Science.gov

Sample records for adp program snap

  1. The ORNL-SNAP shielding program

    NASA Technical Reports Server (NTRS)

    Mynatt, F. R.; Clifford, C. E.; Muckenthaler, F. J.; Gritzner, M. L.

    1972-01-01

    The effort in the ORNL-SNAP shielding program is directed toward the development and verification of computer codes using numerical solutions to the transport equation for the design of optimized radiation shields for SNAP power systems. A brief discussion is given for the major areas of the SNAP shielding program, which are cross-section development, transport code development, and integral experiments. Detailed results are presented for the integral experiments utilizing the TSF-SNAP reactor. Calculated results are compared with experiments for neutron and gamma-ray spectra from the bare reactor and as transmitted through slab shields.

  2. SNAP-8 electrical generating system development program

    NASA Technical Reports Server (NTRS)

    1971-01-01

    The SNAP-8 program has developed the technology base for one class of multikilowatt dynamic space power systems. Electrical power is generated by a turbine-alternator in a mercury Rankine-cycle loop to which heat is transferred and removed by means of sodium-potassium eutectic alloy subsystems. Final system overall criteria include a five-year operating life, restartability, man rating, and deliverable power in the 90 kWe range. The basic technology was demonstrated by more than 400,000 hours of major component endurance testing and numerous startup and shutdown cycles. A test system, comprised of developed components, delivered up to 35 kWe for a period exceeding 12,000 hours. The SNAP-8 system baseline is considered to have achieved a level of technology suitable for final application development for long-term multikilowatt space missions.

  3. SNAP: A computer program for generating symbolic network functions

    NASA Technical Reports Server (NTRS)

    Lin, P. M.; Alderson, G. E.

    1970-01-01

    The computer program SNAP (symbolic network analysis program) generates symbolic network functions for networks containing R, L, and C type elements and all four types of controlled sources. The program is efficient with respect to program storage and execution time. A discussion of the basic algorithms is presented, together with user's and programmer's guides.

  4. Creating a Minnesota Statewide SNAP-Ed Program Evaluation

    ERIC Educational Resources Information Center

    Gold, Abby; Barno, Trina Adler; Sherman, Shelley; Lovett, Kathleen; Hurtado, G. Ali

    2013-01-01

    Systematic evaluation is an essential tool for understanding program effectiveness. This article describes the pilot test of a statewide evaluation tool for the Supplemental Nutrition Assistance Program-Education (SNAP-Ed). A computer algorithm helped Community Nutrition Educators (CNEs) build surveys specific to their varied educational settings…

  5. SNAP-8 refractory boiler development program

    NASA Technical Reports Server (NTRS)

    Fuller, R. A.

    1974-01-01

    Performance and endurance tests of the SNAP-8, SN-1 refractory metal boiler are described. The tests were successful and indicated that the boiler heat transfer area could be reduced significantly primarily because of the wetting characteristics of mercury on tantalum in a contaminant-free environment. A continuous endurance test of more than 10,000 hours was conducted without noticeable change in the thermal performance of the boiler. A conclusion of the metallographic examination of the boiler following the endurance test was that expected boiler life would be of the order of 40,000 hours at observed corrosion rates.

  6. 78 FR 52899 - Supplemental Nutrition Assistance Program (SNAP) Enhancing Retail Food Store Eligibility...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-27

    ... Food and Nutrition Service Supplemental Nutrition Assistance Program (SNAP) Enhancing Retail Food Store Eligibility--Listening Sessions AGENCY: Food and Nutrition Service (FNS), USDA. ACTION: Notice. SUMMARY: This... regarding Supplemental Nutrition Assistance Program (SNAP) retailer eligibility requirements (78 FR...

  7. SNAP Employment and Training: Washington's Basic Food Employment & Training Program (BFET)

    ERIC Educational Resources Information Center

    Mohan, Lavanya

    2014-01-01

    SNAP Employment & Training (E&T) is an important component of SNAP (Supplemental Nutrition Assistance Program, formerly known as the Food Stamp Program) that supports a variety of education, training, employment, and related services for SNAP recipients. It gives recipients opportunities to gain skills, training, or experience that will…

  8. SNAP-27/ALSEP power subsystem used in the Apollo program.

    NASA Technical Reports Server (NTRS)

    Remini, W. C.; Grayson, J. H.

    1972-01-01

    The Apollo Lunar Surface Experiments Package (ALSEP) measures lunar physical and environmental characteristics and transmits the data to receiving stations on earth. The data are used to derive information on the composition and structure of the moon. The electrical power subsystem generates and conditions all the electrical power for operations of the ALSEP system. The power source for the ALSEP is the Systems for Nuclear Auxiliary Power (SNAP) Radioisotope Thermoelectric Generator (RTG). The generator produces electricity by thermoelectric conversion. The radioactive isotope plutonium 238 is used as the energy source for the SNAP-27. By April 1, 1970, the SNAP-27 RTG had produced more than 230 kWh of continuous and stable power for the ALSEP.-

  9. 75 FR 78151 - Supplemental Nutrition Assistance Program (SNAP): Clarifications and Corrections to Recipient...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-15

    ... / Wednesday, December 15, 2010 / Rules and Regulations#0;#0; ] DEPARTMENT OF AGRICULTURE Food and Nutrition Service 7 CFR Parts 271, 272, 273, and 276 RIN 0584-AD25 Supplemental Nutrition Assistance Program (SNAP... Nutrition Service, USDA. ACTION: Final rule. SUMMARY: Supplemental Nutrition Assistance Program...

  10. 78 FR 11967 - Supplemental Nutrition Assistance Program (SNAP): Updated Trafficking Definition and Supplemental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-21

    ... / Thursday, February 21, 2013 / Rules and Regulations#0;#0; ] DEPARTMENT OF AGRICULTURE Food and Nutrition Service 7 CFR Parts 271, 273, and 281 RIN 0584-AD97 Supplemental Nutrition Assistance Program (SNAP): Updated Trafficking Definition and Supplemental Nutrition Assistance Program-- Food Distribution...

  11. 78 FR 12245 - Supplemental Nutrition Assistance Program: Suspension of SNAP Benefit Payments to Retailers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ...; ] DEPARTMENT OF AGRICULTURE Food and Nutrition Service 7 CFR Part 278 RIN 0584-AE22 Supplemental Nutrition Assistance Program: Suspension of SNAP Benefit Payments to Retailers AGENCY: Food and Nutrition Service (FNS), USDA. ACTION: Proposed rule. SUMMARY: Integrity in the Supplemental Nutrition Assistance Program...

  12. SNAP E&T

    ERIC Educational Resources Information Center

    Lower-Basch, Elizabeth

    2014-01-01

    This document provides an overview of Supplemental Nutrition Assistance Program Employment and Training (SNAP E&T). SNAP E&T is a funding source that allows states to provide employment and training and related supportive services to individuals receiving Supplemental Nutrition Assistance Program (SNAP, formerly known as food stamps)…

  13. 76 FR 27603 - Supplemental Nutrition Assistance Program: Civil Rights Protections for SNAP Households

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-12

    ... / Thursday, May 12, 2011 / Rules and Regulations#0;#0; ] DEPARTMENT OF AGRICULTURE Food and Nutrition Service 7 CFR Parts 271 and 272 RIN 0584-AD89 Supplemental Nutrition Assistance Program: Civil Rights Protections for SNAP Households AGENCY: Food and Nutrition Service, USDA. ACTION: Final rule. SUMMARY:...

  14. The Relationship Between Obesity and Participation in the Supplemental Nutrition Assistance Program (SNAP): Is Mental Health a Mediator?

    PubMed Central

    CHAPARRO, M. PIA; HARRISON, GAIL G.; PEBLEY, ANNE R.; WANG, MAY

    2015-01-01

    Focusing on adults from the Los Angeles Family and Neighborhood Survey, we investigated whether mental health was a mediator in the association between obesity (body mass index ≥ 30 kg/m2) and participation in the Supplemental Nutrition Assistance Program (SNAP). The analyses included 1776 SNAP participants and eligible nonparticipants. SNAP participants had higher odds of obesity (odds ratio [OR] =2.6; 95% confidence interval [CI], 1.52–4.36) and of reporting a mental health problem (OR = 3.8; 95% CI, 1.68–8.44) than eligible nonparticipants; however, mental health was not a mediator in the association between SNAP participation and obesity. We recommend changes in SNAP to promote healthier food habits among participants and reduce the stress associated with participation. PMID:26413180

  15. The Relationship Between Obesity and Participation in the Supplemental Nutrition Assistance Program (SNAP): Is Mental Health a Mediator?

    PubMed

    Chaparro, M Pia; Harrison, Gail G; Pebley, Anne R; Wang, May

    2014-10-01

    Focusing on adults from the Los Angeles Family and Neighborhood Survey, we investigated whether mental health was a mediator in the association between obesity (body mass index ≥ 30 kg/m(2)) and participation in the Supplemental Nutrition Assistance Program (SNAP). The analyses included 1776 SNAP participants and eligible nonparticipants. SNAP participants had higher odds of obesity (odds ratio [OR] =2.6; 95% confidence interval [CI], 1.52-4.36) and of reporting a mental health problem (OR = 3.8; 95% CI, 1.68-8.44) than eligible nonparticipants; however, mental health was not a mediator in the association between SNAP participation and obesity. We recommend changes in SNAP to promote healthier food habits among participants and reduce the stress associated with participation.

  16. A qualitative study of diverse experts' views about barriers and strategies to improve the diets and health of Supplemental Nutrition Assistance Program (SNAP) beneficiaries.

    PubMed

    Leung, Cindy W; Hoffnagle, Elena E; Lindsay, Ana C; Lofink, Hayley E; Hoffman, Vanessa A; Turrell, Sophie; Willett, Walter C; Blumenthal, Susan J

    2013-01-01

    The Supplemental Nutrition Assistance Program (SNAP), the largest federal food assistance program, currently serves 44.7 million Americans with a budget of $75 billion in 2011. This study engaged leading experts for in-depth, semi-structured interviews to explore their opinions concerning the existing challenges and barriers to eating nutritiously in SNAP. Experts also proposed strategies for improving nutritional status among SNAP recipients. Twenty-seven individuals were interviewed from advocacy, government, industry, and research organizations. Interviews were recorded, transcribed, coded, and analyzed for thematic content. The high cost of nutrient-rich foods, inadequate SNAP benefits, limited access to purchasing healthy foods, and environmental factors associated with poverty were identified as barriers that influence nutrition among low-income households in the United States. Six themes emerged among respondents from diverse sectors about how to address these challenges, including providing SNAP participants with incentives to purchase nutrient-rich food consistent with the 2010 Dietary Guidelines for Americans, restricting the purchase of nutrient-poor foods and beverages with program benefits, modifying the frequency of SNAP benefit distribution, enhancing nutrition education, improving the SNAP retailer environment, and increasing state and federal level coordination and consistency of program implementation. Given the recent dramatic increase in SNAP enrollment, policymakers must address existing barriers as well as consider new strategies to improve nutrition policies in SNAP so that the program can continue to address food insecurity needs as well as provide a healthful diet for SNAP beneficiaries.

  17. A Qualitative Study of Diverse Experts’ Views About Barriers and Strategies to Improve the Diets and Health of Supplemental Nutrition Assistance Program (SNAP) Beneficiaries

    PubMed Central

    Leung, Cindy W.; Hoffnagle, Elena E.; Lindsay, Ana C.; Lofink, Hayley E.; Hoffman, Vanessa A.; Turrell, Sophie; Willett, Walter C.; Blumenthal, Susan J.

    2012-01-01

    The Supplemental Nutrition Assistance Program (SNAP), the largest federal food assistance program, currently serves 44.7 million Americans with a budget of $75 billion in 2011. This study engaged leading experts for in-depth, semi-structured interviews to explore their opinions concerning the existing challenges and barriers to eating nutritiously in SNAP. Experts also proposed strategies for improving nutritional status among SNAP recipients. Twenty-seven individuals were interviewed from advocacy, government, industry, and research organizations. Interviews were recorded, transcribed, coded and analyzed for thematic content. The high cost of nutrient-rich foods, inadequate SNAP benefits, limited access to purchasing healthy foods, and environmental factors associated with poverty were identified as barriers that influence nutrition among low-income households in the United States. Six themes emerged among respondents from diverse sectors about how to address these challenges including: 1) providing SNAP participants with incentives to purchase nutrient-rich food consistent with the 2010 Dietary Guidelines for Americans; 2) restricting the purchase of nutrient-poor foods and beverages with program benefits; 3) modifying the frequency of SNAP benefit distribution; 4) enhancing nutrition education; 5) improving the SNAP retailer environment and 6) increasing state and federal level coordination and consistency of program implementation. Given the recent dramatic increase in SNAP enrollment, policymakers must address existing barriers as well as consider new strategies to improve nutrition policies in SNAP so that the program can continue to address food insecurity needs as well as provide a healthful diet for SNAP beneficiaries. PMID:23260725

  18. Associations between food insecurity, supplemental nutrition assistance program (SNAP) benefits, and body mass index among adult females.

    PubMed

    Jilcott, Stephanie B; Wall-Bassett, Elizabeth D; Burke, Sloane C; Moore, Justin B

    2011-11-01

    Obesity disproportionately affects low-income and minority individuals and has been linked with food insecurity, particularly among women. More research is needed to examine potential mechanisms linking obesity and food insecurity. Therefore, this study's purpose was to examine cross-sectional associations between food insecurity, Supplemental Nutrition Assistance Program (SNAP) benefits per household member, perceived stress, and body mass index (BMI) among female SNAP participants in eastern North Carolina (n=202). Women were recruited from the Pitt County Department of Social Services between October 2009 and April 2010. Household food insecurity was measured using the validated US Department of Agriculture 18-item food security survey module. Perceived stress was measured using the 14-item Cohen's Perceived Stress Scale. SNAP benefits and number of children in the household were self-reported and used to calculate benefits per household member. BMI was calculated from measured height and weight (as kg/m(2)). Multivariate linear regression was used to examine associations between BMI, SNAP benefits, stress, and food insecurity while adjusting for age and physical activity. In adjusted linear regression analyses, perceived stress was positively related to food insecurity (P<0.0001), even when SNAP benefits were included in the model. BMI was positively associated with food insecurity (P=0.04). Mean BMI was significantly greater among women receiving <$150 in SNAP benefits per household member vs those receiving ≥$150 in benefits per household member (35.8 vs 33.1; P=0.04). Results suggest that provision of adequate SNAP benefits per household member might partially ameliorate the negative effects of food insecurity on BMI.

  19. The SNAP[TM] Under 12 Outreach Project: Effects of a Community Based Program for Children with Conduct Problems

    ERIC Educational Resources Information Center

    Augimeri, Leena K.; Farrington, David P.; Koegl, Christopher J.; Day, David M.

    2007-01-01

    We examined the immediate, short- and long-term effectiveness of the SNAP[TM] Under 12 Outreach Project (ORP)--a community-based program for children under the age of 12 at risk of having police contact. Sixteen pairs of children were matched on age, sex and severity of delinquency at admission, and randomly assigned to the ORP or to a control…

  20. Development of an ADP Training Program to Serve the EPA Data Processing Community.

    DTIC Science & Technology

    1976-07-29

    package and interprCLing output. CLASS SIZE: 10 - 15 COURSE OFFERING LOCATION Any EPA office or lab with access to a computing facility which runs the BMI ...Rort rc:_ EPA Contract-#-68-O1-3357 < PDevelopment of an ADP Training Program to Serve the EPA Data Processing Community: Submitted to Prepared by Mr...Street Technical Operations Branch Alexandria, Virginia 22314 EPA /WSH Washington, DC 20460 ClI- LU Jul-,219, 1976 -- ADVANCED COBOL TARGET AUDIENCE To

  1. SNAP Telescope

    NASA Astrophysics Data System (ADS)

    Lampton, Michael L.; Akerlof, Carl W.; Aldering, Greg; Amanullah, R.; Astier, Pierre; Barrelet, E.; Bebek, Christopher; Bergstrom, Lars; Bercovitz, John; Bernstein, G.; Bester, Manfred; Bonissent, Alain; Bower, C. R.; Carithers, William C., Jr.; Commins, Eugene D.; Day, C.; Deustua, Susana E.; DiGennaro, Richard S.; Ealet, Anne; Ellis, Richard S.; Eriksson, Mikael; Fruchter, Andrew; Genat, Jean-Francois; Goldhaber, Gerson; Goobar, Ariel; Groom, Donald E.; Harris, Stewart E.; Harvey, Peter R.; Heetderks, Henry D.; Holland, Steven E.; Huterer, Dragan; Karcher, Armin; Kim, Alex G.; Kolbe, William F.; Krieger, B.; Lafever, R.; Lamoureux, J.; Levi, Michael E.; Levin, Daniel S.; Linder, Eric V.; Loken, Stewart C.; Malina, Roger; Massey, R.; McKay, Timothy; McKee, Shawn P.; Miquel, Ramon; Mortsell, E.; Mostek, N.; Mufson, Stuart; Musser, J. A.; Nugent, Peter E.; Oluseyi, Hakeem M.; Pain, Reynald; Palaio, Nicholas P.; Pankow, David H.; Perlmutter, Saul; Pratt, R.; Prieto, Eric; Refregier, Alexandre; Rhodes, J.; Robinson, Kem E.; Roe, N.; Sholl, Michael; Schubnell, Michael S.; Smadja, G.; Smoot, George F.; Spadafora, A.; Tarle, Gregory; Tomasch, Andrew D.; von der Lippe, H.; Vincent, R.; Walder, J.-P.; Wang, Guobin

    2002-12-01

    The SuperNova/Acceleration Probe (SNAP) mission will require a two-meter class telescope delivering diffraction limited images spanning a one degree field in the visible and near infrared wavelength regime. This requirement, equivalent to nearly one billion pixel resolution, places stringent demands on its optical system in terms of field flatness, image quality, and freedom from chromatic aberration. We discuss the advantages of annular-field three-mirror anastigmat (TMA) telescopes for applications such as SNAP, and describe the features of the specific optical configuration that we have baselined for the SNAP mission. We discuss the mechanical design and choice of materials for the telescope. Then we present detailed ray traces and diffraction calculations for our baseline optical design. We briefly discuss stray light and tolerance issues, and present a preliminary wavefront error budget for the SNAP Telescope. We conclude by describing some of tasks to be carried out during the upcoming SNAP research and development phase.

  2. SNAP telescope

    SciTech Connect

    Lampton, Michael L.; Akerlof, C.W.; Aldering, G.; Amanullah, R.; Astier, P.; Barrelet, E.; Bebek, C.; Bergstrom, L.; Bercovitz, J.; Bernstein, G.; Bester, M.; Bonissent, A.; Bower, C.; Carithers Jr., W.C.; Commins, E.D.; Day, C.; Deustua, S.E.; DiGennaro, R.; Ealet, A.; Ellis,R.S.; Eriksson, M.; Fruchter, A.; Genat, J.-F.; Goldhaber, G.; Goobar,A.; Groom, D.; Harris, S.E.; Harvey, P.R.; Heetderks, H.D.; Holland,S.E.; Huterer, D.; Karcher, A.; Kim, A.G.; Kolbe, W.; Krieger, B.; Lafever, R.; Lamoureux, J.; Levi, M.E.; Levin, D.S.; Linder, E.V.; Loken,S.C.; Malina, R.; Massey, R.; McKay, T.; McKee, S.P.; Miquel, R.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Nugent, P.; Oluseyi,H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Pratt, R.; Prieto,E.; Refregier, A.; Rhodes, J.; Robinson, K.; Roe, N.; Sholl, M.; Schubnell, M.; Smadja, G.; Smoot, G.; Spadafora, A.; Tarle, G.; Tomasch,A.; von der Lippe, H.; Vincent, R.; Walder, J.-P.; Wang, G.; Wang, G.

    2002-07-29

    The SuperNova/Acceleration Probe (SNAP) mission will require a two-meter class telescope delivering diffraction limited images spanning a one degree field in the visible and near infrared wavelength regime. This requirement, equivalent to nearly one billion pixel resolution, places stringent demands on its optical system in terms of field flatness, image quality, and freedom from chromatic aberration. We discuss the advantages of annular-field three-mirror anastigmat (TMA) telescopes for applications such as SNAP, and describe the features of the specific optical configuration that we have baselined for the SNAP mission. We discuss the mechanical design and choice of materials for the telescope. Then we present detailed ray traces and diffraction calculations for our baseline optical design. We briefly discuss stray light and tolerance issues, and present a preliminary wavefront error budget for the SNAP Telescope. We conclude by describing some of tasks to be carried out during the upcoming SNAP research and development phase.

  3. 76 FR 35787 - Updated Trafficking Definition and Supplemental Nutrition Assistance Program (SNAP)-FDPIR Dual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... definition of trafficking. This rule also addresses Section 4211 (Assessing the Nutritional Value of the Food... disparity in benefit value as a result of the increase in SNAP benefits following the American Recovery...

  4. Dynamics and Control of Orbiting Space Structures NASA Advanced Design Program (ADP)

    NASA Technical Reports Server (NTRS)

    Cruse, T. A.

    1996-01-01

    The report summarizes the advanced design program in the mechanical engineering department at Vanderbilt University for the academic years 1994-1995 and 1995-1996. Approximately 100 students participated in the two years of the subject grant funding. The NASA-oriented design projects that were selected included lightweight hydrogen propellant tank for the reusable launch vehicle, a thermal barrier coating test facility, a piezoelectric motor for space antenna control, and a lightweight satellite for automated materials processing. The NASA supported advanced design program (ADP) has been a success and a number of graduates are working in aerospace and are doing design.

  5. Development of a mercury electromagnetic centrifugal pump for the SNAP-8 refractory boiler development program

    NASA Technical Reports Server (NTRS)

    Fuller, R. A.; Schnacke, A. W.

    1974-01-01

    An electromagnetic pump, in which pressure is developed in mercury because of the interaction of the magnetic field and current which flows as a result of the voltage induced in the mercury contained in the pump duct, was developed for the SNAP-8 refractory boiler test facility. Pump performance results are presented for ten duct configurations and two stator sizes. These test results were used to design and fabricate a pump which met the SNAP-8 criteria of 530 psi developed pressure at 12,500 lb/hr. The pump operated continuously for over 13,000 hours without failure or performance degradation. Included in this report are descriptions of the experimental equipment, measurement techniques, all experimental data, and an analysis of the electrical losses in the pump.

  6. Fact Sheet: Protection of the Stratospheric Ozone: New Substitute in the Motor Vehicle Air Conditioning Sector under the Significant New Alternatives Policy (SNAP) Program

    EPA Pesticide Factsheets

    Under the Significant New Alternatives Policy (SNAP) program, EPA is listing HFO-1234yf as an acceptable substitute for ozone depleting substances (ODS) in motor vehicle air conditioning (MVAC) systems in new cars and other light duty-vehicles and is speci

  7. SNAP Cuts Put Youth at Risk

    ERIC Educational Resources Information Center

    Lower-Basch, Elizabeth

    2013-01-01

    In a typical month in 2011, the Supplemental Nutrition Assistance Program (SNAP, formerly known as the Food Stamp Program) served 4.3 million low-income young adults ages 18-24, helping them buy needed groceries. This brief report demonstrates the detrimental impact the cuts proposed to SNAP in the House-passed Farm bill (H.R. 3102)--which is now…

  8. Healthy store programs and the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), but not the Supplemental Nutrition Assistance Program (SNAP), are associated with corner store healthfulness.

    PubMed

    DeWeese, Robin S; Todd, Michael; Karpyn, Allison; Yedidia, Michael J; Kennedy, Michelle; Bruening, Meg; Wharton, Christopher M; Ohri-Vachaspati, Punam

    2016-12-01

    In response to lack of access to healthy foods, many low-income communities are instituting local healthy corner store programs. Some stores also participate in the United States Department of Agriculture's Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and the Supplemental Nutrition Assistance Program (SNAP). This study used two assessment tools to compare the healthfulness of offerings at stores participating in local healthy store programs (upgraded stores), WIC, and/or SNAP to that of similar non-participating stores. Based on store audits conducted in 315 New Jersey corner stores in 2014, we calculated healthy food availability scores using subsections of the Nutrition Environment Measures Survey for Corner Stores (NEMS-CS-Availability) and a short-form corner store audit tool (SCAT). We used multivariable regression to examine associations between program participation and scores on both instruments. Adjusting for store and block group characteristics, stores participating in a local healthy store program had significantly higher SCAT scores than did non-participating stores (upgraded: M = 3.18, 95% CI 2.65-3.71; non-upgraded: M = 2.52, 95% CI 2.32-2.73); scores on the NEMS-CS-Availability did not differ (upgraded: M = 12.8, 95% CI 11.6-14.1; non-upgraded: M = 12.5, 95% CI 12.0-13.0). WIC-participating stores had significantly higher scores compared to non-participating stores on both tools. Stores participating in SNAP only (and not in WIC) scored significantly lower on both instruments compared to non-SNAP stores. WIC-participating and non-SNAP corner stores had higher healthfulness scores on both assessment tools. Upgraded stores had higher healthfulness scores compared to non-upgraded stores on the SCAT.

  9. The Impact of SNAP-ED and EFNEP on Program Graduates 6 Months after Graduation

    ERIC Educational Resources Information Center

    Koszewski, Wanda; Sehi, Natalie; Behrends, Donnia; Tuttle, Elizabeth

    2011-01-01

    Research was conducted to determine if graduates from either the Supplemental Nutrition Assistance Program-Education or Expanded Food and Nutrition Education Program maintained behavioral changes 6 months after completing the program. Staff asked graduates to complete a 10- or 15-question behavior checklist that was identical to the entry and exit…

  10. STE thrust chamber technology: Main injector technology program and nozzle Advanced Development Program (ADP)

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The purpose of the STME Main Injector Program was to enhance the technology base for the large-scale main injector-combustor system of oxygen-hydrogen booster engines in the areas of combustion efficiency, chamber heating rates, and combustion stability. The initial task of the Main Injector Program, focused on analysis and theoretical predictions using existing models, was complemented by the design, fabrication, and test at MSFC of a subscale calorimetric, 40,000-pound thrust class, axisymmetric thrust chamber operating at approximately 2,250 psi and a 7:1 expansion ratio. Test results were used to further define combustion stability bounds, combustion efficiency, and heating rates using a large injector scale similar to the Pratt & Whitney (P&W) STME main injector design configuration including the tangential entry swirl coaxial injection elements. The subscale combustion data was used to verify and refine analytical modeling simulation and extend the database range to guide the design of the large-scale system main injector. The subscale injector design incorporated fuel and oxidizer flow area control features which could be varied; this allowed testing of several design points so that the STME conditions could be bracketed. The subscale injector design also incorporated high-reliability and low-cost fabrication techniques such as a one-piece electrical discharged machined (EDMed) interpropellant plate. Both subscale and large-scale injectors incorporated outer row injector elements with scarfed tip features to allow evaluation of reduced heating rates to the combustion chamber.

  11. Imaging of snapping phenomena

    PubMed Central

    Guillin, R; Marchand, A J; Roux, A; Niederberger, E; Duvauferrier, R

    2012-01-01

    Snapping phenomena result from the sudden impingement between anatomical and/or heterotopical structures with subsequent abrupt movement and noise. Snaps are variously perceived by patients, from mild discomfort to significant pain requiring surgical management. Identifying the precise cause of snaps may be challenging when no abnormality is encountered on routinely performed static examinations. In this regard, dynamic imaging techniques have been developed over time, with various degrees of success. This review encompasses the main features of each imaging technique and proposes an overview of the main snapping phenomena in the musculoskeletal system. PMID:22744321

  12. 45 CFR 95.621 - ADP reviews.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ASSISTANCE, MEDICAL ASSISTANCE AND STATE CHILDREN'S HEALTH INSURANCE PROGRAMS) Automatic Data Processing... appropriate ADP security requirements based on recognized industry standards or standards governing...

  13. Snapping mechanical metamaterials under tension.

    PubMed

    Rafsanjani, Ahmad; Akbarzadeh, Abdolhamid; Pasini, Damiano

    2015-10-21

    A snapping mechanical metamaterial is designed, which exhibits a sequential snap-through behavior under tension. The tensile response of this mechanical metamaterial can be altered by tuning the architecture of the snapping segments to achieve a range of nonlinear mechanical responses, including monotonic, S-shaped, plateau, and non-monotonic snap-through behavior.

  14. Naval Shipboard Non-Tactical ADP Program (SNAP) Automated Medical System (SAMS) Computer Assisted Medical Diagnosis (CAMD) Module System/Subsystem Specification

    DTIC Science & Technology

    1992-10-01

    BOWEL OBSTRUCTION " C-25 GOAL "PEPTIC...34 = 0.1 ; "PERFORATED DUODENAL ULCER " = 0.1 ; "CHOLECYSTITIS " = 0.1 ; "SMALL BOWEL OBSTRUCTION " = 0.1 ; "PEPTIC ULCER DISEASE " = 0.1 END RULE 2 [10...34CHOLECYSTITIS " = 0.1 ; "SMALL BOWEL OBSTRUCTION " = 0.1 ; "PEPTIC ULCER DISEASE " 0.1 END RULE 3 [10) IF "AGE " >= 0 AND "AGE " <= 9 THEN "APPENDICITIS

  15. Rewarding Healthy Food Choices in SNAP: Behavioral Economic Applications

    PubMed Central

    Richards, Michael R; Sindelar, Jody L

    2013-01-01

    Context American obesity rates continue to escalate, but an effective policy response remains elusive. Specific changes to the Supplemental Nutrition Assistance Program (SNAP) have been proposed as one way to improve nutrition and combat obesity among lower-income populations. While current SNAP proposals hold promise, some important challenges still remain. Methods We discuss the four most common recommendations for changes to SNAP and their benefits and limitations. We then propose three new delivery options for SNAP that take advantage of behavioral economic insights and encourage the selection of healthy foods. Findings Although the existing proposals could help SNAP recipients, they often do not address some important behavioral impediments to buying healthy foods. We believe that behavioral economics can be used to design alternative policies with several advantages, although we recognize and discuss some of their limitations. The first proposal rewards healthy purchases with more SNAP funds and provides an additional incentive to maintain healthier shopping patterns. The second proposal uses the opportunity to win prizes to reward healthy food choices, and the prizes further support healthier habits. The final proposal simplifies healthy food purchases by allowing individuals to commit their SNAP benefits to more nutritious selections in advance. Conclusions Reforming the delivery structure of SNAP's benefits could help improve nutrition, weight, and overall health of lower-income individuals. We advocate for more and diverse SNAP proposals, which should be tested and, possibly, combined. Their implementation, however, would require political will, administrative capacity, and funding. PMID:23758515

  16. Application of IMPLAN to Extension Programs: Economic Impacts of the University of Arizona Cooperative Extension SNAP-Ed Spending

    ERIC Educational Resources Information Center

    Kerna, Ashley; Frisvold, George; Jacobs, Laurel; Farrell, Vanessa A.; Houtkooper, Linda; Misner, Scottie

    2015-01-01

    Many Extension programs are turning to the input-output software IMPLAN to demonstrate economic impacts. IMPLAN is a powerful tool that can be used to estimate the total economic activity associated with an industry, event, or policy. One possible application, therefore, is to use program spending data to estimate the economic effects of…

  17. Reconceiving SNAP: Is Nutritional Assistance Really Income Support?

    ERIC Educational Resources Information Center

    Besharov, Douglas J.

    2016-01-01

    Since its creation, the Supplemental Nutrition Assistance Program (SNAP) has changed from an antihunger program to an income-supplementation program. Because the program (and its predecessor Food Stamp Program) was not designed for this purpose, the result is a program that has many unintended and, many believe, negative effects. The key challenge…

  18. SNAP Telescope Latest Developments

    NASA Astrophysics Data System (ADS)

    Lampton, M.; SNAP Collaboration

    2004-12-01

    The coming era of precision cosmology imposes new demands on space telescopes with regard to spectrophotometric accuracy and image stability. To meet these requirements for SNAP we have developed an all reflecting two-meter-class space telescope of the three-mirror anastigmat type. Our design features a large flat annular field (1.5 degrees = 580mm diameter) and a telephoto advantage of 6, delivering a 22m focal length within an optical package length of only 3.5 meters. The use of highly stable materials (Corning ULE glass and carbon-fiber reinforced cyanate ester resin for the metering structure) combined with agressive distributed thermal control and an L2 orbit location will lead to unmatched figure stability. Owing to our choice of rigid structure with nondeployable solar panels, finite-element models show no structural resonances below 10Hz. An exhaustive stray light study has been completed. Beginning in 2005, two industry studies will develop plans for fabrication, integration and test, bringing SNAP to a highly realistic level of definition. SNAP is supported by the Office of Science, US DoE, under contract DE-AC03-76SF00098.

  19. SNAP Assay Technology.

    PubMed

    O'Connor, Thomas P

    2015-12-01

    The most widely used immunoassay configuration is the enzyme-linked immunosorbent assay (ELISA) because the procedure produces highly sensitive and specific results and generally is easy to use. By definition, ELISAs are immunoassays used to detect a substance (typically an antigen or antibody) in which an enzyme is attached (conjugated) to one of the reactants and an enzymatic reaction is used to amplify the signal if the substance is present. Optimized ELISAs include several steps that are performed in sequence using a defined protocol that typically includes application of sample and an enzyme-conjugated antibody or antigen to an immobilized reagent, followed by wash and enzyme reaction steps. The SNAP assay is an in-clinic device that performs each of the ELISA steps in a timed sequential fashion with little consumer interface. The components and mechanical mechanism of the assay device are described. Detailed descriptions of features of the assay, which minimize nonspecific binding and enhance the ability to read results from weak-positive samples, are given. Basic principles used in assays with fundamentally different reaction mechanisms, namely, antigen-detection, antibody-detection, and competitive assays are given. Applications of ELISA technology, which led to the development of several multianalyte SNAP tests capable of testing for up to 6 analytes using a single-sample and a single-SNAP device are described.

  20. SNAP focal plane

    SciTech Connect

    Lampton, Michael L.; Kim, A.; Akerlof, C.W.; Aldering, G.; Amanullah, R.; Astier, P.; Barrelet, E.; Bebek, C.; Bergstrom, L.; Berkovitz, J.; Bernstein, G.; Bester, M.; Bonissent, A.; Bower, C.; Carithers Jr., W.C.; Commins, E.D.; Day, C.; Deustua, S.E.; DiGennaro,R.; Ealet, A.; Ellis, R.S.; Eriksson, M.; Fruchter, A.; Genat, J.-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Harris, S.E.; Harvey, P.R.; Heetderks, H.D.; Holland, S.E.; Huterer, D.; Karcher, A.; Kolbe, W.; Krieger, B.; Lafever, R.; Lamoureux, J.; Levi, M.E.; Levin, D.S.; Linder,E.V.; Loken, S.C.; Malina, R.; Massey, R.; McKay, T.; McKee, S.P.; Miquel, R.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Pratt, R.; Prieto, E.; Refregier, A.; Rhodes, J.; Robinson, K.; Roe, N.; Sholl, M.; Schubnell, M.; Smadja, G.; Smoot, G.; Spadafora, A.; Tarle, G.; Tomasch,A.; von der Lippe, H.; Vincent, R.; Walder, J.-P.; Wang, G.

