Wnt signalling and initiating invasive cellular activity characteristic of epithelial-mesenchymal transition. Our data suggest a novel mode of regulation by which a delicate balance between β-catenin, Tcf3 and Oct-3/4 regulates maintenance of stem cell identity. Altering the balance between these proteins can direct cell fate decisions and differentiation. PMID:20736927

  13. Nitric Oxide Acts as a Positive Regulator to Induce Metamorphosis of the Ascidian Herdmania momus

    PubMed Central

    Ueda, Nobuo; Degnan, Sandie M.

    2013-01-01

    Marine invertebrates commonly have a biphasic life cycle in which the metamorphic transition from a pelagic larva to a benthic post-larva is mediated by the nitric oxide signalling pathway. Nitric oxide (NO) is synthesised by nitric oxide synthase (NOS), which is a client protein of the molecular chaperon heat shock protein 90 (HSP90). It is notable, then, that both NO and HSP90 have been implicated in regulating metamorphosis in marine invertebrates as diverse as urochordates, echinoderms, molluscs, annelids, and crustaceans. Specifically, the suppression of NOS activity by the application of either NOS- or HSP90-inhibiting pharmacological agents has been shown consistently to induce the initiation of metamorphosis, leading to the hypothesis that a negative regulatory role of NO is widely conserved in biphasic life cycles. Further, the induction of metamorphosis by heat-shock has been demonstrated for multiple species. Here, we investigate the regulatory role of NO in induction of metamorphosis of the solitary tropical ascidian, Herdmania momus. By coupling pharmacological treatments with analysis of HmNOS and HmHSP90 gene expression, we present compelling evidence of a positive regulatory role for NO in metamorphosis of this species, in contrast to all existing ascidian data that supports the hypothesis of NO as a conserved negative regulator of metamorphosis. The exposure of competent H. momus larvae to a NOS inhibitor or an NO donor results in an up-regulation of NOS and HSP90 genes. Heat shock of competent larvae induces metamorphosis in a temperature dependent manner, up to a thermal tolerance that approaches 35°C. Both larval/post-larval survival and the appearance of abnormal morphologies in H. momus post-larvae reflect the magnitude of up-regulation of the HSP90 gene in response to heat-shock. The demonstrated role of NO as a positive metamorphic regulator in H. momus suggests the existence of inter-specific adaptations of NO regulation in ascidian

  14. Liability for managed care decisions: the Employee Retirement Income Security Act (ERISA) and the uneven playing field.

    PubMed Central

    Mariner, W K

    1996-01-01

    As managed care organizations expand their programs of quality assurance and physician evaluation, more medical malpractice lawsuits may be brought against managed care organizations on the ground that, like hospitals, they are legally responsible for negligent corporate acts that injure patients. However, the federal Employee Retirement Income Security Act (ERISA) shields managed care organizations from liability when they are part of an employee group health plan governed by ERISA. Unlike patients with other types of insurance, patients in ERISA health plans do not have a malpractice remedy for a managed care organization's negligence. A few federal appeals courts recently recognized that ERISA plans can be vicariously liable for their physicians' medical malpractice, but only if the physician is the plan's employee or agent. Yet ERISA still prohibits negligence claims against ERISA health plans for injuries resulting from denial of plan benefits, failure to use qualified physicians, utilization review, or improper plan administration. Current managed care operations do not neatly distinguish between administering benefits and controlling quality of care. Neither should the law. ERISA should be amended to provide employees with the same remedies that patients in non-ERISA plans enjoy. PMID:8659664

  15. 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.

  16. Disemployment effects caused by regulation of drilling fluids and produced waters as hazardous under the Resource Conservation and Recovery Act

    SciTech Connect

    Flaim, S.J.

    1988-03-01

    This report reviews and compares several studies of the effects on employment of regulating wastes from oil and natural gas exploration and extraction under the Resource Conservation and Recovery Act (RCRA). The waste management scenarios on which most of the studies were based were developed by the U.S. Environmental Protection Agency. The analyses show that as many as 500,000-700,000 jobs may be lost in the first year if RCRA Subtitle C rules are applied to drilling fluids and produced waters. As a results, unemployment in major oil-producing states could rise by as much as six percentage points. 13 refs., 4 tabs.

  17. Nuclear Regulatory Commission Sunshine Act regulations. Hearing before the Subcommittee on Energy Conservation and Power of the Committee on Energy and Commerce, House of Representatives, Ninety-Ninth Congress, First Session, May 21, 1985

    SciTech Connect

    Not Available

    1985-01-01

    Nuclear Regulatory Commissioners and staff and representatives of Resources for the Future, Center for the Study of Responsive Law, and the Union of Concerned Scientists testified at a hearing held in response to a changed Commission meeting format allowing secret gatherings that would not have a formal transcript or written record for later assessment. Critics of the NRC's new regulation were opposed to both the concept of secret meetings and the fact that the Commissioners approved the plan without public comment. NRC Chairman Palladino countered that the change conforms with congressional intent as interpreted by the Supreme Court in a 1984 decision involving the Sunshine Act. At issue was the intent of the commissioners and the importance of public participation in the decision making process. Additional material submitted for the record follows the testimony of 12 witnesses.

  18. The Activity Centres (Young Persons' Safety) Act 1995, the Adventure Activities Licensing Regulations 1996.

    ERIC Educational Resources Information Center

    Journal of Adventure Education and Outdoor Leadership, 1996

    1996-01-01

    Explains licensing regulations applicable in the United Kingdom to commercial providers of adventure education programs that offer caving, climbing, trekking, and water sports; provides information on license applications, including licensing standards related to risk assessment and safety management procedures; and addresses issues related to the…

  19. 78 FR 59101 - Regulations Implementing the Byrd Amendments to the Black Lung Benefits Act: Determining Coal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-25

    ... public comment. 77 FR 19456-19478 (Mar. 30, 2012). These amendments reinstated two BLBA entitlement... Department recounted the history of these provisions in the NPRM. 77 FR at 19456-58. The Department also... streamlining the regulations where possible. See generally Executive Order 13563, 76 FR 3821 (January 18,...

  20. 78 FR 6621 - Ability To Repay Standards Under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... lending model, and ties to their communities enable them to make more accurate assessments of consumers... deterioration in underwriting standards. See 73 FR 44524 (Jul. 30, 2008). The following is presented as..., which substantially parallels the Board's Regulation Z, 12 CFR part 226. See 76 FR 79767 (Dec. 22,...

  1. 75 FR 68911 - Regulations Under the Genetic Information Nondiscrimination Act of 2008

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ... document. See 74 FR 9056 (March 2, 2009). Several days earlier, on February 25, 2009, the Commission held a... FR 51664. The HHS Office for Civil Rights is responsible for issuing the regulations applicable to GINA section 105 and issued a proposed rule on October 7, 2009 at 74 FR 51698. Among the various...

  2. 77 FR 19455 - Regulations Implementing the Byrd Amendments to the Black Lung Benefits Act: Determining Coal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-30

    ..., 20 CFR 718.2 (2011); 45 FR 13677, 13679 (Feb. 29, 1980). The proposed rule does, however, retain... 65 FR 79920, 80029 (Dec. 20, 2000); 20 CFR 725.4(d) (2011). Consequently, there is no reason to... Federal Regulations in 2000. See 65 FR 79920, 80029 (Dec. 20, 2000); 20 CFR 725.4(d) (2011)....

  3. 77 FR 23196 - Native American Graves Protection and Repatriation Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ... amendments to the regulation concerning: Civil penalties (68 FR 16354, April 3, 2003); Future applicability (72 FR 13189, March 21, 2007); and Disposition of culturally unidentifiable human remains (75 FR 12378... Department of the Interior (Department) published the initial rules to implement NAGPRA (60 FR...

  4. 78 FR 27078 - Native American Graves Protection and Repatriation Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-09

    ... Government Relations with Native American Tribal Governments'' (59 FR 22951, April 29, 1994); Executive Order... Office of the Secretary of the Interior 43 CFR Part 10 RIN 1024-AD99 Native American Graves Protection.... SUMMARY: This final rule revises regulations implementing the Native American Graves Protection...

  5. 77 FR 234 - Rules and Regulations Under the Textile Fiber Products Identification Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    .... SUPPLEMENTARY INFORMATION: On November 7, 2011, the Commission published its ANPR (76 FR 68690) seeking comment...; ] FEDERAL TRADE COMMISSION 16 CFR Part 303 Rules and Regulations Under the Textile Fiber Products... section below. Write ``Textile Rules, 16 CFR Part 303, Project No. P948404'' on your comment, and...

  6. 78 FR 60686 - Regulations Implementing the Byrd Amendments to the Black Lung Benefits Act: Determining Coal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... of Workers' Compensation Programs 20 CFR Parts 718 and 725 RIN 1240-AA04 Regulations Implementing the... Benefits; Correction AGENCY: Office of Workers' Compensation Programs, Labor. ACTION: Final rule; correction. SUMMARY: The Office of Workers' Compensation Programs is correcting the preamble to a final...

  7. 29 CFR 1987.110 - Decision and orders of the Administrative Review Board.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... UNDER SECTION 402 OF THE FDA FOOD SAFETY MODERNIZATION ACT Litigation § 1987.110 Decision and orders of.... 1987.110 Section 1987.110 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND... has been delegated the authority to act for the Secretary and issue final decisions under this...

  8. Strigolactone acts downstream of auxin to regulate bud outgrowth in pea and Arabidopsis.

    PubMed

    Brewer, Philip B; Dun, Elizabeth A; Ferguson, Brett J; Rameau, Catherine; Beveridge, Christine A

    2009-05-01

    During the last century, two key hypotheses have been proposed to explain apical dominance in plants: auxin promotes the production of a second messenger that moves up into buds to repress their outgrowth, and auxin saturation in the stem inhibits auxin transport from buds, thereby inhibiting bud outgrowth. The recent discovery of strigolactone as the novel shoot-branching inhibitor allowed us to test its mode of action in relation to these hypotheses. We found that exogenously applied strigolactone inhibited bud outgrowth in pea (Pisum sativum) even when auxin was depleted after decapitation. We also found that strigolactone application reduced branching in Arabidopsis (Arabidopsis thaliana) auxin response mutants, suggesting that auxin may act through strigolactones to facilitate apical dominance. Moreover, strigolactone application to tiny buds of mutant or decapitated pea plants rapidly stopped outgrowth, in contrast to applying N-1-naphthylphthalamic acid (NPA), an auxin transport inhibitor, which significantly slowed growth only after several days. Whereas strigolactone or NPA applied to growing buds reduced bud length, only NPA blocked auxin transport in the bud. Wild-type and strigolactone biosynthesis mutant pea and Arabidopsis shoots were capable of instantly transporting additional amounts of auxin in excess of endogenous levels, contrary to predictions of auxin transport models. These data suggest that strigolactone does not act primarily by affecting auxin transport from buds. Rather, the primary repressor of bud outgrowth appears to be the auxin-dependent production of strigolactones. PMID:19321710

  9. Thyroid Hormone May Regulate mRNA Abundance in Liver by Acting on MicroRNAs

    PubMed Central

    Dong, Hongyan; Paquette, Martin; Williams, Andrew; Zoeller, R. Thomas; Wade, Mike; Yauk, Carole

    2010-01-01

    MicroRNAs (miRNAs) are extensively involved in diverse biological processes. However, very little is known about the role of miRNAs in mediating the action of thyroid hormones (TH). Appropriate TH levels are known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short-term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed using Taqman Low Density Arrays (containing up to 600 rodent miRNAs). We found the expression of 40 miRNAs was significantly altered in the livers of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miRs-1, 206, 133a and 133b exhibited a massive increase in expression (50- to 500-fold). The regulation of TH on the expression of miRs-1, 206, 133a and 133b was confirmed in various mouse models including: chronic hypothyroid, short-term hyperthyroid and short-term hypothyroid followed by TH supplementation. TH regulation of these miRNAs was also confirmed in mouse hepatocyte AML 12 cells. The expression of precursors of miRs-1, 206, 133a and 133b were examined in AML 12 cells and shown to decrease after TH treatment, only pre-mir-206 and pre-mir-133b reached statistical significance. To identify the targets of these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the short-term hypothyroid mouse model relative to controls. We found transcripts from 92 known genes were significantly altered in these hypothyroid mice. Web-based target predication software (TargetScan and Microcosm) identified 14 of these transcripts as targets of miRs-1, 206, 133a and 133b. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding with the up-regulation of miRs-1, 206, 133a and 133b in hypothyroid mouse liver. To further investigate target genes, miR-206 was over-expressed in AML 12 cells. TH

  10. Past Actions as Self-Signals: How Acting in a Self-Interested Way Influences Environmental Decision Making.

    PubMed

    Lee, Chang-Yuan; Hochman, Guy; Prince, Steven E; Ariely, Dan

    2016-01-01

    In the last few decades, awareness of environmental issues has increased significantly. Little has changed, however, in human activities contributing to environmental damage. Why is it so difficult for us to change our behavior in a domain that is clearly so important to the future of humanity? Here we propose and test the possibility that self-signaling, the way we view ourselves based on our past behaviors, is one of the factors contributing to the difficulty of taking environmental action. In three experiments, we show that previous self-interested thoughts or behaviors serve as important signals that hinder the likelihood of acting in line with an individual's reported concern for the environment. This study not only helps explain the gap between environmental awareness and action, but also suggests alternative strategies for policymakers and environmental agencies to promote proenvironmental behavior. PMID:27447822

  11. Past Actions as Self-Signals: How Acting in a Self-Interested Way Influences Environmental Decision Making

    PubMed Central

    Lee, Chang-Yuan; Hochman, Guy; Prince, Steven E.; Ariely, Dan

    2016-01-01

    In the last few decades, awareness of environmental issues has increased significantly. Little has changed, however, in human activities contributing to environmental damage. Why is it so difficult for us to change our behavior in a domain that is clearly so important to the future of humanity? Here we propose and test the possibility that self-signaling, the way we view ourselves based on our past behaviors, is one of the factors contributing to the difficulty of taking environmental action. In three experiments, we show that previous self-interested thoughts or behaviors serve as important signals that hinder the likelihood of acting in line with an individual’s reported concern for the environment. This study not only helps explain the gap between environmental awareness and action, but also suggests alternative strategies for policymakers and environmental agencies to promote proenvironmental behavior. PMID:27447822

  12. Potential Impact of Clean Air Act Regulations on Nitrogen Fate and Transport in the Neuse River Basin: a Modeling Investigation Using CMAQ and SWAT

    EPA Science Inventory

    There has been extensive analysis of Clean Air Act Amendment (CAAA) regulation impacts to changes in atmospheric nitrogen deposition; however, few studies have focused on watershed nitrogen transfer particularly regarding long-term predictions. In this study, we investigated impa...

  13. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance

    PubMed Central

    Tsang, Chi Kwan; Liu, Yuan; Thomas, Janice; Zhang, Yanjie; Zheng, X. F. Steven

    2015-01-01

    Summary Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signaling: in response to elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H2O2 is sufficient to promote Sod1 nuclear localization, indicating that it is responding to general ROS rather than Sod1 substrate superoxide. ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes. Altogether, our study unravels an unorthodox function of Sod1 as a transcription factor and elucidates the regulatory mechanism for its localization. PMID:24647101

  14. Anaplastic Lymphoma Kinase Acts in the Drosophila Mushroom Body to Negatively Regulate Sleep

    PubMed Central

    Bai, Lei; Sehgal, Amita

    2015-01-01

    Though evidence is mounting that a major function of sleep is to maintain brain plasticity and consolidate memory, little is known about the molecular pathways by which learning and sleep processes intercept. Anaplastic lymphoma kinase (Alk), the gene encoding a tyrosine receptor kinase whose inadvertent activation is the cause of many cancers, is implicated in synapse formation and cognitive functions. In particular, Alk genetically interacts with Neurofibromatosis 1 (Nf1) to regulate growth and associative learning in flies. We show that Alk mutants have increased sleep. Using a targeted RNAi screen we localized the negative effects of Alk on sleep to the mushroom body, a structure important for both sleep and memory. We also report that mutations in Nf1 produce a sexually dimorphic short sleep phenotype, and suppress the long sleep phenotype of Alk. Thus Alk and Nf1 interact in both learning and sleep regulation, highlighting a common pathway in these two processes. PMID:26536237

  15. Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis

    PubMed Central

    Li, Haisen; Yue, Rui; Wei, Bin; Gao, Ge; Du, Jiulin; Pei, Gang

    2014-01-01

    Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. PMID:24829209

  16. Two Group A Streptococcal Peptide Pheromones Act through Opposing Rgg Regulators to Control Biofilm Development

    PubMed Central

    Chang, Jennifer C.; LaSarre, Breah; Jimenez, Juan C.; Aggarwal, Chaitanya; Federle, Michael J.

