Science.gov

Sample records for allowable resistance requirements

  1. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be... rate of 85 liters per minute. (b) The maximum allowable resistance requirements for gas masks are...

  2. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be... rate of 85 liters per minute. (b) The maximum allowable resistance requirements for gas masks are...

  3. Simple PCR Assays Improve the Sensitivity of HIV-1 Subtype B Drug Resistance Testing and Allow Linking of Resistance Mutations

    PubMed Central

    Johnson, Jeffrey A.; Li, Jin-Fen; Wei, Xierong; Lipscomb, Jonathan; Bennett, Diane; Brant, Ashley; Cong, Mian-er; Spira, Thomas; Shafer, Robert W.; Heneine, Walid

    2007-01-01

    Background The success of antiretroviral therapy is known to be compromised by drug-resistant HIV-1 at frequencies detectable by conventional bulk sequencing. Currently, there is a need to assess the clinical consequences of low-frequency drug resistant variants occurring below the detection limit of conventional genotyping. Sensitive detection of drug-resistant subpopulations, however, requires simple and practical methods for routine testing. Methodology We developed highly-sensitive and simple real-time PCR assays for nine key drug resistance mutations and show that these tests overcome substantial sequence heterogeneity in HIV-1 clinical specimens. We specifically used early wildtype virus samples from the pre-antiretroviral drug era to measure background reactivity and were able to define highly-specific screening cut-offs that are up to 67-fold more sensitive than conventional genotyping. We also demonstrate that sequencing the mutation-specific PCR products provided a direct and novel strategy to further detect and link associated resistance mutations, allowing easy identification of multi-drug-resistant variants. Resistance mutation associations revealed in mutation-specific amplicon sequences were verified by clonal sequencing. Significance Combined, sensitive real-time PCR testing and mutation-specific amplicon sequencing provides a powerful and simple approach that allows for improved detection and evaluation of HIV-1 drug resistance mutations. PMID:17653265

  4. 40 CFR 96.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.41 Timing requirements for NOX allowance allocations. (a)...

  5. 40 CFR 96.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.41 Timing requirements for NOX allowance allocations. (a)...

  6. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  7. 40 CFR 97.511 - Timing requirements for TR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for TR NOX Ozone... TRADING PROGRAMS TR NOX Ozone Season Trading Program § 97.511 Timing requirements for TR NOX Ozone Season allowance allocations. (a) Existing units. (1) TR NOX Ozone Season allowances are allocated, for the...

  8. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  9. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  10. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  11. 40 CFR 97.511 - Timing requirements for TR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for TR NOX Ozone... TRADING PROGRAMS TR NOX Ozone Season Trading Program § 97.511 Timing requirements for TR NOX Ozone Season allowance allocations. (a) Existing units. (1) TR NOX Ozone Season allowances are allocated, for the...

  12. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  13. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  14. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  15. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  16. 40 CFR 97.511 - Timing requirements for TR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for TR NOX Ozone... TRADING PROGRAMS TR NOX Ozone Season Trading Program § 97.511 Timing requirements for TR NOX Ozone Season allowance allocations. (a) Existing units. (1) TR NOX Ozone Season allowances are allocated, for the...

  17. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  18. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  19. 40 CFR 96.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Allowance Allocations § 96.141 Timing requirements for CAIR...

  20. 40 CFR 96.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Allowance Allocations § 96.141 Timing requirements for CAIR...

  1. 30 CFR 206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What general requirements regarding processing allowances apply to me? 206.179 Section 206.179 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Indian Gas Processing Allowances §...

  2. 49 CFR 192.328 - Additional construction requirements for steel pipe using alternative maximum allowable operating...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Additional construction requirements for steel pipe using alternative maximum allowable operating pressure. 192.328 Section 192.328 Transportation... Lines and Mains § 192.328 Additional construction requirements for steel pipe using alternative...

  3. 49 CFR 192.328 - Additional construction requirements for steel pipe using alternative maximum allowable operating...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Additional construction requirements for steel pipe using alternative maximum allowable operating pressure. 192.328 Section 192.328 Transportation... Lines and Mains § 192.328 Additional construction requirements for steel pipe using alternative...

  4. 49 CFR 192.328 - Additional construction requirements for steel pipe using alternative maximum allowable operating...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Additional construction requirements for steel pipe using alternative maximum allowable operating pressure. 192.328 Section 192.328 Transportation... Lines and Mains § 192.328 Additional construction requirements for steel pipe using alternative...

  5. College that Requires Workers to Be Christians Allowed to Post Job Ads on Pennsylvania Web Site

    ERIC Educational Resources Information Center

    Bartlett, Thomas

    2007-01-01

    Geneva College, a Christian institution in Pennsylvania, will be allowed to post job advertisements on a state-sponsored Web site even though the college requires employees to be Christians, according to the terms of a settlement reached in federal court. The college had sued the Pennsylvania Department of Labor and Industry and the U.S.…

  6. 30 CFR 206.177 - What general requirements regarding transportation allowances apply to me?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What general requirements regarding transportation allowances apply to me? 206.177 Section 206.177 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Indian Gas Transportation...

  7. 45 CFR 1310.12 - Required use of School Buses or Allowable Alternate Vehicles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Required use of School Buses or Allowable Alternate Vehicles. 1310.12 Section 1310.12 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...

  8. 45 CFR 1310.12 - Required use of School Buses or Allowable Alternate Vehicles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Required use of School Buses or Allowable Alternate Vehicles. 1310.12 Section 1310.12 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...

  9. 45 CFR 1310.12 - Required use of School Buses or Allowable Alternate Vehicles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Required use of School Buses or Allowable Alternate Vehicles. 1310.12 Section 1310.12 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...

  10. 45 CFR 1310.12 - Required use of School Buses or Allowable Alternate Vehicles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Required use of School Buses or Allowable Alternate Vehicles. 1310.12 Section 1310.12 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...

  11. 45 CFR 1310.12 - Required use of School Buses or Allowable Alternate Vehicles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 4 2014-10-01 2014-10-01 false Required use of School Buses or Allowable Alternate Vehicles. 1310.12 Section 1310.12 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION...

  12. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Breathing resistance test; minimum requirements. 84... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance to... resistance requirements for chemical cartridge respirators are as follows: Maximum Resistance Type...

  13. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; minimum requirements. 84... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance to... resistance requirements for chemical cartridge respirators are as follows: Maximum Resistance Type...

  14. Trehalose glycopolymer resists allow direct writing of protein patterns by electron-beam lithography.

    PubMed

    Bat, Erhan; Lee, Juneyoung; Lau, Uland Y; Maynard, Heather D

    2015-03-20

    Direct-write patterning of multiple proteins on surfaces is of tremendous interest for a myriad of applications. Precise arrangement of different proteins at increasingly smaller dimensions is a fundamental challenge to apply the materials in tissue engineering, diagnostics, proteomics and biosensors. Herein, we present a new resist that protects proteins during electron-beam exposure and its application in direct-write patterning of multiple proteins. Polymers with pendant trehalose units are shown to effectively crosslink to surfaces as negative resists, while at the same time providing stabilization to proteins during the vacuum and electron-beam irradiation steps. In this manner, arbitrary patterns of several different classes of proteins such as enzymes, growth factors and immunoglobulins are realized. Utilizing the high-precision alignment capability of electron-beam lithography, surfaces with complex patterns of multiple proteins are successfully generated at the micrometre and nanometre scale without requiring cleanroom conditions.

  15. Trehalose Glycopolymer Resists Allow Direct Writing of Protein Patterns by Electron-Beam Lithography

    PubMed Central

    Bat, Erhan; Lee, Juneyoung; Lau, Uland Y.; Maynard, Heather D.

    2015-01-01

    Direct-write patterning of multiple proteins on surfaces is of tremendous interest for a myriad of applications. Precise arrangement of different proteins at increasingly smaller dimensions is a fundamental challenge to apply the materials in tissue engineering, diagnostics, proteomics and biosensors. Herein we present a new resist that protects proteins during electron beam exposure and its application in direct-write patterning of multiple proteins. Polymers with pendant trehalose units are shown to effectively cross-link to surfaces as negative resists, while at the same time providing stabilization to proteins during the vacuum and electron beam irradiation steps. In this manner, arbitrary patterns of several different classes of proteins such as enzymes, growth factors and immunoglobulins are realized. Utilizing the high precision alignment capability of electron-beam lithography, surfaces with complex patterns of multiple proteins are successfully generated at the micrometer and nanometer scale without requiring cleanroom conditions. PMID:25791943

  16. MALDI-TOF MS fingerprinting allows for discrimination of major methicillin-resistant Staphylococcus aureus lineages.

    PubMed

    Wolters, Manuel; Rohde, Holger; Maier, Thomas; Belmar-Campos, Cristina; Franke, Gefion; Scherpe, Stefanie; Aepfelbacher, Martin; Christner, Martin

    2011-01-01

    Early detection of outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) and initiation of adequate infection control measures are important objectives in hospital hygiene. To reach these goals, prompt determination of epidemiologic relatedness of clinical MRSA isolates is essential. Genetic typing methods like pulsed-field gel electrophoresis (PFGE), spa typing, or multilocus sequence typing (MLST) have a high discriminatory power, however, these methods are time consuming and cost intensive. The aim of this study was to investigate the potential of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) for discrimination of major MRSA lineages. By analysis of mass spectra from 25 representative MRSA isolates belonging to the 5 major hospital-acquired (HA) MRSA clonal complexes (CC5, CC8, CC22, CC30, CC45; deduced from spa typing), reproducible spectrum differences were observed at 13 characteristic m/z values allowing robust discrimination of the clonal complexes. When 60 independent clinical MRSA isolates were tested for the presence or absence of the 13 characteristic MALDI-TOF MS peaks, 15 different profiles (MALDI types) could be detected. Hierarchical clustering of the MALDI types showed high concordance with the clonal complexes. Our results suggest that MALDI-TOF MS has the potential to become a valuable first-line tool for inexpensive and rapid typing of MRSA in infection control.

  17. 30 CFR 1206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... allowances apply to me? 1206.179 Section 1206.179 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Indian Gas Processing Allowances... separate processing allowance for each gas plant product and processing plant relationship. Natural...

  18. 30 CFR 1206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... allowances apply to me? 1206.179 Section 1206.179 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Indian Gas Processing Allowances... separate processing allowance for each gas plant product and processing plant relationship. Natural...

  19. 30 CFR 1206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... allowances apply to me? 1206.179 Section 1206.179 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Indian Gas Processing Allowances... separate processing allowance for each gas plant product and processing plant relationship. Natural...

  20. 20 CFR 641.847 - What uniform allowable cost requirements apply to the use of SCSEP funds?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... subrecipients must follow the uniform allowable cost requirements that apply to their type of organization. For example, a local government subrecipient receiving SCSEP funds from a nonprofit organization must use the allowable cost requirements for governmental organizations in OMB Circular A-87. The...

  1. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be measured in the facepiece or mouthpiece of a gas mask mounted on a breathing machine both before and...

  2. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Breathing resistance test; minimum requirements. 84.203 Section 84.203 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance...

  3. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be measured in the facepiece or mouthpiece of a gas mask mounted on a breathing machine both before and...

  4. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be measured in the facepiece or mouthpiece of a gas mask mounted on a breathing machine both before and...

  5. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Breathing resistance test; minimum requirements. 84.203 Section 84.203 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance...

  6. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Breathing resistance test; minimum requirements. 84.203 Section 84.203 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance...

  7. 42 CFR 84.192 - Cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Cartridges in parallel; resistance requirements. 84... Chemical Cartridge Respirators § 84.192 Cartridges in parallel; resistance requirements. Where two or more cartridges are used in parallel, their resistance to airflow shall be essentially equal....

  8. 42 CFR 84.192 - Cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Cartridges in parallel; resistance requirements. 84... Chemical Cartridge Respirators § 84.192 Cartridges in parallel; resistance requirements. Where two or more cartridges are used in parallel, their resistance to airflow shall be essentially equal....

  9. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation resistance between wiring and ground of continuous inductive automatic cab signal system, automatic...

  10. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation resistance between wiring and ground of continuous inductive automatic cab signal system, automatic...

  11. 42 CFR 84.192 - Cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Cartridges in parallel; resistance requirements. 84... Chemical Cartridge Respirators § 84.192 Cartridges in parallel; resistance requirements. Where two or more cartridges are used in parallel, their resistance to airflow shall be essentially equal....

  12. 42 CFR 84.192 - Cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Cartridges in parallel; resistance requirements. 84... Chemical Cartridge Respirators § 84.192 Cartridges in parallel; resistance requirements. Where two or more cartridges are used in parallel, their resistance to airflow shall be essentially equal....

  13. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation resistance between wiring and ground of continuous inductive automatic cab signal system, automatic...

  14. 42 CFR 84.192 - Cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Cartridges in parallel; resistance requirements. 84... Chemical Cartridge Respirators § 84.192 Cartridges in parallel; resistance requirements. Where two or more cartridges are used in parallel, their resistance to airflow shall be essentially equal....

  15. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation resistance between wiring and ground of continuous inductive automatic cab signal system, automatic...

  16. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation resistance between wiring and ground of continuous inductive automatic cab signal system, automatic...

  17. 49 CFR 192.328 - Additional construction requirements for steel pipe using alternative maximum allowable operating...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... meet this additional construction requirement: (a) Quality assurance (1) The construction of the... 49 Transportation 3 2010-10-01 2010-10-01 false Additional construction requirements for steel... Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS...

  18. 49 CFR 192.328 - Additional construction requirements for steel pipe using alternative maximum allowable operating...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... meet this additional construction requirement: (a) Quality assurance (1) The construction of the... 49 Transportation 3 2013-10-01 2013-10-01 false Additional construction requirements for steel... Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS...

  19. Density-dependent adaptive resistance allows swimming bacteria to colonize an antibiotic gradient.

    PubMed

    Hol, Felix J H; Hubert, Bert; Dekker, Cees; Keymer, Juan E

    2016-01-01

    During antibiotic treatment, antibiotic concentration gradients develop. Little is know regarding the effects of antibiotic gradients on populations of nonresistant bacteria. Using a microfluidic device, we show that high-density motile Escherichia coli populations composed of nonresistant bacteria can, unexpectedly, colonize environments where a lethal concentration of the antibiotic kanamycin is present. Colonizing bacteria establish an adaptively resistant population, which remains viable for over 24 h while exposed to the antibiotic. Quantitative analysis of multiple colonization events shows that collectively swimming bacteria need to exceed a critical population density in order to successfully colonize the antibiotic landscape. After colonization, bacteria are not dormant but show both growth and swimming motility under antibiotic stress. Our results highlight the importance of motility and population density in facilitating adaptive resistance, and indicate that adaptive resistance may be a first step to the emergence of genetically encoded resistance in landscapes of antibiotic gradients.

  20. Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations.

    PubMed

    Brammeld, Jonathan S; Petljak, Mia; Martincorena, Inigo; Williams, Steven P; Alonso, Luz Garcia; Dalmases, Alba; Bellosillo, Beatriz; Robles-Espinoza, Carla Daniela; Price, Stacey; Barthorpe, Syd; Tarpey, Patrick; Alifrangis, Constantine; Bignell, Graham; Vidal, Joana; Young, Jamie; Stebbings, Lucy; Beal, Kathryn; Stratton, Michael R; Saez-Rodriguez, Julio; Garnett, Mathew; Montagut, Clara; Iorio, Francesco; McDermott, Ultan

    2017-04-01

    Drug resistance is an almost inevitable consequence of cancer therapy and ultimately proves fatal for the majority of patients. In many cases, this is the consequence of specific gene mutations that have the potential to be targeted to resensitize the tumor. The ability to uniformly saturate the genome with point mutations without chromosome or nucleotide sequence context bias would open the door to identify all putative drug resistance mutations in cancer models. Here, we describe such a method for elucidating drug resistance mechanisms using genome-wide chemical mutagenesis allied to next-generation sequencing. We show that chemically mutagenizing the genome of cancer cells dramatically increases the number of drug-resistant clones and allows the detection of both known and novel drug resistance mutations. We used an efficient computational process that allows for the rapid identification of involved pathways and druggable targets. Such a priori knowledge would greatly empower serial monitoring strategies for drug resistance in the clinic as well as the development of trials for drug-resistant patients.

  1. Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations

    PubMed Central

    Brammeld, Jonathan S.; Petljak, Mia; Martincorena, Inigo; Williams, Steven P.; Alonso, Luz Garcia; Dalmases, Alba; Bellosillo, Beatriz; Robles-Espinoza, Carla Daniela; Price, Stacey; Barthorpe, Syd; Tarpey, Patrick; Alifrangis, Constantine; Bignell, Graham; Vidal, Joana; Young, Jamie; Stebbings, Lucy; Beal, Kathryn; Stratton, Michael R.; Saez-Rodriguez, Julio; Garnett, Mathew; Montagut, Clara; Iorio, Francesco; McDermott, Ultan

    2017-01-01

    Drug resistance is an almost inevitable consequence of cancer therapy and ultimately proves fatal for the majority of patients. In many cases, this is the consequence of specific gene mutations that have the potential to be targeted to resensitize the tumor. The ability to uniformly saturate the genome with point mutations without chromosome or nucleotide sequence context bias would open the door to identify all putative drug resistance mutations in cancer models. Here, we describe such a method for elucidating drug resistance mechanisms using genome-wide chemical mutagenesis allied to next-generation sequencing. We show that chemically mutagenizing the genome of cancer cells dramatically increases the number of drug-resistant clones and allows the detection of both known and novel drug resistance mutations. We used an efficient computational process that allows for the rapid identification of involved pathways and druggable targets. Such a priori knowledge would greatly empower serial monitoring strategies for drug resistance in the clinic as well as the development of trials for drug-resistant patients. PMID:28179366

  2. 30 CFR 1206.177 - What general requirements regarding transportation allowances apply to me?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... unprocessed gas, residue gas, or gas plant product. For purposes of this section, natural gas liquids are... transportation allowances apply to me? 1206.177 Section 1206.177 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Indian Gas...

  3. 30 CFR 1206.177 - What general requirements regarding transportation allowances apply to me?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... unprocessed gas, residue gas, or gas plant product. For purposes of this section, natural gas liquids are... transportation allowances apply to me? 1206.177 Section 1206.177 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Indian Gas...

  4. 30 CFR 1206.177 - What general requirements regarding transportation allowances apply to me?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... unprocessed gas, residue gas, or gas plant product. For purposes of this section, natural gas liquids are... transportation allowances apply to me? 1206.177 Section 1206.177 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Indian Gas...

  5. 30 CFR 1206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue PRODUCT VALUATION Indian Gas Processing... separate processing allowance for each gas plant product and processing plant relationship. Natural gas... value any gas plant product under § 1206.174, you may deduct from value the reasonable actual costs...

  6. Corrosion-resistant fuel cladding allow for liquid metal fast breeder reactors

    DOEpatents

    Brehm, Jr., William F.; Colburn, Richard P.

    1982-01-01

    An aluminide coating for a fuel cladding tube for LMFBRs (liquid metal fast breeder reactors) such as those using liquid sodium as a heat transfer agent. The coating comprises a mixture of nickel-aluminum intermetallic phases and presents good corrosion resistance to liquid sodium at temperatures up to 700.degree. C. while additionally presenting a barrier to outward diffusion of .sup.54 Mn.

  7. Regulatory Requirements for Staphylococcus aureus Nitric Oxide Resistance

    PubMed Central

    Grosser, Melinda R.; Weiss, Andy; Shaw, Lindsey N.

    2016-01-01

    ABSTRACT The ability of Staphylococcus aureus to resist host innate immunity augments the severity and pervasiveness of its pathogenesis. Nitric oxide (NO˙) is an innate immune radical that is critical for the efficient clearance of a wide range of microbial pathogens. Exposure of microbes to NO˙ typically results in growth inhibition and induction of stress regulons. S. aureus, however, induces a metabolic state in response to NO˙ that allows for continued replication and precludes stress regulon induction. The regulatory factors mediating this distinctive response remain largely undefined. Here, we employ a targeted transposon screen and transcriptomics to identify and characterize five regulons essential for NO˙ resistance in S. aureus: three virulence regulons not formerly associated with NO˙ resistance, SarA, CodY, and Rot, as well as two regulons with established roles, Fur and SrrAB. We provide new insights into the contributions of Fur and SrrAB during NO˙ stress and show that the S. aureus ΔsarA mutant, the most sensitive of the newly identified mutants, exhibits metabolic dysfunction and widespread transcriptional dysregulation following NO˙ exposure. Altogether, our results broadly characterize the regulatory requirements for NO˙ resistance in S. aureus and suggest an intriguing overlap between the regulation of NO˙ resistance and virulence in this well-adapted human pathogen. IMPORTANCE The prolific human pathogen Staphylococcus aureus is uniquely capable of resisting the antimicrobial radical nitric oxide (NO˙), a crucial component of the innate immune response. However, a complete understanding of how S. aureus regulates an effective response to NO˙ is lacking. Here, we implicate three central virulence regulators, SarA, CodY, and Rot, as major players in the S. aureus NO˙ response. Additionally, we elaborate on the contribution of two regulators, SrrAB and Fur, already known to play a crucial role in S. aureus NO˙ resistance. Our study

  8. 20 CFR 641.847 - What uniform allowable cost requirements apply to the use of SCSEP funds?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What uniform allowable cost requirements apply to the use of SCSEP funds? 641.847 Section 641.847 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT...

  9. 20 CFR 641.847 - What uniform allowable cost requirements apply to the use of SCSEP funds?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false What uniform allowable cost requirements apply to the use of SCSEP funds? 641.847 Section 641.847 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT...

  10. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... PRESCRIPTIONS Obtaining and Using Digital Certificates for Electronic Orders § 1311.45 Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates under their DEA registration....

  11. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... PRESCRIPTIONS (Eff. 6-1-10) Obtaining and Using Digital Certificates for Electronic Orders § 1311.45 Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates under their...

  12. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... PRESCRIPTIONS Obtaining and Using Digital Certificates for Electronic Orders § 1311.45 Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates under their DEA registration....

  13. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... PRESCRIPTIONS Obtaining and Using Digital Certificates for Electronic Orders § 1311.45 Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates under their DEA registration....

  14. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... PRESCRIPTIONS Obtaining and Using Digital Certificates for Electronic Orders § 1311.45 Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates under their DEA registration....

  15. Natural diversity in the model legume Medicago truncatula allows identifying distinct genetic mechanisms conferring partial resistance to Verticillium wilt.

    PubMed

    Ben, Cécile; Toueni, Maoulida; Montanari, Sara; Tardin, Marie-Claire; Fervel, Magalie; Negahi, Azam; Saint-Pierre, Laure; Mathieu, Guillaume; Gras, Marie-Christine; Noël, Dominique; Prospéri, Jean-Marie; Pilet-Nayel, Marie-Laure; Baranger, Alain; Huguet, Thierry; Julier, Bernadette; Rickauer, Martina; Gentzbittel, Laurent

    2013-01-01

    Verticillium wilt is a major threat to alfalfa (Medicago sativa) and many other crops. The model legume Medicago truncatula was used as a host for studying resistance and susceptibility to Verticillium albo-atrum. In addition to presenting well-established genetic resources, this wild plant species enables to investigate biodiversity of the response to the pathogen and putative crosstalk between disease and symbiosis. Symptom scoring after root inoculation and modelling of disease curves allowed assessing susceptibility levels in recombinant lines of three crosses between susceptible and resistant lines, in a core collection of 32 lines, and in mutants affected in symbiosis with rhizobia. A GFP-expressing V. albo-atrum strain was used to study colonization of susceptible plants. Symptoms and colonization pattern in infected M. truncatula plants were typical of Verticillium wilt. Three distinct major quantitative trait loci were identified using a multicross, multisite design, suggesting that simple genetic mechanisms appear to control Verticillium wilt resistance in M. truncatula lines A17 and DZA45.5. The disease functional parameters varied largely in lines of the core collection. This biodiversity with regard to disease response encourages the development of association genetics and ecological approaches. Several mutants of the resistant line, impaired in different steps of rhizobial symbiosis, were affected in their response to V. albo-atrum, which suggests that mechanisms involved in the establishment of symbiosis or disease might have some common regulatory control points.

  16. Decompensated lamivudine-resistant hepatitis B virus-related cirrhosis treated successfully with adefovir dipivoxil allowing surgery for hepatocellular carcinoma.

    PubMed

    Takamura, Masaaki; Ichida, Takafumi; Ohkoshi, Shogo; Tsubata, Shunsuke; Osaki, Akihiko; Aoyagi, Tomoya; Nomoto, Minoru; Uehara, Kazuhiro; Terada, Haruo; Aoyagi, Yutaka

    2007-01-01

    We describe a 64-year-old man with decompensated hepatitis B virus (HBV)-related cirrhosis who became resistant to lamivudine. He was started on adefovir at 10 mg daily while continuing lamivudine therapy. Several months later, his liver function improved and subsequently his ascites disappeared. The serum HBV-DNA level became undetectable 11 months later. Twenty months after the start of additional treatment with adefovir, one hepatocellular carcinoma (HCC) was detected, and the patient underwent a successful hepatectomy. Our findings suggest that the addition of adefovir to ongoing lamivudine therapy is useful for improving liver function in patients with decompensated lamivudine-resistant HBV-related cirrhosis, allowing surgery for HCC.

  17. HIGH RESOLUTION RESISTIVITY LEAK DETECTION DATA PROCESSING & EVALUATION MEHTODS & REQUIREMENTS

    SciTech Connect

    SCHOFIELD JS

    2007-10-04

    This document has two purposes: {sm_bullet} Describe how data generated by High Resolution REsistivity (HRR) leak detection (LD) systems deployed during single-shell tank (SST) waste retrieval operations are processed and evaluated. {sm_bullet} Provide the basic review requirements for HRR data when Hrr is deployed as a leak detection method during SST waste retrievals.

  18. A single mutation in the GSTe2 gene allows tracking of metabolically based insecticide resistance in a major malaria vector

    PubMed Central

    2014-01-01

    Background Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. Results Here, we demonstrate that the single amino acid change L119F in an upregulated glutathione S-transferase gene, GSTe2, confers high levels of metabolic resistance to DDT in the malaria vector Anopheles funestus. Genome-wide transcription analysis revealed that GSTe2 was the most over-expressed detoxification gene in DDT and permethrin-resistant mosquitoes from Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated that over-transcription of this gene alone confers DDT resistance and cross-resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the point mutation is tightly associated with metabolic resistance to DDT and its geographical distribution strongly correlates with DDT resistance patterns across Africa. Functional characterization of recombinant GSTe2 further supports the role of the L119F mutation, with the resistant allele being more efficient at metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2 directly metabolizes the pyrethroid permethrin. Structural analysis reveals that the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity, leading to increased DDT access and metabolism. Furthermore, we show that GSTe2 is under strong directional selection in resistant populations, and a restriction of gene flow is observed between African regions, enabling the prediction of the future spread of this resistance. Conclusions This first DNA-based metabolic resistance marker in mosquitoes provides an essential tool to track the evolution of resistance and to design suitable resistance management strategies. PMID:24565444

  19. An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells.

    PubMed

    Li, Jing; Wang, Jiajia; Wen, Liuqing; Zhu, He; Li, Shanshan; Huang, Kenneth; Jiang, Kuan; Li, Xu; Ma, Cheng; Qu, Jingyao; Parameswaran, Aishwarya; Song, Jing; Zhao, Wei; Wang, Peng George

    2016-11-18

    O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. Therefore, selective and potent probes are needed to assess this modification. We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. Furthermore, the O-4dGlcNAz modification was resistant to the hydrolysis of O-GlcNAcase (OGA), which greatly enhanced the efficiency of incorporation for O-GlcNAcylation. Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates.

  20. Global warming mitigation by sulphur loading in the stratosphere: dependence of required emissions on allowable residual warming rate

    NASA Astrophysics Data System (ADS)

    Eliseev, Alexey V.; Chernokulsky, Alexandr V.; Karpenko, Andrey A.; Mokhov, Igor I.

    2010-07-01

    An approach to mitigate global warming via sulphur loading in the stratosphere (geoengineering) is studied, employing a large ensemble of numerical experiments with the climate model of intermediate complexity IAP RAS CM. The model is forced by the historical+SRES A1B anthropogenic greenhouse gases+tropospheric sulphates scenario for 1860-2100 with additional sulphur emissions in the stratosphere in the twenty-first century. Different ensemble members are constructed by varying values of the parameters governing mass, horizontal distribution and radiative forcing of the stratospheric sulphates. It is obtained that, given a global loading of the sulphates in the stratosphere, among those studied in this paper latitudinal distributions of geoengineering aerosols, the most efficient one at the global basis is that peaked between 50° N and 70° N and with a somewhat smaller burden in the tropics. Uniform latitudinal distribution of stratospheric sulphates is a little less efficient. Sulphur emissions in the stratosphere required to stop the global temperature at the level corresponding to the mean value for 2000-2010 amount to more than 10 TgS/year in the year 2100. These emissions may be reduced if some warming is allowed to occur in the twenty-first century. For instance, if the global temperature trend S g in every decade of this century is limited not to exceed 0.10 K/decade (0.15 K/decade), geoengineering emissions of 4-14 TgS/year (2-7 TgS/year) would be sufficient. Even if the global warming is stopped, temperature changes in different regions still occur with a magnitude up to 1 K. Their horizontal pattern depends on implied latitudinal distribution of stratospheric sulphates. In addition, for the stabilised global mean surface air temperature, global precipitation decreases by about 10%. If geoengineering emissions are stopped after several decades of implementation, their climatic effect is removed within a few decades. In this period, surface air

  1. Race Against Antimicrobial Resistance Requires Coordinated Action – An Overview

    PubMed Central

    Premanandh, J.; Samara, B. S.; Mazen, A. N.

    2016-01-01

    Resistance developed by microbes is challenging success stories of treatment of infectious diseases with anti-microbials. Developing new antimicrobials against these resistant organisms does not progress at the same speed. In an effort to address this key issue, this work overviews the role of different stakeholders and discusses preventative and control measures for effective management of available resources. Roles and concerns of physicians, pharmacists and the public are also discussed. More than anything, this situation requires immediate action to establish antimicrobial stewardship program, control over the counter sale and promote public awareness. The paper also confronts the idea of curbing the use of antimicrobials using mass media, while detailing the consequences of non-therapeutic use. The role of policy makers in taking global action is essential to establishing authority or agency for formulating national guidelines and regulations for prudently using antimicrobials. To do this, this paper recommend the establishment of a global fund. In conclusion, the race against resistance is a collective responsibility requiring coordinated action at local, national, regional and international levels to ensure sustained utilization of antimicrobials. PMID:26869998

  2. Compassionate Allowances

    MedlinePlus

    Skip to content Social Security Search Menu Languages Sign in / up Compassionate Allowances Featured Items Compassionate Allowances Conditions CAL conditions are selected using information received ...

  3. Interfamilial recombination between viruses led to acquisition of a novel translation-enhancing RNA element that allows resistance breaking

    PubMed Central

    Miras, Manuel; Sempere, Raquel N.; Kraft, Jelena J.; Miller, W. Allen; Aranda, Miguel A.; Truniger, Veronica

    2015-01-01

    Summary Many plant viruses depend on functional RNA elements, called 3′-UTR cap-independent translation enhancers (3′-CITEs), for translation of their RNAs. In this manuscript we provide direct proof for the existing hypothesis that 3′-CITEs are modular and transferable by recombination in nature, and that this is associated with an advantage for the created virus. By characterizing a newly identified Melon necrotic spot virus (MNSV; Tombusviridae) isolate, which is able to overcome eukaryotic translation initiation factor 4E (eIF4E)-mediated resistance, we found that it contains a 55 nucleotide insertion in its 3′-UTR. We provide strong evidence that this insertion was acquired by interfamilial recombination with the 3′-UTR of an Asiatic Cucurbit aphid-borne yellows virus (CABYV; Luteoviridae). By constructing chimeric viruses, we showed that this recombined sequence is responsible for resistance breaking. Analysis of the translational efficiency of reporter constructs showed that this sequence functions as a novel 3′-CITE in both resistant and susceptible plants, being essential for translation control in resistant plants. In conclusion, we showed that a recombination event between two clearly identified viruses from different families led to the transfer of exactly the sequence corresponding to a functional RNA element, giving rise to a new isolate with the capacity to infect an otherwise non-susceptible host. PMID:24372390

  4. 20 CFR 641.850 - Are there other specific allowable and unallowable cost requirements for the SCSEP?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT...) Minor repair and rehabilitation of publicly used facilities for the general benefit of the community... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Are there other specific allowable...

  5. 20 CFR 641.850 - Are there other specific allowable and unallowable cost requirements for the SCSEP?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT...) Minor repair and rehabilitation of publicly used facilities for the general benefit of the community... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Are there other specific allowable...

  6. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

    PubMed Central

    Frise, Rebecca; Bradley, Konrad; van Doremalen, Neeltje; Galiano, Monica; Elderfield, Ruth A.; Stilwell, Peter; Ashcroft, Jonathan W.; Fernandez-Alonso, Mirian; Miah, Shahjahan; Lackenby, Angie; Roberts, Kim L.; Donnelly, Christl A.; Barclay, Wendy S.