    2002-07-29

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square-degree field sensitive in the visible and near-infrared wavelength regime. We describe the requirements for the instrument suite and the evolution of the focal plane design to the present concept in which all the instrumentation--visible and near-infrared imagers, spectrograph, and star guiders--share one common focal plane.

  1. Child hunger and the protective effects of supplemental nutrition assistance program (SNAP) and alternative food sources among Mexican-origin families in Texas border colonias

    PubMed Central

    2013-01-01

    ), increased household composition, full-time unemployment, and participation in the National School Lunch Program were significantly associated with increased odds for child hunger, while participation in Supplemental Nutrition Assistance Program (SNAP) and purchasing food from a neighbor were significantly associated with decreased odds for child hunger. Conclusions This study not only emphasizes the alarming rates of child hunger among this sample of Mexican-origin families, but also identifies economic and family factors that increased the odds for child hunger as well as community strategies that reduced the odds. It is unsettling that so many children did not participate in school-based nutrition programs, and that many who participated in federal nutrition assistance programs remained hungry. This study underscores the importance of identifying the presence of child hunger among low-income Mexican-origin children in Texas border colonias and increasing access to nutrition-related resources. Hunger-associated health inequities at younger ages among colonia residents are likely to persist across the life span and into old age. PMID:24034599

  2. The Classroom Animal: Snapping Turtles.

    ERIC Educational Resources Information Center

    Kramer, David C.

    1987-01-01

    Describes the distinctive features of the common snapping turtle. Discusses facts and misconceptions held about the turtle. Provides guidelines for proper care and treatment of a young snapper in a classroom environment. (ML)

  3. Snap-through and Continuation

    DTIC Science & Technology

    2012-02-01

    This system will be scrutinized using classical analysis techniques as well as experimental verification to shed light on the issue of dynamic snap... prestress on the free vibration characteristics of clamped rectangular plates: theory and experiment. Journal of Vibration and Acoustics, 119:243–249...the critical snap-free temperature for members of general geometry and loading pattern; the analogy between mechanical prestress and thermal strain

  4. The SNAP near infrared detectors

    SciTech Connect

    Tarle, G.; Akerlof, C.; Aldering, G.; Amanullah, R.; Astier, P.; Barrelet, E.; Bebek, C.; Bergstrom, L.; Bercovitz, J.; Bernstein, G.; Bester, M.; Bonissent, A.; Bower, C.; Carithers, W.; Commins, E.D.; Day, C.; Deustua, S.; DiGennaro, R.; Ealet, Anne; Ellis, R.S.; Eriksson, M.; Fruchter, A.; Genat, J.-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Harris, S.; Harvey, P.; Heetderks, H.; Holland, S.; Huterer, D.; Karcher, A.; Kim, A.; Kolbe, W.; Krieger, B.; Lafever, R.; Lamoureux, J.; Lampton, M.; Levi, M.E.; Levin, D.; Linder, E.; Loken, S.; Malina, R.; Massey, R.; Miguel, R.; McKay, T.; McKee, S.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Pratt, R.; Prieto, E.; Refregier, A.; Rhodes, J.; Robinson, K.; Roe, N.; Sholl, M.; Schubnell, M.; Smadja, G.; Smoot, G.; Spadafora, A.; Tomasch, A.; von der Lippe, H.; Vincent, R.; Walder, J.; Wang, G.

    2002-07-29

    The SuperNova/Acceleration Probe (SNAP) will measure precisely the cosmological expansion history over both the acceleration and deceleration epochs and thereby constrain the nature of the dark energy that dominates our universe today. The SNAP focal plane contains equal areas of optical CCDs and NIR sensors and an integral field spectrograph. Having over 150 million pixels and a field-of-view of 0.34 square degrees, the SNAP NIR system will be the largest yet constructed. With sensitivity in the range 0.9-1.7 {micro}m, it will detect Type Ia supernovae between z = 1 and 1.7 and will provide follow-up precision photometry for all supernovae. HgCdTe technology, with a cut-off tuned to 1.7 {micro}m, will permit passive cooling at 140 K while maintaining noise below zodiacal levels. By dithering to remove the effects of intrapixel variations and by careful attention to other instrumental effects, we expect to control relative photometric accuracy below a few hundredths of a magnitude. Because SNAP continuously revisits the same fields we will be able to achieve outstanding statistical precision on the photometry of reference stars in these fields, allowing precise monitoring of our detectors. The capabilities of the NIR system for broadening the science reach of SNAP are discussed.

  5. Superlattice nanowire pattern transfer (SNAP).

    PubMed

    Heath, James R

    2008-12-01

    During the past 15 years or so, nanowires (NWs) have emerged as a new and distinct class of materials. Their novel structural and physical properties separate them from wires that can be prepared using the standard methods for manufacturing electronics. NW-based applications that range from traditional electronic devices (logic and memory) to novel biomolecular and chemical sensors, thermoelectric materials, and optoelectronic devices, all have appeared during the past few years. From a fundamental perspective, NWs provide a route toward the investigation of new physics in confined dimensions. Perhaps the most familiar fabrication method is the vapor-liquid-solid (VLS) growth technique, which produces semiconductor nanowires as bulk materials. However, other fabrication methods exist and have their own advantages. In this Account, I review a particular class of NWs produced by an alternative method called superlattice nanowire pattern transfer (SNAP). The SNAP method is distinct from other nanowire preparation methods in several ways. It can produce large NW arrays from virtually any thin-film material, including metals, insulators, and semiconductors. The dimensions of the NWs can be controlled with near-atomic precision, and NW widths and spacings can be as small as a few nanometers. In addition, SNAP is almost fully compatible with more traditional methods for manufacturing electronics. The motivation behind the development of SNAP was to have a general nanofabrication method for preparing electronics-grade circuitry, but one that would operate at macromolecular dimensions and with access to a broad materials set. Thus, electronics applications, including novel demultiplexing architectures; large-scale, ultrahigh-density memory circuits; and complementary symmetry nanowire logic circuits, have served as drivers for developing various aspects of the SNAP method. Some of that work is reviewed here. As the SNAP method has evolved into a robust nanofabrication

  6. ADP's ABCs of Training

    ERIC Educational Resources Information Center

    Weinstein, Margery

    2010-01-01

    When a company's core competence is processing data, it is sometimes easy to lose sight of the obvious--the information right under its nose. In the case of Automatic Data Processing, Inc. (ADP), a business outsourcing company specializing in human resources, payroll, tax, and benefits administrations solutions, that is not a problem. Through…

  7. Associations between body mass index, shopping behaviors, amenity density, and characteristics of the neighborhood food environment among female adult Supplemental Nutrition Assistance Program (SNAP) participants in eastern North Carolina.

    PubMed

    Jilcott Pitts, Stephanie B; McGuirt, Jared T; Carr, Lucas J; Wu, Qiang; Keyserling, Thomas C

    2012-01-01

    We examined associations between body mass index (BMI) and the food environment among adult female Supplemental Nutrition Assistance Program (SNAP) participants (N = 197) in eastern North Carolina. Food venue proximity to residential addresses was calculated using a geographic information system. Walk Score was used as a measure of amenity density. Correlation and linear regression analyses were used to examine associations between BMI and distance to and use of food venues, and residential amenity density. Frequency of supercenter use was significantly inversely associated with distance to supercenters. Walk Score was significantly inversely associated with BMI. BMI was not associated with distance to or use of any particular food venue. Future studies should examine specific health-promoting elements of amenity-dense neighborhoods accessible to limited-income populations.

  8. Raman gains of ADP and KDP crystals

    NASA Astrophysics Data System (ADS)

    Zhou, Hai-Liang; Zhang, Qing-Hua; Wang, Bo; Xu, Xin-Guang; Wang, Zheng-Ping; Sun, Xun; Zhang, Fang; Zhang, Li-Song; Liu, Bao-An; Chai, Xiang-Xu

    2015-04-01

    In this paper, the Raman gain coefficients of ammonium dihydrogen phosphate (ADP) and potassium dihydrogen phosphate (KDP) crystals are measured. By using a pump source of a 30-ps, 532-nm laser, the gain coefficients of ADP and KDP are 1.22 cm/GW, and 0.91 cm/GW, respectively. While for a 20-ps, 355-nm pump laser, the gain coefficients of these two crystals are similar, which are 1.95 cm/GW for ADP and 1.86 for KDP. The present results indicate that for ultra-violet frequency conversion, the problem of stimulated Raman scattering for ADP crystal will not be more serious than that for KDP crystal. Considering other advantages such the larger nonlinear optical coefficient, higher laser damage threshold, and lower noncritical phase-matching temperature, it can be anticipated that ADP will be a powerful competitor to KDP in large aperture, high energy third-harmonic generation or fourth-harmonic generation applications. Project supported by the National Natural Science Foundation of China (Grant Nos. 51323002 and 51402173), the Independent Innovation Foundation of Shandong University, China (Grant Nos. IIFSDU and 2012JC016), the Program for New Century Excellent Talents in University, China (Grant No. NCET-10-0552), the Fund from the Key Laboratory of Neutron Physics, China Academy of Engineering Physics (Grant No. 2014BB07), and the Natural Science Foundation for Distinguished Young Scholar of Shandong Province, China (Grant No. JQ201218).

  9. Experimental Criticality Benchmarks for SNAP 10A/2 Reactor Cores

    SciTech Connect

    Krass, A.W.

    2005-12-19

    This report describes computational benchmark models for nuclear criticality derived from descriptions of the Systems for Nuclear Auxiliary Power (SNAP) Critical Assembly (SCA)-4B experimental criticality program conducted by Atomics International during the early 1960's. The selected experimental configurations consist of fueled SNAP 10A/2-type reactor cores subject to varied conditions of water immersion and reflection under experimental control to measure neutron multiplication. SNAP 10A/2-type reactor cores are compact volumes fueled and moderated with the hydride of highly enriched uranium-zirconium alloy. Specifications for the materials and geometry needed to describe a given experimental configuration for a model using MCNP5 are provided. The material and geometry specifications are adequate to permit user development of input for alternative nuclear safety codes, such as KENO. A total of 73 distinct experimental configurations are described.

  10. Mapping snap bean (Phaseolus vulgaris L.) pod and color traits, in a dry bean x snap bean recombinant inbred population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Snap bean (Phaseolus vulgaris) breeding programs are tasked with developing varieties that meet the standards of the vegetable processing industry and ultimately that of the consumer; all the while matching or exceeding the field performance of existing varieties. While traditional breeding methods ...

  11. Defense ADP Acquisition Study.

    DTIC Science & Technology

    1981-11-30

    management issues. It also provides broad insight into the nature and causes of problems in the ADP acquisition process and offers several strategies ... strategy planning fails to provide the appropriate mission perspective. Curfent top-down strategic planning does not pro- vide the necessary guidance for the...recommendations presented here are more appropriately labeled strategies for change, rather than specific actions for improvement. (1) There Must Be a

  12. The effects of childhood SNAP use and neighborhood conditions on adult body mass index.

    PubMed

    Vartanian, Thomas P; Houser, Linda

    2012-08-01

    The disproportionate number of individuals who are obese or overweight in the low-income U.S. population has raised interest in the influence of neighborhood conditions and public assistance programs on weight and health. Generally, neighborhood effects and program participation effects have been explored in separate studies. We unite these two areas of inquiry, using the 1968-2005 Panel Study of Income Dynamics (PSID) to examine the long-term effects of childhood Supplemental Nutrition Assistance Program (SNAP) participation, neighborhood conditions, and the interaction of these two, on adult body mass index (BMI). Using sibling fixed-effects models to account for selection bias, we find that relative to children in other low-income families, children in SNAP-recipient households have higher average adult BMI values. However, the effects of childhood SNAP usage are sensitive to both residential neighborhood and age at receipt. For those growing up in advantaged neighborhoods, projected adult BMI is higher for children in SNAP-recipient households than for children in low-income, nonrecipient households. In contrast, for those growing up in less-advantaged areas, adult BMI differences between children in SNAP-recipient and those in low-income, nonrecipient households are small. SNAP usage during preschool years (0 to 4) has no impact on adult BMI scores. However, at later childhood ages, the time elapsed receiving SNAP income increases adult BMI values relative to a condition of low-income nonreceipt.

  13. SnapShot: Interferon Signaling.

    PubMed

    Chow, Kwan T; Gale, Michael

    2015-12-17

    Interferons (IFNs) are crucial cytokines of antimicrobial, antitumor, and immunomodulatory activity. The three types of IFN (I, II, and III) are classified by their receptor specificity and sequence homology. IFNs are produced and secreted by cells in response to specific stimuli. Here, we review the subsequent IFN signaling events occurring through unique receptors leading to regulation of gene expression for modulation of innate and adaptive immunity. To view this SnapShot, open or download the PDF.

  14. Near infrared detectors for SNAP

    SciTech Connect

    Schubnell, M.; Barron, N.; Bebek, C.; Brown, M.G.; Borysow, M.; Cole, D.; Figer, D.; Lorenzon, W.; Mostek, N.; Mufson, S.; Seshadri, S.; Smith, R.; Tarle, G.

    2006-05-23

    Large format (1k x 1k and 2k x 2k) near infrared detectors manufactured by Rockwell Scientific Center and Raytheon Vision Systems are characterized as part of the near infrared R&D effort for SNAP (the Super-Nova/Acceleration Probe). These are hybridized HgCdTe focal plane arrays with a sharp high wavelength cut-off at 1.7 um. This cut-off provides a sufficiently deep reach in redshift while it allows at the same time low dark current operation of the passively cooled detectors at 140 K. Here the baseline SNAP near infrared system is briefly described and the science driven requirements for the near infrared detectors are summarized. A few results obtained during the testing of engineering grade near infrared devices procured for the SNAP project are highlighted. In particular some recent measurements that target correlated noise between adjacent detector pixels due to capacitive coupling and the response uniformity within individual detector pixels are discussed.

  15. Arthroscopic Taloplasty for an Anterolateral Snapping Ankle.

    PubMed

    Lui, Tun Hing

    2016-12-01

    Anterior ankle snapping syndrome is rare. Snapping of the extensor digitorum longus due to attenuated inferior extensor retinaculum and snapping due to hypertrophied or low-lying peroneal tertius muscle have been reported. We reported a new mechanism of anterolateral snapping due to a hypertrophied talar head. Anterolateral snapping ankle can be revealed by active dorsiflexion and plantarflexion of the ankle with the foot inverted. Foot inversion will tension the inferior extensor retinaculum and uncover the dorsolateral prominence of the talar head. The dorsolateral prominence of the talar head will snap over the proximal edge of the inferior extensor retinaculum. This technical note reports the technique of arthroscopic contouring of the talar head via extra-articular ankle arthroscopy. We named this technique arthroscopic taloplasty.

  16. The Curious Acoustic Behavior of Estuarine Snapping Shrimp: Temporal Patterns of Snapping Shrimp Sound in Sub-Tidal Oyster Reef Habitat.

    PubMed

    Bohnenstiehl, DelWayne R; Lillis, Ashlee; Eggleston, David B

    2016-01-01

    Ocean soundscapes convey important sensory information to marine life. Like many mid-to-low latitude coastal areas worldwide, the high-frequency (>1.5 kHz) soundscape of oyster reef habitat within the West Bay Marine Reserve (36°N, 76°W) is dominated by the impulsive, short-duration signals generated by snapping shrimp. Between June 2011 and July 2012, a single hydrophone deployed within West Bay was programmed to record 60 or 30 seconds of acoustic data every 15 or 30 minutes. Envelope correlation and amplitude information were then used to count shrimp snaps within these recordings. The observed snap rates vary from 1500-2000 snaps per minute during summer to <100 snaps per minute during winter. Sound pressure levels are positively correlated with snap rate (r = 0.71-0.92) and vary seasonally by ~15 decibels in the 1.5-20 kHz range. Snap rates are positively correlated with water temperatures (r = 0.81-0.93), as well as potentially influenced by climate-driven changes in water quality. Light availability modulates snap rate on diurnal time scales, with most days exhibiting a significant preference for either nighttime or daytime snapping, and many showing additional crepuscular increases. During mid-summer, the number of snaps occurring at night is 5-10% more than predicted by a random model; however, this pattern is reversed between August and April, with an excess of up to 25% more snaps recorded during the day in the mid-winter. Diurnal variability in sound pressure levels is largest in the mid-winter, when the overall rate of snapping is at its lowest, and the percentage difference between daytime and nighttime activity is at its highest. This work highlights our lack of knowledge regarding the ecology and acoustic behavior of one of the most dominant soniforous invertebrate species in coastal systems. It also underscores the necessity of long-duration, high-temporal-resolution sampling in efforts to understand the bioacoustics of animal behaviors and

  17. The Curious Acoustic Behavior of Estuarine Snapping Shrimp: Temporal Patterns of Snapping Shrimp Sound in Sub-Tidal Oyster Reef Habitat

    PubMed Central

    Bohnenstiehl, DelWayne R.; Lillis, Ashlee; Eggleston, David B.

    2016-01-01

    Ocean soundscapes convey important sensory information to marine life. Like many mid-to-low latitude coastal areas worldwide, the high-frequency (>1.5 kHz) soundscape of oyster reef habitat within the West Bay Marine Reserve (36°N, 76°W) is dominated by the impulsive, short-duration signals generated by snapping shrimp. Between June 2011 and July 2012, a single hydrophone deployed within West Bay was programmed to record 60 or 30 seconds of acoustic data every 15 or 30 minutes. Envelope correlation and amplitude information were then used to count shrimp snaps within these recordings. The observed snap rates vary from 1500–2000 snaps per minute during summer to <100 snaps per minute during winter. Sound pressure levels are positively correlated with snap rate (r = 0.71–0.92) and vary seasonally by ~15 decibels in the 1.5–20 kHz range. Snap rates are positively correlated with water temperatures (r = 0.81–0.93), as well as potentially influenced by climate-driven changes in water quality. Light availability modulates snap rate on diurnal time scales, with most days exhibiting a significant preference for either nighttime or daytime snapping, and many showing additional crepuscular increases. During mid-summer, the number of snaps occurring at night is 5–10% more than predicted by a random model; however, this pattern is reversed between August and April, with an excess of up to 25% more snaps recorded during the day in the mid-winter. Diurnal variability in sound pressure levels is largest in the mid-winter, when the overall rate of snapping is at its lowest, and the percentage difference between daytime and nighttime activity is at its highest. This work highlights our lack of knowledge regarding the ecology and acoustic behavior of one of the most dominant soniforous invertebrate species in coastal systems. It also underscores the necessity of long-duration, high-temporal-resolution sampling in efforts to understand the bioacoustics of animal behaviors

  18. Snapping Pes Syndrome after Unicompartmental Knee Arthroplasty

    PubMed Central

    Taketomi, Shuji; Yamagami, Ryota; Tahara, Keitaro; Tanaka, Sakae

    2016-01-01

    Snapping pes syndrome is defined as a snapping sensation in the medial knee caused by pes anserinus and rarely occurs. Snapping pes syndrome after unicompartmental knee arthroplasty (UKA) has not been reported yet. We experienced two cases with this syndrome after UKA. Conservative treatment was effective in one case, while surgical excision of the gracilis tendon was necessary to relieve painful snapping in the other case. The main cause of the first case might be posteromedial overhang of the tibial tray that reached up to 5 mm. The probable cause of the second case was posteromedial overhang of the mobile bearing. PMID:27274476

  19. Genetic diversity of maize kernel starch-synthesis genes with SNAPs.

    PubMed

    Shin, Ji-Hyun; Kwon, Soon-Jae; Lee, Ju Kyong; Min, Hwang-Kee; Kim, Nam-Soo

    2006-10-01

    Measuring genetic diversity in populations of a crop species is very important for understanding the genetic structure of and subsequently improving the crop species by genetic manipulation. Single-nucleotide amplified polymorphisms (SNAPs) among and within maize populations of waxy, dent, and sweet corns at 25 single-nucleotide polymorphism (SNP) sites in 6 kernel starch-synthesis genes (sh2, bt2, su1, ae1, wx1, and sh1) were determined. Because of the intensive selection of some favorable alleles in starch-synthesis genes during the breeding process, and the resultant strong linkage disequilibrium (LD), the number of haplotypes in each population was far less than expected. Subsequent phenetic clustering analysis with the SNAPs indicated that the dent, waxy, and sweet corns formed distinct subclusters, except in a few incidences. LD was surveyed among SNAPs of intragenic, intergenic, and intrachromosomal SNPs in whole and subpopulations, which revealed that some SNAPs showed high LD with many other SNAPs, but some SNAPs showed low or no significant LD with others, depending on the subpopulation, indicating that these starch genes have undergone different selection in each subpopulation during the breeding process. Because the starch synthesis genes used in this study are important in maize breeding, the genetic diversity, LD, and accessions having rare SNAP alleles might be valuable in maize improvement programs.

  20. SNAP Satellite Focal Plane Development

    SciTech Connect

    Bebek, C.; Akerlof, C.; Aldering, G.; Amanullah, R.; Astier, P.; Baltay, C.; Barrelet, E.; Basa, S.; Bercovitz, J.; Bergstrom, L.; Berstein, G.P.; Bester, M.; Bohlin, R.; Bonissent, A.; Bower, C.; Campbell, M.; Carithers, W.; Commins, E.; Day, C.; Deustua, S.; DiGennaro, R.; Ealet, A.; Ellis, R.; Emmett, W.; Eriksson, M.; Fouchez,D.; Fruchter, A.; Genat, J-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Heetderks, H.; Holland, S.; Huterer, D.; Johnson, W.; Kadel, R.; Karcher,A.; Kim, A.; Kolbe, W.; Lafever, R.; Lamoureaux, J.; Lampton, M.; Lefevre, O.; Levi, M.; Levin, D.; Linder, E.; Loken, S.; Malina, R.; Mazure, A.; McKay, T.; McKee, S.; Miquel, R.; Morgan, N.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Roe, N.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Prieto, E.; Rabinowitz,D.; Refregier, A.; Rhodes, J.; Schubnell, M.; Sholl, M.; Smadja, G.; Smith, R.; Smoot, G.; Snyder, J.; Spadafora, A.; Szymkowiak, A.; Tarle,G.; Taylor, K.; Tilquin, A.; Tomasch, A.; Vincent, D.; von der Lippe, H.; Walder, J-P.; Wang, G.

    2003-07-07

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square degree field in the visible and near-infrared wavelength regime. The requirements for the instrument suite and the present configuration of the focal plane concept are presented. A two year R&D phase, largely supported by the Department of Energy, is just beginning. We describe the development activities that are taking place to advance our preparedness for mission proposal in the areas of detectors and electronics.

  1. Internal snapping hip syndrome in dynamic ultrasonography

    PubMed Central

    Maczuch, Jarosław; Skupiński, Jarosław; Kukawska-Sysio, Karolina; Wawrzynek, Wojciech

    2016-01-01

    Snapping hip syndrome is an audible or palpable snap in a hip joint during movement which may be accompanied by pain or locking. It is typically seen in young athletes performing activities requiring repeated extreme movements of the hip. It may also follow a physical trauma, intramuscular injections or surgeries. There are two main forms of snapping hip: extra- or intra-articular. Extra-articular snapping hip is elicited by an abnormal movement of specific tendons and is divided into two forms: internal and external. The internal form of snapping hip syndrome is attributed to an abrupt movement of an iliopsoas tendon against an iliopectineal eminence. Radiograph results in patients with this form of snapping tend to be normal. Dynamic ultrasound is the gold standard diagnostic technique in both forms of extra-articular snapping hip syndrome. The objective of the following text is to describe a step-by-step dynamic ultrasonography examination in internal extra-articular snapping hip syndrome in accordance to the proposed checklist protocol. To evaluate abrupt movement of an involved tendon, the patient needs to perform specific provocation tests during the examination. With its real-time imaging capabilities, dynamic ultrasonography detects the exact mechanism of the abnormal tendon friction during hip movement in a noninvasive way. It also allows for a diagnosis of additional hip tissue changes which may be causing the pain. PMID:27679733

  2. Snap-in compressible biomedical electrode

    NASA Technical Reports Server (NTRS)

    Frost, J. D., Jr.; Hillman, C. E., Jr. (Inventor)

    1977-01-01

    A replaceable, prefilled electrode enclosed in a plastic seal and suitably adapted for attachment to a reusable, washable cap having snaps thereon is disclosed. The apparatus is particularly adapted for quick positioning of electrodes to obtain an EEG. The individual electrodes are formed of a sponge body which is filled with a conductive electrolyte gel during manufacture. The sponge body is adjacent to a base formed of a conductive plastic material. The base has at its center a male gripper snap. The cap locates the female snap to enable the electrode to be positioned. The electrode can be stored and used quickly by attaching to the female gripper snap. The snap is correctly positioned and located by mounting it in a stretchable cap. The cap is reusable with new electrodes for each use. The electrolyte gel serves as the contact electrode to achieve a good ohmic contact with the scalp.

  3. Understanding and Treating the Snapping Hip

    PubMed Central

    Yen, Yi-Meng; Lewis, Cara L.; Kim, Young-Jo

    2016-01-01

    Snapping hip, or coxa saltans is a palpable or auditory snapping with movement of the hip joint. Extra-articular snapping is divided into external and internal types, and is caused laterally by the iliotibial band and anteriorly by the iliopsoas tendon. Snapping of the iliopsoas usually requires contraction of the hip flexors and may be difficult to distinguish from intra-articualar coxa saltans. Ultrasound can be a useful modality to dynamically detect tendon translation during hip movement to support the diagnosis of extra-articular snapping. Coxa saltans is typically treated with conservative measures including anti-inflammatories, stretching and avoidance of inciting activities. Recalcitrant cases are treated with surgery to lengthen the iliopsoas or iliotibial band. PMID:26524554

  4. How the Venus flytrap snaps.

    PubMed

    Forterre, Yoël; Skotheim, Jan M; Dumais, Jacques; Mahadevan, L

    2005-01-27

    The rapid closure of the Venus flytrap (Dionaea muscipula) leaf in about 100 ms is one of the fastest movements in the plant kingdom. This led Darwin to describe the plant as "one of the most wonderful in the world". The trap closure is initiated by the mechanical stimulation of trigger hairs. Previous studies have focused on the biochemical response of the trigger hairs to stimuli and quantified the propagation of action potentials in the leaves. Here we complement these studies by considering the post-stimulation mechanical aspects of Venus flytrap closure. Using high-speed video imaging, non-invasive microscopy techniques and a simple theoretical model, we show that the fast closure of the trap results from a snap-buckling instability, the onset of which is controlled actively by the plant. Our study identifies an ingenious solution to scaling up movements in non-muscular engines and provides a general framework for understanding nastic motion in plants.

  5. How the Venus flytrap snaps

    NASA Astrophysics Data System (ADS)

    Forterre, Yoël; Skotheim, Jan M.; Dumais, Jacques; Mahadevan, L.

    2005-01-01

    The rapid closure of the Venus flytrap (Dionaea muscipula) leaf in about 100ms is one of the fastest movements in the plant kingdom. This led Darwin to describe the plant as ``one of the most wonderful in the world''. The trap closure is initiated by the mechanical stimulation of trigger hairs. Previous studies have focused on the biochemical response of the trigger hairs to stimuli and quantified the propagation of action potentials in the leaves. Here we complement these studies by considering the post-stimulation mechanical aspects of Venus flytrap closure. Using high-speed video imaging, non-invasive microscopy techniques and a simple theoretical model, we show that the fast closure of the trap results from a snap-buckling instability, the onset of which is controlled actively by the plant. Our study identifies an ingenious solution to scaling up movements in non-muscular engines and provides a general framework for understanding nastic motion in plants.

  6. Wide-field surveys from the SNAP mission

    SciTech Connect

    agkim@lbl.gov

    2002-07-23

    The Supernova/Acceleration Probe (SNAP) is a proposed space-borne observatory that will survey the sky with a wide-field optical/NIR imager. The images produced by SNAP will have an unprecedented combination of depth, solid-angle, angular resolution, and temporal sampling. Two 7.5 square-degree fields will be observed every four days over 16 months to a magnitude depth of AB = 27.7 in each of nine filters. Co-adding images over all epochs will give an AB = 30.3 per filter. A 300 square-degree field will be surveyed with no repeat visits to AB = 28 per filter. The nine filters span 3500-17000 {angstrom}. Although the survey strategy is tailored for supernova and weak gravitational lensing observations, the resulting data supports a broad range of auxiliary science programs.

  7. Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

    PubMed Central

    Hassa, Paul O.; Haenni, Sandra S.; Elser, Michael; Hottiger, Michael O.

    2006-01-01

    Since poly-ADP ribose was discovered over 40 years ago, there has been significant progress in research into the biology of mono- and poly-ADP-ribosylation reactions. During the last decade, it became clear that ADP-ribosylation reactions play important roles in a wide range of physiological and pathophysiological processes, including inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis. ADP-ribosylation reactions are phylogenetically ancient and can be classified into four major groups: mono-ADP-ribosylation, poly-ADP-ribosylation, ADP-ribose cyclization, and formation of O-acetyl-ADP-ribose. In the human genome, more than 30 different genes coding for enzymes associated with distinct ADP-ribosylation activities have been identified. This review highlights the recent advances in the rapidly growing field of nuclear mono-ADP-ribosylation and poly-ADP-ribosylation reactions and the distinct ADP-ribosylating enzyme families involved in these processes, including the proposed family of novel poly-ADP-ribose polymerase-like mono-ADP-ribose transferases and the potential mono-ADP-ribosylation activities of the sirtuin family of NAD+-dependent histone deacetylases. A special focus is placed on the known roles of distinct mono- and poly-ADP-ribosylation reactions in physiological processes, such as mitosis, cellular differentiation and proliferation, telomere dynamics, and aging, as well as “programmed necrosis” (i.e., high-mobility-group protein B1 release) and apoptosis (i.e., apoptosis-inducing factor shuttling). The proposed molecular mechanisms involved in these processes, such as signaling, chromatin modification (i.e., “histone code”), and remodeling of chromatin structure (i.e., DNA damage response, transcriptional regulation, and insulator function), are described. A potential cross talk between nuclear

  8. 7 CFR 272.10 - ADP/CIS Model Plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE FOOD STAMP AND FOOD DISTRIBUTION PROGRAM REQUIREMENTS FOR PARTICIPATING STATE AGENCIES § 272.10 ADP/CIS... automate their food stamp program operations and computerize their systems for obtaining,...

  9. [Genetic diversity of starch synthesis genes of Chinese maize (Zea mays L.) with SNAPs].

    PubMed

    Cao, Wen-Bo; Zheng, Lu-Lu; Zhang, Zheng-Feng; Li, Xue-Bao

    2009-01-01

    Analysis of genetic diversity in maize populations is a very important step for understanding genetic structure and subsequently for genetic manipulations in maize breeding. Sh2, Bt2, Sh1, Wx1, Ae1 and Su1 involved in starch biosynthesis are important genes associated with yield and quality traits in maize breeding programs. In this study, genetic diversity of these six genes in 67 Chinese elite maize inbred lines was measured using single-nucleotide amplified polymorphisms (SNAPs). The results indicated that the number of haplotypes of each gene and population was far less than theoretically expected 2(n) (n = the number of the SNAPs). Phenetic clustering analysis showed that the kernel phonetic (semi-) dent and (semi-) flint lines were belong to distinct subclusters based on haplotypes of SNAPs, with a few exceptions. In addition, the genetic origin of these maize inbred lines was associated with the clustered subgroups. Intragenic linkage disequilibrium (LD) was observed in some of the SNAPs in Bt2, Sh1 and Ae1, while intergenic LD was observed in some of the SNAPs in Bt2, Sh1 and Su1. Association study of kernel phenotypes and SNAP haplotypes showed that the (semi-) dent and (semi-) flint lines had the common haplotype of TA and CC at two SNAP sites in Bt2 (Bt2-2 and Bt2-5), respectively. Two haplotypes of ATGT and GTGC at four SNAP sites in Sh1 (Sh1-2, Sh1-3, Sh1-4 and Sh1-5) were associated with temperature and tropical origin of the maize inbred lines, respectively.

  10. Food Insecurity and SNAP Participation in Mexican Immigrant Families: The Impact of the Outreach Initiative

    PubMed Central

    Kaushal, Neeraj; Waldfogel, Jane; Wight, Vanessa

    2016-01-01

    We study the factors associated with food insecurity and participation in the Supplemental Nutrition Assistance Program (SNAP) in Mexican immigrant families in the US. Estimates from analyses that control for a rich set of economic, demographic, and geographic variables show that children in Mexican immigrant families are more likely to be food insecure than children in native families, but are less likely to participate in SNAP. Further, more vulnerable groups such as the first-generation Mexican immigrant families, families in the US for less than 5 years, and families with non-citizen children – that are at a higher risk of food insecurity are the least likely to participate in SNAP. Our analysis suggests that the US Department of Agriculture outreach initiative and SNAP expansion under the American Recovery and Reinvestment Act increased SNAP participation of the mixed-status Mexican families. We do not find any evidence that the outreach and ARRA expansion increased SNAP receipt among Mexican immigrant families with only non-citizen members who are likely to be undocumented. PMID:27570576

  11. Radiation load to the SNAP CCD

    SciTech Connect

    N. V. Mokhov, I. L. Rakhno and S. I. Striganov

    2003-08-14

    Results of an express Monte Carlo analysis with the MARS14 code of radiation load to the CCD optical detectors in the Supernova Acceleration Project (SNAP) mission presented for realistic radiation environment over the satellite orbit.

  12. The snapping medial antebrachial cutaneous nerve.

    PubMed

    Cesmebasi, Alper; O'driscoll, Shawn W; Smith, Jay; Skinner, John A; Spinner, Robert J

    2015-10-01

    Snapping elbow is a well-known condition where elbow flexion and extension elicits a painful, popping sensation. The most frequent etiology is anterior dislocation of the ulnar nerve over the medial epicondyle. Four patients (3 females and 1 male) presented with complaints of a popping sensation in the elbow, pain over the medial aspect of the forearm, and ulnar neuritis. All patients underwent preoperative dynamic ultrasound and surgical exploration of the medial elbow. Intraoperatively, snapping of the MABC over the medial epicondyle was discovered in all four patients. In three patients, there was abnormal displacement of the medial triceps and ulnar nerve: in two of these, both structures dislocated over the medial epicondyle and in one patient both structures subluxated. In each case, the MABC was decompressed (n = 1) and transposed (n = 3), and in three cases, the medial triceps and ulnar nerve were addressed as well. Symptomatic improvement was achieved in all cases. Retrospective review of the ultrasound revealed the snapping MABC, though it was less effective prospectively in the cases when snapping MABC was not suspected. In conclusion, snapping of the MABC broadens the spectrum of disorders that results in snapping elbow. To our knowledge, we are unaware of prior reports of this entity.

  13. Structure and dynamics of [gamma]-SNAP: Insight into flexibility of proteins from the SNAP family

    SciTech Connect

    Bitto, Eduard; Bingman, Craig A.; Kondrashov, Dmitry A.; McCoy, Jason G.; Bannen, Ryan M.; Wesenberg, Gary E.; Phillips, Jr., George N.