    2011-01-01

    Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human commensal that occasionally causes localized infections and less frequently causes severe invasive disease with high mortality rates. How GAS regulates expression of factors used to colonize the host and avoid immune responses remains poorly understood. Intercellular communication is an important means by which bacteria coordinate gene expression to defend against host assaults and competing bacteria, yet no conserved cell-to-cell signaling system has been elucidated in GAS. Encoded within the GAS genome are four rgg-like genes, two of which (rgg2 and rgg3) have no previously described function. We tested the hypothesis that rgg2 or rgg3 rely on extracellular peptides to control target-gene regulation. We found that Rgg2 and Rgg3 together tightly regulate two linked genes encoding new peptide pheromones. Rgg2 activates transcription of and is required for full induction of the pheromone genes, while Rgg3 plays an antagonistic role and represses pheromone expression. The active pheromone signals, termed SHP2 and SHP3, are short and hydrophobic (DI[I/L]IIVGG), and, though highly similar in sequence, their ability to disrupt Rgg3-DNA complexes were observed to be different, indicating that specificity and differential activation of promoters are characteristics of the Rgg2/3 regulatory circuit. SHP-pheromone signaling requires an intact oligopeptide permease (opp) and a metalloprotease (eep), supporting the model that pro-peptides are secreted, processed to the mature form, and subsequently imported to the cytoplasm to interact directly with the Rgg receptors. At least one consequence of pheromone stimulation of the Rgg2/3 pathway is increased biogenesis of biofilms, which counteracts negative regulation of biofilms by RopB (Rgg1). These data provide the first demonstration that Rgg-dependent quorum sensing functions in GAS and substantiate the role that Rggs play as peptide receptors across the

  17. Phosphorylation acts positively and negatively to regulate MRTF-A subcellular localisation and activity.

    PubMed

    Panayiotou, Richard; Miralles, Francesc; Pawlowski, Rafal; Diring, Jessica; Flynn, Helen R; Skehel, Mark; Treisman, Richard

    2016-01-01

    The myocardin-related transcription factors (MRTF-A and MRTF-B) regulate cytoskeletal genes through their partner transcription factor SRF. The MRTFs bind G-actin, and signal-regulated changes in cellular G-actin concentration control their nuclear accumulation. The MRTFs also undergo Rho- and ERK-dependent phosphorylation, but the function of MRTF phosphorylation, and the elements and signals involved in MRTF-A nuclear export are largely unexplored. We show that Rho-dependent MRTF-A phosphorylation reflects relief from an inhibitory function of nuclear actin. We map multiple sites of serum-induced phosphorylation, most of which are S/T-P motifs and show that S/T-P phosphorylation is required for transcriptional activation. ERK-mediated S98 phosphorylation inhibits assembly of G-actin complexes on the MRTF-A regulatory RPEL domain, promoting nuclear import. In contrast, S33 phosphorylation potentiates the activity of an autonomous Crm1-dependent N-terminal NES, which cooperates with five other NES elements to exclude MRTF-A from the nucleus. Phosphorylation thus plays positive and negative roles in the regulation of MRTF-A. PMID:27304076

  18. Phosphorylation acts positively and negatively to regulate MRTF-A subcellular localisation and activity

    PubMed Central

    Panayiotou, Richard; Miralles, Francesc; Pawlowski, Rafal; Diring, Jessica; Flynn, Helen R; Skehel, Mark; Treisman, Richard

    2016-01-01

    The myocardin-related transcription factors (MRTF-A and MRTF-B) regulate cytoskeletal genes through their partner transcription factor SRF. The MRTFs bind G-actin, and signal-regulated changes in cellular G-actin concentration control their nuclear accumulation. The MRTFs also undergo Rho- and ERK-dependent phosphorylation, but the function of MRTF phosphorylation, and the elements and signals involved in MRTF-A nuclear export are largely unexplored. We show that Rho-dependent MRTF-A phosphorylation reflects relief from an inhibitory function of nuclear actin. We map multiple sites of serum-induced phosphorylation, most of which are S/T-P motifs and show that S/T-P phosphorylation is required for transcriptional activation. ERK-mediated S98 phosphorylation inhibits assembly of G-actin complexes on the MRTF-A regulatory RPEL domain, promoting nuclear import. In contrast, S33 phosphorylation potentiates the activity of an autonomous Crm1-dependent N-terminal NES, which cooperates with five other NES elements to exclude MRTF-A from the nucleus. Phosphorylation thus plays positive and negative roles in the regulation of MRTF-A. DOI: http://dx.doi.org/10.7554/eLife.15460.001 PMID:27304076

  19. Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells

    PubMed Central

    Kresoja-Rakic, Jelena; Kapaklikaya, Esra; Ziltener, Gabriela; Dalcher, Damian; Santoro, Raffaella; Christensen, Brock C.; Johnson, Kevin C.; Schwaller, Beat; Weder, Walter; Stahel, Rolf A.; Felley-Bosco, Emanuela

    2016-01-01

    Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2′-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the −161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis-regulatory elements within this −161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells. PMID:26848772

  20. Should consensus be 'the commission method' in the US? The perspective of the Federal Advisory Committee Act, regulations, and case law.

    PubMed

    Spielman, Bethany

    2003-08-01

    This paper examines the drive for consensus from the perspective of the good government framework for federal advisory commissions in the United States. Specifically, the paper examines the Federal Advisory Committee Act (FACA)--the statute, its regulations, and case law. It shows that the FACA was intended to be an antidote to abuses in consensus-making processes, including the failure to fully include competing views on commissions. The index of suspicion in the FACA scheme rises when a group work product--including a consensus report--is to be the basis of recommendations to federal officials. Once FACA's requirements regarding committee composition are satisfied, the index of suspicion drops and FACA is indifferent to consensus-making; but the conditions for informed, meaningful participation apply to members who dissent from, as well as those who participate in, consensus. In negotiated rulemaking, the push for consensus and closure creates unacceptable tension with the good government goals of openness and accountability. Proponents of consensus-only bioethics commissions can learn from FACA-related legislative, agency, and judicial insights that consensus-seeking is not always desired by government officials; is rarely cost free; and that diversity and dissent enhance openness, accountability, and fairness. The burden of proof is therefore on proponents of a consensus-only standard for bioethics commissions to demonstrate that a drive for consensus furthers sound decision-making by government officials more than it sets back openness and accountability to a diverse public. PMID:14569979

  1. 25 CFR 309.1 - How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990? 309.1 Section 309.1 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.1 How do the regulations in this part carry out the Indian Arts and Crafts Act...

  2. 25 CFR 309.1 - How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990? 309.1 Section 309.1 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.1 How do the regulations in this part carry out the Indian Arts and Crafts Act...

  3. 25 CFR 309.1 - How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990? 309.1 Section 309.1 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.1 How do the regulations in this part carry out the Indian Arts and Crafts Act...

  4. 25 CFR 309.1 - How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990? 309.1 Section 309.1 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.1 How do the regulations in this part carry out the Indian Arts and Crafts Act...

  5. 25 CFR 309.1 - How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990? 309.1 Section 309.1 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.1 How do the regulations in this part carry out the Indian Arts and Crafts Act...

  6. CDH2 and CDH11 as Regulators of Stem Cell Fate Decisions

    PubMed Central

    Alimperti, Stella; Andreadis, Stelios T.

    2015-01-01

    Accumulating evidence suggests that the mechanical and biochemical signals originating from cell-cell adhesion are critical for stem cell lineage specification. In this review, we focus on the role of cadherin mediated signaling in development and stem cell differentiation, with emphasis on two well-known cadherins, cadherin-2 (CDH2) (N-cadherin) and cadherin-11 (CDH11) (OB-cadherin). We summarize the existing knowledge regarding the role of CDH2 and CDH11 during development and differentiation in vivo and in vitro. We also discuss engineering strategies to control stem cell fate decisions by fine-tuning the extent of cell-cell adhesion through surface chemistry and microtopology. These studies may be greatly facilitated by novel strategies that enable monitoring of stem cell specification in real time. We expect that better understanding of how intercellular adhesion signaling affects lineage specification may impact biomaterial and scaffold design to control stem cell fate decisions in three-dimensional context with potential implications for tissue engineering and regenerative medicine. PMID:25771201

  7. Functional overlap in the cis-acting regulation of the V(D)J recombination at the TCRβ locus

    PubMed Central

    Khor, Bernard; Mahowald, Grace; Khor, Katrina; Sleckman, Barry P.

    2009-01-01

    The second exon of lymphocyte antigen receptor genes is assembled in developing lymphocytes from component V, J and, in some cases, D gene segments through the process of V(D)J recombination. This process is initiated by an endonuclease comprised of the Rag-1 and Rag-2 proteins, collectively referred to as Rag. Rag binds to recombination signals (RSs) and catalyzes the pair-wise introduction of DNA double strand breaks (DSBs) at recombining gene segments. DNA cleavage by Rag is restricted both by intrinsic features of RSs, as well as the activity of other cis-acting elements, such as promoters and enhancers that regulate the accessibility of gene segments to Rag. In the TCRβ locus, accessibility of the Dβ1-Jβ1 gene segment cluster relies on the function of an enhancer, Eβ, and a promoter, PDβ1. Here we demonstrate that deletion of a small genomic region containing 5 of the 6 Jβ1 gene segments, but no known transcriptional regulatory elements, leads to a marked decrease in transcription and rearrangements involving the Dβ1 and Jβ1.1 gene segments. Surprisingly, point mutations in the RS of the Jβ1.1 gene segment not only impact Rag cleavage, but also lead to diminished transcription through the Dβ1-Jβ1 gene segment cluster. Our findings demonstrate that cis-acting elements that regulate transcription and accessibility of the TCRβ locus may functionally overlap with RS sequences, which are known primarily to direct Rag-mediated cleavage. PMID:19070901

  8. An Arabidopsis F-box protein acts as a transcriptional co-factor to regulate floral development.

    PubMed

    Chae, Eunyoung; Tan, Queenie K-G; Hill, Theresa A; Irish, Vivian F

    2008-04-01

    Plants flower in response to both environmental and endogenous signals. The Arabidopsis LEAFY (LFY) transcription factor is crucial in integrating these signals, and acts in part by activating the expression of multiple floral homeotic genes. LFY-dependent activation of the homeotic APETALA3 (AP3) gene requires the activity of UNUSUAL FLORAL ORGANS (UFO), an F-box component of an SCF ubiquitin ligase, yet how this regulation is effected has remained unclear. Here, we show that UFO physically interacts with LFY both in vitro and in vivo, and this interaction is necessary to recruit UFO to the AP3 promoter. Furthermore, a transcriptional repressor domain fused to UFO reduces endogenous LFY activity in plants, supporting the idea that UFO acts as part of a transcriptional complex at the AP3 promoter. Moreover, chemical or genetic disruption of proteasome activity compromises LFY-dependent AP3 activation, indicating that protein degradation is required to promote LFY activity. These results define an unexpected role for an F-box protein in functioning as a DNA-associated transcriptional co-factor in regulating floral homeotic gene expression. These results suggest a novel mechanism for promoting flower development via protein degradation and concomitant activation of the LFY transcription factor. This mechanism may be widely conserved, as homologs of UFO and LFY have been identified in a wide array of plant species. PMID:18287201

  9. Do we need a new law or regulation? The public health decision process.

    PubMed

    Benjamin, Georges; O'Brien, Daniel J; Trotter, Donne

    2002-01-01

    New laws or regulations may not be a practical response to a public health threat. While in some instances legislation or regulation may be the only alternative to protecting the public's health, in many situations public health authorities and their legal counsel must consider alternative approaches to abating threats. This article provides an overview of the alternatives available to the public health official by providing discussion of a "legal tool box" available to public health officials. It also presents scenarios, with commentary, that serve as the basis for illustration of other means of intervention. PMID:12508501

  10. 17 CFR 239.500 - Form D, notice of sales of securities under Regulation D and section 4(6) of the Securities Act...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Form D, notice of sales of securities under Regulation D and section 4(6) of the Securities Act of 1933. 239.500 Section 239.500 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION FORMS PRESCRIBED UNDER THE SECURITIES ACT OF 1933 Forms Pertaining to...

  11. The Texas space flight liability act and efficient regulation for the private commercial space flight era

    NASA Astrophysics Data System (ADS)

    Johnson, Christopher D.

    2013-12-01

    In the spring of 2011, the American state of Texas passed into law an act limiting the liability of commercial space flight entities. Under it, those companies would not be liable for space flight participant injuries, except in cases of intentional injury or injury proximately caused by the company's gross negligence. An analysis within the framework of international and national space law, but especially informed by the academic discipline of law and economics, discusses the incentives of all relevant parties and attempts to understand whether the law is economically "efficient" (allocating resources so as to yield maximum utility), and suited to further the development of the fledgling commercial suborbital tourism industry. Insights into the Texas law are applicable to other states hoping to foster commercial space tourism and considering space tourism related legislation.

  12. 43 CFR 10010.47 - Pre-decision referrals to CEQ.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... POLICY ACT Relationship to Decision-Making § 10010.47 Pre-decision referrals to CEQ. (a) Upon receipt of... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Pre-decision referrals to CEQ. 10010.47 Section 10010.47 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH...

  13. 43 CFR 10010.47 - Pre-decision referrals to CEQ.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... POLICY ACT Relationship to Decision-Making § 10010.47 Pre-decision referrals to CEQ. (a) Upon receipt of... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Pre-decision referrals to CEQ. 10010.47 Section 10010.47 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH...

  14. 43 CFR 10010.47 - Pre-decision referrals to CEQ.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... POLICY ACT Relationship to Decision-Making § 10010.47 Pre-decision referrals to CEQ. (a) Upon receipt of... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Pre-decision referrals to CEQ. 10010.47 Section 10010.47 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH...

  15. 43 CFR 10010.47 - Pre-decision referrals to CEQ.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... POLICY ACT Relationship to Decision-Making § 10010.47 Pre-decision referrals to CEQ. (a) Upon receipt of... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Pre-decision referrals to CEQ. 10010.47 Section 10010.47 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH...

  16. Polyadenylation in Rice Tungro Bacilliform Virus: cis-Acting Signals and Regulation

    PubMed Central

    Rothnie, Helen M.; Chen, Gang; Fütterer, Johannes; Hohn, Thomas

    2001-01-01

    The polyadenylation signal of rice tungro bacilliform virus (RTBV) was characterized by mutational and deletion analysis. The cis-acting signals required to direct polyadenylation conformed to what is known for plant poly(A) signals in general and were very similar to those of the related cauliflower mosaic virus. Processing was directed by a canonical AAUAAA poly(A) signal, an upstream UG-rich region considerably enhanced processing efficiency, and sequences downstream of the cleavage site were not required. When present at the end of a transcription unit, the cis-acting signals for 3′-end processing were highly efficient in both monocot (rice) and dicot (Nicotiana plumbaginifolia) protoplasts. In a promoter-proximal position, as in the viral genome, the signal was also efficiently processed in rice protoplasts, giving rise to an abundant “short-stop” (SS-) RNA. The proportion of SS-RNA was considerably lower in N. plumbaginifolia protoplasts. In infected plants, SS-RNA was hardly detectable, suggesting either that SS-RNA is unstable in infected plants or that read-through of the promoter-proximal poly(A) site is very efficient. SS-RNA is readily detectable in transgenic rice plants (A. Klöti, C. Henrich, S. Bieri, X. He, G. Chen, P. K. Burkhardt, J. Wünn, P. Lucca, T. Hohn, I. Potrylus, and J. Fütterer, 1999. Plant Mol. Biol. 40:249–266), thus the absence of SS-RNA in infected plants can be attributed to poly(A) site bypass in the viral context to ensure production of the full-length pregenomic viral RNA. RTBV poly(A) site suppression thus depends both on context and the expression system; our results suggest that the circular viral minichromosome directs assembly of a transcription-processing complex with specific properties to effect read-through of the promoter-proximal poly(A) signal. PMID:11287568

  17. Sclerostin Is a Locally Acting Regulator of Late-Osteoblast/Preosteocyte Differentiation and Regulates Mineralization Through a MEPE-ASARM-Dependent Mechanism

    PubMed Central

    Atkins, Gerald J; Rowe, Peter S; Lim, Hui P; Welldon, Katie J; Ormsby, Renee; Wijenayaka, Asiri R; Zelenchuk, Lesya; Evdokiou, Andreas; Findlay, David M