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution. PMID:27430528

  7. 48 CFR 211.170 - Requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-resistant rayon fiber. 211.170 Section 211.170 Federal Acquisition Regulations System DEFENSE ACQUISITION... Developing Requirements Documents 211.170 Requiring the use of fire-resistant rayon fiber. See 225.7016 for the statutory prohibition on requiring the use of fire-resistant rayon fiber....

  8. 48 CFR 211.170 - Requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...-resistant rayon fiber. 211.170 Section 211.170 Federal Acquisition Regulations System DEFENSE ACQUISITION... Developing Requirements Documents 211.170 Requiring the use of fire-resistant rayon fiber. See 225.7016 for the statutory prohibition on requiring the use of fire-resistant rayon fiber....

  9. 48 CFR 211.170 - Requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...-resistant rayon fiber. 211.170 Section 211.170 Federal Acquisition Regulations System DEFENSE ACQUISITION... Developing Requirements Documents 211.170 Requiring the use of fire-resistant rayon fiber. See 225.7016 for the statutory prohibition on requiring the use of fire-resistant rayon fiber....

  10. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Approved fire-resistant hydraulic fluids... Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment § 75.1107-2 Approved fire-resistant hydraulic fluids; minimum requirements. Fire-resistant hydraulic fluids...

  11. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Approved fire-resistant hydraulic fluids... Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment § 75.1107-2 Approved fire-resistant hydraulic fluids; minimum requirements. Fire-resistant hydraulic fluids...

  12. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Approved fire-resistant hydraulic fluids... Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment § 75.1107-2 Approved fire-resistant hydraulic fluids; minimum requirements. Fire-resistant hydraulic fluids...

  13. Comparative transcriptome analysis between resistant and susceptible tomato allows the identification of lncRNA16397 conferring resistance to Phytophthora infestans by co-expressing glutaredoxin.

    PubMed

    Cui, Jun; Luan, Yushi; Jiang, Ning; Bao, Hang; Meng, Jun

    2017-02-01

    The rapid development of omics sequencing technology has facilitated the identification of thousands of long non-coding (lnc)RNAs in plant species, but the role of lncRNAs in plant-pathogen interactions remains largely unexplored. We used comparative transcriptome analysis of Phytophthora infestans-resistant and -susceptible tomatoes to identify differentially expressed genes (DEGs) and lncRNAs (DELs), and examine lncRNA-mRNA networks. A total of 1037 DEGs and 688 DELs were identified between P. infestans-resistant and -susceptible tomatoes. The co-localization networks, including 128 DEGs and 127 DELs, were performed. We found that lncRNA16397 acted as an antisense transcript of SlGRX22 to regulate its expression, and also induced SlGRX21 expression when lncRNA16397 was overexpressed. In addition, disease symptoms and reactive oxygen species (ROS) accumulation in tomatoes overexpressing lncRNA16397 and SpGRX were fewer and lower than those in wild-type after P. infestans infection. This result suggests that tomato lncRNA16397 induces SlGRX expression to reduce ROS accumulation and alleviate cell membrane injury, resulting in enhanced resistance to P. infestans. Our results provide insight into lncRNAs involved in the response of tomato to P. infestans infection, demonstrate that the lncRNA16397-GRXs network is an important component of the P. infestans network in tomato, and provide candidates for breeding to enhance biotic stress-resistance in tomato.

  14. 32 CFR 37.680 - Must I require a participant to report when it enters into a subaward allowing a for-profit firm...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Must I require a participant to report when it enters into a subaward allowing a for-profit firm to use an IPA? 37.680 Section 37.680 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS...

  15. 48 CFR 225.7016 - Prohibition on requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the use of fire-resistant rayon fiber. 225.7016 Section 225.7016 Federal Acquisition Regulations... 225.7016 Prohibition on requiring the use of fire-resistant rayon fiber. In accordance with section... include the use of fire-resistant rayon fiber. However, this does not preclude issuing a solicitation...

  16. 48 CFR 225.7016 - Prohibition on requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the use of fire-resistant rayon fiber. 225.7016 Section 225.7016 Federal Acquisition Regulations... 225.7016 Prohibition on requiring the use of fire-resistant rayon fiber. In accordance with section... include the use of fire-resistant rayon fiber. However, this does not preclude issuing a solicitation...

  17. 48 CFR 225.7016 - Prohibition on requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the use of fire-resistant rayon fiber. 225.7016 Section 225.7016 Federal Acquisition Regulations... 225.7016 Prohibition on requiring the use of fire-resistant rayon fiber. In accordance with section... include the use of fire-resistant rayon fiber. However, this does not preclude issuing a solicitation...

  18. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Airflow resistance tests; all dust, fume, and mist... Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements. (a) Resistance to airflow will be measured in the facepiece,...

  19. 42 CFR 84.112 - Canisters and cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Canisters and cartridges in parallel; resistance... DEVICES Gas Masks § 84.112 Canisters and cartridges in parallel; resistance requirements. Where two or more canisters or cartridges are used in parallel, their resistance to airflow shall be...

  20. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Airflow resistance tests; all dust, fume, and mist... Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements. (a) Resistance to airflow will be measured in the facepiece,...

  1. 42 CFR 84.112 - Canisters and cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Canisters and cartridges in parallel; resistance... DEVICES Gas Masks § 84.112 Canisters and cartridges in parallel; resistance requirements. Where two or more canisters or cartridges are used in parallel, their resistance to airflow shall be...

  2. 42 CFR 84.112 - Canisters and cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Canisters and cartridges in parallel; resistance... DEVICES Gas Masks § 84.112 Canisters and cartridges in parallel; resistance requirements. Where two or more canisters or cartridges are used in parallel, their resistance to airflow shall be...

  3. 42 CFR 84.112 - Canisters and cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Canisters and cartridges in parallel; resistance... DEVICES Gas Masks § 84.112 Canisters and cartridges in parallel; resistance requirements. Where two or more canisters or cartridges are used in parallel, their resistance to airflow shall be...

  4. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Airflow resistance tests; all dust, fume, and mist... Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements. (a) Resistance to airflow will be measured in the facepiece,...

  5. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Airflow resistance tests; all dust, fume, and mist... Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements. (a) Resistance to airflow will be measured in the facepiece,...

  6. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Airflow resistance tests; all dust, fume, and mist... Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements. (a) Resistance to airflow will be measured in the facepiece,...

  7. 42 CFR 84.112 - Canisters and cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Canisters and cartridges in parallel; resistance... DEVICES Gas Masks § 84.112 Canisters and cartridges in parallel; resistance requirements. Where two or more canisters or cartridges are used in parallel, their resistance to airflow shall be...

  8. Identification of Two Genes Required in Tomato for Full Cf-9-Dependent Resistance to Cladosporium fulvum.

    PubMed Central

    Hammond-Kosack, K. E.; Jones, D. A.; Jones, JDG.

    1994-01-01

    Mutagenesis was used to identify and characterize plant genes required for fungal disease resistance gene function in tomato. Seed of a stock homozygous for the Cf-9 gene for resistance to Cladosporium fulvum were treated with ethyl methanesulfonate, and 568 M2 families were screened for mutations to C. fulvum sensitivity. Eight mutants with reduced resistance were isolated. Four mutations, all of which mapped to the Cf-9 gene, lost both resistance and response to the race-specific AVR9 elicitor. The other four mutations partially lost resistance and response to the AVR9 elicitor. Cytological analysis revealed that a unique host cell staining pattern accompanied the reduced-resistance phenotype in three mutants. Two of the mutants with reduced resistance mapped to Cf-9, and two mapped to two distinct loci designated Rcr-1 and Rcr-2 (Required for Cladosporium resistance) that are unlinked to Cf-9. PMID:12244240

  9. 32 CFR 37.680 - Must I require a participant to report when it enters into a subaward allowing a for-profit firm...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Must I require a participant to report when it enters into a subaward allowing a for-profit firm to use an IPA? 37.680 Section 37.680 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Award Terms...

  10. RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance.

    PubMed

    Pan, Guo-Zheng; Zhai, Feng-Xian; Lu, Yin; Fang, Zhi-Gang; Fan, Rui-Fang; Liu, Xiang-Fu; Lin, Dong-Jun

    2016-10-01

    The interaction between bone marrow stromal cells and leukemia cells is critical for the persistence and progression of leukemia, and this interaction may account for residual disease. However, the link between leukemia cells and their environment is still poorly understood. In our study, runt‑related transcription factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and involved in mesenchymal stem cell (MSC)‑mediated protection of leukemia cells from As2O3‑induced apoptosis. We observed induction of RUNX3 expression and the translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells. In K562 chronic myeloid leukemia cells, downregulation of endogenous RUNX3 compromised As2O3‑induced growth inhibition, cell cycle arrest, and apoptosis. In the presence of MSC, As2O3‑induced expression of RUNX3 was reduced significantly and this reduction was modulated by CXCL12/CXCR4 signaling. Furthermore, overexpression of RUNX3 restored, at least in part, the sensitivity of leukemic cells to As2O3. We conclude that RUNX3 plays an important role in As2O3‑induced cellular responses and allows cells to overcome MSC‑mediated drug resistance. Therefore, RUNX3 is a promising target for therapeutic approaches to overcome MSC‑mediated drug resistance.

  11. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... concentrates required to be employed in the hydraulic system of underground equipment in accordance with the... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approved fire-resistant hydraulic fluids... Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment §...

  12. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... concentrates required to be employed in the hydraulic system of underground equipment in accordance with the... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Approved fire-resistant hydraulic fluids... Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment §...

  13. Adaptive Resistance in Bacteria Requires Epigenetic Inheritance, Genetic Noise, and Cost of Efflux Pumps

    PubMed Central

    Motta, Santiago Sandoval; Cluzel, Philippe; Aldana, Maximino

    2015-01-01

    Adaptive resistance emerges when populations of bacteria are subjected to gradual increases of antibiotics. It is characterized by a rapid emergence of resistance and fast reversibility to the non-resistant phenotype when the antibiotic is removed from the medium. Recent work shows that adaptive resistance requires epigenetic inheritance and heterogeneity of gene expression patterns that are, in particular, associated with the production of porins and efflux pumps. However, the precise mechanisms by which inheritance and variability govern adaptive resistance, and what processes cause its reversibility remain unclear. Here, using an efflux pump regulatory network (EPRN) model, we show that the following three mechanisms are essential to obtain adaptive resistance in a bacterial population: 1) intrinsic variability in the expression of the EPRN transcription factors; 2) epigenetic inheritance of the transcription rate of EPRN associated genes; and 3) energetic cost of the efflux pumps activity that slows down cell growth. While the first two mechanisms acting together are responsible for the emergence and gradual increase of the resistance, the third one accounts for its reversibility. In contrast with the standard assumption, our model predicts that adaptive resistance cannot be explained by increased mutation rates. Our results identify the molecular mechanism of epigenetic inheritance as the main target for therapeutic treatments against the emergence of adaptive resistance. Finally, our theoretical framework unifies known and newly identified determinants such as the burden of efflux pumps that underlie bacterial adaptive resistance to antibiotics. PMID:25781931

  14. Adaptive resistance in bacteria requires epigenetic inheritance, genetic noise, and cost of efflux pumps.

    PubMed

    Motta, Santiago Sandoval; Cluzel, Philippe; Aldana, Maximino

    2015-01-01

    Adaptive resistance emerges when populations of bacteria are subjected to gradual increases of antibiotics. It is characterized by a rapid emergence of resistance and fast reversibility to the non-resistant phenotype when the antibiotic is removed from the medium. Recent work shows that adaptive resistance requires epigenetic inheritance and heterogeneity of gene expression patterns that are, in particular, associated with the production of porins and efflux pumps. However, the precise mechanisms by which inheritance and variability govern adaptive resistance, and what processes cause its reversibility remain unclear. Here, using an efflux pump regulatory network (EPRN) model, we show that the following three mechanisms are essential to obtain adaptive resistance in a bacterial population: 1) intrinsic variability in the expression of the EPRN transcription factors; 2) epigenetic inheritance of the transcription rate of EPRN associated genes; and 3) energetic cost of the efflux pumps activity that slows down cell growth. While the first two mechanisms acting together are responsible for the emergence and gradual increase of the resistance, the third one accounts for its reversibility. In contrast with the standard assumption, our model predicts that adaptive resistance cannot be explained by increased mutation rates. Our results identify the molecular mechanism of epigenetic inheritance as the main target for therapeutic treatments against the emergence of adaptive resistance. Finally, our theoretical framework unifies known and newly identified determinants such as the burden of efflux pumps that underlie bacterial adaptive resistance to antibiotics.

  15. Indicator Amino Acid-Derived Estimate of Dietary Protein Requirement for Male Bodybuilders on a Nontraining Day Is Several-Fold Greater than the Current Recommended Dietary Allowance.

    PubMed

    Bandegan, Arash; Courtney-Martin, Glenda; Rafii, Mahroukh; Pencharz, Paul B; Lemon, Peter Wr

    2017-02-08

    Background: Despite a number of studies indicating increased dietary protein needs in bodybuilders with the use of the nitrogen balance technique, the Institute of Medicine (2005) has concluded, based in part on methodologic concerns, that "no additional dietary protein is suggested for healthy adults undertaking resistance or endurance exercise."Objective: The aim of the study was to assess the dietary protein requirement of healthy young male bodybuilders ( with ≥3 y training experience) on a nontraining day by measuring the oxidation of ingested l-[1-(13)C]phenylalanine to (13)CO2 in response to graded intakes of protein [indicator amino acid oxidation (IAAO) technique].Methods: Eight men (means ± SDs: age, 22.5 ± 1.7 y; weight, 83.9 ± 11.6 kg; 13.0% ± 6.3% body fat) were studied at rest on a nontraining day, on several occasions (4-8 times) each with protein intakes ranging from 0.1 to 3.5 g ⋅ kg(-1) ⋅ d(-1), for a total of 42 experiments. The diets provided energy at 1.5 times each individual's measured resting energy expenditure and were isoenergetic across all treatments. Protein was fed as an amino acid mixture based on the protein pattern in egg, except for phenylalanine and tyrosine, which were maintained at constant amounts across all protein intakes. For 2 d before the study, all participants consumed 1.5 g protein ⋅ kg(-1) ⋅ d(-1) On the study day, the protein requirement was determined by identifying the breakpoint in the F(13)CO2 with graded amounts of dietary protein [mixed-effects change-point regression analysis of F(13)CO2 (labeled tracer oxidation in breath)].Results: The Estimated Average Requirement (EAR) of protein and the upper 95% CI RDA for these young male bodybuilders were 1.7 and 2.2 g ⋅ kg(-1) ⋅ d(-1), respectively.Conclusion: These IAAO data suggest that the protein EAR and recommended intake for male bodybuilders at rest on a nontraining day exceed the current recommendations of the Institute of Medicine by ∼2

  16. The Concept of Electrical Resistance: How Cassirer's Philosophy, and the Early Developments of Electric Circuit Theory, Allow a Better Understanding of Students' Learning Difficulties.

    ERIC Educational Resources Information Center

    Viard, Jerome; Khantine-Langlois, Francoise

    2001-01-01

    Investigates the difficulties students are confronted with when facing the concept of electrical resistance. Discusses the nature of the electrical resistance concept in light of Cassirer philosophy and its origin in the 19th century. Presents an analysis of the way this concept is taught in French high schools. (SAH)

  17. Directly observed treatment, short-course strategy and multidrug-resistant tuberculosis: are any modifications required?

    PubMed Central

    Bastian, I.; Rigouts, L.; Van Deun, A.; Portaels, F.

    2000-01-01

    Multidrug-resistant tuberculosis (MDRTB) should be defined as tuberculosis with resistance to at least isoniazid and rifampicin because these drugs are the cornerstone of short-course chemotherapy, and combined isoniazid and rifampicin resistance requires prolonged treatment with second-line agents. Short-course chemotherapy is a key ingredient in the tuberculosis control strategy known as directly observed treatment, short-course (DOTS). For populations in which multidrug-resistant tuberculosis is endemic, the outcome of the standard short-course chemotherapy regimen remains uncertain. Unacceptable failure rates have been reported and resistance to additional agents may be induced. As a consequence there have been calls for well-functioning DOTS programmes to provide additional services in areas with high rates of multidrug-resistant tuberculosis. These "DOTS-plus for MDRTB programmes" may need to modify all five elements of the DOTS strategy: the treatment may need to be individualized rather than standardized; laboratory services may need to provide facilities for on-site culture and antibiotic susceptibility testing; reliable supplies of a wide range of expensive second-line agents would have to be supplied; operational studies would be required to determine the indications for and format of the expanded programmes; financial and technical support from international organizations and Western governments would be needed in addition to that obtained from local governments. PMID:10743297

  18. The Concept of Electrical Resistance: How Cassirer's Philosophy, and the Early Developments of Electric Circuit Theory, Allow a Better Understanding of Students' Learning Difficulties

    NASA Astrophysics Data System (ADS)

    Viard, Jerome; Khantine-Langlois, Francoise

    While students' difficulties concerning the concepts of voltage and intensity have been investigated by many science education researchers, difficulties related to the concept of electrical resistance and circuit are less known. Some researchers in science education even state that students have no preconception about this concept before being taught. Our observations are in disagreement with this assumption. In the first section of this paper the main basic features of the difficulties of students confronted with the concept of electrical resistance are investigated. In the second section we discuss the nature of the electrical resistance concept in the light of Cassirer philosophy while in the third section we give an analysis of this concept going back to its origins in the nineteenth century. Finally, an analysis of the way this concept is taught in French high schools is presented and the first results of a experimentation using an alternative teaching strategy are briefly reported.c

  19. The WRKY45-Dependent Signaling Pathway Is Required For Resistance against Striga hermonthica Parasitism.

    PubMed

    Mutuku, J Musembi; Yoshida, Satoko; Shimizu, Takafumi; Ichihashi, Yasunori; Wakatake, Takanori; Takahashi, Akira; Seo, Mitsunori; Shirasu, Ken

    2015-07-01

    The root hemiparasite witchweed (Striga spp.) is a devastating agricultural pest that causes losses of up to $1 billion US annually in sub-Saharan Africa. Development of resistant crops is one of the cost-effective ways to address this problem. However, the molecular mechanisms underlying resistance are not well understood. To understand molecular events upon Striga spp. infection, we conducted genome-scale RNA sequencing expression analysis using Striga hermonthica-infected rice (Oryza sativa) roots. We found that transcripts grouped under the Gene Ontology term defense response were significantly enriched in up-regulated differentially expressed genes. In particular, we found that both jasmonic acid (JA) and salicylic acid (SA) pathways were induced, but the induction of the JA pathway preceded that of the SA pathway. Foliar application of JA resulted in higher resistance. The hebiba mutant plants, which lack the JA biosynthesis gene allene oxide cyclase, exhibited severe S. hermonthica susceptibility. The resistant phenotype was recovered by application of JA. By contrast, the SA-deficient NahG rice plants were resistant against S. hermonthica, indicating that endogenous SA is not required for resistance. However, knocking down WRKY45, a regulator of the SA/benzothiadiazole pathway, resulted in enhanced susceptibility. Interestingly, NahG plants induced the JA pathway, which was down-regulated in WRKY45-knockdown plants, linking the resistant and susceptible phenotypes to the JA pathway. Consistently, the susceptibility phenotype in the WRKY45-knockdown plants was recovered by foliar JA application. These results point to a model in which WRKY45 modulates a cross talk in resistance against S. hermonthica by positively regulating both SA/benzothiadiazole and JA pathways.

  20. The WRKY45-Dependent Signaling Pathway Is Required For Resistance against Striga hermonthica Parasitism1[OPEN

    PubMed Central

    Yoshida, Satoko; Takahashi, Akira; Seo, Mitsunori

    2015-01-01

    The root hemiparasite witchweed (Striga spp.) is a devastating agricultural pest that causes losses of up to $1 billion US annually in sub-Saharan Africa. Development of resistant crops is one of the cost-effective ways to address this problem. However, the molecular mechanisms underlying resistance are not well understood. To understand molecular events upon Striga spp. infection, we conducted genome-scale RNA sequencing expression analysis using Striga hermonthica-infected rice (Oryza sativa) roots. We found that transcripts grouped under the Gene Ontology term defense response were significantly enriched in up-regulated differentially expressed genes. In particular, we found that both jasmonic acid (JA) and salicylic acid (SA) pathways were induced, but the induction of the JA pathway preceded that of the SA pathway. Foliar application of JA resulted in higher resistance. The hebiba mutant plants, which lack the JA biosynthesis gene ALLENE OXIDE CYCLASE, exhibited severe S. hermonthica susceptibility. The resistant phenotype was recovered by application of JA. By contrast, the SA-deficient NahG rice plants were resistant against S. hermonthica, indicating that endogenous SA is not required for resistance. However, knocking down WRKY45, a regulator of the SA/benzothiadiazole pathway, resulted in enhanced susceptibility. Interestingly, NahG plants induced the JA pathway, which was down-regulated in WRKY45-knockdown plants, linking the resistant and susceptible phenotypes to the JA pathway. Consistently, the susceptibility phenotype in the WRKY45-knockdown plants was recovered by foliar JA application. These results point to a model in which WRKY45 modulates a cross talk in resistance against S. hermonthica by positively regulating both SA/benzothiadiazole and JA pathways. PMID:26025049

  1. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Airflow resistance test, Type A and Type AE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.153 Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will...

  2. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  3. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Airflow resistance test; Type B and Type BE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall...

  4. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Airflow resistance test; Type B and Type BE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall...

  5. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Airflow resistance test, Type A and Type AE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.153 Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will...

  6. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  7. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  8. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Airflow resistance test, Type A and Type AE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.153 Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will...

  9. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Airflow resistance test; Type B and Type BE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall...

  10. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Airflow resistance test; Type B and Type BE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall...

  11. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  12. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Airflow resistance test, Type A and Type AE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.153 Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will...

  13. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  14. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Airflow resistance test; Type B and Type BE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall...

  15. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Airflow resistance test, Type A and Type AE... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.153 Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will...

  16. Calcineurin is required for pseudohyphal growth, virulence, and drug resistance in Candida lusitaniae.

    PubMed

    Zhang, Jing; Silao, Fitz Gerald S; Bigol, Ursela G; Bungay, Alice Alma C; Nicolas, Marilou G; Heitman, Joseph; Chen, Ying-Lien

    2012-01-01

    Candida lusitaniae is an emerging fungal pathogen that infects immunocompromised patients including HIV/AIDS, cancer, and neonatal pediatric patients. Though less prevalent than other Candida species, C. lusitaniae is unique in its ability to develop resistance to amphotericin B. We investigated the role of the calcium-activated protein phosphatase calcineurin in several virulence attributes of C. lusitaniae including pseudohyphal growth, serum survival, and growth at 37°C. We found that calcineurin and Crz1, a C. albicans Crz1 homolog acting as a downstream target of calcineurin, are required for C. lusitaniae pseudohyphal growth, a process for which the underlying mechanism remains largely unknown in C. lusitaniae but hyphal growth is fundamental to C. albicans virulence. We demonstrate that calcineurin is required for cell wall integrity, ER stress response, optimal growth in serum, virulence in a murine systemic infection model, and antifungal drug tolerance in C. lusitaniae. To further examine the potential of targeting the calcineurin signaling cascade for antifungal drug development, we examined the activity of a calcineurin inhibitor FK506 in combination with caspofungin against echinocandin resistant C. lusitaniae clinical isolates. Broth microdilution and drug disk diffusion assays demonstrate that FK506 has synergistic fungicidal activity with caspofungin against echinocandin resistant isolates. Our findings reveal that pseudohyphal growth is controlled by the calcineurin signaling cascade, and highlight the potential use of calcineurin inhibitors and caspofungin for emerging drug-resistant C. lusitaniae infections.

  17. MurAA Is Required for Intrinsic Cephalosporin Resistance of Enterococcus faecalis

    PubMed Central

    Vesić, Dušanka

    2012-01-01

    Enterococcus faecalis is a low-GC Gram-positive bacterium that is intrinsically resistant to cephalosporins, antibiotics that target cell wall biosynthesis. To probe the mechanistic basis for intrinsic resistance, a library of transposon mutants was screened to identify E. faecalis strains that are highly susceptible to ceftriaxone, revealing a transposon mutant with a disruption in murAA. murAA is predicted to encode a UDP-N-acetylglucosamine 1-carboxyvinyl transferase that catalyzes the first committed step in peptidoglycan synthesis: phosphoenolpyruvate (PEP)-dependent conversion of UDP-N-acetylglucosamine to UDP-N-acetylglucosamine-enolpyruvate. In-frame deletion of murAA, but not its homolog in the E. faecalis genome (murAB), led to increased susceptibility of E. faecalis to cephalosporins. Furthermore, expression of murAA enhanced cephalosporin resistance in an E. faecalis mutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance. Further genetic analysis revealed that MurAA catalytic activity is necessary but not sufficient for this role. Collectively, our data indicate that MurAA and MurAB have distinct roles in E. faecalis physiology and suggest that MurAA possesses a unique property or activity that enables it to enhance intrinsic resistance of E. faecalis to cephalosporins. PMID:22290954

  18. Genetic Studies of Sulfadiazine-resistant and Methionine-requiring Neisseria Isolated From Clinical Material

    PubMed Central

    Catlin, B. Wesley

    1967-01-01

    Deoxyribonucleate (DNA) preparations were extracted from Neisseria meningitidis (four isolates from spinal fluid and blood) and N. gonorrhoeae strains, all of which were resistant to sulfadiazine upon primary isolation. These DNA preparations, together with others from in vitro mutants of N. meningitidis and N. perflava, were examined in transformation tests by using as recipient a drug-susceptible strain of N. meningitidis (Ne 15 Sul-s Met+) which was able to grow in a methionine-free defined medium. The sulfadiazine resistance typical of each donor was introduced into the uniform constitution of this recipient. Production of p-aminobenzoic acid was not significantly altered thereby. Transformants elicited by DNA from the N. meningitidis clinical isolates were resistant to at least 200 μg of sulfadiazine/ml, and did not show a requirement for methionine (Sul-r Met+). DNA from six strains of N. gonorrhoeae, which were isolated during the period of therapeutic use of sulfonamides, conveyed lower degrees of resistance and, invariably, a concurrent methionine requirement (Sul-r/Met−). The requirement of these transformants, and that of in vitro mutants selected on sulfadiazine-agar, was satisfied by methionine, but not by vitamin B12, homocysteine, cystathionine, homoserine, or cysteine. Sul-r Met+ and Sul-r/Met− loci could coexist in the same genome, but were segregated during transformation. On the other hand, the dual Sul-r/Met− properties were not separated by recombination, but were eliminated together. DNA from various Sul-r/Met− clones tested against recipients having nonidentical Sul-r/Met− mutant sites yielded Sul-s Met+ transformants. The met locus involved is genetically complex, and will be a valuable tool for studies of genetic fine structure of members of Neisseria, and of genetic homology between species. Images PMID:4962305

  19. Functional diversification of hsp40: distinct j-protein functional requirements for two prions allow for chaperone-dependent prion selection.

    PubMed

    Harris, Julia M; Nguyen, Phil P; Patel, Milan J; Sporn, Zachary A; Hines, Justin K

    2014-07-01

    Yeast prions are heritable amyloid aggregates of functional yeast proteins; their propagation to subsequent cell generations is dependent upon fragmentation of prion protein aggregates by molecular chaperone proteins. Mounting evidence indicates the J-protein Sis1 may act as an amyloid specificity factor, recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act in prion fragmentation. Chaperone interactions with prions, however, can be affected by variations in amyloid-core structure resulting in distinct prion variants or 'strains'. Our genetic analysis revealed that Sis1 domain requirements by distinct variants of [PSI+] are strongly dependent upon overall variant stability. Notably, multiple strong [PSI+] variants can be maintained by a minimal construct of Sis1 consisting of only the J-domain and glycine/phenylalanine-rich (G/F) region that was previously shown to be sufficient for cell viability and [RNQ+] prion propagation. In contrast, weak [PSI+] variants are lost under the same conditions but maintained by the expression of an Sis1 construct that lacks only the G/F region and cannot support [RNQ+] propagation, revealing mutually exclusive requirements for Sis1 function between these two prions. Prion loss is not due to [PSI+]-dependent toxicity or dependent upon a particular yeast genetic background. These observations necessitate that Sis1 must have at least two distinct functional roles that individual prions differentially require for propagation and which are localized to the glycine-rich domains of the Sis1. Based on these distinctions, Sis1 plasmid-shuffling in a [PSI+]/[RNQ+] strain permitted J-protein-dependent prion selection for either prion. We also found that, despite an initial report to the contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation in place of Sis1. This conservation of function is also prion-variant dependent, indicating that only one of the two Sis1-prion functions may have

  20. State Health Department Requirements for Reporting of Antibiotic-Resistant Infections by Providers, United States, 2013 and 2015.

    PubMed

    Pogorzelska-Maziarz, Monika; Carter, Eileen J; Manning, Mary Lou; Larson, Elaine L

    Due to the high burden of antibiotic-resistant infections, several US states mandate public reporting of these infections. To examine the extent to which state departments of health require reporting of antibiotic-resistant infections, we abstracted data from lists of reportable conditions from all 50 states at 2 time points, May 2013 and May 2015. Requirements varied substantially by state. In 2015, most states (n = 44) required reporting of at least 1 antibiotic-resistant infection; vancomycin-intermediate and/or vancomycin-resistant Staphylococcus aureus was the most frequently reportable infection (n = 40). Few states required reporting of methicillin-resistant S aureus (n = 11), multidrug-resistant gram-negative bacteria (n = 9), or vancomycin-resistant enterococci (n = 8). During the 2 years we studied, 2013 and 2015, 4 states removed and 9 added at least 1 reporting requirement. The changes in reporting requirements suggest flexibility in health departments' response to local surveillance needs and emerging threats. Future studies should assess how data on antibiotic-resistant infections through different sources are used at the state level to drive prevention and control efforts.

  1. Conformational flexibility of the glycosidase NagZ allows it to bind structurally diverse inhibitors to suppress β-lactam antibiotic resistance.

    PubMed

    Vadlamani, Grishma; Stubbs, Keith A; Désiré, Jérôme; Blériot, Yves; Vocadlo, David J; Mark, Brian L

    2017-03-28

    NagZ is an N-acetyl-β-d-glucosaminidase that participates in the peptidoglycan (PG) recycling pathway of Gram-negative bacteria by removing N-acetyl-glucosamine (GlcNAc) from PG fragments that have been excised from the cell wall during growth. The 1,6-anhydromuramoyl-peptide products generated by NagZ activate β-lactam resistance in many Gram-negative bacteria by inducing the expression of AmpC β-lactamase. Blocking NagZ activity can thereby suppress β-lactam antibiotic resistance in these bacteria. The NagZ active site is dynamic and it accommodates distortion of the glycan substrate during catalysis using a mobile catalytic loop that carries a histidine residue which serves as the active site general acid/base catalyst. Here, we show that flexibility of this catalytic loop also accommodates structural differences in small molecule inhibitors of NagZ, which could be exploited to improve inhibitor specificity. X-ray structures of NagZ bound to the potent yet non-selective N-acetyl-β-glucosaminidase inhibitor PUGNAc (O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate), and two NagZ-selective inhibitors - EtBuPUG, a PUGNAc derivative bearing a 2-N-ethylbutyryl group, and MM-156, a 3-N-butyryl trihydroxyazepane, revealed that the phenylcarbamate moiety of PUGNAc and EtBuPUG completely displaces the catalytic loop from the NagZ active site to yield a catalytically incompetent form of the enzyme. In contrast, the catalytic loop was found positioned in the catalytically active conformation within the NagZ active site when bound to MM-156, which lacks the phenylcarbamate extension. Displacement of the catalytic loop by PUGNAc and its N-acyl derivative EtBuPUG alters the active site conformation of NagZ, which presents an additional strategy to improve the potency and specificity of NagZ inhibitors.

  2. Tn5-mediated bleomycin resistance in Escherichia coli requires the expression of host genes.

    PubMed

    Blot, M; Heitman, J; Arber, W

    1993-06-01

    The transposon Tn5 expresses a gene, ble, whose product increases the viability of Escherichia coli and also confers resistance to the DNA-cleaving antibiotic bleomycin and the DNA-alkylating agent ethylmethanesulphonate. We find that the Ble protein induces expression of an alkylation inducible gene, aidC, and that both the AidC gene product and DNA polymerase I are required for Ble to confer bleomycin resistance. These findings support models in which Ble enhances DNA repair and suggest that Tn5 confers a fitness advantage to the host bacterium by increasing the repair of spontaneous DNA lesions. Such co-operation between a transposon and its host suggests that Tn5 is a symbiotic rather than a selfish DNA element.