    2010-02-19

    Soluble N-ethylmaleimide-sensitive factor attachment protein gamma ({gamma}-SNAP) is a member of an eukaryotic protein family involved in intracellular membrane trafficking. The X-ray structure of Brachydanio rerio {gamma}-SNAP was determined to 2.6 {angstrom} and revealed an all-helical protein comprised of an extended twisted-sheet of helical hairpins with a helical-bundle domain on its carboxy-terminal end. Structural and conformational differences between multiple observed {gamma}-SNAP molecules and Sec17, a SNAP family protein from yeast, are analyzed. Conformational variation in {gamma}-SNAP molecules is matched with great precision by the two lowest frequency normal modes of the structure. Comparison of the lowest-frequency modes from {gamma}-SNAP and Sec17 indicated that the structures share preferred directions of flexibility, corresponding to bending and twisting of the twisted sheet motif. We discuss possible consequences related to the flexibility of the SNAP proteins for the mechanism of the 20S complex disassembly during the SNAP receptors recycling.

  14. Replacing SNAP-25b with SNAP-25a expression results in metabolic disease.

    PubMed

    Valladolid-Acebes, Ismael; Daraio, Teresa; Brismar, Kerstin; Harkany, Tibor; Ögren, Sven Ove; Hökfelt, Tomas G M; Bark, Christina

    2015-08-04

    Synaptosomal-associated protein of 25 kDa (SNAP-25) is a key molecule in the soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE) complex mediating fast Ca(2+)-triggered release of hormones and neurotransmitters, and both splice variants, SNAP-25a and SNAP-25b, can participate in this process. Here we explore the hypothesis that minor alterations in the machinery mediating regulated membrane fusion can increase the susceptibility for metabolic disease and precede obesity and type 2 diabetes. Thus, we used a mouse mutant engineered to express normal levels of SNAP-25 but only SNAP-25a. These SNAP-25b-deficient mice were exposed to either a control or a high-fat/high-sucrose diet. Monitoring of food intake, body weight, hypothalamic function, and lipid and glucose homeostases showed that SNAP-25b-deficient mice fed with control diet developed hyperglycemia, liver steatosis, and adipocyte hypertrophy, conditions dramatically exacerbated when combined with the high-fat/high-sucrose diet. Thus, modified SNARE function regulating stimulus-dependent exocytosis can increase the vulnerability to and even provoke metabolic disease. When combined with a high-fat/high-sucrose diet, this vulnerability resulted in diabesity. Our SNAP-25b-deficient mouse may represent a diabesity model.

  15. Recent Developments in the Recovery of SNAP-DYN Technical Data Base

    SciTech Connect

    Determan, William R.; Grimmett, David

    2007-01-30

    SNAP-DYN was a concept for a multi-kilowatt class (i.e., 10 to 50 kWe) of space nuclear electric power systems based on the SNAP reactor, shield, and liquid metal heat transfer technologies developed in the 1960s and coupled with dynamic power conversion hardware and state of the art space radiator technologies. The basic concept minimized the system's development costs by utilizing established technologies for each of the major components within the power system to reduce its overall development schedule. Three power conversion technologies were evaluated for the SNAP-DYN concept including Organic Rankine Cycle (ORC) with a peak cycle temperature of 672 K, a closed Brayton cycle (CBC) with a peak cycle temperature of 906 K, and a free piston Stirling cycle (FPSC) with a peak cycle temperature of 870 K. Net system conversion efficiencies were estimated to range from 16 to 19 % over the 10 to 50 kWe power range. Specific power levels for these systems were estimated to range from 6.4 to 13 W/kg over the same power range. SNAP-DYN reactor thermal power levels varied from 55 to 260 kWt, but a much longer lifetime (5 to 10 years vs. 1.3 years) was being evaluated for this power system application than had been demonstrated in the 1960s SNAP reactor development program. The last SNAP reactor under development at the end of the program in 1973 was designed for a 5-year mission life at a nominal thermal power level of 110 kWt with a coolant outlet temperature capability of 922 K. This reactor technology formed the basis for the SNAP-DYN reactor concept.

  16. Disaster Planning for Navy ADP Systems.

    DTIC Science & Technology

    1983-06-01

    including contingency planning . The National Bureau of Standards enhanced FIPS publication 31 in 1981 with its Guidelines for ADP Contingency Planning ... National Bureau of Standards, Federal Information Processing Standards Publication 87, Guidelines for ADP Contingency Planning , 27 March 1981. 62 14... Planning , Contingency , ADP, Department of the Navy, Risk Analysis 2. AGSTAC? ;= a i bsie -f tem. eseeem d Idmu~r Wy 68ek semle.) ADP systems have become

  17. 7 CFR 272.10 - ADP/CIS Model Plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... those which result in effective programs or in cost effective reductions in errors and improvements in...) transferable system is incompatible with it; the State agency's data base management software is incompatible with the transferable system; the State agency's ADP experts are not familiar with the...

  18. 7 CFR 272.10 - ADP/CIS Model Plan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... those which result in effective programs or in cost effective reductions in errors and improvements in...) transferable system is incompatible with it; the State agency's data base management software is incompatible with the transferable system; the State agency's ADP experts are not familiar with the...

  19. 7 CFR 272.10 - ADP/CIS Model Plan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... those which result in effective programs or in cost effective reductions in errors and improvements in...) transferable system is incompatible with it; the State agency's data base management software is incompatible with the transferable system; the State agency's ADP experts are not familiar with the...

  20. 7 CFR 272.10 - ADP/CIS Model Plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... those which result in effective programs or in cost effective reductions in errors and improvements in...) transferable system is incompatible with it; the State agency's data base management software is incompatible with the transferable system; the State agency's ADP experts are not familiar with the...

  1. ADP correspondence system: Unsolicited proposal evaluation tracking application

    NASA Technical Reports Server (NTRS)

    Greene, W. A.; Goodwin, D. J.

    1976-01-01

    A complete description of a correspondence control system, designed to be used by non-ADP clerical personnel is provided. In addition to operating instructions, sufficient design and conceptual information is provided to allow use or adaption of the system in related applications. The complete COBOL program and documentation are available.

  2. Elastocapillary-driven snap-through instability

    NASA Astrophysics Data System (ADS)

    Fargette, Aurelie; Antkowiak, Arnaud; Neukirch, Sebastien

    2012-02-01

    The snap-through instability, which is present in a wide range of systems ranging from carnivorous plants to MEMS, is a well-known phenomenon in solid mechanics : when a buckled elastic beam is subjected to a transverse force, above a critical load value the buckling mode is switched. Here, we revisit this phenomenon by studying snap-through under capillary forces. In our experiment, a droplet (which replaces the usual dry load) is deposited on a buckled thin strip, clamped horizontally at both ends. In this setup both the weight of the drop and capillary forces jointly act toward the instability. The possibility of reverse elastocapillary snap-through, where the droplet is put under the beam, is then tested and successfully observed, showing the predominance of capillary forces at small enough scales.

  3. Comparative kinematical analyses of Venus flytrap (Dionaea muscipula) snap traps.

    PubMed

    Poppinga, Simon; Kampowski, Tim; Metzger, Amélie; Speck, Olga; Speck, Thomas

    2016-01-01

    Although the Venus flytrap (Dionaea muscipula) can be considered as one of the most extensively investigated carnivorous plants, knowledge is still scarce about diversity of the snap-trap motion, the functionality of snap traps under varying environmental conditions, and their opening motion. By conducting simple snap-trap closure experiments in air and under water, we present striking evidence that adult Dionaea snaps similarly fast in aerial and submersed states and, hence, is potentially able to gain nutrients from fast aquatic prey during seasonal inundation. We reveal three snapping modes of adult traps, all incorporating snap buckling, and show that millimeter-sized, much slower seedling traps do not yet incorporate such elastic instabilities. Moreover, opening kinematics of young and adult Dionaea snap traps reveal that reverse snap buckling is not performed, corroborating the assumption that growth takes place on certain trap lobe regions. Our findings are discussed in an evolutionary, biomechanical, functional-morphological and biomimetic context.

  4. Comparative kinematical analyses of Venus flytrap (Dionaea muscipula) snap traps

    PubMed Central

    Kampowski, Tim; Metzger, Amélie; Speck, Olga; Speck, Thomas

    2016-01-01

    Summary Although the Venus flytrap (Dionaea muscipula) can be considered as one of the most extensively investigated carnivorous plants, knowledge is still scarce about diversity of the snap-trap motion, the functionality of snap traps under varying environmental conditions, and their opening motion. By conducting simple snap-trap closure experiments in air and under water, we present striking evidence that adult Dionaea snaps similarly fast in aerial and submersed states and, hence, is potentially able to gain nutrients from fast aquatic prey during seasonal inundation. We reveal three snapping modes of adult traps, all incorporating snap buckling, and show that millimeter-sized, much slower seedling traps do not yet incorporate such elastic instabilities. Moreover, opening kinematics of young and adult Dionaea snap traps reveal that reverse snap buckling is not performed, corroborating the assumption that growth takes place on certain trap lobe regions. Our findings are discussed in an evolutionary, biomechanical, functional–morphological and biomimetic context. PMID:27335756

  5. Biophysics. For certain shrimp, life's a snap.

    PubMed

    Brown, K

    2000-09-22

    On page 2114 of this issue, physicists report that a collapsing bubble outside the claw of the snapping shrimp Alpheus heterochaelis causes its characteristic clack. According to this new study, A. heterochaelis clamps its claw so rapidly that a water jet gushing from the claw first loses and then gains pressure, causing an air bubble in the jet to swell and collapse with a pronounced "snap!" The imploding bubble generates shock waves that stun nearby prey and ward off other shrimp, who have learned to keep their distance.

  6. Implementation of wireless terminals at farmers' markets: impact on SNAP redemption and overall sales.

    PubMed

    Bertmann, Farryl M W; Ohri-Vachaspati, Punam; Buman, Matthew P; Wharton, Christopher M

    2012-07-01

    Although farmers' markets offer healthy foods for purchase, many lack the equipment necessary to process convenient, card-based transactions. We assessed the impact of providing wireless terminals to 5 markets on overall sales and redemption of Supplemental Nutrition Assistance Program (SNAP) benefits. Sales increased significantly at 4 of the 5 markets after implementation of the terminals, and overall sales increased above and beyond SNAP redemption alone. Implementation of wireless terminals may be important for improving the financial stability and accessibility of farmers' markets.

  7. SNAP Participants’ Eating Patterns over the Benefit Month: A Time Use Perspective

    PubMed Central

    2016-01-01

    Individuals receiving monthly benefits through the U.S. Supplemental Nutrition Assistance Program (SNAP) often fall short of food at the end of the month and some report feelings of hunger. To investigate this situation, we used time diaries from the 2006–08 American Time Use Survey and Eating & Health Module to identify the timing of days where respondents reported no eating occurrences. Analysis includes descriptive statistics, a logit model, and a simulated benefit month. We found that SNAP participants were increasingly more likely than nonparticipants to report a day with no eating occurrences over the benefit issuance cycle. This supports the view that there is a monthly cycle in food consumption associated with the SNAP monthly benefit issuance policy. PMID:27410962

  8. Electrostatic anchoring precedes stable membrane attachment of SNAP25/SNAP23 to the plasma membrane

    PubMed Central

    Weber, Pascal; Batoulis, Helena; Rink, Kerstin M; Dahlhoff, Stefan; Pinkwart, Kerstin; Söllner, Thomas H; Lang, Thorsten

    2017-01-01

    The SNAREs SNAP25 and SNAP23 are proteins that are initially cytosolic after translation, but then become stably attached to the cell membrane through palmitoylation of cysteine residues. For palmitoylation to occur, membrane association is a prerequisite, but it is unclear which motif may increase the affinities of the proteins for the target membrane. In experiments with rat neuroendocrine cells, we find that a few basic amino acids in the cysteine-rich region of SNAP25 and SNAP23 are essential for plasma membrane targeting. Reconstitution of membrane-protein binding in a liposome assay shows that the mechanism involves protein electrostatics between basic amino acid residues and acidic lipids such as phosphoinositides that play a primary role in these interactions. Hence, we identify an electrostatic anchoring mechanism underlying initial plasma membrane contact by SNARE proteins, which subsequently become palmitoylated at the plasma membrane. DOI: http://dx.doi.org/10.7554/eLife.19394.001 PMID:28240595

  9. SnapShot: chronic lymphocytic leukemia.

    PubMed

    Ciccone, Maria; Ferrajoli, Alessandra; Keating, Michael J; Calin, George A

    2014-11-10

    Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in western countries. This SnapShot depicts the origins and evolution of this B cell malignancy, describes prognostic factors and CLL animal models, and illustrates therapies in preclinical and clinical development against CLL.

  10. SNAP Participation in Preschool-Aged Children and Prevalence of Overweight and Obesity

    ERIC Educational Resources Information Center

    Simmons, Shannon; Alexander, Jeffrey L.; Ewing, Helen; Whetzel, Stephanie

    2012-01-01

    Background: An increased prevalence of overweight and obesity for adults on government-funded nutrition assistance, such as the Supplemental Nutrition Assistance Program (SNAP), has been observed; however, this association among preschool-aged children is not well understood. Longitudinal research designs tracking changes in body mass…

  11. Dismantlement of the TSF-SNAP Reactor Assembly

    SciTech Connect

    Peretz, Fred J

    2009-01-01

    This paper describes the dismantlement of the Tower Shielding Facility (TSF)?Systems for Nuclear Auxiliary Power (SNAP) reactor, a SNAP-10A reactor used to validate radiation source terms and shield performance models at Oak Ridge National Laboratory (ORNL) from 1967 through 1973. After shutdown, it was placed in storage at the Y-12 National Security Complex (Y-12), eventually falling under the auspices of the Highly Enriched Uranium (HEU) Disposition Program. To facilitate downblending of the HEU present in the fuel elements, the TSF-SNAP was moved to ORNL on June 24, 2006. The reactor assembly was removed from its packaging, inspected, and the sodium-potassium (NaK) coolant was drained. A superheated steam process was used to chemically react the residual NaK inside the reactor assembly. The heat exchanger assembly was removed from the top of the reactor vessel, and the criticality safety sleeve was exchanged for a new safety sleeve that allowed for the removal of the vessel lid. A chain-mounted tubing cutter was used to separate the lid from the vessel, and the 36 fuel elements were removed and packaged in four U.S. Department of Transportation 2R/6M containers. The fuel elements were returned to Y-12 on July 13, 2006. The return of the fuel elements and disposal of all other reactor materials accomplished the formal objectives of the dismantlement project. In addition, a project model was established for the handling of a fully fueled liquid-metal?cooled reactor assembly. Current criticality safety codes have been benchmarked against experiments performed by Atomics International in the 1950s and 1960s. Execution of this project provides valuable experience applicable to future projects addressing space and liquid-metal-cooled reactors.

  12. 45 CFR 95.621 - ADP reviews.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Physical security of ADP resources; (B) Equipment security to protect equipment from theft and unauthorized use; (C) Software and data security; (D) Telecommunications security; (E) Personnel security;...

  13. Demonstration/Validation of the Snap Sampler

    DTIC Science & Technology

    2011-06-01

    low-flow sampling. 5. Carefully selecting a sampling order that reduces sampler impacts on subsequent sam- pling events. 5.1.2 Baseline...flow sampling.  Carefully selecting a sampling order that reduces sampler impacts on subsequent sam- pling events. 5.2.2 Baseline Characterization...ER D C/ CR R EL T R -1 1 -1 1 Project ER-063 Demonstration/Validation of the Snap Sampler Cost and Performance: Final Report C ol d R eg

  14. Habitat Suitability Index Models: Snapping turtle

    USGS Publications Warehouse

    Graves, Brent M.; Anderson, Stanley H.

    1987-01-01

    A review and synthesis of existing information were used to develop a Habitat Suitability Index (HSI) model for the snapping turtle (Chelydra serpentina). The model consolidates habitat use information into a framework appropriate for field application, and is scaled to produce an index between 0.0 (unsuitable habitat) and 1.0 (optimum habitat). HSI models are designed to be used with Habitat Evaluation Procedures previously developed by the U.S. Fish and Wildlife Service.

  15. SNAP: An Astrophysical Camp That Flies High!

    NASA Astrophysics Data System (ADS)

    Forbes, D.; English, D.

    2010-08-01

    It has become widely recognized that there is a shortage of students coming out of provincial high schools who plan to pursue careers in scientific and technical fields. We aim to capture the interest and excite the imaginations of Grade 11 students in a three-day camp. The School for Nuclei, Astrophysics, and Particles (SNAP) will combine an introduction to astrophysics with the building and flying of a balloon-borne cosmic-ray detector to the very edge of space.

  16. Triggered Snap-Through of Bistable Shells

    NASA Astrophysics Data System (ADS)

    Cai, Yijie; Huang, Shicheng; Trase, Ian; Hu, Nan; Chen, Zi

    Elastic bistable shells are common structures in nature and engineering, such as the lobes of the Venus flytrap or the surface of a toy jumping poppers. Despite their ubiquity, the parameters that control the bistability of such structures are not well understood. In this study, we explore how the geometrical features of radially symmetric elastic shells affect the shape and potential energy of a shell's stable states, and how to tune certain parameters in order to generate a snap-through transition from a convex semi-stable state to concave stable state. We fabricated a series of elastic shells with varying geometric parameters out of silicone rubber and measured the resulting potential energy in the semi-stable state. Finite element simulations were also conducted in order to determine the deformation and stress in the shells during snap-through. It was found that the energy of the semi-stable state is controlled by only two geometric parameters and a dimensionless ratio. We also noted two distinct transitions during snap-through, one between monostability and semi-bistability (the state a popper toy is in before it snaps-through and jumps), and a second transition between semi-bistability and true bistability. This work shows that it is possible to use a set of simple parameters to tailor the energy landscape of an elastic shell in order to generate complex trigger motions for their potential use in smart applications. Z.C. acknowledge support from Society in Science-Branco Weiss Fellowship, administered by ETH Zurich.

  17. SnapShot: GI tract development.

    PubMed

    McGrath, Patrick S; Wells, James M

    2015-03-26

    The endoderm germ layer contributes to the respiratory and gastrointestinal (GI) lineages during development, giving rise to an array of specialized epithelial cell types lining organs, including the thyroid, thymus, lungs, liver, biliary system, pancreas, and intestines. This SnapShot timelines and summarizes key stages following gastrulation, including endoderm patterning, organ specification, and organogenesis. A lineage tree of the developing endocrine pancreas is outlined to further illustrate this process.

  18. Vortex Formation with a Snapping Shrimp Claw

    PubMed Central

    Hess, David; Brücker, Christoph; Hegner, Franziska; Balmert, Alexander; Bleckmann, Horst

    2013-01-01

    Snapping shrimp use one oversized claw to generate a cavitating high speed water jet for hunting, defence and communication. This work is an experimental investigation about the jet generation. Snapping shrimp (Alpheus-bellulus) were investigated by using an enlarged transparent model reproducing the closure of the snapper claw. Flow inside the model was studied using both High-Speed Particle Image Velocimetry (HS-PIV) and flow visualization. During claw closure a channel-like cavity was formed between the plunger and the socket featuring a nozzle-type contour at the orifice. Closing the mechanism led to the formation of a leading vortex ring with a dimensionless formation number of approximate ΔT*≈4. This indicates that the claw might work at maximum efficiency, i.e. maximum vortex strength was achieved by a minimum of fluid volume ejected. The subsequent vortex cavitation with the formation of an axial reentrant jet is a reasonable explanation for the large penetration depth of the water jet. That snapping shrimp can reach with their claw-induced flow. Within such a cavitation process, an axial reentrant jet is generated in the hollow cylindrical core of the cavitated vortex that pushes the front further downstream and whose length can exceed the initial jet penetration depth by several times. PMID:24244273

  19. Gasket and snap ring installation tool

    DOEpatents

    Southerland, Jr., James M.; Barringer, Jr., Curtis N.

    1994-01-01

    A tool for installing a gasket and a snap ring including a shaft, a first plate attached to the forward end of the shaft, a second plate slidably carried by the shaft, a spring disposed about the shaft between the first and second plates, and a sleeve that is free to slide over the shaft and engage the second plate. The first plate has a loading surface with a loading groove for receiving a snap ring and a shoulder for holding a gasket. A plurality of openings are formed through the first plate, communicating with the loading groove and approximately equally spaced about the groove. A plurality of rods are attached to the second plate, each rod slidable in one of the openings. In use, the loaded tool is inserted into a hollow pipe or pipe fitting having an internal flange and an internal seating groove, such that the gasket is positioned against the flange and the ring is in the approximate plane of the seating groove. The sleeve is pushed against the second plate, sliding the second plate towards the first plate, compressing the spring and sliding the rods forwards in the openings. The rods engage the snap ring and urge the ring from the loading groove into the seating groove.

  20. Concentration of Tobacco Advertisements at SNAP and WIC Stores, Philadelphia, Pennsylvania, 2012

    PubMed Central

    Chilton, Mariana; Zhao, Qian-Wei; Szymkowiak, Dorota; Coffman, Ryan; Mallya, Giridhar

    2015-01-01

    Introduction Tobacco advertising is widespread in urban areas with racial/ethnic minority and low-income households that participate in nutrition assistance programs. Tobacco sales and advertising are linked to smoking behavior, which may complicate matters for low-income families struggling with disparate health risks relating to nutrition and chronic disease. We investigated the relationship between the amount and type of tobacco advertisements on tobacco outlets and the outlet type and location. Methods By using field visits and online images, we inspected all licensed tobacco retail outlets in Philadelphia (N = 4,639). Point pattern analyses were used to identify significant clustering of tobacco outlets and outlets with exterior tobacco advertisements. Logistic regression was used to analyze the relationship between the outlet’s acceptance of Supplemental Nutrition Assistance Program (SNAP) and Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and the presence of tobacco advertisements. Results Tobacco outlets with exterior tobacco advertisements were significantly clustered in several high-poverty areas. Controlling for racial/ethnic and income composition and land use, SNAP and WIC vendors were significantly more likely to have exterior (SNAP odds ratio [OR], 2.11; WIC OR, 1.59) and interior (SNAP OR, 3.43; WIC OR, 1.69) tobacco advertisements than other types of tobacco outlets. Conclusion Tobacco advertising is widespread at retail outlets, particularly in low-income and racial/ethnic minority neighborhoods. Policy makers may be able to mitigate the effects of this disparate exposure through tobacco retail licensing, local sign control rules, and SNAP and WIC authorization. PMID:25654220

  1. Comparative Analysis of Government and Private Sector ADP Acquisition.

    DTIC Science & Technology

    1984-03-01

    perscnnel, procedures, and equipment (including ADPE) which is designed , built, operated and maintained to collect, process, store, retrieve, and display...Automatic Data Ptrocessing and Teleccmmunica-ticns Management Policy), FPMR 101-36 (Autcmatic Data Processing aanagement), and FPMR 101-37...Circular A-109 within DOC. It was initially intended tc apply to those programs designated by the Secretary cf 26 Defenss as "M!a~cr systems Acqui’Siticn

  2. Snap-Through Instability Patterns in Truss Structures

    NASA Technical Reports Server (NTRS)

    Hrinda, Glenn A.

    2010-01-01

    Geometrically nonlinear truss structures with snap-through behavior are demonstrated by using an arc length approach within a finite element analysis. The instability patterns are equilibrium paths that are plotted throughout the snap-through event. Careful observation of these patterns helps to identify weak designs in large space structures, as well as identify desirable snap-through behavior in the miniaturization of electronic devices known as microelectromechanical systems (MEMS). Examples of highly nonlinear trusses that show snap-through behavior are examined by tracing their equilibrium paths.

  3. SNAP: Spreadsheet Nebular Analysis Package

    NASA Astrophysics Data System (ADS)

    Komljenovic, M.; Krawchuk, C.; McCall, M.; Kingsburgh, R.; Richer, Michael; Stevenson, C.

    1996-12-01

    A flexible and extensible software package for two dimensional nebular analyses has been implemented using Visual Basic within Microsoft Excel (version 5). From a calibrated list of fluxes and errors for each spectral row (or object), the program first identifies the lines by their source ions by referring to wavelengths generated from atomic data. The atomic data used in all the calculations is easily updated or augmented by the user. Colour excesses can be computed from a reddening law and ratio of total to selective extinction of a user's choice. For each spectral row, line fluxes can be corrected for stellar absorption and reddening and reported in a format suitable for publication. Temperatures, densities, emission coefficients, and ionic abundances are computed using an adaptation of the FIVEL five-level atom routine. The user has complete control over which spectral lines are used in an analysis -- there are no pre-ordained methods. Abundance analyses can be performed using physical conditions either measured or specified for each spectrum. Since the software is embedded in Microsoft Excel, graphical representations of the data are easily created, and extended analyses using the full functionality of the spreadsheet are easily implemented.

  4. Detection and quantification of poly-ADP-ribosylated cellular proteins of spleen and liver tissues of mice in vivo by slot and Western blot immunoprobing using polyclonal antibody against mouse ADP-ribose polymer.

    PubMed

    Sharan, R N; Devi, B Jaylata; Humtsoe, J O; Saikia, Jyoti R; Kma, L

    2005-10-01

    Poly-ADP-ribosylation (PAR) of cellular proteins has been shown to have decisive roles in diverse cellular functions including carcinogenesis. There are indications that metabolic level of poly-ADP-ribosylated cellular proteins might indicate carcinogenesis and, therefore, could be potentially used in cancer screening program. Keeping in mind the limitations of currently available assays of cellular PAR, a new assay is being reported that measures the metabolic level of poly-ADP-ribosylated cellular proteins. The ELISA based slot and Western blot immunoassay used polyclonal antibody against natural, heterogeneous ADP-ribose polymers. It could be successfully employed to qualitatively and quantitatively assay metabolic levels of poly-ADP-ribosylated proteins of spleen and liver tissues of normal mice or mice exposed to dimethylnitrosamine for up to 8 weeks; potentially PAR of cellular proteins could be assayed in any tissue or biopsy. Implications of the results in cancer screening program have been discussed.

  5. Behavioral Economics and the Supplemental Nutrition Assistance Program:: Making the Healthy Choice the Easy Choice.

    PubMed

    Ammerman, Alice S; Hartman, Terry; DeMarco, Molly M

    2017-02-01

    The Supplemental Nutrition Assistance Program (SNAP) serves as an important nutritional safety net program for many Americans. Given its aim to use traditional economic levers to provide access to food, the SNAP program includes minimal nutritional requirements and restrictions. As food choices are influenced by more than just economic constraints, behavioral economics may offer insights and tools for altering food purchases for SNAP users. This manuscript outlines behavioral economics strategies that have potential to encourage healthier food choices within the SNAP program.

  6. SNAP25 Expression in Mammalian Retinal Horizontal Cells

    PubMed Central

    Hirano, Arlene A.; Brandstätter, Johann Helmut; Morgans, Catherine W.; Brecha, Nicholas C.

    2014-01-01

    Horizontal cells mediate inhibitory feedforward and feedback lateral interactions in the outer retina at photoreceptor terminals and bipolar cell dendrites; however, the mechanisms that underlie synaptic transmission from mammalian horizontal cells are poorly understood. The localization of a vesicular γ-aminobutyric acid (GABA) transporter (VGAT) to horizontal cell processes in primate and rodent retinae suggested that mammalian horizontal cells release transmitter in a vesicular manner. Toward determining whether the molecular machinery for vesicular transmitter release is present in horizontal cells, we investigated the expression of SNAP25 (synaptosomal-associated protein of 25 kDa), a key SNARE protein, by immunocytochemistry with cell type-specific markers in the retinae of mouse, rat, rabbit, and monkey. Different commercial antibodies to SNAP25 were tested on vertical sections of retina. We report the robust expression of SNAP25 in both plexiform layers. Double labeling with SNAP25 and calbindin antibodies demonstrated that horizontal cell processes and their endings in photoreceptor triad synapses were strongly labeled for both proteins in mouse, rat, rabbit, and monkey retinae. Double labeling with parvalbumin antibodies in monkey retina verified SNAP25 immunoreactivity in all horizontal cells. Pre-embedding immunoelectron microscopy in rabbit retina confirmed expression of SNAP25 in lateral elements within photoreceptor triad synapses. The SNAP25 immunoreactivity in the plexiform layers and outer nuclear layer fell into at least three patterns depending on the antibody, suggesting a differential distribution of SNAP25 isoforms. The presence of SNAP25a and SNAP25b isoforms in mouse retina was established by reverse transcriptase-polymerase chain reaction. SNAP25 expression in mammalian horizontal cells along with other SNARE proteins is consistent with vesicular exocytosis. PMID:21280047

  7. A document review to characterize Atomic International SNAP fuels shipped to INEL 1966--1973

    SciTech Connect

    Wahnschaffe, S.D.; Lords, R.E.; Kneff, D.W.; Nagel, W.E.; Pearlman, H.; Schaubert, V.J.

    1995-09-01

    This report provides the results of a document search and review study to obtain information on the spent fuels for the following six Nuclear Auxiliary Power (SNAP) reactor cores now stored at the Idaho National Engineering Laboratory (INEL): SNAP-2 Experimental Reactor, SNAP-2 Development Reactor, SNAP-10A Ground Test Reactor, SNAP-8 Experimental Reactor, SNAP-8 Development Reactor, and Shield Test Reactor. The report also covers documentation on SNAP fuel materials from four in-pile materials tests: NAA-82-1, NAA-115-2, NAA-117-1, and NAA-121. Pieces of these fuel materials are also stored at INEL as part of the SNAP fuel shipments.

  8. Molecular Dynamics Study of Hsp90 and ADP: Hydrogen Bond Analysis for ADP Dissociation

    NASA Astrophysics Data System (ADS)

    Kawaguchi, Kazutomo; Saito, Hiroaki; Nagao, Hidemi

    The contacts between the N-terminal domain of heat shock protein 90 (N-Hsp90) and ADP involve both direct and water-mediated hydrogen bonds in X-ray crystallographic structure. We perform all-atom molecular dynamics (MD) simulations of N-Hsp90 and ADP to investigate the changes of the hydrogen bond lengths during ADP dissociation. We show the difference between the hydrogen bonds in the crystal structure and MD simulations. Moreover, the N6 group of ADP does not contact with the Cγ group of Asp93, and the hydrogen bonds between Asn51 side chain and ADP are stable in the early step of ADP dissociation.

  9. Critical slowing down in purely elastic 'snap-through' instabilities

    NASA Astrophysics Data System (ADS)

    Gomez, Michael; Moulton, Derek E.; Vella, Dominic

    2016-10-01

    Many elastic structures have two possible equilibrium states: from umbrellas that become inverted in a sudden gust of wind, to nanoelectromechanical switches, origami patterns and the hopper popper, which jumps after being turned inside-out. These systems typically transition from one state to the other via a rapid `snap-through’. Snap-through allows plants to gradually store elastic energy, before releasing it suddenly to generate rapid motions, as in the Venus flytrap. Similarly, the beak of the hummingbird snaps through to catch insects mid-flight, while technological applications are increasingly exploiting snap-through instabilities. In all of these scenarios, it is the ability to repeatedly generate fast motions that gives snap-through its utility. However, estimates of the speed of snap-through suggest that it should occur more quickly than is usually observed. Here, we study the dynamics of snap-through in detail, showing that, even without dissipation, the dynamics slow down close to the snap-through transition. This is reminiscent of the slowing down observed in critical phenomena, and provides a handheld demonstration of such phenomena, as well as a new tool for tuning dynamic responses in applications of elastic bistability.

  10. Snapping Supernovae at z>1.7

    SciTech Connect

    Aldering, Greg; Kim, Alex G.; Kowalski, Marek; Linder, Eric V.; Perlmutter, Saul

    2006-07-03

    We examine the utility of very high redshift Type Ia supernovae for cosmology and systematic uncertainty control. Next generation space surveys such as the Supernova/Acceleration Probe (SNAP) will obtain thousands of supernovae at z>1.7, beyond the design redshift for which the supernovae will be exquisitely characterized. We find that any z gtrsim 2 standard candles' use for cosmological parameter estimation is quite modest and subject to pitfalls; we examine gravitational lensing, redshift calibration, and contamination effects in some detail. The very high redshift supernovae - both thermonuclear and core collapse - will provide copious interesting information on star formation, environment, and evolution. However, the new observational systematics that must be faced, as well as the limited expansion of SN-parameter space afforded, does not point to high value for 1.7SNAP can already achieve at z<1.7. Synergy with observations from JWST and thirty meter class telescopes afford rich opportunities for advances throughout astrophysics.

  11. SNAP Visible Detectors: Status and Plans

    NASA Astrophysics Data System (ADS)

    Bailey, S. J.; Bebek, C. J.; SNAP

    2004-12-01

    The SuperNova / Acceleration Probe (SNAP) will measure approximately 2000 type Ia supernovae from redshift z=0.3 to 1.7 in nine photometric bands and perform a wide area weak lensing survey. This requires radiation hard CCDs with high resolution, low noise, low dark current, and high quantum efficiency (QE) from blue to near-infrared wavelengths. On this poster we report the current status and recent progress of the SNAP CCD development using UCB/LBNL thick (200-300 μ m) fully depleted CCDs. These CCDs have QE > 80% from 450 to 950 nm and maintain QE 50% at 1000 nm. This CCD technology has been deployed on 4 telescopes and has been selected as the technology choice for DECam, a 520 megapixel camera planned for installation at the Blanco 4-m telescope at CTIO. We describe the current performance, production, and packaging for these CCDs as well as future plans. This work has been supported by the U.S. Dept. of Energy, Office of Science, under contract DE-AC03-76SF00098.

  12. Nitric oxide-donor SNAP induces Xenopus eggs activation.

    PubMed

    Jeseta, Michal; Marin, Matthieu; Tichovska, Hana; Melicharova, Petra; Cailliau-Maggio, Katia; Martoriati, Alain; Lescuyer-Rousseau, Arlette; Beaujois, Rémy; Petr, Jaroslav; Sedmikova, Marketa; Bodart, Jean-François

    2012-01-01

    Nitric oxide (NO) is identified as a signaling molecule involved in many cellular or physiological functions including meiotic maturation and parthenogenetic activation of mammalian oocytes. We observed that nitric oxide donor SNAP was potent to induce parthenogenetic activation in Xenopus eggs. NO-scavenger CPTIO impaired the effects of SNAP, providing evidence for the effects of the latter to be specific upon NO release. In Xenopus eggs, SNAP treatment induced pigment rearrangement, pronucleus formation and exocytosis of cortical granules. At a biochemical level, SNAP exposure lead to MAPK and Rsk inactivation within 30 minutes whereas MPF remained active, in contrast to calcium ionophore control where MPF activity dropped rapidly. MAPK inactivation could be correlated to pronuclear envelope reformation observed. In SNAP-treated eggs, a strong increase in intracellular calcium level was observed. NO effects were impaired in calcium-free or calcium limited medium, suggesting that that parthenogenetic activation of Xenopus oocytes with a NO donor was mainly calcium-dependent.

  13. 26 CFR 1.401(k)-2 - ADP test.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false ADP test. 1.401(k)-2 Section 1.401(k)-2 Internal... TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(k)-2 ADP test. (a) Actual deferral percentage (ADP) test—(1) In general—(i) ADP test formula. A cash or deferred...