    2012-01-01

    The identity of the cell type responsive to sclerostin, a negative regulator of bone mass, is unknown. Since sclerostin is expressed in vivo by mineral-embedded osteocytes, we tested the hypothesis that sclerostin would regulate the behavior of cells actively involved in mineralization in adult bone, the preosteocyte. Differentiating cultures of human primary osteoblasts exposed to recombinant human sclerostin (rhSCL) for 35 days displayed dose- and time-dependent inhibition of in vitro mineralization, with late cultures being most responsive in terms of mineralization and gene expression. Treatment of advanced (day 35) cultures with rhSCL markedly increased the expression of the preosteocyte marker E11 and decreased the expression of mature markers DMP1 and SOST. Concomitantly, matrix extracellular phosphoglycoprotein (MEPE) expression was increased by rhSCL at both the mRNA and protein levels, whereas PHEX was decreased, implying regulation through the MEPE-ASARM axis. We confirmed that mineralization by human osteoblasts is exquisitely sensitive to the triphosphorylated ASARM-PO4 peptide. Immunostaining revealed that rhSCL increased the endogenous levels of MEPE-ASARM. Importantly, antibody-mediated neutralization of endogenous MEPE-ASARM antagonized the effect of rhSCL on mineralization, as did the PHEX synthetic peptide SPR4. Finally, we found elevated Sost mRNA expression in the long bones of HYP mice, suggesting that sclerostin may drive the increased MEPE-ASARM levels and mineralization defect in this genotype. Our results suggest that sclerostin acts through regulation of the PHEX/MEPE axis at the preosteocyte stage and serves as a master regulator of physiologic bone mineralization, consistent with its localization in vivo and its established role in the inhibition of bone formation. PMID:21312267

  18. Cyclic AMP Receptor Protein Acts as a Transcription Regulator in Response to Stresses in Deinococcus radiodurans

    PubMed Central

    Wang, Jiali; Liu, Chengzhi; Lu, Huizhi; Liu, Mengjia; Zhao, Ye; Tian, Bing; Wang, Liangyan; Hua, Yuejin

    2016-01-01

    The cyclic AMP receptor protein family of transcription factors regulates various metabolic pathways in bacteria, and also play roles in response to environmental changes. Here, we identify four homologs of the CRP family in Deinococcus radiodurans, one of which tolerates extremely high levels of oxidative stress and DNA-damaging reagents. Transcriptional levels of CRP were increased under hydrogen peroxide (H2O2) treatment during the stationary growth phase, indicating that CRPs function in response to oxidative stress. By constructing all CRP single knockout mutants, we found that the dr0997 mutant showed the lowest tolerance toward H2O2, ultraviolet radiation, ionizing radiation, and mitomycin C, while the phenotypes of the dr2362, dr0834, and dr1646 mutants showed slight or no significant differences from those of the wild-type strain. Taking advantage of the conservation of the CRP-binding site in many bacteria, we found that transcription of 18 genes, including genes encoding chromosome-partitioning protein (dr0998), Lon proteases (dr0349 and dr1974), NADH-quinone oxidoreductase (dr1506), thiosulfate sulfurtransferase (dr2531), the DNA repair protein UvsE (dr1819), PprA (dra0346), and RecN (dr1447), are directly regulated by DR0997. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses showed that certain genes involved in anti-oxidative responses, DNA repair, and various cellular pathways are transcriptionally attenuated in the dr0997 mutant. Interestingly, DR0997 also regulate the transcriptional levels of all CRP genes in this bacterium. These data suggest that DR0997 contributes to the extreme stress resistance of D. radiodurans via its regulatory role in multiple cellular pathways, such as anti-oxidation and DNA repair pathways. PMID:27182600

  19. 45 CFR 1703.201 - Decision to hold meeting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Decision to hold meeting. 1703.201 Section 1703.201 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL COMMISSION ON LIBRARIES AND INFORMATION SCIENCE GOVERNMENT IN THE SUNSHINE ACT Procedures Governing Decisions About...

  20. 45 CFR 1703.201 - Decision to hold meeting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Decision to hold meeting. 1703.201 Section 1703.201 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL COMMISSION ON LIBRARIES AND INFORMATION SCIENCE GOVERNMENT IN THE SUNSHINE ACT Procedures Governing Decisions About...

  1. 31 CFR 501.741 - Review of decision or ruling.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Review of decision or ruling. 501.741 Section 501.741 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Trading With the Enemy Act (TWEA) Penalties § 501.741 Review of decision or ruling. (a) Availability....

  2. 31 CFR 501.741 - Review of decision or ruling.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Review of decision or ruling. 501.741 Section 501.741 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Trading With the Enemy Act (TWEA) Penalties § 501.741 Review of decision or ruling. (a) Availability....

  3. 31 CFR 501.741 - Review of decision or ruling.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Review of decision or ruling. 501.741 Section 501.741 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Trading With the Enemy Act (TWEA) Penalties § 501.741 Review of decision or ruling. (a) Availability....

  4. 31 CFR 501.741 - Review of decision or ruling.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Review of decision or ruling. 501.741 Section 501.741 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Trading With the Enemy Act (TWEA) Penalties § 501.741 Review of decision or ruling. (a) Availability....

  5. 31 CFR 501.741 - Review of decision or ruling.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Review of decision or ruling. 501.741 Section 501.741 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... Trading With the Enemy Act (TWEA) Penalties § 501.741 Review of decision or ruling. (a) Availability....

  6. 10 CFR 780.23 - Hearing and decision.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Hearing and decision. 780.23 Section 780.23 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Declaring Patents Affected With the Public Interest Under Section 153a of the Atomic Energy Act of 1954 § 780.23 Hearing and decision. If a...

  7. 10 CFR 780.44 - Hearing and decision.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Hearing and decision. 780.44 Section 780.44 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153c of the Atomic Energy Act of 1954 § 780.44 Hearing and decision. In accordance with section 153d...

  8. 10 CFR 780.33 - Hearing and decision.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Hearing and decision. 780.33 Section 780.33 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153b(2) of the Atomic Energy Act of 1954 § 780.33 Hearing and decision. If any party requests a...

  9. 10 CFR 780.33 - Hearing and decision.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Hearing and decision. 780.33 Section 780.33 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153b(2) of the Atomic Energy Act of 1954 § 780.33 Hearing and decision. If any party requests a...

  10. 10 CFR 780.23 - Hearing and decision.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Hearing and decision. 780.23 Section 780.23 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Declaring Patents Affected With the Public Interest Under Section 153a of the Atomic Energy Act of 1954 § 780.23 Hearing and decision. If a...

  11. 10 CFR 780.44 - Hearing and decision.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Hearing and decision. 780.44 Section 780.44 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153c of the Atomic Energy Act of 1954 § 780.44 Hearing and decision. In accordance with section 153d...

  12. 20 CFR 349.5 - Notice of revised decision.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Notice of revised decision. 349.5 Section 349.5 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.5 Notice...

  13. 20 CFR 349.5 - Notice of revised decision.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Notice of revised decision. 349.5 Section 349.5 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.5 Notice...

  14. 20 CFR 349.6 - Effect of revised decision.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Effect of revised decision. 349.6 Section 349.6 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.6 Effect...

  15. 20 CFR 349.1 - Reopening and revising decisions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Reopening and revising decisions. 349.1 Section 349.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.1...

  16. 20 CFR 349.1 - Reopening and revising decisions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Reopening and revising decisions. 349.1 Section 349.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.1...

  17. 20 CFR 349.6 - Effect of revised decision.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Effect of revised decision. 349.6 Section 349.6 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.6 Effect...

  18. 20 CFR 349.6 - Effect of revised decision.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Effect of revised decision. 349.6 Section 349.6 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.6 Effect...

  19. 20 CFR 349.6 - Effect of revised decision.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Effect of revised decision. 349.6 Section 349.6 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.6 Effect...

  20. 20 CFR 349.5 - Notice of revised decision.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Notice of revised decision. 349.5 Section 349.5 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.5 Notice...

  1. 20 CFR 349.5 - Notice of revised decision.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Notice of revised decision. 349.5 Section 349.5 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.5 Notice...

  2. 20 CFR 349.1 - Reopening and revising decisions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Reopening and revising decisions. 349.1 Section 349.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.1...

  3. 20 CFR 349.5 - Notice of revised decision.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Notice of revised decision. 349.5 Section 349.5 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.5 Notice...

  4. 20 CFR 349.1 - Reopening and revising decisions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Reopening and revising decisions. 349.1 Section 349.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.1...

  5. 20 CFR 349.6 - Effect of revised decision.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Effect of revised decision. 349.6 Section 349.6 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.6 Effect...

  6. 20 CFR 349.1 - Reopening and revising decisions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Reopening and revising decisions. 349.1 Section 349.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.1...

  7. 45 CFR 1703.201 - Decision to hold meeting.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 4 2014-10-01 2014-10-01 false Decision to hold meeting. 1703.201 Section 1703.201 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL COMMISSION ON LIBRARIES AND INFORMATION SCIENCE GOVERNMENT IN THE SUNSHINE ACT Procedures Governing Decisions About...

  8. 45 CFR 1703.201 - Decision to hold meeting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Decision to hold meeting. 1703.201 Section 1703.201 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL COMMISSION ON LIBRARIES AND INFORMATION SCIENCE GOVERNMENT IN THE SUNSHINE ACT Procedures Governing Decisions About...

  9. 45 CFR 1703.203 - Decision to close meeting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Decision to close meeting. 1703.203 Section 1703.203 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL COMMISSION ON LIBRARIES AND INFORMATION SCIENCE GOVERNMENT IN THE SUNSHINE ACT Procedures Governing Decisions About...

  10. 45 CFR 1203.10 - Decisions and notices.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Decisions and notices. 1203.10 Section 1203.10 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS-EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 1203.10 Decisions and notices....

  11. 20 CFR 703.303 - Decision on employer's application.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Decision on employer's application. 703.303 Section 703.303 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR WORKERS' COMPENSATION ACT AND RELATED STATUTES INSURANCE REGULATIONS Authorization of Self-Insurers § 703.303 Decision...

  12. 10 CFR 780.44 - Hearing and decision.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Hearing and decision. 780.44 Section 780.44 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153c of the Atomic Energy Act of 1954 § 780.44 Hearing and decision. In accordance with section 153d...

  13. 10 CFR 780.44 - Hearing and decision.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Hearing and decision. 780.44 Section 780.44 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153c of the Atomic Energy Act of 1954 § 780.44 Hearing and decision. In accordance with section 153d...

  14. 10 CFR 780.33 - Hearing and decision.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Hearing and decision. 780.33 Section 780.33 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153b(2) of the Atomic Energy Act of 1954 § 780.33 Hearing and decision. If any party requests a...

  15. 10 CFR 780.23 - Hearing and decision.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Hearing and decision. 780.23 Section 780.23 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Declaring Patents Affected With the Public Interest Under Section 153a of the Atomic Energy Act of 1954 § 780.23 Hearing and decision. If a...

  16. 10 CFR 780.23 - Hearing and decision.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Hearing and decision. 780.23 Section 780.23 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Declaring Patents Affected With the Public Interest Under Section 153a of the Atomic Energy Act of 1954 § 780.23 Hearing and decision. If a...

  17. 10 CFR 780.33 - Hearing and decision.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Hearing and decision. 780.33 Section 780.33 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153b(2) of the Atomic Energy Act of 1954 § 780.33 Hearing and decision. If any party requests a...

  18. 10 CFR 780.33 - Hearing and decision.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Hearing and decision. 780.33 Section 780.33 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153b(2) of the Atomic Energy Act of 1954 § 780.33 Hearing and decision. If any party requests a...

  19. 10 CFR 780.23 - Hearing and decision.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Hearing and decision. 780.23 Section 780.23 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Declaring Patents Affected With the Public Interest Under Section 153a of the Atomic Energy Act of 1954 § 780.23 Hearing and decision. If a...

  20. 10 CFR 780.44 - Hearing and decision.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Hearing and decision. 780.44 Section 780.44 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153c of the Atomic Energy Act of 1954 § 780.44 Hearing and decision. In accordance with section 153d...

  1. Cued to Act on Impulse: More Impulsive Choice and Risky Decision Making by Women Susceptible to Overeating after Exposure to Food Stimuli

    PubMed Central

    Yeomans, Martin R.; Brace, Aaron

    2015-01-01

    There is increasing evidence that individual differences in tendency to overeat relate to impulsivity, possibly by increasing reactivity to food-related cues in the environment. This study tested whether acute exposure to food cues enhanced impulsive and risky responses in women classified on tendency to overeat, indexed by scores on the three factor eating questionnaire disinhibition (TFEQ-D), restraint (TFEQ-R) and hunger scales. Ninety six healthy women completed two measures of impulsive responding (delayed discounting, DDT and a Go No-Go, GNG, task) and a measure of risky decision making (the balloon analogue risk task, BART) as well as questionnaire measures of impulsive behaviour either after looking at a series of pictures of food or visually matched controls. Impulsivity (DDT) and risk-taking (BART) were both positively associated with TFEQ-D scores, but in both cases this effect was exacerbated by prior exposure to food cues. No effects of restraint were found. TFEQ-D scores were also related to more commission errors on the GNG, while restrained women were slower on the GNG, but neither effect was modified by cue exposure. Overall these data suggest that exposure to food cues act to enhance general impulsive responding in women at risk of overeating and tentatively suggest an important interaction between tendency for impulsive decision making and food cues that may help explain a key underlying risk factor for overeating. PMID:26378459

  2. CHD1 acts via the Hmgpi pathway to regulate mouse early embryogenesis.

    PubMed

    Suzuki, Shinnosuke; Nozawa, Yusuke; Tsukamoto, Satoshi; Kaneko, Takehito; Manabe, Ichiro; Imai, Hiroshi; Minami, Naojiro

    2015-07-01

    The protein CHD1 is a member of the family of ATPase-dependent chromatin remodeling factors. CHD1, which recognizes trimethylated histone H3 lysine 4, has been implicated in transcriptional activation in organisms ranging from yeast to humans. It is required for pre-mRNA maturation, maintenance of mouse embryonic stem cell pluripotency and rapid growth of the mouse epiblast. However, the function(s) of CHD1 in mouse preimplantation embryos has not yet been examined. Here, we show that loss of CHD1 function led to embryonic lethality after implantation. In mouse embryos in which Chd1 was targeted by siRNA microinjection, the expression of the key regulators of cell fate specification Pou5f1 (also known as Oct4), Nanog and Cdx2 was dramatically decreased, starting at mid-preimplantation gene activation (MGA). Moreover, expression of Hmgpi and Klf5, which regulate Pou5f1, Nanog and Cdx2, was also significantly suppressed at zygotic gene activation (ZGA). Suppression of Hmgpi expression in Chd1-knockdown embryos continued until the blastocyst stage, whereas suppression of Klf5 expression was relieved by the morula stage. Next, we rescued HMGPI expression via Hmgpi mRNA microinjection in Chd1-knockdown embryos. Consequently, Pou5f1, Nanog and Cdx2 expression was restored at MGA and live offspring were recovered. These findings indicate that CHD1 plays important roles in mouse early embryogenesis via activation of Hmgpi at ZGA. PMID:26092847

  3. Two-Step Regulation of a Meristematic Cell Population Acting in Shoot Branching in Arabidopsis.

    PubMed

    Shi, Bihai; Zhang, Cui; Tian, Caihuan; Wang, Jin; Wang, Quan; Xu, Tengfei; Xu, Yan; Ohno, Carolyn; Sablowski, Robert; Heisler, Marcus G; Theres, Klaus; Wang, Ying; Jiao, Yuling

    2016-07-01

    Shoot branching requires the establishment of new meristems harboring stem cells; this phenomenon raises questions about the precise regulation of meristematic fate. In seed plants, these new meristems initiate in leaf axils to enable lateral shoot branching. Using live-cell imaging of leaf axil cells, we show that the initiation of axillary meristems requires a meristematic cell population continuously expressing the meristem marker SHOOT MERISTEMLESS (STM). The maintenance of STM expression depends on the leaf axil auxin minimum. Ectopic expression of STM is insufficient to activate axillary buds formation from plants that have lost leaf axil STM expressing cells. This suggests that some cells undergo irreversible commitment to a developmental fate. In more mature leaves, REVOLUTA (REV) directly up-regulates STM expression in leaf axil meristematic cells, but not in differentiated cells, to establish axillary meristems. Cell type-specific binding of REV to the STM region correlates with epigenetic modifications. Our data favor a threshold model for axillary meristem initiation, in which low levels of STM maintain meristematic competence and high levels of STM lead to meristem initiation. PMID:27398935

  4. Two-Step Regulation of a Meristematic Cell Population Acting in Shoot Branching in Arabidopsis

    PubMed Central

    Tian, Caihuan; Wang, Jin; Xu, Tengfei; Xu, Yan; Ohno, Carolyn; Sablowski, Robert; Heisler, Marcus G.; Theres, Klaus; Wang, Ying