  3. Coil-dependent signaling pathway is not required for Mi-1-mediated potato aphid resistance.

    PubMed

    Bhattarai, Kishor K; Xie, Qi-Guang; Pourshalimi, Daniel; Younglove, Ted; Kaloshian, Isgouhi

    2007-03-01

    Tomato (Solanum lycopersicum) has a unique resistance gene, Mi-1, that confers resistance to animals from distinct taxa, nematodes, and piercing and sucking insects. Mi-1 encodes a protein with a nucleotide-binding site and leucine-rich repeat motifs. Early in the potato aphid (Macrosiphum euphorbiae)--tomato interactions, aphid feeding induces the expression of the jasmonic acid (JA)-regulated proteinase inhibitor genes, Pin1 and Pin2. The jail-1 (jasmonic acid insensitive 1) tomato mutant, which is impaired in JA perception, was used to gain additional insight into the JA signaling pathway and its role in the Mi-1-mediated aphid resistance. The jail-1 mutant has a deletion in the Coil gene that encodes a putative F-box protein. In this study, aphid colonization, survival, and fecundity were compared on wild-type tomato and jail-1 mutant. In choice assays, the jail-1 mutant showed higher colonization by potato aphids compared with wild-type tomato. In contrast, no-choice assays showed no difference in potato aphid survival or fecundity between jail-1 and the wild-type parent. Plants homozygous for Mi-1 and for the jail mutation were not compromised in resistance to potato aphids, using either choice or no-choice assays. In addition, the accumulation of JA-regulated Pin1 transcripts after aphid feeding was Coil dependent. Taken together, these data indicate that, although potato aphids activate Coil-dependent defense response in tomato, this response is not required for Mi-1-mediated resistance to aphids.

  4. Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes.

    PubMed

    Labenski, Verena; Suerth, Julia D; Barczak, Elke; Heckl, Dirk; Levy, Camille; Bernadin, Ornellie; Charpentier, Emmanuelle; Williams, David A; Fehse, Boris; Verhoeyen, Els; Schambach, Axel

    2016-08-01

    Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering.

  5. Surgical Stress Resistance Induced by Single Amino Acid Deprivation Requires Gcn2 in Mice

    PubMed Central

    Peng, Wei; Robertson, Lauren; Gallinetti, Jordan; Mejia, Pedro; Vose, Sarah; Charlip, Allison; Chu, Timothy; Mitchell, James R.

    2012-01-01

    Dietary restriction, or reduced food intake without malnutrition, increases life span, health span, and acute stress resistance in model organisms from yeast to nonhuman primates. Although dietary restriction is beneficial for human health, this treatment is not widely used in the clinic. Here, we show that short-term, ad libitum feeding of diets lacking essential nutrients increased resistance to surgical stress in a mouse model of ischemia reperfusion injury. Dietary preconditioning by 6 to 14 days of total protein deprivation, or removal of the single essential amino acid tryptophan, protected against renal and hepatic ischemic injury, resulting in reduced inflammation and preserved organ function. Pharmacological treatment with halofuginone, which activated the amino acid starvation response within 3 days by mimicking proline deprivation, was also beneficial. Both dietary and pharmacological interventions required the amino acid sensor and eIF2α (eukaryotic translation initiation factor 2α) kinase Gcn2 (general control nonderepressible 2), implicating the amino acid starvation response and translational control in stress protection. Thus, short-term dietary or pharmacological interventions that modulate amino acid sensing can confer stress resistance in models of surgical ischemia reperfusion injury. PMID:22277968

  6. Characterization of a Pipecolic Acid Biosynthesis Pathway Required for Systemic Acquired Resistance.

    PubMed

    Ding, Pingtao; Rekhter, Dmitrij; Ding, Yuli; Feussner, Kirstin; Busta, Lucas; Haroth, Sven; Xu, Shaohua; Li, Xin; Jetter, Reinhard; Feussner, Ivo; Zhang, Yuelin

    2016-10-01

    Systemic acquired resistance (SAR) is an immune response induced in the distal parts of plants following defense activation in local tissue. Pipecolic acid (Pip) accumulation orchestrates SAR and local resistance responses. Here, we report the identification and characterization of SAR-DEFICIENT4 (SARD4), which encodes a critical enzyme for Pip biosynthesis in Arabidopsis thaliana Loss of function of SARD4 leads to reduced Pip levels and accumulation of a Pip precursor, Δ(1)-piperideine-2-carboxylic acid (P2C). In Escherichia coli, expression of the aminotransferase ALD1 leads to production of P2C and addition of SARD4 results in Pip production, suggesting that a Pip biosynthesis pathway can be reconstituted in bacteria by coexpression of ALD1 and SARD4. In vitro experiments showed that ALD1 can use l-lysine as a substrate to produce P2C and P2C is converted to Pip by SARD4. Analysis of sard4 mutant plants showed that SARD4 is required for SAR as well as enhanced pathogen resistance conditioned by overexpression of the SAR regulator FLAVIN-DEPENDENT MONOOXYGENASE1. Compared with the wild type, pathogen-induced Pip accumulation is only modestly reduced in the local tissue of sard4 mutant plants, but it is below detection in distal leaves, suggesting that Pip is synthesized in systemic tissue by SARD4-mediated reduction of P2C and biosynthesis of Pip in systemic tissue contributes to SAR establishment.

  7. Neither Dectin-2 nor the Mannose Receptor Is Required for Resistance to Coccidioides immitis in Mice

    PubMed Central

    Viriyakosol, Suganya; Jimenez, Maria del Pilar; Saijo, Sinobu

    2014-01-01

    We investigated the roles of the mannose receptor (MR) and Dectin-2 in resistance to pulmonary coccidioidomycosis in C57BL/6 (B6) mice and in the interaction of myeloid cells with spherules, using B6 mice with targeted mutations in Mrc1 and Clec4n. Spherules are the tissue form of Coccidioides, and we determined that the MR on bone marrow-derived dendritic cells (BMDC) was important for recognition of spherules (formalin-killed spherules [FKS]) and for secretion of interleukin 10 (IL-10) and proinflammatory cytokines in response to FKS by both elicited macrophages and BMDC. Infected MR knockout (KO) mice produced more IL-10 in their lungs than did B6 mice, and MR KO mice also made more protective Th-17 cytokines. In contrast to the MR, Dectin-2 was not required for recognition of FKS by BMDC or for the production of cytokines by BMDC in response to FKS. However, Dectin-2 KO was required for stimulation of elicited peritoneal macrophages. Despite that, lung cytokine levels were not significantly different in Dectin-2 KO mice and B6 mice 14 days after infection, except for IL-1β, which was higher in Dectin-2 KO lungs. Although both Dectin-2−/− and MR−/− myeloid cells had reduced proinflammatory cytokine responses to FKS in vitro, neither MR nor Dectin-2 deficiency reduced the resistance of B6 mice to pulmonary coccidioidomycosis. PMID:24379281

  8. Contemporary Issues in Protein Requirements and Consumption for Resistance Trained Athletes

    PubMed Central

    Wilson, Jacob; Wilson, Gabriel J

    2006-01-01

    In recent years an explosion of research papers concerning protein consumption has been published. The need to consolidate this information has become critical from both practical and future research standpoints. For this reason, the following paper presents an in depth analysis of contemporary issues in protein requirements and consumption for resistance trained athletes. Specifically, the paper covers: 1.) protein requirements for resistance trained athletes; 2.) the effect of the digestion rate of protein on muscular protein balance; 3.) the optimal timing of protein intake relative to exercise; 4.) the optimal pattern of protein ingestion, relative to how an individual should consume their protein throughout a 24 hour period, and what sources are utilized during this time frame; 5.) protein composition and its interaction with measures of protein balance and strength performance; 6.) the combination of protein and carbohydrates on plasma insulin levels and protein balance; 7.) the efficacy of protein supplements and whole food protein sources. Our goal is to provide the reader with practical information in optimizing protein intake as well as for provision of sound advice to their clients. Finally, special care was taken to provide future research implications. PMID:18500966

  9. Akt2 is required for hepatic lipid accumulation in models of insulin resistance

    PubMed Central

    Leavens, Karla F.; Easton, Rachael M.; Shulman, Gerald I.; Previs, Stephen F.; Birnbaum, Morris J.

    2009-01-01

    Summary Insulin drives the global anabolic response to nutrient ingestion, regulating both carbohydrate and lipid metabolism. Previous studies have demonstrated that Akt2/protein kinase B is critical to insulin’s control of glucose metabolism, but its role in lipid metabolism has remained controversial. Here we show that Akt2 is required for hepatic lipid accumulation in obese, insulin-resistant states induced by either leptin-deficiency or high fat diet feeding. Lepob/ob mice lacking hepatic Akt2 failed to amass triglycerides in their livers, associated with and most likely due to a decrease in lipogenic gene expression and de novo lipogenesis. However, Akt2 is also required for steatotic pathways unrelated to fatty acid synthesis, as mice fed high fat diet had reduced liver triglycerides in the absence of hepatic Akt2 but did not exhibit changes in lipogenesis. These data demonstrate that Akt2 is a requisite component of the insulin-dependent regulation of lipid metabolism during insulin resistance. PMID:19883618

  10. Purple Acid Phosphatase5 is required for maintaining basal resistance against Pseudomonas syringae in Arabidopsis

    PubMed Central

    2013-01-01

    Background Plants have evolved an array of constitutive and inducible defense strategies to restrict pathogen ingress. However, some pathogens still manage to invade plants and impair growth and productivity. Previous studies have revealed several key regulators of defense responses, and efforts have been made to use this information to develop disease resistant crop plants. These efforts are often hampered by the complexity of defense signaling pathways. To further elucidate the complexity of defense responses, we screened a population of T-DNA mutants in Colombia-0 background that displayed altered defense responses to virulent Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Results In this study, we demonstrated that the Arabidopsis Purple Acid Phosphatse5 (PAP5) gene, induced under prolonged phosphate (Pi) starvation, is required for maintaining basal resistance to certain pathogens. The expression of PAP5 was distinctly induced only under prolonged Pi starvation and during the early stage of Pst DC3000 infection (6 h.p.i). T-DNA tagged mutant pap5 displayed enhanced susceptibility to the virulent bacterial pathogen Pst DC3000. The pap5 mutation greatly reduced the expression of pathogen inducible gene PR1 compared to wild-type plants. Similarly, other defense related genes including ICS1 and PDF1.2 were impaired in pap5 plants. Moreover, application of BTH (an analog of SA) restored PR1 expression in pap5 plants. Conclusion Taken together, our results demonstrate the requirement of PAP5 for maintaining basal resistance against Pst DC3000. Furthermore, our results provide evidence that PAP5 acts upstream of SA accumulation to regulate the expression of other defense responsive genes. We also provide the first experimental evidence indicating the role PAP5 in plant defense responses. PMID:23890153

  11. Arabidopsis dual resistance proteins, both RPS4 and RRS1, are required for resistance to bacterial wilt in transgenic Brassica crops.

    PubMed

    Narusaka, Mari; Hatakeyama, Katsunori; Shirasu, Ken; Narusaka, Yoshihiro

    2014-01-01

    Bacterial wilt phytopathogen Ralstonia solanacearum is a serious soil-borne disease that attacks several economically important plants worldwide, including Brassicaceae. Previous studies indicate that recognition of avirulence (Avr)-effector PopP2 by resistance (R) protein, RRS1-R, and physical interaction between RRS1-R and PopP2 in the nucleus are required for resistance. Of late, we showed that a pair of Arabidopsis thaliana TIR-NLR proteins, RRS1 and RPS4, function together in disease resistance against multiple pathogen isolates. Here, we report that dual R proteins, RRS1 and RPS4, from A. thaliana ecotype Wassilewskija confer resistance to bacterial wilt in transgenic Brassica crops. For practical applications, this finding may provide a new strategy for developing disease resistant plants that express R genes from other plants.

  12. Arabidopsis thaliana FLOWERING LOCUS D is required for systemic acquired resistance.

    PubMed

    Singh, Vijayata; Roy, Shweta; Giri, Mrunmay Kumar; Chaturvedi, Ratnesh; Chowdhury, Zulkarnain; Shah, Jyoti; Nandi, Ashis Kumar

    2013-09-01

    Localized infection in plants often induces systemic acquired resistance (SAR), which provides long-term protection against subsequent infections. A signal originating in the SAR-inducing organ is transported to the distal organs, where it stimulates salicylic acid (SA) accumulation and priming, a mechanism that results in more robust activation of defenses in response to subsequent pathogen infection. In recent years, several metabolites that promote long-distance SAR signaling have been identified. However, the mechanism or mechanisms by which plants perceive and respond to the SAR signals are largely obscure. Here, we show that, in Arabidopsis thaliana, the FLOWERING LOCUS D (FLD) is required for responding to the SAR signals leading to the systemic accumulation of SA and enhancement of disease resistance. Although the fld mutant was competent in accumulating the SAR-inducing signal, it was unable to respond to the SAR signal that accumulates in petiole exudates of wild-type leaves inoculated with a SAR-inducing pathogen. Supporting FLD's role in systemic SAR signaling, we observed that dehydroabietinal and azelaic acid, two metabolites that, in wild-type plants, promote SAR-associated systemic accumulation of SA and priming, respectively, were unable to promote SAR in the fld mutant. FLD also participates in flowering, where it functions to repress expression of the flowering repressor FLOWERING LOCUS C (FLC). However, epistasis analysis indicates that FLD's function in SAR is independent of FLC.

  13. SOR1, a gene required for photosensitizer and singlet oxygen resistance in Cercospora fungi, is highly conserved in divergent organisms.

    PubMed

    Ehrenshaft, M; Jenns, A E; Chung, K R; Daub, M E

    1998-03-01

    Filamentous Cercospora fungi are resistant to photosensitizing compounds that generate singlet oxygen. C. nicotianae photosensitizer-sensitive mutants were restored to full resistance by transformation with SOR1 (Singlet Oxygen Resistance 1), a gene recovered from a wild-type genomic library. SOR1 null mutants generated via targeted gene replacement confirmed the requirement for SOR1 in photosensitizer resistance. SOR1 RNA is present throughout the growth cycle. Although resistance to singlet oxygen is rare in biological systems, SOR1, a gene with demonstrated activity against singlet-oxygen-generating photosensitizers, is highly conserved in organisms from widely diverse taxa. The characterization of SOR1 provides an additional phenotype to this large group of evolutionarily conserved genes.

  14. A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity

    PubMed Central

    Oláhová, Monika; Veal, Elizabeth A

    2015-01-01

    Peroxiredoxins (Prx) are abundant thiol peroxidases with a conserved anti-ageing role. In contrast to most animals, the nematode worm, Caenorhabditis elegans, encodes a single cytosolic 2-Cys Prx, PRDX-2, rendering it an excellent model for examining how peroxiredoxins affect animal physiology and ageing. Our previous work revealed that, although PRDX-2 protects against the toxicity of peroxides, enigmatically, prdx-2-mutant animals are hyper-resistant to other forms of oxidative stress. Here, we have investigated the basis for this increased resistance. Mammalian FOXO and Nrf2 transcription factors directly promote the expression of a range of detoxification enzymes. We show that the FOXO orthologue, DAF-16, and the Nrf2 orthologue, SKN-1, are required for the increased stress resistance of prdx-2-mutant worms. Our data suggest that PRDX-2 is required for normal levels of insulin secretion and hence the inhibition of DAF-16 and SKN-1 by insulin/IGF-1-like signalling (IIS) under nutrient-rich conditions. Intriguingly, loss of PRDX-2 increases DAF-16 and SKN-1 activities sufficiently to increase arsenite resistance without initiating other IIS-inhibited processes. Together, these data suggest that loss of peroxiredoxin function may increase stress resistance by reducing insulin secretion, but that further changes in insulin signalling are required for the reprogramming of development and fat metabolism. In addition, we reveal that the temperature-dependent prolongevity function of PRDX-2 is required for the extended lifespan associated with several pathways, including further reductions in IIS. PMID:25808059

  15. Mycobacterium tuberculosis Requires Phosphate-Responsive Gene Regulation To Resist Host Immunity

    PubMed Central

    Leistikow, Rachel L.; Kirksey, Meghan A.; Voskuil, Martin I.; McKinney, John D.

    2013-01-01

    Mycobacterium tuberculosis persists in the tissues of mammalian hosts despite inducing a robust immune response dominated by the macrophage-activating cytokine gamma interferon (IFN-γ). We identified the M. tuberculosis phosphate-specific transport (Pst) system component PstA1 as a factor required to resist IFN-γ-dependent immunity. A ΔpstA1 mutant was fully virulent in IFN-γ−/− mice but attenuated in wild-type (WT) mice and mice lacking specific IFN-γ-inducible immune mechanisms: nitric oxide synthase (NOS2), phagosome-associated p47 GTPase (Irgm1), or phagocyte oxidase (phox). These phenotypes suggest that ΔpstA1 bacteria are sensitized to an IFN-γ-dependent immune mechanism(s) other than NOS2, Irgm1, or phox. In other species, the Pst system has a secondary role as a negative regulator of phosphate starvation-responsive gene expression through an interaction with a two-component signal transduction system. In M. tuberculosis, we found that ΔpstA1 bacteria exhibited dysregulated gene expression during growth in phosphate-rich medium that was mediated by the two-component sensor kinase/response regulator system SenX3-RegX3. Remarkably, deletion of the regX3 gene suppressed the replication and virulence defects of ΔpstA1 bacteria in NOS2−/− mice, suggesting that M. tuberculosis requires the Pst system to negatively regulate activity of RegX3 in response to available phosphate in vivo. We therefore speculate that inorganic phosphate is readily available during replication in the lung and is an important signal controlling M. tuberculosis gene expression via the Pst-SenX3-RegX3 signal transduction system. Inability to sense this environmental signal, due to Pst deficiency, results in dysregulation of gene expression and sensitization of the bacteria to the host immune response. PMID:23132496

  16. Pertactin is required for Bordetella species to resist neutrophil-mediated clearance.

    PubMed

    Inatsuka, Carol S; Xu, Qian; Vujkovic-Cvijin, Ivan; Wong, Sandy; Stibitz, Scott; Miller, Jeff F; Cotter, Peggy A

    2010-07-01

    Pertactin (PRN) is an autotransporter protein produced by all members of the Bordetella bronchiseptica cluster, which includes B. pertussis, B. parapertussis, and B. bronchiseptica. It is a primary component of acellular pertussis vaccines, and anti-PRN antibody titers correlate with protection. In vitro studies have suggested that PRN functions as an adhesin and that an RGD motif located in the center of the passenger domain is important for this function. Two regions of PRN that contain sequence repeats (region 1 [R1] and R2) show polymorphisms among strains and have been implicated in vaccine-driven evolution. We investigated the role of PRN in pathogenesis using B. bronchiseptica and natural-host animal models. A Deltaprn mutant did not differ from wild-type B. bronchiseptica in its ability to adhere to epithelial and macrophage-like cells in vitro or to establish respiratory infection in rats but was cleared much faster than wild-type bacteria in a mouse lung inflammation model. Unlike wild-type B. bronchiseptica, the Deltaprn mutant was unable to cause a lethal infection in SCID-Bg mice, but, like wild-type bacteria, it was lethal for neutropenic mice. These results suggest that PRN plays a critical role in allowing Bordetella to resist neutrophil-mediated clearance. Mutants producing PRN proteins in which the RGD motif was replaced with RGE or in which R1 and R2 were deleted were indistinguishable from wild-type bacteria in all assays, suggesting that these sequences do not contribute to PRN function.

  17. DL-beta-aminobutyric acid-induced resistance of potato against Phytophthora infestans requires salicylic acid but not oxylipins.

    PubMed

    Eschen-Lippold, Lennart; Altmann, Simone; Rosahl, Sabine

    2010-05-01

    Inducing systemic resistance responses in crop plants is a promising alternative way of disease management. To understand the underlying signaling events leading to induced resistance, functional analyses of plants defective in defined signaling pathway steps are required. We used potato, one of the economically most-important crop plants worldwide, to examine systemic resistance against the devastating late blight pathogen Phytophthora infestans, induced by treatment with dl-beta-aminobutyric acid (BABA). Transgenic plants impaired in either the 9-lipoxygenase pathway, which produces defense-related compounds, or the 13-lipoxygenase pathway, which generates jasmonic acid-derived signals, expressed wild-type levels of BABA-induced resistance. Plants incapable of accumulating salicylic acid (SA), on the other hand, failed to mount this type of induced resistance. Consistently, treatment of these plants with the SA analog 2,6-dichloroisonicotinic acid restored BABA-induced resistance. Together, these results demonstrate the indispensability of a functional SA pathway for systemic resistance in potato induced by BABA.

  18. TaCPK2-A, a calcium-dependent protein kinase gene that is required for wheat powdery mildew resistance enhances bacterial blight resistance in transgenic rice.

    PubMed

    Geng, Shuaifeng; Li, Aili; Tang, Lichuan; Yin, Lingjie; Wu, Liang; Lei, Cailin; Guo, Xiuping; Zhang, Xin; Jiang, Guanghuai; Zhai, Wenxue; Wei, Yuming; Zheng, Youliang; Lan, Xiujin; Mao, Long

    2013-08-01

    Calcium-dependent protein kinases (CPKs) are important Ca2+ signalling components involved in complex immune and stress signalling networks; but the knowledge of CPK gene functions in the hexaploid wheat is limited. Previously, TaCPK2 was shown to be inducible by powdery mildew (Blumeria graminis tritici, Bgt) infection in wheat. Here, its functions in disease resistance are characterized further. This study shows the presence of defence-response and cold-response cis-elements on the promoters of the A subgenome homoeologue (TaCPK2-A) and D subgenome homoeologue (TaCPK2-D), respectively. Their expression patterns were then confirmed by quantitative real-time PCR (qRT-PCR) using genome-specific primers, where TaCPK2-A was induced by Bgt treatment while TaCPK2-D mainly responded to cold treatment. Downregulation of TaCPK2-A by virus-induced gene silencing (VIGS) causes loss of resistance to Bgt in resistant wheat lines, indicating that TaCPK2-A is required for powdery mildew resistance. Furthermore, overexpression of TaCPK2-A in rice enhanced bacterial blight (Xanthomonas oryzae pv. oryzae, Xoo) resistance. qRT-PCR analysis showed that overexpression of TaCPK2-A in rice promoted the expression of OsWRKY45-1, a transcription factor involved in both fungal and bacterial resistance by regulating jasmonic acid and salicylic acid signalling genes. The opposite effect was found in wheat TaCPK2-A VIGS plants, where the homologue of OsWRKY45-1 was significantly repressed. These data suggest that modulation of WRKY45-1 and associated defence-response genes by CPK2 genes may be the common mechanism for multiple disease resistance in grass species, which may have undergone subfunctionalization in promoters before the formation of hexaploid wheat.

  19. TaCPK2-A, a calcium-dependent protein kinase gene that is required for wheat powdery mildew resistance enhances bacterial blight resistance in transgenic rice

    PubMed Central

    Geng, Shuaifeng; Li, Aili; Tang, Lichuan; Lan, Xiujin; Mao, Long

    2013-01-01

    Calcium-dependent protein kinases (CPKs) are important Ca2+ signalling components involved in complex immune and stress signalling networks; but the knowledge of CPK gene functions in the hexaploid wheat is limited. Previously, TaCPK2 was shown to be inducible by powdery mildew (Blumeria graminis tritici, Bgt) infection in wheat. Here, its functions in disease resistance are characterized further. This study shows the presence of defence-response and cold-response cis-elements on the promoters of the A subgenome homoeologue (TaCPK2-A) and D subgenome homoeologue (TaCPK2-D), respectively. Their expression patterns were then confirmed by quantitative real-time PCR (qRT-PCR) using genome-specific primers, where TaCPK2-A was induced by Bgt treatment while TaCPK2-D mainly responded to cold treatment. Downregulation of TaCPK2-A by virus-induced gene silencing (VIGS) causes loss of resistance to Bgt in resistant wheat lines, indicating that TaCPK2-A is required for powdery mildew resistance. Furthermore, overexpression of TaCPK2-A in rice enhanced bacterial blight (Xanthomonas oryzae pv. oryzae, Xoo) resistance. qRT-PCR analysis showed that overexpression of TaCPK2-A in rice promoted the expression of OsWRKY45-1, a transcription factor involved in both fungal and bacterial resistance by regulating jasmonic acid and salicylic acid signalling genes. The opposite effect was found in wheat TaCPK2-A VIGS plants, where the homologue of OsWRKY45-1 was significantly repressed. These data suggest that modulation of WRKY45-1 and associated defence-response genes by CPK2 genes may be the common mechanism for multiple disease resistance in grass species, which may have undergone subfunctionalization in promoters before the formation of hexaploid wheat. PMID:23918959

  20. Physical association of the NB-LRR resistance protein Rx with a Ran GTPase-activating protein is required for extreme resistance to Potato virus X.

    PubMed

    Tameling, Wladimir I L; Baulcombe, David C

    2007-05-01

    Nucleotide binding leucine-rich repeat (NB-LRR) proteins play an important role in plant and mammalian innate immunity. In plants, these resistance proteins recognize specific pathogen-derived effector proteins. Recognition subsequently triggers a rapid and efficient defense response often associated with the hypersensitive response and other poorly understood processes that suppress the pathogen. To investigate mechanisms associated with the activation of disease resistance responses, we investigated proteins binding to the potato (Solanum tuberosum) NB-LRR protein Rx that confers extreme resistance to Potato virus X (PVX) in potato and Nicotiana benthamiana. By affinity purification experiments, we identified an endogenous N. benthamiana Ran GTPase-Activating Protein2 (RanGAP2) as an Rx-associated protein in vivo. Further characterization confirmed the specificity of this interaction and showed that the association occurs through their N-terminal domains. By specific virus-induced gene silencing of RanGAP2 in N. benthamiana carrying Rx, we demonstrated that this interaction is required for extreme resistance to PVX and suggest that RanGAP2 is part of the Rx signaling complex. These results implicate RanGAP-mediated cellular mechanisms, including nucleocytoplasmic trafficking, in the activation of disease resistance.

  1. PmrD is required for modifications to escherichia coli endotoxin that promote antimicrobial resistance.

    PubMed

    Rubin, Erica J; Herrera, Carmen M; Crofts, Alexander A; Trent, M Stephen

    2015-04-01

    In Salmonella enterica, PmrD is a connector protein that links the two-component systems PhoP-PhoQ and PmrA-PmrB. While Escherichia coli encodes a PmrD homolog, it is thought to be incapable of connecting PhoPQ and PmrAB in this organism due to functional divergence from the S. enterica protein. However, our laboratory previously observed that low concentrations of Mg(2+), a PhoPQ-activating signal, leads to the induction of PmrAB-dependent lipid A modifications in wild-type E. coli (C. M. Herrera, J. V. Hankins, and M. S. Trent, Mol Microbiol 76:1444-1460, 2010, http://dx.doi.org/10.1111/j.1365-2958.2010.07150.x). These modifications include phosphoethanolamine (pEtN) and 4-amino-4-deoxy-l-arabinose (l-Ara4N), which promote bacterial resistance to cationic antimicrobial peptides (CAMPs) when affixed to lipid A. Here, we demonstrate that pmrD is required for modification of the lipid A domain of E. coli lipopolysaccharide (LPS) under low-Mg(2+) growth conditions. Further, RNA sequencing shows that E. coli pmrD influences the expression of pmrA and its downstream targets, including genes coding for the modification enzymes that transfer pEtN and l-Ara4N to the lipid A molecule. In line with these findings, a pmrD mutant is dramatically impaired in survival compared with the wild-type strain when exposed to the CAMP polymyxin B. Notably, we also reveal the presence of an unknown factor or system capable of activating pmrD to promote lipid A modification in the absence of the PhoPQ system. These results illuminate a more complex network of protein interactions surrounding activation of PhoPQ and PmrAB in E. coli than previously understood.

  2. Cell polarization is required for ricin sensitivity in a Caco-2 cell line selected for ricin resistance.

    PubMed Central

    Jackman, M R; Ellis, J A; Gray, S R; Shurety, W; Luzio, J P

    1999-01-01

    It has been proposed that killing of mammalian cells by ricin requires efficient endocytic delivery to the trans-Golgi network (TGN) prior to retrograde transport to the endoplasmic reticulum and entry to the cytosol. In polarized epithelial cells, an efficient membrane-traffic pathway to the TGN is present from the basolateral but not the apical plasma-membrane domain. Thus one can hypothesize that a ricin-resistant phenotype might be demonstrated by polarized cells that fail to differentiate and thus fail to develop an efficient membrane-traffic pathway from the basolateral plasma membrane to the TGN. We have isolated and studied a ricin-resistant Caco-2 cell clone (Caco-2-RCAr clone 2) which, when grown on plastic, was deficient in differentiation, measured by the development of polarized-cell-surface marker enzymes. The deficiency in differentiation was partially reversed, and ricin sensitivity was restored, when the cells were grown on filter supports. Our data provide the first evidence of a ricin-resistant cell line where resistance is due to the lack of development of polarized cell surfaces. The observed ricin resistance is consistent with the requirement that ricin is delivered to the TGN before its A chain enters the cytosol to mediate cell killing. PMID:10393089

  3. Transfer of plasmid-mediated ampicillin resistance from Haemophilus to Neisseria gonorrhoeae requires an intervening organism.

    PubMed

    McNicol, P J; Albritton, W L; Ronald, A R

    1986-01-01

    Haemophilus species have been implicated as the source of plasmid-mediated ampicillin resistance in Neisseria gonorrhoeae. Previous attempts to transfer conjugally the resistance plasmids from Haemophilus species to N. gonorrhoeae have met with limited success. Using both biparental and triparental mating systems, it was found that transfer will occur if the commensal Neisseria species, Neisseria cinerea, is used as a transfer intermediate. This organism stably maintains resistance plasmids of Haemophilus and facilitates transfer of these plasmids to N. gonorrhoeae, in a triparental mating system, at a transfer frequency of 10(-8). Both Haemophilus ducreyi and N. gonorrhoeae carry mobilizing plasmids capable of mediating conjugal transfer of the same resistance plasmids. However, restriction endonuclease mapping and DNA hybridization studies indicate that the mobilizing plasmids are distinctly different molecules. Limited homology is present within the transfer region of these plasmids.

  4. 43 CFR 12.927 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Allowable costs. 12.927 Section 12.927... COST PRINCIPLES FOR ASSISTANCE PROGRAMS Uniform Administrative Requirements for Grants and Agreements... Requirements § 12.927 Allowable costs. Federal awarding agencies shall determine allowable costs in...

  5. Arabidopsis WRKY70 is required for full RPP4-mediated disease resistance and basal defense against Hyaloperonospora parasitica.

    PubMed

    Knoth, Colleen; Ringler, Jon; Dangl, Jeffery L; Eulgem, Thomas

    2007-02-01

    AtWRKY70, encoding a WRKY transcription factor, is co-expressed with a set of Arabidopsis genes that share a pattern of RPP4- and RPP7-dependent late upregulation in response to Hyaloperonospora parasitica infection (LURP) genes. We show that AtWRKY70 is required for both full RPP4-mediated resistance and basal defense against H. parasitica. These two defense pathways are related to each other, because they require PAD4 and salicylic acid (SA). RPP7 function, which is independent from PAD4 and SA, is not affected by insertions in AtWRKY70. Although AtWRKY70 is required for RPP4-resistance, it appears not to contribute significantly to RPP4-triggered cell death. Furthermore, our data indicate that AtWRKY70 functions downstream of defense-associated reactive oxygen intermediates and SA. Constitutive and RPP4-induced transcript levels of two other LURP genes are reduced in AtWRKY70 T-DNA mutants, indicating a direct or indirect role for AtWRKY70 in their regulation. We propose that AtWRKY70 is a component of a basal defense mechanism that is boosted by engagement of either RPP4 or RPP7 and is required for RPP4-mediated resistance.

  6. 45 CFR 602.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 602.22 Section 602.22 Public... Requirements § 602.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable...

  7. 15 CFR 14.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Allowable costs. 14.27 Section 14.27... ORGANIZATIONS Post-Award Requirements Financial and Program Management § 14.27 Allowable costs. For each kind of recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs...

  8. 45 CFR 2543.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Allowable costs. 2543.27 Section 2543.27 Public... ORGANIZATIONS Post-Award Requirements Financial and Program Management § 2543.27 Allowable costs. For each kind of recipient, there is a set of Federal principles for determining allowable costs. Allowability...

  9. Cryptococcus neoformans Yap1 is required for normal fluconazole and oxidative stress resistance.

    PubMed

    Paul, Sanjoy; Doering, Tamara L; Moye-Rowley, W Scott

    2015-01-01

    Cryptococcus neoformans is a pathogen that is the most common cause of fungal meningitis. As with most fungal pathogens, the most prevalent clinical antifungal used to treat Cryptococcosis is orally administered fluconazole. Resistance to this antifungal is an increasing concern in treatment of fungal disease in general. Our knowledge of the specific determinants involved in fluconazole resistance in Cryptococcus is limited. Here we report the identification of an important genetic determinant of fluconazole resistance in C. neoformans that encodes a basic region-leucine zipper transcription factor homologous to Saccharomyces cerevisiae Yap1. Expression of a codon-optimized form of the Cn YAP1 cDNA in S. cerevisiae complemented defects caused by loss of the endogenous S. cerevisiae YAP1 gene and activated transcription from a reporter gene construct. Mutant strains of C. neoformans lacking YAP1 were hypersensitive to a range of oxidative stress agents but importantly also to fluconazole. Loss of Yap1 homologues from other fungal pathogens like Candida albicans or Aspergillus fumigatus was previously found to cause oxidant hypersensitivity but had no detectable effect on fluconazole resistance. Our data provide evidence for a unique biological role of Yap1 in wild-type fluconazole resistance in C. neoformans.