  14. Poly(ADP-ribosyl)ation in carcinogenesis.

    PubMed

    Masutani, Mitsuko; Fujimori, Hiroaki

    2013-12-01

    Cancer develops through diverse genetic, epigenetic and other changes, so-called 'multi-step carcinogenesis', and each cancer harbors different alterations and properties. Here in this article we review how poly(ADP-ribosyl)ation is involved in multi-step and diverse pathways of carcinogenesis. Involvement of poly- and mono-ADP-ribosylation in carcinogenesis has been studied at molecular and cellular levels, and further by animal models and human genetic approaches. PolyADP-ribosylation acts in DNA damage repair response and maintenance mechanisms of genomic stability. Several DNA repair pathways, including base-excision repair and double strand break repair pathways, involve PARP and PARG functions. These care-taker functions of poly(ADP-ribosyl)ation suggest that polyADP-ribosyation may mainly act in a tumor suppressive manner because genomic instability caused by defective DNA repair response could serve as a driving force for tumor progression, leading to invasion, metastasis and relapse of cancer. On the other hand, the new concept of 'synthetic lethality by PARP inhibition' suggests the significance of PARP activities for survival of cancer cells that harbor defects in DNA repair. Accumulating evidence has revealed that some PARP family molecules are involved in various signaling cascades other than DNA repair, including epigenetic and transcriptional regulations, inflammation/immune response and epithelial-mesenchymal transition, suggesting that poly(ADP-ribosyl)ation both promotes and suppresses carcinogenic processes depending on the conditions. Expanding understanding of poly(ADP-ribosyl)ation suggests that strategies to achieve cancer prevention targeting poly(ADP-ribosyl)ation for genome protection against life-long exposure to environmental carcinogens and endogenous carcinogenic stimuli.

  15. Kinesin ATPase: Rate-Limiting ADP Release

    NASA Astrophysics Data System (ADS)

    Hackney, David D.

    1988-09-01

    The ATPase rate of kinesin isolated from bovine brain by the method of S. A. Kuznetsov and V. I. Gelfand [(1986) Proc. Natl. Acad. Sci. USA 83, 8530-8534)] is stimulated 1000-fold by interaction with tubulin (turnover rate per 120-kDa peptide increases from ≈ 0.009 sec-1 to 9 sec-1). The tubulin-stimulated reaction exhibits no extra incorporation of water-derived oxygens over a wide range of ATP and tubulin concentrations, indicating that Pi release is faster than the reversal of hydrolysis. ADP release, however, is slow for the basal reaction and its release is rate limiting as indicated by the very tight ADP binding (Ki < 5 nM), the retention of a stoichiometric level of bound ADP through ion-exchange chromatography and dialysis, and the reversible labeling of a bound ADP by [14C]ATP at the steady-state ATPase rate as shown by centrifuge gel filtration and inaccessibility to pyruvate kinase. Tubulin accelerates the release of the bound ADP consistent with its activation of the net ATPase reaction. The detailed kinetics of ADP release in the presence of tubulin are biphasic indicating apparent heterogeneity with a fraction of the kinesin active sites being unaffected by tubulin.

  16. Targeting poly(ADP-ribose) polymerase activity for cancer therapy

    PubMed Central

    Mégnin-Chanet, Frédérique; Bollet, Marc A.

    2010-01-01

    Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated. PMID:20725763

  17. Analytical Design Package (ADP2): A computer aided engineering tool for aircraft transparency design

    NASA Technical Reports Server (NTRS)

    Wuerer, J. E.; Gran, M.; Held, T. W.

    1994-01-01

    The Analytical Design Package (ADP2) is being developed as a part of the Air Force Frameless Transparency Program (FTP). ADP2 is an integrated design tool consisting of existing analysis codes and Computer Aided Engineering (CAE) software. The objective of the ADP2 is to develop and confirm an integrated design methodology for frameless transparencies, related aircraft interfaces, and their corresponding tooling. The application of this methodology will generate high confidence for achieving a qualified part prior to mold fabrication. ADP2 is a customized integration of analysis codes, CAE software, and material databases. The primary CAE integration tool for the ADP2 is P3/PATRAN, a commercial-off-the-shelf (COTS) software tool. The open architecture of P3/PATRAN allows customized installations with different applications modules for specific site requirements. Integration of material databases allows the engineer to select a material, and those material properties are automatically called into the relevant analysis code. The ADP2 materials database will be composed of four independent schemas: CAE Design, Processing, Testing, and Logistics Support. The design of ADP2 places major emphasis on the seamless integration of CAE and analysis modules with a single intuitive graphical interface. This tool is being designed to serve and be used by an entire project team, i.e., analysts, designers, materials experts, and managers. The final version of the software will be delivered to the Air Force in Jan. 1994. The Analytical Design Package (ADP2) will then be ready for transfer to industry. The package will be capable of a wide range of design and manufacturing applications.

  18. The SNAP-25 Linker as an Adaptation Toward Fast Exocytosis

    PubMed Central

    Nagy, Gábor; Milosevic, Ira; Mohrmann, Ralf; Wiederhold, Katrin; Walter, Alexander M.

    2008-01-01

    The assembly of four soluble N-ethylmaleimide-sensitive factor attachment protein receptor domains into a complex is essential for membrane fusion. In most cases, the four SNARE-domains are encoded by separate membrane-targeted proteins. However, in the exocytotic pathway, two SNARE-domains are present in one protein, connected by a flexible linker. The significance of this arrangement is unknown. We characterized the role of the linker in SNAP-25, a neuronal SNARE, by using overexpression techniques in synaptosomal-associated protein of 25 kDa (SNAP-25) null mouse chromaffin cells and fast electrophysiological techniques. We confirm that the palmitoylated linker-cysteines are important for membrane association. A SNAP-25 mutant without cysteines supported exocytosis, but the fusion rate was slowed down and the fusion pore duration prolonged. Using chimeric proteins between SNAP-25 and its ubiquitous homologue SNAP-23, we show that the cysteine-containing part of the linkers is interchangeable. However, a stretch of 10 hydrophobic and charged amino acids in the C-terminal half of the SNAP-25 linker is required for fast exocytosis and in its absence the calcium dependence of exocytosis is shifted toward higher concentrations. The SNAP-25 linker therefore might have evolved as an adaptation toward calcium triggering and a high rate of execution of the fusion process, those features that distinguish exocytosis from other membrane fusion pathways. PMID:18579690

  19. Mild cognitive impairment with suspected nonamyloid pathology (SNAP)

    PubMed Central

    Caroli, Anna; Prestia, Annapaola; Galluzzi, Samantha; Ferrari, Clarissa; van der Flier, Wiesje M.; Ossenkoppele, Rik; Van Berckel, Bart; Barkhof, Frederik; Teunissen, Charlotte; Wall, Anders E.; Carter, Stephen F.; Schöll, Michael; Choo, Il Han; Grimmer, Timo; Redolfi, Alberto; Nordberg, Agneta; Scheltens, Philip; Drzezga, Alexander

    2015-01-01

    Objectives: The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non–Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI). Methods: We measured markers of amyloid pathology (CSF β-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [18F]-fluorodeoxyglucose–PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A− and N+/N− based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A−N+ cases. Results: The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A−N−, A+N−, SNAP, and A+N+, respectively; the proportion of APOE ε4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N− and A+N+ groups (p ≤ 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A−N−, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N− patients did not (hazard ratio = 1.13, p = 0.771). In A+N− and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073). Conclusions: Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile. PMID:25568301

  20. FlexSnap: Flexible Non-sequential Protein Structure Alignment

    NASA Astrophysics Data System (ADS)

    Salem, Saeed; Zaki, Mohammed J.; Bystroff, Chris

    Proteins have evolved subject to energetic selection pressure for stability and flexibility. Structural similarity between proteins which have gone through conformational changes can be captured effectively if flexibility is considered. Topologically unrelated proteins that preserve secondary structure packing interactions can be detected if both flexibility and sequence permutations are considered. We propose the FlexSnap algorithm for flexible non-topological protein structural alignment. The effectiveness of FlexSnap is demonstrated by measuring the agreement of its alignments with manually curated non-sequential structural alignments. FlexSnap showed competitive results against state-of-the-art algorithms, like DALI, SARF2, MultiProt, FlexProt, and FATCAT.

  1. SNAP sky background at the north ecliptic pole

    SciTech Connect

    Aldering, Greg

    2002-07-01

    I summarize the extant direct and indirect data on the sky background SNAP will see at the North Ecliptic Pole over the wavelength range 0.4 < {lambda} < 1.7 {micro}m. At the spatial resolution of SNAP the sky background due to stars and galaxies is resolved, so the only source considered is zodiacal light. Several models are explored to provide interpolation in wavelength between the broadband data from HST and COBE observations. I believe the input data are now established well enough that the accuracy of the sky background presented here is sufficient for SNAP simulations, and that it will stand up to scrutiny by reviewers.

  2. Food Assistance Programs and Child Health

    ERIC Educational Resources Information Center

    Gundersen, Craig

    2015-01-01

    Food assistance programs--including the Supplemental Nutrition Assistance Program (SNAP, or food stamps), the National School Lunch Program, and the School Breakfast Program--have been remarkably successful at their core mission: reducing food insecurity among low-income children. Moreover, writes Craig Gundersen, SNAP in particular has also been…

  3. SNAP: A General Purpose Network Analysis and Graph Mining Library.

    PubMed

    Leskovec, Jure; Sosič, Rok

    2016-10-01

    Large networks are becoming a widely used abstraction for studying complex systems in a broad set of disciplines, ranging from social network analysis to molecular biology and neuroscience. Despite an increasing need to analyze and manipulate large networks, only a limited number of tools are available for this task. Here, we describe Stanford Network Analysis Platform (SNAP), a general-purpose, high-performance system that provides easy to use, high-level operations for analysis and manipulation of large networks. We present SNAP functionality, describe its implementational details, and give performance benchmarks. SNAP has been developed for single big-memory machines and it balances the trade-off between maximum performance, compact in-memory graph representation, and the ability to handle dynamic graphs where nodes and edges are being added or removed over time. SNAP can process massive networks with hundreds of millions of nodes and billions of edges. SNAP offers over 140 different graph algorithms that can efficiently manipulate large graphs, calculate structural properties, generate regular and random graphs, and handle attributes and meta-data on nodes and edges. Besides being able to handle large graphs, an additional strength of SNAP is that networks and their attributes are fully dynamic, they can be modified during the computation at low cost. SNAP is provided as an open source library in C++ as well as a module in Python. We also describe the Stanford Large Network Dataset, a set of social and information real-world networks and datasets, which we make publicly available. The collection is a complementary resource to our SNAP software and is widely used for development and benchmarking of graph analytics algorithms.

  4. Seeing the Nature of the Accelerating Physics: It's a SNAP

    SciTech Connect

    Albert, J.; Aldering, G.; Allam, S.; Althouse, W.; Amanullah, R.; Annis, J.; Astier, P.; Aumeunier, M.; Bailey, S.; Baltay, C.; Barrelet, E.; Basa, S.; Bebek, C.; Bergstom, L.; Bernstein, G.; Bester, M.; Besuner, B.; Bigelow, B.; Blandford, R.; Bohlin, R.; Bonissent, A.; /Caltech /LBL, Berkeley /Fermilab /SLAC /Stockholm U. /Paris, IN2P3 /Marseille, CPPM /Marseille, Lab. Astrophys. /Yale U. /Pennsylvania U. /UC, Berkeley /Michigan U. /Baltimore, Space Telescope Sci. /Indiana U. /Caltech, JPL /Australian Natl. U., Canberra /American Astron. Society /Chicago U. /Cambridge U. /Saclay /Lyon, IPN

    2005-08-05

    For true insight into the nature of dark energy, measurements of the precision and accuracy of the Supernova/Acceleration Probe (SNAP) are required. Precursor or scaled-down experiments are unavoidably limited, even for distinguishing the cosmological constant. They can pave the way for, but should not delay, SNAP by developing calibration, refinement, and systematics control (and they will also provide important, exciting astrophysics).

  5. SNAP: A General Purpose Network Analysis and Graph Mining Library

    PubMed Central

    Leskovec, Jure; Sosič, Rok

    2016-01-01

    Large networks are becoming a widely used abstraction for studying complex systems in a broad set of disciplines, ranging from social network analysis to molecular biology and neuroscience. Despite an increasing need to analyze and manipulate large networks, only a limited number of tools are available for this task. Here, we describe Stanford Network Analysis Platform (SNAP), a general-purpose, high-performance system that provides easy to use, high-level operations for analysis and manipulation of large networks. We present SNAP functionality, describe its implementational details, and give performance benchmarks. SNAP has been developed for single big-memory machines and it balances the trade-off between maximum performance, compact in-memory graph representation, and the ability to handle dynamic graphs where nodes and edges are being added or removed over time. SNAP can process massive networks with hundreds of millions of nodes and billions of edges. SNAP offers over 140 different graph algorithms that can efficiently manipulate large graphs, calculate structural properties, generate regular and random graphs, and handle attributes and meta-data on nodes and edges. Besides being able to handle large graphs, an additional strength of SNAP is that networks and their attributes are fully dynamic, they can be modified during the computation at low cost. SNAP is provided as an open source library in C++ as well as a module in Python. We also describe the Stanford Large Network Dataset, a set of social and information real-world networks and datasets, which we make publicly available. The collection is a complementary resource to our SNAP software and is widely used for development and benchmarking of graph analytics algorithms. PMID:28344853

  6. Common snapping turtle preys on an adult western grebe

    USGS Publications Warehouse

    Igl, L.D.; Peterson, S.L.

    2010-01-01

    The identification of predators of aquatic birds can be difficult. The Common Snapping Turtle (Chelydra serpentine) is considered a major predator of waterfowl and other aquatic birds, but the evidence for this reputation is based largely on circumstantial or indirect evidence rather than direct observations. Herein, the first documented observations of a snapping turtle attacking and killing an adult Western Grebe (Aechmophorus occidentalis) are described.

  7. The Supplemental Nutrition Assistance Program

    PubMed Central

    Pomeranz, Jennifer L.; Chriqui, Jamie F.

    2015-01-01

    Under the current version of the Supplemental Nutrition Assistance Program (SNAP), participants can purchase virtually any food or beverage (collectively, food). Research indicates that SNAP recipients may have worse dietary quality than income-eligible nonparticipants. Policymakers have urged the U.S. Department of Agriculture (USDA) to pilot SNAP purchasing restrictions intended to support a healthier diet, and state legislators have proposed similar bills. The USDA rejected these invitations, stating that it would be administratively and logistically difficult to differentiate among products, amid other concerns. However, the USDA’s Dietary Guidelines for Americans and the Supplemental Nutrition Program for Women, Infants, and Children (WIC) do just that. Further, state governments define and differentiate among foods and beverages for tax purposes. This paper reviews several factors intended to inform future policy decisions: the science indicating that SNAP recipients have poorer diet quality than income-eligible nonparticipants; the public’s support for revising the SNAP program; federal, state, and city legislators’ formal proposals to amend SNAP based on nutrition criteria and the USDA’s public position in opposition to these proposals; state bills to amend eligible foods purchasable with SNAP benefits; state retail food tax laws; and the retail administration and program requirements for both WIC and SNAP. The paper finds that the government has a clear ability to align SNAP benefits with nutrition science and operationalize this into law. PMID:26091926

  8. SNP identification and SNAP marker development for a GmNARK gene controlling supernodulation in soybean.

    PubMed

    Kim, M Y; Van, K; Lestari, P; Moon, J-K; Lee, S-H

    2005-04-01

    Supernodulation in soybean (Glycine max L. Merr.) is an important source of nitrogen supply to subterranean ecological systems. Single nucleotide-amplified polymorphism (SNAP) markers for supernodulation should allow rapid screening of the trait in early growth stages, without the need for inoculation and phenotyping. The gene GmNARK (Glycine max nodule autoregulation receptor kinase), controlling autoregulation of nodulation, was found to have a single nucleotide polymorphism (SNP) between the wild-type cultivar Sinpaldalkong 2 and its supernodulating mutant, SS2-2. Transversion of A to T at the 959-bp position of the GmNARK sequence results in a change of lysine (AAG) to a stop codon (TAG), thus terminating its translation in SS2-2. Based on the identified SNP in GmNARK, five primer pairs specific to each allele were designed using the WebSnaper program to develop a SNAP marker for supernodulation. One A-specific primer pair produced a band present in only Sinpaldalkong 2, while two T-specific pairs showed a band in only SS2-2. Both complementary PCRs, using each allele-specific primer pair were performed to genotype supernodulation against F2 progeny of Sinpaldalkong 2 x SS2-2. Among 28 individuals with the normal phenotype, eight individuals having only the A-allele-specific band were homozygous and normal, while 20 individuals were found to be heterozygous at the SNP having both A and T bands. Twelve supernodulating individuals showed only the band specific to the T allele. This SNAP marker for supernodulation could easily be analyzed through simple PCR and agarose gel electrophoresis. Therefore, use of this SNAP marker might be faster, cheaper, and more reproducible than using other genotyping methods, such as a cleaved amplified polymorphic sequence marker, which demand of restriction enzymes.

  9. 42 CFR 457.230 - FFP for State ADP expenditures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false FFP for State ADP expenditures. 457.230 Section 457...; Reduction of Federal Medical Payments § 457.230 FFP for State ADP expenditures. FFP is available for State ADP expenditures for the design, development, or installation of mechanized claims processing...

  10. 32 CFR Appendix J to Part 154 - ADP Position Categories and Criteria for Designating Positions

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., and implementation of a computer security program; major responsibility for the direction, planning... judgement as to the unique characteristics of the system or the safeguards protecting the system. Criteria... categories is as follows: Category Criteria ADP-I Responsibility or the development and administration...

  11. 32 CFR Appendix J to Part 154 - ADP Position Categories and Criteria for Designating Positions

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., and implementation of a computer security program; major responsibility for the direction, planning... judgement as to the unique characteristics of the system or the safeguards protecting the system. Criteria... categories is as follows: Category Criteria ADP-I Responsibility or the development and administration...

  12. 32 CFR Appendix J to Part 154 - ADP Position Categories and Criteria for Designating Positions

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., and implementation of a computer security program; major responsibility for the direction, planning... judgement as to the unique characteristics of the system or the safeguards protecting the system. Criteria... categories is as follows: Category Criteria ADP-I Responsibility or the development and administration...

  13. The NASA/USRA ADP at the University of Central Florida

    NASA Technical Reports Server (NTRS)

    Anderson, L. A.; Armitage, P. K.

    1992-01-01

    An approach to learning engineering design is discussed with particular attention given to the impact of the NASA/Universities Space Research Association (USRA) Advanced Design Program (ADP) on that process. Attention is also given to a teaching method stressing science discipline and creativity and various selected space related designs.

  14. Office of Inspector General report on audit of controls over the ADP support services contract

    SciTech Connect

    1997-08-15

    In March 1995, the Department awarded a cost-plus-award-fee contract to DynCorp valued at approximately $246 million over 5 years for ADP support services at Headquarters. The performance period for the contract was a 3-year base period with two 1-year options. The contract statement of work identified 24 information management functional areas that required technical support services, including Automated Office Systems Support and Local Area Network support. The purpose of the audit was to evaluate the cost-plus-award-fee contract for ADP support services at Headquarters. The objective was to determine whether the Department`s program offices at Headquarters were managing their ADP support services contract costs.

  15. Endoscopic release of internal snapping hip: a review of literature

    PubMed Central

    Via, Alessio Giai; Basile, Attilio; Wainer, Mauricio; Musa, Carlos; Padulo, Johnny; Mardones, Rodrigo

    2016-01-01

    Summary Background Internal snapping hip is a common clinical condition, characterized by an audible or palpable snap of the medial compartment of the hip. In most cases it is asymptomatic, while in a few patients, mostly in athletes who participate in activities requiring extremes of hip range of motion, the snap may become painful (internal snapping hip syndrome - ISHS). Materials and methods This is a review of current literature, focused on the pathogenesis, diagnosis and treatment of ISHS. Conclusion The pathogenesis of ISHS is multifactorial, and it is traditionally believed to be caused by the tendon snapping over the anterior femoral head or the iliopectineal ridge. Most cases of ISHS resolve with conservative treatment, which includes avoidance of aggravating activities, stretching, and NSAIDs. In recalcitrant cases, surgery may be indicated. Better results have been reported with endoscopic iliopsoas tendon release compared with open techniques, which may be related to the treatment of concomitant intra-articular pathologies. Furthermore, endoscopic treatment showed fewer complications, decreased failure rate and postop erative pain. It is important to remember that in most cases, a multiple iliopsoas tendon may exist, and that the incomplete release of the iliopsoas tendon can be a reason for refractory pain and poor results. Then, even if of not clinical relevance at long term follow-up, patients should be told about the inevitable loss of flexion strength after iliopsoas tenotomy. Level of evidence II. PMID:28066743

  16. SNAP-25, a Known Presynaptic Protein with Emerging Postsynaptic Functions

    PubMed Central

    Antonucci, Flavia; Corradini, Irene; Fossati, Giuliana; Tomasoni, Romana; Menna, Elisabetta; Matteoli, Michela

    2016-01-01

    A hallmark of synaptic specializations is their dependence on highly organized complexes of proteins that interact with each other. The loss or modification of key synaptic proteins directly affects the properties of such networks, ultimately impacting synaptic function. SNAP-25 is a component of the SNARE complex, which is central to synaptic vesicle exocytosis, and, by directly interacting with different calcium channels subunits, it negatively modulates neuronal voltage-gated calcium channels, thus regulating intracellular calcium dynamics. The SNAP-25 gene has been associated with distinct brain diseases, including Attention Deficit Hyperactivity Disorder (ADHD), schizophrenia and bipolar disorder, indicating that the protein may act as a shared biological substrate among different “synaptopathies”. The mechanisms by which alterations in SNAP-25 may concur to these psychiatric diseases are still undefined, although alterations in neurotransmitter release have been indicated as potential causative processes. This review summarizes recent work showing that SNAP-25 not only controls exo/endocytic processes at the presynaptic terminal, but also regulates postsynaptic receptor trafficking, spine morphogenesis, and plasticity, thus opening the possibility that SNAP-25 defects may contribute to psychiatric diseases by impacting not only presynaptic but also postsynaptic functions. PMID:27047369

  17. [A new sock and snap electrode for epicardial mapping].

    PubMed

    Iwa, T; Misaki, T; Tsubota, M

    1990-06-01

    Simultaneous recording of epicardial activation from multiple sites during anti-arrhythmic surgery is essential to determine the location of the arrhythmic source. We formed a new sock from Presnet tubular dressing material with 87 snap electrodes. Bipolar recording sites, 1.0 mm in diameter and separated 1.5 mm, are constructed of gold and attached to steel wire directly at the male snap without button. This new Sock and Snap electrode was used to record in 7 patients; 5 of WPW syndrome and 2 of non-ischemic ventricular tachycardia. Satisfactory epicardial contact was obtained in all patients without any hemodynamic change. We could get a rapid display of epicardial mapping using a computer.

  18. Structurally-Tailorable, Nonlinear, Snap-Through Spring

    NASA Technical Reports Server (NTRS)

    Starnes, James H., Jr.; Farley, Gary L.; Mantay, Wayne R.

    1989-01-01

    Abrupt change in load/deflection response controllable and predictable. Structurally-tailorable, nonlinear, snap-through spring (STNSTS) exhibits controllable and predictable abrupt change in load/deflection response and based upon known phenomenon of snap-through structural response. Composed of pin-connected two-bar linkage which depicts combined tension/compression springs. As load applied to STNSTS, stiffness is function of internal spring and bending stiffness of pin-connected bars. As load increases, bars deform laterally until they collapse and snap through. Has application in passively-tailored rotor-blade flap, pitch, and lag response, to improve aerodynamic performance and stability characteristics of rotors; in aerodynamically- and aeroelastically-tailored wing spars and ribs, to produce tailored deformation state for improved effectiveness in maneuvering, aerodynamic performance, and stability characteristics; and in energy absorbers for automobile bumpers and aircraft land

  19. Snap-in of particles at curved liquid interfaces

    NASA Astrophysics Data System (ADS)

    Li, Chao; Moradiafrapoli, Momene; Marston, Jeremy

    2016-11-01

    The contact of particles with liquid interfaces constitutes the first stage in the formation of a particle-laden interface, the so-called "snap-in effect". Here, we report on an experimental study using high-speed video to directly visualize the snap-in process and the approach to the equilibrium state of a particle at a curved liquid interface (i.e. droplet surface). We image the evolution of the contact line, which is found to follow a power-law scaling in time, and the dynamic contact angle during the snap-in. Both hydrophilic and hydrophobic particles are explored and we match the lift-off stage of the particles with a simple force balance. We also explore some multi-particle experiments, eluding to the dynamics of particle-laden interface formation.

  20. Observation of a snap-through instability in graphene

    NASA Astrophysics Data System (ADS)

    Scharfenberg, Scott; Mansukhani, Nikhita; Chialvo, Cesar; Weaver, Richard L.; Mason, Nadya

    2012-01-01

    We examine the competition between adhesive and bending energies for few-layer graphene (FLG) samples placed on microscale-corrugated metallic substrates. Using atomic force microscopy, we show that the graphene undergoes a sharp "snap-through" transition as a function of layer thickness, where the material transitions between conforming to the substrate and lying flat on top of the substrate. By utilizing the critical snap-through thickness in an elasticity model for the FLG's bending, we extract a value for graphene-surface adhesion energy of 1.1 eV/nm2.

  1. Beyond velocity and acceleration: jerk, snap and higher derivatives

    NASA Astrophysics Data System (ADS)

    Eager, David; Pendrill, Ann-Marie; Reistad, Nina

    2016-11-01

    The higher derivatives of motion are rarely discussed in the teaching of classical mechanics of rigid bodies; nevertheless, we experience the effect not only of acceleration, but also of jerk and snap. In this paper we will discuss the third and higher order derivatives of displacement with respect to time, using the trampolines and theme park roller coasters to illustrate this concept. We will also discuss the effects on the human body of different types of acceleration, jerk, snap and higher derivatives, and how they can be used in physics education to further enhance the learning and thus the understanding of classical mechanics concepts.

  2. Evaluation of the Snap Sampler for Sampling Ground Water Monitoring Wells for Inorganic Analytes

    DTIC Science & Technology

    2008-12-01

    within the well. The slits in the two discs were misaligned to limit water exchange. The discs are attached to the Snap Sampler trigger line with...ER D C/ CR R EL T R -0 8 -2 5 Evaluation of the Snap Sampler for Sampling Ground Water Monitoring Wells for Inorganic Analytes...Louise V. Parker, Nathan D. Mulherin, and Gordon E. Gooch December 2008 Well Screen Baffle Snap Sampler Trigger Line Pump Tubing Top Snap Sampler RGC

  3. Progress in the function and regulation of ADP-Ribosylation.

    PubMed

    Hottiger, Michael O; Boothby, Mark; Koch-Nolte, Friedrich; Lüscher, Bernhard; Martin, Niall M B; Plummer, Ruth; Wang, Zhao-Qi; Ziegler, Mathias

    2011-05-24

    Adenosine 5'-diphosphate (ADP)-ribosylation is a protein posttranslational modification that is catalyzed by ADP-ribosyltransferases (ARTs), using nicotinamide adenine dinucleotide (NAD(+)) as a substrate. Mono-ribosylation can be extended into polymers of ADP-ribose (PAR). Poly(ADP-ribosyl)polymerase (PARP) 1, the best-characterized cellular enzyme catalyzing this process, is the prototypical member of a family of mono- and poly(ADP-ribosyl)transferases. The physiological consequences of ADP-ribosylation are inadequately understood. PARP2010, the 18th International Conference on ADP-Ribosylation, attracted scientists from all over the world to Zurich, Switzerland. Highlights from this meeting include promising clinical trials with PARP inhibitors and new insights into cell, structural, and developmental biology of ARTs and the (glyco)hydrolase proteins that catalyze de-ADP-ribosylation of mono- or poly-ADP-ribosylated proteins. Moreover, potential links to the NAD-dependent sirtuin family were explored on the basis of a shared dependence on cellular NAD(+) concentrations and the relationship of ADP-ribosylation with intermediary metabolism and cellular energetics.

  4. ADP ribosylation adapts an ER chaperone response to short-term fluctuations in unfolded protein load

    PubMed Central

    Petrova, Kseniya; Tomba, Giulia; Vendruscolo, Michele

    2012-01-01

    Gene expression programs that regulate the abundance of the chaperone BiP adapt the endoplasmic reticulum (ER) to unfolded protein load. However, such programs are slow compared with physiological fluctuations in secreted protein synthesis. While searching for mechanisms that fill this temporal gap in coping with ER stress, we found elevated levels of adenosine diphosphate (ADP)–ribosylated BiP in the inactive pancreas of fasted mice and a rapid decline in this modification in the active fed state. ADP ribosylation mapped to Arg470 and Arg492 in the substrate-binding domain of hamster BiP. Mutations that mimic the negative charge of ADP-ribose destabilized substrate binding and interfered with interdomain allosteric coupling, marking ADP ribosylation as a rapid posttranslational mechanism for reversible inactivation of BiP. A kinetic model showed that buffering fluctuations in unfolded protein load with a recruitable pool of inactive chaperone is an efficient strategy to minimize both aggregation and costly degradation of unfolded proteins. PMID:22869598

  5. Analysis of variation for white mold resistance in the BeanCAP snap bean panel

    Technology Transfer Automated Retrieval System (TEKTRAN)

    White mold disease caused by Sclerotinia sclerotiorum Lib. de Bary, is one of the most devastated diseases that infect snap and dry beans (Miklas et al. 2013). The USDA-NIFA supported Bean Coordinated Agricultural Project (CAP) has assembled and genotyped dry and a snap bean panels. The snap bean pa...

  6. The SNAP Platform: Social Networking for Academic Purposes

    ERIC Educational Resources Information Center

    Kirkwood, Keith

    2010-01-01

    Purpose: This paper aims to introduce an enterprise-wide Web 2.0 learning support platform--SNAP, developed at Victoria University in Melbourne, Australia. Design/methodology/approach: Pointing to the evolution of the social web, the paper discusses the potential for the development of e-learning platforms that employ constructivist, connectivist,…

  7. 40 CFR 82.180 - Agency review of SNAP submissions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... conditions of use are met to minimize risks to human health and the environment. Where users intending to... adverse effects to human health and the environment and that other alternatives exist that reduce overall... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Agency review of SNAP submissions....

  8. 40 CFR 82.180 - Agency review of SNAP submissions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... evaluate: (i) Atmospheric effects and related health and environmental impacts; (ii) General population... 40 Protection of Environment 18 2012-07-01 2012-07-01 false Agency review of SNAP submissions. 82.180 Section 82.180 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...

  9. 40 CFR 82.180 - Agency review of SNAP submissions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... evaluate: (i) Atmospheric effects and related health and environmental impacts; (ii) General population... 40 Protection of Environment 17 2011-07-01 2011-07-01 false Agency review of SNAP submissions. 82.180 Section 82.180 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...

  10. 40 CFR 82.180 - Agency review of SNAP submissions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... evaluate: (i) Atmospheric effects and related health and environmental impacts; (ii) General population... 40 Protection of Environment 18 2013-07-01 2013-07-01 false Agency review of SNAP submissions. 82.180 Section 82.180 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...

  11. The Supplemental Nutrition Assistance Program: Analysis of Program Administration and Food Law Definitions.

    PubMed

    Pomeranz, Jennifer L; Chriqui, Jamie F

    2015-09-01

    Under the current version of the Supplemental Nutrition Assistance Program (SNAP), participants can purchase virtually any food or beverage (collectively, food). Research indicates that SNAP recipients may have worse dietary quality than income-eligible nonparticipants. Policymakers have urged the U.S. Department of Agriculture (USDA) to pilot SNAP purchasing restrictions intended to support a healthier diet, and state legislators have proposed similar bills. The USDA rejected these invitations, stating that it would be administratively and logistically difficult to differentiate among products, amid other concerns. However, the USDA's Dietary Guidelines for Americans and the Supplemental Nutrition Program for Women, Infants, and Children (WIC) do just that. Further, state governments define and differentiate among foods and beverages for tax purposes. This paper reviews several factors intended to inform future policy decisions: the science indicating that SNAP recipients have poorer diet quality than income-eligible nonparticipants; the public's support for revising the SNAP program; federal, state, and city legislators' formal proposals to amend SNAP based on nutrition criteria and the USDA's public position in opposition to these proposals; state bills to amend eligible foods purchasable with SNAP benefits; state retail food tax laws; and the retail administration and program requirements for both WIC and SNAP. The paper finds that the government has a clear ability to align SNAP benefits with nutrition science and operationalize this into law.

  12. ADP-ribosylation of histones by ARTD1: an additional module of the histone code?

    PubMed

    Hottiger, Michael O

    2011-06-06

    ADP-ribosylation is a covalent post-translational protein modification catalyzed by ADP-ribosyltransferases and is involved in important processes such as cell cycle regulation, DNA damage response, replication or transcription. Histones are ADP-ribosylated by ADP-ribosyltransferase diphtheria toxin-like 1 at specific amino acid residues, in particular lysines, of the histones tails. Specific ADP-ribosyl hydrolases and poly-ADP-ribose glucohydrolases degrade the ADP-ribose polymers. The ADP-ribose modification is read by zinc finger motifs or macrodomains, which then regulate chromatin structure and transcription. Thus, histone ADP-ribosylation may be considered an additional component of the histone code.

  13. ADP Analysis project for the Human Resources Management Division

    NASA Technical Reports Server (NTRS)

    Tureman, Robert L., Jr.

    1993-01-01

    The ADP (Automated Data Processing) Analysis Project was conducted for the Human Resources Management Division (HRMD) of NASA's Langley Research Center. The three major areas of work in the project were computer support, automated inventory analysis, and an ADP study for the Division. The goal of the computer support work was to determine automation needs of Division personnel and help them solve computing problems. The goal of automated inventory analysis was to find a way to analyze installed software and usage on a Macintosh. Finally, the ADP functional systems study for the Division was designed to assess future HRMD needs concerning ADP organization and activities.

  14. LACIE ADP/PI joint case study: ADP analysis guidelines. [using ERTS 1 photographs

    NASA Technical Reports Server (NTRS)

    Minter, T. C.

    1974-01-01

    The procedure is described which was used to train automatic data processing (ADP) analysts to process ERTS 1 imagery from a 5 nm by 6 nm area in Delisle, Canada, and to estimate wheat acreage using training fields provided by photointerpreters. The exercise also served to evaluate and test current large area crop inventory experiment (LACIE) procedures.

  15. Kinesin-1 plays a role in transport of SNAP-25 to the plasma membrane

    SciTech Connect

    Morton, April M.; Cunningham, Anthony L.; Diefenbach, Russell J.

    2010-01-01

    The cellular molecular motor kinesin-1 mediates the microtubule-dependent transport of a range of cargo. We have previously identified an interaction between the cargo-binding domain of kinesin-1 heavy chain KIF5B and the membrane-associated SNARE proteins SNAP-25 and SNAP-23. In this study we further defined the minimal SNAP-25 binding domain in KIF5B to residues 874-894. Overexpression of a fragment of KIF5B (residues 594-910) resulted in significant colocalization with SNAP-25 with resulting blockage of the trafficking of SNAP-25 to the periphery of cells. This indicates that kinesin-1 facilitates the transport of SNAP-25 containing vesicles as a prerequisite to SNAP-25 driven membrane fusion events.