    2016-01-01

    Shoot branching requires the establishment of new meristems harboring stem cells; this phenomenon raises questions about the precise regulation of meristematic fate. In seed plants, these new meristems initiate in leaf axils to enable lateral shoot branching. Using live-cell imaging of leaf axil cells, we show that the initiation of axillary meristems requires a meristematic cell population continuously expressing the meristem marker SHOOT MERISTEMLESS (STM). The maintenance of STM expression depends on the leaf axil auxin minimum. Ectopic expression of STM is insufficient to activate axillary buds formation from plants that have lost leaf axil STM expressing cells. This suggests that some cells undergo irreversible commitment to a developmental fate. In more mature leaves, REVOLUTA (REV) directly up-regulates STM expression in leaf axil meristematic cells, but not in differentiated cells, to establish axillary meristems. Cell type-specific binding of REV to the STM region correlates with epigenetic modifications. Our data favor a threshold model for axillary meristem initiation, in which low levels of STM maintain meristematic competence and high levels of STM lead to meristem initiation. PMID:27398935

  5. Tmem178 acts in a novel negative feedback loop targeting NFATc1 to regulate bone mass

    PubMed Central

    Decker, Corinne E.; Yang, Zhengfeng; Rimer, Ryan; Park-Min, Kyung-Hyun; Macaubas, Claudia; Mellins, Elizabeth D.; Novack, Deborah V.; Faccio, Roberta

    2015-01-01

    Phospholipase C gamma-2 (PLCγ2)-dependent calcium (Ca2+) oscillations are indispensable for nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) activation and downstream gene transcription driving osteoclastogenesis during skeletal remodeling and pathological bone loss. Here we describe, to our knowledge, the first known function of transmembrane protein 178 (Tmem178), a PLCγ2 downstream target gene, as a critical modulator of the NFATc1 axis. In surprising contrast to the osteopetrotic phenotype of PLCγ2−/− mice, Tmem178−/− mice are osteopenic in basal conditions and are more susceptible to inflammatory bone loss, owing to enhanced osteoclast formation. Mechanistically, Tmem178 localizes to the ER membrane and regulates RANKL-induced Ca2+ fluxes, thus controlling NFATc1 induction. Importantly, down-regulation of Tmem178 is observed in human CD14+ monocytes exposed to plasma from systemic juvenile idiopathic arthritis patients. Similar to the mouse model, reduced Tmem178 expression in human cells correlates with excessive osteoclastogenesis. In sum, these findings identify an essential role for Tmem178 to maintain skeletal mass and limit pathological bone loss. PMID:26644563

  6. The ZEB1 Transcription Factor Acts in a Negative Feedback Loop with miR200 Downstream of Ras and Rb1 to Regulate Bmi1 Expression*

    PubMed Central

    Liu, Yongqing; Sánchez-Tilló, Ester; Lu, Xiaoqin; Huang, Li; Clem, Brian; Telang, Sucheta; Jenson, Alfred B.; Cuatrecasas, Miriam; Chesney, Jason; Postigo, Antonio; Dean, Douglas C.

    2014-01-01

    Ras mutations are frequent in cancer cells where they drive proliferation and resistance to apoptosis. However in primary cells, mutant Ras instead can cause oncogene-induced senescence, a tumor suppressor function linked to repression of the polycomb factor Bmi1, which normally regulates cell cycle inhibitory cyclin-dependent kinase inhibitors (cdki). It is unclear how Ras causes repression of Bmi1 in primary cells to suppress tumor formation while inducing the gene in cancer cells to drive tumor progression. Ras also induces the EMT transcription factor ZEB1 to trigger tumor invasion and metastasis. Beyond its well-documented role in EMT, ZEB1 is important for maintaining repression of cdki. Indeed, heterozygous mutation of ZEB1 is sufficient for elevated cdki expression, leading to premature senescence of primary cells. A similar phenotype is evident with Bmi1 mutation. We show that activation of Rb1 in response to mutant Ras causes dominant repression of ZEB1 in primary cells, but loss of the Rb1 pathway is a hallmark of cancer cells and in the absence of such Rb1 repression Ras induces ZEB1 in cancer cells. ZEB1 represses miR-200 in the context of a mutual repression loop. Because miR-200 represses Bmi1, induction of ZEB1 leads to induction of Bmi1. Rb1 pathway status then dictates the opposing effects of mutant Ras on the ZEB1-miR-200 loop in primary versus cancer cells. This loop not only triggers EMT, surprisingly we show it acts downstream of Ras to regulate Bmi1 expression and thus the critical decision between oncogene-induced senescence and tumor initiation. PMID:24371144

  7. Nucleoside diphosphate regulation of overall rates of protein biosynthesis acting at the level of initiation.

    PubMed

    Hucul, J A; Henshaw, E C; Young, D A

    1985-12-15

    A sensitive assay method developed to examine the effects of subtle, physiologically relevant, changes in the levels of adenine and guanine mono-, di-, and triphosphorylated nucleotides specifically on the initiation of protein synthesis is described. Initiation rates are quantified by measuring the amount of protein synthesis resulting from the run-off of ribosomes which have initiated during defined intervals in a modified in vitro protein-synthesizing system developed from Ehrlich ascites tumor cell lysates (Henshaw, E.C., and Panniers, R. (1983) Methods Enzymol. 101, 616-629). The modifications include the attenuation of the ATP-regenerating system so that the relative nucleotide levels more nearly reflect actual intracellular conditions. With this system the rate of initiation is highly sensitive to changes in the ADP:ATP and GDP:GTP ratios, but indifferent to the absolute levels of either diphosphate. While the tight coupling of these two ratios by endogenous nucleoside diphosphate kinase activity prevents the independent manipulation of either ratio, the data do eliminate both AMP and GMP per se as inhibitory species. The close agreement of our data calculated in terms of energy charge to previously published results on overall rates of protein synthesis in rat thymocytes (Mendelsohn, S.K., Nordeen, S.K., and Young, D.A. (1977) Biochem. Biophys. Res. Commun. 79, 53-60) continues to suggest a physiologically relevant regulatory influence of subtle changes in nucleotides acting at the level of the initiation reaction. PMID:2999123

  8. LGI1 acts presynaptically to regulate excitatory synaptic transmission during early postnatal development.

    PubMed

    Boillot, Morgane; Lee, Chun-Yao; Allene, Camille; Leguern, Eric; Baulac, Stéphanie; Rouach, Nathalie

    2016-01-01

    The secreted leucine-rich glioma inactivated 1 (LGI1) protein is an important actor for human seizures of both genetic and autoimmune etiology: mutations in LGI1 cause inherited temporal lobe epilepsy, while LGI1 is involved in antibody-mediated encephalitis. Remarkably, Lgi1-deficient (Lgi1(-/-)) mice recapitulate the epileptic disorder and display early-onset spontaneous seizures. To understand how Lgi1-deficiency leads to seizures during postnatal development, we here investigated the early functional and structural defects occurring before seizure onset in Lgi1(-/-) mice. We found an increased excitatory synaptic transmission in hippocampal slices from Lgi1(-/-) mice. No structural alteration in the morphology of pyramidal cell dendrites and synapses was observed at this stage, indicating that Lgi1-deficiency is unlikely to trigger early developmental abnormalities. Consistent with the presynaptic subcellular localization of the protein, Lgi1-deficiency caused presynaptic defects, with no alteration in postsynaptic AMPA receptor activity in Lgi1-/- pyramidal cells before seizure onset. Presynaptic dysfunction led to increased synaptic glutamate levels, which were associated with hyperexcitable neuronal networks. Altogether, these data show that Lgi1 acts presynaptically as a negative modulator of excitatory synaptic transmission during early postnatal development. We therefore here reveal that increased presynaptic glutamate release is a key early event resulting from Lgi1-deficiency, which likely contributes to epileptogenesis. PMID:26878798

  9. LGI1 acts presynaptically to regulate excitatory synaptic transmission during early postnatal development

    PubMed Central

    Boillot, Morgane; Lee, Chun-Yao; Allene, Camille; Leguern, Eric; Baulac, Stéphanie; Rouach, Nathalie

    2016-01-01

    The secreted leucine-rich glioma inactivated 1 (LGI1) protein is an important actor for human seizures of both genetic and autoimmune etiology: mutations in LGI1 cause inherited temporal lobe epilepsy, while LGI1 is involved in antibody-mediated encephalitis. Remarkably, Lgi1-deficient (Lgi1−/−) mice recapitulate the epileptic disorder and display early-onset spontaneous seizures. To understand how Lgi1-deficiency leads to seizures during postnatal development, we here investigated the early functional and structural defects occurring before seizure onset in Lgi1−/− mice. We found an increased excitatory synaptic transmission in hippocampal slices from Lgi1−/− mice. No structural alteration in the morphology of pyramidal cell dendrites and synapses was observed at this stage, indicating that Lgi1-deficiency is unlikely to trigger early developmental abnormalities. Consistent with the presynaptic subcellular localization of the protein, Lgi1-deficiency caused presynaptic defects, with no alteration in postsynaptic AMPA receptor activity in Lgi1−/− pyramidal cells before seizure onset. Presynaptic dysfunction led to increased synaptic glutamate levels, which were associated with hyperexcitable neuronal networks. Altogether, these data show that Lgi1 acts presynaptically as a negative modulator of excitatory synaptic transmission during early postnatal development. We therefore here reveal that increased presynaptic glutamate release is a key early event resulting from Lgi1-deficiency, which likely contributes to epileptogenesis. PMID:26878798

  10. Ubiquitin-Fold Modifier 1 Acts as a Positive Regulator of Breast Cancer

    PubMed Central

    Yoo, Hee Min; Park, Jong Ho; Jeon, Young Joo; Chung, Chin Ha

    2015-01-01

    Estrogen receptor-α (ERα) is a steroid hormone-sensitive transcription factor that plays a critical role in development of breast cancer. The binding of estrogen to ERα triggers the recruitment of transcriptional co-activators as well as chromatin remodeling factors to estrogen-responsive elements (ERE) of ERα target genes. This process is tightly associated with post-translational modifications (PTMs) of ERα and its co-activators for promotion of transcriptional activation, which leads to proliferation of a large subset of breast tumor cells. These PTMs include phosphorylation, acetylation, methylation, and conjugation by ubiquitin and ubiquitin-like proteins. Ubiquitin-fold modifier 1 (UFM1), one of ubiquitin-like proteins, has recently been shown to be ligated to activating signal co-integrator 1 (ASC1), which acts as a transcriptional co-activator of nuclear receptors. Here, we discuss the mechanistic connection between ASC1 modification by UFM1 and ERα transactivation, and highlight how the interplay of these processes is involved in development of breast cancer. We also discuss potential use of UFM1-conjugating system as therapeutic targets against not only breast cancer but also other nuclear receptor-mediated cancers. PMID:25852645

  11. Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions

    PubMed Central

    Dong, Xintong; Chiu, Hui; Park, Yeonhee Jenny; Zou, Wei; Zou, Yan; Özkan, Engin; Chang, Chieh; Shen, Kang

    2016-01-01

    Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis. DOI: http://dx.doi.org/10.7554/eLife.11008.001 PMID:26974341

  12. miR-145 and miR-143 Regulate Smooth Muscle Cell Fate Decisions

    PubMed Central

    Cordes, Kimberly R.; Sheehy, Neil T.; White, Mark; Berry, Emily; Morton, Sarah U.; Muth, Alecia N.; Lee, Ting-Hein; Miano, Joseph M.; Ivey, Kathryn N.; Srivastava, Deepak

    2009-01-01

    SUMMARY microRNAs are regulators of myriad cellular events, but evidence for a single microRNA that can efficiently differentiate multipotent cells into a specific lineage or regulate direct reprogramming of cells into an alternate cell fate has been elusive. Here, we show that miR-145 and miR-143 are co-transcribed in multipotent cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem cell–derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2.5, and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4, myocardin, and Elk-1 to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells. PMID:19578358

  13. Paralogous Antirepressors Acting on the Master Regulator for Biofilm Formation in Bacillus subtilis

    PubMed Central

    Chai, Yunrong; Kolter, Roberto; Losick, Richard

    2009-01-01

    Summary Matrix production during biofilm formation by Bacillus subtilis is governed by a gene control circuit at the heart of which are three dedicated regulatory proteins, the antirepressor SinI, the repressor SinR, and the downstream regulator SlrR. Matrix production is triggered by the synthesis of SinI, which binds to and inactivates SinR, thereby derepressing genes for matrix production as well as the gene for SlrR. Recently, two additional regulators of matrix genes were identified: SlrA, which was reported to be an activator of SlrR, and YwcC, a repressor of SlrA synthesis. We present evidence indicating that SlrA, which is a paralog of SinI, is like SinI, an antirepressor that binds to, and inactivates, SinR. We also show that SlrA does not activate SlrR for expression of matrix genes. Instead, SlrR binds to, and inhibits the activity of, SlrA. Thus, the YwcC-SlrA-SinR-SlrR pathway is a negative feedback loop in which SlrA indirectly stimulates the synthesis of SlrR, and SlrR, in turn, inhibits the activity of SlrA. Finally, we report that under standard laboratory conditions SlrA makes only a small contribution to the expression of genes for matrix production. We propose that in response to an unknown signal recognized by the YwcC repressor, SlrA transiently boosts matrix production. PMID:19788541

  14. Prostanoids regulate angiogenesis acting primarily on IP and EP4 receptors.

    PubMed

    Hoang, Khuyen Gia; Allison, Sarah; Murray, Michael; Petrovic, Nenad

    2015-09-01

    Angiogenesis is regulated by numerous activators and inhibitors, including prostanoids. Although many studies have identified their roles in inflammation, regulatory functions of prostanoids in angiogenesis are poorly understood. Here, we compared the activation of angiogenesis in vitro by two prostanoids with important vascular roles: prostaglandin E2 (PGE2) - thought to be the most important prostanoid activator of angiogenesis - and prostaglandin I2 (prostacyclin or PGI2), whose receptors are predominantly expressed in endothelial cells. Both of these prostanoids activate G-protein coupled receptors: EP1, EP2, EP3 and EP4 by PGE2 and IP by prostacyclin. Human umbilical vein endothelial cells (HUVECs) were used to characterize two pivotal pro-angiogenic processes in vitro: cell migration (using the matrigel droplet assay developed in our laboratory) and "tube formation" (a widely accepted method of assessing formation of blood vessel precursors). The suppression of cell migration and tube formation by the IP-specific antagonist CAY10441 was more extensive (~80%) than by the EP4-specific antagonist L-161,982 (~20%). AH6809, an antagonist of EP1, EP2 and EP3 receptors did not significantly suppress angiogenesis. Expression of the pro-angiogenic receptors KDR and Tie-2 in HUVECs was preferentially suppressed by antagonism of IP and EP4 receptors, respectively. EP4 and IP receptor agonists elicited biphasic actions on angiogenic processes in which there was activation at low concentration, and rapid desensitization at high concentrations - a characteristic common to many G-protein coupled receptors. Together these findings suggest that the prostacyclin-IP pathway plays a major role in the regulation of pro-angiogenic processes in HUVECs. PMID:26188701

  15. 45 CFR 681.35 - Can a party request reconsideration of the initial decision?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Can a party request reconsideration of the initial decision? 681.35 Section 681.35 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Decisions and Appeals § 681.35 Can a...

  16. 45 CFR 681.35 - Can a party request reconsideration of the initial decision?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Can a party request reconsideration of the initial decision? 681.35 Section 681.35 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Decisions and Appeals § 681.35 Can a...