  10. Extensively Drug-Resistant Tuberculosis: Report and Literature Review on Two Cases Requiring Prolonged Treatment

    PubMed Central

    Matos-Tocasca, Martha; De la Cruz-Ku, Gabriel; Auccacusi, Erick; Fernandez-Salas, Diego; García-Ahuanari, Tatiana; Valcarcel-Valdivia, Bryan

    2016-01-01

    Case series Patient: Female, 28 • Male, 20 Final Diagnosis: Extensively drug-resistant tuberculosis Symptoms: Cough productive • dyspnea • hemoptysis • respiratory failure • weight loss Medication: — Clinical Procedure: — Specialty: Pulmonology Objective: Unusual clinical course Background: Extensively drug-resistant tuberculosis (XDR-TB) is a global problem due to the high morbidity and mortality it causes. Peru is one of the countries with the highest numbers of cases of XDR-TB, which increase every year. Case Report: We present the case of two siblings who developed XDR-TB, underwent surgery twice, and were in individualized treatment for more than 6 years. Finally they achieved remission of symptoms, despite not having standardized treatment schemes during their diagnosis period. Conclusions: Extensively drug-resistant tuberculosis can be cured with a treatment that involves both medical care and patient actions to achieve remission of the disease. PMID:27807339

  11. History Teaches Us That Confronting Antibiotic Resistance Requires Stronger Global Collective Action.

    PubMed

    Podolsky, Scott H; Bud, Robert; Gradmann, Christoph; Hobaek, Bård; Kirchhelle, Claas; Mitvedt, Tore; Santesmases, María Jesús; Thoms, Ulrike; Berild, Dag; Kveim Lie, Anne

    2015-01-01

    Antibiotic development and usage, and antibiotic resistance in particular, are today considered global concerns, simultaneously mandating local and global perspectives and actions. Yet such global considerations have not always been part of antibiotic policy formation, and those who attempt to formulate a globally coordinated response to antibiotic resistance will need to confront a history of heterogeneous, often uncoordinated, and at times conflicting reform efforts, whose legacies remain apparent today. Historical analysis permits us to highlight such entrenched trends and processes, helping to frame contemporary efforts to improve access, conservation and innovation.

  12. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... oral hygiene products and vaginal products are not now packaged in tamper-resistant retail packages... liquid oral hygiene product or vaginal product for retail sale shall package the product in a tamper... product (except vaginal tablets) packaged for retail sale on or after that date, except for...

  13. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... oral hygiene products and vaginal products are not now packaged in tamper-resistant retail packages... liquid oral hygiene product or vaginal product for retail sale shall package the product in a tamper... product (except vaginal tablets) packaged for retail sale on or after that date, except for...

  14. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... oral hygiene products and vaginal products are not now packaged in tamper-resistant retail packages... liquid oral hygiene product or vaginal product for retail sale shall package the product in a tamper... product (except vaginal tablets) packaged for retail sale on or after that date, except for...

  15. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... oral hygiene products and vaginal products are not now packaged in tamper-resistant retail packages... liquid oral hygiene product or vaginal product for retail sale shall package the product in a tamper... product (except vaginal tablets) packaged for retail sale on or after that date, except for...

  16. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... oral hygiene products and vaginal products are not now packaged in tamper-resistant retail packages... liquid oral hygiene product or vaginal product for retail sale shall package the product in a tamper... product (except vaginal tablets) packaged for retail sale on or after that date, except for...

  17. High-Level Chromate Resistance in Arthrobacter sp. strain FB24 Requires Previously Uncharacterized Accessory Genes

    SciTech Connect

    Henne, Kristene L.; Nakatsu, Cindy N.; Thompson, Dorothea K.; Konopka, Allan

    2009-09-24

    The annotated genome sequence of Arthrobacter sp. strain FB24 revealed a chromate resistance determinant (CRD): a cluster of 8 genes located on a 10.6 kb fragment of a 96 kb plasmid. The CRD includes chrA, which encodes a putative chromate efflux protein, and three genes with amino acid similarities to the amino and carboxy termini of ChrB, a putative regulatory protein. There are also three novel genes that have not been previously associated with chromate resistance in other bacteria; they encode an oxidoreductase (most similar to malate:quinone oxidoreductase), a functionally unknown protein with a WD40 repeat domain and a lipoprotein. A chromate-sensitive mutant (strain D11) was generated by curing FB24 of its 96-kb plasmid. Elemental analysis indicated that chromate-exposed cells of strain D11 accumulated three times more chromium than strain FB24. Introduction of the CRD into strain D11 conferred chromate resistance comparable to wild-type levels, whereas deletion of specific regions of the CRD led to decreased resistance. Using real-time reverse transcriptase PCR, we show that expression of each gene within the CRD is specifically induced in response to chromate but not by lead, hydrogen peroxide or arsenate. Higher levels of chrA expression were achieved when the chrB orthologs and the WD40 repeat domain genes were present, suggesting their regulatory roles. Collectively, our findings indicate that chromate resistance in strain FB24 is primarily achieved by plasmid-mediated chromate efflux with the contribution of previously unrecognized accessory genes.

  18. Effective Global Action on Antibiotic Resistance Requires Careful Consideration of Convening Forums.

    PubMed

    Rizvi, Zain; Hoffman, Steven J

    2015-01-01

    Global collective action is needed to address the growing transnational threat of antibiotic resistance (ABR). Some commentators have recommended an international legal agreement as the most promising mechanism for coordinating such action. While much has been said about what must be done to address ABR, far less work has analyzed how or where such collective action should be facilitated - even though the success of any international agreement depends greatly on where it is negotiated and implemented. This article evaluates four different forums that states may use to develop an international legal agreement for antibiotic resistance: (1) a self-organized venue; (2) the World Health Organization; (3) the World Trade Organization; and (4) the United Nations General Assembly. The need for a multisectoral approach and the diverse institutional landscape suggest that an effective response may best be coordinated through linked action pursued through multiple forums.

  19. Sterol Biosynthesis Is Required for Heat Resistance but Not Extracellular Survival in Leishmania

    PubMed Central

    Xu, Wei; Hsu, Fong-Fu; Baykal, Eda; Huang, Juyang; Zhang, Kai

    2014-01-01

    Sterol biosynthesis is a crucial pathway in eukaryotes leading to the production of cholesterol in animals and various C24-alkyl sterols (ergostane-based sterols) in fungi, plants, and trypanosomatid protozoa. Sterols are important membrane components and precursors for the synthesis of powerful bioactive molecules, including steroid hormones in mammals. Their functions in pathogenic protozoa are not well characterized, which limits the development of sterol synthesis inhibitors as drugs. Here we investigated the role of sterol C14α-demethylase (C14DM) in Leishmania parasites. C14DM is a cytochrome P450 enzyme and the primary target of azole drugs. In Leishmania, genetic or chemical inactivation of C14DM led to a complete loss of ergostane-based sterols and accumulation of 14-methylated sterols. Despite the drastic change in lipid composition, C14DM-null mutants (c14dm−) were surprisingly viable and replicative in culture. They did exhibit remarkable defects including increased membrane fluidity, failure to maintain detergent resistant membrane fraction, and hypersensitivity to heat stress. These c14dm− mutants showed severely reduced virulence in mice but were highly resistant to itraconazole and amphotericin B, two drugs targeting sterol synthesis. Our findings suggest that the accumulation of toxic sterol intermediates in c14dm− causes strong membrane perturbation and significant vulnerability to stress. The new knowledge may help improve the efficacy of current drugs against pathogenic protozoa by exploiting the fitness loss associated with drug resistance. PMID:25340392

  20. The Multidrug-Resistant Gram-negative Superbugs Threat Require Intelligent Use of the Last Weapon.

    PubMed

    Deris, Zakuan Zainy

    2015-09-01

    The global emergence and dissemination of multidrug-resistant Gram-negative superbugs, particularly carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae, lead to the limited effectiveness of antibiotics for treating nosocomial infections. In most cases, polymyxins are the last resort therapy, and these antibiotics must be used intelligently to prolong their efficacy in clinical practice. Polymyxin B and colistin (polymyxin E) were introduced prior to modern drug regulation, and the majority of the 'old' drug information is unreliable. Recent pharmacokinetic data do not support the renal dose adjustment of intravenous (IV) polymyxin B as suggested by the manufacturer, and this drug must be scaled by the total body weight. Whereas IV colistin is formulated as an inactive prodrug, colistin methanesulfonate (CMS) has different pharmacokinetic profiles than polymyxin B. To achieve maximum efficacy, CMS should be administered as a loading dose scaled to body weight and a maintenance dose according to the renal profiles. Polymyxin combination therapy is suggested due to a sub-therapeutic plasma concentration in a significant proportion of patients and a high incidence of polymyxin hetero-resistance among Gram-negative superbugs. In conclusion, polymyxins must be reserved as a last resort and should be wisely used when truly indicated.

  1. Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells.

    PubMed

    Samanta, Debangshu; Gilkes, Daniele M; Chaturvedi, Pallavi; Xiang, Lisha; Semenza, Gregg L

    2014-12-16

    Triple negative breast cancers (TNBCs) are defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expression, and are treated with cytotoxic chemotherapy such as paclitaxel or gemcitabine, with a durable response rate of less than 20%. TNBCs are enriched for the basal subtype gene expression profile and the presence of breast cancer stem cells, which are endowed with self-renewing and tumor-initiating properties and resistance to chemotherapy. Hypoxia-inducible factors (HIFs) and their target gene products are highly active in TNBCs. Here, we demonstrate that HIF expression and transcriptional activity are induced by treatment of MDA-MB-231, SUM-149, and SUM-159, which are human TNBC cell lines, as well as MCF-7, which is an ER(+)/PR(+) breast cancer line, with paclitaxel or gemcitabine. Chemotherapy-induced HIF activity enriched the breast cancer stem cell population through interleukin-6 and interleukin-8 signaling and increased expression of multidrug resistance 1. Coadministration of HIF inhibitors overcame the resistance of breast cancer stem cells to paclitaxel or gemcitabine, both in vitro and in vivo, leading to tumor eradication. Increased expression of HIF-1α or HIF target genes in breast cancer biopsies was associated with decreased overall survival, particularly in patients with basal subtype tumors and those treated with chemotherapy alone. Based on these results, clinical trials are warranted to test whether treatment of patients with TNBC with a combination of cytotoxic chemotherapy and HIF inhibitors will improve patient survival.

  2. Functional characterization of SOR1, a gene required for resistance to photosensitizing toxins in the fungus Cercospora nicotianae.

    PubMed

    Ehrenshaft, M; Chung, K R; Jenns, A E; Daub, M E

    1999-01-01

    The Cercospora nicotianae SOR1 gene is required for resistance to singlet oxygen-generating photosensitizers. SOR1 was characterized in the wild-type and in five photosensitizer-sensitive mutant strains which are complemented to photosensitizer resistance by transformation with SOR1. Sequence analysis determined that three of the mutants contain SOR1 copies with mutations encoding substitutions in the protein-coding sequence; however, two other mutants had wild-type SOR1 protein and promoter sequences. All five mutants accumulate SOR1 mRNA at levels comparable to that of the wild-type strain. In the wild-type strain, SOR1 accumulation is enhanced two-fold by light, but is unaffected by the presence of cercosporin, the photosensitizer synthesized by C. nicotianae. Southern analysis indicates that SOR1 is present in other fungi that synthesize structurally related perylenequinone photosensitizers.

  3. 43 CFR 12.62 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Allowable costs. 12.62 Section 12.62... COST PRINCIPLES FOR ASSISTANCE PROGRAMS Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments Post-Award Requirements § 12.62 Allowable costs. (a) Limitation...

  4. 7 CFR 3016.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Allowable costs. 3016.22 Section 3016.22 Agriculture... GOVERNMENTS Post-Award Requirements Financial Administration § 3016.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees...

  5. 45 CFR 2541.220 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Allowable costs. 2541.220 Section 2541.220 Public... Post-Award Requirements § 2541.220 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for— (1) The allowable costs of the grantees, subgrantees and cost-type...

  6. 24 CFR 85.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Allowable costs. 85.22 Section 85... TRIBAL GOVERNMENTS Post-Award Requirements Financial Administration § 85.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the...

  7. 24 CFR 85.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Allowable costs. 85.22 Section 85... TRIBAL GOVERNMENTS Post-Award Requirements Financial Administration § 85.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the...

  8. 36 CFR 1207.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Allowable costs. 1207.22... GOVERNMENTS Post-Award Requirements Financial Administration § 1207.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees...

  9. 38 CFR 43.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Allowable costs. 43.22... Requirements Financial Administration § 43.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type...

  10. Leptospira interrogans catalase is required for resistance to H2O2 and for virulence.

    PubMed

    Eshghi, Azad; Lourdault, Kristel; Murray, Gerald L; Bartpho, Thanatchaporn; Sermswan, Rasana W; Picardeau, Mathieu; Adler, Ben; Snarr, Brendan; Zuerner, Richard L; Cameron, Caroline E

    2012-11-01

    Pathogenic Leptospira spp. are likely to encounter higher concentrations of reactive oxygen species induced by the host innate immune response. In this study, we characterized Leptospira interrogans catalase (KatE), the only annotated catalase found within pathogenic Leptospira species, by assessing its role in resistance to H(2)O(2)-induced oxidative stress and during infection in hamsters. Pathogenic L. interrogans bacteria had a 50-fold-higher survival rate under H(2)O(2)-induced oxidative stress than did saprophytic L. biflexa bacteria, and this was predominantly catalase dependent. We also characterized KatE, the only annotated catalase found within pathogenic Leptospira species. Catalase assays performed with recombinant KatE confirmed specific catalase activity, while protein fractionation experiments localized KatE to the bacterial periplasmic space. The insertional inactivation of katE in pathogenic Leptospira bacteria drastically diminished leptospiral viability in the presence of extracellular H(2)O(2) and reduced virulence in an acute-infection model. Combined, these results suggest that L. interrogans KatE confers in vivo resistance to reactive oxygen species induced by the host innate immune response.

  11. Mitochondrial ClpP activity is required for cisplatin resistance in human cells

    PubMed Central

    Zhang, Yang; Maurizi, Michael R.

    2016-01-01

    In human cells ClpP and ClpX are imported into the mitochondrial matrix, where they interact to form the ATP-dependent protease ClpXP and play a role in the mitochondrial unfolded protein response. We find that reducing the levels of mitochondrial ClpP or ClpX renders human cancer cells more sensitive to cisplatin, a widely used anti-cancer drug. Conversely, overexpression of HClpP desensitizes cells to cisplatin. Overexpression of inactive HClpP-S97A had no effect. Cisplatin resistance correlated with decreased cellular accumulation of cisplatin and decreased levels of diguanosine-cisplatin adducts in both mitochondrial and genomic DNA. In contrast, higher levels of cisplatin-DNA adducts were found in cells in which HClpP had been depleted. Changes in the levels of ClpP had no effect on the levels of CTR1, a copper transporter that contributes to cisplatin uptake. However, the levels of ATP7A and ATP7B, copper efflux pumps that help eliminate cisplatin from cells, were increased when HClpP was overexpressed. HClpP levels were elevated in cervical carcinoma cells (KB-CP) and hepatoma cells (BEL-7404) independently selected for cisplatin resistance. The data indicate that robust HClpXP activity positively affects the ability of cells to efflux cisplatin and suggest that targeting HClpP or HClpX would offer a novel mechanism for sensitizing cancer cells to cisplatin. PMID:26675528

  12. Is osmotic adjustment required for water stress resistance in the Mediterranean shrub Atriplex halimus L?

    PubMed

    Martìnez, Juan-Pablo; Lutts, Stanley; Schanck, André; Bajji, Mohammed; Kinet, Jean-Marie

    2004-09-01

    The effect of water stress was investigated in plants from two populations of Atriplex halimus L: Tensift issued from a salt-affected coastal area and Kairouan, originating from an inland dried site. Water deficit was applied by withholding water for 22 days. Shoot dry weight (shoot DW), leaf relative water content (RWC), turgid weight to dry weight ratio (TW/DW), osmotic potential (psis), osmotic adjustment (OA), proline, glycinebetaine, and sugar content were determined 1, 8, 15 and 22 days after withholding watering. Water stress induced a decrease in shoot DW, RWC, psis, and TW/DW, but an increase in glycinebetaine and sugar leaf contents. The decrease of psis and TW/DW was more marked in Kairouan than in Tensift. At the end of the stress period, Kairouan showed a greater OA compared with Tensift. However, the contribution of net solute accumulation (OAacc) was similar in both populations in response to stress. Water stress resistance could thus not be associated with higher OA, although the ability of plants to regulate these metabolic and physiological functions could play an important role under harmful conditions. The possible roles of osmolyte accumulations are discussed in relation to the specific physiological strategy of water-stress-resistance in this species.

  13. The Histone Deacetylase Gene Rpd3 Is Required for Starvation Stress Resistance

    PubMed Central

    Nakajima, Ei; Shimaji, Kouhei; Umegawachi, Takanari; Tomida, Saki; Yoshida, Hideki; Yoshimoto, Nana; Izawa, Shingo; Kimura, Hiroshi; Yamaguchi, Masamitsu

    2016-01-01

    Epigenetic regulation in starvation is important but not fully understood yet. Here we identified the Rpd3 gene, a Drosophila homolog of histone deacetylase 1, as a critical epigenetic regulator for acquiring starvation stress resistance. Immunostaining analyses of Drosophila fat body revealed that the subcellular localization and levels of Rpd3 dynamically changed responding to starvation stress. In response to starvation stress, the level of Rpd3 rapidly increased, and it accumulated in the nucleolus in what appeared to be foci. These observations suggest that Rpd3 plays a role in regulation of rRNA synthesis in the nucleolus. The RT-qPCR and ChIP-qPCR analyses clarified that Rpd3 binds to the genomic region containing the rRNA promoters and activates rRNA synthesis in response to starvation stress. Polysome analyses revealed that the amount of polysomes was decreased in Rpd3 knockdown flies under starvation stress compared with the control flies. Since the autophagy-related proteins are known to be starvation stress tolerance proteins, we examined autophagy activity, and it was reduced in Rpd3 knockdown flies. Taken together, we conclude that Rpd3 accumulates in the nucleolus in the early stage of starvation, upregulates rRNA synthesis, maintains the polysome amount for translation, and finally increases stress tolerance proteins, such as autophagy-related proteins, to acquire starvation stress resistance. PMID:27907135

  14. Nitric oxide and reactive oxygen species are required for systemic acquired resistance in plants.

    PubMed

    El-Shetehy, Mohamed; Wang, Caixia; Shine, M B; Yu, Keshun; Kachroo, Aardra; Kachroo, Pradeep

    2015-01-01

    Systemic acquired resistance (SAR) is a form of broad-spectrum disease resistance that is induced in response to primary infection and that protects uninfected portions of the plant against secondary infections by related or unrelated pathogens. SAR is associated with an increase in chemical signals that operate in a collective manner to confer protection against secondary infections. These include, the phytohormone salicylic acid (SA), glycerol-3-phosphate (G3P), azelaic acid (AzA) and more recently identified signals nitric oxide (NO) and reactive oxygen species (ROS). NO, ROS, AzA and G3P function in the same branch of the SAR pathway, and in parallel to the SA-regulated branch. NO and ROS function upstream of AzA/G3P and different reactive oxygen species functions in an additive manner to mediate chemical cleavage of the C9 double bond on C18 unsaturated fatty acids to generate AzA. The parallel and additive functioning of various chemical signals provides important new insights in the overlapping pathways leading to SAR.

  15. A novel gene required for cercosporin toxin resistance in the fungus Cercospora nicotianae.

    PubMed

    Chung, K R; Jenns, A E; Ehrenshaft, M; Daub, M E

    1999-09-01

    Cercosporin, a photosensitizing perylenequinone toxin produced by the plant pathogenic Cercospora fungi, generates the highly toxic singlet oxygen (1O2) upon exposure to light. Cercosporin shows broad toxicity against a wide range of organisms, including bacteria, fungi, plants, and animals; however, Cercospora fungi are resistant to its effects. A novel gene, crg1 (cercosporin-resistance gene) was isolated from a wild-type strain of C. nicotianae by genetic complementation of a C. nicotianae mutant (CS10) which is cercosporin sensitive and down-regulated in cercosporin production. Sequence analysis indicated that crg1 encodes a putative protein of 550 amino acids with four putative transmembrane helical regions, however CRG1 shows no strong similarity to any other protein in sequence databases. Northern analysis identified two transcripts (4.5 and 2.6 kb) that are unaffected by the presence of light or cercosporin. Southern analysis demonstrated that crg1 is present in a single copy in the C. nicotianae genome and can be detected only in Cercospora species. Targeted disruption of crg1 resulted in mutants that, like CS10, are sensitive to cercosporin. However, unlike CS10, crg1 disruption mutants are not down-regulated in toxin production. Both CS10 and the crg1 disruption mutants are unaffected in their response to other 1O2-generating photosensitizers, suggesting that CRG1 functions specifically against cercosporin, rather than against 1O2.

  16. [Management of TB suspected cases of drug resistant tuberculosis requiring a second treatment].

    PubMed

    Caminero, José A

    2004-06-01

    The management of patients with resistance to anti tuberculous drugs is complex and therefore must be managed by physician specialists. The most difficult patients are the cases in retreatment, where some very different possibilities are possible, as abandonment, failures and relapses. Patients with multi-drug resistant (MDR) tuberculosis are the most difficult to treat; MDR appears in all the failures or non-adherences to the treatment regime. To elaborate a scheme of retreatment for these patients, two guidelines must be followed: (1) do not rely on outcomes of drug susceptibility tests and (2) a detailed history of drug treatment must be considered of paramount importance. With this information, a retreatment scheme can be formulated that involves the use of at least three drugs not previously taken by the patient. For a successful control of tuberculosis, the national tuberculosis programs in Latin American countries must assure careful management of newly diagnosed patients. Secondly, if resources are available, a bank of second-line drugs must be ready for managing retreatment situations (e.g., 3 Z-Kn-Eth-Of/15 Z-Eth-Of) if first line drug treatments fail. Using individualized retreatment with second line drugs is recommended only in industrialized countries, and for a few middle income countries as a last resort.

  17. Mitochondrial localization of fission yeast manganese superoxide dismutase is required for its lysine acetylation and for cellular stress resistance and respiratory growth

    SciTech Connect

    Takahashi, Hidekazu; Shirai, Atsuko; Matsuyama, Akihisa; Yoshida, Minoru

    2011-03-04

    Research highlights: {yields} Fission yeast manganese superoxide dismutase (MnSOD) is acetylated. {yields} The mitochondrial targeting sequence (MTS) is required for the acetylation of MnSOD. {yields} The MTS is not crucial for MnSOD activity, but is important for respiratory growth. {yields} Posttranslational regulation of MnSOD differs between budding and fission yeast. -- Abstract: Manganese-dependent superoxide dismutase (MnSOD) is localized in the mitochondria and is important for oxidative stress resistance. Although transcriptional regulation of MnSOD has been relatively well studied, much less is known about the protein's posttranslational regulation. In budding yeast, MnSOD is activated after mitochondrial import by manganese ion incorporation. Here we characterize posttranslational modification of MnSOD in the fission yeast Schizosaccharomyces pombe. Fission yeast MnSOD is acetylated at the 25th lysine residue. This acetylation was diminished by deletion of N-terminal mitochondrial targeting sequence, suggesting that MnSOD is acetylated after import into mitochondria. Mitochondrial localization of MnSOD is not essential for the enzyme activity, but is crucial for oxidative stress resistance and growth under respiratory conditions of fission yeast. These results suggest that, unlike the situation in budding yeast, S. pombe MnSOD is already active even before mitochondrial localization; nonetheless, mitochondrial localization is critical to allow the cell to cope with reactive oxygen species generated inside or outside of mitochondria.

  18. The MAP kinase Pmk1 and protein kinase A are required for rotenone resistance in the fission yeast, Schizosaccharomyces pombe

    SciTech Connect

    Wang, Yiwei; Gulis, Galina; Buckner, Scott; Johnson, P. Connor; Sullivan, Daniel; Busenlehner, Laura; Marcus, Stevan

    2010-08-20

    Research highlights: {yields} Rotenone induces generation of ROS and mitochondrial fragmentation in fission yeast. {yields} The MAPK Pmk1 and PKA are required for rotenone resistance in fission yeast. {yields} Pmk1 and PKA are required for ROS clearance in rotenone treated fission yeast cells. {yields} PKA plays a role in ROS clearance under normal growth conditions in fission yeast. -- Abstract: Rotenone is a widely used pesticide that induces Parkinson's disease-like symptoms in rats and death of dopaminergic neurons in culture. Although rotenone is a potent inhibitor of complex I of the mitochondrial electron transport chain, it can induce death of dopaminergic neurons independently of complex I inhibition. Here we describe effects of rotenone in the fission yeast, Schizosaccharomyces pombe, which lacks complex I and carries out rotenone-insensitive cellular respiration. We show that rotenone induces generation of reactive oxygen species (ROS) as well as fragmentation of mitochondrial networks in treated S. pombe cells. While rotenone is only modestly inhibitory to growth of wild type S. pombe cells, it is strongly inhibitory to growth of mutants lacking the ERK-type MAP kinase, Pmk1, or protein kinase A (PKA). In contrast, cells lacking the p38 MAP kinase, Spc1, exhibit modest resistance to rotenone. Consistent with these findings, we provide evidence that Pmk1 and PKA, but not Spc1, are required for clearance of ROS in rotenone treated S. pombe cells. Our results demonstrate the usefulness of S. pombe for elucidating complex I-independent molecular targets of rotenone as well as mechanisms conferring resistance to the toxin.

  19. Interplay between seven secondary metal uptake systems is required for full metal resistance of Cupriavidus metallidurans.

    PubMed

    Herzberg, M; Bauer, L; Kirsten, A; Nies, D H

    2016-03-01

    The beta-proteobacterium Cupriavidus metallidurans is able to grow in metal-contaminated environments due to having sophisticated metal efflux systems. Here, the contribution of all seven known secondary metal uptake systems (ZupT, PitA, CorA1, CorA2, CorA3, ZntB, HoxN) to metal resistance is characterized. In a strategic deletion approach, all ten double deletion mutants, a variety of triple and quadruple mutants, and from the Δ4 mutant (ΔzupT ΔcorA1 ΔcorA2 ΔcorA3) the mutants Δ5 (=Δ4 ΔpitA), Δ6 (=Δ4 ΔpitA ΔzntB), and finally Δ7 (ΔzupT ΔcorA1 ΔcorA2 ΔcorA3 ΔpitA ΔzntB ΔhoxN) were constructed. Metal resistance, metal content, and regulation of expression of these genes were characterized in these mutants. The ΔzupT single deletion strain exhibited an extended lag phase in Tris-buffered liquid mineral salts medium (TMM) compared to its parent strain AE104, indicating a decreased fitness level. Further deletions up to Δ6 did not influence growth in TMM without added metals but fitness of the Δ7 strain dropped to a lower level compared to Δ6, Δ5 and ΔzupT. The cells of the Δ7 multiple deletion strain still contained all essential metals, demonstrating that additional metal import systems must exist in C. metallidurans. PitA was an important contributor of metal:phosphate complexes to C. metallidurans. Up to Δ5 no evidence was found for increased expression of the transporter genes to recruit substitutes for the deleted importers. Only the hoxN-lacZ reporter gene fusion displayed a changed expression pattern in the Δ6 strain, indicating recruitment of HoxN. Metal resistance of the deletion strains decreased along the deletion series although all strains still contained metal efflux systems: up to the Δ6 mutant the overall fitness was kept at the ΔzupT mutant strain level at the cost of a diminished competence to handle μM concentrations of transition metals. Together, these data demonstrated an important contribution of the seven

  20. Candida albicans virulence and drug-resistance requires the O-acyltransferase Gup1p

    PubMed Central

    2010-01-01

    Background GUP1 gene was primarily identified in Saccharomyces cerevisiae being connected with glycerol uptake defects in association with osmotic stress response. Soon after, Gup1p was implicated in a complex and extensive series of phenotypes involving major cellular processes. These include membrane and wall maintenance, lipid composition, bud-site selection, cytoskeleton orientation, vacuole morphology, secretory/endocytic pathway, GPI anchors remodelling, and lipid-ordered domains assembly, which is compatible with their inclusion in the Membrane Bound O-acyl transferases (MBOAT) family. In mammals, it has been described as a negative regulator of the Sonic hedgehog pathway involved in morphogenesis, differentiation, proliferation, among other processes. Results We show that Candida albicans Gup1p strongly interferes with the capacity of cells to develop hyphae, to adhere, to invade, and to form a biofilm, all of which are significant virulence factors. Furthermore, the mutant colonies exhibited an aberrant morphology/differentiation pattern. Identically to S. cerevisiae, Cagup1Δ null mutant was more resistant to antifungals like fluconazole, ketoconazole, and clotrimazole, and displayed an abnormal even sterol distribution at the plasma membrane. Conclusions This work is the first study in the opportunistic yeast Candida albicans, showing a role for the GUP1 gene in virulence as well as in the mechanisms underlying antifungal resistance. Moreover, its impact is even more significant since these results, taken together with all the knowledge about GUP1 gene (from S. cerevisiae and mammals) give consistence to the possibility that Gup1p may be part of a yeast morphogenic pathway parallel to the mammalian Hedgehog. PMID:20843317

  1. The ABC transporter YejABEF is required for resistance to antimicrobial peptides and the virulence of Brucella melitensis

    PubMed Central

    Wang, Zhen; Bie, Pengfei; Cheng, Jie; Lu, Lin; Cui, Buyun; Wu, Qingmin

    2016-01-01

    The ability to resist the killing effects of host antimicrobial peptides (AMPs) plays a vital role in the virulence of pathogens. The Brucella melitensis NI genome has a gene cluster that encodes ABC transport. In this study, we constructed yejA1, yejA2, yejB, yejE, yejF, and whole yej operon deletion mutants, none of which exhibited discernible growth defect in TSB or minimal medium. Unlike their parental strain, the mutants showed a significantly increased sensitivity to acidic stress. The NIΔyejE and NIΔyejABEF mutants were also more sensitive than B. melitensis NI to polymyxin B, and the expression of yej operon genes was induced by polymyxin B. Moreover, cell and mouse infection assays indicated that NIΔyejE and NIΔyejABEF have restricted invasion and replication abilities inside macrophages and are rapidly cleared from the spleens of infected mice. These findings indicate that the ABC transporter YejABEF is required for the virulence of Brucella, suggesting that resistance to host antimicrobials is a key mechanism for Brucella to persistently survive in vivo. This study provided insights that led us to further investigate the potential correlation of AMP resistance with the mechanisms of immune escape and persistent infection by pathogens. PMID:27550726

  2. The ABC transporter YejABEF is required for resistance to antimicrobial peptides and the virulence of Brucella melitensis.

    PubMed

    Wang, Zhen; Bie, Pengfei; Cheng, Jie; Lu, Lin; Cui, Buyun; Wu, Qingmin

    2016-08-23

    The ability to resist the killing effects of host antimicrobial peptides (AMPs) plays a vital role in the virulence of pathogens. The Brucella melitensis NI genome has a gene cluster that encodes ABC transport. In this study, we constructed yejA1, yejA2, yejB, yejE, yejF, and whole yej operon deletion mutants, none of which exhibited discernible growth defect in TSB or minimal medium. Unlike their parental strain, the mutants showed a significantly increased sensitivity to acidic stress. The NIΔyejE and NIΔyejABEF mutants were also more sensitive than B. melitensis NI to polymyxin B, and the expression of yej operon genes was induced by polymyxin B. Moreover, cell and mouse infection assays indicated that NIΔyejE and NIΔyejABEF have restricted invasion and replication abilities inside macrophages and are rapidly cleared from the spleens of infected mice. These findings indicate that the ABC transporter YejABEF is required for the virulence of Brucella, suggesting that resistance to host antimicrobials is a key mechanism for Brucella to persistently survive in vivo. This study provided insights that led us to further investigate the potential correlation of AMP resistance with the mechanisms of immune escape and persistent infection by pathogens.

  3. Neisseria gonorrhoeae Metalloprotease NGO1686 Is Required for Full Piliation, and Piliation Is Required for Resistance to H2O2- and Neutrophil-Mediated Killing

    PubMed Central

    Stohl, Elizabeth A.; Dale, Erin M.; Criss, Alison K.; Seifert, H. Steven

    2013-01-01

    ABSTRACT The sexually transmitted infection gonorrhea is caused exclusively by the human-specific pathogen Neisseria gonorrhoeae. Type IV pili are an essential virulence factor uniformly expressed on clinical gonococcal isolates and are required for several aspects of gonococcal pathogenesis, including adherence to host tissues, autoagglutination, twitching motility, and the uptake of DNA during transformation. Symptomatic gonococcal infection is characterized by the influx of neutrophils or polymorphonuclear leukocytes (PMNs) to the site of infection. PMNs are a key component of gonococcal pathogenesis, mediating the innate immune response through the use of oxidative and nonoxidative killing mechanisms. The M23B family zinc metallopeptidase NGO1686 is required for gonococci to survive oxidative killing by H2O2- and PMN-mediated killing through unknown mechanisms, but the only known target of NGO1686 is peptidoglycan. We report that the effect of NGO1686 on survival after exposure to H2O2 and PMNs is mediated through its role in elaborating pili and that nonpiliated mutants of N. gonorrhoeae are less resistant to killing by H2O2, LL-37, and PMNs than the corresponding piliated strains. These findings add to the various virulence-associated functions attributable to gonococcal pili and may explain the selection basis for piliation in clinical isolates of N. gonorrhoeae. PMID:23839218

  4. PmrD is Required for Modifications to Escherichia Coli Endotoxin that Promote Antimicrobial Resistance

    DTIC Science & Technology

    2015-01-20

    for modification of the lipid A domain of E. coli lipopolysaccharide (LPS) under low-Mg(2+) growth conditions. Further, RNA sequencing shows that E...that pmrD is required for modifi- cation of the lipid A domain of E. coli lipopolysaccharide (LPS) under low-Mg2 growth conditions. Further, RNA ...as shown by RNA sequencing ( RNA -seq) analysis. Intriguingly, our findings also uncover the existence of a second PhoPQ-independent system that

  5. Chest Press Exercises With Different Stability Requirements Result in Similar Muscle Damage Recovery in Resistance-Trained Men.