  16. Space nuclear system volume accumulator development (SNAP program)

    NASA Technical Reports Server (NTRS)

    Whitaker, W. D.; Shimazaki, T. T.

    1973-01-01

    The engineering, design, and fabrication status of the volume accumulator units to be employed in the NaK primary and secondary coolant loops of the 5-kwe reactor thermoelectric system are described. Three identical VAU's are required - two for the primary coolant loop, and one for the secondary coolant loop. The VAU's utilize nested-formed bellows as the flexing member, are hermetically sealed, provide double containment and utilize a combination of gas pressure force and bellows spring force to obtain the desired pressure regulation of the coolant loops. All parts of the VAU, except the NaK inlet tube, are to be fabricated from Inconel 718.

  17. Ca2+, Mg2+-dependent endonuclease and ADP-ribosylation.

    PubMed

    Yoshihara, K; Tanaka, Y; Kamiya, T

    1983-01-01

    The molecular mechanism of the inhibition of Ca2+, Mg2+-dependent endonuclease by ADP-ribosylation was studied by using purified bull seminal plasma Ca2+, Mg2+-dependent endonuclease, endonuclease-stimulating proteins, and poly-(ADP-ribose) polymerase. The activity of an essentially homogeneous preparation of the endonuclease was markedly suppressed by its preincubation with NAD+, poly-(ADP-ribose) polymerase, DNA, and Mg2+. These four components of the incubation mixture were all essential for the suppression of the activity. Analyses of the initial and the chased reaction product by Sephadex G-100 column chromatography and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis revealed that Ca2+, Mg2+-dependent endonuclease was ADP-ribosylated during the incubation and its activity was markedly inhibited by the elongation of the ADP-ribose polymer covalently attached to the endonuclease. When the suppressed enzymes were mildly treated with an alkaline pH of 10.0, the activity was restored almost to the level of the unmodified control sample. These facts indicate that the linkage between the enzyme and poly(ADP-ribose) is hydrolyzed at this pH, and that the liberated polymer itself does not appreciably affect the endonuclease activity. These results also suggest that an electric repulsion between negative charges on DNA and poly(ADP-ribose) attached to Ca2+, Mg2+-dependent endonuclease is the basis for the observed suppression of the enzyme by ADP-ribosylation. Though histone H2B and H1 are shown to be as good endonuclease-stimulators (1) as they are good acceptors of ADP-ribose in poly(ADP-ribose) polymerase reaction (2), ADP-ribosylation of these two proteins did not affect their endonuclease-stimulating ability appreciably, at least under the conditions used.

  18. ADP-ribosylation of dinitrogenase reductase in Rhodobacter capsulatus

    SciTech Connect

    Jouanneau, Y.; Roby, C.; Meyer, C.M.; Vignais, P.M. )

    1989-07-25

    In the photosynthetic bacterium Rhodobacter capsulatus, nitrogenase is regulated by a reversible covalent modification of Fe protein or dinitrogenase reductase (Rc2). The linkage of the modifying group to inactive Rc2 was found to be sensitive to alkali and to neutral hydroxylamine. Complete release of the modifying group was achieved by incubation of inactive Rc2 in 0.4 or 1 M hydroxylamine. After hydroxylamine treatment of the Rc2 preparation, the modifying group could be isolated and purified by affinity chromatography and ion-exchange HPLC. The modifying group comigrated with ADP-ribose on both ion-exchange HPLC and thin-layer chromatography. Analyses by {sup 31}P NMR spectroscopy and mass spectrometry provided further evidence that the modifying group was ADP-ribose. The NMR spectrum of inactive Rc2 exhibited signals characteristic of ADP-ribose; integration of these signals allowed calculation of a molar ration ADP-ribose/Rc2 of 0.63. A hexapeptide carrying the ADP-ribose moiety was purified from a subtilisin digest of inactive Rc2. The structure of this peptide, determined by amino acid analysis and sequencing, is Gly-Arg(ADP-ribose)-Gly-Val-Ile-Thr. This structure allows identification of the binding site for ADP-ribose as Arg 101 of the polypeptide chain of Rc2. It is concluded that nitrogenase activity in R. capsulatus is regulated by reversible ADP-ribosylation of a specific arginyl residue of dinitrogenase reductase.

  19. ADP-MAS: A Math and Science Curriculum.

    ERIC Educational Resources Information Center

    National Council of La Raza, Washington, DC.

    This curriculum, Academia del Pueblo-Math and Science (ADP-MAS), is an outgrowth of the National Council of La Raza's Project EXCEL, a supplemental educational enrichment model for at-risk Latino students to be operated by Latino community-based organizations or public institutions, including schools with substantial Latino populations. ADP-MAS…

  20. SNAP (Space Nuclear Auxiliary Power) Reactor Overview

    DTIC Science & Technology

    1984-08-01

    Although the program did not proceed past the developmental stage, Pratt and Whitney were commended by the Chairman of the AEC, Dr. Glenn Seaborg , for a...34Shift is Urged from CANEL on Nuclear Project," HTFG Courant, May 1965. 17. Seaborg Says CANEL Halt No Reflection on Its Work, Middletown Press, 7-6-65

  1. SnapShot: Nucleic acid immune sensors, part 2.

    PubMed

    Hornung, Veit

    2014-12-18

    The innate immune system has evolved sensors that can detect specific molecular fingerprints of non-self RNA or DNA. At the same time, some receptors respond to nucleic acids of both exogenous and endogenous origin, yet they are spatially segregated from endogenous nucleic acids. This SnapShot schematizes families and individual members of nucleic acid sensors with a focus on their ligands and the signaling pathways they employ.

  2. Status of NASA Goddard Space Flight Center's Participation in SNAP

    NASA Technical Reports Server (NTRS)

    Rauscher, Bernard

    2007-01-01

    Dr. Rauscher will present programatic status and high-level/summary information on the technical status of NASA Goddard Space Flight Center's participation in the SuperNova Acceleration Probe (SNAP). Goddard's participation falls into four areas, and status in each of these will be covered. These areas are as follows: (I) focal plane array and packaging, (2) Teledyne HAWAII-4RG sensor chip assembly, (3) communications studies, and (4) integration and test studies.

  3. SnapShot: Hormones of the gastrointestinal tract.

    PubMed

    Coate, Katie C; Kliewer, Steven A; Mangelsdorf, David J

    2014-12-04

    Specialized endocrine cells secrete a variety of peptide hormones all along the gastrointestinal (GI) tract, making it one of the largest endocrine organs in the body. Nutrients and developmental and neural cues trigger the secretion of gastrointestinal (GI) hormones from specialized endocrine cells along the GI tract. These hormones act in target tissues to facilitate digestion and regulate energy homeostasis. This SnapShot summarizes the production and functions of GI hormones.

  4. Conflicts, snapping and instability of the tendons. Pictorial essay

    PubMed Central

    Fantino, Olivier; Borne, J.; Bordet, Bertrand

    2012-01-01

    Conflicts, snapping and instability of the tendons are common, and ultrasound (US) is the method of choice for evidencing these conditions thanks to the possibility to perform dynamic maneuvers during imaging studies. A conflict can occur between a tendon and a bone structure, other tendons, the retinacula or pulleys. Snapping can occur due to instability caused by rupture of the retinaculum, conflict between a thickened retinaculum and a bone prominence or due to an abnormal position of the tendon. Instability can occur due to insufficient ability of the retinaculum to keep the tendons in the bone groove or its failure to hold the tendons applied to the bone. The technique for evidencing conflicts, snapping and instability of the tendons is very demanding because it requires a thorough knowledge of the US appearance and dynamic maneuvers. However, at the present time US examination completed with dynamic maneuvers is the investigation of choice for evidencing these disorders and providing the clinicians with the necessary information. PMID:23396604

  5. Contactless, photoinitiated snap-through in azobenzene-functionalized polymers

    PubMed Central

    Shankar, M. Ravi; Smith, Matthew L.; Tondiglia, Vincent P.; Lee, Kyung Min; McConney, Michael E.; Wang, David H.; Tan, Loon-Seng; White, Timothy J.

    2013-01-01

    Photomechanical effects in polymeric materials and composites transduce light into mechanical work. The ability to control the intensity, polarization, placement, and duration of light irradiation is a distinctive and potentially useful tool to tailor the location, magnitude, and directionality of photogenerated mechanical work. Unfortunately, the work generated from photoresponsive materials is often slow and yields very small power densities, which diminish their potential use in applications. Here, we investigate photoinitiated snap-through in bistable arches formed from samples composed of azobenzene-functionalized polymers (both amorphous polyimides and liquid crystal polymer networks) and report orders-of-magnitude enhancement in actuation rates (approaching 102 mm/s) and powers (as much as 1 kW/m3). The contactless, ultra-fast actuation is observed at irradiation intensities <<100 mW/cm2. Due to the bistability and symmetry of the snap-through, reversible and bidirectional actuation is demonstrated. A model is developed to elucidate the underlying mechanics of the snap-through, specifically focusing on isolating the role of sample geometry, mechanical properties of the materials, and photomechanical strain. Using light to trigger contactless, ultrafast actuation in an otherwise passive structure is a potentially versatile tool to use in mechanical design at the micro-, meso-, and millimeter scales as actuators, as well as switches that can be triggered from large standoff distances, impulse generators for microvehicles, microfluidic valves and mixers in laboratory-on-chip devices, and adaptive optical elements. PMID:24190994

  6. Hunting for ghosts in elastic snap-through

    NASA Astrophysics Data System (ADS)

    Gomez, Michael; Moulton, Derek E.; Vella, Dominic

    Elastic `snap-through' is a striking instability often seen when an elastic system loses bistability, e.g. due to a change in geometry or external loading. The switch from one state to another is generally rapid and hence is used to generate fast motions in biology and engineering. While the onset of instability has been well studied, the dynamics of the transition itself remain much less well understood. For example, the dynamics exhibited by children's jumping popper toys, or the leaves of the Venus flytrap plant, are much slower than would be expected based on a naive estimate of the elastic timescales. To explain this discrepancy, the natural conclusion has been drawn that some other effect, such as viscoelasticity, must play a role. We demonstrate here that purely elastic systems may show similar `slow' dynamics during snap-through. This behaviour is due to a remnant (or `ghost') of the snap-through bifurcation underlying the instability, analogously to bottleneck phenomena in 1-D dynamical systems. This slowness is a generic consequence of being close to bifurcation -- it does not require dissipation. We obtain scaling laws for the length of the delay and compare these to numerical simulations and experiments on real samples.

  7. SNAP (Sentinel Application Platform) and the ESA Sentinel 3 Toolbox

    NASA Astrophysics Data System (ADS)

    Zuhlke, Marco; Fomferra, Norman; Brockmann, Carsten; Peters, Marco; Veci, Luis; Malik, Julien; Regner, Peter

    2015-12-01

    ESA is developing three new free open source Toolboxes for the scientific exploitation of the Sentinel-1, Sentinel-2 and Sentinel-3 missions. The Toolboxes are based on a common software platform, namely the Sentinel Application Platform (SNAP). SNAP is an evolution of the proven ESA BEAM/NEST architecture inheriting all current BEAM and NEST functionality including multi-mission support for SAR and optical missions to support ESA and third party missions for years to come. The Sentinel-3 Toolbox includes generic function for visualisation and analysis of Sentinel-3 OLCI and SLSTR Level 1 and Level 2 data, as well as specific processing tools such as cloud screening, water constituent retrieval and SST retrieval. The Toolbox will put emphasis on access to remote in-situ databases such as Felyx or MERMAID, and exploitation of the data-uncertainty information which is included in the Sentinel-3 data products. New image classification, segmentation and filtering methods, as well as interoperability with the ORFEO Toolbox and the GDAL libraries will be additional new tools. New challenges stemming from Sentinel-3 sensors, such as raster data in different resolutions within a single dataset, will be supported gracefully. The development of SNAP and the Sentinel Toolboxes is funded through the “Scientific Exploitation of Operational Missions (SEOM)” programme, a new programme element of ESA’s fourth period of the Earth Observation Envelope Programme (2013-2017).

  8. Conflicts, snapping and instability of the tendons. Pictorial essay.

    PubMed

    Fantino, Olivier; Borne, J; Bordet, Bertrand

    2012-02-01

    Conflicts, snapping and instability of the tendons are common, and ultrasound (US) is the method of choice for evidencing these conditions thanks to the possibility to perform dynamic maneuvers during imaging studies. A conflict can occur between a tendon and a bone structure, other tendons, the retinacula or pulleys. Snapping can occur due to instability caused by rupture of the retinaculum, conflict between a thickened retinaculum and a bone prominence or due to an abnormal position of the tendon. Instability can occur due to insufficient ability of the retinaculum to keep the tendons in the bone groove or its failure to hold the tendons applied to the bone.The technique for evidencing conflicts, snapping and instability of the tendons is very demanding because it requires a thorough knowledge of the US appearance and dynamic maneuvers. However, at the present time US examination completed with dynamic maneuvers is the investigation of choice for evidencing these disorders and providing the clinicians with the necessary information.

  9. Overview of the SuperNova/Acceleration probe (SNAP)

    SciTech Connect

    galdering@lbl.gov

    2002-07-29

    The SuperNova/Acceleration Probe (SNAP) is a space-based experiment to measure the expansion history of the Universe and study both its dark energy and the dark matter. The experiment is motivated by the startling discovery that the expansion of the Universe is accelerating. A 0.7 square-degree imager comprised of 36 large format fully-depleted n-type CCD's sharing a focal plane with 36 HgCdTe detectors forms the heart of SNAP, allowing discovery and lightcurve measurements simultaneously for many supernovae. The imager and a high-efficiency low-resolution integral field spectrograph are coupled to a 2-m three mirror anastigmat wide-field telescope, which will be placed in a high-earth orbit. The SNAP mission can obtain high-signal-to-noise calibrated light-curves and spectra for over 2000 Type Ia supernovae at redshifts between z = 0.1 and 1.7. The resulting data set can not only determine the amount of dark energy with high precision, but test the nature of the dark energy by examining its equation of state. In particular, dark energy due to a cosmological constant can be differentiated from alternatives such as ''quintessence'', by measuring the dark energy's equation of state to an accuracy of {+-} 0.05, and by studying its time dependence.

  10. The Transformation of the Supplemental Nutrition Assistance Program

    ERIC Educational Resources Information Center

    Klerman, Jacob Alex; Danielson, Caroline

    2011-01-01

    Between 2000 and 2005, the Supplemental Nutrition Assistance Program (SNAP, until recently, the Food Stamp Program) caseload increased by half. As the Great Recession unfolded, the SNAP caseload grew even more rapidly. Further, over the past two decades the composition of the caseload has shifted sharply away from families combining food and cash…

  11. A Study of the St. Cloud, Minnesota, Adult Diploma Program: A School Choice Program. [and] Minnesota Legislation on Choice: A Study of Learners in the St. Cloud, Minnesota, Adult Diploma Program.

    ERIC Educational Resources Information Center

    Randall, Ruth E.; And Others

    A study examined the Adult Diploma Program (ADP), a project of the Minnesota High School Graduation Incentives Program, which gives 2 years of state aid to qualified learners to complete their requirements. Its purpose was to explore how persons enrolled in ADP find out about it, factors that led to making the decision to enroll in ADP, daily…

  12. NIP-SNAP-1 and -2 mitochondrial proteins are maintained by heat shock protein 60.

    PubMed

    Yamamoto, Soh; Okamoto, Tomoya; Ogasawara, Noriko; Hashimoto, Shin; Shiraishi, Tsukasa; Sato, Toyotaka; Yamamoto, Keisuke; Tsutsumi, Hiroyuki; Takano, Kenichi; Himi, Testuo; Itoh, Hideaki; Yokota, Shin-Ichi

    2017-02-12

    NIP-SNAP-1 and -2 are ubiquitous proteins thought to be associated with maintenance of mitochondrial function, neuronal transmission, and autophagy. However, their physiological functions remain largely unknown. To elucidate their functional importance, we screened for proteins that interact with NIP-SNAP-1 and -2, resulting in identification of HSP60 and P62/SQSTM1 as binding proteins. NIP-SNAP-1 and -2 localized in the mitochondrial inner membrane space, whereas HSP60 localized in the matrix. Native gel electrophoresis and filter trap assays revealed that human HSP60 prevented aggregation of newly synthesized NIP-SNAP-2 in an in vitro translation system. Moreover, expression levels of NIP-SNAP-1 and -2 in cells were decreased by knockdown of HSP60, but not HSP10. These findings indicate that HSP60 promotes folding and maintains the stability of NIP-SNAP-1 and -2.

  13. Snap-through buckling of initially curved microbeam subject to an electrostatic force

    PubMed Central

    Chen, X.; Meguid, S. A.

    2015-01-01

    In this paper, the snap-through buckling of an initially curved microbeam subject to an electrostatic force, accounting for fringing field effect, is investigated. The general governing equations of the curved microbeam are developed using Euler–Bernoulli beam theory and used to develop a new criterion for the snap-through buckling of that beam. The size effect of the microbeam is accounted for using the modified couple stress theory, and intermolecular effects, such as van der Waals and Casimir forces, are also included in our snap-through formulations. The snap-through governing equations are solved using Galerkin decomposition of the deflection. The results of our work enable us to carefully characterize the snap-through behaviour of the initially curved microbeam. They further reveal the significant effect of the beam size, and to a much lesser extent, the effect of fringing field and intermolecular forces, upon the snap-through criterion for the curved beam. PMID:27547104

  14. Chromosomal protein poly(ADP-ribosyl)ation in pancreatic nucleosomes.

    PubMed

    Aubin, R J; Dam, V T; Miclette, J; Brousseau, Y; Poirier, G G

    1982-03-01

    When pancreatic chromatin fragments were prepared and resolved in the presence of 80 mM NaCl, endogenous poly(ADP-ribose) polymerase activity was found to be maximal in nucleosome periodicities of four to five units and did not respond to any further increases in nucleosomal architecture. Furthermore, in nucleosome complexities spanning 1 through 14 and over unit lengths, polyacrylamide gel electrophoresis on acid-urea and acid-urea-Triton gels has shown pancreatic histone H1 to be the only actively ADP-ribosylated histone species. The extent of ADP-ribosylation of histone H1 was also demonstrated to retard the protein's mobility in acid-urea, acid-urea-Triton, and lithium dodecyl sulfate polyacrylamide gels and to consist of at least 12 distinct ADP-ribosylated species extractable in all nucleosome complexities studied. Finally, extraction and subsequent electrophoresis of total chromosomal proteins in the presence of lithium dodecyl sulfate also evidenced heavy ADP-ribosylation at the level of nonhistone chromosomal proteins of the high mobility group comigrating in the core histone region, as well as in the topmost region of the gels where poly(ADP-ribose) polymerase was found to form a poly(ADP-ribosyl)ated aggregate.

  15. Glycation and glycoxidation of histones by ADP-ribose.

    PubMed

    Cervantes-Laurean, D; Jacobson, E L; Jacobson, M K

    1996-05-03

    The reaction of long lived proteins with reducing sugars has been implicated in the pathophysiology of aging and age-related diseases. A likely intranuclear source of reducing sugar is ADP-ribose, which is generated following DNA damage from the turnover of ADP-ribose polymers. In this study, ADP-ribose has been shown to be a potent histone glycation and glycoxidation agent in vitro. Incubation of ADP-ribose with histones H1, H2A, H2B, and H4 at pH 7.5 resulted in the formation of ketoamine glycation conjugates. Incubation of histone H1 with ADP-ribose also rapidly resulted in the formation of protein carboxymethyllysine residues, protein-protein cross-links, and highly fluorescent products with properties similar to the advanced glycosylation end product pentosidine. The formation of glycoxidation products was related to the degradation of ketoamine glycation conjugates by two different pathways. One pathway resulted in the formation of protein carboxymethyllysine residues and release of an ADP moiety containing a glyceric acid fragment. A second pathway resulted in the release of ADP, and it is postulated that this pathway is involved in the formation of histone-histone cross-links and fluorescent advanced glycosylation end products.

  16. Creatine kinase inhibits ADP-induced platelet aggregation

    PubMed Central

    Horjus, D. L.; Nieuwland, R.; Boateng, K. B.; Schaap, M. C. L.; van Montfrans, G. A.; Clark, J. F.; Sturk, A.; Brewster, L. M.

    2014-01-01

    Bleeding risk with antiplatelet therapy is an increasing clinical challenge. However, the inter-individual variation in this risk is poorly understood. We assessed whether the level of plasma creatine kinase, the enzyme that utilizes ADP and phosphocreatine to rapidly regenerate ATP, may modulate bleeding risk through a dose-dependent inhibition of ADP-induced platelet activation. Exogenous creatine kinase (500 to 4000 IU/L, phosphocreatine 5 mM) added to human plasma induced a dose-dependent reduction to complete inhibition of ADP-induced platelet aggregation. Accordingly, endogenous plasma creatine kinase, studied in 9 healthy men (mean age 27.9 y, SE 3.3; creatine kinase 115 to 859 IU/L, median 358), was associated with reduced ADP-induced platelet aggregation (Spearman's rank correlation coefficient, −0.6; p < 0.05). After exercise, at an endogenous creatine kinase level of 4664, ADP-induced platelet aggregation was undetectable, normalizing after rest, with a concomitant reduction of creatine kinase to normal values. Thus, creatine kinase reduces ADP-induced platelet activation. This may promote bleeding, in particular when patients use platelet P2Y12 ADP receptor inhibitors. PMID:25298190

  17. Imaging changes in the cytosolic ATP-to-ADP ratio

    PubMed Central

    Tantama, Mathew; Yellen, Gary

    2015-01-01

    Adenosine triphosphate (ATP) is a central metabolite that plays fundamental roles as an energy transfer molecule, a phosphate donor, and a signaling molecule inside cells. The phosphoryl group transfer potential of ATP provides a thermodynamic driving force for many metabolic reactions, and phosphorylation of both small metabolites and large proteins can serve as a regulatory modification. In the process of phosphoryl transfer from ATP, the diphosphate ADP is produced, and as a result, the ATP-to-ADP ratio is an important physiological control parameter. The ATP-to-ADP ratio is directly proportional to cellular energy charge and phosphorylation potential. Furthermore, several ATP-dependent enzymes and signaling proteins are regulated by ADP, and their activation profiles are a function of the ATP-to-ADP ratio. Finally, regeneration of ATP from ADP can serve as an important readout of energy metabolism and mitochondrial function. We therefore developed a genetically-encoded fluorescent biosensor tuned to sense ATP-to-ADP ratios in the physiological range of healthy mammalian cells. Here we present a protocol for using this biosensor to visualize energy status using live-cell fluorescence microscopy. PMID:25416365

  18. Evaluation of the Snap Sampler for Sampling Ground Water Monitoring Wells for VOCs and Explosives

    DTIC Science & Technology

    2007-08-01

    ER D C/ CR R EL T R -0 7 -1 4 Evaluation of the Snap Sampler for Sampling Ground Water Monitoring Wells for VOCs and Explosives Louise...release; distribution is unlimited. ERDC/CRREL TR-07-14 August 2007 Evaluation of the Snap Sampler for Sampling Ground Water Monitoring...determine the ability of the Snap Sampler to recover representative concentrations of VOC and explosives in ground water . For the laboratory studies

  19. SNAP-23 participates in SNARE complex assembly in rat adipose cells.

    PubMed Central

    St-Denis, J F; Cabaniols, J P; Cushman, S W; Roche, P A

    1999-01-01

    SNARE proteins are required for vesicle docking and fusion in eukaryotic cells in processes as diverse as homotypic membrane fusion and synaptic vesicle exocytosis [SNARE stands for SNAP receptor, where SNAP is soluble NSF attachment protein]. The SNARE proteins syntaxin 4 and vesicle-associated membrane protein (VAMP) 2/3 also participate in the insulin-stimulated translocation of GLUT4 from intracellular vesicles to the plasma membrane in adipose cells. We now report the molecular cloning and characterization of rat SNAP-23, a ubiquitously expressed homologue of the essential neuronal SNARE protein SNAP-25 (synaptosomal-associated protein of 25 kDa). Rat SNAP-23 is 86% and 98% identical respectively to human and mouse SNAP-23. Southern blot analysis reveals that the rat, mouse and human SNAP-23 genes encode species-specific isoforms of the same protein. Co-immunoprecipitation of syntaxin 4 and SNAP-23 shows association of these two proteins in rat adipose cell plasma membranes, and insulin stimulation does not alter the SNAP-23/syntaxin 4 complex. In addition, we demonstrate for the first time the participation of SNAP-23, along with syntaxin 4 and VAMP2/3, in the formation of 20S SNARE complexes prepared using rat adipose cell membranes and recombinant alpha-SNAP and NSF proteins. The stoichiometry of the SNARE complexes formed is essentially identical using membranes from either unstimulated or insulin-stimulated adipose cells. These data demonstrate that rat SNAP-23 associates with syntaxin 4 before insulin stimulation and is present in the SNARE complexes known to mediate the translocation of GLUT4 from intracellular vesicles to the plasma membrane of rat adipose cells. PMID:10051443

  20. Validation of a Computerized Adaptive Version of the Schedule for Nonadaptive and Adaptive Personality (SNAP)

    ERIC Educational Resources Information Center

    Simms, Leonard J.; Clark, Lee Anna

    2005-01-01

    This is a validation study of a computerized adaptive (CAT) version of the Schedule for Nonadaptive and Adaptive Personality (SNAP) conducted with 413 undergraduates who completed the SNAP twice, 1 week apart. Participants were assigned randomly to 1 of 4 retest groups: (a) paper-and-pencil (P&P) SNAP, (b) CAT, (c) P&P/CAT, and (d) CAT/P&P. With…

  1. Lateral sided snapping elbow caused by a meniscus: two case reports and literature review.

    PubMed

    Kang, Shin-Taek; Kim, Tae-Ho

    2010-06-01

    Lateral sided snapping elbow is an unusual condition, and it is apt to be misdiagnosed as lateral epicondylitis. The causes of lateral sided snapping elbow have been attributed to intraarticular loose bodies, instability, synovial plicae and torn annular ligament. We report our experiences for treating lateral sided snapping elbow caused by a meniscus in the radio-humeral joint. In the present cases, the cause of snapping was detected using double contrast arthrogram under fluoroscopic control, and histology revealed that it was a meniscus. Complete removal of the meniscus allowed immediate relief of the symptom, and there was no recurrence in both cases.

  2. Evolving Darwin's 'most wonderful' plant: ecological steps to a snap-trap.

    PubMed

    Gibson, Thomas C; Waller, Donald M

    2009-08-01

    Among carnivorous plants, Darwin was particularly fascinated by the speed and sensitivity of snap-traps in Dionaea and Aldrovanda. Recent molecular work confirms Darwin's conjecture that these monotypic taxa are sister to Drosera, meaning that snap-traps evolved from a 'flypaper' trap. Transitions include tentacles being modified into trigger hairs and marginal 'teeth', the loss of sticky tentacles, depressed digestive glands, and rapid leaf movement. Pre-adaptations are known for all these traits in Drosera yet snap-traps only evolved once. We hypothesize that selection to catch and retain large insects favored the evolution of elongate leaves and snap-tentacles in Drosera and snap-traps. Although sticky traps efficiently capture small prey, they allow larger prey to escape and may lose nutrients. Dionaea's snap-trap efficiently captures and processes larger prey providing higher, but variable, rewards. We develop a size-selective model and parametrize it with field data to demonstrate how selection to capture larger prey strongly favors snap-traps. As prey become larger, they also become rarer and gain the power to rip leaves, causing returns to larger snap-traps to plateau. We propose testing these hypotheses with specific field data and Darwin-like experiments. The complexity of snap-traps, competition with pitfall traps, and their association with ephemeral habitats all help to explain why this curious adaptation only evolved once.

  3. Farmers’ markets and the local food environment: Identifying perceived accessibility barriers for SNAP consumers receiving Temporary Assistance for Needy Families (TANF) in an urban Oklahoma community

    PubMed Central

    Wetherill, Marianna; Gray, Karen A.

    2015-01-01

    Objective To examine barriers to farmer’s market (FM) use by Supplemental Nutrition Assistance Program (SNAP) consumers receiving TANF. Design Focus groups. Setting An urban community in Oklahoma. Participants SNAP beneficiaries receiving TANF (n = 64, across 8 focus groups). Phenomenon of Interest Perceptions about FM foods and barriers to FM use. Analysis Transcript-based content analysis using the five dimensions of access framework. Results Few participants ate fresh produce regularly and most appreciated the convenience of shopping at a supermarket. FMs were not perceived as available or accommodating to shopping needs and affordability and acceptability concerns were expressed. Few were aware of FMs that accepted SNAP. Emerging themes suggested residential segregation and cultural barriers to FM use. Conclusions and Implications FM managers, community nutritionists, and researchers should develop interventions that correct common misperceptions about FM products, minimize access barriers, and increase awareness of SNAP payment options. Residential segregation and cultural barriers may play a role in FM use and should be explored further. PMID:25754298

  4. Design of a 25-kWe Surface Reactor System Based on SNAP Reactor Technologies

    NASA Astrophysics Data System (ADS)

    Dixon, David D.; Hiatt, Matthew T.; Poston, David I.; Kapernick, Richard J.

    2006-01-01

    A Hastelloy-X clad, sodium-potassium (NaK-78) cooled, moderated spectrum reactor using uranium zirconium hydride (UZrH) fuel based on the SNAP program reactors is a promising design for use in surface power systems. This paper presents a 98 kWth reactor for a power system the uses multiple Stirling engines to produce 25 kWe-net for 5 years. The design utilizes a pin type geometry containing UZrHx fuel clad with Hastelloy-X and NaK-78 flowing around the pins as coolant. A compelling feature of this design is its use of 49.9% enriched U, allowing it to be classified as a category III-D attractiveness and reducing facility costs relative to highly-enriched space reactor concepts. Presented below are both the design and an analysis of this reactor's criticality under various safety and operations scenarios.

  5. Design of a 25-kWe Surface Reactor System Based on SNAP Reactor Technologies

    SciTech Connect

    Dixon, David D.; Hiatt, Matthew T.; Poston, David I.; Kapernick, Richard J.

    2006-01-20

    A Hastelloy-X clad, sodium-potassium (NaK-78) cooled, moderated spectrum reactor using uranium zirconium hydride (UZrH) fuel based on the SNAP program reactors is a promising design for use in surface power systems. This paper presents a 98 kWth reactor for a power system the uses multiple Stirling engines to produce 25 kWe-net for 5 years. The design utilizes a pin type geometry containing UZrHx fuel clad with Hastelloy-X and NaK-78 flowing around the pins as coolant. A compelling feature of this design is its use of 49.9% enriched U, allowing it to be classified as a category III-D attractiveness and reducing facility costs relative to highly-enriched space reactor concepts. Presented below are both the design and an analysis of this reactor's criticality under various safety and operations scenarios.

  6. Type 2 Diabetes and ADP Receptor Blocker Therapy

    PubMed Central

    Samoš, Matej; Fedor, Marián; Kovář, František; Mokáň, Michal; Bolek, Tomáš; Galajda, Peter; Kubisz, Peter; Mokáň, Marián

    2016-01-01

    Type 2 diabetes (T2D) is associated with several abnormalities in haemostasis predisposing to thrombosis. Moreover, T2D was recently connected with a failure in antiplatelet response to clopidogrel, the most commonly used ADP receptor blocker in clinical practice. Clopidogrel high on-treatment platelet reactivity (HTPR) was repeatedly associated with the risk of ischemic adverse events. Patients with T2D show significantly higher residual platelet reactivity on ADP receptor blocker therapy and are more frequently represented in the group of patients with HTPR. This paper reviews the current knowledge about possible interactions between T2D and ADP receptor blocker therapy. PMID:26824047

  7. Viral Macro Domains Reverse Protein ADP-Ribosylation

    PubMed Central

    Li, Changqing; Debing, Yannick; Jankevicius, Gytis; Neyts, Johan; Ahel, Ivan

    2016-01-01

    ABSTRACT ADP-ribosylation is a posttranslational protein modification in which ADP-ribose is transferred from NAD+ to specific acceptors to regulate a wide variety of cellular processes. The macro domain is an ancient and highly evolutionarily conserved protein domain widely distributed throughout all kingdoms of life, including viruses. The human TARG1/C6orf130, MacroD1, and MacroD2 proteins can reverse ADP-ribosylation by acting on ADP-ribosylated substrates through the hydrolytic activity of their macro domains. Here, we report that the macro domain from hepatitis E virus (HEV) serves as an ADP-ribose-protein hydrolase for mono-ADP-ribose (MAR) and poly(ADP-ribose) (PAR) chain removal (de-MARylation and de-PARylation, respectively) from mono- and poly(ADP)-ribosylated proteins, respectively. The presence of the HEV helicase in cis dramatically increases the binding of the macro domain to poly(ADP-ribose) and stimulates the de-PARylation activity. Abrogation of the latter dramatically decreases replication of an HEV subgenomic replicon. The de-MARylation activity is present in all three pathogenic positive-sense, single-stranded RNA [(+)ssRNA] virus families which carry a macro domain: Coronaviridae (severe acute respiratory syndrome coronavirus and human coronavirus 229E), Togaviridae (Venezuelan equine encephalitis virus), and Hepeviridae (HEV), indicating that it might be a significant tropism and/or pathogenic determinant. IMPORTANCE Protein ADP-ribosylation is a covalent posttranslational modification regulating cellular protein activities in a dynamic fashion to modulate and coordinate a variety of cellular processes. Three viral families, Coronaviridae, Togaviridae, and Hepeviridae, possess macro domains embedded in their polyproteins. Here, we show that viral macro domains reverse cellular ADP-ribosylation, potentially cutting the signal of a viral infection in the cell. Various poly(ADP-ribose) polymerases which are notorious guardians of cellular

  8. Arginine-Specific Mono ADP-Ribosylation In Vitro of Antimicrobial Peptides by ADP-Ribosylating Toxins

    PubMed Central

    Castagnini, Marta; Picchianti, Monica; Talluri, Eleonora; Biagini, Massimiliano; Del Vecchio, Mariangela; Di Procolo, Paolo; Norais, Nathalie; Nardi-Dei, Vincenzo; Balducci, Enrico

    2012-01-01

    Among the several toxins used by pathogenic bacteria to target eukaryotic host cells, proteins that exert ADP-ribosylation activity represent a large and studied family of dangerous and potentially lethal toxins. These proteins alter cell physiology catalyzing the transfer of the ADP-ribose unit from NAD to cellular proteins involved in key metabolic pathways. In the present study, we tested the capability of four of these toxins, to ADP-ribosylate α- and β- defensins. Cholera toxin (CT) from Vibrio cholerae and heat labile enterotoxin (LT) from Escherichia coli both modified the human α-defensin (HNP-1) and β- defensin-1 (HBD1), as efficiently as the mammalian mono-ADP-ribosyltransferase-1. Pseudomonas aeruginosa exoenzyme S was inactive on both HNP-1 and HBD1. Neisseria meningitidis NarE poorly recognized HNP-1 as a substrate but it was completely inactive on HBD1. On the other hand, HNP-1 strongly influenced NarE inhibiting its transferase activity while enhancing auto-ADP-ribosylation. We conclude that only some arginine-specific ADP-ribosylating toxins recognize defensins as substrates in vitro. Modifications that alter the biological activities of antimicrobial peptides may be relevant for the innate immune response. In particular, ADP-ribosylation of antimicrobial peptides may represent a novel escape mechanism adopted by pathogens to facilitate colonization of host tissues. PMID:22879887

  9. Arginine-specific mono ADP-ribosylation in vitro of antimicrobial peptides by ADP-ribosylating toxins.

    PubMed

    Castagnini, Marta; Picchianti, Monica; Talluri, Eleonora; Biagini, Massimiliano; Del Vecchio, Mariangela; Di Procolo, Paolo; Norais, Nathalie; Nardi-Dei, Vincenzo; Balducci, Enrico

    2012-01-01

    Among the several toxins used by pathogenic bacteria to target eukaryotic host cells, proteins that exert ADP-ribosylation activity represent a large and studied family of dangerous and potentially lethal toxins. These proteins alter cell physiology catalyzing the transfer of the ADP-ribose unit from NAD to cellular proteins involved in key metabolic pathways. In the present study, we tested the capability of four of these toxins, to ADP-ribosylate α- and β- defensins. Cholera toxin (CT) from Vibrio cholerae and heat labile enterotoxin (LT) from Escherichia coli both modified the human α-defensin (HNP-1) and β- defensin-1 (HBD1), as efficiently as the mammalian mono-ADP-ribosyltransferase-1. Pseudomonas aeruginosa exoenzyme S was inactive on both HNP-1 and HBD1. Neisseria meningitidis NarE poorly recognized HNP-1 as a substrate but it was completely inactive on HBD1. On the other hand, HNP-1 strongly influenced NarE inhibiting its transferase activity while enhancing auto-ADP-ribosylation. We conclude that only some arginine-specific ADP-ribosylating toxins recognize defensins as substrates in vitro. Modifications that alter the biological activities of antimicrobial peptides may be relevant for the innate immune response. In particular, ADP-ribosylation of antimicrobial peptides may represent a novel escape mechanism adopted by pathogens to facilitate colonization of host tissues.