  17. DOCK2 and DOCK5 Act Additively in Neutrophils To Regulate Chemotaxis, Superoxide Production, and Extracellular Trap Formation

    PubMed Central

    Watanabe, Mayuki; Terasawa, Masao; Miyano, Kei; Yanagihara, Toyoshi; Uruno, Takehito; Sanematsu, Fumiyuki; Nishikimi, Akihiko; Côté, Jean-François; Sumimoto, Hideki; Fukui, Yoshinori

    2015-01-01

    Neutrophils are highly motile leukocytes that play important roles in the innate immune response to invading pathogens. Neutrophils rapidly migrate to the site of infections and kill pathogens by producing reactive oxygen species (ROS). Neutrophil chemotaxis and ROS production require activation of Rac small GTPase. DOCK2, an atypical guanine nucleotide exchange factor (GEF), is one of the major regulators of Rac in neutrophils. However, because DOCK2 deficiency does not completely abolish fMLF-induced Rac activation, other Rac GEFs may also participate in this process. In this study, we show that DOCK5 acts with DOCK2 in neutrophils to regulate multiple cellular functions. We found that fMLF- and PMA-induced Rac activation were almost completely lost in mouse neutrophils lacking both DOCK2 and DOCK5. Although β2 integrin–mediated adhesion occurred normally even in the absence of DOCK2 and DOCK5, mouse neutrophils lacking DOCK2 and DOCK5 exhibited a severe defect in chemotaxis and ROS production. Similar results were obtained when human neutrophils were treated with CPYPP, a small-molecule inhibitor of these DOCK GEFs. Additionally, we found that DOCK2 and DOCK5 regulate formation of neutrophil extracellular traps (NETs). Because NETs are involved in vascular inflammation and autoimmune responses, DOCK2 and DOCK5 would be a therapeutic target for controlling NET-mediated inflammatory disorders. PMID:25339677

  18. The conserved Misshapen-Warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila

    PubMed Central

    Li, Qi; Li, Shuangxi; Mana-Capelli, Sebastian; Roth Flach, Rachel J.; Danai, Laura V.; Amcheslavsky, Alla; Nie, Yingchao; Kaneko, Satoshi; Yao, Xiaohao; Chen, Xiaochu; Cotton, Jennifer L.; Mao, Junhao; McCollum, Dannel; Jiang, Jin; Czech, Michael P.; Xu, Lan; Ip, Y. Tony

    2014-01-01

    SUMMARY Similar to the mammalian intestine, the Drosophila adult midgut has resident stem cells that support growth and regeneration. How the niche regulates intestinal stem cell activity in both mammals and flies is not well understood. Here we show that the conserved germinal center protein kinase Misshapen restricts intestinal stem cell division by repressing the expression of the JAK-STAT pathway ligand Upd3 in differentiating enteroblasts. Misshapen, a distant relative to the prototypic Warts activating kinase Hippo, interacts with and activates Warts to negatively regulate the activity of Yorkie and the expression of Upd3. The mammalian Misshapen homolog MAP4K4 similarly interacts with LATS (Warts homolog) and promotes inhibition of YAP (Yorkie homolog). Together, this work reveals that the Misshapen-Warts-Yorkie pathway acts in enteroblasts to control niche signaling to intestinal stem cells. These findings also provide a model in which to study requirements for MAP4K4-related kinases in MST1/2-independent regulation of LATS and YAP. PMID:25453828

  19. Transferrin synthesis by small cell lung cancer cells acts as an autocrine regulator of cellular proliferation.

    PubMed Central

    Vostrejs, M; Moran, P L; Seligman, P A

    1988-01-01

    Since transferrin is required for cellular proliferation, we investigated transferrin synthesis by a small cell lung cancer line (NCI-H510) that survives in serum-free media without added transferrin. Immunoassays for human transferrin demonstrated that these cells contained immunoreactive human transferrin. Immunofluorescence studies showed that the protein is expressed on the surface of cells, presumably bound to transferrin receptor. Media conditioned by NCI-H510 cells support proliferation of human leukemic cells that would not survive in media lacking transferrin. [35S]Methionine incorporation documented transferrin synthesis by NCI-H510 cells as well as three other small cell lines. Transferrin synthesis by NCI-H510 cells increased more than 10-fold when cells entered active phases of the cell cycle, and this increase was seen before large increases in transferrin-receptor expression. Further experiments examining the effects of agents that affect iron metabolism show that the addition of transferrin-iron or hemin to the media is associated with a more rapid initial rate of proliferation and lower rates of transferrin synthesis than control cells. Gallium salts, which inhibit iron uptake, inhibited proliferation of these cells. If the cells recovered from this effect, transferrin synthesis remained greatly increased compared to control. We conclude that transferrin synthesis by these malignant cells is ultimately related to an iron requirement for cellular proliferation. It appears that this synthesized transferrin acts as part of an important autocrine mechanism permitting proliferation of these cells, and perhaps permitting tumor cell growth in vivo in areas not well vascularized. Images PMID:2839550

  20. National health information privacy: regulations under the Health Insurance Portability and Accountability Act.

    PubMed

    Gostin, L O

    2001-06-20

    Health information privacy is important in US society, but existing federal and state law does not offer adequate protection. The Department of Health and Human Services, under powers granted by the Health Insurance Portability and Accountability Act of 1996, recently issued a final rule providing systematic, nationwide health information privacy protection. The rule is extensive in its scope, applying to health plans, health care clearinghouses, and health care providers (hospitals, clinics, and health departments) who conduct financial transactions electronically ("covered entities"). The rule applies to personally identifiable information in any form, whether communicated electronically, on paper, or orally. The rule does not preempt state law that affords more stringent privacy protection; thus, the health care industry will have to comply with multiple layers of federal and state law. The rule affords patients rights to education about privacy safeguards, access to their medical records, and a process for correction of records. It also requires the patient's permission for disclosures of personal information. While privacy is an important value, it may conflict with public responsibilities to use data for social goods. The rule has special provisions for disclosure of health information for research, public health, law enforcement, and commercial marketing. The privacy debate will continue in Congress and within the president's administration. The primary focus will be on the costs and burdens on health care providers, the ability of health care professionals to use and share full medical information when treating patients, the provision of patient care in a timely and efficient manner, and parents' access to information about the health of their children. PMID:11410101

  1. Four Tomato FLOWERING LOCUS T-Like Proteins Act Antagonistically to Regulate Floral Initiation.

    PubMed

    Cao, Kai; Cui, Lirong; Zhou, Xiaoting; Ye, Lin; Zou, Zhirong; Deng, Shulin

    2015-01-01

    The transition from vegetative growth to floral meristems in higher plants is regulated through the integration of internal cues and environmental signals. We were interested to examine the molecular mechanism of flowering in the day-neutral plant tomato (Solanum lycopersicum L.) and the effect of environmental conditions on tomato flowering. Analysis of the tomato genome uncovered 13 PEBP (phosphatidylethanolamine-binding protein) genes, and found six of them were FT-like genes which named as SlSP3D, SlSP6A, SlSP5G, SlSP5G1, SlSP5G2, and SlSP5G3. Six FT-like genes were analyzed to clarify their functional roles in flowering using transgenic and expression analyses. We found that SlSP5G, SlSP5G2, and SlSP5G3 proteins were floral inhibitors whereas only SlSP3D/SFT (SINGLE FLOWER TRUSS) was a floral inducer. SlSP5G was expressed at higher levels in long day (LD) conditions compared to short day (SD) conditions while SlSP5G2 and SlSP5G3 showed the opposite expression patterns. The silencing of SlSP5G by VIGS (Virus induced gene silencing) resulted in tomato plants that flowered early under LD conditions and the silencing of SlSP5G2 and SlSP5G3 led to early flowering under SD conditions. The higher expression levels of SlSP5G under LD conditions were not seen in phyB1 mutants, and the expression levels of SlSP5G2 and SlSP5G3 were increased in phyB1 mutants under both SD and LD conditions compared to wild type plants. These data suggest that SlSP5G, SlSP5G2, and SlSP5G3 are controlled by photoperiod, and the different expression patterns of FT-like genes under different photoperiod may contribute to tomato being a day neutral plant. In addition, PHYB1 mediate the expression of SlSP5G, SlSP5G2, and SlSP5G3 to regulate flowering in tomato. PMID:26793202

  2. Four Tomato FLOWERING LOCUS T-Like Proteins Act Antagonistically to Regulate Floral Initiation

    PubMed Central

    Cao, Kai; Cui, Lirong; Zhou, Xiaoting; Ye, Lin; Zou, Zhirong; Deng, Shulin

    2016-01-01

    The transition from vegetative growth to floral meristems in higher plants is regulated through the integration of internal cues and environmental signals. We were interested to examine the molecular mechanism of flowering in the day-neutral plant tomato (Solanum lycopersicum L.) and the effect of environmental conditions on tomato flowering. Analysis of the tomato genome uncovered 13 PEBP (phosphatidylethanolamine-binding protein) genes, and found six of them were FT-like genes which named as SlSP3D, SlSP6A, SlSP5G, SlSP5G1, SlSP5G2, and SlSP5G3. Six FT-like genes were analyzed to clarify their functional roles in flowering using transgenic and expression analyses. We found that SlSP5G, SlSP5G2, and SlSP5G3 proteins were floral inhibitors whereas only SlSP3D/SFT (SINGLE FLOWER TRUSS) was a floral inducer. SlSP5G was expressed at higher levels in long day (LD) conditions compared to short day (SD) conditions while SlSP5G2 and SlSP5G3 showed the opposite expression patterns. The silencing of SlSP5G by VIGS (Virus induced gene silencing) resulted in tomato plants that flowered early under LD conditions and the silencing of SlSP5G2 and SlSP5G3 led to early flowering under SD conditions. The higher expression levels of SlSP5G under LD conditions were not seen in phyB1 mutants, and the expression levels of SlSP5G2 and SlSP5G3 were increased in phyB1 mutants under both SD and LD conditions compared to wild type plants. These data suggest that SlSP5G, SlSP5G2, and SlSP5G3 are controlled by photoperiod, and the different expression patterns of FT-like genes under different photoperiod may contribute to tomato being a day neutral plant. In addition, PHYB1 mediate the expression of SlSP5G, SlSP5G2, and SlSP5G3 to regulate flowering in tomato. PMID:26793202

  3. Cis-acting elements are required for selenium regulation of glutathione peroxidase-1 mRNA levels.

    PubMed Central

    Weiss, S L; Sunde, R A

    1998-01-01

    Classical glutathione peroxidase (GPX1) mRNA levels can decrease to less than 10% in selenium (Se)-deficient rat liver. The cis-acting nucleic acid sequence requirements for Se regulation of GPX1 mRNA levels were studied by transfecting Chinese hamster ovary (CHO) cells with GPX1 DNA constructs in which specific regions of the GPX1 gene were mutated, deleted, or replaced by comparable regions from unregulated genes such as phospholipid hydroperoxide glutathione peroxidase (GPX4). For each construct, stable transfectants were pooled two weeks after transfection, divided into Se-deficient (2 nM Se) or Se-adequate (200 nM Se) medium, and grown for an additional four days. On day of harvest, Se-deficient GPX1 and GPX4 activities averaged 13 +/- 2% and 15 +/- 2% of Se adequate levels, confirming that cellular Se status was dramatically altered by Se supplementation. RNA was isolated from replicate plates of cells and transfected mRNA levels were specifically determined by RNase protection assay. Analysis of chimeric GPX1/GPX4 constructs showed that the GPX4 3'-UTR can completely replace the GPX1 3'-UTR in Se regulation of GPX1 mRNA. We did not find any GPX1 coding regions that could be replaced by the corresponding GPX4 coding regions without diminishing or eliminating Se regulation of the transfected GPX1 mRNA. Further analysis of the GPX1 coding region demonstrated that the GPX1 Sec codon (UGA) and the GPX1 intron sequences are required for full Se regulation of transfected GPX1 mRNA levels. Mutations that moved the GPX1 Sec codon to three different positions within the GPX1 coding region suggest that the mechanism for Se regulation of GPX1 mRNA requires a Sec codon within exon 1. Lastly, we found that addition of the GPX1 3'-UTR to beta-globin mRNA can convey significant Se regulation to beta-globin mRNA levels when a UGA codon is placed within exon 1. We conclude that Se regulation of GPX1 mRNA requires a functional selenocysteine insertion sequence (SECIS) in the 3

  4. Adolescent-onset GABAA α1 silencing regulates reward-related decision making.

    PubMed

    Butkovich, Laura M; DePoy, Lauren M; Allen, Amanda G; Shapiro, Lauren P; Swanson, Andrew M; Gourley, Shannon L

    2015-08-01

    The GABAA receptor mediates fast, inhibitory signaling, and cortical expression of the α1 subunit increases during postnatal development. Certain pathological stimuli such as stressors or prenatal cocaine exposure can interfere with this process, but causal relationships between GABAA α1 deficiency and complex behavioral outcomes remain unconfirmed. We chronically reduced GABAA α1 expression selectively in the medial prefrontal cortex (prelimbic subregion) of mice using viral-mediated gene silencing of Gabra1. Adolescent-onset Gabra1 knockdown delayed the acquisition of a cocaine-reinforced instrumental response but spared cocaine seeking in extinction and in a cue-induced reinstatement procedure. To determine whether response acquisition deficits could be associated with impairments in action-outcome associative learning and memory, we next assessed behavioral sensitivity to instrumental contingency degradation. In this case, the predictive relationship between familiar actions and their outcomes is violated. Adolescent-onset knockdown, although not adult-onset knockdown, delayed the expression of goal-directed response strategies in this task, resulting instead in inflexible habit-like modes of response. Thus, the maturation of medial prefrontal cortex GABAA α1 systems during adolescence appears necessary for goal-directed reward-related decision making in adulthood. These findings are discussed in the light of evidence that prolonged Gabra1 deficiency may impair synaptic plasticity. PMID:26096050

  5. 16 CFR 700.8 - Warrantor's decision as final.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Warrantor's decision as final. 700.8 Section 700.8 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE MAGNUSON-MOSS WARRANTY ACT INTERPRETATIONS OF MAGNUSON-MOSS WARRANTY ACT § 700.8...

  6. 16 CFR 700.8 - Warrantor's decision as final.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Warrantor's decision as final. 700.8 Section 700.8 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE MAGNUSON-MOSS WARRANTY ACT INTERPRETATIONS OF MAGNUSON-MOSS WARRANTY ACT § 700.8...

  7. 16 CFR 700.8 - Warrantor's decision as final.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Warrantor's decision as final. 700.8 Section 700.8 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE MAGNUSON-MOSS WARRANTY ACT INTERPRETATIONS OF MAGNUSON-MOSS WARRANTY ACT § 700.8...

  8. 16 CFR 700.8 - Warrantor's decision as final.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Warrantor's decision as final. 700.8 Section 700.8 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE MAGNUSON-MOSS WARRANTY ACT INTERPRETATIONS OF MAGNUSON-MOSS WARRANTY ACT § 700.8...

  9. Regulation of DNA replication in irradiated cells by trans-acting factors

    SciTech Connect

    Wang, Y.; Huq, M.S.; Cheng, X.; Iliakis, G.

    1995-05-01

    We compared DNA replication activity in cytoplasmic extracts prepared from irradiated and nonirradiated HeLa cells using a simian virus 40 (SV40)-based in vitro replication assay. The assay measures semi-conservative DNA replication in a plasmid carrying the SV40 origin of replication and requires SV40 T antigen as the sole noncellular protein. The plasmid DNA used in the replication reaction is never exposed to radiation. We find that replication of plasmid DNA is significantly reduced when cytoplasmic extracts from irradiated cells are used. Since plasmid replication proceeds to completion in extracts from irradiated cells, the observed reduction in the overall replication activity is probably due to a reduction in the efficiency of initiation events. The degree of inhibition of DNA replication after exposure to 10, 30 and 50 Gy X rays as measured in vitro using this assay is similar to that measured in intact cells immediately before processing for extract preparation. These observations are compatible with the induction or activation by ionizing radiation of a factor(s) that inhibits in trans DNA replication. The results contribute to our understanding of the mechanism(s) developed by the cells to regulate DNA replication when exposed to clastogenic agents. Such processes may be of significance in the restoration of DNA integrity, and may define yet another checkpoint operating during S at the level of clusters of replicons. 26 refs., 4 figs.