    PubMed

    Ferreira, Diogo V; Ferreira-Júnior, João B; Soares, Saulo R S; Cadore, Eduardo L; Izquierdo, Mikel; Brown, Lee E; Bottaro, Martim

    2017-01-01

    Ferreira, DV, Ferreira-Júnior, JB, Soares, SRS, Cadore, EL, Izquierdo, M, Brown, LE, and Bottaro, M. Chest press exercises with different stability requirements result in similar muscle damage recovery in resistance trained men. J Strength Cond Res 31(1): 71-79, 2017-This study investigated the time course of 96 hours of muscle recovery after 3 different chest press exercises with different stability requirements in resistance-trained men. Twenty-seven men (23.5 ± 3.8 years) were randomly assigned to one of the 3 groups: (a) Smith machine bench press; (b) barbell bench press; or (c) dumbbell bench press. Participants performed 8 sets of 10 repetition maximum with 2 minutes rest between sets. Muscle thickness, peak torque (PT), and soreness were measured pre, post, 24, 48, 72, and 96 hours after exercise. There were no differences in the time course of PT or muscle thickness values of the pectoralis major (p = 0.98 and p = 0.91, respectively) or elbow extensors (p = 0.07 and p = 0.86, respectively) between groups. Muscle soreness of the pectoralis major was also not different between groups (p > 0.05). However, the Smith machine and barbell groups recovered from triceps brachii muscle soreness by 72 hours after exercise (p > 0.05), whereas the dumbbell group did not present any triceps brachii muscle soreness after exercise (p > 0.05). In conclusion, resistance-trained men experience similar muscle damage recovery after Smith machine, barbell, and dumbbell chest press exercise. However, muscle soreness of the elbow extensors takes a longer time to recover after using a barbell chest press exercise.

  6. Predicting antibiotic resistance.

    PubMed

    Martínez, José L; Baquero, Fernando; Andersson, Dan I

    2007-12-01

    The treatment of bacterial infections is increasingly complicated because microorganisms can develop resistance to antimicrobial agents. This article discusses the information that is required to predict when antibiotic resistance is likely to emerge in a bacterial population. Indeed, the development of the conceptual and methodological tools required for this type of prediction represents an important goal for microbiological research. To this end, we propose the establishment of methodological guidelines that will allow researchers to predict the emergence of resistance to a new antibiotic before its clinical introduction.

  7. The Steroid Receptor Coactivator-3 Is Required for the Development of Castration-resistant Prostate Cancer

    PubMed Central

    Tien, Jean Ching-Yi; Liu, Zhaoliang; Liao, Lan; Wang, Fen; Xu, Yixiang; Wu, Ye-Lin; Zhou, Niya; Ittmann, Michael; Xu, Jianming

    2013-01-01

    The transcriptional coactivator SRC-3 plays a key role to enhance prostate cancer (CaP) cell proliferation. Although SRC-3 is highly expressed in advanced CaP, its role in castration resistant CaP (CRPC) driven by PTEN mutation is unknown. We documented elevated SRC-3 in human CRPC and in PTEN-negative human CaP. Patients with high SRC-3 and undetectable PTEN exhibited decreased recurrence-free survival. To explore the causal relationship in these observations, we generated mice in which both Pten and SRC-3 were inactivated in prostate epithelial cells (Pten3CKO mice), comparing them to mice in which only Pten was inactivated in these cells (PtenCKO mice). SRC-3 deletion impaired cellular proliferation and reduced tumor size. Notably, while castration of PtenCKO control mice increased the aggressiveness of prostate tumors relative to non-castrated counterparts, deletion of SRC-3 in Pten3CKO mice reversed all these changes. In support of this finding, castrated Pten3CKO mice also exhibited decreased levels of phospho-Akt, S6 kinase (RPS6KB1) and phosphorylated S6 protein (RPS6), all of which mediate cell growth and proliferation. Moreover, these tumors appeared to be more differentiated as evidenced by higher levels of Fkbp5, an AR-responsive gene that inhibits Akt signaling. Lastly, these tumors also displayed lower levels of certain androgen-repressed genes such as cyclin E2 and MMP10. Together, our results show that SRC-3 drives CRPC formation and offer preclinical proof of concept for a transcriptional coactivator as a therapeutic target to abrogate CRPC progression. PMID:23650284

  8. Venezuelan equine encephalitis virus entry mechanism requires late endosome formation and resists cell membrane cholesterol depletion

    SciTech Connect

    Kolokoltsov, Andrey A.; Fleming, Elisa H.; Davey, Robert A. . E-mail: radavey@utmb.edu

    2006-04-10

    Virus envelope proteins determine receptor utilization and host range. The choice of receptor not only permits specific targeting of cells that express it, but also directs the virus into specific endosomal trafficking pathways. Disrupting trafficking can result in loss of virus infectivity due to redirection of virions to non-productive pathways. Identification of the pathway or pathways used by a virus is, thus, important in understanding virus pathogenesis mechanisms and for developing new treatment strategies. Most of our understanding of alphavirus entry has focused on the Old World alphaviruses, such as Sindbis and Semliki Forest virus. In comparison, very little is known about the entry route taken by more pathogenic New World alphaviruses. Here, we use a novel contents mixing assay to identify the cellular requirements for entry of a New World alphavirus, Venezuelan equine encephalitis virus (VEEV). Expression of dominant negative forms of key endosomal trafficking genes shows that VEEV must access clathrin-dependent endocytic vesicles for membrane fusion to occur. Unexpectedly, the exit point is different from Old World alphaviruses that leave from early endosomes. Instead, VEEV also requires functional late endosomes. Furthermore, unlike the Old World viruses, VEEV entry is insensitive to cholesterol sequestration from cell membranes and may reflect a need to access an endocytic compartment that lacks cholesterol. This indicates fundamental differences in the entry route taken by VEEV compared to Old World alphaviruses.

  9. A nuclear localization for Avr2 from Fusarium oxysporum is required to activate the tomato resistance protein I-2

    PubMed Central

    Ma, Lisong; Cornelissen, Ben J. C.; Takken, Frank L. W.

    2013-01-01

    Plant pathogens secrete effector proteins to promote host colonization. During infection of tomato xylem vessels, Fusarium oxysporum f. sp. lycopersici (Fol) secretes the Avr2 effector protein. Besides being a virulence factor, Avr2 is recognized intracellularly by the tomato I-2 resistance protein, resulting in the induction of host defenses. Here, we show that AVR2 is highly expressed in root- and xylem-colonizing hyphae three days post inoculation of roots. Co-expression of I-2 with AVR2 deletion constructs using agroinfiltration in Nicotiana benthamiana leaves revealed that, except for the N-terminal 17 amino acids, the entire AVR2 protein is required to trigger I-2-mediated cell death. The truncated Avr2 variants are still able to form homo-dimers, showing that the central region of Avr2 is required for dimerization. Simultaneous production of I-2 and Avr2 chimeras carrying various subcellular localization signals in N. benthamiana leaves revealed that a nuclear localization of Avr2 is required to trigger I-2-dependent cell death. Nuclear exclusion of Avr2 prevented its activation of I-2, suggesting that Avr2 is recognized by I-2 in the nucleus. PMID:23596453

  10. 20 CFR 435.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, OTHER NON-PROFIT ORGANIZATIONS, AND COMMERCIAL... Organizations.” (c) Allowability of costs incurred by institutions of higher education is determined...

  11. SlWRKY70 is required for Mi-1-mediated resistance to aphids and nematodes in tomato.

    PubMed

    Atamian, Hagop S; Eulgem, Thomas; Kaloshian, Isgouhi

    2012-02-01

    Plant resistance (R) gene-mediated defense responses against biotic stresses include vast transcriptional reprogramming. In several plant-pathogen systems, members of the WRKY family of transcription factors have been demonstrated to act as both positive and negative regulators of plant defense transcriptional networks. To identify the possible roles of tomato (Solanum lycopersicum) WRKY transcription factors in defense mediated by the R gene Mi-1 against potato aphid, Macrosiphum euphorbiae, and root-knot nematode (RKN), Meloidogyne javanica, we used tobacco rattle virus (TRV)-based virus-induced gene silencing and transcriptionally suppressed SlWRKY70, a tomato ortholog of the Arabidopsis thaliana WRKY70 gene. Silencing SlWRKY70 attenuated Mi-1-mediated resistance against both potato aphid and RKN showing that SlWRKY70 is required for Mi-1 function. Furthermore, we found SlWRKY70 transcripts to be inducible in response to aphid infestation and RKN inoculation. Mi-1-mediated recognition of these pests modulates this transcriptional response. As previously described for AtWRKY70, we found SlWRKY70 transcript levels to be up-regulated by salicylic acid and suppressed by methyl jasmonate. This indicates that some aspects of WRKY70 regulation are conserved among distantly related eudicots.

  12. GWT1 encoding an inositol acyltransferase homolog is required for laccase repression and stress resistance in the basidiomycete Cryptococcus neoformans.

    PubMed

    Zhao, Qiang; Wei, Dongsheng; Li, Zhongming; Wang, Yu; Zhu, Xiangyang; Zhu, Xudong

    2015-12-01

    The transcriptional expression of laccase, which has been confirmed to contribute to the virulence of Cryptococcus neoformans, is often repressed by a high concentration of glucose in many fungi, including C. neoformans. The underlying mechanism of the repression remains largely unknown. In this study, we found that a GWT1 gene that encodes a glycosylphosphatidylinositol (GPI) anchor biosynthesis-related protein is required for laccase repression by glucose in the basidiomycete C. neoformans. Disruption of GWT1 with the Agrobacterium tumefaciens-mediated T-DNA random insertional mutagenesis (ATMT) method resulted in constitutive expression of the laccase gene LAC1 and constant melanin formation. The loss of GWT1 also dramatically affected the cell membrane integrity and stress resistance. Our results revealed a GPI-dependent glucose repression mechanism in C. neoformans, and it may be helpful for understanding the virulence of C. neoformans.

  13. 22 CFR 226.27 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Financial and Program Management § 226.27 Allowable costs. For each kind... Development Under Grants and Contracts with Hospitals.” The allowability of costs incurred by...

  14. 22 CFR 226.27 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Financial and Program Management § 226.27 Allowable costs. For each kind... Development Under Grants and Contracts with Hospitals.” The allowability of costs incurred by...

  15. 24 CFR 85.22 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Allowable costs. 85.22 Section 85.22 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development... TRIBAL GOVERNMENTS Post-Award Requirements Financial Administration § 85.22 Allowable costs....

  16. 22 CFR 226.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Financial and Program Management § 226.27 Allowable costs. For each kind... Development Under Grants and Contracts with Hospitals.” The allowability of costs incurred by...

  17. 22 CFR 226.27 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Financial and Program Management § 226.27 Allowable costs. For each kind... Development Under Grants and Contracts with Hospitals.” The allowability of costs incurred by...

  18. 24 CFR 85.22 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Allowable costs. 85.22 Section 85.22 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development... TRIBAL GOVERNMENTS Post-Award Requirements Financial Administration § 85.22 Allowable costs....

  19. 24 CFR 85.22 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Allowable costs. 85.22 Section 85.22 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development... TRIBAL GOVERNMENTS Post-Award Requirements Financial Administration § 85.22 Allowable costs....

  20. The role of oxidoreductases in determining the function of the neisserial lipid A phosphoethanolamine transferase required for resistance to polymyxin.

    PubMed

    Piek, Susannah; Wang, Zhirui; Ganguly, Jhuma; Lakey, Adam M; Bartley, Stephanie N; Mowlaboccus, Shakeel; Anandan, Anandhi; Stubbs, Keith A; Scanlon, Martin J; Vrielink, Alice; Azadi, Parastoo; Carlson, Russell W; Kahler, Charlene M

    2014-01-01

    The decoration of the lipid A headgroups of the lipooligosaccharide (LOS) by the LOS phosphoethanolamine (PEA) transferase (LptA) in Neisseria spp. is central for resistance to polymyxin. The structure of the globular domain of LptA shows that the protein has five disulphide bonds, indicating that it is a potential substrate of the protein oxidation pathway in the bacterial periplasm. When neisserial LptA was expressed in Escherichia coli in the presence of the oxidoreductase, EcDsbA, polymyxin resistance increased 30-fold. LptA decorated one position of the E. coli lipid A headgroups with PEA. In the absence of the EcDsbA, LptA was degraded in E. coli. Neisseria spp. express three oxidoreductases, DsbA1, DsbA2 and DsbA3, each of which appear to donate disulphide bonds to different targets. Inactivation of each oxidoreductase in N. meningitidis enhanced sensitivity to polymyxin with combinatorial mutants displaying an additive increase in sensitivity to polymyxin, indicating that the oxidoreductases were required for multiple pathways leading to polymyxin resistance. Correlates were sought between polymyxin sensitivity, LptA stability or activity and the presence of each of the neisserial oxidoreductases. Only meningococcal mutants lacking DsbA3 had a measurable decrease in the amount of PEA decoration on lipid A headgroups implying that LptA stability was supported by the presence of DsbA3 but did not require DsbA1/2 even though these oxidoreductases could oxidise the protein. This is the first indication that DsbA3 acts as an oxidoreductase in vivo and that multiple oxidoreductases may be involved in oxidising the one target in N. meningitidis. In conclusion, LptA is stabilised by disulphide bonds within the protein. This effect was more pronounced when neisserial LptA was expressed in E. coli than in N. meningitidis and may reflect that other factors in the neisserial periplasm have a role in LptA stability.

  1. 28 CFR 66.22 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Allowable costs. 66.22 Section 66.22 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements...

  2. 28 CFR 66.22 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Allowable costs. 66.22 Section 66.22 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements...

  3. 28 CFR 66.22 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Allowable costs. 66.22 Section 66.22 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements...

  4. 28 CFR 66.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Allowable costs. 66.22 Section 66.22 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements...

  5. 32 CFR 34.17 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....16(f). (b) Other types of organizations. Allowability of costs incurred by other types of... ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH FOR-PROFIT ORGANIZATIONS Post-award Requirements... accordance with the cost principles applicable to the type of entity incurring the costs, as follows: (a)...

  6. 40 CFR 35.2025 - Allowance and advance of allowance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... facilities planning and design of the project and Step 7 agreements will include an allowance for facility planning in accordance with appendix B of this subpart. (b) Advance of allowance to potential grant... grant applicants for facilities planning and project design. (2) The State may request that the right...

  7. Bacterial subversion of cAMP signalling inhibits cathelicidin expression, which is required for innate resistance to Mycobacterium tuberculosis.

    PubMed

    Gupta, Shashank; Winglee, Kathryn; Gallo, Richard; Bishai, William R

    2017-01-18

    Antimicrobial peptides such as cathelicidins are important components of innate immune defence against inhaled microorganisms, and have shown antimicrobial activity against Mycobacterium tuberculosis in in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide gene (Cramp), the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulation of protective immunity during M. tuberculosis infection in vivo. We used Cramp(-/-) mice in a validated model of pulmonary tuberculosis, and conducted cell-based assays with macrophages from these mice. We evaluated the in vivo susceptibility of Cramp(-/-) mice to infection, and also dissected various pro-inflammatory immune responses against M. tuberculosis. We observed increased susceptibility of Cramp(-/-) mice to M. tuberculosis as compared with wild-type mice. Macrophages from Cramp(-/-) mice were unable to control M. tuberculosis growth in an in vitro infection model, were deficient in intracellular calcium influx, and were defective in stimulating T cells. Additionally, CD4(+) and CD8(+) T cells from Cramp(-/-) mice produced less interferon-β upon stimulation. Furthermore, bacterial-derived cAMP modulated cathelicidin expression in macrophages. Our results demonstrate that cathelicidin is required for innate resistance to M. tuberculosis in a relevant animal model and is a key mediator in regulation of the levels of pro-inflammatory cytokines by calcium and cyclic nucleotides. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. High-level fluoroquinolone resistance in Streptococcus pneumoniae requires mutations in parC and gyrA.

    PubMed Central

    Janoir, C; Zeller, V; Kitzis, M D; Moreau, N J; Gutmann, L

    1996-01-01

    The mechanism of high-level fluoroquinolone resistance was studied in strains of Streptococcus pneumoniae, either selected in vitro or isolated from clinical samples. By using DNA from these high-level-resistant strains, low-level-resistant transformants (MIC of pefloxacin, > or = 32 micrograms/ml; MIC of ciprofloxacin, 4 micrograms/ml; MIC of sparfloxacin, 0.50 micrograms/ml) were obtained at high frequencies (ca.10(-2)), while high-level-resistant transformants (MIC of pefloxacin, > or = 64 micrograms/ml; MIC of ciprofloxacin, 16 to 64 micrograms/ml; MIC of sparfloxacin, > or = 8 micrograms/ml) were obtained only at low frequencies (ca.10(-4)). This suggested that mutations in at least two unlinked genes were necessary to obtain high-level resistance. Low-level resistance was associated with ParC mutations (change from Ser to Tyr at position 79 [Ser79Tyr], Ser79Phe, or Asp83Gly). ParC mutations were associated, in high-level-resistant strains and transformants, with alterations in the quinolone resistance-determining region of GyrA (Ser84Tyr, Ser84Phe, and/or Glu88Lys). Low-level resistance was shown to be necessary for expression of the gyrA mutations. No mutation in the region corresponding to the quinolone resistance-determining region of GyrB and no alteration of drug accumulation were found. PMID:9124836

  9. A PmrB-Regulated Deacetylase Required for Lipid A Modification and Polymyxin Resistance in Acinetobacter baumannii.

    PubMed

    Chin, Chui-Yoke; Gregg, Kelsey A; Napier, Brooke A; Ernst, Robert K; Weiss, David S

    2015-12-01

    Emerging resistance to "last-resort" polymyxin antibiotics in Gram-negative bacteria is a significant threat to public health. We identified the Acinetobacter baumannii NaxD deacetylase as a critical mediator of lipid A modification resulting in polymyxin resistance and demonstrated that naxD is regulated by the sensor kinase PmrB. This represents the first description of a specific PmrB-regulated gene contributing to polymyxin resistance in A. baumannii and highlights NaxD as a putative drug target to reverse polymyxin resistance.

  10. A PmrB-Regulated Deacetylase Required for Lipid A Modification and Polymyxin Resistance in Acinetobacter baumannii

    PubMed Central

    Chin, Chui-Yoke; Gregg, Kelsey A.; Napier, Brooke A.; Ernst, Robert K.

    2015-01-01

    Emerging resistance to “last-resort” polymyxin antibiotics in Gram-negative bacteria is a significant threat to public health. We identified the Acinetobacter baumannii NaxD deacetylase as a critical mediator of lipid A modification resulting in polymyxin resistance and demonstrated that naxD is regulated by the sensor kinase PmrB. This represents the first description of a specific PmrB-regulated gene contributing to polymyxin resistance in A. baumannii and highlights NaxD as a putative drug target to reverse polymyxin resistance. PMID:26459891

  11. Long-term strength and allowable stresses of grade 10Kh9MFB and X10CrMoVNb9-1 (T91/P91) chromium heat-resistant steels

    NASA Astrophysics Data System (ADS)

    Skorobogatykh, V. N.; Danyushevskiy, I. A.; Schenkova, I. A.; Prudnikov, D. A.

    2015-04-01

    Currently, grade X10CrMoVNb9-1 (T91, P91) and 10Kh9MFB (10Kh9MFB-Sh) chromium steels are widely applied in equipment manufacturing for thermal power plants in Russia and abroad. Compilation and comparison of tensile, impact, and long-term strength tests results accumulated for many years of investigations of foreign grade X10CrMoVNb9-1, T91, P91, and domestic grade 10Kh9MFB (10Kh9MFB-Sh) steels is carried out. The property identity of metals investigated is established. High strength and plastic properties of steels, from which pipes and other products are made, for operation under creep conditions are confirmed. Design characteristics of long-term strength on the basis of tests with more than one million of hour-samples are determined ( and at temperatures of 500-650°C). The table of recommended allowable stresses for grade 10Kh9MFB, 10Kh9MFB-SH, X10CrMoVNb9-1, T91, and P91 steels is developed. The long-time properties of pipe welded joints of grade 10Kh9MFB+10Kh9MFB, 10Kh9MFB-Sh+10Kh9MFB-Sh, X10CrMoVNb9-1+X10CrMoVNb9-1, P91+P91, T91+T91, 10Kh9MFB (10Kh9MFB-Sh)+X10CrMoVNb9-1(T/P91) steels is researched. The welded joint reduction factor is experimentally determined.

  12. Structural features of piperazinyl-linked ciprofloxacin dimers required for activity against drug-resistant strains of Staphylococcus aureus.

    PubMed

    Kerns, Robert J; Rybak, Michael J; Kaatz, Glenn W; Vaka, Flamur; Cha, Raymond; Grucz, Richard G; Diwadkar, Veena U

    2003-07-07

    We previously demonstrated that piperazinyl-linked fluoroquinolone dimers possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus. In this study, we report the preparation and evaluation of a series of incomplete dimers toward ascertaining structural features of piperazinyl-linked ciprofloxacin dimers that render these agents refractory to fluoroquinolone-resistance mechanisms in Staphylococcus aureus.

  13. 38 CFR 49.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER...-Profit Organizations.” The allowability of costs incurred by institutions of higher education is... of Appendix E of 45 CFR part 74, “Principles for Determining Costs Applicable to Research...

  14. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER...-Profit Organizations.” The allowability of costs incurred by institutions of higher education is..., however, pay consultants more than this amount.) This limitation applies to consultation services...

  15. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... the applicable cost principles. For the costs of a— Use the principles in— State, local or...

  16. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... the applicable cost principles. For the costs of a— Use the principles in— State, local or...

  17. 34 CFR 74.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial...— Private nonprofit organization other than (1) An institution of higher education; (2) a hospital; or (3... 34 Education 1 2010-07-01 2010-07-01 false Allowable costs. 74.27 Section 74.27 Education...

  18. 34 CFR 74.27 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial...— Private nonprofit organization other than (1) An institution of higher education; (2) a hospital; or (3... 34 Education 1 2012-07-01 2012-07-01 false Allowable costs. 74.27 Section 74.27 Education...

  19. 24 CFR 84.27 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Allowable costs. 84.27 Section 84.27 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management §...

  20. 24 CFR 84.27 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Allowable costs. 84.27 Section 84.27 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management §...

  1. 24 CFR 84.27 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Allowable costs. 84.27 Section 84.27 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management §...

  2. 45 CFR 1180.56 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS General Conditions Which Must Be Met... OMB circulars. (b) No costs shall be allowed for the purchase of any object to be included in the collection of a museum, except library, literary, or archival material specifically required for a...

  3. 45 CFR 1180.56 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS General Conditions Which Must Be Met... OMB circulars. (b) No costs shall be allowed for the purchase of any object to be included in the collection of a museum, except library, literary, or archival material specifically required for a...

  4. 45 CFR 1180.56 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS General Conditions Which Must Be Met... OMB circulars. (b) No costs shall be allowed for the purchase of any object to be included in the collection of a museum, except library, literary, or archival material specifically required for a...

  5. 45 CFR 1180.56 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS General Conditions Which Must Be Met... OMB circulars. (b) No costs shall be allowed for the purchase of any object to be included in the collection of a museum, except library, literary, or archival material specifically required for a...

  6. 50 CFR 80.15 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.15 Allowable costs. (a) What are... designed to include purposes other than those eligible under either the Dingell-Johnson Sport...

  7. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Allowable costs. 30.27 Section 30.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND...

  8. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Allowable costs. 30.27 Section 30.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND...

  9. 32 CFR 32.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 32.27 Allowable... subrecipients or contractors under awards subject to this part is determined in accordance with the provisions... awards, is determined in accordance with the provisions of OMB Circular A-122, “Cost Principles for...

  10. AIB1 is required for the acquisition of epithelial growth factor receptor-mediated tamoxifen resistance in breast cancer cells

    SciTech Connect

    Zhao Wenhui; Zhang Qingyuan Kang Xinmei; Jin Shi; Lou Changjie

    2009-03-13

    Acquired resistance to tamoxifen has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this condition has not been completely elucidated. In this study, a tamoxifen-resistant (Tam-R) MCF-7 breast cancer cell line was developed to mimic the occurrence of acquired tamoxifen resistance as seen in clinical practice. Increased expression levels of HER1, HER2 and the estrogen receptor (ER)-AIB1 complex were found in tamoxifen-resistant cells. EGF stimulation and gefitinib inhibition experiments further demonstrated that HER1/HER2 signaling and AIB1 were involved in the proliferation of cells that had acquired Tam resistance. However, when AIB1 was silenced with AIB1-siRNA in Tam-R cells, the cell growth stimulated by the HER1/HER2 signaling pathway was significantly reduced, and the cells were again found to be inhibited by tamoxifen. These results suggest that the AIB1 protein could be a limiting factor in the HER1/HER2-mediated hormone-independent growth of Tam-R cells. Thus, AIB1 may be a new therapeutic target, and the removal of AIB1 may decrease the crosstalk between ER and the HER1/HER2 pathway, resulting in the restoration of tamoxifen sensitivity in tamoxifen-resistant cells.

  11. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance

    PubMed Central

    Bonapace, Laura; Bornhauser, Beat C.; Schmitz, Maike; Cario, Gunnar; Ziegler, Urs; Niggli, Felix K.; Schäfer, Beat W.; Schrappe, Martin; Stanulla, Martin; Bourquin, Jean-Pierre

    2010-01-01

    In vivo resistance to first-line chemotherapy, including to glucocorticoids, is a strong predictor of poor outcome in children with acute lymphoblastic leukemia (ALL). Modulation of cell death regulators represents an attractive strategy for subverting such drug resistance. Here we report complete resensitization of multidrug-resistant childhood ALL cells to glucocorticoids and other cytotoxic agents with subcytotoxic concentrations of obatoclax, a putative antagonist of BCL-2 family members. The reversal of glucocorticoid resistance occurred through rapid activation of autophagy-dependent necroptosis, which bypassed the block in mitochondrial apoptosis. This effect was associated with dissociation of the autophagy inducer beclin-1 from the antiapoptotic BCL-2 family member myeloid cell leukemia sequence 1 (MCL-1) and with a marked decrease in mammalian target of rapamycin (mTOR) activity. Consistent with a protective role for mTOR in glucocorticoid resistance in childhood ALL, combination of rapamycin with the glucocorticoid dexamethasone triggered autophagy-dependent cell death, with characteristic features of necroptosis. Execution of cell death, but not induction of autophagy, was strictly dependent on expression of receptor-interacting protein (RIP-1) kinase and cylindromatosis (turban tumor syndrome) (CYLD), two key regulators of necroptosis. Accordingly, both inhibition of RIP-1 and interference with CYLD restored glucocorticoid resistance completely. Together with evidence for a chemosensitizing activity of obatoclax in vivo, our data provide a compelling rationale for clinical translation of this pharmacological approach into treatments for patients with refractory ALL. PMID:20200450

  12. Riboflavin-Induced Disease Resistance Requires the Mitogen-Activated Protein Kinases 3 and 6 in Arabidopsis thaliana

    PubMed Central

    Nie, Shengjun; Xu, Huilian

    2016-01-01

    As a resistance elicitor, riboflavin (vitamin B2) protects plants against a wide range of pathogens. At molecular biological levels, it is important to elucidate the signaling pathways underlying the disease resistance induced by riboflavin. Here, riboflavin was tested to induce resistance against virulent Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000) in Arabidopsis. Results showed that riboflavin induced disease resistance based on MAPK-dependent priming for the expression of PR1 gene. Riboflavin induced transient expression of PR1 gene. However, following Pst DC3000 inoculation, riboflavin potentiated stronger PR1 gene transcription. Further was suggested that the transcript levels of mitogen-activated protein kinases, MPK3 and MPK6, were primed under riboflavin. Upon infection by Pst DC3000, these two enzymes were more strongly activated. The elevated activation of both MPK3 and MPK6 was responsible for enhanced defense gene expression and resistance after riboflavin treatment. Moreover, riboflavin significantly reduced the transcript levels of MPK3 and MPK6 by application of AsA and BAPTA, an H2O2 scavenger and a calcium (Ca2+) scavenger, respectively. In conclusion, MPK3 and MPK6 were responsible for riboflavin-induced resistance, and played an important role in H2O2- and Ca2+-related signaling pathways, and this study could provide a new insight into the mechanistic study of riboflavin-induced defense responses. PMID:27054585

  13. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila.

    PubMed

    Ghimire, Saurav; Kim, Man Su

    2015-01-01

    Dietary restriction (DR) is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS) that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  14. The Arabidopsis Elongator complex is required for nonhost resistance against the bacterial pathogens Xanthomonas citri subsp. citri and Pseudomonas syringae pv. phaseolicola NPS3121.

    PubMed

    An, Chuanfu; Wang, Chenggang; Mou, Zhonglin

    2017-01-30

    Although in recent years nonhost resistance has attracted considerable attention for its broad spectrum and durability, the genetic and mechanistic components of nonhost resistance have not been fully understood. We used molecular and histochemical approaches including quantitative PCR, chromatin immunoprecipitation, and 3,3'-diaminobenzidine and aniline blue staining. The evolutionarily conserved histone acetyltransferase complex Elongator was identified as a major component of nonhost resistance against Xanthomonas citri subsp. citri (Xcc) and Pseudomonas syringae pv. phaseolicola (Psp) NPS3121. Mutations in Elongator genes inhibit Xcc-, Psp NPS3121- and/or flg22-induced defense responses including defense gene expression, callose deposition, and reactive oxygen species (ROS) and salicylic acid (SA) accumulation. Mutations in Elongator also attenuate the ROS-SA amplification loop. We show that suppressed ROS and SA accumulation in Elongator mutants is correlated with reduced expression of the Arabidopsis respiratory burst oxidase homologue AtrbohD and the SA biosynthesis gene ISOCHORISMATE SYNTHASE1 (ICS1). Furthermore, we found that the Elongator subunit ELP2 is associated with the chromatin of AtrbohD and ICS1 and is required for maintaining basal histone H3 acetylation levels in these key defense genes. As both AtrbohD and ICS1 contribute to nonhost resistance against Xcc, our results reveal an epigenetic mechanism by which Elongator regulates nonhost resistance in Arabidopsis.

  15. Infectious Bronchitis Coronavirus Inhibits STAT1 Signaling and Requires Accessory Proteins for Resistance to Type I Interferon Activity

    PubMed Central

    Kint, Joeri; Dickhout, Annemiek; Kutter, Jasmin; Maier, Helena J.; Britton, Paul; Koumans, Joseph; Pijlman, Gorben P.; Fros, Jelke J.; Wiegertjes, Geert F.

    2015-01-01

    ABSTRACT The innate immune response is the first line of defense against viruses, and type I interferon (IFN) is a critical component of this response. Similar to other viruses, the gammacoronavirus infectious bronchitis virus (IBV) has evolved under evolutionary pressure to evade and counteract the IFN response to enable its survival. Previously, we reported that IBV induces a delayed activation of the IFN response. In the present work, we describe the resistance of IBV to IFN and the potential role of accessory proteins herein. We show that IBV is fairly resistant to the antiviral state induced by IFN and identify that viral accessory protein 3a is involved in resistance to IFN, as its absence renders IBV less resistant to IFN treatment. In addition to this, we found that independently of its accessory proteins, IBV inhibits IFN-mediated phosphorylation and translocation of STAT1. In summary, we show that IBV uses multiple strategies to counteract the IFN response. IMPORTANCE In the present study, we show that infectious bronchitis virus (IBV) is resistant to IFN treatment and identify a role for accessory protein 3a in the resistance against the type I IFN response. We also demonstrate that, in a time-dependent manner, IBV effectively interferes with IFN signaling and that its accessory proteins are dispensable for this activity. This study demonstrates that the gammacoronavirus IBV, similar to its mammalian counterparts, has evolved multiple strategies to efficiently counteract the IFN response of its avian host, and it identifies accessory protein 3a as multifaceted antagonist of the avian IFN system. PMID:26401035

  16. Allowance trading: Market operations and regulatory response

    SciTech Connect

    Bailey, K.A.; South, D.W.; McDermott, K.A.

    1992-12-31

    The use of the SO{sub 2} allowance system as defined by Title IV of the 1990 Clean Air Act Amendments offers utilities greater compliance flexibility than EPA technology standards, State Implementation Plan (SEP) performance standards, or EPA bubble/offset strategies. Traditional methods at best offered the utility the ability to trade emissions between different units at a particular plant. The SO{sub 2} emissions trading system advocated under Title IV will allow a utility to trade emissions across its utility system, and/or trade emissions between utilities to take advantage of interfirm control cost differences. The use of transferable emission allowances offers utilities greater flexibility in the choice of how to control emissions: the choices include fuel switching, flue gas scrubbing, environmental dispatch, repowering, and even the choice not to control emissions [as long as the New Source Performance Standards (NSPS) and Prevention of Significant Deterioration (PSD) requirements are met]. The added flexibility allows utilities to choose the least cost manner of compliance with Title IV requirements. It is hoped (intended) that pollution control cost-minimization by individual utilities will in turn reduce the cost of controlling SO{sub 2} for the electric utility industry in aggregate. In addition, through the use of NO{sub x} emission averaging, the utility would average NO{sub x} emissions from different point sources in order to comply with the prescribed emission standard.