  10. ADP-ribosylation of proteins: Enzymology and biological significance

    SciTech Connect

    Althaus, F.R.; Richter, C.

    1987-01-01

    This book presents an overview of the molecular and biological consequences of the posttranslational modification of proteins with ADP-ribose monomers and polymers. Part one focuses on chromatin-associated poly ADP-ribosylation reactions which have evolved in higher eukaryotes as modulators of chromatin functions. The significance of poly ADP-ribosylation in DNA repair, carcinogenesis, and gene expression during terminal differentiation is discussed. Part two reviews mono ADP-ribosylation reactions which are catalyzed by prokaryotic and eukaryotic enzymes. Consideration is given to the action of bacterial toxins, such as cholera toxin, pertussis toxin, and diphtheria toxin. These toxins have emerged as tools for the molecular probing of proteins involved in signal transduction and protein biosynthesis.

  11. Association between SNAP-25 gene polymorphisms and cognition in autism: functional consequences and potential therapeutic strategies

    PubMed Central

    Braida, D; Guerini, F R; Ponzoni, L; Corradini, I; De Astis, S; Pattini, L; Bolognesi, E; Benfante, R; Fornasari, D; Chiappedi, M; Ghezzo, A; Clerici, M; Matteoli, M; Sala, M

    2015-01-01

    Synaptosomal-associated protein of 25 kDa (SNAP-25) is involved in different neuropsychiatric disorders, including schizophrenia and attention-deficit/hyperactivity disorder. Consistently, SNAP-25 polymorphisms in humans are associated with hyperactivity and/or with low cognitive scores. We analysed five SNAP-25 gene polymorphisms (rs363050, rs363039, rs363043, rs3746544 and rs1051312) in 46 autistic children trying to correlate them with Childhood Autism Rating Scale and electroencephalogram (EEG) abnormalities. The functional effects of rs363050 single-nucleotide polymorphism (SNP) on the gene transcriptional activity, by means of the luciferase reporter gene, were evaluated. To investigate the functional consequences that SNAP-25 reduction may have in children, the behaviour and EEG of SNAP-25+/− adolescent mice (SNAP-25+/+) were studied. Significant association of SNAP-25 polymorphism with decreasing cognitive scores was observed. Analysis of transcriptional activity revealed that SNP rs363050 encompasses a regulatory element, leading to protein expression decrease. Reduction of SNAP-25 levels in adolescent mice was associated with hyperactivity, cognitive and social impairment and an abnormal EEG, characterized by the occurrence of frequent spikes. Both EEG abnormalities and behavioural deficits were rescued by repeated exposure for 21 days to sodium salt valproate (VLP). A partial recovery of SNAP-25 expression content in SNAP-25+/− hippocampi was also observed by means of western blotting. A reduced expression of SNAP-25 is responsible for the cognitive deficits in children affected by autism spectrum disorders, as presumably occurring in the presence of rs363050(G) allele, and for behavioural and EEG alterations in adolescent mice. VLP treatment could result in novel therapeutic strategies. PMID:25629685

  12. Association between SNAP-25 gene polymorphisms and cognition in autism: functional consequences and potential therapeutic strategies.

    PubMed

    Braida, D; Guerini, F R; Ponzoni, L; Corradini, I; De Astis, S; Pattini, L; Bolognesi, E; Benfante, R; Fornasari, D; Chiappedi, M; Ghezzo, A; Clerici, M; Matteoli, M; Sala, M

    2015-01-27

    Synaptosomal-associated protein of 25 kDa (SNAP-25) is involved in different neuropsychiatric disorders, including schizophrenia and attention-deficit/hyperactivity disorder. Consistently, SNAP-25 polymorphisms in humans are associated with hyperactivity and/or with low cognitive scores. We analysed five SNAP-25 gene polymorphisms (rs363050, rs363039, rs363043, rs3746544 and rs1051312) in 46 autistic children trying to correlate them with Childhood Autism Rating Scale and electroencephalogram (EEG) abnormalities. The functional effects of rs363050 single-nucleotide polymorphism (SNP) on the gene transcriptional activity, by means of the luciferase reporter gene, were evaluated. To investigate the functional consequences that SNAP-25 reduction may have in children, the behaviour and EEG of SNAP-25(+/-) adolescent mice (SNAP-25(+/+)) were studied. Significant association of SNAP-25 polymorphism with decreasing cognitive scores was observed. Analysis of transcriptional activity revealed that SNP rs363050 encompasses a regulatory element, leading to protein expression decrease. Reduction of SNAP-25 levels in adolescent mice was associated with hyperactivity, cognitive and social impairment and an abnormal EEG, characterized by the occurrence of frequent spikes. Both EEG abnormalities and behavioural deficits were rescued by repeated exposure for 21 days to sodium salt valproate (VLP). A partial recovery of SNAP-25 expression content in SNAP-25(+/-) hippocampi was also observed by means of western blotting. A reduced expression of SNAP-25 is responsible for the cognitive deficits in children affected by autism spectrum disorders, as presumably occurring in the presence of rs363050(G) allele, and for behavioural and EEG alterations in adolescent mice. VLP treatment could result in novel therapeutic strategies.

  13. A preliminary shield design for a SNAP-8 power system

    NASA Technical Reports Server (NTRS)

    Karp, I. M.; Soffer, L.; Clark, M. R.

    1972-01-01

    A preliminary shield design for a nuclear power system utilizing a SNAP-8 reactor for space base application is presented. A representative space base configuration was selected to set the geometry constraints imposed on the design. The base utilizes two independent power packages each with a reactor operating at 600 kwt and each producing about 50 kwe. The crew compartment is located about 200 feet from each reactor and is large enough in extent to intercept a total shadow angle of 60 deg measured about the center line of each reactor.

  14. An integral field spectrograph for SNAP supernova studies

    SciTech Connect

    Ealet, Anne; Prieto, E.; Bonissent, A.; Malina, R.; Basa, S.; LeFevre, O.; Mazure, A.; Tarle, G.; Akerlof, C.W.; Aldering, G.; Amidei, D.E.; Astier, P.; Baden, A.R.; Bebek, C.; Bergstrom, L.; Bernstein, G.M.; Bower, C.R.; Campbell, M.; Carithers Jr., W.C.; Commins, E.D.; Curtis, D.W.; Deustua, S.E.; Edwards, W.R.; Ellis, R.S.; Fruchter, A.; Frye, B.L.; Genat, J.; Goldhaber, G.; Goobar, A.; Goodman, J.A.; Graham, J.R.; Hardin, D.; Harris, S.E.; Harvey, P.R.; Heetderks, H.D.; Honeycutt, R.; Holland, S.E.; Hook, I.; Huterer, D.; Kasen, D.N.; Kim, A.G.; Knop, R.A.; Lafever, R.; Lampton, M.L.; Levi, M.E.; Levin, D.S.; Levy, J.M.; Lidman, C.; Lin, R.P.; Linder, E.V.; Loken, S.C.; McKay, T.; McKee, S.P.; Metzger, M.R.; Miquel, R.; Mourao, A.; Mufson, S.; Musser, J.A.; Nugent, P.E.; Pain, R.; Pankow, D.H.; Pennypacker, C.R.; Perlmutter, S.; Refregier, A.; Rich, J.; Robinson, K.E.; Schahmaneche, K.; Schubnell, M.S.; Spadafora, A.; Smoot, G.F.; Sullivan, G.W.; Tomasch, A.D.; SNAP Collaboration

    2002-07-29

    A well-adapted spectrograph concept has been developed for the SNAP (SuperNova/Acceleration Probe) experiment. The goal is to ensure proper identification of Type Ia supernovae and to standardize the magnitude of each candidate by determining explosion parameters. An instrument based on an integral field method with the powerful concept of imager slicing has been designed and is presented in this paper. The spectrograph concept is optimized to have very high efficiency and low spectral resolution (R {approx} 100), constant through the wavelength range (0.35-1.7{micro}m), adapted to the scientific goals of the mission.

  15. SNAP 19 Pioneer F and G. Final Report

    DOE R&D Accomplishments Database

    1973-06-01

    The generator developed for the Pioneer mission evolved from the SNAP 19 RTG`s launched aboard the NIMBUS III spacecraft. In order to satisfy the power requirements and environment of earth escape trajectory, significant modifications were made to the thermoelectric converter, heat source, and structural configuration. Specifically, a TAGS 2N thermoelectric couple was designed to provide higher efficiency and improved long term power performance, and the electrical circuitry was modified to yield very low magnetic field from current flow in the RTG. A new heat source was employed to satisfy operational requirements and its integration with the generator required alteration to the method of providing support to the fuel capsule.

  16. Pinning control of complex networks via edge snapping

    NASA Astrophysics Data System (ADS)

    DeLellis, P.; di Bernardo, M.; Porfiri, M.

    2011-09-01

    In this paper, we propose a hierarchy of novel decentralized adaptive pinning strategies for controlled synchronization of complex networks. This hierarchy addresses the fundamental need of selecting the sites to pin through a fully decentralized approach based on edge snapping. Specifically, we present three different strategies of increasing complexity which use a combination of network evolution and adaptation of the coupling and control gains. Theoretical results are complemented by extensive numerical investigations of the performance of the proposed strategies on a set of testbed examples.

  17. Snapping knee caused by the thickening of the medial hamstrings.

    PubMed

    de la Hera Cremades, B; Escribano Rueda, L; Lara Rubio, A

    2016-11-17

    We report a case of symptomatic subluxation of the semitendinosus and gracilis over the medial condyle of the tibia caused by the thickening of its tendons. Snapping was reproduced on active extension. Clinical examination and, above all, dynamic ultrasound were the key for the diagnosis because other imaging tests were normal. Due to failure of conservative treatment with physiotherapy and infiltrations, surgery was undertaken, involving desinsertion and excision of distal 8cm segment of the semitendinosus and gracilis tendons. At the present time (6 months postoperatively), the patient is symptom-free and has returned to the previous normal life activities.

  18. Amelogenesis Imperfecta, Facial Esthetics and Snap-On Smile.

    PubMed

    Wilson, Lee; Bradshaw, Jonathan P; Marks, Murray K

    2015-01-01

    Amelogenesis imperfecta is a hereditary enamel protein disorder affecting deciduous and secondary crown formation. The prevalence ranges from 1:700 to 1:14,000 depending on the population. These teeth may be hypoplastic, hypomineralized, or hypermineralized and are often discolored, sensitive and caries vulnerable. Patients often present with psychosocial issues due to appearance. Primary teeth are often treated with stainless steel crowns while secondary teeth are treated with full coverage esthetic crowns. The presenting preteen male here was fitted with Snap-On Smile? (www.snaponsmile.com). This treatment option provided cosmetic enhancement of the patient's appearance besides stabilization without altering the primary and secondary dentition during adolescent development.

  19. Intracellular Mono-ADP-Ribosylation in Signaling and Disease

    PubMed Central

    Bütepage, Mareike; Eckei, Laura; Verheugd, Patricia; Lüscher, Bernhard

    2015-01-01

    A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD+)-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADP-ribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases. PMID:26426055

  20. Structure-based Mechanism of ADP-ribosylation by Sirtuins

    SciTech Connect

    Hawse, William F.; Wolberger, Cynthia

    2009-12-01

    Sirtuins comprise a family of enzymes found in all organisms, where they play a role in diverse processes including transcriptional silencing, aging, regulation of transcription, and metabolism. The predominant reaction catalyzed by these enzymes is NAD{sup +}-dependent lysine deacetylation, although some sirtuins exhibit a weaker ADP-ribosyltransferase activity. Although the Sir2 deacetylation mechanism is well established, much less is known about the Sir2 ADP-ribosylation reaction. We have studied the ADP-ribosylation activity of a bacterial sirtuin, Sir2Tm, and show that acetylated peptides containing arginine or lysine 2 residues C-terminal to the acetyl lysine, the +2 position, are preferentially ADP-ribosylated at the +2 residue. A structure of Sir2Tm bound to the acetylated +2 arginine peptide shows how this arginine could enter the active site and react with a deacetylation reaction intermediate to yield an ADP-ribosylated peptide. The new biochemical and structural studies presented here provide mechanistic insights into the Sir2 ADP-ribosylation reaction and will aid in identifying substrates of this reaction.

  1. Regulation of Bone Morphogenetic Protein Signaling by ADP-ribosylation*

    PubMed Central

    Watanabe, Yukihide; Papoutsoglou, Panagiotis; Maturi, Varun; Tsubakihara, Yutaro; Hottiger, Michael O.; Heldin, Carl-Henrik; Moustakas, Aristidis

    2016-01-01

    We previously established a mechanism of negative regulation of transforming growth factor β signaling mediated by the nuclear ADP-ribosylating enzyme poly-(ADP-ribose) polymerase 1 (PARP1) and the deribosylating enzyme poly-(ADP-ribose) glycohydrolase (PARG), which dynamically regulate ADP-ribosylation of Smad3 and Smad4, two central signaling proteins of the pathway. Here we demonstrate that the bone morphogenetic protein (BMP) pathway can also be regulated by the opposing actions of PARP1 and PARG. PARG positively contributes to BMP signaling and forms physical complexes with Smad5 and Smad4. The positive role PARG plays during BMP signaling can be neutralized by PARP1, as demonstrated by experiments where PARG and PARP1 are simultaneously silenced. In contrast to PARG, ectopic expression of PARP1 suppresses BMP signaling, whereas silencing of endogenous PARP1 enhances signaling and BMP-induced differentiation. The two major Smad proteins of the BMP pathway, Smad1 and Smad5, interact with PARP1 and can be ADP-ribosylated in vitro, whereas PARG causes deribosylation. The overall outcome of this mode of regulation of BMP signal transduction provides a fine-tuning mechanism based on the two major enzymes that control cellular ADP-ribosylation. PMID:27129221

  2. Shock and vibration tests of a SNAP-8 NaK pump

    NASA Technical Reports Server (NTRS)

    Stromquist, A. J.; Nelson, R. B.; Hibben, L.

    1971-01-01

    The pump used for reactor cooling in the SNAP 8 space power system was subjected to the expected vehicle launch vibration, and shock loading in accordance with the SNAP 8 environmental specification. Subsequent disassembly revealed damage to the thrust bearing pins, which should be redesigned and strengthened. The unit was operational, however, when run in a test loop after reassembly.

  3. The SNAP Rating Scale for the Diagnosis of the Attention Deficit Disorder.

    ERIC Educational Resources Information Center

    Swanson, James M.; And Others

    The correlation of ratings from the SNAP Rating Scale with the ratings from the established Conners' Ratinq Scale are discussed as a method for assessing the validity of the new Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria for attention deficient disorder with hyper-activity (ADDH). The questionnaire of SNAP items and…

  4. Epileptiform activity and cognitive deficits in SNAP-25(+/-) mice are normalized by antiepileptic drugs.

    PubMed

    Corradini, Irene; Donzelli, Andrea; Antonucci, Flavia; Welzl, Hans; Loos, Maarten; Martucci, Roberta; De Astis, Silvia; Pattini, Linda; Inverardi, Francesca; Wolfer, David; Caleo, Matteo; Bozzi, Yuri; Verderio, Claudia; Frassoni, Carolina; Braida, Daniela; Clerici, Mario; Lipp, Hans-Peter; Sala, Mariaelvina; Matteoli, Michela

    2014-02-01

    Synaptosomal-associated protein of 25 kDa (SNAP-25) is a protein that participates in the regulation of synaptic vesicle exocytosis through the formation of the soluble NSF attachment protein receptor complex and modulates voltage-gated calcium channels activity. The Snap25 gene has been associated with schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder, and lower levels of SNAP-25 have been described in patients with schizophrenia. We used SNAP-25 heterozygous (SNAP-25(+/-)) mice to investigate at which extent the reduction of the protein levels affects neuronal network function and mouse behavior. As interactions of genotype with the specific laboratory conditions may impact behavioral results, the study was performed through a multilaboratory study in which behavioral tests were replicated in at least 2 of 3 distinct European laboratories. Reductions of SNAP-25 levels were associated with a moderate hyperactivity, which disappeared in the adult animals, and with impaired associative learning and memory. Electroencephalographic recordings revealed the occurrence of frequent spikes, suggesting a diffuse network hyperexcitability. Consistently, SNAP-25(+/-) mice displayed higher susceptibility to kainate-induced seizures, paralleled by degeneration of hilar neurons. Notably, both EEG profile and cognitive defects were improved by antiepileptic drugs. These results indicate that reduction of SNAP-25 expression is associated to generation of epileptiform discharges and cognitive dysfunctions, which can be effectively treated by antiepileptic drugs.

  5. Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis

    PubMed Central

    Fossati, G; Morini, R; Corradini, I; Antonucci, F; Trepte, P; Edry, E; Sharma, V; Papale, A; Pozzi, D; Defilippi, P; Meier, J C; Brambilla, R; Turco, E; Rosenblum, K; Wanker, E E; Ziv, N E; Menna, E; Matteoli, M

    2015-01-01

    Impairment of synaptic function can lead to neuropsychiatric disorders collectively referred to as synaptopathies. The SNARE protein SNAP-25 is implicated in several brain pathologies and, indeed, brain areas of psychiatric patients often display reduced SNAP-25 expression. It has been recently found that acute downregulation of SNAP-25 in brain slices impairs long-term potentiation; however, the processes through which this occurs are still poorly defined. We show that in vivo acute downregulation of SNAP-25 in CA1 hippocampal region affects spine number. Consistently, hippocampal neurons from SNAP-25 heterozygous mice show reduced densities of dendritic spines and defective PSD-95 dynamics. Finally, we show that, in brain, SNAP-25 is part of a molecular complex including PSD-95 and p140Cap, with p140Cap being capable to bind to both SNAP-25 and PSD-95. These data demonstrate an unexpected role of SNAP-25 in controlling PSD-95 clustering and open the possibility that genetic reductions of the protein levels – as occurring in schizophrenia – may contribute to the pathology through an effect on postsynaptic function and plasticity. PMID:25678324

  6. SNAP-25 in hippocampal CA3 region is required for long-term memory formation

    SciTech Connect

    Hou Qiuling; Gao Xiang; Lu Qi; Zhang Xuehan; Tu Yanyang; Jin Meilei; Zhao Guoping; Yu Lei; Jing Naihe; Li Baoming . E-mail: bmli@fudan.edu.cn

    2006-09-08

    SNAP-25 is a synaptosomal protein of 25 kDa, a key component of synaptic vesicle-docking/fusion machinery, and plays a critical role in exocytosis and neurotransmitter release. We previously reported that SNAP-25 in the hippocampal CA1 region is involved in consolidation of contextual fear memory and water-maze spatial memory (Hou et al. European J Neuroscience, 20: 1593-1603, 2004). SNAP-25 is expressed not only in the CA1 region, but also in the CA3 region, and the SNAP-25 mRNA level in the CA3 region is higher than in the CA1 region. Here, we provide evidence that SNAP-25 in the CA3 region is also involved in learning/memory. Intra-CA3 infusion of SNAP-25 antisense oligonucleotide impaired both long-term contextual fear memory and water-maze spatial memory, with short-term memory intact. Furthermore, the SNAP-25 antisense oligonucleotide suppressed the long-term potentiation (LTP) of field excitatory post-synaptic potential (fEPSP) in the mossy-fiber pathway (DG-CA3 pathway), with no effect on paired-pulse facilitation of the fEPSP. These results are consistent with the notion that SNAP-25 in the hippocampal CA3 region is required for long-term memory formation.

  7. Analysis and Down Select of Flow Passages for Thermal Hydraulic Testing of a SNAP Derived Reactor

    NASA Technical Reports Server (NTRS)

    Godfroy, T. J.; Sadasivan, P.; Masterson, S.

    2007-01-01

    As past of the Vision for Space Exploration, man will return to the moon. To enable safe and productive time on the lunar surface will require adequate power resources. To provide the needed power and to give mission planners all landing site possibilities, including a permanently dark crater, a nuclear reactor provides the most options. Designed to be l00kWt providing approx. 25kWe this power plants would be very effective in delivering dependable, site non-specific power to crews or robotic missions on the lunar surface. An affordable reference reactor based upon the successful SNAP program of the 1960's and early 1970's has been designed by Los Alamos National Laboratory that will meet such a requirement. Considering current funding, environmental, and schedule limitations this lunar surface power reactor will be tested using non-nuclear simulators to simulate the heat from fission reactions. Currently a 25kWe surface power SNAP derivative reactor is in the early process of design and testing with collaboration between Los Alamos National Laboratory, Idaho National Laboratory, Glenn Research Center, Marshall Space Flight Center, and Sandia National Laboratory to ensure that this new design is affordable and can be tested using non-nuclear methods as have proven so effective in the past. This paper will discuss the study and down selection of a flow passage concept for a approx. 25kWe lunar surface power reactor. Several different flow passages designs were evaluated using computational fluid dynamics to determine pressure drop and a structural assessment to consider thermal and stress of the passage walls. The reactor design basis conditions are discussed followed by passage problem setup and results for each concept. A recommendation for passage design is made with rationale for selection.

  8. Geometrically controlled snapping transitions in shells with curved creases

    PubMed Central

    Bende, Nakul Prabhakar; Evans, Arthur A.; Innes-Gold, Sarah; Marin, Luis A.; Cohen, Itai; Hayward, Ryan C.; Santangelo, Christian D.

    2015-01-01

    Curvature and mechanics are intimately connected for thin materials, and this coupling between geometry and physical properties is readily seen in folded structures from intestinal villi and pollen grains to wrinkled membranes and programmable metamaterials. While the well-known rules and mechanisms behind folding a flat surface have been used to create deployable structures and shape transformable materials, folding of curved shells is still not fundamentally understood. Shells naturally deform by simultaneously bending and stretching, and while this coupling gives them great stability for engineering applications, it makes folding a surface of arbitrary curvature a nontrivial task. Here we discuss the geometry of folding a creased shell, and demonstrate theoretically the conditions under which it may fold smoothly. When these conditions are violated we show, using experiments and simulations, that shells undergo rapid snapping motion to fold from one stable configuration to another. Although material asymmetry is a proven mechanism for creating this bifurcation of stability, for the case of a creased shell, the inherent geometry itself serves as a barrier to folding. We discuss here how two fundamental geometric concepts, creases and curvature, combine to allow rapid transitions from one stable state to another. Independent of material system and length scale, the design rule that we introduce here explains how to generate snapping transitions in arbitrary surfaces, thus facilitating the creation of programmable multistable materials with fast actuation capabilities. PMID:26294253

  9. Wrinkling, Crumpling and Snapping for Surface Property Control

    NASA Astrophysics Data System (ADS)

    Crosby, Alfred

    2008-03-01

    Upon the development of a critical stress, many materials and geometries experience a mechanical instability, which produces significant changes in geometry with very small changes in stress. In nature, mechanical instabilities are ubiquitous with the definition of shape, morphology, and function. Examples range from wrinkles on human skin to the snapping of Venus Flytrap leaflets. Inspired by these examples and others, we use elastic instabilities to control the morphology and function of soft polymer surfaces. We present three strategies. The first is a novel approach for the development of surface wrinkles on a top-constrained elastomer surface. We demonstrate and understand the control of kinetically-trapped and equilibrium wrinkle morphologies associated with changes in the materials properties and geometric constraint. These structures are stabilized to create surfaces with enhanced adhesion and advantageous optical properties. A second strategy is based on the controlled buckling of surface attached sheets. This method allows the fabrication of responsive surface structures that are prone to snap-through instabilities and the fabrication of pattern features that are difficult, if not impossible, to achieve with any other method. The third strategy brings the bio-inspired surface control full circle with the use of mechanical instabilities to control and characterize monolayer sheets of biological cells.

  10. Geometrically controlled snapping transitions in shells with curved creases.

    PubMed

    Bende, Nakul Prabhakar; Evans, Arthur A; Innes-Gold, Sarah; Marin, Luis A; Cohen, Itai; Hayward, Ryan C; Santangelo, Christian D

    2015-09-08

    Curvature and mechanics are intimately connected for thin materials, and this coupling between geometry and physical properties is readily seen in folded structures from intestinal villi and pollen grains to wrinkled membranes and programmable metamaterials. While the well-known rules and mechanisms behind folding a flat surface have been used to create deployable structures and shape transformable materials, folding of curved shells is still not fundamentally understood. Shells naturally deform by simultaneously bending and stretching, and while this coupling gives them great stability for engineering applications, it makes folding a surface of arbitrary curvature a nontrivial task. Here we discuss the geometry of folding a creased shell, and demonstrate theoretically the conditions under which it may fold smoothly. When these conditions are violated we show, using experiments and simulations, that shells undergo rapid snapping motion to fold from one stable configuration to another. Although material asymmetry is a proven mechanism for creating this bifurcation of stability, for the case of a creased shell, the inherent geometry itself serves as a barrier to folding. We discuss here how two fundamental geometric concepts, creases and curvature, combine to allow rapid transitions from one stable state to another. Independent of material system and length scale, the design rule that we introduce here explains how to generate snapping transitions in arbitrary surfaces, thus facilitating the creation of programmable multistable materials with fast actuation capabilities.

  11. Structure and function of the ARH family of ADP-ribosyl-acceptor hydrolases.

    PubMed

    Mashimo, Masato; Kato, Jiro; Moss, Joel

    2014-11-01

    ADP-ribosylation is a post-translational protein modification, in which ADP-ribose is transferred from nicotinamide adenine dinucleotide (NAD(+)) to specific acceptors, thereby altering their activities. The ADP-ribose transfer reactions are divided into mono- and poly-(ADP-ribosyl)ation. Cellular ADP-ribosylation levels are tightly regulated by enzymes that transfer ADP-ribose to acceptor proteins (e.g., ADP-ribosyltransferases, poly-(ADP-ribose) polymerases (PARP)) and those that cleave the linkage between ADP-ribose and acceptor (e.g., ADP-ribosyl-acceptor hydrolases (ARH), poly-(ADP-ribose) glycohydrolases (PARG)), thereby constituting an ADP-ribosylation cycle. This review summarizes current findings related to the ARH family of proteins. This family comprises three members (ARH1-3) with similar size (39kDa) and amino acid sequence. ARH1 catalyzes the hydrolysis of the N-glycosidic bond of mono-(ADP-ribosyl)ated arginine. ARH3 hydrolyzes poly-(ADP-ribose) (PAR) and O-acetyl-ADP-ribose. The different substrate specificities of ARH1 and ARH3 contribute to their unique roles in the cell. Based on a phenotype analysis of ARH1(-/-) and ARH3(-/-) mice, ARH1 is involved in the action by bacterial toxins as well as in tumorigenesis. ARH3 participates in the degradation of PAR that is synthesized by PARP1 in response to oxidative stress-induced DNA damage; this hydrolytic reaction suppresses PAR-mediated cell death, a pathway termed parthanatos.

  12. ADP and Other Metabolites Released from Acanthamoeba castellanii Lead to Human Monocytic Cell Death through Apoptosis and Stimulate the Secretion of Proinflammatory Cytokines

    PubMed Central

    Mattana, A.; Cappai, V.; Alberti, L.; Serra, C.; Fiori, P. L.; Cappuccinelli, P.

    2002-01-01

    Monocytes/macrophages are thought to be involved in Acanthamoeba infections. The aim of this work was to study whether soluble metabolites (ADP and other compounds) released by Acanthamoeba castellanii trophozoites could induce morphological and biochemical changes in human monocytic cells in vitro. We demonstrate here that ADP constitutively released in the medium by A. castellanii, interacting with specific P2y2 purinoceptors expressed on the monocytic cell membrane, caused a biphasic rise in [Ca2+]i, morphological changes characteristics of cells undergoing apoptosis, caspase-3 activation, and secretion of tumor necrosis factor alpha (TNF-α). The same results were found in monocytes exposed to purified ADP. Cell damage and TNF-α release induced by amoebic ADP were blocked by the P2y2 inhibitor suramin. Other metabolites contained in amoebic cell-free supernatants, with molecular masses of, respectively, >30 kDa and between 30 and 10 kDa, also caused morphological modifications and activation of intracellular caspase-3, characteristics of programmed cell death. Nevertheless, mechanisms by which these molecules trigger cell damage appeared to differ from that of ADP. In addition, other amoebic thermolable metabolites with molecular masses of <10 kDa caused the secretion of interleukin-1β. These findings suggest that pathogenic free-living A. castellanii by release of ADP and other metabolites lead to human monocytic cell death through apoptosis and stimulate the secretion of proinflammatory cytokines. PMID:12117953

  13. Evaluation of a semiquantitative SNAP test for measurement of bile acids in dogs.

    PubMed

    Seibert, Rachel L; Tobias, Karen M; Reed, Ann; Snyder, Karl R

    2014-01-01

    Background. Serum bile acids (SBA) are used as a routine screening tool of liver function in dogs. Serum samples are usually shipped to a referral laboratory for quantitative analysis with an enzymatic chemistry analyzer. The canine SNAP Bile Acids Test (SNAP-BAT) provides an immediate, semi-quantitative measurement of bile acid concentrations in-house. With the SNAP-BAT, bile acids concentrations of 5-30 µmol/L are quantified, and results outside of that range are classified as <5 or >30 µmol/L. Agreement of the SNAP-BAT with the enzymatic method has not been extensively investigated. Objectives. The purposes of this prospective clinical study were to assess the precision of the SNAP-BAT and determine agreement of SNAP-BAT with results from an in-house chemistry analyzer. Methods. After verifying intra-assay precision of the SNAP-BAT, a prospective analysis was performed using blood samples collected from 56 dogs suspected to have liver disease. Each sample was analyzed with an enzymatic, in-house chemistry analyzer and the SNAP-BAT. Agreement between the two methods was statistically assessed using the κ index of agreement. Results. Intra-assay variability was minimal. The κ index for agreement between the SNAP-BAT and routine chemistry analyzer was between 0.752 and 0.819, indicating substantial to near perfect agreement. Conclusions. The SNAP-BAT is a highly accurate, semi-quantitative test that yields immediate results, and has very little intra-assay variability, particularly for results >30 µmol/L.

  14. ADP1 Affects Plant Architecture by Regulating Local Auxin Biosynthesis

    PubMed Central

    Li, Shibai; Qin, Genji; Novák, Ondřej; Pěnčík, Aleš; Ljung, Karin; Aoyama, Takashi; Liu, Jingjing; Murphy, Angus; Gu, Hongya; Tsuge, Tomohiko; Qu, Li-Jia

    2014-01-01

    Plant architecture is one of the key factors that affect plant survival and productivity. Plant body structure is established through the iterative initiation and outgrowth of lateral organs, which are derived from the shoot apical meristem and root apical meristem, after embryogenesis. Here we report that ADP1, a putative MATE (multidrug and toxic compound extrusion) transporter, plays an essential role in regulating lateral organ outgrowth, and thus in maintaining normal architecture of Arabidopsis. Elevated expression levels of ADP1 resulted in accelerated plant growth rate, and increased the numbers of axillary branches and flowers. Our molecular and genetic evidence demonstrated that the phenotypes of plants over-expressing ADP1 were caused by reduction of local auxin levels in the meristematic regions. We further discovered that this reduction was probably due to decreased levels of auxin biosynthesis in the local meristematic regions based on the measured reduction in IAA levels and the gene expression data. Simultaneous inactivation of ADP1 and its three closest homologs led to growth retardation, relative reduction of lateral organ number and slightly elevated auxin level. Our results indicated that ADP1-mediated regulation of the local auxin level in meristematic regions is an essential determinant for plant architecture maintenance by restraining the outgrowth of lateral organs. PMID:24391508

  15. ADP1 affects plant architecture by regulating local auxin biosynthesis.

    PubMed

    Li, Ruixi; Li, Jieru; Li, Shibai; Qin, Genji; Novák, Ondřej; Pěnčík, Aleš; Ljung, Karin; Aoyama, Takashi; Liu, Jingjing; Murphy, Angus; Gu, Hongya; Tsuge, Tomohiko; Qu, Li-Jia

    2014-01-01

    Plant architecture is one of the key factors that affect plant survival and productivity. Plant body structure is established through the iterative initiation and outgrowth of lateral organs, which are derived from the shoot apical meristem and root apical meristem, after embryogenesis. Here we report that ADP1, a putative MATE (multidrug and toxic compound extrusion) transporter, plays an essential role in regulating lateral organ outgrowth, and thus in maintaining normal architecture of Arabidopsis. Elevated expression levels of ADP1 resulted in accelerated plant growth rate, and increased the numbers of axillary branches and flowers. Our molecular and genetic evidence demonstrated that the phenotypes of plants over-expressing ADP1 were caused by reduction of local auxin levels in the meristematic regions. We further discovered that this reduction was probably due to decreased levels of auxin biosynthesis in the local meristematic regions based on the measured reduction in IAA levels and the gene expression data. Simultaneous inactivation of ADP1 and its three closest homologs led to growth retardation, relative reduction of lateral organ number and slightly elevated auxin level. Our results indicated that ADP1-mediated regulation of the local auxin level in meristematic regions is an essential determinant for plant architecture maintenance by restraining the outgrowth of lateral organs.

  16. Identification of the platelet ADP receptor targeted by antithrombotic drugs.

    PubMed

    Hollopeter, G; Jantzen, H M; Vincent, D; Li, G; England, L; Ramakrishnan, V; Yang, R B; Nurden, P; Nurden, A; Julius, D; Conley, P B

    2001-01-11

    Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.