  10. GABAA receptor-acting neurosteroids: A role in the development and regulation of the stress response

    PubMed Central

    Gunn, Benjamin G.; Cunningham, Linda; Mitchell, Scott G.; Swinny, Jerome D.; Lambert, Jeremy J.; Belelli, Delia

    2015-01-01

    Regulation of hypothalamic–pituitary–adrenocortical (HPA) axis activity by stress is a fundamental survival mechanism and HPA-dysfunction is implicated in psychiatric disorders. Adverse early life experiences, e.g. poor maternal care, negatively influence brain development and programs an abnormal stress response by encoding long-lasting molecular changes, which may extend to the next generation. How HPA-dysfunction leads to the development of affective disorders is complex, but may involve GABAA receptors (GABAARs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABAARs and exhibit stress-protective properties. Importantly, neurosteroid levels rise rapidly during acute stress, are perturbed in chronic stress and are implicated in the behavioural changes associated with early-life adversity. We will appraise how GABAAR-active neurosteroids may impact on HPA axis development and the orchestration of the stress-evoked response. The significance of these actions will be discussed in the context of stress-associated mood disorders. PMID:24929099

  11. Vinculin acts as a sensor in lipid regulation of adhesion-site turnover.

    PubMed

    Chandrasekar, Indra; Stradal, Theresia E B; Holt, Mark R; Entschladen, Frank; Jockusch, Brigitte M; Ziegler, Wolfgang H

    2005-04-01

    The dynamics of cell adhesion sites control cell morphology and motility. Adhesion-site turnover is thought to depend on the local availability of the acidic phospholipid phosphatidylinositol-4,5-bisphosphate (PIP(2)). PIP(2) can bind to many cell adhesion proteins such as vinculin and talin, but the consequences of this interaction are poorly understood. To study the significance of phospholipid binding to vinculin for adhesion-site turnover and cell motility, we constructed a mutant, vinculin-LD, deficient in acidic phospholipid binding yet with functional actin-binding sites. When expressed in cells, vinculin-LD was readily recruited to adhesion sites, as judged by fluorescence recovery after photobleaching (FRAP) analysis, but cell spreading and migration were strongly impaired, and PIP(2)-dependent disassembly of adhesions was suppressed. Thus, PIP(2) binding is not essential for vinculin activation and recruitment, as previously suggested. Instead, we propose that PIP(2) levels can regulate the uncoupling of adhesion sites from the actin cytoskeleton, with vinculin functioning as a sensor. PMID:15769850

  12. Definition of spouse under the Family and Medical Leave Act. Final rule.

    PubMed

    2015-02-25

    The Department of Labor's (Department) Wage and Hour Division (WHD) revises the regulation defining "spouse" under the Family and Medical Leave Act of 1993 (FMLA or the Act) in light of the United States Supreme Court's decision in United States v. Windsor, which found section 3 of the Defense of Marriage Act (DOMA) to be unconstitutional. PMID:25898422

  13. FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation

    PubMed Central

    Roth, Martin; Bonev, Boyan; Lindsay, Jennefer; Lea, Robert; Panagiotaki, Niki; Houart, Corinne; Papalopulu, Nancy

    2010-01-01

    FoxG1 is a conserved transcriptional repressor that plays a key role in the specification, proliferation and differentiation of the telencephalon, and is expressed from the earliest stages of telencephalic development through to the adult. How the interaction with co-factors might influence the multiplicity and diversity of FoxG1 function is not known. Here, we show that interaction of FoxG1 with TLE2, a Xenopus tropicalis co-repressor of the Groucho/TLE family, is crucial for regulating the early activity of FoxG1. We show that TLE2 is co-expressed with FoxG1 in the ventral telencephalon from the early neural plate stage and functionally cooperates with FoxG1 in an ectopic neurogenesis assay. FoxG1 has two potential TLE binding sites: an N-terminal eh1 motif and a C-terminal YWPMSPF motif. Although direct binding seems to be mediated by the N-terminal motif, both motifs appear important for functional synergism. In the neurogenesis assay, mutation of either motif abolishes functional cooperation of TLE2 with FoxG1, whereas in the forebrain deletion of both motifs renders FoxG1 unable to induce the ventral telencephalic marker Nkx2.1. Knocking down either FoxG1 or TLE2 disrupts the development of the ventral telencephalon, supporting the idea that endogenous TLE2 and FoxG1 work together to specify the ventral telencephalon. PMID:20356955

  14. IL-4 acts as a homeostatic regulator of IL-2-induced TNF and IFN-gamma.

    PubMed Central

    Bello-Fernandez, C; Oblakowski, P; Meager, A; Duncombe, A S; Rill, D M; Hoffbrand, A V; Brenner, M K

    1991-01-01

    Interleukin-4 (IL-4) is a cytokine secreted by interleukin-2 (IL-2)-activated lymphocytes. IL-2-stimulated lymphocytes also secrete two cytokines, tumour necrosis factor (TNF) and gamma-interferon (IFN-gamma), which contribute to effector function and which may themselves recruit fresh, cytokine-secreting effector cells. We have now investigated whether the IL-4 induced is able to homeostatically regulate secretion of the TNF and IFN-gamma. Peripheral blood mononuclear cells or lymphocytes from normal donors and from patients with neoplastic disease were cultured in the presence of IL-2 alone, IL-4 alone or with both cytokines. IL-2 induced high levels of TNF and IFN-gamma secretion in both groups. The addition of recombinant IL-4 to these IL-2-stimulated cultures lead to significant inhibition of IFN-gamma and TNF production. IFN-gamma secretion was reduced by 50-99% in normal donors and by between 11% and 99% in patients (P less than 0.001). TNF levels induced by IL-2 were similarly reduced by IL-4 both in normal donors (P less than 0.003) and in patients (P less than 0.01). These inhibitory effects were produced by IL-4 at doses of IL-2 attainable in vivo. Inhibition appears to represent a homeostatic regulatory mechanism which may limit recruitment of fresh activated killer (AK) cells. When endogenous IL-4 activity in IL-2-activated lymphocytes was blocked by anti-IL-4 antibody, significantly higher levels of IFN-gamma and TNF were secreted (P less than 0.05). Since both TNF and IFN-gamma may contribute to the anti-neoplastic action of IL-2, manipulating the level of IL-4 activity in vivo could augment the benefits of IL-2 immunotherapy. PMID:1901829

  15. The pif1 helicase, a negative regulator of telomerase, acts preferentially at long telomeres.

    PubMed

    Phillips, Jane A; Chan, Angela; Paeschke, Katrin; Zakian, Virginia A

    2015-04-01

    Telomerase, the enzyme that maintains telomeres, preferentially lengthens short telomeres. The S. cerevisiae Pif1 DNA helicase inhibits both telomerase-mediated telomere lengthening and de novo telomere addition at double strand breaks (DSB). Here, we report that the association of the telomerase subunits Est2 and Est1 at a DSB was increased in the absence of Pif1, as it is at telomeres, suggesting that Pif1 suppresses de novo telomere addition by removing telomerase from the break. To determine how the absence of Pif1 results in telomere lengthening, we used the single telomere extension assay (STEX), which monitors lengthening of individual telomeres in a single cell cycle. In the absence of Pif1, telomerase added significantly more telomeric DNA, an average of 72 nucleotides per telomere compared to the 45 nucleotides in wild type cells, and the fraction of telomeres lengthened increased almost four-fold. Using an inducible short telomere assay, Est2 and Est1 no longer bound preferentially to a short telomere in pif1 mutant cells while binding of Yku80, a telomere structural protein, was unaffected by the status of the PIF1 locus. Two experiments demonstrate that Pif1 binding is affected by telomere length: Pif1 (but not Yku80) -associated telomeres were 70 bps longer than bulk telomeres, and in the inducible short telomere assay, Pif1 bound better to wild type length telomeres than to short telomeres. Thus, preferential lengthening of short yeast telomeres is achieved in part by targeting the negative regulator Pif1 to long telomeres. PMID:25906395

  16. Phosphorylation of the Synaptonemal Complex Protein Zip1 Regulates the Crossover/Noncrossover Decision during Yeast Meiosis

    PubMed Central

    Chen, Xiangyu; Suhandynata, Ray T.; Sandhu, Rima; Rockmill, Beth; Mohibullah, Neeman; Niu, Hengyao; Liang, Jason; Lo, Hsiao-Chi; Miller, Danny E.; Zhou, Huilin; Börner, G. Valentin; Hollingsworth, Nancy M.

    2015-01-01

    Interhomolog crossovers promote proper chromosome segregation during meiosis and are formed by the regulated repair of programmed double-strand breaks. This regulation requires components of the synaptonemal complex (SC), a proteinaceous structure formed between homologous chromosomes. In yeast, SC formation requires the “ZMM” genes, which encode a functionally diverse set of proteins, including the transverse filament protein, Zip1. In wild-type meiosis, Zmm proteins promote the biased resolution of recombination intermediates into crossovers that are distributed throughout the genome by interference. In contrast, noncrossovers are formed primarily through synthesis-dependent strand annealing mediated by the Sgs1 helicase. This work identifies a conserved region on the C terminus of Zip1 (called Zip1 4S), whose phosphorylation is required for the ZMM pathway of crossover formation. Zip1 4S phosphorylation is promoted both by double-strand breaks (DSBs) and the meiosis-specific kinase, MEK1/MRE4, demonstrating a role for MEK1 in the regulation of interhomolog crossover formation, as well as interhomolog bias. Failure to phosphorylate Zip1 4S results in meiotic prophase arrest, specifically in the absence of SGS1. This gain of function meiotic arrest phenotype is suppressed by spo11Δ, suggesting that it is due to unrepaired breaks triggering the meiotic recombination checkpoint. Epistasis experiments combining deletions of individual ZMM genes with sgs1-md zip1-4A indicate that Zip1 4S phosphorylation functions prior to the other ZMMs. These results suggest that phosphorylation of Zip1 at DSBs commits those breaks to repair via the ZMM pathway and provides a mechanism by which the crossover/noncrossover decision can be dynamically regulated during yeast meiosis. PMID:26682552

  17. Hemoglobin Control of Cell Survival/Death Decision Regulates in Vitro Plant Embryogenesis1[W][OPEN

    PubMed Central

    Huang, Shuanglong; Hill, Robert D.; Wally, Owen S.D.; Dionisio, Giuseppe; Ayele, Belay T.; Jami, Sravan Kumar; Stasolla, Claudio

    2014-01-01

    Programmed cell death (PCD) in multicellular organisms is a vital process in growth, development, and stress responses that contributes to the formation of tissues and organs. Although numerous studies have defined the molecular participants in apoptotic and PCD cascades, successful identification of early master regulators that target specific cells to live or die is limited. Using Zea mays somatic embryogenesis as a model system, we report that the expressions of two plant hemoglobin (Hb) genes (ZmHb1 and ZmHb2) regulate the cell survival/death decision that influences somatic embryogenesis through their cell-specific localization patterns. Suppression of either of the two ZmHbs is sufficient to induce PCD through a pathway initiated by elevated NO and Zn2+ levels and mediated by production of reactive oxygen species. The effect of the death program on the fate of the developing embryos is dependent on the localization patterns of the two ZmHbs. During somatic embryogenesis, ZmHb2 transcripts are restricted to a few cells anchoring the embryos to the subtending embryogenic tissue, whereas ZmHb1 transcripts extend to several embryonic domains. Suppression of ZmHb2 induces PCD in the anchoring cells, allowing the embryos to develop further, whereas suppression of ZmHb1 results in massive PCD, leading to abortion. We conclude that regulation of the expression of these ZmHbs has the capability to determine the developmental fate of the embryogenic tissue during somatic embryogenesis through their effect on PCD. This unique regulation might have implications for development and differentiation in other species. PMID:24784758

  18. The Exosome and Trans-Acting Small Interfering RNAs Regulate Cuticular Wax Biosynthesis during Arabidopsis Inflorescence Stem Development1[OPEN

    PubMed Central

    Lam, Patricia; Zhao, Lifang; Eveleigh, Nathan; Yu, Yu; Chen, Xuemei

    2015-01-01

    The primary aerial surfaces of land plants are covered with a cuticle, a protective layer composed of the cutin polyester matrix and cuticular waxes. Previously, we discovered a unique mechanism of regulating cuticular wax biosynthesis during Arabidopsis (Arabidopsis thaliana) stem elongation that involves ECERIFERUM7 (CER7), a core subunit of the exosome. Because loss-of-function mutations in CER7 result in reduced expression of the wax biosynthetic gene CER3, we proposed that CER7 is involved in degrading a messenger RNA encoding a CER3 repressor. To identify this putative repressor, we performed a cer7 suppressor screen that resulted in the isolation of the posttranscriptional gene-silencing components RNA-DEPENDENT RNA POLYMERASE1 and SUPPRESSOR OF GENE SILENCING3, indicating that small RNAs regulate CER3 expression. To establish the identity of the effector RNA species and determine whether these RNAs control CER3 transcript levels directly, we cloned additional genes identified in our suppressor screen and performed next-generation sequencing of small RNA populations that differentially accumulate in the cer7 mutant in comparison with the wild type. Our results demonstrate that the trans-acting small interfering RNA class of small RNAs are the effector molecules involved in direct silencing of CER3 and that the expression of five additional genes (EARLY RESPONSE TO DEHYDRATION14, AUXIN RESISTANT1, a translation initiation factor SUI1 family protein, and two genes of unknown function) is controlled by both CER7 and trans-acting small interfering RNAs. PMID:25502190

  19. Diversification of a Transcription Factor Family Led to the Evolution of Antagonistically Acting Genetic Regulators of Root Hair Growth.

    PubMed

    Breuninger, Holger; Thamm, Anna; Streubel, Susanna; Sakayama, Hidetoshi; Nishiyama, Tomoaki; Dolan, Liam

    2016-06-20

    Streptophytes colonized the land some time before 470 million years ago [1-3]. The colonization coincided with an increase in morphological and cellular diversity [4-7]. This increase in diversity is correlated with a proliferation in transcription factors encoded in genomes [8-10]. This suggests that gene duplication and subsequent diversification of function was instrumental in the generation of land plant diversity. Here, we investigate the diversification of the streptophyte-specific Lotus japonicus ROOTHAIRLESS LIKE (LRL) transcription factor (TF) [11, 12] subfamily of basic loop helix (bHLH) proteins by comparing gene function in early divergent and derived land plant species. We report that the single Marchantia polymorpha LRL gene acts as a general growth regulator required for rhizoid development, a function that has been partially conserved throughout multicellular streptophytes. In contrast, the five relatively derived Arabidopsis thaliana LRL genes comprise two antagonistically acting groups of differentially expressed genes. The diversification of LRL genes accompanied the evolution of an antagonistic regulatory element controlling root hair development. PMID:27265398

  20. 45 CFR 681.37 - What are the procedures for appealing the ALJ decision?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SCIENCE FOUNDATION PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Decisions and Appeals § 681.37 What are... initial 30-day period and shows good cause. (c) The defendant's appeal will not be considered until...

  1. 45 CFR 681.37 - What are the procedures for appealing the ALJ decision?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SCIENCE FOUNDATION PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Decisions and Appeals § 681.37 What are... initial 30-day period and shows good cause. (c) The defendant's appeal will not be considered until...

  2. 45 CFR 681.37 - What are the procedures for appealing the ALJ decision?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SCIENCE FOUNDATION PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Decisions and Appeals § 681.37 What are... initial 30-day period and shows good cause. (c) The defendant's appeal will not be considered until...

  3. 45 CFR 681.37 - What are the procedures for appealing the ALJ decision?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SCIENCE FOUNDATION PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Decisions and Appeals § 681.37 What are... initial 30-day period and shows good cause. (c) The defendant's appeal will not be considered until...

  4. 45 CFR 681.37 - What are the procedures for appealing the ALJ decision?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SCIENCE FOUNDATION PROGRAM FRAUD CIVIL REMEDIES ACT REGULATIONS Decisions and Appeals § 681.37 What are... initial 30-day period and shows good cause. (c) The defendant's appeal will not be considered until...

  5. The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity

    PubMed Central

    2011-01-01

    Background Thousands of different long non-coding RNAs are expressed during embryonic development, but the function of these molecules remains largely unexplored. Results Here we characterize the expression and function of Six3OS, a long non-coding RNA that is transcribed from the distal promoter region of the gene encoding the homeodomain transcription factor Six3. Overexpression and knockdown analysis of Six3OS reveals that it plays an essential role in regulating retinal cell specification. We further observe that Six3OS regulates Six3 activity in developing retina, but does not do so by modulating Six3 expression. Finally, we show that Six3OS binds directly to Ezh2 and Eya family members, indicating that Six3OS can act as a molecular scaffold to recruit histone modification enzymes to Six3 target genes. Conclusions Our findings demonstrate a novel mechanism by which promoter-associated long non-coding RNAs can modulate the activity of their associated protein coding genes, and highlight the importance of this diverse class of molecules in the control of neural development. PMID:21936910

  6. c-Myb acts in parallel and cooperatively with Cebp1 to regulate neutrophil maturation in zebrafish.