  17. Allowance trading: Market operations and regulatory response

    SciTech Connect

    Bailey, K.A.; South, D.W.; McDermott, K.A.

    1992-01-01

    The use of the SO[sub 2] allowance system as defined by Title IV of the 1990 Clean Air Act Amendments offers utilities greater compliance flexibility than EPA technology standards, State Implementation Plan (SEP) performance standards, or EPA bubble/offset strategies. Traditional methods at best offered the utility the ability to trade emissions between different units at a particular plant. The SO[sub 2] emissions trading system advocated under Title IV will allow a utility to trade emissions across its utility system, and/or trade emissions between utilities to take advantage of interfirm control cost differences. The use of transferable emission allowances offers utilities greater flexibility in the choice of how to control emissions: the choices include fuel switching, flue gas scrubbing, environmental dispatch, repowering, and even the choice not to control emissions [as long as the New Source Performance Standards (NSPS) and Prevention of Significant Deterioration (PSD) requirements are met]. The added flexibility allows utilities to choose the least cost manner of compliance with Title IV requirements. It is hoped (intended) that pollution control cost-minimization by individual utilities will in turn reduce the cost of controlling SO[sub 2] for the electric utility industry in aggregate. In addition, through the use of NO[sub x] emission averaging, the utility would average NO[sub x] emissions from different point sources in order to comply with the prescribed emission standard.

  18. The WRKY45-2 WRKY13 WRKY42 transcriptional regulatory cascade is required for rice resistance to fungal pathogen.

    PubMed

    Cheng, Hongtao; Liu, Hongbo; Deng, Yong; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2015-03-01

    Blast caused by fungal Magnaporthe oryzae is a devastating disease of rice (Oryza sativa) worldwide, and this fungus also infects barley (Hordeum vulgare). At least 11 rice WRKY transcription factors have been reported to regulate rice response to M. oryzae either positively or negatively. However, the relationships of these WRKYs in the rice defense signaling pathway against M. oryzae are unknown. Previous studies have revealed that rice WRKY13 (as a transcriptional repressor) and WRKY45-2 enhance resistance to M. oryzae. Here, we show that rice WRKY42, functioning as a transcriptional repressor, suppresses resistance to M. oryzae. WRKY42-RNA interference (RNAi) and WRKY42-overexpressing (oe) plants showed increased resistance and susceptibility to M. oryzae, accompanied by increased or reduced jasmonic acid (JA) content, respectively, compared with wild-type plants. JA pretreatment enhanced the resistance of WRKY42-oe plants to M. oryzae. WRKY13 directly suppressed WRKY42. WRKY45-2, functioning as a transcriptional activator, directly activated WRKY13. In addition, WRKY13 directly suppressed WRKY45-2 by feedback regulation. The WRKY13-RNAi WRKY45-2-oe and WRKY13-oe WRKY42-oe double transgenic lines showed increased susceptibility to M. oryzae compared with WRKY45-2-oe and WRKY13-oe plants, respectively. These results suggest that the three WRKYs form a sequential transcriptional regulatory cascade. WRKY42 may negatively regulate rice response to M. oryzae by suppressing JA signaling-related genes, and WRKY45-2 transcriptionally activates WRKY13, whose encoding protein in turn transcriptionally suppresses WRKY42 to regulate rice resistance to M. oryzae.

  19. Nicotiana benthamiana calreticulin 3a is required for the ethylene-mediated production of phytoalexins and disease resistance against oomycete pathogen Phytophthora infestans.

    PubMed

    Matsukawa, Mizuki; Shibata, Yusuke; Ohtsu, Mina; Mizutani, Aki; Mori, Hitoshi; Wang, Ping; Ojika, Makoto; Kawakita, Kazuhito; Takemoto, Daigo

    2013-08-01

    Mature Nicotiana benthamiana shows strong resistance to the potato late blight pathogen Phytophthora infestans. By screening using virus-induced random gene silencing, we isolated a gene for plant-specific calreticulin NbCRT3a as a required gene for resistance of N. benthamiana against P. infestans. NbCRT3a encodes an endoplasmic reticulum quality-control (ERQC) chaperone for the maturation of glycoproteins, including glycosylated cell-surface receptors. NbCRT3a-silenced plants showed no detectable growth defects but resistance to P. infestans was significantly compromised. Defense responses induced by the treatment with INF1 (a secretory protein of P. infestans), such as production of reactive oxygen species and accumulation of phytoalexins, were suppressed in NbCRT3a-silenced N. benthamiana. Expression of an ethylene-regulated gene for phytoalexin biosynthesis, NbEAS, was reduced in NbCRT3a-silenced plants, whereas the expression of salicylic acid-regulated NbPR-1a was not affected. Consistently, induction of ethylene production by INF1 was suppressed in NbCRT3a-silenced plants. Resistance reactions induced by a hyphal wall components elicitor prepared from P. infestans were also impaired in NbCRT3a-silenced plants. However, cell death induced by active mitogen-activated protein kinase kinase (NbMEK2(DD)) was not affected by the silencing of NbCRT3a. Thus, NbCRT3a is required for the initiation of resistance reactions of N. benthamiana in response to elicitor molecules derived from P. infestans.

  20. Nonproductive Factor Allowance. (Pilot Study).

    DTIC Science & Technology

    1980-03-31

    a separate factor for each size of facility, i.e., MEDCEN, Large MEDDAC, and Small MEDDAC. f. In a GAO audit report, "Development and Use of Military...measurement in determining and Justifying staffing requirements. g. Another GAO audit report, "Uniform Accounting and Workload Measurement Systems Needed for...Effective Writing, AFIT, Survival, TDY, Technical Training, IDEA High School, CDC and Survey Taking. Also taking tests such as PFE , SKT, AF Sup Exam, CLEP

  1. The major outer membrane protein OmpU of Vibrio splendidus contributes to host antimicrobial peptide resistance and is required for virulence in the oyster Crassostrea gigas.

    PubMed

    Duperthuy, Marylise; Binesse, Johan; Le Roux, Frédérique; Romestand, Bernard; Caro, Audrey; Got, Patrice; Givaudan, Alain; Mazel, Didier; Bachère, Evelyne; Destoumieux-Garzón, Delphine

    2010-04-01

    Vibrio splendidus, strain LGP32, is an oyster pathogen associated with the summer mortalities affecting the production of Crassostrea gigas oysters worldwide. Vibrio splendidus LGP32 was shown to resist to up to 10 microM Cg-Def defensin and Cg-BPI bactericidal permeability increasing protein, two antimicrobial peptides/proteins (AMPs) involved in C. gigas immunity. The resistance to both oyster Cg-Def and Cg-BPI and standard AMPs (polymyxin B, protegrin, human BPI) was dependent on the ompU gene. Indeed, upon ompU inactivation, minimal bactericidal concentrations decreased by up to fourfold. AMP resistance was restored upon ectopic expression of ompU. The susceptibility of bacterial membranes to AMP-induced damages was independent of the ompU-mediated AMP resistance. Besides its role in AMP resistance, ompU proved to be essential for the adherence of V. splendidus LGP32 to fibronectin. Interestingly, in vivo, ompU was identified as a major determinant of V. splendidus pathogenicity in oyster experimental infections. Indeed, the V. splendidus-induced oyster mortalities dropped from 56% to 11% upon ompU mutation (Kaplan-Meier survival curves, P < 0.01). Moreover, in co-infection assays, the ompU mutant was out competed by the wild-type strain with competitive indexes in the range of 0.1-0.2. From this study, ompU is required for virulence of V. splendidus. Contributing to AMP resistance, conferring adhesive properties to V. splendidus, and being essential for in vivo fitness, the OmpU porin appears as an essential effector of the C. gigas/V. splendidus interaction.

  2. Identification of an amino acid residue required for differential recognition of a viral movement protein by the Tomato mosaic virus resistance gene Tm-2(2).

    PubMed

    Kobayashi, Michie; Yamamoto-Katou, Ayako; Katou, Shinpei; Hirai, Katsuyuki; Meshi, Tetsuo; Ohashi, Yuko; Mitsuhara, Ichiro

    2011-07-01

    The Tm-2 gene of tomato and its allelic gene, Tm-2(2), confer resistance to Tomato mosaic virus (ToMV) and encode a member of the coiled-coil/nucleotide binding-ARC/leucine-rich repeat (LRR) protein class of plant resistance (R) genes. Despite exhibiting only four amino acid differences between the products of Tm-2 and Tm-2(2), Tm-2(2) confers resistance to ToMV mutant B7, whereas Tm-2 is broken by ToMV-B7. An Agrobacterium-mediated transient expression system was used to study the mechanism of differential recognition of the movement proteins (MPs), an avirulence factor for ToMV resistance, of ToMV-B7 by Tm-2 and Tm-2(2). Although resistance induced by Tm-2 and Tm-2(2) is not usually accompanied by hypersensitive response (HR), Tm-2 and Tm-2(2) induced HR-like cell death by co-expression with MP of a wild-type ToMV, a strain that causes resistance for these R genes, and Tm-2(2) but not Tm-2 induced cell death with B7-MP in this system. Site-directed amino acid mutagenesis revealed that Tyr-767 in the LRR of Tm-2(2) is required for the specific recognition of the B7-MP. These results suggest that the Tyr residue in LRR contributes to the recognition of B7-MP, and that Tm-2 and Tm-2(2) are involved in HR cell death.

  3. CFP, the putative cercosporin transporter of Cercospora kikuchii, is required for wild type cercosporin production, resistance, and virulence on soybean.

    PubMed

    Callahan, T M; Rose, M S; Meade, M J; Ehrenshaft, M; Upchurch, R G

    1999-10-01

    Many species of the fungal genus Cercospora, including the soybean pathogen C. kikuchii, produce the phytotoxic polyketide cercosporin. Cercosporin production is induced by light. Previously, we identified several cDNA clones of mRNA transcripts that exhibited light-enhanced accumulation in C. kikuchii. Targeted disruption of the genomic copy of one of these, now designated CFP (cercosporin facilitator protein), results in a drastic reduction in cercosporin production, greatly reduced virulence of the fungus to soybean, and increased sensitivity to exogenous cercosporin. Sequence analysis of CFP reveals an 1,821-bp open reading frame encoding a 65.4-kDa protein similar to several members of the major facilitator superfamily (MFS) of integral membrane transporter proteins known to confer resistance to various antibiotics and toxins in fungi and bacteria. We propose that CFP encodes a cercosporin transporter that contributes resistance to cercosporin by actively exporting cercosporin, thus maintaining low cellular concentrations of the toxin.

  4. Characterization of a mitogen-activated protein kinase gene from cucumber required for trichoderma-conferred plant resistance.

    PubMed

    Shoresh, Michal; Gal-On, Amit; Leibman, Diana; Chet, Ilan

    2006-11-01

    The fungal biocontrol agent Trichoderma asperellum has been recently shown to induce systemic resistance in plants through a mechanism that employs jasmonic acid and ethylene signal transduction pathways. Mitogen-activated protein kinase (MAPK) proteins have been implicated in the signal transduction of a wide variety of plant stress responses. Here we report the identification and characterization of a Trichoderma-induced MAPK (TIPK) gene function in cucumber (Cucumis sativus). Similar to its homologs, wound-induced protein kinase, MPK3, and MPK3a, TIPK is also induced by wounding. Normally, preinoculation of roots with Trichoderma activates plant defense mechanisms, which result in resistance to the leaf pathogen Pseudomonas syringae pv lachrymans. We used a unique attenuated virus vector, Zucchini yellow mosaic virus (ZYMV-AGII), to overexpress TIPK protein and antisense (AS) RNA. Plants overexpressing TIPK were more resistant to pathogenic bacterial attack than control plants, even in the absence of Trichoderma preinoculation. On the other hand, plants expressing TIPK-AS revealed increased sensitivity to pathogen attack. Moreover, Trichoderma preinoculation could not protect these AS plants against subsequent pathogen attack. We therefore demonstrate that Trichoderma exerts its protective effect on plants through activation of the TIPK gene, a MAPK that is involved in signal transduction pathways of defense responses.

  5. Interpretative Ruling: Allowable Emissions Baseline

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  6. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice.

    PubMed

    Holland, William L; Bikman, Benjamin T; Wang, Li-Ping; Yuguang, Guan; Sargent, Katherine M; Bulchand, Sarada; Knotts, Trina A; Shui, Guanghou; Clegg, Deborah J; Wenk, Markus R; Pagliassotti, Michael J; Scherer, Philipp E; Summers, Scott A

    2011-05-01

    Obesity is associated with an enhanced inflammatory response that exacerbates insulin resistance and contributes to diabetes, atherosclerosis, and cardiovascular disease. One mechanism accounting for the increased inflammation associated with obesity is activation of the innate immune signaling pathway triggered by TLR4 recognition of saturated fatty acids, an event that is essential for lipid-induced insulin resistance. Using in vitro and in vivo systems to model lipid induction of TLR4-dependent inflammatory events in rodents, we show here that TLR4 is an upstream signaling component required for saturated fatty acid-induced ceramide biosynthesis. This increase in ceramide production was associated with the upregulation of genes driving ceramide biosynthesis, an event dependent of the activity of the proinflammatory kinase IKKβ. Importantly, increased ceramide production was not required for TLR4-dependent induction of inflammatory cytokines, but it was essential for TLR4-dependent insulin resistance. These findings suggest that sphingolipids such as ceramide might be key components of the signaling networks that link lipid-induced inflammatory pathways to the antagonism of insulin action that contributes to diabetes.

  7. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid–induced ceramide biosynthesis in mice

    PubMed Central

    Holland, William L.; Bikman, Benjamin T.; Wang, Li-Ping; Yuguang, Guan; Sargent, Katherine M.; Bulchand, Sarada; Knotts, Trina A.; Shui, Guanghou; Clegg, Deborah J.; Wenk, Markus R.; Pagliassotti, Michael J.; Scherer, Philipp E.; Summers, Scott A.

    2011-01-01

    Obesity is associated with an enhanced inflammatory response that exacerbates insulin resistance and contributes to diabetes, atherosclerosis, and cardiovascular disease. One mechanism accounting for the increased inflammation associated with obesity is activation of the innate immune signaling pathway triggered by TLR4 recognition of saturated fatty acids, an event that is essential for lipid-induced insulin resistance. Using in vitro and in vivo systems to model lipid induction of TLR4-dependent inflammatory events in rodents, we show here that TLR4 is an upstream signaling component required for saturated fatty acid–induced ceramide biosynthesis. This increase in ceramide production was associated with the upregulation of genes driving ceramide biosynthesis, an event dependent of the activity of the proinflammatory kinase IKKβ. Importantly, increased ceramide production was not required for TLR4-dependent induction of inflammatory cytokines, but it was essential for TLR4-dependent insulin resistance. These findings suggest that sphingolipids such as ceramide might be key components of the signaling networks that link lipid-induced inflammatory pathways to the antagonism of insulin action that contributes to diabetes. PMID:21490391

  8. Vietnam recommended dietary allowances 2007.

    PubMed

    Khan, Nguyen Cong; Hoan, Pham Van

    2008-01-01

    It has been well acknowledged that Vietnam is undergoing a nutrition transition. With a rapid change in the country's reform and economic growth, food supply at the macronutrient level has improved. Changes of the Vietnamese diet include significantly more foods of animal origin, and an increase of fat/oils, and ripe fruits. Consequently, nutritional problems in Vietnam now include not only malnutrition but also overweight/obesity, metabolic syndrome and other chronic diseases related to nutrition and lifestyles. The recognition of these shifts, which is also associated with morbidity and mortality, was a major factor in the need to review and update the Recommended Dietary Allowances (RDA) for the Vietnamese population. This revised RDA established an important science-based tool for evaluation of nutrition adequacy, for teaching, and for scientific communications within Vietnam. It is expected that the 2007 Vietnam RDA and its conversion to food-based dietary guidelines will facilitate education to the public, as well as the policy implementation of programs for prevention of non-communicable chronic diseases and addressing the double burden of both under and over nutrition.

  9. The outer membrane protein TolC is required for phytoalexin resistance and virulence of the fire blight pathogen Erwinia amylovora.

    PubMed

    Al-Karablieh, Nehaya; Weingart, Helge; Ullrich, Matthias S

    2009-07-01

    Erwinia amylovora causes fire blight on several plant species such as apple and pear, which produce diverse phytoalexins as defence mechanisms. An evolutionary successful pathogen thus must develop resistance mechanisms towards these toxic compounds. The E. amylovora outer membrane protein, TolC, might mediate phytoalexin resistance through its interaction with the multidrug efflux pump, AcrAB. To prove this, a tolC mutant and an acrB/tolC double mutant were constructed. The minimal inhibitory concentrations of diverse antimicrobials and phytoalexins were determined for these mutants and compared with that of a previously generated acrB mutant. The tolC and arcB/tolC mutants were considerably more susceptible than the wild type but showed similar levels as the acrB mutant. The results clearly indicated that neither TolC nor AcrAB significantly interacted with other transport systems during the efflux of the tested toxic compounds. Survival and virulence assays on inoculated apple plants showed that pathogenicity and the ability of E. amylovora to colonize plant tissue were equally impaired by mutations of tolC and acrB/tolC. Our results allowed the conclusion that TolC plays an important role as a virulence and fitness factor of E. amylovora by mediating resistance towards phytoalexins through its exclusive interaction with AcrAB.

  10. Pithy protection: Nicotiana attenuata's jasmonic acid-mediated defenses are required to resist stem-boring weevil larvae.

    PubMed

    Diezel, Celia; Kessler, Danny; Baldwin, Ian T

    2011-04-01

    Folivory is the best studied plant-herbivore interaction, but it is unclear whether the signaling and resistance traits important for the defense of leaves are also important for other plant parts. Larvae of the tobacco stem weevil, Trichobaris mucorea, burrow into stems of Nicotiana attenuata and feed on the pith. Transgenic N. attenuata lines silenced in signaling and foliar defense traits were evaluated in a 2-year field study for resistance against attack by naturally occurring T. mucorea larva. Plants silenced in early jasmonic acid (JA) biosynthesis (antisense [as]-lipoxygenase3 [lox3]; inverted repeat [ir]-allene oxide cyclase), JA perception (as-coronatine insensitive1), proteinase inhibitors (ir-pi), and nicotine (ir-putrescine methyl-transferase) direct defenses and lignin (ir-cad) biosynthesis were infested more frequently than wild-type plants. Plants unable to emit C(6) aldehydes (as-hpl) had lower infestation rates, while plants silenced in late steps in JA biosynthesis (ir-acyl-coenzyme A oxidase, ir-opr) and silenced in diterpene glycoside production (ir-geranylgeranyl pyrophosphate synthase) did not differ from wild type. Pith choice assays revealed that ir-putrescine methyl-transferase, ir-coronatine insensitive1, and ir-lox3 pith, which all had diminished nicotine levels, were preferred by larvae compared to wild-type pith. The lack of preference for ir-lox2 and ir-cad piths, suggest that oviposition attraction and vascular defense, rather than pith palatability accounts for the higher attack rates observed for these plants. We conclude that traits that influence a plant's apparency, stem hardness, and pith direct defenses all contribute to resistance against this herbivore whose attack can be devastating to N. attenuata's fitness.

  11. The S2 Cu(i) site in CupA from Streptococcus pneumoniae is required for cellular copper resistance.

    PubMed

    Fu, Yue; Bruce, Kevin E; Wu, Hongwei; Giedroc, David P

    2016-01-01

    Pathogenic bacteria have evolved copper homeostasis and resistance systems for fighting copper toxicity imposed by the human immune system. Streptococcus pneumoniae is a respiratory pathogen that encodes an obligatorily membrane-anchored Cu(i) binding protein, CupA, and a P1B-type ATPase efflux transporter, CopA. The soluble, cytoplasmic domain of CupA (sCupA) contains a binuclear Cu(i) cluster consisting of S1 and S2 Cu(i) ions. The NMR solution structure of apo-sCupA reveals the same cupredoxin fold of Cu2-sCupA, except that the Cu(i) binding loop (residues 112-116, harboring S2 Cu ligands M113 and M115) is highly dynamic as documented by both backbone and side chain methionine methyl order parameters. In contrast to the more solvent exposed, lower affinity S2 Cu site, the high affinity S1 Cu-coordinating cysteines (C74, C111) are pre-organized in the apo-sCupA structure. Biological experiments reveal that the S1 site is largely dispensable for cellular Cu resistance and may be involved in buffering low cytoplasmic Cu(i). In contrast, the S2 site is essential for Cu resistance. Expression of a chimeric CopZ chaperone fused to the CupA transmembrane helix does not protect S. pneumoniae from copper toxicity and substitution of a predicted cytoplasm-facing Cu(i) entry metal-binding site (MBS) on CopA also gives rise to a Cu-sensitivity phenotype. These findings suggest that CupA and CopA may interact and filling of the CupA S2 site with Cu(i) results in stimulation of cellular copper efflux by CopA.

  12. The CroRS Two-Component Regulatory System Is Required for Intrinsic β-Lactam Resistance in Enterococcus faecalis

    PubMed Central

    Comenge, Yannick; Quintiliani, Richard; Li, Ling; Dubost, Lionnel; Brouard, Jean-Paul; Hugonnet, Jean-Emmanuel; Arthur, Michel

    2003-01-01

    Enterococcus faecalis produces a specific penicillin-binding protein (PBP5) that mediates high-level resistance to the cephalosporin class of β-lactam antibiotics. Deletion of a locus encoding a previously uncharacterized two-component regulatory system of E. faecalis (croRS) led to a 4,000-fold reduction in the MIC of the expanded-spectrum cephalosporin ceftriaxone. The cytoplasmic domain of the sensor kinase (CroS) was purified and shown to catalyze ATP-dependent autophosphorylation followed by transfer of the phosphate to the mated response regulator (CroR). The croR and croS genes were cotranscribed from a promoter (croRp) located in the rrnC-croR intergenic region. A putative seryl-tRNA synthetase gene (serS) located immediately downstream from croS did not appear to be a target of CroRS regulation or to play a role in ceftriaxone resistance. A plasmid-borne croRp-lacZ fusion was trans-activated by the CroRS system in response to the presence of ceftriaxone in the culture medium. The fusion was also induced by representatives of other classes of β-lactam antibiotics and by inhibitors of early and late steps of peptidoglycan synthesis. The croRS null mutant produced PBP5, and expression of an additional copy of pbp5 under the control of a heterologous promoter did not restore ceftriaxone resistance. Deletion of croRS was not associated with any defect in the synthesis of the nucleotide precursor UDP-MurNAc-pentapeptide or of the d-Ala4→l-Ala-l-Ala-Lys3 peptidoglycan cross-bridge. Thus, the croRS mutant was susceptible to ceftriaxone despite the production of PBP5 and the synthesis of wild-type peptidoglycan precursors. These observations constitute the first description of regulatory genes essential for PBP5-mediated β-lactam resistance in enterococci. PMID:14645279

  13. Members of the Conserved DedA Family Are Likely Membrane Transporters and Are Required for Drug Resistance in Escherichia coli

    PubMed Central

    Kumar, Sujeet

    2014-01-01

    Bacterial resistance to antibiotics and biocides is an increasing public health problem. Genes encoding integral membrane proteins belonging to the DedA family are present in most bacterial genomes, including Escherichia coli. An E. coli strain lacking partially redundant DedA family genes yqjA and yghB (strain BC202) displays temperature sensitivity and cell division defects. These phenotypes can be corrected by overexpression of mdfA, an Na+-K+/H+ antiporter of the major facilitator superfamily. We show that BC202 is hypersensitive to several biocides and cationic compounds that are known substrates of several multidrug resistance transporters, including MdfA, EmrE, and AcrB. The introduction of deletions of genes encoding these drug transporters into BC202 results in additional sensitivity. Expression of wild-type yghB or yqjA can restore drug resistance, but this is eliminated upon mutation of two membrane-embedded acidic amino acids (E39 or D51 in either protein). This dependence upon membrane-embedded acidic amino acids is a hallmark of proton-dependent antiporters. Overexpression of mdfA in BC202 or artificially restoring proton motive force (PMF) restores wild-type resistance to substrates of MdfA as well as other drug resistance transporters such as EmrE and AcrAB. These results suggest that YqjA and YghB may be membrane transporters required for PMF-dependent drug efflux in E. coli. PMID:24277026

  14. Nucleocytoplasmic Distribution Is Required for Activation of Resistance by the Potato NB-LRR Receptor Rx1 and Is Balanced by Its Functional Domains[W

    PubMed Central

    Slootweg, Erik; Roosien, Jan; Spiridon, Laurentiu N.; Petrescu, Andrei-Jose; Tameling, Wladimir; Joosten, Matthieu; Pomp, Rikus; van Schaik, Casper; Dees, Robert; Borst, Jan Willem; Smant, Geert; Schots, Arjen; Bakker, Jaap; Goverse, Aska

    2010-01-01

    The Rx1 protein, as many resistance proteins of the nucleotide binding–leucine-rich repeat (NB-LRR) class, is predicted to be cytoplasmic because it lacks discernable nuclear targeting signals. Here, we demonstrate that Rx1, which confers extreme resistance to Potato virus X, is located both in the nucleus and cytoplasm. Manipulating the nucleocytoplasmic distribution of Rx1 or its elicitor revealed that Rx1 is activated in the cytoplasm and cannot be activated in the nucleus. The coiled coil (CC) domain was found to be required for accumulation of Rx1 in the nucleus, whereas the LRR domain promoted the localization in the cytoplasm. Analyses of structural subdomains of the CC domain revealed no autonomous signals responsible for active nuclear import. Fluorescence recovery after photobleaching and nuclear fractionation indicated that the CC domain binds transiently to large complexes in the nucleus. Disruption of the Rx1 resistance function and protein conformation by mutating the ATP binding phosphate binding loop in the NB domain, or by silencing the cochaperone SGT1, impaired the accumulation of Rx1 protein in the nucleus, while Rx1 versions lacking the LRR domain were not affected in this respect. Our results support a model in which interdomain interactions and folding states determine the nucleocytoplasmic distribution of Rx1. PMID:21177483

  15. A Major Facilitator Superfamily Transporter-Mediated Resistance to Oxidative Stress and Fungicides Requires Yap1, Skn7, and MAP Kinases in the Citrus Fungal Pathogen Alternaria alternata.

    PubMed

    Chen, Li-Hung; Tsai, Hsieh-Chin; Yu, Pei-Ling; Chung, Kuang-Ren

    2017-01-01

    Major Facilitator Superfamily (MFS) transporters play an important role in multidrug resistance in fungi. We report an AaMFS19 gene encoding a MFS transporter required for cellular resistance to oxidative stress and fungicides in the phytopathogenic fungus Alternaria alternata. AaMFS19, containing 12 transmembrane domains, displays activity toward a broad range of substrates. Fungal mutants lacking AaMFS19 display profound hypersensitivities to cumyl hydroperoxide, potassium superoxide, many singlet oxygen-generating compounds (eosin Y, rose Bengal, hematoporphyrin, methylene blue, and cercosporin), and the cell wall biosynthesis inhibitor, Congo red. AaMFS19 mutants also increase sensitivity to copper ions, clotrimazole, fludioxonil, and kocide fungicides, 2-chloro-5-hydroxypyridine (CHP), and 2,3,5-triiodobenzoic acid (TIBA). AaMFS19 mutants induce smaller necrotic lesions on leaves of a susceptible citrus cultivar. All observed phenotypes in the mutant are restored by introducing and expressing a wild-type copy of AaMFS19. The wild-type strain of A. alternata treated with either CHP or TIBA reduces radial growth and formation and germination of conidia, increases hyphal branching, and results in decreased expression of the AaMFS19 gene. The expression of AaMFS19 is regulated by the Yap1 transcription activator, the Hog1 and Fus3 mitogen-activated protein (MAP) kinases, the 'two component' histidine kinase, and the Skn7 response regulator. Our results demonstrate that A. alternata confers resistance to different chemicals via a membrane-bound MFS transporter.

  16. Allowable stresses in FRP marine vessels

    NASA Astrophysics Data System (ADS)

    Visuri, Manuri

    The publication consists of a literature survey of allowable stresses used in fiber-reinforced plastic (FRP) structures, and a new method for the determination of allowable stresses is presented. In the literature survey, primary attention has been paid to the marine industry (including classification societies), the aerospace industry, and to pressure vessel and pipe standards. Generally the subject is only briefly discussed in the literature. This is a drawback, since the conservatism dominating the rules used today often means unnecessary weight penalties. High factors of safety (FoS), except in the aerospace industry, are used in most designs. The short experience of structures in service, wide variety of material combinations and the rather complicated mechanical behavior are the most important factors in this regard. The presented determination method for allowable stresses aims at introducing a more rational way for dimensioning. The method is based on the partial factors of safety concept. A statistical analysis can be included for better accuracy. This requires enough data of material and load behavior. The method is flexible and can be tailored to various needs. One major drawback is the lack of information concerning material behavior under long-term loads. The method is aimed to be expanded in the future.

  17. Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics.

    PubMed

    Majiduddin, Fahd K; Palzkill, Timothy

    2003-03-01

    Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

  18. Rapamycin-Resistant mTOR Activity Is Required for Sensory Axon Regeneration Induced by a Conditioning Lesion

    PubMed Central

    Lu, Na; Ding, Yue; Chan, Leung Ting; Wang, Xu; Gao, Xin; Jiang, Songshan

    2016-01-01

    Abstract Neuronal mammalian target of rapamycin (mTOR) activity is a critical determinant of the intrinsic regenerative ability of mature neurons in the adult central nervous system (CNS). However, whether its action also applies to peripheral nervous system (PNS) neurons after injury remains elusive. To address this issue unambiguously, we used genetic approaches to determine the role of mTOR signaling in sensory axon regeneration in mice. We showed that deleting mTOR in dorsal root ganglion (DRG) neurons suppressed the axon regeneration induced by conditioning lesions. To establish whether the impact of mTOR on axon regeneration results from functions of mTOR complex 1 (mTORC1) or 2 (mTORC2), two distinct kinase complexes, we ablated either Raptor or Rictor in DRG neurons. We found that suppressing mTORC1 signaling dramatically decreased the conditioning lesion effect. In addition, an injury to the peripheral branch boosts mTOR activity in DRG neurons that cannot be completely inhibited by rapamycin, a widely used mTOR-specific inhibitor. Unexpectedly, examining several conditioning lesion–induced pro-regenerative pathways revealed that Raptor deletion but not rapamycin suppressed Stat3 activity in neurons. Therefore, our results demonstrate that crosstalk between mTOR and Stat3 signaling mediates the conditioning lesion effect and provide genetic evidence that rapamycin-resistant mTOR activity contributes to the intrinsic axon growth capacity in adult sensory neurons after injury. PMID:28101526

  19. Medicago truncatula natural resistance-associated macrophage Protein1 is required for iron uptake by rhizobia-infected nodule cells.

    PubMed

    Tejada-Jiménez, Manuel; Castro-Rodríguez, Rosario; Kryvoruchko, Igor; Lucas, M Mercedes; Udvardi, Michael; Imperial, Juan; González-Guerrero, Manuel

    2015-05-01

    Iron is critical for symbiotic nitrogen fixation (SNF) as a key component of multiple ferroproteins involved in this biological process. In the model legume Medicago truncatula, iron is delivered by the vasculature to the infection/maturation zone (zone II) of the nodule, where it is released to the apoplast. From there, plasma membrane iron transporters move it into rhizobia-containing cells, where iron is used as the cofactor of multiple plant and rhizobial proteins (e.g. plant leghemoglobin and bacterial nitrogenase). MtNramp1 (Medtr3g088460) is the M. truncatula Natural Resistance-Associated Macrophage Protein family member, with the highest expression levels in roots and nodules. Immunolocalization studies indicate that MtNramp1 is mainly targeted to the plasma membrane. A loss-of-function nramp1 mutant exhibited reduced growth compared with the wild type under symbiotic conditions, but not when fertilized with mineral nitrogen. Nitrogenase activity was low in the mutant, whereas exogenous iron and expression of wild-type MtNramp1 in mutant nodules increased nitrogen fixation to normal levels. These data are consistent with a model in which MtNramp1 is the main transporter responsible for apoplastic iron uptake by rhizobia-infected cells in zone II.

  20. Requirement of UNC93B1 reveals a critical role for Toll-Like Receptor 7 in host resistance to primary infection with Trypanosoma cruzi1,2

    PubMed Central

    Caetano, Braulia C.; Carmo, Bianca B.; Melo, Mariane B.; Cerny, Anna; dos Santos, Sara L.; Bartholomeu, Daniella C.; Golenbock, Douglas T.; Gazzinelli, Ricardo T.