  17. Reprogramming cellular events by poly(ADP-ribose)-binding proteins

    PubMed Central

    Pic, Émilie; Ethier, Chantal; Dawson, Ted M.; Dawson, Valina L.; Masson, Jean-Yves; Poirier, Guy G.; Gagné, Jean-Philippe

    2013-01-01

    Poly(ADP-ribosyl)ation is a posttranslational modification catalyzed by the poly(ADP-ribose) polymerases (PARPs). These enzymes covalently modify glutamic, aspartic and lysine amino acid side chains of acceptor proteins by the sequential addition of ADP-ribose (ADPr) units. The poly(ADP-ribose) (pADPr) polymers formed alter the physico-chemical characteristics of the substrate with functional consequences on its biological activities. Recently, non-covalent binding to pADPr has emerged as a key mechanism to modulate and coordinate several intracellular pathways including the DNA damage response, protein stability and cell death. In this review, we describe the basis of non-covalent binding to pADPr that has led to the emerging concept of pADPr-responsive signaling pathways. This review emphasizes the structural elements and the modular strategies developed by pADPr-binding proteins to exert a fine-tuned control of a variety of pathways. Poly(ADP-ribosyl)ation reactions are highly regulated processes, both spatially and temporally, for which at least four specialized pADPr-binding modules accommodate different pADPr structures and reprogram protein functions. In this review, we highlight the role of well-characterized and newly discovered pADPr-binding modules in a diverse set of physiological functions. PMID:23268355

  18. Technological implications of SNAP reactor power system development on future space nuclear power systems

    SciTech Connect

    Anderson, R.V.

    1982-11-16

    Nuclear reactor systems are one method of satisfying space mission power needs. The development of such systems must proceed on a path consistent with mission needs and schedules. This path, or technology roadmap, starts from the power system technology data base available today. Much of this data base was established during the 1960s and early 1970s, when government and industry developed space nuclear reactor systems for steady-state power and propulsion. One of the largest development programs was the Systems for Nuclear Auxiliary Power (SNAP) Program. By the early 1970s, a technology base had evolved from this program at the system, subsystem, and component levels. There are many implications of this technology base on future reactor power systems. A review of this base highlights the need for performing a power system technology and mission overview study. Such a study is currently being performed by Rockwell's Energy Systems Group for the Department of Energy and will assess power system capabilities versus mission needs, considering development, schedule, and cost implications. The end product of the study will be a technology roadmap to guide reactor power system development.

  19. Modelling radiation loads to detectors in a SNAP mission.

    PubMed

    Mokhov, N V; Rakhno, I L; Striganov, S I; Peterson, T J

    2005-01-01

    In order to investigate the degradation of optical detectors of the Supernova Acceleration Project (SNAP) space mission because of irradiation, a three-dimensional model of the satellite has been developed. A realistic radiation environment at the satellite orbit, including both galactic cosmic rays and cosmic ray trapped in radiation belts, has been taken into account. The modelling has been performed with the MARS14 Monte Carlo code. In a current design, the main contribution to dose accumulated in the photo-detectors is shown to be due to trapped protons. The contribution of primary alpha particles is estimated. Predicted performance degradation for the photodetector for a four-year space mission is 40% and this can be reduced further by means of shielding optimisation.

  20. Modeling radiation loads to detectors in a SNAP mission

    SciTech Connect

    Nikolai V. Mokhov et al.

    2004-05-12

    In order to investigate degradation of optical detectors of the Supernova Acceleration Project (SNAP) space mission due to irradiation, a three-dimensional model of the satellite has been developed. Realistic radiation environment at the satellite orbit, including both galactic and trapped in radiation belts cosmic rays, has been taken into account. The modeling has been performed with the MARS14 Monte Carlo code. In a current design, the main contribution to dose accumulated in the photodetectors is shown to be due to trapped protons. A contribution of primary {alpha}-particles is estimated. Predicted performance degradation for the photo-detector for a 4-year space mission is 40% and can be reduced further by means of shielding optimization.

  1. Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances.

    PubMed

    Södergren, Anna L; Svensson Holm, Ann-Charlotte B; Ramström, Sofia; Lindström, Eva G; Grenegård, Magnus; Öllinger, Karin

    2016-01-01

    Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. The mechanisms that regulate lysosomal exocytosis in platelets are, however, still unclear. The aim of this study was to identify the pathways underlying platelet lysosomal secretion and elucidate how this process is controlled by platelet inhibitors. We found that high concentrations of thrombin induced partial lysosomal exocytosis as assessed by analysis of the activity of released N-acetyl-β-glucosaminidase (NAG) and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by flow cytometry. Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y12 antagonist cangrelor, while inhibition of thromboxane A2 formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug S-nitroso-N-acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I2 (PGI2) significantly suppressed lysosomal exocytosis. We conclude that platelet inhibitors that mimic functional endothelium such as PGI2 or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y12 receptors is important for efficient platelet lysosomal exocytosis by thrombin.

  2. Association of SNAP-25 Gene Ddel and Mnll Polymorphisms with Adult Attention Deficit Hyperactivity Disorder

    PubMed Central

    Herken, Hasan; Erdal, Mehmet Emin; Ünal, Gonca Ayşe; Çakaloz, Burcu; Ay, Mustafa Ertan; Yücel, Erinç; Edgünlü, Tuba; Şengül, Cem

    2014-01-01

    Objective The synaptosomal-associated protein of 25 kDa (SNAP-25) gene is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters. Previously, several studies reported association between SNAP-25 and attention deficit hyperactivity disorder (ADHD). We investigated whether these SNAP-25 polymorphisms (MnlI T/G and DdelI T/C) were also associated with ADHD in the Turkish population. Methods Our study comprised unrelated 139 subjects who met DSM-IV criteria for ADHD and 73 controls and all were of Turkish origin. Genetic analyses were performed and patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. Results SNAP-25 DdelI polymorphism was not associated with ADHD but there was a statistically significant difference between ADHD patients and controls for SNAP-25 MnlI polymorphism. For SNAP-25 MnlI polymorphism patients with G/G genotype of the SNAP-25 gene MnlI polymorphism had higher Wender-Utah scores and higher scores in the 1st and 3rd parts of adult ADD/ADHD Scale. Conclusion We detected a significant association of the MnlI polymorphism in our ADHD sample which was similar to previous findings. Our study also revealed that SNAP-25 MnlI polymorphism was also associated with symptom severity of ADHD. This study is also, the first report on the association of SNAP-25 with ADHD in the Turkish population. PMID:25395980

  3. The family of bacterial ADP-ribosylating exotoxins.

    PubMed Central

    Krueger, K M; Barbieri, J T

    1995-01-01

    Pathogenic bacteria utilize a variety of virulence factors that contribute to the clinical manifestation of their pathogenesis. Bacterial ADP-ribosylating exotoxins (bAREs) represent one family of virulence factors that exert their toxic effects by transferring the ADP-ribose moiety of NAD onto specific eucaryotic target proteins. The observations that some bAREs ADP-ribosylate eucaryotic proteins that regulate signal transduction, like the heterotrimeric GTP-binding proteins and the low-molecular-weight GTP-binding proteins, has extended interest in bAREs beyond the bacteriology laboratory. Molecular studies have shown that bAREs possess little primary amino acid homology and have diverse quaternary structure-function organization. Underlying this apparent diversity, biochemical and crystallographic studies have shown that several bAREs have conserved active-site structures and possess a conserved glutamic acid within their active sites. PMID:7704894

  4. 45 CFR 95.621 - ADP reviews.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GENERAL ADMINISTRATION-GRANT PROGRAMS (PUBLIC ASSISTANCE, MEDICAL ASSISTANCE AND STATE CHILDREN'S HEALTH INSURANCE PROGRAMS) Automatic Data Processing... CFR part 74 and the conditions of this subpart and to determine the efficiency, economy...

  5. SNAP: fabrication of long coupled microresonator chains with sub-angstrom precision.

    PubMed

    Sumetsky, M; Dulashko, Y

    2012-12-03

    Based on the recently-introduced Surface Nanoscale Axial Photonics (SNAP) platform, we demonstrate a chain of 30 coupled SNAP microresonators spaced by 50 micron along an optical fiber, which is fabricated with the precision of 0.7 angstrom and a standard deviation of 0.12 angstrom in effective microresonator radius. To the best of our knowledge, this result surpasses those achieved in other super-low-loss photonic technologies developed to date by two orders of magnitude. The chain exhibits bandgaps in both the discrete and continuous spectrum in excellent agreement with theory. The developed method enables robust fabrication of SNAP devices with sub-angstrom precision.

  6. Low back pain associated with internal snapping hip syndrome in a competitive cyclist.

    PubMed

    Little, T L; Mansoor, J

    2008-04-01

    Low back pain is a common complaint among cyclists. Here we present the case of a competitive master cyclist with low back pain and whose symptoms ultimately resolved when he was treated for internal snapping hip syndrome. Internal snapping hip syndrome is a painful lesion of the iliopsoas caused by snapping of the tendon over the iliopectineal eminence or anterior femoral head when the femur is extended from a flexed position. This is the first published report that we are aware of that describes this syndrome as a potential cause of low back pain in a competitive cyclist.

  7. Snap Down Voltage of a Fast-Scanning Micromirror with Vertical Electrostatic Combdrives

    NASA Astrophysics Data System (ADS)

    Wada, Hiroyuki; Lee, Daesung; Zappe, Stefan; Krishnamoorthy, Uma; Solgaard, Olav

    2004-02-01

    The parallel transition mode of the snap down of a fast-scanning mirror with vertical combdrives was analyzed. The snap down voltage of such a mirror significantly decreased when offsets between the ideal and actual upper movable comb teeth were more than 0.1 μm. When gap between the upper and lower comb teeth was decreased to increase torque, snap down voltage significantly decreased. The largest offset is induced by the lithography step in the fabrication process of the mirror. Self-alignment is required to increase the resonant frequency of the scanning mirror.

  8. Snapping scapula syndrome: current concepts review in conservative and surgical treatment

    PubMed Central

    Merolla, Giovanni; Cerciello, Simone; Paladini, Paolo; Porcellini, Giuseppe

    2013-01-01

    Summary The snapping scapula, also called “washboard syndrome” is a controversial condition attributed to bony and soft tissue abnormalities. The syndrome was understimated for long time and often associated only with specific osseous abnormalities. The nodal point in the overview of the syndrome is that crepitus associated with symptomatic bursitis may be physiologic and is not uncommon a clinical presentation without any form of crepitus or craquement. In the current rewiew we analyzed the current concepts in the conservative and surgical management of snapping scapula syndrome, preceded by a description of scapular anatomy, pathophysiology of scapulothoracic articulation and clinical features of snapping scapula. PMID:23888290

  9. ADP Bid Protests: Better Disclosure and Accountability of Settlements Needed

    DTIC Science & Technology

    1990-03-01

    but Few A With Mosey S -7 The.Census Bureaus expeice and concern about ossCA’s bid 1rotest procedures prompted.a DN Aft•ment of Commerce official in...GAO/GGD-S-13 ADP Bid Protest Settlements * 4 r 0 @ Appendix I ADP Bid Protests Fil With the GSBCA and£ G O From April to September 30, 18N General...J. Socolar Special Assistant to the Comptroller General General Accounting Office 蚉 G Street, N.V. Vashington, D.C. 20548 Subject: Analysis of

  10. The alpha-glycosidic bonds of poly(ADP-ribose) are acid-labile.

    PubMed

    Panzeter, P L; Zweifel, B; Althaus, F R

    1992-04-15

    The poly(ADP-ribosyl)ation system of higher eukaryotes produces multiple ADP-ribose polymers of distinct sizes which exhibit different binding affinities for histones. Although precipitation with trichloroacetic acid (TCA) is the standard procedure for isolation of poly(ADP-ribose) from biological material, we show here that poly(ADP-ribose) is not stable under acidic conditions. Storage of poly(ADP-ribose) as TCA pellets results in acid hydrolysis of polymers, the extent of which is dependent on storage time and temperature. The alpha-glycosidic, inter-residue bonds are the preferred sites of attack, thus reducing polymer sizes by integral numbers of ADP-ribose to yield artefactually more and smaller polymers than originally present. Therefore, poly(ADP-ribosyl)ation studies involving TCA precipitation, histone extraction with acids, or acidic incubations of ADP-ribose polymers must account for the impact of acids on resulting polymer populations.

  11. A New Software Metric to Complement Function Points: The Software Non-functional Assessment Process (SNAP)

    DTIC Science & Technology

    2013-08-01

    industries: Aerospace, Auto- motive , Banking, Government, Fast Moving Consumer Goods, Financial Services, Insurance, Manufacturing, Systems Integra...dards Committee Chair is Talmon Ben- Cnaan . Other SNAP team members were Wendy Bloomfield, Steve Chizar, Peter R. Hill, Kathy Lamoureaux, Abinash Sahoo

  12. Snapping shrimp prefer natural as opposed to artificial materials as their habitat in laboratory conditions

    NASA Astrophysics Data System (ADS)

    Sim, Lai Kean; Ghazali, Shahriman M.

    2014-09-01

    This study analyzed the habitat selection behavior of the snapping shrimp, Alpheus spp., comparing natural shelters (Rocks with oysters attached on the surface Sh; rocks with smooth surface, Ro and coral rubble, Co with plastic bottle. Controlled laboratory experiments were conducted to assess the habitat preference, effect of photoperiod and shrimp orientation at shelter. The current study indicated that snapping shrimp preferred natural materials but rejected plastic bottle as their shelter. Among the natural shelters, coral rubble was the most preferred habitat followed by shell and rock. Photoperiod showed minimum effect on the shrimp where they spend most of the time inside and underneath the shelters. In conclusion the current study showed that snapping shrimp preferred coral rubble as opposed to other natural material and plastic bottle. The result also suggested that plastic debris in the marine environment is not an alternative habitat for snapping shrimp.

  13. α-SNAP Prevents Docking of the Acrosome during Sperm Exocytosis because It Sequesters Monomeric Syntaxin

    PubMed Central

    Rodríguez, Facundo; Bustos, Matías A.; Zanetti, María N.; Ruete, María C.; Mayorga, Luis S.; Tomes, Claudia N.

    2011-01-01

    α-SNAP has an essential role in membrane fusion that consists of bridging cis SNARE complexes to NSF. α-SNAP stimulates NSF, which releases itself, α-SNAP, and individual SNAREs that subsequently re-engage in the trans arrays indispensable for fusion. α-SNAP also binds monomeric syntaxin and NSF disengages the α-SNAP/syntaxin dimer. Here, we examine why recombinant α-SNAP blocks secretion in permeabilized human sperm despite the fact that the endogenous protein is essential for membrane fusion. The only mammalian organism with a genetically modified α-SNAP is the hyh mouse strain, which bears a M105I point mutation; males are subfertile due to defective sperm exocytosis. We report here that recombinant α-SNAP-M105I has greater affinity for the cytosolic portion of immunoprecipitated syntaxin than the wild type protein and in consequence NSF is less efficient in releasing the mutant. α-SNAP-M105I is a more potent sperm exocytosis blocker than the wild type and requires higher concentrations of NSF to rescue its effect. Unlike other fusion scenarios where SNAREs are subjected to an assembly/disassembly cycle, the fusion machinery in sperm is tuned so that SNAREs progress uni-directionally from a cis configuration in resting cells to monomeric and subsequently trans arrays in cells challenged with exocytosis inducers. By means of functional and indirect immunofluorescense assays, we show that recombinant α-SNAPs — wild type and M105I — inhibit exocytosis because they bind monomeric syntaxin and prevent this SNARE from assembling with its cognates in trans. Sequestration of free syntaxin impedes docking of the acrosome to the plasma membrane assessed by transmission electron microscopy. The N-terminal deletion mutant α-SNAP-(160–295), unable to bind syntaxin, affects neither docking nor secretion. The implications of this study are twofold: our findings explain the fertility defect of hyh mice and indicate that assembly of SNAREs in trans complexes is

  14. Macroalgae culture to treat anaerobic digestion piggery effluent (ADPE).

    PubMed

    Nwoba, Emeka Godfrey; Moheimani, Navid Reza; Ubi, Benjamin Ewa; Ogbonna, James Chukwuma; Vadiveloo, Ashiwin; Pluske, John R; Huisman, John Marinus

    2017-03-01

    Environmental consequences of high productivity piggeries are significant and can result in negative environmental impacts, hence bioremediation techniques (in particular using macroalgae) are therefore of great interest. Here, the growth potential of several freshwater macroalgae in anaerobic digestion piggery effluent (ADPE), their nutrient removal rates and biochemical composition of the biomass were investigated under outdoor climatic conditions. A consortium of two macroalgae, Rhizoclonium sp. and Ulothrix sp. was isolated and could efficiently grow in the ADPE. Maximum ammonium removal rate (30.6±6.50mg NH4(+)-NL(-1)d(-1)) was achieved at ADPE concentration equivalent to 248mgNH4(+)-NL(-1). Mean biomass productivity of 31.1±1.14g ash-free dry weight (AFDW) m(-2)d(-1) was achieved. Total carbohydrate and protein contents ranged between 42.8-54.8 and 43.4-45.0% AFDW, respectively, while total lipid content was very low. The study indicates the potential use of this macroalgal consortium for treating ADPE as well as source of animal feed production.

  15. A genetically encoded fluorescent reporter of ATP/ADP ratio

    PubMed Central

    Berg, Jim; Hung, Yin Pun; Yellen, Gary

    2008-01-01

    A fluorescent sensor of adenylate nucleotides was constructed by combining a circularly permuted variant of green fluorescent protein with a bacterial regulatory protein, GlnK1, from Methanococcus jannaschii. The affinity for Mg-ATP is below 100 nM, as seen for the other members of the bacterial PII regulator family – a surprisingly high affinity given normal intracellular [ATP] in the millimolar range. ADP binds to the same site, competing with Mg-ATP but producing a smaller change in fluorescence. With normal physiological concentrations of ATP and ADP, the binding site is saturated, but competition between the two substrates causes the sensor to behave as a nearly ideal reporter of the ATP/ADP concentration ratio. This principle for sensing the ratio of two analytes by competition at a high affinity site probably underlies the normal functioning of PII regulatory proteins. The engineered sensor, Perceval, can be used to monitor the ATP/ADP ratio during live cell imaging. PMID:19122669

  16. Immunohistochemical demonstration of syntaxin and SNAP-25 in chromaffin cells of the frog adrenal gland.

    PubMed

    Quintanar, J L; Salinas, E; Reig, J A

    1998-08-01

    The release of catecholamines from chromaffin cells involves specific proteins such as synaptobrevin present in the secretory vesicles as well as syntaxin and synaptosomal-associated protein of 25 kDa (SNAP-25), both present in the plasma membrane. We have found syntaxin and SNAP-25 in chromaffin cells of the frog adrenal gland by immunohistochemistry. This result suggests that the secretion of catecholamines from chromaffin cells involves these proteins in the frog.

  17. A Highly Specific Monoclonal Antibody for Botulinum Neurotoxin Type A-Cleaved SNAP25

    PubMed Central

    Rhéaume, Catherine; Cai, Brian B.; Wang, Joanne; Fernández-Salas, Ester; Aoki, K. Roger; Francis, Joseph; Broide, Ron S.

    2015-01-01

    Botulinum neurotoxin type-A (BoNT/A), as onabotulinumtoxinA, is approved globally for 11 major therapeutic and cosmetic indications. While the mechanism of action for BoNT/A at the presynaptic nerve terminal has been established, questions remain regarding intracellular trafficking patterns and overall fate of the toxin. Resolving these questions partly depends on the ability to detect BoNT/A’s location, distribution, and movement within a cell. Due to BoNT/A’s high potency and extremely low concentrations within neurons, an alternative approach has been employed. This involves utilizing specific antibodies against the BoNT/A-cleaved SNAP25 substrate (SNAP25197) to track the enzymatic activity of toxin within cells. Using our highly specific mouse monoclonal antibody (mAb) against SNAP25197, we generated human and murine recombinant versions (rMAb) using specific backbone immunoglobulins. In this study, we validated the specificity of our anti-SNAP25197 rMAbs in several different assays and performed side-by-side comparisons to commercially-available and in-house antibodies against SNAP25. Our rMAbs were highly specific for SNAP25197 in all assays and on several different BoNT/A-treated tissues, showing no cross-reactivity with full-length SNAP25. This was not the case with other reportedly SNAP25197-selective antibodies, which were selective in some, but not all assays. The rMAbs described herein represent effective new tools for detecting BoNT/A activity within cells. PMID:26114335

  18. SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex

    PubMed Central

    Thompson, Peter M.; Cruz, Dianne A.; Fucich, Elizabeth A.; Olukotun, Dianna Y.; Takahashi, Masami; Itakura, Makoto

    2015-01-01

    SNAP-25 is a neurotransmitter vesicular docking protein which has been associated with brain disorders such as attention deficit hyperactivity disorder, bipolar disorder and schizophrenia. In this project, we were interested if clinical factors are associated with differential SNAP-25 expression. We examined the SNAP-25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9) and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical variables including mood state in the last week of life and lifetime impulsiveness. We found affected subjects with a diagnosis of alcohol use disorder (AUD) had a lower level of SNAP-25b BA24 protein compared to those without AUD. Hispanic subjects had lower levels of SNAP-25a, b and BA9 mRNA than Anglo-American subjects. Subjects who smoked had a total pan (total) SNAP-25 BA9/BA24 ratio. Subjects in the group with a low level of anxious-psychotic symptoms had higher SNAP-25a BA24 mRNA compared to normal controls, and both the high and low symptoms groups had higher pan (total) SNAP-25 BA9/BA24 ratios than normal controls. These data expand our understanding of clinical factors associated with SNAP-25. They suggest that SNAP-25 total and isoform levels may be useful biomarkers beyond limited neurological and psychiatric diagnostic categories. PMID:27606314

  19. American Diploma Project (ADP) End-of-Course Exams: 2010 Annual Report

    ERIC Educational Resources Information Center

    Achieve, Inc., 2010

    2010-01-01

    To assess the raised expectations of college and career readiness for all students, a group of American Diploma Project (ADP) Network states formed the ADP Assessment Consortium in 2005. The Consortium created Algebra I and II end-of-course exams, based in large part on Achieve's ADP mathematics benchmarks, which would provide an honest assessment…

  20. Method to Control Dynamic Snap-Through Instability of Dielectric Elastomers

    NASA Astrophysics Data System (ADS)

    Zhang, Junshi; Chen, Hualing; Li, Dichen

    2016-12-01

    Dielectric elastomers (DEs) are a category of soft materials that are capable of large deformation, however, the actuation performance is affected by snap-through instability. In this article, a dynamics model is developed to investigate the dynamic snap-through instability of DEs by applying the triangle and sinusoidal voltages. The DE materials with different limiting stretches are considered. When the DE is under a triangle voltage or a sinusoidal voltage, the snap-through behavior may emerge during the response in time domain, and the DEs with a large value of limiting stretch are susceptible to dynamic snap-through instability. By tuning the mechanical tensile force, the occurrence of dynamic snap-through instability can be controlled. With the increase of tensile force, the dynamic snap-through behavior initially does not emerge during vibration, then accompanies the vibration, and eventually disappears. Phase paths and Poincaré maps are utilized to explore the dynamic stability evolution of the DE systems.

  1. Phosphate and ADP Differently Inhibit Coordinated Smooth Muscle Myosin Groups

    PubMed Central

    Hilbert, Lennart; Balassy, Zsombor; Zitouni, Nedjma B.; Mackey, Michael C.; Lauzon, Anne-Marie

    2015-01-01

    Actin filaments propelled in vitro by groups of skeletal muscle myosin motors exhibit distinct phases of active sliding or arrest, whose occurrence depends on actin length (L) within a range of up to 1.0 μm. Smooth muscle myosin filaments are exponentially distributed with ≈150 nm average length in vivo—suggesting relevance of the L-dependence of myosin group kinetics. Here, we found L-dependent actin arrest and sliding in in vitro motility assays of smooth muscle myosin. We perturbed individual myosin kinetics with varying, physiological concentrations of phosphate (Pi, release associated with main power stroke) and adenosine diphosphate (ADP, release associated with minor mechanical step). Adenosine triphosphate was kept constant at physiological concentration. Increasing [Pi] lowered the fraction of time for which actin was actively sliding, reflected in reduced average sliding velocity (ν) and motile fraction (fmot, fraction of time that filaments are moving); increasing [ADP] increased the fraction of time actively sliding and reduced the velocity while sliding, reflected in reduced ν and increased fmot. We introduced specific Pi and ADP effects on individual myosin kinetics into our recently developed mathematical model of actin propulsion by myosin groups. Simulations matched our experimental observations and described the inhibition of myosin group kinetics. At low [Pi] and [ADP], actin arrest and sliding were reflected by two distinct chemical states of the myosin group. Upon [Pi] increase, the probability of the active state decreased; upon [ADP] increase, the probability of the active state increased, but the active state became increasingly similar to the arrested state. PMID:25650929

  2. Phosphate and ADP differently inhibit coordinated smooth muscle myosin groups.

    PubMed

    Hilbert, Lennart; Balassy, Zsombor; Zitouni, Nedjma B; Mackey, Michael C; Lauzon, Anne-Marie

    2015-02-03

    Actin filaments propelled in vitro by groups of skeletal muscle myosin motors exhibit distinct phases of active sliding or arrest, whose occurrence depends on actin length (L) within a range of up to 1.0 μm. Smooth muscle myosin filaments are exponentially distributed with ≈150 nm average length in vivo--suggesting relevance of the L-dependence of myosin group kinetics. Here, we found L-dependent actin arrest and sliding in in vitro motility assays of smooth muscle myosin. We perturbed individual myosin kinetics with varying, physiological concentrations of phosphate (Pi, release associated with main power stroke) and adenosine diphosphate (ADP, release associated with minor mechanical step). Adenosine triphosphate was kept constant at physiological concentration. Increasing [Pi] lowered the fraction of time for which actin was actively sliding, reflected in reduced average sliding velocity (ν) and motile fraction (fmot, fraction of time that filaments are moving); increasing [ADP] increased the fraction of time actively sliding and reduced the velocity while sliding, reflected in reduced ν and increased fmot. We introduced specific Pi and ADP effects on individual myosin kinetics into our recently developed mathematical model of actin propulsion by myosin groups. Simulations matched our experimental observations and described the inhibition of myosin group kinetics. At low [Pi] and [ADP], actin arrest and sliding were reflected by two distinct chemical states of the myosin group. Upon [Pi] increase, the probability of the active state decreased; upon [ADP] increase, the probability of the active state increased, but the active state became increasingly similar to the arrested state.

  3. Phylogenetic approach for inferring the origin and functional evolution of bacterial ADP-ribosylation superfamily.

    PubMed

    Chellapandi, P; Sakthishree, S; Bharathi, M

    2013-09-01

    Bacterial ADP-ribosyltransferases (BADPRTs) are extensively contributed to determine the strain-specific virulence state and pathogenesis in human hosts. Understanding molecular evolution and functional diversity of the BADPRTs is an important standpoint to describe the fundamental behind in the vaccine designing for bacterial infections. In the present study, we have evaluated the origin and functional evolution of conserved domains within the BADPRTs by analyzing their sequence-function relationship. To represent the evolution history of BADPRTs, phylogenetic trees were constructed based on their protein sequence, structure and conserved domains using different evolutionary programs. Sequence divergence and genetic diversity were studied herein to deduce the functional evolution of conserved domains across the family and superfamily. The results of sequence similarity search have shown that three hypothetical proteins (above 90%) were identical to the members of BADPRTs and their functions were annotated by phylogenetic approach. Phylogenetic analysis of this study has revealed the family members of BADPRTs were phylogenetically related to one another, functionally diverged within the same family, and dispersed into closely related bacteria. The presence of core substitution pattern in the conserved domains would determine the family-specific function of BADPRTs. Functional diversity of the BADPRTs was exclusively distinguished by Darwinian positive selection (diphtheria toxin C and pertussis toxin S) and neutral selection (arginine ADP-ribosyltransferase, enterotoxin A and binary toxin A) acting on the existing domains. Many of the family members were sharing their sequence-specific features from members in the arginine ADP-ribosyltransferase family. Conservative functions of members in the BADPRTs have shown to be expanded only within closely related families, and retained as such in pathogenic bacteria by evolutionary process (domain duplication or

  4. Programmable snapping composites with bio-inspired architecture.

    PubMed

    Schmied, Jascha U; Le Ferrand, Hortense; Ermanni, Paolo; Studart, André R; Arrieta, Andres F

    2017-03-13

    The development of programmable self-shaping materials enables the onset of new and innovative functionalities in many application fields. Commonly, shape adaptation is achieved by exploiting diffusion-driven swelling or nano-scale phase transition, limiting the change of shape to slow motion predominantly determined by the environmental conditions and/or the materials specificity. To address these shortcomings, we report shape adaptable programmable shells that undergo morphing via a snap-through mechanism inspired by the Dionaea muscipula leaf, known as the Venus fly trap. The presented shells are composite materials made of epoxy reinforced by stiff anisotropic alumina micro-platelets oriented in specific directions. By tailoring the microstructure via magnetically-driven alignment of the platelets, we locally tune the pre-strain and stiffness anisotropy of the composite. This novel approach enables the fabrication of complex shapes showing non-orthotropic curvatures and stiffness gradients, radically extending the design space when compared to conventional long-fibre reinforced multi-stable composites. The rare combination of large stresses, short actuation times and complex shapes, results in hinge-free artificial shape adaptable systems with large design freedom for a variety of morphing applications.

  5. Snap-off in constricted capillary with elastic interface

    NASA Astrophysics Data System (ADS)

    Hoyer, P.; Alvarado, V.; Carvalho, M. S.

    2016-01-01

    Snap-off of bubbles and drops in constricted capillaries occurs in many different situations, from bio-fluid to multiphase flow in porous media. The breakup process has been extensively analyzed both by theory and experiments, but most work has been limited to pure interfaces, at which the surface stress is isotropic and fully defined by the interfacial tension and interface curvature. Complex interfaces may present viscous and elastic behavior leading to a complex stress state that may change the dynamics of the interface deformation and breakup. We extend the available asymptotic model based on lubrication approximation to include elastic interfacial stress. Drop breakup time is determined as a function of the capillary geometry and liquid properties, including the interfacial elastic modulus. Results show that the interfacial elasticity has a stabilizing effect by slowing down the growth of the liquid collar, leading to a larger break-up time. This stabilizing effect has been observed experimentally in different, but related flows [Alvarado et al., "Interfacial visco-elasticity of crude oil-brine: An alternative EOR mechanism in smart waterflooding," in SPE-169127 Improved Oil Recovery Symposium (Society of Petroleum Engineers, 2014)].

  6. The ARTT motif and a unified structural understanding of substrate recognition in ADP-ribosylating bacterial toxins and eukaryotic ADP-ribosyltransferases.

    PubMed

    Han, Seungil; Tainer, John A

    2002-02-01

    ADP-ribosylation is a widely occurring and biologically critical covalent chemical modification process in pathogenic mechanisms, intracellular signaling systems, DNA repair, and cell division. The reaction is catalyzed by ADP-ribosyltransferases, which transfer the ADP-ribose moiety of NAD to a target protein with nicotinamide release. A family of bacterial toxins and eukaryotic enzymes has been termed the mono-ADP-ribosyltransferases, in distinction to the poly-ADP-ribosyltransferases, which catalyze the addition of multiple ADP-ribose groups to the carboxyl terminus of eukaryotic nucleoproteins. Despite the limited primary sequence homology among the different ADP-ribosyltransferases, a central cleft bearing the NAD-binding pocket formed by the two perpendicular beta-sheet cores has been remarkably conserved between bacterial toxins and eukaryotic mono- and poly-ADP-ribosyltransferases. The majority of bacterial toxins and eukaryotic mono-ADP-ribosyltransferases are characterized by conserved His and catalytic Glu residues. In contrast, diphtheria toxin, Pseudomonas exotoxin A, and eukaryotic poly-ADP-ribosytransferases are characterized by conserved Arg and catalytic Glu residues. Structural and mutagenic studies of the NAD-binding core of a binary toxin and a C3-like toxin identified an ARTT motif (ADP-ribosylating turn-turn motif) that is implicated in substrate specificity and recognition. Here we apply structure-based sequence alignment and comparative structural analyses of all known structures of ADP-ribosyltransfeases to suggest that this ARTT motif is functionally important in many ADP-ribosylating enzymes that bear a NAD-binding cleft as characterized by conserved Arg and catalytic Glu residues. Overall, structure-based sequence analysis reveals common core structures and conserved active sites of ADP-ribosyltransferases to support similar NAD-binding mechanisms but differing mechanisms of target protein binding via sequence variations within the ARTT

  7. Should We Have Blind Faith in Bioinformatics Software? Illustrations from the SNAP Web-Based Tool

    PubMed Central

    Robiou-du-Pont, Sébastien; Li, Aihua; Christie, Shanice; Sohani, Zahra N.; Meyre, David

    2015-01-01

    Bioinformatics tools have gained popularity in biology but little is known about their validity. We aimed to assess the early contribution of 415 single nucleotide polymorphisms (SNPs) associated with eight cardio-metabolic traits at the genome-wide significance level in adults in the Family Atherosclerosis Monitoring In earLY Life (FAMILY) birth cohort. We used the popular web-based tool SNAP to assess the availability of the 415 SNPs in the Illumina Cardio-Metabochip genotyped in the FAMILY study participants. We then compared the SNAP output with the Cardio-Metabochip file provided by Illumina using chromosome and chromosomal positions of SNPs from NCBI Human Genome Browser (Genome Reference Consortium Human Build 37). With the HapMap 3 release 2 reference, 201 out of 415 SNPs were reported as missing in the Cardio-Metabochip by the SNAP output. However, the Cardio-Metabochip file revealed that 152 of these 201 SNPs were in fact present in the Cardio-Metabochip array (false negative rate of 36.6%). With the more recent 1000 Genomes Project release, we found a false-negative rate of 17.6% by comparing the outputs of SNAP and the Illumina product file. We did not find any ‘false positive’ SNPs (SNPs specified as available in the Cardio-Metabochip by SNAP, but not by the Cardio-Metabochip Illumina file). The Cohen’s Kappa coefficient, which calculates the percentage of agreement between both methods, indicated that the validity of SNAP was fair to moderate depending on the reference used (the HapMap 3 or 1000 Genomes). In conclusion, we demonstrate that the SNAP outputs for the Cardio-Metabochip are invalid. This study illustrates the importance of systematically assessing the validity of bioinformatics tools in an independent manner. We propose a series of guidelines to improve practices in the fast-moving field of bioinformatics software implementation. PMID:25742008

  8. α-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels

    PubMed Central

    Li, Peiyao; Miao, Yong; Dani, Adish; Vig, Monika

    2016-01-01

    Orai1 forms a highly calcium-selective pore of the calcium release activated channel, and α-SNAP is necessary for its function. Here we show that α-SNAP regulates on-site assembly of Orai1 dimers into calcium-selective multimers. We find that Orai1 is a dimer in resting primary mouse embryonic fibroblasts but displays variable stoichiometry in the plasma membrane of store-depleted cells. Remarkably, α-SNAP depletion induces formation of higher-order Orai1 oligomers, which permeate significant levels of sodium via Orai1 channels. Sodium permeation in α-SNAP–deficient cells cannot be corrected by tethering multiple Stim1 domains to Orai1 C-terminal tail, demonstrating that α-SNAP regulates functional assembly and calcium selectivity of Orai1 multimers independently of Stim1 levels. Fluorescence nanoscopy reveals sustained coassociation of α-SNAP with Stim1 and Orai1, and α-SNAP–depleted cells show faster and less constrained mobility of Orai1 within ER-PM junctions, suggesting Orai1 and Stim1 coentrapment without stable contacts. Furthermore, α-SNAP depletion significantly reduces fluorescence resonance energy transfer between Stim1 and Orai1 N-terminus but not C-terminus. Taken together, these data reveal a unique role of α-SNAP in the on-site functional assembly of Orai1 subunits and suggest that this process may, in part, involve enabling crucial low-affinity interactions between Orai1 N-terminus and Stim1. PMID:27335124

  9. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions.