    PubMed

    Jin, Hao; Huang, Zhibin; Chi, Yali; Wu, Mei; Zhou, Riyang; Zhao, Lingfeng; Xu, Jin; Zhen, Fenghua; Lan, Yahui; Li, Li; Zhang, Wenqing; Wen, Zilong; Zhang, Yiyue

    2016-07-21

    Neutrophils are the key effectors for generating innate immunity in response to pathogenic infection and tissue injury in vertebrates. Dysregulation of neutrophil development and function is known to associate with various human disorders. Yet, the genetic network that orchestrates lineage commitment, differentiation, and maturation of neutrophils remains incompletely defined. Here, we present an in vivo study to delineate the genetic program underlying neutrophil development during zebrafish embryonic myelopoiesis. We show that loss of c-Myb function has no effect on macrophages but severely impairs neutrophil terminal differentiation, resulting in the accumulation of neutrophils with unsegmented nuclei and scant granule. This neutrophilic defect, which resembles the neutrophil-specific granule deficiency (SGD) caused by the mutations in CCAAT/enhancer-binding protein ε (C/EBPε) in humans, is attributed, at least in part, to the downregulation of the granule protein transcription. Likewise, genetic inactivation of Cebp1, the zebrafish functional homolog of mammalian C/EBPε, also leads to a similar SGD-like phenotype in zebrafish. Genetic epistasis and biochemical analysis further reveals that c-Myb and Cebp1 act in parallel and cooperatively to control neutrophil differentiation by directly regulating granule protein gene transcription. Our study indicates that c-MYB is an intrinsic master regulator for neutrophil terminal differentiation and a potential target in SGD patients. PMID:27268086

  7. Hsa-miR-495 acts as a tumor suppressor gene in glioma via the negative regulation of MYB.

    PubMed

    Zhang, Benping; Yuan, Fei; Liu, Jie; Li, Yang; Zhou, Fucheng; Liu, Xuanxi; Hao, Zhen; Li, Qingsong; Zheng, Yongri; Wang, Weizhi

    2016-07-01

    MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Previous studies have reported that there are causative links between the abnormal regulation of miRNAs and cancer development. Hsa‑miR‑495 has previously been demonstrated to be downregulated, and to function as a tumor suppressor, in numerous types of human cancer. However, the function and molecular mechanism of hsa‑miR‑495 in glioma remains unclear. In the current study, the expression and effects of hsa‑miR‑495 on glioma were evaluated. It was identified that the expression levels of hsa-miR-495 were downregulated in glioma tissues and cell lines. Furthermore, restoration of hsa-miR-495 inhibited glioma cell proliferation and invasion in vitro. Notably, a luciferase reporter assay revealed that hsa‑miR‑495 was able to directly target v‑myb avian myeloblastosis viral oncogene homolog (MYB) in glioma cells. In addition, an RNA interference assay indicated that MYB knockdown inhibited glioma cell proliferation and invasion in vitro. In conclusion, the results of the present study suggested that hsa‑miR‑495 may act as a tumor suppressor gene in glioma by directly inhibiting MYB expression, which may provide a novel therapeutic strategy for the treatment of glioma. PMID:27220777

  8. Cooperative and Antagonistic Contributions of Two Heterochromatin Proteins to Transcriptional Regulation of the Drosophila Sex Determination Decision

    PubMed Central

    Li, Hui; Rodriguez, Janel; Yoo, Youngdong; Shareef, Momin Mohammed; Badugu, RamaKrishna

    2011-01-01

    Eukaryotic nuclei contain regions of differentially staining chromatin (heterochromatin), which remain condensed throughout the cell cycle and are largely transcriptionally silent. RNAi knockdown of the highly conserved heterochromatin protein HP1 in Drosophila was previously shown to preferentially reduce male viability. Here we report a similar phenotype for the telomeric partner of HP1, HOAP, and roles for both proteins in regulating the Drosophila sex determination pathway. Specifically, these proteins regulate the critical decision in this pathway, firing of the establishment promoter of the masterswitch gene, Sex-lethal (Sxl). Female-specific activation of this promoter, SxlPe, is essential to females, as it provides SXL protein to initiate the productive female-specific splicing of later Sxl transcripts, which are transcribed from the maintenance promoter (SxlPm) in both sexes. HOAP mutants show inappropriate SxlPe firing in males and the concomitant inappropriate splicing of SxlPm-derived transcripts, while females show premature firing of SxlPe. HP1 mutants, by contrast, display SxlPm splicing defects in both sexes. Chromatin immunoprecipitation assays show both proteins are associated with SxlPe sequences. In embryos from HP1 mutant mothers and Sxl mutant fathers, female viability and RNA polymerase II recruitment to SxlPe are severely compromised. Our genetic and biochemical assays indicate a repressing activity for HOAP and both activating and repressing roles for HP1 at SxlPe. PMID:21695246

  9. Decision Point 2 of Statement of Project Objectives (SOPO) “Recovery Act: Development of ITM Oxygen Technology for Integration with Advanced Industrial Systems”

    SciTech Connect

    Armstrong, Phillip

    2011-08-01

    Air Products is carrying out a scope of work under Phase 5 of the ITM Oxygen Cooperative Agreement to design, build, and operate a ceramic membrane fabrication facility (the “CerFab”) to enable production of membrane modules to supply a conceptual 2000 ton per day (TPD) ITM Oxygen facility (the “ITM Oxygen Development Facility”), and to perform supporting development tasks in materials development an engineering development toward industrial, carbon capture and sequestration applications. Air Products is executing this project under the American Recovery and Reinvestment Act (ARRA) with the objective to accelerate the adoption of ITM Oxygen technology to help meet the country’s goals for deploying clean power plants. The objective of this Topical Report is to address the requirements of Decision Point 2, which pertains to progress in Materials Development, Engineering Development, and construction of the CerFab, with an emphasis on establishing the environmental permitting required prior to the next Decision Point. In the area of Materials Development, Air Products has specified a high pressure dilatometer system which will enable measurements of material expansion of ITM ceramic compounds at very high oxygen partial pressures consistent with CCS applications. Also in this area, Ceramatec has made significant progress in developing Advanced Architecture wafers and modules by advancing in parallel with two production methods of the Advanced Architecture components and determining the appropriate equipment required to make these components at high volume in the CerFab. Work in this area continues to refine the CerFab requirements. Under Engineering Development, Air Products has developed various concepts around use of ITM in industrial applications to reduce carbon footprint though process integrations that result in less fuel requirement. Air Products also developed notions around hybrid cryogenic air separation plants with ITM Oxygen plants for scale

  10. CK2 acts as a potent negative regulator of receptor-mediated insulin release in vitro and in vivo.

    PubMed

    Rossi, Mario; Ruiz de Azua, Inigo; Barella, Luiz F; Sakamoto, Wataru; Zhu, Lu; Cui, Yinghong; Lu, Huiyan; Rebholz, Heike; Matschinsky, Franz M; Doliba, Nicolai M; Butcher, Adrian J; Tobin, Andrew B; Wess, Jürgen

    2015-12-01

    G protein-coupled receptors (GPCRs) regulate virtually all physiological functions including the release of insulin from pancreatic β-cells. β-Cell M3 muscarinic receptors (M3Rs) are known to play an essential role in facilitating insulin release and maintaining proper whole-body glucose homeostasis. As is the case with other GPCRs, M3R activity is regulated by phosphorylation by various kinases, including GPCR kinases and casein kinase 2 (CK2). At present, it remains unknown which of these various kinases are physiologically relevant for the regulation of β-cell activity. In the present study, we demonstrate that inhibition of CK2 in pancreatic β-cells, knockdown of CK2α expression, or genetic deletion of CK2α in β-cells of mutant mice selectively augmented M3R-stimulated insulin release in vitro and in vivo. In vitro studies showed that this effect was associated with an M3R-mediated increase in intracellular calcium levels. Treatment of mouse pancreatic islets with CX4945, a highly selective CK2 inhibitor, greatly reduced agonist-induced phosphorylation of β-cell M3Rs, indicative of CK2-mediated M3R phosphorylation. We also showed that inhibition of CK2 greatly enhanced M3R-stimulated insulin secretion in human islets. Finally, CX4945 treatment protected mice against diet-induced hyperglycemia and glucose intolerance in an M3R-dependent fashion. Our data demonstrate, for the first time to our knowledge, the physiological relevance of CK2 phosphorylation of a GPCR and suggest the novel concept that kinases acting on β-cell GPCRs may represent novel therapeutic targets. PMID:26598688

  11. p53 Acts as a Co-Repressor to Regulate Keratin 14 Expression during Epidermal Cell Differentiation

    PubMed Central

    Chao, Chung-Faye; Lu, Mei-Hua; Lin, Hwang-Chi; Chiou, Shih-Hwa; Tao, Pao-Luh; Chen, Jang-Yi

    2012-01-01

    During epidermal cell differentiation, keratin 14 (K14) expression is down-regulated, p53 expression varies, and the expression of the p53 target genes, p21 and 14-3-3σ, increases. These trends suggest that the relative transcriptional activity of p53 is increased during epidermal cell differentiation. To determine the relationship between K14 and p53, we constructed K14 promoters of various sizes and found that wild-type p53 could repress the promoter activity of all of the K14 promoter constructs in H1299 cells. K14-p160 contains an SP1 binding site mutation that prevents p53 from repressing K14 expression. Using a DNA affinity precipitation assay, we confirmed that p53 forms a complex with SP1 at the SP1 binding site between nucleotides -48 and -43 on the K14 promoter. Thus, our data indicate that p53 acts as a co-repressor to down-regulate K14 expression by binding to SP1. Next, we used a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal cell differentiation model to examine the inhibition of K14 expression caused by increased p53 activity. Human ovarian teratocarcinoma C9 cells were treated with TPA to induce differentiation. Over-expression of the dominant negative p53 mutant ΔTAp53, which inhibits p53 activity, prevented the TPA-induced K14 down-regulation in C9 cells. Furthermore, treatment of normal primary human foreskin keratinocytes (PHFK) with the p53 inhibitor pifithrin-α (PFT-α) showed that the inhibition of p53 activity relieves K14 repression during epidermal cell differentiation. Finally, we found that TPA induces the phosphorylation of p53 at residue 378, which enhances the affinity of p53 to bind to Sp1 and repress K14 expression. PMID:22911849

  12. Microsimulation of Private Health Insurance and Medicaid Take-Up Following the U.S. Supreme Court Decision Upholding the Affordable Care Act

    PubMed Central

    Parente, Stephen T; Feldman, Roger

    2013-01-01

    Objective To predict take-up of private health insurance and Medicaid following the U.S. Supreme Court decision upholding the Affordable Care Act (ACA). Data Sources Data came from three large employers and a sampling of premiums from http://ehealthinsurance.com. We supplemented the employer data with information on state Medicaid eligibility and costs from the Kaiser Family Foundation. National predictions were based on the MEPS Household Component. Study Design We estimated a conditional logit model of health plan choice in the large group market. Using the coefficients from the choice model, we predicted take-up in the group and individual health insurance markets. Following ACA implementation, we added choices to the individual market corresponding to plans that will be available in state and federal exchanges. Depending on eligibility for premium subsidies, we reduced the out-of-pocket premiums for those choices. We simulated several possible patterns for states opting out of the Medicaid expansion, as allowed by the Supreme Court. Principal Findings The ACA will increase coverage substantially in the private insurance market and Medicaid. HSAs will remain desirable in both the individual and employer markets. Conclusions If states opt out of the Medicaid expansion, this could increase the federal cost of health reform, while reducing the number of newly covered lives. PMID:23398372

  13. 28 CFR Appendix D to Subpart G of... - OJARS' Regulations Under the Omnibus Crime Control and Safe Streets Act, as Amended, Which Apply...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Crime Control and Safe Streets Act, as Amended, Which Apply to This Subpart (28 CFR 42.205 and 42.206) D..., App. D Appendix D to Subpart G of Part 42—OJARS' Regulations Under the Omnibus Crime Control and Safe Streets Act, as Amended, Which Apply to This Subpart (28 CFR 42.205 and 42.206) Editorial Note: For...

  14. 28 CFR Appendix D to Subpart G of... - OJARS' Regulations Under the Omnibus Crime Control and Safe Streets Act, as Amended, Which Apply...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Crime Control and Safe Streets Act, as Amended, Which Apply to This Subpart (28 CFR 42.205 and 42.206) D..., App. D Appendix D to Subpart G of Part 42—OJARS' Regulations Under the Omnibus Crime Control and Safe Streets Act, as Amended, Which Apply to This Subpart (28 CFR 42.205 and 42.206) Editorial Note: For...

  15. Testing decisions of the TSCA Interagency Testing Committee for chemicals on the Canadian Environmental Protection Act Domestic Substances List and Priority Substances List: Di-tert-butylphenol, ethyl benzene, brominated flame retardants, phthalate esters, chloroparaffins, chlorinated benzenes, and anilines

    SciTech Connect

    Walker, J.D.

    1996-12-31

    In 1976, under section 4(e) of the Toxic Substances Control Act (TSCA), the US Congress created the TSCA Interagency Testing Committee (ITC) to decide which chemicals should be recommended to the Administrator of the US Environmental Protection Agency for testing. In 1988, under the Canadian Environmental Protection Act (CEPA), the Government of Canada created the Domestic Substances List and Priority Substances List. This paper briefly describes the ITC, the different ITC testing decisions and a few of the ITC`s 11,150 testing decisions for the 21,413 chemicals on the CEPA Domestic Substances List and some of the 24 testing decisions for the 44 chemicals and chemical groups on the CEPA.

  16. Regulation D Study Act

    THOMAS, 113th Congress

    Rep. Pittenger, Robert [R-NC-9

    2013-10-03

    12/03/2014 Received in the Senate and Read twice and referred to the Committee on Banking, Housing, and Urban Affairs. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  17. HRS1 Acts as a Negative Regulator of Abscisic Acid Signaling to Promote Timely Germination of Arabidopsis Seeds

    PubMed Central

    Wang, Ran; Liu, Hong; Yang, Huixia; Rodriguez, Pedro L.; Qin, Huanju; Liu, Xin; Wang, Daowen

    2012-01-01

    In this work, we conducted functional analysis of Arabidopsis HRS1 gene in order to provide new insights into the mechanisms governing seed germination. Compared with wild type (WT) control, HRS1 knockout mutant (hrs1-1) exhibited significant germination delays on either normal medium or those supplemented with abscisic acid (ABA) or sodium chloride (NaCl), with the magnitude of the delay being substantially larger on the latter media. The hypersensitivity of hrs1-1 germination to ABA and NaCl required ABI3, ABI4 and ABI5, and was aggravated in the double mutant hrs1-1abi1-2 and triple mutant hrs1-1hab1-1abi1-2, indicating that HRS1 acts as a negative regulator of ABA signaling during seed germination. Consistent with this notion, HRS1 expression was found in the embryo axis, and was regulated both temporally and spatially, during seed germination. Further analysis showed that the delay of hrs1-1 germination under normal conditions was associated with reduction in the elongation of the cells located in the lower hypocotyl (LH) and transition zone (TZ) of embryo axis. Interestingly, the germination rate of hrs1-1 was more severely reduced by the inhibitor of cell elongation, and more significantly decreased by the suppressors of plasmalemma H+-ATPase activity, than that of WT control. The plasmalemma H+-ATPase activity in the germinating seeds of hrs1-1 was substantially lower than that exhibited by WT control, and fusicoccin, an activator of this pump, corrected the transient germination delay of hrs1-1. Together, our data suggest that HRS1 may be needed for suppressing ABA signaling in germinating embryo axis, which promotes the timely germination of Arabidopsis seeds probably by facilitating the proper function of plasmalemma H+-ATPase and the efficient elongation of LH and TZ cells. PMID:22545134

  18. Recovery Act: Head Start Grantees Expand Services, but More Consistent Communication Could Improve Accountability and Decisions about Spending. Report to the Congress. GAO-11-166

    ERIC Educational Resources Information Center

    Ashby, Cornelia M.; Jones, Yvonne D.

    2010-01-01

    This report responds to two mandates for GAO under the American Recovery and Reinvestment Act of 2009 (Recovery Act). First, it is the latest report on the uses of and accountability for Recovery Act funds in selected states and localities. Second, it comments on recipients' reports of the jobs created and retained. The Recovery Act provided $2.1…

  19. Impacts & Compliance Implementation Plans & Required Deviations for Toxic Substance Control Act (TSCA) Regulation of Double Shell Tanks (DST)

    SciTech Connect

    MULKEY, C.H.

    2000-08-22

    In May 2000, the U.S. Department of Energy, Office of River Protection (DOE-ORP) and the U.S. Environmental Protection Agency (EPA) held meetings regarding the management of polychlorinated biphenyls (PCBs) in the Hanford tank waste. It was decided that the radioactive waste currently stored in the double-shell tanks (DSTs) contain waste which will become subject to the Toxic Substance Control Act (TSCA) (40 CFR 761). As a result, DOE-ORP directed the River Protection Project tank farm contractor (TFC) to prepare plans for managing the PCB inventory in the DSTs. Two components of the PCB management plans are this assessment of the operational impacts of TSCA regulation and the identifications of deviations from TSCA that are required to accommodate tank farm unique limitations. This plan provides ORP and CH2M HILL Hanford Group, Inc. (CHG) with an outline of TSCA PCB requirements and their applicability to tank farm activities, and recommends a compliance/implementation approach. Where strict compliance is not possible, the need for deviations from TSCA PCB requirements is identified. The purpose of assembling this information is to enhance the understanding of PCB management requirements, identify operational impacts and select impact mitigation strategies. This information should be useful in developing formal agreements with EPA where required.