    2011-01-01

    UNC93B1 associates with Toll-Like Receptor (TLR) 3, 7 and 9, mediating their translocation from the endoplasmic reticulum to the endolysosome, thus allowing proper activation by microbial nucleic acids. We found that the triple deficient ‘3d’ mice, which lack functional UNC93B1 as well as functional endossomal TLRs, are highly susceptible to infection with Trypanosoma cruzi. The enhanced parasitemia and mortality in 3d animals were associated with impaired pro-inflammatory response, including reduced levels of IL-12p40 and IFN-γ. Importantly, the phenotype of 3d mice was intermediary between MyD88−/− (highly susceptible) and TLR9−/− (less susceptible), indicating the involvement of an additional UN93B1-dependent-TLR(s) on host resistance to T. cruzi. Hence, our experiments also revealed that TLR7 is a critical innate immune receptor involved in recognition of parasite RNA, induction of IL-12p40 by dendritic cells, and consequent IFN-γ by T lymphocytes. Furthermore, we show that upon T. cruzi infection triple TLR3/7/9−/− mice had similar phenotype than 3d mice. These data imply that the nucleic acid-sensing TLRs are critical determinants of host resistance to primary infection with T. cruzi. PMID:21753151

  1. A Major Facilitator Superfamily Transporter-Mediated Resistance to Oxidative Stress and Fungicides Requires Yap1, Skn7, and MAP Kinases in the Citrus Fungal Pathogen Alternaria alternata

    PubMed Central

    Chen, Li-Hung; Tsai, Hsieh-Chin; Yu, Pei-Ling

    2017-01-01

    Major Facilitator Superfamily (MFS) transporters play an important role in multidrug resistance in fungi. We report an AaMFS19 gene encoding a MFS transporter required for cellular resistance to oxidative stress and fungicides in the phytopathogenic fungus Alternaria alternata. AaMFS19, containing 12 transmembrane domains, displays activity toward a broad range of substrates. Fungal mutants lacking AaMFS19 display profound hypersensitivities to cumyl hydroperoxide, potassium superoxide, many singlet oxygen-generating compounds (eosin Y, rose Bengal, hematoporphyrin, methylene blue, and cercosporin), and the cell wall biosynthesis inhibitor, Congo red. AaMFS19 mutants also increase sensitivity to copper ions, clotrimazole, fludioxonil, and kocide fungicides, 2-chloro-5-hydroxypyridine (CHP), and 2,3,5-triiodobenzoic acid (TIBA). AaMFS19 mutants induce smaller necrotic lesions on leaves of a susceptible citrus cultivar. All observed phenotypes in the mutant are restored by introducing and expressing a wild-type copy of AaMFS19. The wild-type strain of A. alternata treated with either CHP or TIBA reduces radial growth and formation and germination of conidia, increases hyphal branching, and results in decreased expression of the AaMFS19 gene. The expression of AaMFS19 is regulated by the Yap1 transcription activator, the Hog1 and Fus3 mitogen-activated protein (MAP) kinases, the ‘two component’ histidine kinase, and the Skn7 response regulator. Our results demonstrate that A. alternata confers resistance to different chemicals via a membrane-bound MFS transporter. PMID:28060864

  2. Acid resistance systems required for survival of Escherichia coli O157:H7 in the bovine gastrointestinal tract and in apple cider are different.

    PubMed

    Price, Stuart B; Wright, James C; DeGraves, Fred J; Castanie-Cornet, Marie-Pierre; Foster, John W

    2004-08-01

    Escherichia coli O157:H7 is a highly acid-resistant food-borne pathogen that survives in the bovine and human gastrointestinal tracts and in acidic foods such as apple cider. This property is thought to contribute to the low infectious dose of the organism. Three acid resistance (AR) systems are expressed in stationary-phase cells. AR system 1 is sigma(S) dependent, while AR systems 2 and 3 are glutamate and arginine dependent, respectively. In this study, we sought to determine which AR systems are important for survival in acidic foods and which are required for survival in the bovine intestinal tract. Wild-type and mutant E. coli O157:H7 strains deficient in AR system 1, 2, or 3 were challenged with apple cider and inoculated into calves. Wild-type cells, adapted at pH 5.5 in the absence of glucose (AR system 1 induced), survived well in apple cider. Conversely, the mutant deficient in AR system 1, shown previously to survive poorly in calves, was susceptible to apple cider (pH 3.5), and this sensitivity was shown to be caused by low pH. Interestingly, the AR system 2-deficient mutant survived in apple cider at high levels, but its shedding from calves was significantly decreased compared to that of wild-type cells. AR system 3-deficient cells survived well in both apple cider and calves. Taken together, these results indicate that E. coli O157:H7 utilizes different acid resistance systems based on the type of acidic environment encountered.

  3. Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae.

    PubMed

    Molin, Mikael; Yang, Junsheng; Hanzén, Sarah; Toledano, Michel B; Labarre, Jean; Nyström, Thomas

    2011-09-02

    Caloric restriction (CR) extends the life span of organisms ranging from yeast to primates. Here, we show that the thiol-dependent peroxiredoxin Tsa1 and its partner sulfiredoxin, Srx1, are required for CR to extend the replicative life span of yeast cells. Tsa1 becomes hyperoxidized/inactive during aging, and CR mitigates such oxidation by elevating the levels of Srx1, which is required to reduce/reactivate hyperoxidized Tsa1. CR, by lowering cAMP-PKA activity, enhances Gcn2-dependent SRX1 translation, resulting in increased resistance to H(2)O(2) and life span extension. Moreover, an extra copy of the SRX1 gene is sufficient to extend the life span of cells grown in high glucose concentrations by 20% in a Tsa1-dependent and Sir2-independent manner. The data demonstrate that Tsa1 is required to ensure yeast longevity and that CR extends yeast life span, in part, by counteracting age-induced hyperoxidation of this peroxiredoxin.

  4. uspB, a New ςS-Regulated Gene in Escherichia coli Which Is Required for Stationary-Phase Resistance to Ethanol

    PubMed Central

    Farewell, Anne; Kvint, Kristian; Nyström, Thomas

    1998-01-01

    The open reading frame immediately upstream of uspA is demonstrated to encode a 14-kDa protein which we named UspB (universal stress protein B) because of its general responsiveness to different starvation and stress conditions. UspB is predicted to be an integral membrane protein with at least one and perhaps two membrane-spanning domains. Overexpression of UspB causes cell death in stationary phase, whereas mutants of uspB are sensitive to exposure to ethanol but not heat in stationary phase. In contrast to uspA, stationary-phase induction of uspB requires the sigma factor ςS. The expression of uspB is modulated by H-NS, consistent with the role of H-NS in altering ςS levels. Our results demonstrate that a gene of the RpoS regulon is involved in the development of stationary-phase resistance to ethanol, in addition to the regulon’s previously known role in thermotolerance, osmotolerance, and oxidative stress resistance. PMID:9829921

  5. Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity

    PubMed Central

    Gandhi, Anita K; Mendy, Derek; Waldman, Michelle; Chen, Gengxin; Rychak, Emily; Miller, Karen; Gaidarova, Svetlana; Ren, Yan; Wang, Maria; Breider, Michael; Carmel, Gilles; Mahmoudi, Afshin; Jackson, Pilgrim; Abbasian, Mahan; Cathers, Brian E; Schafer, Peter H; Daniel, Tom O; Lopez-Girona, Antonia; Thakurta, Anjan; Chopra, Rajesh

    2014-01-01

    Cereblon, a member of the cullin 4 ring ligase complex (CRL4), is the molecular target of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide and is required for the antiproliferative activity of these agents in multiple myeloma (MM) and immunomodulatory activity in T cells. Cereblon's central role as a target of lenalidomide and pomalidomide suggests potential utility as a predictive biomarker of response or resistance to IMiD therapy. Our studies characterized a cereblon monoclonal antibody CRBN65, with high sensitivity and specificity in Western analysis and immunohistochemistry that is superior to commercially available antibodies. We identified multiple cereblon splice variants in both MM cell lines and primary cells, highlighting challenges with conventional gene expression assays given this gene complexity. Using CRBN65 antibody and TaqMan quantitative reverse transcription polymerase chain reaction assays, we showed lack of correlation between cereblon protein and mRNA levels. Furthermore, lack of correlation between cereblon expression in MM cell lines and sensitivity to lenalidomide was shown. In cell lines made resistant to lenalidomide and pomalidomide, cereblon protein is greatly reduced. These studies show limitations to the current approaches of cereblon measurement that rely on commercial reagents and assays. Standardized reagents and validated assays are needed to accurately assess the role of cereblon as a predictive biomarker. PMID:24206017

  6. Inhibition of seed germination and induction of systemic disease resistance by Pseudomonas chlororaphis O6 requires phenazine production regulated by the global regulator, gacS.

    PubMed

    Kang, Beom Ryong; Han, Song Hee; Zdor, Rob E; Anderson, Anne J; Spencer, Matt; Yang, Kwang Yeol; Kim, Yong Hwan; Lee, Myung Chul; Cho, Baik Ho; Kim, Young Cheol

    2007-04-01

    Seed coating by a phenazine-producing bacterium, Pseudomonas chlororaphis O6, induced dose-dependent inhibition of germination in wheat and barley seeds, but did not inhibit germination of rice or cucumber seeds. In wheat seedlings grown from inoculated seeds, phenazine production levels near the seed were higher than in the roots. Deletion of the gacS gene reduced transcription from the genes required for phenazine synthesis, the regulatory phzI gene and the biosynthetic phzA gene. The inhibition of seed germination and the induction of systemic disease resistance against a bacterial soft-rot pathogen, Erwinia carotovora subsp. carotovora, were impaired in the gacS and phzA mutants of P chlororaphis O6. Culture filtrates of the gacS and phzA mutants of P chlororaphis 06 did not inhibit seed germination of wheat, whereas that of the wild-type was inhibitory. Our results showed that the production of phenazines by P chlororaphis O6 was correlated with reduced germination of barley and wheat seeds, and the level of systemic resistance in tobacco against E. carotovora.

  7. The catalytic subunit of DNA-dependent protein kinase is required for cellular resistance to oxidative stress independent of DNA double-strand break repair.

    PubMed

    Li, Mengxia; Lin, Yu-Fen; Palchik, Guillermo A; Matsunaga, Shinji; Wang, Dong; Chen, Benjamin P C

    2014-11-01

    DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated (ATM) are the two major kinases involved in DNA double-strand break (DSB) repair, and are required for cellular resistance to ionizing radiation. Whereas ATM is the key upstream kinase for DSB signaling, DNA-PKcs is primarily involved in DSB repair through the nonhomologous end-joining (NHEJ) mechanism. In addition to DSB repair, ATM has been shown to be involved in the oxidative stress response and could be activated directly in vitro on hydrogen peroxide (H2O2) treatment. However, the role of DNA-PKcs in cellular response to oxidative stress is not clear. We hypothesize that DNA-PKcs may participate in the regulation of ATM activation in response to oxidative stress, and that this regulatory role is independent of its role in DNA double-strand break repair. Our findings reveal that H2O2 induces hyperactivation of ATM signaling in DNA-PKcs-deficient, but not Ligase 4-deficient cells, suggesting an NHEJ-independent role for DNA-PKcs. Furthermore, DNA-PKcs deficiency leads to the elevation of reactive oxygen species (ROS) production, and to a decrease in cellular survival against H2O2. For the first time, our results reveal that DNA-PKcs plays a noncanonical role in the cellular response to oxidative stress, which is independent from its role in NHEJ. In addition, DNA-PKcs is a critical regulator of the oxidative stress response and contributes to the maintenance of redox homeostasis. Our findings reveal that DNA-PKcs is required for cellular resistance to oxidative stress and suppression of ROS buildup independently of its function in DSB repair.

  8. 40 CFR 96.42 - NOX allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS... calculating NOX allowance allocations for each NOX Budget unit under § 96.4 will be: (i) For a NOX allowance... the NOX Budget unit was otherwise subject to the requirements of part 75 of this chapter for the...

  9. 40 CFR 96.42 - NOX allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS... calculating NOX allowance allocations for each NOX Budget unit under § 96.4 will be: (i) For a NOX allowance... the NOX Budget unit was otherwise subject to the requirements of part 75 of this chapter for the...

  10. 45 CFR 2522.245 - How are living allowances disbursed?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... NATIONAL AND COMMUNITY SERVICE AMERICORPS PARTICIPANTS, PROGRAMS, AND APPLICANTS Participant Eligibility, Requirements, and Benefits § 2522.245 How are living allowances disbursed? A living allowance is not a wage and... only be made to a participant during the participant's term of service and must cease when...

  11. 45 CFR 2400.50 - Allowances and Summer Institute costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Allowances and Summer Institute costs. 2400.50 Section 2400.50 Public Welfare Regulations Relating to Public Welfare (Continued) JAMES MADISON MEMORIAL FELLOWSHIP FOUNDATION FELLOWSHIP PROGRAM REQUIREMENTS Graduate Study § 2400.50 Allowances and...

  12. 45 CFR 2400.50 - Allowances and Summer Institute costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Allowances and Summer Institute costs. 2400.50 Section 2400.50 Public Welfare Regulations Relating to Public Welfare (Continued) JAMES MADISON MEMORIAL FELLOWSHIP FOUNDATION FELLOWSHIP PROGRAM REQUIREMENTS Graduate Study § 2400.50 Allowances and...

  13. 48 CFR 31.201-2 - Determining allowability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Certain cost principles in this subpart incorporate the measurement, assignment, and allocability rules of... GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.201-2 Determining allowability. (a) A cost is allowable only when the cost complies with all...

  14. 36 CFR 1210.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Allowable costs. 1210.27... Management § 1210.27 Allowable costs. For each kind of recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall be determined in accordance with the cost...

  15. 45 CFR 1183.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 1183.22 Section 1183.22 Public....22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in...

  16. 45 CFR 74.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Allowable costs. 74.27 Section 74.27 Public... Allowable costs. (a) For each kind of recipient, there is a particular set of Federal principles that applies in determining allowable costs. Allowability of costs shall be determined in accordance with...

  17. 45 CFR 1157.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 1157.22 Section 1157.22 Public... Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form...

  18. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and....22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in...

  19. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Allowable costs. 304.21 Section 304.21 Education... Grantee § 304.21 Allowable costs. In addition to the allowable costs established in the Education... allowable expenditures by projects funded under the program: (a) Cost of attendance, as defined in Title...

  20. 34 CFR 74.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Allowable costs. 74.27 Section 74.27 Education Office... and Program Management § 74.27 Allowable costs. (a) For each kind of recipient, there is a set of cost principles for determining allowable costs. Allowability of costs are determined in accordance with the...

  1. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true Allowable costs. 304.21 Section 304.21 Education... Grantee § 304.21 Allowable costs. In addition to the allowable costs established in the Education... allowable expenditures by projects funded under the program: (a) Cost of attendance, as defined in Title...

  2. 45 CFR 1174.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 1174.22 Section 1174.22 Public....22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in...

  3. 34 CFR 80.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Allowable costs. 80.22 Section 80.22 Education Office... Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form...

  4. 24 CFR 84.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Allowable costs. 84.27 Section 84....27 Allowable costs. For each kind of recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall be determined in accordance with the cost principles...

  5. 15 CFR 24.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Allowable costs. 24.22 Section 24.22... Administration § 24.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in...

  6. 49 CFR 266.11 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Allowable costs. 266.11 Section 266.11... TRANSPORTATION ACT § 266.11 Allowable costs. Allowable costs include only the following costs which are properly allocable to the work performed: Planning and program operation costs which are allowed under...

  7. 34 CFR 80.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Allowable costs. 80.22 Section 80.22 Education Office... Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form...

  8. 2 CFR 215.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Allowable costs. 215.27 Section 215.27... § 215.27 Allowable costs. For each kind of recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall be determined in accordance with the cost...

  9. 7 CFR 3019.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Allowable costs. 3019.27 Section 3019.27 Agriculture... Management § 3019.27 Allowable costs. For each kind of recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall be determined in accordance with the cost...

  10. 24 CFR 84.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Allowable costs. 84.27 Section 84....27 Allowable costs. For each kind of recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall be determined in accordance with the cost principles...

  11. 20 CFR 617.46 - Travel allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Travel allowance. 617.46 Section 617.46... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.46 Travel allowance. (a) Computation. The amount of travel allowance (including lodging and meals) payable under § 617.45(a)(1)...

  12. 20 CFR 617.46 - Travel allowance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Travel allowance. 617.46 Section 617.46... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.46 Travel allowance. (a) Computation. The amount of travel allowance (including lodging and meals) payable under § 617.45(a)(1)...

  13. 20 CFR 617.46 - Travel allowance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Travel allowance. 617.46 Section 617.46... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.46 Travel allowance. (a) Computation. The amount of travel allowance (including lodging and meals) payable under § 617.45(a)(1)...

  14. 20 CFR 617.46 - Travel allowance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Travel allowance. 617.46 Section 617.46... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.46 Travel allowance. (a) Computation. The amount of travel allowance (including lodging and meals) payable under § 617.45(a)(1)...

  15. 20 CFR 617.46 - Travel allowance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Travel allowance. 617.46 Section 617.46... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.46 Travel allowance. (a) Computation. The amount of travel allowance (including lodging and meals) payable under § 617.45(a)(1)...

  16. 38 CFR 3.810 - Clothing allowance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Clothing allowance. 3.810..., Compensation, and Dependency and Indemnity Compensation Special Benefits § 3.810 Clothing allowance. (a) Except... therefor, to an annual clothing allowance as specified in 38 U.S.C. 1162. The annual clothing allowance...

  17. 20 CFR 617.47 - Moving allowance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Moving allowance. 617.47 Section 617.47... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.47 Moving allowance. (a) Computation. The amount of a moving allowance payable under § 617.45(a)(2) shall be 90 percent of the total...

  18. 20 CFR 617.47 - Moving allowance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Moving allowance. 617.47 Section 617.47... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.47 Moving allowance. (a) Computation. The amount of a moving allowance payable under § 617.45(a)(2) shall be 90 percent of the total...

  19. 20 CFR 617.47 - Moving allowance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Moving allowance. 617.47 Section 617.47... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.47 Moving allowance. (a) Computation. The amount of a moving allowance payable under § 617.45(a)(2) shall be 90 percent of the total...

  20. 20 CFR 617.47 - Moving allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Moving allowance. 617.47 Section 617.47... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.47 Moving allowance. (a) Computation. The amount of a moving allowance payable under § 617.45(a)(2) shall be 90 percent of the total...

  1. 20 CFR 617.47 - Moving allowance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Moving allowance. 617.47 Section 617.47... FOR WORKERS UNDER THE TRADE ACT OF 1974 Relocation Allowances § 617.47 Moving allowance. (a) Computation. The amount of a moving allowance payable under § 617.45(a)(2) shall be 90 percent of the total...

  2. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  3. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  4. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  5. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  6. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  7. Accumulation of a soluble form of human nectin-2 is required for exerting the resistance against herpes simplex virus type 2 infection in transfected cells.

    PubMed

    Fujimoto, Y; Ozaki, K; Iwamori, N; Takakuwa, H; Ono, E

    2016-03-01

    Cell entry of herpes simplex virus type 2 (HSV-2) requires the interaction of viral glycoprotein D (gD) with the receptor nectin-1 and herpesvirus entry mediator (HVEM). In addition, it is known that nectin-2 is also functional as a receptor for HSV-2, although the binding to the gD is weak. To examine an antiviral potential of a soluble form of human nectin-2 (hNectin-2Ig), transfected Vero cells expressing the entire ectodomain of nectin-2 fused to the Fc portion of human IgG were established. Specific binding of hNectin-2Ig to HSV-2 gD was confirmed by ELISA. Competitive ELISA demonstrated that accumulation of hNectin-2Ig in transfected cells increased significantly in a cell culture time dependent manner. Viral growth of several HSV-2 strains was significantly inhibited in the transfected cells that were cultured for 72 hr compared with control Vero cells, but not in cells that were cultured for 24 hr. These results indicate that accumulation of a soluble form of nectin-2 is required for exerting the resistance against HSV-2 infection.

  8. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  9. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  10. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  11. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  12. Assessing allowable take of migratory birds

    USGS Publications Warehouse

    Runge, M.C.; Sauer, J.R.; Avery, M.L.; Blackwell, B.F.; Koneff, M.D.

    2009-01-01

    Legal removal of migratory birds from the wild occurs for several reasons, including subsistence, sport harvest, damage control, and the pet trade. We argue that harvest theory provides the basis for assessing the impact of authorized take, advance a simplified rendering of harvest theory known as potential biological removal as a useful starting point for assessing take, and demonstrate this approach with a case study of depredation control of black vultures (Coragyps atratus) in Virginia, USA. Based on data from the North American Breeding Bird Survey and other sources, we estimated that the black vulture population in Virginia was 91,190 (95% credible interval = 44,520?212,100) in 2006. Using a simple population model and available estimates of life-history parameters, we estimated the intrinsic rate of growth (rmax) to be in the range 7?14%, with 10.6% a plausible point estimate. For a take program to seek an equilibrium population size on the conservative side of the yield curve, the rate of take needs to be less than that which achieves a maximum sustained yield (0.5 x rmax). Based on the point estimate for rmax and using the lower 60% credible interval for population size to account for uncertainty, these conditions would be met if the take of black vultures in Virginia in 2006 was <3,533 birds. Based on regular monitoring data, allowable harvest should be adjusted annually to reflect changes in population size. To initiate discussion about how this assessment framework could be related to the laws and regulations that govern authorization of such take, we suggest that the Migratory Bird Treaty Act requires only that take of native migratory birds be sustainable in the long-term, that is, sustained harvest rate should be requirements of the National Environmental Protection Act.

  13. Assessing allowable take of migratory birds

    USGS Publications Warehouse

    Runge, M.C.; Sauer, J.R.; Avery, M.L.; Blackwell, B.F.; Koneff, M.D.

    2009-01-01

    Legal removal of migratory birds from the wild occurs for several reasons, including subsistence, sport harvest, damage control, and the pet trade. We argue that harvest theory provides the basis for assessing the impact of authorized take, advance a simplified rendering of harvest theory known as potential biological removal as a useful starting point for assessing take, and demonstrate this approach with a case study of depredation control of black vultures (Coragyps atratus) in Virginia, USA. Based on data from the North American Breeding Bird Survey and other sources, we estimated that the black vulture population in Virginia was 91,190 (95% credible interval = 44,520?212,100) in 2006. Using a simple population model and available estimates of life-history parameters, we estimated the intrinsic rate of growth (rmax) to be in the range 7?14%, with 10.6% a plausible point estimate. For a take program to seek an equilibrium population size on the conservative side of the yield curve, the rate of take needs to be less than that which achieves a maximum sustained yield (0.5 x rmax). Based on the point estimate for rmax and using the lower 60% credible interval for population size to account for uncertainty, these conditions would be met if the take of black vultures in Virginia in 2006 was < 3,533 birds. Based on regular monitoring data, allowable harvest should be adjusted annually to reflect changes in population size. To initiate discussion about how this assessment framework could be related to the laws and regulations that govern authorization of such take, we suggest that the Migratory Bird Treaty Act requires only that take of native migratory birds be sustainable in the long-term, that is, sustained harvest rate should be < rmax. Further, the ratio of desired harvest rate to 0.5 x rmax may be a useful metric for ascertaining the applicability of specific requirements of the National Environmental Protection Act.

  14. Conversion of raft associated prion protein to the protease-resistant state requires insertion of PrP-res (PrP(Sc)) into contiguous membranes.

    PubMed

    Baron, Gerald S; Wehrly, Kathy; Dorward, David W; Chesebro, Bruce; Caughey, Byron

    2002-03-01

    Prion protein (PrP) is usually attached to membranes by a glycosylphosphatidylinositol-anchor that associates with detergent-resistant membranes (DRMs), or rafts. To model the molecular processes that might occur during the initial infection of cells with exogenous transmissible spongiform encephalopathy (TSE) agents, we examined the effect of membrane association on the conversion of the normal protease-sensitive PrP isoform (PrP-sen) to the protease-resistant isoform (PrP-res). A cell-free conversion reaction approximating physiological conditions was used, which contained purified DRMs as a source of PrP-sen and brain microsomes from scrapie-infected mice as a source of PrP-res. Interestingly, DRM-associated PrP-sen was not converted to PrP-res until the PrP-sen was either released from DRMs by treatment with phosphatidylinositol-specific phospholipase C (PI-PLC), or the combined membrane fractions were treated with the membrane-fusing agent polyethylene glycol (PEG). PEG-assisted conversion was optimal at pH 6--7, and acid pre-treating the DRMs was not sufficient to permit conversion without PI-PLC or PEG, arguing against late endosomes/lysosomes as primary compartments for PrP conversion. These observations raise the possibility that generation of new PrP-res during TSE infection requires (i) removal of PrP-sen from target cells; (ii) an exchange of membranes between cells; or (iii) insertion of incoming PrP-res into the raft domains of recipient cells.

  15. Two Genes Encoding Structurally Different CC-NB-LRR Proteins are Required for Lr10-Mediated Leaf Rust Resistance in Wheat of Two Ploidy Levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gene pools of crop plant relatives have been proposed as a source of new functional resistance genes to broaden the basis of genetic resistance. Here, we have studied the allelic diversity of the Lr10 leaf rust resistance gene, encoding a CC-NBS-LRR protein originally identified in hexaploid bre...

  16. 42 CFR 417.802 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Allowable costs. 417.802 Section 417.802 Public... PLANS Health Care Prepayment Plans § 417.802 Allowable costs. (a) General rule. The costs that are considered allowable for HCPP reimbursement are the same as those for reasonable cost HMOs and CMPs...

  17. 45 CFR 92.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Allowable costs. 92.22 Section 92.22 Public... Financial Administration § 92.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors,...

  18. 42 CFR 417.802 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Allowable costs. 417.802 Section 417.802 Public... PLANS Health Care Prepayment Plans § 417.802 Allowable costs. (a) General rule. The costs that are considered allowable for HCPP reimbursement are the same as those for reasonable cost HMOs and CMPs...

  19. 29 CFR 1470.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Allowable costs. 1470.22 Section 1470.22 Labor Regulations... Financial Administration § 1470.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors,...

  20. 50 CFR 85.41 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Allowable costs. 85.41 Section 85.41... Use/Acceptance of Funds § 85.41 Allowable costs. (a) Allowable grant costs are limited to those costs... applicable Federal cost principles in 43 CFR 12.60(b). Purchase of informational signs, program signs,...

  1. 34 CFR 675.33 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false Allowable costs. 675.33 Section 675.33 Education... costs. (a)(1) Allowable and unallowable costs. Except as provided in paragraph (a)(2) of this section, costs reasonably related to carrying out the programs described in § 675.32 are allowable. (2)...

  2. 45 CFR 1180.56 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 1180.56 Section 1180.56 Public... by a Grantee General Administrative Responsibilities § 1180.56 Allowable costs. (a) Determination of costs allowable under a grant is made in accordance with government-wide cost principles in...

  3. 42 CFR 417.534 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Allowable costs. 417.534 Section 417.534 Public... PLANS Medicare Payment: Cost Basis § 417.534 Allowable costs. (a) Definition—Allowable costs means the direct and indirect costs, including normal standby costs incurred by the HMO or CMP, that are proper...

  4. 38 CFR 49.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Allowable costs. 49.27... costs. For each kind of recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall be determined in accordance with the cost principles applicable to the...

  5. 20 CFR 632.37 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Allowable costs. 632.37 Section 632.37... EMPLOYMENT AND TRAINING PROGRAMS Administrative Standards and Procedures § 632.37 Allowable costs. (a) General. To be allowable, a cost must be necessary and reasonable for proper and efficient...

  6. 20 CFR 633.303 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Allowable costs. 633.303 Section 633.303... FARMWORKER PROGRAMS Program Design and Administrative Procedures § 633.303 Allowable costs. (a) General. To be allowable, a cost must be necessary and reasonable for proper and efficient administration of...

  7. 42 CFR 405.2468 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Allowable costs. 405.2468 Section 405.2468 Public... Allowable costs. (a) Applicability of general Medicare principles. In determining whether and to what extent a specific type or item of cost is allowable, such as interest, depreciation, bad debts and...

  8. 44 CFR 206.228 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs. 206.228 Section 206.228 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Allowable costs. General policies for determining allowable costs are established in 44 CFR...

  9. 44 CFR 206.228 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Allowable costs. 206.228 Section 206.228 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Allowable costs. General policies for determining allowable costs are established in 44 CFR...

  10. 44 CFR 206.228 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Allowable costs. 206.228 Section 206.228 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Allowable costs. General policies for determining allowable costs are established in 44 CFR...

  11. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  12. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  13. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  14. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  15. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  16. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  17. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  18. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  19. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  20. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  1. 5 CFR 591.305 - Allowance rates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Allowance Based on Duty at Remote Worksites § 591.305 Allowance rates. (a) General. An allowance rate may... remote under § 591.304, and shall be terminated or adjusted as warranted. In determining the amount of... commuting to the remote post of duty as compared to transportation expenses (including cost of...

  2. 5 CFR 591.305 - Allowance rates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Allowance Based on Duty at Remote Worksites § 591.305 Allowance rates. (a) General. An allowance rate may... remote under § 591.304, and shall be terminated or adjusted as warranted. In determining the amount of... commuting to the remote post of duty as compared to transportation expenses (including cost of...

  3. The rpg4-mediated resistance to wheat stem rust (Puccinia graminis) in barley (Hordeum vulgare) requires Rpg5, a second NBS-LRR gene, and an actin depolymerization factor.

    PubMed

    Wang, X; Richards, J; Gross, T; Druka, A; Kleinhofs, A; Steffenson, B; Acevedo, M; Brueggeman, R

    2013-04-01

    The rpg4 gene confers recessive resistance to several races of wheat stem rust (Puccinia graminis f. sp. tritici) and Rpg5 provides dominant resistance against isolates of the rye stem rust (P. graminis f. sp. secalis) in barley. The rpg4 and Rpg5 genes are tightly linked on chromosome 5H, and positional cloning using high-resolution populations clearly separated the genes, unambiguously identifying Rpg5; however, the identity of rpg4 remained unclear. High-resolution genotyping of critical recombinants at the rpg4/Rpg5 locus, designated here as rpg4-mediated resistance locus (RMRL) delimited two distinct yet tightly linked loci required for resistance, designated as RMRL1 and RMRL2. Utilizing virus-induced gene silencing, each gene at RMRL1, i.e., HvRga1 (a nucleotide-binding site leucine-rich repeat [NBS-LRR] domain gene), Rpg5 (an NBS-LRR-protein kinase domain gene), and HvAdf3 (an actin depolymerizing factor-like gene), was individually silenced followed by inoculation with P. graminis f. sp. tritici race QCCJ. Silencing each gene changed the reaction type from incompatible to compatible, indicating that all three genes are required for rpg4-mediated resistance. This stem rust resistance mechanism in barley follows the emerging theme of unrelated pairs of genetically linked NBS-LRR genes required for specific pathogen recognition and resistance. It also appears that actin cytoskeleton dynamics may play an important role in determining resistance against several races of stem rust in barley.

  4. Directed self assembly on resist-limited guiding patterns for hole grapho-epitaxy: Can DSA help lower EUV's source power requirements?

    NASA Astrophysics Data System (ADS)

    Torres, J. A.; Jiang, Fan; Ma, Yuansheng; Mellman, Joerg; Lai, Kafai; Raghunathan, Ananthan; Xu, Yongan; Liu, Chi-Chun; Chi, Cheng

    2015-03-01

    We have performed a systematic study regarding the diblock composition to keep the size of the cylinders relatively constant despite the shape of the guiding pattern. We have also explored how some guiding patterns shapes provide acceptable cylindrical assembly using an EUV exposure system. This study assumes that LER is a random phenomenon which conformably follows the shape of the guiding pattern. While the edges of the guiding pattern have fluctuations related to the LER of the EUV resist, as long as the centroid of the guiding pattern remains constant, the rectification characteristics of DSA permits adequate hole formation. In this paper we include the level of LER a guiding pattern can exhibit given a pre-determined diblock copolymer / homopolymer mixture. As the amount of homopolymer increases, the size and placement of the assembled diblock becomes less sensitive to the guiding pattern's edge roughness. This study also explores how the addition of homopolymer is only effective up to a point, as a homopolymer-rich blend is not able to assemble properly. One of the concerns about homopolymer-rich mixtures is the effect it has in the formation of defects. Such effect has not been fully characterized but this study serves as the basis for testing optimal combinations of materials and lithography settings for an EUV system, with the end goal to enable contact/via printing at lower EUV source power requirements.

  5. Iron-regulated metabolites produced by Pseudomonas fluorescens WCS374r are not required for eliciting induced systemic resistance against Pseudomonas syringae pv. tomato in Arabidopsis.

    PubMed

    Djavaheri, Mohammad; Mercado-Blanco, Jesús; Versluis, C; Meyer, J-M; Loon, L C; Bakker, Peter A H M

    2012-09-01

    The plant growth-promoting rhizobacterium Pseudomonas fluorescens WCS374r produces several iron-regulated metabolites, including the fluorescent siderophore pseudobactin (Psb374), salicylic acid (SA), and pseudomonine (Psm), a siderophore that contains a SA moiety. After purification of Psb374 from culture supernatant of WCS374r, its structure was determined following isoelectrofocusing and tandem mass spectrometry, and found to be identical to the fluorescent siderophore produced by P. fluorescens ATCC 13525. To study the role of SA and Psm production in colonization of Arabidopsis thaliana roots and in induced systemic resistance (ISR) against Pseudomonas syringae pv. tomato (Pst) by strain WCS374r, mutants disrupted in the production of these metabolites were obtained by homologous recombination. These mutants were further subjected to transposon Tn5 mutagenesis to generate mutants also deficient in Psb374 production. The mutants behaved similar to the wild type in both their Arabidopsis rhizosphere-colonizing capacity and their ability to elicit ISR against Pst. We conclude that Psb374, SA, and Psm production by P. fluorescens WCS374r are not required for eliciting ISR in Arabidopsis.