  20. miR-203 Acts as a Tumor Suppressor Gene in Osteosarcoma by Regulating RAB22A

    PubMed Central

    Yang, Dawei; Liu, Guangpeng; Wang, Kunzheng

    2015-01-01

    microRNAs (miRNAs), small noncoding RNAs of 19–25 nt, play an important roles in the pathological processes of tumorigenesis. The object of this study was to study the expression and function of miR-203 and to found its target gene in osteosarcoma. In our study, we found the expression level of miR-203 was significantly downregulated in osteosarcoma cell lines and tissues. In addition, overexpression of miR-203 inhibited the osteosarcoma cell proliferation and migration and inhibited Mesenchymal-to-Epithelial reversion Transition (MErT). Moreover, we identified RAB22A as a direct target of miR-203 and RAB22A overexpression blocks the roles of miR-203 in osteosarcoma cell. Furthermore, we demonstrated that RAB22A expression was upregulated in human osteosarcoma cell lines and tissues. Take together, our results demonstrated that miR-203 act as a tumor suppressor miRNA through regulating RAB22A expression and suggested its involvement in osteosarcoma progression and carcinogenesis. PMID:26382657

  1. NPD1-mediated stereoselective regulation of BIRC3 expression through cREL is decisive for neural cell survival

    PubMed Central

    Calandria, J M; Asatryan, A; Balaszczuk, V; Knott, E J; Jun, B K; Mukherjee, P K; Belayev, L; Bazan, N G

    2015-01-01

    Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived mediator, induces cell survival in uncompensated oxidative stress (OS), neurodegenerations or ischemic stroke. The molecular principles underlying this protection remain unresolved. We report here that, in retinal pigment epithelial cells, NPD1 induces nuclear translocation and cREL synthesis that, in turn, mediates BIRC3 transcription. NPD1 activates NF-κB by an alternate route to canonical signaling, so the opposing effects of TNFR1 and NPD1 on BIRC3 expression are not due to interaction/s between NF-κB pathways. RelB expression follows a similar pattern as BIRC3, indicating that NPD1 also is required to activate cREL-mediated RelB expression. These results suggest that cREL, which follows a periodic pattern augmented by the lipid mediator, regulates a cluster of NPD1-dependent genes after cREL nuclear translocation. BIRC3 silencing prevents NPD1 induction of survival against OS. Moreover, brain NPD1 biosynthesis and selective neuronal BIRC3 abundance are increased by DHA after experimental ischemic stroke followed by remarkable neurological recovery. Thus, NPD1 bioactivity governs key counter-regulatory gene transcription decisive for retinal and brain neural cell integrity when confronted with potential disruptions of homeostasis. PMID:25633199

  2. NPD1-mediated stereoselective regulation of BIRC3 expression through cREL is decisive for neural cell survival.

    PubMed

    Calandria, J M; Asatryan, A; Balaszczuk, V; Knott, E J; Jun, B K; Mukherjee, P K; Belayev, L; Bazan, N G

    2015-08-01

    Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived mediator, induces cell survival in uncompensated oxidative stress (OS), neurodegenerations or ischemic stroke. The molecular principles underlying this protection remain unresolved. We report here that, in retinal pigment epithelial cells, NPD1 induces nuclear translocation and cREL synthesis that, in turn, mediates BIRC3 transcription. NPD1 activates NF-κB by an alternate route to canonical signaling, so the opposing effects of TNFR1 and NPD1 on BIRC3 expression are not due to interaction/s between NF-κB pathways. RelB expression follows a similar pattern as BIRC3, indicating that NPD1 also is required to activate cREL-mediated RelB expression. These results suggest that cREL, which follows a periodic pattern augmented by the lipid mediator, regulates a cluster of NPD1-dependent genes after cREL nuclear translocation. BIRC3 silencing prevents NPD1 induction of survival against OS. Moreover, brain NPD1 biosynthesis and selective neuronal BIRC3 abundance are increased by DHA after experimental ischemic stroke followed by remarkable neurological recovery. Thus, NPD1 bioactivity governs key counter-regulatory gene transcription decisive for retinal and brain neural cell integrity when confronted with potential disruptions of homeostasis. PMID:25633199

  3. 26 CFR 1.267(a)-2T - Temporary regulations; questions and answers arising under the Tax Reform Act of 1984 (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Temporary regulations; questions and answers arising under the Tax Reform Act of 1984 (temporary). 1.267(a)-2T Section 1.267(a)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible §...

  4. 28 CFR Appendix C to Subpart G of... - Department Regulations Under Title VI of the Civil Rights Act of 1964 (28 CFR 42.106-42.110...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Department Regulations Under Title VI of the Civil Rights Act of 1964 (28 CFR 42.106-42.110) Which Apply to This Subpart C Appendix C to... CFR 42.106-42.110) Which Apply to This Subpart Editorial Note: For the text of appendix C, see §§...

  5. 28 CFR Appendix C to Subpart G of... - Department Regulations Under Title VI of the Civil Rights Act of 1964 (28 CFR 42.106-42.110...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Department Regulations Under Title VI of the Civil Rights Act of 1964 (28 CFR 42.106-42.110) Which Apply to This Subpart C Appendix C to... CFR 42.106-42.110) Which Apply to This Subpart Editorial Note: For the text of appendix C, see §§...

  6. 28 CFR Appendix C to Subpart G of... - Department Regulations Under Title VI of the Civil Rights Act of 1964 (28 CFR 42.106-42.110...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Department Regulations Under Title VI of the Civil Rights Act of 1964 (28 CFR 42.106-42.110) Which Apply to This Subpart C Appendix C to... CFR 42.106-42.110) Which Apply to This Subpart Editorial Note: For the text of appendix C, see §§...

  7. 28 CFR Appendix C to Subpart G of... - Department Regulations Under Title VI of the Civil Rights Act of 1964 (28 CFR 42.106-42.110...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Department Regulations Under Title VI of the Civil Rights Act of 1964 (28 CFR 42.106-42.110) Which Apply to This Subpart C Appendix C to... CFR 42.106-42.110) Which Apply to This Subpart Editorial Note: For the text of appendix C, see §§...

  8. MicroRNAs as master regulators of the plant NB-LRR defense gene family via the production of phased, trans-acting siRNAs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Legumes and many nonleguminous plants enter symbiotic interactions with microbes, and it is poorly understood how host plants respond to promote beneficial, symbiotic microbial interactions while suppressing those that are deleterious or pathogenic. Trans-acting siRNAs (tasiRNAs) negatively regulate...

  9. End-of-life medical decisions in France: a death certificate follow-up survey 5 years after the 2005 act of parliament on patients’ rights and end of life

    PubMed Central

    2012-01-01

    Background The “Patients’ Rights and End of Life Care” Act came into force in France in 2005. It allows withholding/withdrawal of life-support treatment, and intensified use of medications that may hasten death through a double effect, as long as hastening death is not the purpose of the decision. It also specifies the requirements of the decision-making process. This study assesses the situation by examining the frequency of end-of-life decisions by patients’ and physicians’ characteristics, and describes the decision-making processes. Methods We conducted a nationwide retrospective study of a random sample of adult patients who died in December 2009. Questionnaires were mailed to the physicians who certified/attended these deaths. Cases were weighted to adjust for response rate bias. Bivariate analyses and logistic regressions were performed for each decision. Results Of all deaths, 16.9% were sudden deaths with no information about end of life, 12.2% followed a decision to do everything possible to prolong life, and 47.7% followed at least one medical decision that may certainly or probably hasten death: withholding (14.6%) or withdrawal (4.2%) of treatments, intensified use of opioids and/or benzodiazepines (28.1%), use of medications to deliberately hasten death (i.e. not legally authorized) (0.8%), at the patient’s request (0.2%) or not (0.6%). All other variables held constant, cause of death, patient's age, doctor’s age and specialty, and place of death, influenced the frequencies of decisions. When a decision was made, 20% of the persons concerned were considered to be competent. The decision was discussed with the patient if competent in 40% (everything done) to 86% (intensification of alleviation of symptoms) of cases. Legal requirements regarding decision-making for incompetent patients were frequently not complied with. Conclusions This study shows that end-of-life medical decisions are common in France. Most are in compliance with the

  10. RanBPM Protein Acts as a Negative Regulator of BLT2 Receptor to Attenuate BLT2-mediated Cell Motility*

    PubMed Central

    Wei, Jun-Dong; Kim, Joo-Young; Kim, Ae-Kyoung; Jang, Sung Key; Kim, Jae-Hong

    2013-01-01

    BLT2, a low affinity receptor for leukotriene B4 (LTB4), is a member of the G protein-coupled receptor family and is involved in many signal transduction pathways associated with various cellular phenotypes, including chemotactic motility. However, the regulatory mechanism for BLT2 has not yet been demonstrated. To understand the regulatory mechanism of BLT2, we screened and identified the proteins that bind to BLT2. Using a yeast two-hybrid assay with the BLT2 C-terminal domain as bait, we found that RanBPM, a previously proposed scaffold protein, interacts with BLT2. We demonstrated the specific interaction between BLT2 and RanBPM by GST pulldown assay and co-immunoprecipitation assay. To elucidate the biological function of the RanBPM-BLT2 interaction, we evaluated the effects of RanBPM overexpression or knockdown. We found that BLT2-mediated motility was severely attenuated by RanBPM overexpression and that knockdown of endogenous RanBPM by shRNA strongly promoted BLT2-mediated motility, suggesting a negative regulatory function of RanBPM toward BLT2. Furthermore, we observed that the addition of BLT2 ligands caused the dissociation of BLT2 and RanBPM, thus releasing the negative regulatory effect of RanBPM. Finally, we propose that Akt-induced BLT2 phosphorylation at residue Thr355, which occurs after the addition of BLT2 ligands, is a potential mechanism by which BLT2 dissociates from RanBPM, resulting in stimulation of BLT2 signaling. Taken together, our results suggest that RanBPM acts as a negative regulator of BLT2 signaling to attenuate BLT2-mediated cell motility. PMID:23928309

  11. Capacity constraints, pricing and investment decisions in regulated firms with a special emphasis on the Argentine electricity transmission system

    NASA Astrophysics Data System (ADS)

    Torres Gomez, Clemencia

    Restructuring the electricity sector has fostered competition in generation and distribution but has reinforced the need for better regulation to ensure efficiency of transmission networks. This dissertation assesses the impact of the Argentinean reforms in electricity on transmission efficiency. It then goes beyond the Argentinean case and analyzes some regulatory issues affecting transmission. Chapter 2 shows that the Argentinean reforms increased reliability and brought prices closer to costs. However, regulatory fine-tuning is required to ensure sustainability. Chapter 3 examines the impact of unbundling on the construction of the transmission link to the Yacyreta generation complex. A long-term commercial contract in an unbundled industry allowed competition to reduce investment cost and facilitated better monitoring by outsiders. Chapter 4 analyzes investment procedures in the context of the proposal to build a fourth line in the Comahue corridor. While procedures are mostly coherent, some rules appear to distort incentives to expand. The narrow definition of beneficiaries limits the number of participants in the decision-making. Grid users' limited accountability reduces incentives to pay for expansion. Long term contracts could increase the cost of the constraints for the party with the obligation to deliver. Chapter 5 analyzes incentives to promote grid expansion under uncertain demand using a single period-single generator model. The monopolist underinvests in comparison to an unconstrained system to reduce the likelihood of having to pay for unutilized capacity, under lower than expected demand. Optimal transmission capacity is monotonically decreasing in the cost of capital, and weakly increasing in the probability of experiencing high demand. Two possible equilibrium values for grid capacity are identified, associated with the rationing prices for either low or high demand. Chapter 6 analyzes the Laffont/Tirole model of monopoly regulation under

  12. ANNOTATION TAKEN, IN THE PERSPECTIVE OF CRIMINAL AND CONSTITUTIONAL LAW, AS WELL AS IN CRIMINOLOGY, TO THE DECISION OF THE PORTUGUESE CONSTITUTIONAL COURT, OF JANUARY 13, 2011--WITH RESPECT TO THE PROBLEMS OF "CONSENT" AND "MEDICAL ACT".

    PubMed

    Bandeira, Gonçalo S de Melo

    2014-07-01

    1--Summary of the decision taken by the Portuguese Constitutional Court, of January 13, 2011; 2--Complete text of the decision of the Portuguese Constitutional Court, of January 13, 2011, Judge Maria João ANTUNES (Reporter), Judge Carlos Pamplona de OLIVEIRA, Judge José Borges SOEIRO, Judge Gil GALVÃO, Judge Rui Manuel Moura RAMOS (President)--in terms of the appositive declaration to the sentence n. 487/2010: t.c.http://www. tribunalconstitucional.pt, August 1, 2011; 3--Brief annotation to the problem of the "medical act"; 3.1--Plus some conclusions on the brief annotation to the problem of the "medical act"; 3.2--Brief annotation to the problem of "consent"--continuation of the previous comments; 4--Conclusions. It must never be forgotten that "consent" does not stand as the only cause of exclusion of unlawfulness. PMID:27359009

  13. Living "a Life like Ours": Support Workers' Accounts of Substitute Decision-Making in Residential Care Homes for Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Dunn, M. C.; Clare, I. C. H.; Holland, A. J.

    2010-01-01

    Background: In England and Wales, the "Mental Capacity Act 2005" (MCA) provides a new legal framework to regulate substitute decision-making relating to the welfare of adults who lack the capacity to make one or more autonomous decisions about their care and support. Any substitute decision made on behalf of an adult lacking capacity must be in…

  14. Decision Point 1 of Statement of Project Objectives (SOPO)Recovery Act: Development of ITM Oxygen Technology for Integration with Advanced Industrial Systems

    SciTech Connect

    Armstrong, Phillip

    2011-04-11

    Air Products is designing, building, and operating a ceramic membrane fabrication facility (the “CerFab”) to enable production of membrane modules to supply a conceptual 2000 ton per day (TPD) ITM Oxygen facility (the “ITM Oxygen Development Facility”). Air Products is executing this project under the American Recovery and Reinvestment Act (ARRA) with the objective to accelerate the adoption of ITM Oxygen technology to help meet the country’s goals for deploying clean power plants. The objective of this Topical Report is to address the requirements of Decision Point 1, which pertains to the Site Selection for the CerFab. Air Products with subcontractor Ceramatec, Inc., has determined a ceramic membrane module manufacturing process and the building and site requirements of the process consistent with the manufacturing objectives of the ITM Oxygen development program and this ARRA project. Based on cost estimates for new construction and refurbishments of existing sites, Air Products chose to consider only existing buildings rather than new construction. The Salt Lake City, Utah, region was selected as the preferred location for the CerFab to enable Ceramatec, Inc., to support the Phase V project and on-going Phase III development activities. Twenty available properties were screened in this region, from which one property emerged clearly as the most suitable property to house the CerFab. The site meets the requirements of the CerFab in terms of floor space, power and other utilities, and building structural features. The site also meets criteria for ease of obtaining the requirement environmental permits, and is within the project cost allocation for the building site. Moreover, the site formerly housed a manufacturing company that ceased operations in 2010 as a result of the economic recession of 2008-9; the region of the site has experienced more than a doubling of the unemployment rate since 2007. Restarting a manufacturing operation in the same

  15. 77 FR 75464 - Order Granting Limited Exemptions From Exchange Act Rules 101 and 102 of Regulation M to Shares...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-20

    ... Approving a Proposed Rule Change to List and Trade Shares of the JPM XF Physical Copper Trust Pursuant to NYSE Arca Equities Rule 8.201, Securities Exchange Act Release No. 68440;----FR---- (``Approval Order... day. See Securities Exchange Act Release No. 66816 (April 16, 2012); 77 FR 23772, 23779...

  16. 77 FR 33635 - Amendment to the Bank Secrecy Act Regulations-Requirement That Clerks of Court Report Certain...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-07

    ...\\ 66 FR 67680 (December 31, 2001), codified at 31 CFR 1010.330. \\7\\ 26 CFR 1.6050I-1. As amended... Financial Transactions Reporting Act of 1970, as amended by the USA PATRIOT Act of 2001 and other... protect against international terrorism.\\2\\ The Secretary has delegated to the Director of FinCEN...

  17. 29 CFR 1987.109 - Decision and orders of the administrative law judge.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... OF THE FDA FOOD SAFETY MODERNIZATION ACT Litigation § 1987.109 Decision and orders of the... 29 Labor 9 2014-07-01 2014-07-01 false Decision and orders of the administrative law judge. 1987.109 Section 1987.109 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND...

  18. 10 CFR 780.46 - Communication of decision to General Counsel.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Communication of decision to General Counsel. 780.46 Section 780.46 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153c of the Atomic Energy Act of 1954 § 780.46 Communication of decision to...

  19. 10 CFR 780.35 - Communication of decision to General Counsel.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Communication of decision to General Counsel. 780.35 Section 780.35 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153b(2) of the Atomic Energy Act of 1954 § 780.35 Communication of decision to...

  20. 10 CFR 780.35 - Communication of decision to General Counsel.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Communication of decision to General Counsel. 780.35 Section 780.35 Energy DEPARTMENT OF ENERGY PATENT COMPENSATION BOARD REGULATIONS Application for a License Pursuant to Section 153b(2) of the Atomic Energy Act of 1954 § 780.35 Communication of decision to...