  6. Development of a Real-Time PCR Protocol Requiring Minimal Handling for Detection of Vancomycin-Resistant Enterococci with the Fully Automated BD Max System.

    PubMed

    Dalpke, Alexander H; Hofko, Marjeta; Zimmermann, Stefan

    2016-09-01

    Vancomycin-resistant enterococci (VRE) are an important cause of health care-associated infections, resulting in significant mortality and a significant economic burden in hospitals. Active surveillance for at-risk populations contributes to the prevention of infections with VRE. The availability of a combination of automation and molecular detection procedures for rapid screening would be beneficial. Here, we report on the development of a laboratory-developed PCR for detection of VRE which runs on the fully automated Becton Dickinson (BD) Max platform, which combines DNA extraction, PCR setup, and real-time PCR amplification. We evaluated two protocols: one using a liquid master mix and the other employing commercially ordered dry-down reagents. The BD Max VRE PCR was evaluated in two rounds with 86 and 61 rectal elution swab (eSwab) samples, and the results were compared to the culture results. The sensitivities of the different PCR formats were 84 to 100% for vanA and 83.7 to 100% for vanB; specificities were 96.8 to 100% for vanA and 81.8 to 97% for vanB The use of dry-down reagents and the ExK DNA-2 kit for extraction showed that the samples were less inhibited (3.3%) than they were by the use of the liquid master mix (14.8%). Adoption of a cutoff threshold cycle of 35 for discrimination of vanB-positive samples allowed an increase of specificity to 87.9%. The performance of the BD Max VRE assay equaled that of the BD GeneOhm VanR assay, which was run in parallel. The use of dry-down reagents simplifies the assay and omits any need to handle liquid PCR reagents.

  7. Novel transparent electrodes allow sustainable production of electronic devices

    SciTech Connect

    Constant, Kristen

    2010-12-27

    -particle-count clean-room facilities and multimillion-dollar equipment. On the other hand, the novel process we developed uses a method that makes use of polymer molds and standard deposition techniques in an ambient laboratory environment. The final structure consists of tall ribbons of metal (standing on edge) that are so thin that they do not block light but are very good conductors. The advantage of this design is that it avoids the competition between conductivity and transparency inherent in transparent oxide electrodes. By making the structure taller, conductivity can be increased without impacting transparency. We have measured both electrical conductivity and transparency for these structures. We performed two-wire electrical measurements to quantify the structures resistance using metal contacts deposited on each end. The total sample area was 4 x 4mm{sup 2}. We measured a resistance of structures with 40nm gold sidewalls of 7.3{Omega}, which is lower than that of ITO glass (which has a sheet resistance around 10O/square). We investigated the structures optical properties based on both specular- and total-transmission measurements. Specular transmission is measured by collecting the transmitted light at normal incidence, while total transmission is obtained by collecting transmitted light at normal incidence and diffracted light using an integrating sphere. Figure 3 shows the total transmission of a grating with 40nm gold or silver sidewalls on a glass substrate compared to that of ITO. Additionally, the transparency changes very little within 30{sup o} off normal incidence. This high visible-light transmission of our metal-patterned structures is very promising for their application as transparent electrodes, because most visible light was allowed to propagate through the patterned metallic/polymeric structures. Researchers in our group continue to refine the fabrication methods and are investigating methods to make large-scale structures for use in a variety of

  8. 15 CFR 921.81 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Allowable costs. 921.81 Section 921.81... costs. (a) Allowable costs will be determined in accordance with applicable OMB Circulars and guidance... Department of Commerce and NOAA directives. The term “costs” applies to both the Federal and...

  9. 44 CFR 204.63 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... HOMELAND SECURITY DISASTER ASSISTANCE FIRE MANAGEMENT ASSISTANCE GRANT PROGRAM Grant Administration § 204.63 Allowable costs. 44 CFR 13.22 establishes general policies for determining allowable costs. (a) We will reimburse direct costs for the administration of a fire management assistance grant under 44...

  10. 38 CFR 3.954 - Burial allowance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Burial allowance. 3.954..., Compensation, and Dependency and Indemnity Compensation Protection § 3.954 Burial allowance. When any person who had a status under any law in effect on December 31, 1957, which afforded entitlement to...

  11. 38 CFR 3.954 - Burial allowance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Burial allowance. 3.954..., Compensation, and Dependency and Indemnity Compensation Protection § 3.954 Burial allowance. When any person who had a status under any law in effect on December 31, 1957, which afforded entitlement to...

  12. 38 CFR 3.954 - Burial allowance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Burial allowance. 3.954..., Compensation, and Dependency and Indemnity Compensation Protection § 3.954 Burial allowance. When any person who had a status under any law in effect on December 31, 1957, which afforded entitlement to...

  13. 38 CFR 3.954 - Burial allowance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Burial allowance. 3.954..., Compensation, and Dependency and Indemnity Compensation Protection § 3.954 Burial allowance. When any person who had a status under any law in effect on December 31, 1957, which afforded entitlement to...

  14. 38 CFR 3.954 - Burial allowance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Burial allowance. 3.954..., Compensation, and Dependency and Indemnity Compensation Protection § 3.954 Burial allowance. When any person who had a status under any law in effect on December 31, 1957, which afforded entitlement to...

  15. 30 CFR 725.21 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Allowable costs. 725.21 Section 725.21 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR INITIAL PROGRAM REGULATIONS REIMBURSEMENTS TO STATES § 725.21 Allowable costs. (a) The Director or his authorized...

  16. 30 CFR 735.24 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Allowable costs. 735.24 Section 735.24 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR PERMANENT... AND ENFORCEMENT § 735.24 Allowable costs. The Director or his authorized designee shall...

  17. 30 CFR 725.21 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Allowable costs. 725.21 Section 725.21 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR INITIAL PROGRAM REGULATIONS REIMBURSEMENTS TO STATES § 725.21 Allowable costs. (a) The Director or his authorized...

  18. 30 CFR 735.24 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Allowable costs. 735.24 Section 735.24 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR PERMANENT... AND ENFORCEMENT § 735.24 Allowable costs. The Director or his authorized designee shall...

  19. 20 CFR 631.84 - Allowable projects.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Allowable projects. 631.84 Section 631.84... THE JOB TRAINING PARTNERSHIP ACT Disaster Relief Employment Assistance § 631.84 Allowable projects...) Shall be used exclusively to provide employment on projects that provide food, clothing, shelter...

  20. 30 CFR 206.160 - Operating allowances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Operating allowances. 206.160 Section 206.160 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Federal Gas § 206.160 Operating allowances. Notwithstanding any other provisions...

  1. 20 CFR 632.258 - Allowable activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Allowable activities. 632.258 Section 632.258 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR INDIAN AND NATIVE AMERICAN EMPLOYMENT AND TRAINING PROGRAMS Summer Youth Employment and Training Programs § 632.258 Allowable...

  2. 28 CFR 100.11 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Allowable costs. 100.11 Section 100.11 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) COST RECOVERY REGULATIONS, COMMUNICATIONS ASSISTANCE FOR LAW ENFORCEMENT ACT OF 1994 § 100.11 Allowable costs. (a) Costs that are eligible...

  3. Moral Appraisals Affect Doing/Allowing Judgments

    ERIC Educational Resources Information Center

    Cushman, Fiery; Knobe, Joshua; Sinnott-Armstrong, Walter

    2008-01-01

    An extensive body of research suggests that the distinction between doing and allowing plays a critical role in shaping moral appraisals. Here, we report evidence from a pair of experiments suggesting that the converse is also true: moral appraisals affect doing/allowing judgments. Specifically, morally bad behavior is more likely to be construed…

  4. 44 CFR 13.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors but not any fee or profit (or other... of organization, there is a set of Federal principles for determining allowable costs....

  5. 13 CFR 143.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including... cost-type contractors but not any fee or profit (or other increment above allowable costs) to the grantee or subgrantee. (b) Applicable cost principles. For each kind of organization, there is a set...

  6. 36 CFR 1207.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors but not any fee or profit (or other... of organization, there is a set of Federal principles for determining allowable costs....

  7. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors...) Applicable cost principles. For each kind of organization, there is a set of Federal principles...

  8. 15 CFR 24.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors...) Applicable cost principles. For each kind of organization, there is a set of Federal principles...

  9. 32 CFR 33.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors but not any fee or profit (or other increment above allowable costs) to the grantee or subgrantee. (b) Applicable cost principles. For each kind of...

  10. 38 CFR 43.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors... profit to cost-type contractors but not any fee or profit (or other increment above allowable costs) to the grantee or subgrantee. (b) Applicable cost principles. For each kind of organization, there is...

  11. 28 CFR 66.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors...) Applicable cost principles. For each kind of organization, there is a set of Federal principles...

  12. 40 CFR 31.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... be used only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors... profit to cost-type contractors but not any fee or profit (or other increment above allowable costs) to the grantee or sub-grantee. (b) Applicable cost principles. For each kind of organization, there is...

  13. 45 CFR 92.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... only for: (1) The allowable costs of the grantees, subgrantees and cost-type contractors, including... cost-type contractors but not any fee or profit (or other increment above allowable costs) to the grantee or subgrantee. (b) Applicable cost principles. For each kind of organization, there is a set...

  14. 14 CFR 1273.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type.... (b) Applicable cost principles. For each kind of organization, there is a set of Federal...

  15. 20 CFR 631.84 - Allowable projects.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Allowable projects. 631.84 Section 631.84... THE JOB TRAINING PARTNERSHIP ACT Disaster Relief Employment Assistance § 631.84 Allowable projects...) Shall be used exclusively to provide employment on projects that provide food, clothing, shelter...

  16. 20 CFR 631.84 - Allowable projects.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Allowable projects. 631.84 Section 631.84... THE JOB TRAINING PARTNERSHIP ACT Disaster Relief Employment Assistance § 631.84 Allowable projects...) Shall be used exclusively to provide employment on projects that provide food, clothing, shelter...

  17. 30 CFR 1206.160 - Operating allowances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue PRODUCT VALUATION Federal Gas § 1206.160 Operating allowances. Notwithstanding any other provisions in these regulations, an operating allowance may be used for the purpose of computing...

  18. 30 CFR 1206.160 - Operating allowances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Federal Gas § 1206.160 Operating allowances. Notwithstanding any other provisions in these regulations, an operating allowance may be used for the purpose of computing...

  19. 21 CFR 1315.24 - Inventory allowance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Inventory allowance. 1315.24 Section 1315.24 Food... EPHEDRINE, PSEUDOEPHEDRINE, AND PHENYLPROPANOLAMINE Individual Manufacturing Quotas § 1315.24 Inventory... registered manufacturer shall be allowed as a part of the quota an amount sufficient to maintain an...

  20. 21 CFR 1303.24 - Inventory allowance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Inventory allowance. 1303.24 Section 1303.24 Food... Quotas § 1303.24 Inventory allowance. (a) For the purpose of determining individual manufacturing quotas... sufficient to maintain an inventory equal to, (1) For current manufacturers, 50 percent of his...

  1. 21 CFR 1315.24 - Inventory allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Inventory allowance. 1315.24 Section 1315.24 Food... EPHEDRINE, PSEUDOEPHEDRINE, AND PHENYLPROPANOLAMINE Individual Manufacturing Quotas § 1315.24 Inventory... registered manufacturer shall be allowed as a part of the quota an amount sufficient to maintain an...

  2. 21 CFR 1303.24 - Inventory allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Inventory allowance. 1303.24 Section 1303.24 Food... Quotas § 1303.24 Inventory allowance. (a) For the purpose of determining individual manufacturing quotas... sufficient to maintain an inventory equal to, (1) For current manufacturers, 50 percent of his...

  3. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Credit allowance. 28.334... OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  4. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Credit allowance. 28.334... OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  5. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Credit allowance. 28.334... OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  6. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Credit allowance. 28.334... OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  7. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Credit allowance. 28.334... OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  8. Allocation of Allowances and Associated Family Practices.

    ERIC Educational Resources Information Center

    Kerr, M. Kaye; Cheadle, Tannis

    This study gathered information on general family practices concerning allowances given to children, parental reasons for the provision of allowances, the bases for their administration, and the frequency of conflicts generated around them. The subjects were 81 parents of elementary school children in a midwest Canadian city. Subjects completed…

  9. 10 CFR 600.222 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Allowable costs. 600.222 Section 600.222 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS FINANCIAL ASSISTANCE RULES Uniform Administrative....222 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1)...

  10. 10 CFR 600.222 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Allowable costs. 600.222 Section 600.222 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS FINANCIAL ASSISTANCE RULES Uniform Administrative....222 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1)...

  11. Family Allowances and Fertility: Socioeconomic Differences

    PubMed Central

    SCHELLEKENS, JONA

    2009-01-01

    This article explores socioeconomic differences in the effect of family allowances on fertility. Although several studies have examined the relationship between cash benefits and fertility, few studies have addressed the possible differential effects of cash benefits on families of different income or education levels. I reconstructed the birth histories of women in the past two Israeli censuses of 1983 and 1995 to study socioeconomic differences in the effect of family allowances up to the seventh parity. The results indicate that family allowances have a significant effect at every parity. Using female education as an indicator of socioeconomic status, I find that socioeconomic status is a significant modifier of the effect of family allowances. Family allowances seem to have a relatively large impact on more-educated women. PMID:19771939

  12. TaADF4, an actin-depolymerizing factor from wheat, is required for resistance to the stripe rust pathogen Puccinia striiformis f. sp. tritici.

    PubMed

    Zhang, Bing; Hua, Yuan; Wang, Juan; Huo, Yan; Shimono, Masaki; Day, Brad; Ma, Qing

    2017-03-01

    Actin filament assembly in plants is a dynamic process, requiring the activity of more than 75 actin-binding proteins. Central to the regulation of filament assembly and stability is the activity of a conserved family of actin-depolymerizing factors (ADFs), whose primarily function is to regulate the severing and depolymerization of actin filaments. In recent years, the activity of ADF proteins has been linked to a variety of cellular processes, including those associated with response to stress. Herein, a wheat ADF gene, TaADF4, was identified and characterized. TaADF4 encodes a 139-amino-acid protein containing five F-actin-binding sites and two G-actin-binding sites, and interacts with wheat (Triticum aestivum) Actin1 (TaACT1), in planta. Following treatment of wheat, separately, with jasmonic acid, abscisic acid or with the avirulent race, CYR23, of the stripe rust pathogen Puccinia striiformis f. sp. tritici, we observed a rapid induction in accumulation of TaADF4 mRNA. Interestingly, accumulation of TaADF4 mRNA was diminished in response to inoculation with a virulent race, CYR31. Silencing of TaADF4 resulted in enhanced susceptibility to CYR23, demonstrating a role for TaADF4 in defense signaling. Using a pharmacological-based approach, coupled with an analysis of host response to pathogen infection, we observed that treatment of plants with the actin-modifying agent latrunculin B enhanced resistance to CYR23, including increased production of reactive oxygen species and enhancement of localized hypersensitive cell death. Taken together, these data support the hypothesis that TaADF4 positively modulates plant immunity in wheat via the modulation of actin cytoskeletal organization.

  13. Allowance Holdings and Transfers Data Inventory

    EPA Pesticide Factsheets

    The Allowance Holdings and Transfers Data Inventory contains measured data on holdings and transactions of allowances under the NOx Budget Trading Program (NBP), a market-based cap and trade program created to reduce the regional transport of NOx emissions from power plants and other large combustion sources that contribute to ozone nonattainment.The statutory authority leading to the collection of this information comes from Title V of the Clean Air Act. Sustance classes include SO2 and NOx. Data of allowance holdings and transfers are made available in real time.

  14. 38 CFR 3.810 - Clothing allowance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... a wheelchair) because of such disability and such disability is the loss or loss of use of a hand or... wheelchair. (b) Effective August 1, 1972, the initial lump sum clothing allowance is due and payable...

  15. 10 CFR 600.317 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... organization is determined as follows: (i) Institutions of higher education. Allowability is determined in... prior approval of the contracting officer, DOE may pay those costs incurred within the ninety...

  16. 10 CFR 600.317 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... organization is determined as follows: (i) Institutions of higher education. Allowability is determined in... prior approval of the contracting officer, DOE may pay those costs incurred within the ninety...

  17. 10 CFR 600.317 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... organization is determined as follows: (i) Institutions of higher education. Allowability is determined in... prior approval of the contracting officer, DOE may pay those costs incurred within the ninety...

  18. 10 CFR 600.317 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... organization is determined as follows: (i) Institutions of higher education. Allowability is determined in... prior approval of the contracting officer, DOE may pay those costs incurred within the ninety...

  19. 20 CFR 632.37 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... EMPLOYMENT AND TRAINING PROGRAMS Administrative Standards and Procedures § 632.37 Allowable costs. (a... or consortium administrative entity for the purpose of carrying out programs under the Act....

  20. Regulatory treatment of allowances and compliance costs

    SciTech Connect

    Rose, K.

    1993-07-01

    The Clean Air Act Amendments of 1990 (CAAA) established a national emission allowance trading system, a market-based form of environmental regulation designed to reduce and limit sulfur dioxide emissions. However, the allowance trading system is being applied primarily to an economically regulated electric utility industry. The combining of the new form of environmental regulation and economic regulation of electric utilities has raised a number of questions including what the role should be of the federal and state utility regulating commissions and how those actions will affect the decision making process of the utilities and the allowance market. There are several dimensions to the regulatory problems that commissions face. Allowances and utility compliance expenditures have implications for least-cost/IPR (integrated resource planning), prudence review procedures, holding company and multistate utility regulation and ratemaking treatment. The focus of this paper is on the ratemaking treatment. The following topics are covered: ratemaking treatment of allowances and compliance costs; Traditional cost-recovery mechanisms; limitations to the traditional approach; traditional approach and the allowance trading market; market-based cost recovery mechanisms; methods of determining the benchmark; determining the split between ratepayers and the utility; other regulatory approaches; limitations of incentive mechanisms.

  1. 9 CFR 53.10 - Claims not allowed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Claims not allowed. 53.10 Section 53.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... complied with all quarantine requirements. (b) Expenses for the care and feeding of animals held...

  2. 9 CFR 53.10 - Claims not allowed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Claims not allowed. 53.10 Section 53.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... complied with all quarantine requirements. (b) Expenses for the care and feeding of animals held...

  3. 9 CFR 53.10 - Claims not allowed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Claims not allowed. 53.10 Section 53.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... complied with all quarantine requirements. (b) Expenses for the care and feeding of animals held...

  4. 9 CFR 53.10 - Claims not allowed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Claims not allowed. 53.10 Section 53.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... complied with all quarantine requirements. (b) Expenses for the care and feeding of animals held...

  5. 9 CFR 53.10 - Claims not allowed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Claims not allowed. 53.10 Section 53.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... complied with all quarantine requirements. (b) Expenses for the care and feeding of animals held...

  6. Salicylic acid is required for Mi-1-mediated resistance of tomato to whitefly Bemisia tabaci, but not for basal defense to this insect pest.

    PubMed

    Rodríguez-Álvarez, C I; López-Climent, M F; Gómez-Cadenas, A; Kaloshian, I; Nombela, G

    2015-10-01

    Plant defense to pests or pathogens involves global changes in gene expression mediated by multiple signaling pathways. A role for the salicylic acid (SA) signaling pathway in Mi-1-mediated resistance of tomato (Solanum lycopersicum) to aphids was previously identified and its implication in the resistance to root-knot nematodes is controversial, but the importance of SA in basal and Mi-1-mediated resistance of tomato to whitefly Bemisia tabaci had not been determined. SA levels were measured before and after B. tabaci infestation in susceptible and resistant Mi-1-containing tomatoes, and in plants with the NahG bacterial transgene. Tomato plants of the same genotypes were also screened with B. tabaci (MEAM1 and MED species, before known as B and Q biotypes, respectively). The SA content in all tomato genotypes transiently increased after infestation with B. tabaci albeit at variable levels. Whitefly fecundity or infestation rates on susceptible Moneymaker were not significantly affected by the expression of NahG gene, but the Mi-1-mediated resistance to B. tabaci was lost in VFN NahG plants. Results indicated that whiteflies induce both SA and jasmonic acid accumulation in tomato. However, SA has no role in basal defense of tomato against B. tabaci. In contrast, SA is an important component of the Mi-1-mediated resistance to B. tabaci in tomato.

  7. 20 CFR 437.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 437... the applicable cost principles. For the costs of a— Use the principles in— (1) State, local or...

  8. 20 CFR 437.22 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 437... the applicable cost principles. For the costs of a— Use the principles in— (1) State, local or...

  9. 20 CFR 437.22 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 437... the applicable cost principles. For the costs of a— Use the principles in— (1) State, local or...

  10. 20 CFR 437.22 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 437... the applicable cost principles. For the costs of a— Use the principles in— (1) State, local or...

  11. Increase in tartrate-resistant acid phosphatase of bone at the early stage of ascorbic acid deficiency in the ascorbate-requiring Osteogenic Disorder Shionogi (ODS) rat.

    PubMed

    Goto, A; Tsukamoto, I

    2003-08-01

    The effect of ascorbic acid deficiency on bone metabolism was evaluated using the ascorbate-requiring Osteogenic Disorder Shionogi (ODS) rat model. Ascorbic acid (Asc)-deficient rats gained body weight in a manner similar to Asc-supplemented rats (control) during 3 weeks, but began to lose weight during the 4th week of Asc deficiency. The tartrate-resistant acid phosphatase (TRAP) activity in serum increased to about 2-fold the control value in the rats fed the Asc-free diet for 2, 3, and 4 weeks (AscD2, AscD3, and AscD4), while a decrease in the alkaline phosphatase (ALP) activity was observed only in AscD4 rats. The serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) level significantly increased to 1.3-, 1.4-, and 1.9-fold of that in the controls in AscD2, D3, and D4, respectively. The ALP activity in the distal femur was unchanged in AscD1, D2, and D3, but decreased to 50% of the control level in AscD4 rats. The TRAP activity in the distal femur increased to about 2-fold of that in the controls in the AscD2 and D3 and decreased to the control level in the AscD4 rats. The amount of hydroxyproline in the distal femur significantly decreased to about 80%, 70%, and 60% of the control in AscD2, D3, and D4 rats, respectively. These decreases were associated with a similar reduction in the calcium content of the distal femur. Histochemical analysis of the distal femur showed an increase in TRAP-positive cells in AscD2 and AscD3 rats and a decrease in the trabecular bone in AscD2, D3, and D4 rats. These results suggested that a deficiency of Asc stimulated bone resorption at an early stage, followed by a decrease in bone formation in mature ODS rats which already had a well-developed collagen matrix and fully differentiated osteoblasts.

  12. 33 CFR 136.229 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.229 Section 136.229 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  13. 33 CFR 136.211 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.211 Section 136.211 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  14. 33 CFR 136.235 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.235 Section 136.235 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  15. 33 CFR 136.205 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.205 Section 136.205 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  16. 33 CFR 136.223 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.223 Section 136.223 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  17. 33 CFR 136.217 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.217 Section 136.217 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  18. 15 CFR 14.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, OTHER NON-PROFIT, AND COMMERCIAL... Organizations.” The allowability of costs incurred by institutions of higher education is determined in... CFR part 74, “Principles for Determining Costs Applicable to Research and Development Under Grants...

  19. 38 CFR 3.810 - Clothing allowance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... prosthetic or orthopedic appliance (including, but not limited to, a wheelchair) which tends to wear or tear... appliance (including, but not limited to, a wheelchair) which tends to wear or tear clothing; or (B) A... allowance for each prosthetic or orthopedic appliance (including, but not limited to, a wheelchair)...

  20. 44 CFR 208.41 - Administrative allowance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Administrative allowance. 208.41 Section 208.41 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE NATIONAL URBAN SEARCH AND RESCUE RESPONSE SYSTEM...

  1. 34 CFR 675.33 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false Allowable costs. 675.33 Section 675.33 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL WORK-STUDY PROGRAMS Job Location and Development Program § 675.33...

  2. 34 CFR 675.33 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false Allowable costs. 675.33 Section 675.33 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL WORK-STUDY PROGRAMS Job Location and Development Program § 675.33...

  3. 34 CFR 675.33 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false Allowable costs. 675.33 Section 675.33 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL WORK-STUDY PROGRAMS Job Location and Development Program § 675.33...

  4. 44 CFR 208.33 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Allowable costs. 208.33 Section 208.33 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... sets out in this subpart. (d) Indirect costs. Indirect costs beyond the administrative and...

  5. 44 CFR 79.8 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Allowable costs. 79.8 Section... Management Costs—(i) Grantee. States are eligible to receive management costs consisting of a maximum of 10... directly to FEMA is eligible for management costs consisting of a maximum of 10 percent of grants...

  6. 44 CFR 79.8 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Allowable costs. 79.8 Section... Management Costs—(i) Grantee. States are eligible to receive management costs consisting of a maximum of 10... directly to FEMA is eligible for management costs consisting of a maximum of 10 percent of grants...

  7. 44 CFR 206.439 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Allowable costs. 206.439 Section 206.439 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... section. (b) Administrative and management costs for major disasters will be paid in accordance with...

  8. 44 CFR 79.8 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Allowable costs. 79.8 Section... Management Costs—(i) Grantee. States are eligible to receive management costs consisting of a maximum of 10... directly to FEMA is eligible for management costs consisting of a maximum of 10 percent of grants...

  9. 44 CFR 206.228 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Allowable costs. 206.228 Section 206.228 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF.... (3) Administrative and management costs for major disasters and emergencies will be paid...

  10. 44 CFR 206.439 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Allowable costs. 206.439 Section 206.439 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... section. (b) Administrative and management costs for major disasters will be paid in accordance with...

  11. 44 CFR 79.8 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Allowable costs. 79.8 Section... Management Costs—(i) Grantee. States are eligible to receive management costs consisting of a maximum of 10... directly to FEMA is eligible for management costs consisting of a maximum of 10 percent of grants...

  12. 44 CFR 208.33 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Allowable costs. 208.33 Section 208.33 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... sets out in this subpart. (d) Indirect costs. Indirect costs beyond the administrative and...

  13. 44 CFR 206.439 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Allowable costs. 206.439 Section 206.439 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... section. (b) Administrative and management costs for major disasters will be paid in accordance with...

  14. 44 CFR 206.228 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Allowable costs. 206.228 Section 206.228 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF.... (3) Administrative and management costs for major disasters and emergencies will be paid...

  15. 44 CFR 79.8 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs. 79.8 Section... Management Costs—(i) Grantee. States are eligible to receive management costs consisting of a maximum of 10... directly to FEMA is eligible for management costs consisting of a maximum of 10 percent of grants...

  16. 44 CFR 208.33 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Allowable costs. 208.33 Section 208.33 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... sets out in this subpart. (d) Indirect costs. Indirect costs beyond the administrative and...

  17. 44 CFR 208.33 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs. 208.33 Section 208.33 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... sets out in this subpart. (d) Indirect costs. Indirect costs beyond the administrative and...

  18. 44 CFR 208.33 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Allowable costs. 208.33 Section 208.33 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... sets out in this subpart. (d) Indirect costs. Indirect costs beyond the administrative and...

  19. 44 CFR 206.439 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Allowable costs. 206.439 Section 206.439 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... section. (b) Administrative and management costs for major disasters will be paid in accordance with...

  20. 44 CFR 206.439 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs. 206.439 Section 206.439 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... section. (b) Administrative and management costs for major disasters will be paid in accordance with...

  1. 21 CFR 1303.24 - Inventory allowance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... estimated net disposal for the current calendar year and the last preceding calendar year; or (2) For new manufacturers, 50 percent of his reasonably estimated net disposal for the next calendar year as determined by the Administrator. (b) During each calendar year each registered manufacturer shall be allowed...

  2. 42 CFR 417.534 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... typical “provider” costs, and costs (such as marketing, enrollment, membership, and operation of the HMO... principles applicable to provider costs, as set forth in § 417.536. (2) The allowability of other costs is determined in accordance with principles set forth in §§ 417.538 through 417.550. (3) Costs for...

  3. 20 CFR 633.303 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., or committee for section 402 program purposes, and reimbursement of actual expenses connected with... grantee per quarter. (2) Allowances and loss of wages. Any individual or family member who is a member of... family income does not exceed either 70 percent of the lower living standard income level or the...

  4. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Allowable costs. 304.21 Section 304.21 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION SERVICE OBLIGATIONS UNDER SPECIAL...

  5. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false Allowable costs. 304.21 Section 304.21 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION SERVICE OBLIGATIONS UNDER SPECIAL...

  6. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true Allowable costs. 304.21 Section 304.21 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION SERVICE OBLIGATIONS UNDER SPECIAL...

  7. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Development Under Grants and Contracts with Hospitals.” The allowability of costs incurred by commercial... with their normal travel reimbursement practices. Contracts with firms for services which are awarded... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE...

  8. 33 CFR 136.223 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.223 Section 136.223 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.223...

  9. 33 CFR 136.217 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.217 Section 136.217 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.217...

  10. 33 CFR 136.241 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.241 Section 136.241 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.241...

  11. 33 CFR 136.235 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.235 Section 136.235 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.235...

  12. 33 CFR 136.205 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.205 Section 136.205 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.205...

  13. 33 CFR 136.229 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.229 Section 136.229 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.229...

  14. 33 CFR 136.211 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.211 Section 136.211 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.211...

  15. 29 CFR 15.22 - Allowable claims.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... service with the Department and: (l) The damage or loss was not caused wholly or partly by the negligent... the other provisions of this subpart, any claim for damage to, or loss, of personal property incident... authorized places. Claims may be allowable for damage to, or loss of, property arising from fire,...

  16. 20 CFR 632.37 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Allowable costs. 632.37 Section 632.37 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR INDIAN AND NATIVE AMERICAN... applicable State and local law, rules or regulations as determined by the Native American grantee. (b)...

  17. 22 CFR 135.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors but not any fee or profit... principles. For each kind of organization, there is a set of Federal principles for determining...

  18. 15 CFR 921.81 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Allowable costs. 921.81 Section 921.81 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC... program in either the current or a prior award period. (d) General guidelines for the non-Federal...

  19. 29 CFR 15.41 - Allowable claims.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Arising Out of the Operation of the Job Corps § 15.41 Allowable claims. (a)(1) A claim for damage to persons or property arising out of an act or omission of a student enrolled in the Job Corps may...

  20. 45 CFR 34.4 - Allowable claims.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the claimant to save human life or government property. (4) Property used for the benefit of the... 45 Public Welfare 1 2011-10-01 2011-10-01 false Allowable claims. 34.4 Section 34.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CLAIMS FILED UNDER THE MILITARY PERSONNEL...

  1. 45 CFR 34.4 - Allowable claims.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the claimant to save human life or government property. (4) Property used for the benefit of the... 45 Public Welfare 1 2010-10-01 2010-10-01 false Allowable claims. 34.4 Section 34.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CLAIMS FILED UNDER THE MILITARY PERSONNEL...

  2. 33 CFR 136.211 - Compensation allowable.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Compensation allowable. 136.211 Section 136.211 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  3. 33 CFR 136.229 - Compensation allowable.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Compensation allowable. 136.229 Section 136.229 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  4. 33 CFR 136.211 - Compensation allowable.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Compensation allowable. 136.211 Section 136.211 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  5. 33 CFR 136.241 - Compensation allowable.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Compensation allowable. 136.241 Section 136.241 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  6. 33 CFR 136.229 - Compensation allowable.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Compensation allowable. 136.229 Section 136.229 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  7. 33 CFR 136.211 - Compensation allowable.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Compensation allowable. 136.211 Section 136.211 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  8. 33 CFR 136.223 - Compensation allowable.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Compensation allowable. 136.223 Section 136.223 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  9. 33 CFR 136.205 - Compensation allowable.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Compensation allowable. 136.205 Section 136.205 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  10. 33 CFR 136.217 - Compensation allowable.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Compensation allowable. 136.217 Section 136.217 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  11. 33 CFR 136.229 - Compensation allowable.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Compensation allowable. 136.229 Section 136.229 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  12. 33 CFR 136.205 - Compensation allowable.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Compensation allowable. 136.205 Section 136.205 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  13. 33 CFR 136.217 - Compensation allowable.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Compensation allowable. 136.217 Section 136.217 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  14. 33 CFR 136.241 - Compensation allowable.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Compensation allowable. 136.241 Section 136.241 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  15. 33 CFR 136.235 - Compensation allowable.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Compensation allowable. 136.235 Section 136.235 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  16. 33 CFR 136.241 - Compensation allowable.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Compensation allowable. 136.241 Section 136.241 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  17. 33 CFR 136.223 - Compensation allowable.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Compensation allowable. 136.223 Section 136.223 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  18. 33 CFR 136.205 - Compensation allowable.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Compensation allowable. 136.205 Section 136.205 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  19. 33 CFR 136.241 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.241 Section 136.241 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  20. 33 CFR 136.223 - Compensation allowable.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Compensation allowable. 136.223 Section 136.223 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...