    PubMed Central

    D'Amours, D; Desnoyers, S; D'Silva, I; Poirier, G G

    1999-01-01

    Poly(ADP-ribosyl)ation is a post-translational modification of proteins. During this process, molecules of ADP-ribose are added successively on to acceptor proteins to form branched polymers. This modification is transient but very extensive in vivo, as polymer chains can reach more than 200 units on protein acceptors. The existence of the poly(ADP-ribose) polymer was first reported nearly 40 years ago. Since then, the importance of poly(ADP-ribose) synthesis has been established in many cellular processes. However, a clear and unified picture of the physiological role of poly(ADP-ribosyl)ation still remains to be established. The total dependence of poly(ADP-ribose) synthesis on DNA strand breaks strongly suggests that this post-translational modification is involved in the metabolism of nucleic acids. This view is also supported by the identification of direct protein-protein interactions involving poly(ADP-ribose) polymerase (113 kDa PARP), an enzyme catalysing the formation of poly(ADP-ribose), and key effectors of DNA repair, replication and transcription reactions. The presence of PARP in these multiprotein complexes, in addition to the actual poly(ADP-ribosyl)ation of some components of these complexes, clearly supports an important role for poly(ADP-ribosyl)ation reactions in DNA transactions. Accordingly, inhibition of poly(ADP-ribose) synthesis by any of several approaches and the analysis of PARP-deficient cells has revealed that the absence of poly(ADP-ribosyl)ation strongly affects DNA metabolism, most notably DNA repair. The recent identification of new poly(ADP-ribosyl)ating enzymes with distinct (non-standard) structures in eukaryotes and archaea has revealed a novel level of complexity in the regulation of poly(ADP-ribose) metabolism. PMID:10455009

  10. Complete Nucleotide Sequence and Organization of the Atrazine Catabolic Plasmid pADP-1 from Pseudomonas sp. Strain ADP

    PubMed Central

    Martinez, Betsy; Tomkins, Jeffrey; Wackett, Lawrence P.; Wing, Rod; Sadowsky, Michael J.

    2001-01-01

    The complete 108,845-nucleotide sequence of catabolic plasmid pADP-1 from Pseudomonas sp. strain ADP was determined. Plasmid pADP-1 was previously shown to encode AtzA, AtzB, and AtzC, which catalyze the sequential hydrolytic removal of s-triazine ring substituents from the herbicide atrazine to yield cyanuric acid. Computational analyses indicated that pADP-1 encodes 104 putative open reading frames (ORFs), which are predicted to function in catabolism, transposition, and plasmid maintenance, transfer, and replication. Regions encoding transfer and replication functions of pADP-1 had 80 to 100% amino acid sequence identity to pR751, an IncPβ plasmid previously isolated from Enterobacter aerogenes. pADP-1 was shown to contain a functional mercury resistance operon with 99% identity to Tn5053. Complete copies of transposases with 99% amino acid sequence identity to TnpA from IS1071 and TnpA from Pseudomonas pseudoalcaligenes were identified and flank each of the atzA, atzB, and atzC genes, forming structures resembling nested catabolic transposons. Functional analyses identified three new catabolic genes, atzD, atzE, and atzF, which participate in atrazine catabolism. Crude extracts from Escherichia coli expressing AtzD hydrolyzed cyanuric acid to biuret. AtzD showed 58% amino acid sequence identity to TrzD, a cyanuric acid amidohydrolase, from Pseudomonas sp. strain NRRLB-12227. Two other genes encoding the further catabolism of cyanuric acid, atzE and atzF, reside in a contiguous cluster adjacent to a potential LysR-type transcriptional regulator. E. coli strains bearing atzE and atzF were shown to encode a biuret hydrolase and allophanate hydrolase, respectively. atzDEF are cotranscribed. AtzE and AtzF are members of a common amidase protein family. These data reveal the complete structure of a catabolic plasmid and show that the atrazine catabolic genes are dispersed on three disparate regions of the plasmid. These results begin to provide insight into how

  11. The 1994 NASA/USRA/ADP Design Projects

    NASA Technical Reports Server (NTRS)

    Cruse, Thomas; Richardson, Joseph; Tryon, Robert

    1994-01-01

    The NASA/USRA/ADP Design Projects from Vanderbilt University, Department of Mechanical Engineering (1994) are enclosed in this final report. Design projects include: (1) Protein Crystal Growth, both facilities and methodology; (2) ACES Deployable Space Boom; (3) Hybrid Launch System designs for both manned and unmanned systems; (4) LH2 Fuel Tank design (SSTO); (5) SSTO design; and (6) Pressure Tank Feed System design.

  12. Structure of Plasmodium falciparum ADP-ribosylation factor 1

    SciTech Connect

    Cook, William J.; Smith, Craig D.; Senkovich, Olga; Holder, Anthony A.; Chattopadhyay, Debasish

    2011-09-26

    Vesicular trafficking may play a crucial role in the pathogenesis and survival of the malaria parasite. ADP-ribosylation factors (ARFs) are among the major components of vesicular trafficking pathways in eukaryotes. The crystal structure of ARF1 GTPase from Plasmodium falciparum has been determined in the GDP-bound conformation at 2.5 {angstrom} resolution and is compared with the structures of mammalian ARF1s.

  13. Magnesium Modulates Actin Binding and ADP Release in Myosin Motors*

    PubMed Central

    Swenson, Anja M.; Trivedi, Darshan V.; Rauscher, Anna A.; Wang, Yuan; Takagi, Yasuharu; Palmer, Bradley M.; Málnási-Csizmadia, András; Debold, Edward P.; Yengo, Christopher M.

    2014-01-01

    We examined the magnesium dependence of five class II myosins, including fast skeletal muscle myosin, smooth muscle myosin, β-cardiac myosin (CMIIB), Dictyostelium myosin II (DdMII), and nonmuscle myosin IIA, as well as myosin V. We found that the myosins examined are inhibited in a Mg2+-dependent manner (0.3–9.0 mm free Mg2+) in both ATPase and motility assays, under conditions in which the ionic strength was held constant. We found that the ADP release rate constant is reduced by Mg2+ in myosin V, smooth muscle myosin, nonmuscle myosin IIA, CMIIB, and DdMII, although the ADP affinity is fairly insensitive to Mg2+ in fast skeletal muscle myosin, CMIIB, and DdMII. Single tryptophan probes in the switch I (Trp-239) and switch II (Trp-501) region of DdMII demonstrate these conserved regions of the active site are sensitive to Mg2+ coordination. Cardiac muscle fiber mechanic studies demonstrate cross-bridge attachment time is increased at higher Mg2+ concentrations, demonstrating that the ADP release rate constant is slowed by Mg2+ in the context of an activated muscle fiber. Direct measurements of phosphate release in myosin V demonstrate that Mg2+ reduces actin affinity in the M·ADP·Pi state, although it does not change the rate of phosphate release. Therefore, the Mg2+ inhibition of the actin-activated ATPase activity observed in class II myosins is likely the result of Mg2+-dependent alterations in actin binding. Overall, our results suggest that Mg2+ reduces the ADP release rate constant and rate of attachment to actin in both high and low duty ratio myosins. PMID:25006251

  14. Noncovalent protein interaction with poly(ADP-ribose).

    PubMed

    Malanga, Maria; Althaus, Felix R

    2011-01-01

    Compared to most common posttranslational modifications of proteins, a peculiarity of poly(ADP-ribosyl)ation is the molecular heterogeneity and complexity of the reaction product, poly(ADP-ribose) (PAR). In fact, protein-bound PAR consists of variously sized (2-200 ADP-ribose residues) linear or branched molecules, negatively charged at physiological pH. It is now clear that PAR not only affects the function of the polypeptide to which it is covalently bound, but it can also influence the activity of other proteins by engaging specific noncovalent interactions. In the last 10 years, the family of PAR-binding proteins has been rapidly growing and functional studies have expanded the regulatory potential of noncovalent -protein targeting by PAR far beyond initial assumptions.In this chapter, methods are described for: (1) PAR synthesis and analysis; (2) detecting PAR-binding proteins in protein mixtures; (3) defining affinity and specificity of PAR binding to individual proteins or protein fragments; and (4) identifying PAR molecules selectively involved in the interaction.

  15. Reflective Polyethylene Mulch Reduces Mexican Bean Beetle (Coleoptera: Coccinellidae) Densities and Damage in Snap Beans.

    PubMed

    Nottingham, L B; Kuhar, T P

    2016-08-01

    Mexican bean beetle, Epilachna varivestis Mulsant, is a serious pest of snap beans, Phaseolus vulgaris L., in the eastern United States. These beetles are intolerant to direct sunlight, explaining why individuals are typically found on the undersides of leaves and in the lower portion of the plant canopy. We hypothesized that snap beans grown on reflective, agricultural polyethylene (plastic mulch) would have fewer Mexican bean beetles and less injury than those grown on black plastic or bare soil. In 2014 and 2015, beans were seeded into beds of metallized, white, and black plastic, and bare soil, in field plots near Blacksburg, VA. Mexican bean beetle density, feeding injury, predatory arthropods, and snap bean yield were sampled. Reflected light intensity, temperature, and humidity were monitored using data loggers. Pyranometer readings showed that reflected light intensity was highest over metallized plastic and second highest over white plastic; black plastic and bare soil were similarly low. Temperature and humidity were unaffected by treatments. Significant reductions in Mexican bean beetle densities and feeding injury were observed in both metallized and white plastic plots compared to black plastic and bare soil, with metallized plastic having the fewest Mexican bean beetle life stages and injury. Predatory arthropod densities were not reduced by reflective plastic. Metallized plots produced the highest yields, followed by white. The results of this study suggest that growing snap beans on reflective plastic mulch can suppress the incidence and damage of Mexican bean beetle, and increase yield in snap beans.

  16. Transcription termination between polo and snap, two closely spaced tandem genes of D. melanogaster.

    PubMed

    Henriques, Telmo; Ji, Zhe; Tan-Wong, Sue Mei; Carmo, Alexandre M; Tian, Bin; Proudfoot, Nicholas J; Moreira, Alexandra

    2012-01-01

    Transcription termination of RNA polymerase II between closely spaced genes is an important, though poorly understood, mechanism. This is true, in particular, in the Drosophila genome, where approximately 52% of tandem genes are separated by less than 1 kb. We show that a set of Drosophila tandem genes has a negative correlation of gene expression and display several molecular marks indicative of promoter pausing. We find that an intergenic spacing of 168 bp is sufficient for efficient transcription termination between the polo-snap tandem gene pair, by a mechanism that is independent of Pcf11 and Xrn2. In contrast, analysis of a tandem gene pair containing a longer intergenic region reveals that termination occurs farther downstream of the poly(A) signal and is, in this case, dependent on Pcf11 and Xrn2. For polo-snap, displacement of poised polymerase from the snap promoter by depletion of the initiation factor TFIIB results in an increase of polo transcriptional read-through. This suggests that poised polymerase is necessary for transcription termination. Interestingly, we observe that polo forms a TFIIB dependent gene loop between its promoter and terminator regions. Furthermore, in a plasmid containing the polo-snap locus, deletion of the polo promoter causes an increase in snap expression, as does deletion of polo poly(A) signals. Taken together, our results indicate that polo forms a gene loop and polo transcription termination occurs by an Xrn2 and Pcf11 independent mechanism that requires TFIIB.

  17. Phosphorylation of αSNAP is Required for Secretory Organelle Biogenesis in Toxoplasma gondii.

    PubMed

    Stewart, Rebecca J; Ferguson, David J P; Whitehead, Lachlan; Bradin, Clare H; Wu, Hong J; Tonkin, Christopher J

    2016-02-01

    Upon infection, apicomplexan parasites quickly invade host cells and begin a replicative cycle rapidly increasing in number over a short period of time, leading to tissue lysis and disease. The secretory pathway of these highly polarized protozoan parasites tightly controls, in time and space, the biogenesis of specialized structures and organelles required for invasion and intracellular survival. In other systems, regulation of protein trafficking can occur by phosphorylation of vesicle fusion machinery. Previously, we have shown that Toxoplasma gondii αSNAP - a protein that controls the disassembly of cis-SNARE complexes--is phosphorylated. Here, we show that this post-translational modification is required for the correct function of αSNAP in controlling secretory traffic. We demonstrate that during intracellular development conditional expression of a non-phosphorylatable form of αSNAP results in Golgi fragmentation and vesiculation of all downstream secretory organelles. In addition, we show that the vestigial plastid (termed apicoplast), although reported not to be reliant on Golgi trafficking for biogenesis, is also affected upon overexpression of αSNAP and is much more sensitive to the levels of this protein than targeting to other organelles. This work highlights the importance of αSNAP and its phosphorylation in Toxoplasma organelle biogenesis and exposes a hereto fore-unexplored mechanism of regulation of vesicle fusion during secretory pathway trafficking in apicomplexan parasites.

  18. The soybean GmSNAP18 gene underlies two types of resistance to soybean cyst nematode

    PubMed Central

    Liu, Shiming; Kandoth, Pramod K.; Lakhssassi, Naoufal; Kang, Jingwen; Colantonio, Vincent; Heinz, Robert; Yeckel, Greg; Zhou, Zhou; Bekal, Sadia; Dapprich, Johannes; Rotter, Bjorn; Cianzio, Silvia; Mitchum, Melissa G.; Meksem, Khalid

    2017-01-01

    Two types of resistant soybean (Glycine max (L.) Merr.) sources are widely used against soybean cyst nematode (SCN, Heterodera glycines Ichinohe). These include Peking-type soybean, whose resistance requires both the rhg1-a and Rhg4 alleles, and PI 88788-type soybean, whose resistance requires only the rhg1-b allele. Multiple copy number of PI 88788-type GmSNAP18, GmAAT, and GmWI12 in one genomic segment simultaneously contribute to rhg1-b resistance. Using an integrated set of genetic and genomic approaches, we demonstrate that the rhg1-a Peking-type GmSNAP18 is sufficient for resistance to SCN in combination with Rhg4. The two SNAPs (soluble NSF attachment proteins) differ by only five amino acids. Our findings suggest that Peking-type GmSNAP18 is performing a different role in SCN resistance than PI 88788-type GmSNAP18. As such, this is an example of a pathogen resistance gene that has evolved to underlie two types of resistance, yet ensure the same function within a single plant species. PMID:28345654

  19. ADP-ribosylation of transducin by pertussis toxin

    SciTech Connect

    Watkins, P.A.; Burns, D.L.; Kanaho, Y.; Liu, T.Y.; Hewlett, E.L.; Moss, J.

    1985-11-05

    Transducin, the guanyl nucleotide-binding regulatory protein of retinal rod outer segments that couples the photon receptor, rhodopsin, with the light-activated cGMP phosphodiesterase, can be resolved into two functional components, T alpha and T beta gamma. T alpha (39 kDa), which is (TSP)ADP-ribosylated by pertussis toxin and (TSP)NAD in rod outer segments and in purified transducin, was also labeled by the toxin after separation from T beta gamma (36 kDa and approximately 10 kDa); neither component of T beta gamma was a pertussis toxin substrate. Labeling of T alpha was enhanced by T beta gamma and was maximal at approximately 1:1 molar ratio of T alpha : T beta gamma. Limited proteolysis by trypsin of T alpha in the presence of guanyl-5'-yl imidodiphosphate (Gpp(NH)p) resulted in the sequential appearance of proteins of 38 and TS kDa. The amino terminus of both 38- and TS-kDa proteins was leucine, whereas that of T alpha could not be identified and was assumed to be blocked. The TS-kDa peptide was not a pertussis toxin substrate. Labeling of the 38-kDa protein was poor and was not enhanced by T beta gamma. Trypsin treatment of (TSP)ADP-ribosyl-T alpha produced a labeled 37-38-kDa doublet followed by appearance of radioactivity at the dye front. It appears, therefore, that, although the 38-kDa protein was poor toxin substrate, it contained the ADP-ribosylation site. Without rhodopsin, labeling of T alpha (in the presence of T beta gamma) was unaffected by Gpp(NH)p, guanosine 5'-O-(thiotriphosphate) (GTP gamma S), GTP, GDP, and guanosine 5'-O-(thiodiphosphate) (GDP beta S) but was increased by ATP. When photolyzed rhodopsin and T beta gamma were present, Gpp(NH)p and GTP gamma S decreased (TSP)ADP-ribosylation by pertussis toxin. Thus, pertussis toxin-catalyzed (TSP)ADP-ribosylation of T alpha was affected by nucleotides, rhodopsin and light in addition to T beta gamma.

  20. Cortical Granule Exocytosis Is Mediated by Alpha-SNAP and N-Ethilmaleimide Sensitive Factor in Mouse Oocytes.

    PubMed

    de Paola, Matilde; Bello, Oscar Daniel; Michaut, Marcela Alejandra

    2015-01-01

    Cortical granule exocytosis (CGE), also known as cortical reaction, is a calcium- regulated secretion that represents a membrane fusion process during meiotic cell division of oocytes. The molecular mechanism of membrane fusion during CGE is still poorly understood and is thought to be mediated by the SNARE pathway; nevertheless, it is unkown if SNAP (acronym for soluble NSF attachment protein) and NSF (acronym for N-ethilmaleimide sensitive factor), two key proteins in the SNARE pathway, mediate CGE in any oocyte model. In this paper, we documented the gene expression of α-SNAP, γ-SNAP and NSF in mouse oocytes. Western blot analysis showed that the expression of these proteins maintains a similar level during oocyte maturation and early activation. Their localization was mainly observed at the cortical region of metaphase II oocytes, which is enriched in cortical granules. To evaluate the function of these proteins in CGE we set up a functional assay based on the quantification of cortical granules metaphase II oocytes activated parthenogenetically with strontium. Endogenous α-SNAP and NSF proteins were perturbed by microinjection of recombinant proteins or antibodies prior to CGE activation. The microinjection of wild type α-SNAP and the negative mutant of α-SNAP L294A in metaphase II oocytes inhibited CGE stimulated by strontium. NEM, an irreversibly inhibitor of NSF, and the microinjection of the negative mutant NSF D1EQ inhibited cortical reaction. The microinjection of anti-α-SNAP and anti-NSF antibodies was able to abolish CGE in activated metaphase II oocytes. The microinjection of anti-γ SNAP antibody had no effect on CGE. Our findings indicate, for the first time in any oocyte model, that α-SNAP, γ-SNAP, and NSF are expressed in mouse oocytes. We demonstrate that α-SNAP and NSF have an active role in CGE and propose a working model.

  1. Cortical Granule Exocytosis Is Mediated by Alpha-SNAP and N-Ethilmaleimide Sensitive Factor in Mouse Oocytes

    PubMed Central

    de Paola, Matilde; Bello, Oscar Daniel; Michaut, Marcela Alejandra

    2015-01-01

    Cortical granule exocytosis (CGE), also known as cortical reaction, is a calcium- regulated secretion that represents a membrane fusion process during meiotic cell division of oocytes. The molecular mechanism of membrane fusion during CGE is still poorly understood and is thought to be mediated by the SNARE pathway; nevertheless, it is unkown if SNAP (acronym for soluble NSF attachment protein) and NSF (acronym for N-ethilmaleimide sensitive factor), two key proteins in the SNARE pathway, mediate CGE in any oocyte model. In this paper, we documented the gene expression of α-SNAP, γ-SNAP and NSF in mouse oocytes. Western blot analysis showed that the expression of these proteins maintains a similar level during oocyte maturation and early activation. Their localization was mainly observed at the cortical region of metaphase II oocytes, which is enriched in cortical granules. To evaluate the function of these proteins in CGE we set up a functional assay based on the quantification of cortical granules metaphase II oocytes activated parthenogenetically with strontium. Endogenous α-SNAP and NSF proteins were perturbed by microinjection of recombinant proteins or antibodies prior to CGE activation. The microinjection of wild type α-SNAP and the negative mutant of α-SNAP L294A in metaphase II oocytes inhibited CGE stimulated by strontium. NEM, an irreversibly inhibitor of NSF, and the microinjection of the negative mutant NSF D1EQ inhibited cortical reaction. The microinjection of anti-α-SNAP and anti-NSF antibodies was able to abolish CGE in activated metaphase II oocytes. The microinjection of anti-γ SNAP antibody had no effect on CGE. Our findings indicate, for the first time in any oocyte model, that α-SNAP, γ-SNAP, and NSF are expressed in mouse oocytes. We demonstrate that α-SNAP and NSF have an active role in CGE and propose a working model. PMID:26267363

  2. Submaximal ADP-stimulated respiration is impaired in ZDF rats and recovered by resveratrol.

    PubMed

    Smith, Brennan K; Perry, Christopher G R; Herbst, Eric A F; Ritchie, Ian R; Beaudoin, Marie-Soleil; Smith, Jeffrey C; Neufer, P Darrell; Wright, David C; Holloway, Graham P

    2013-12-01

    Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in the aetiology of skeletal muscle insulin resistance, although there is considerable controversy regarding these concepts. Mitochondrial function has been traditionally assessed in the presence of saturating ADP, but ATP turnover and the resultant ADP is thought to limit respiration in vivo. Therefore, we investigated the potential link between submaximal ADP-stimulated respiration rates, ROS generation and skeletal muscle insulin sensitivity in a model of type 2 diabetes mellitus, the ZDF rat. Utilizing permeabilized muscle fibres we observed that submaximal ADP-stimulated respiration rates (250-2000 μm ADP) were lower in ZDF rats than in lean controls, which coincided with decreased adenine nucleotide translocase 2 (ANT2) protein content. This decrease in submaximal ADP-stimulated respiration occurred in the absence of a decrease in electron transport chain function. Treating ZDF rats with resveratrol improved skeletal muscle insulin resistance and this was associated with elevated submaximal ADP-stimulated respiration rates as well as an increase in ANT2 protein content. These results coincided with a greater ability of ADP to attenuate mitochondrial ROS emission and an improvement in cellular redox balance. Together, these data suggest that mitochondrial dysfunction is present in skeletal muscle insulin resistance when assessed at submaximal ADP concentrations and that ADP dynamics may influence skeletal muscle insulin sensitivity through alterations in the propensity for mitochondrial ROS emission.

  3. The genes pme-1 and pme-2 encode two poly(ADP-ribose) polymerases in Caenorhabditis elegans.

    PubMed

    Gagnon, Steve N; Hengartner, Michael O; Desnoyers, Serge

    2002-11-15

    Poly(ADP-ribose) polymerases (PARPs) are an expanding, well-conserved family of enzymes found in many metazoan species, including plants. The enzyme catalyses poly(ADP-ribosyl)ation, a post-translational modification that is important in DNA repair and programmed cell death. In the present study, we report the finding of an endogenous source of poly(ADP-ribosyl)ation in total extracts of the nematode Caenorhabditis elegans. Two cDNAs encoding highly similar proteins to human PARP-1 (huPARP-1) and huPARP-2 are described, and we propose to name the corresponding enzymes poly(ADP-ribose) metabolism enzyme 1 (PME-1) and PME-2 respectively. PME-1 (108 kDa) shares 31% identity with huPARP-1 and has an overall structure similar to other PARP-1 subfamily members. It contains sequences having considerable similarity to zinc-finger motifs I and II, as well as with the catalytic domain of huPARP-1. PME-2 (61 kDa) has structural similarities with the catalytic domain of PARPs in general and shares 24% identity with huPARP-2. Recombinant PME-1 and PME-2 display PARP activity, which may partially account for the similar activity found in the worm. A partial duplication of the pme-1 gene with pseudogene-like features was found in the nematode genome. Messenger RNA for pme-1 are 5'-tagged with splice leader 1, whereas those for pme - 2 are tagged with splice leader 2, suggesting an operon-like expression for pme - 2. The expression pattern of pme-1 and pme-2 is also developmentally regulated. Together, these results show that PARP-1 and -2 are conserved in evolution and must have important functions in multicellular organisms. We propose using C. elegans as a model to understand better the functions of these enzymes.

  4. Identified members of the Streptomyces lividans AdpA regulon involved in differentiation and secondary metabolism

    PubMed Central

    2014-01-01

    Background AdpA is a key transcriptional regulator involved in the complex growth cycle of Streptomyces. Streptomyces are Gram-positive bacteria well-known for their production of secondary metabolites and antibiotics. Most work on AdpA has been in S. griseus, and little is known about the pathways it controls in other Streptomyces spp. We recently discovered interplay between ClpP peptidases and AdpA in S. lividans. Here, we report the identification of genes directly regulated by AdpA in S. lividans. Results Microarray experiments revealed that the expression of hundreds of genes was affected in a S. lividans adpA mutant during early stationary phase cultures in YEME liquid medium. We studied the expression of the S. lividans AdpA-regulated genes by quantitative real-time PCR analysis after various times of growth. In silico analysis revealed the presence of potential AdpA-binding sites upstream from these genes; electrophoretic mobility shift assays indicated that AdpA binds directly to their promoter regions. This work identifies new pathways directly controlled by AdpA and that are involved in S. lividans development (ramR, SLI7885 also known as hyaS and SLI6586), and primary (SLI0755-SLI0754 encoding CYP105D5 and Fdx4) or secondary (cchA, cchB, and hyaS) metabolism. Conclusions We characterised six S. lividans AdpA-dependent genes whose expression is directly activated by this pleiotropic regulator. Several of these genes are orthologous to bldA-dependent genes in S. coelicolor. Furthermore, in silico analysis suggests that over hundred genes may be directly activated or repressed by S. lividans AdpA, although few have been described as being part of any Streptomyces AdpA regulons. This study increases the number of known AdpA-regulated pathways in Streptomyces spp. PMID:24694298

  5. Proteomic investigation of phosphorylation sites in poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase.

    PubMed

    Gagné, Jean-Philippe; Moreel, Xavier; Gagné, Pierre; Labelle, Yves; Droit, Arnaud; Chevalier-Paré, Mélissa; Bourassa, Sylvie; McDonald, Darin; Hendzel, Michael J; Prigent, Claude; Poirier, Guy G

    2009-02-01

    Phosphorylation is a very common post-translational modification event known to modulate a wide range of biological responses. Beyond the regulation of protein activity, the interrelation of phosphorylation with other post-translational mechanisms is responsible for the control of diverse signaling pathways. Several observations suggest that phosphorylation of poly(ADP-ribose) polymerase-1 (PARP-1) regulates its activity. There is also accumulating evidence to suggest the establishment of phosphorylation-dependent assembly of PARP-1-associated multiprotein complexes. Although it is relatively straightforward to demonstrate phosphorylation of a defined target, identification of the actual amino acids involved still represents a technical challenge for many laboratories. With the use of a combination of bioinformatics-based predictions tools for generic and kinase-specific phosphorylation sites, in vitro phosphorylation assays and mass spectrometry analysis, we investigated the phosphorylation profile of PARP-1 and poly(ADP-ribose) glycohydrolase (PARG), two major enzymes responsible for poly(ADP-ribose) turnover. Mass spectrometry analysis revealed the phosphorylation of several serine/threonine residues within important regulatory domains and motifs of both enzymes. With the use of in vivo microirradiation-induced DNA damage, we show that altered phosphorylation at specific sites can modify the dynamics of assembly and disassembly of PARP-1 at sites of DNA damage. By documenting and annotating a collection of known and newly identified phosphorylation sites, this targeted proteomics study significantly advances our understanding of the roles of phosphorylation in the regulation of PARP-1 and PARG.

  6. Evaluating the Impact of Six Supplemental Nutrition Assistance Program Education Interventions on Children's At-Home Diets

    ERIC Educational Resources Information Center

    Williams, Pamela A.; Cates, Sheryl C.; Blitstein, Jonathan L.; Hersey, James C.; Kosa, Katherine M.; Long, Valerie A.; Singh, Anita; Berman, Danielle

    2015-01-01

    Background: Nutrition education in the Supplemental Nutrition Assistance Program Education (SNAP-Ed) is designed to promote healthy eating behaviors in a low-income target population. Purpose: To evaluate the effectiveness of six SNAP-Ed interventions delivered in child care centers or elementary school settings in increasing participating…

  7. Arthroscopic Resection of Osteochondroma of Hip Joint Associated with Internal Snapping: A Case Report

    PubMed Central

    Jung, Heung-Tae; Hwang, Deuk-Soo; Jeon, Yoo-Sun

    2015-01-01

    A 16-year old male patient visited the hospital complaining of inguinal pain and internal snapping of right hip joint. In physical examination, the patient was presumed to be diagnosed femoroacetabular impingement (FAI) and acetabular labral tear. In radiologic evaluation, FAI and acetabular labral tear were identified and bony tumor associated with internal snapping was found on the posteromedial portion of the femoral neck. Despite of conservative treatment, there was no symptomatic improvement. So arthroscopic labral repair, osteoplasty and resection of bony tumor were performed. The tumor was pathologically diagnosed as osteochondroma through biopsy and all symptoms improved after surgery. There was no recurrence, complication or abnormal finding during 1 year follow up. Osteochondroma located at posteromedial portion of femoral neck can be a cause of internal snapping hip and although technical demands are challenging, arthroscopic resection can be a good treatment option. PMID:27536601

  8. Proteolysis of synaptobrevin, syntaxin, and SNAP-25 in alveolar epithelial type II cells.

    PubMed

    Zimmerman, U J; Malek, S K; Liu, L; Li, H L

    1999-10-01

    Synaptobrevin-2, syntaxin-1, and SNAP-25 were identified in rat alveolar epithelial type II cells by Western blot analysis. Synaptobrevin-2 was localized in the lamellar bodies, and syntaxin-1 and SNAP-25 were found in 0.4% Nonidet P40-soluble and -insoluble fractions, respectively, of the type II cells. When the isolated type II cells were stimulated for secretion with calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, these proteins were found to have been proteolyzed. Preincubation of cells with calpain inhibitor II (N-acetylleucylleucylmethionine), however, prevented the proteolysis. Treatment of the cell lysate with exogenous calpain resulted in a time-dependent decrease of these proteins. The data suggest that synaptobrevin, syntaxin, and SNAP-25 are subject to proteolytic modification by activated calpain in intact type II cells stimulated for secretion.

  9. Improving Nutrition by Increasing Supplemental Nutrition Assistance Program Benefits.

    PubMed

    Collins, Ann M; Klerman, Jacob A

    2017-02-01

    The diets of Americans fall far short of recommended dietary guidelines, and those who live in low-income households have even poorer diets than higher-income households. Many low-income Americans rely on the Supplemental Nutrition Assistance Program (SNAP). The program's dual goals are to improve food security and nutrition. Among the possible strategies to address dietary shortfalls among low-income Americans is to increase the SNAP benefit. This article uses data from the random assignment evaluation of the Summer Electronic Benefit Transfer for Children demonstration to add new insights on the impact of SNAP on diet quality for households receiving SNAP who also received SNAP-like benefits through Summer Electronic Benefit Transfer for Children. Households received $60 each month per eligible school-aged child. The objective of the evaluation was to see if Summer Electronic Benefit Transfer for Children improved children's food security and nutrition. The evaluation surveyed these households to collect information about food expenditures, food security, and children's diets. For households receiving SNAP in sites that used the SNAP Electronic Benefit Transfer delivery system, the analysis showed increases in food expenditures and decreases in levels of food insecurity. The analysis also indicates improvements in dietary quality among school-aged children, but the impacts were modest.

  10. Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability

    PubMed Central

    Selcen, Duygu; Brengman, Joan

    2014-01-01

    Objective: To identify and characterize the molecular basis of a syndrome associated with myasthenia, cortical hyperexcitability, cerebellar ataxia, and intellectual disability. Methods: We performed in vitro microelectrode studies of neuromuscular transmission, performed exome and Sanger sequencing, and analyzed functional consequences of the identified mutation in expression studies. Results: Neuromuscular transmission at patient endplates was compromised by reduced evoked quantal release. Exome sequencing identified a dominant de novo variant, p.Ile67Asn, in SNAP25B, a SNARE protein essential for exocytosis of synaptic vesicles from nerve terminals and of dense-core vesicles from endocrine cells. Ca2+-triggered exocytosis is initiated when synaptobrevin attached to synaptic vesicles (v-SNARE) assembles with SNAP25B and syntaxin anchored in the presynaptic membrane (t-SNAREs) into an α-helical coiled-coil held together by hydrophobic interactions. Pathogenicity of the Ile67Asn mutation was confirmed by 2 measures. First, the Ca2+ triggered fusion of liposomes incorporating v-SNARE with liposomes containing t-SNAREs was hindered when t-SNAREs harbored the mutant SNAP25B moiety. Second, depolarization of bovine chromaffin cells transfected with mutant SNAP25B or with mutant plus wild-type SNAP25B markedly reduced depolarization-evoked exocytosis compared with wild-type transfected cells. Conclusion: Ile67Asn variant in SNAP25B is pathogenic because it inhibits synaptic vesicle exocytosis. We attribute the deleterious effects of the mutation to disruption of the hydrophobic α-helical coiled-coil structure of the SNARE complex by replacement of a highly hydrophobic isoleucine by a strongly hydrophilic asparagine. PMID:25381298

  11. High-speed video analysis of wing-snapping in two manakin clades (Pipridae: Aves).

    PubMed

    Bostwick, Kimberly S; Prum, Richard O

    2003-10-01

    Basic kinematic and detailed physical mechanisms of avian, non-vocal sound production are both unknown. Here, for the first time, field-generated high-speed video recordings and acoustic analyses are used to test numerous competing hypotheses of the kinematics underlying sonations, or non-vocal communicative sounds, produced by two genera of Pipridae, Manacus and Pipra (Aves). Eleven behaviorally and acoustically distinct sonations are characterized, five of which fall into a specific acoustic class of relatively loud, brief, broad-frequency sound pulses, or snaps. The hypothesis that one kinematic mechanism of snap production is used within and between birds in general, and manakins specifically, is rejected. Instead, it is verified that three of four competing hypotheses of the kinematic mechanisms used for producing snaps, namely: (1). above-the-back wing-against-wing claps, (2). wing-against-body claps and (3). wing-into-air flicks, are employed between these two clades, and a fourth mechanism, (4). wing-against-tail feather interactions, is discovered. The kinematic mechanisms used to produce snaps are invariable within each identified sonation, despite the fact that a diversity of kinematic mechanisms are used among sonations. The other six sonations described are produced by kinematic mechanisms distinct from those used to create snaps, but are difficult to distinguish from each other and from the kinematics of flight. These results provide the first detailed kinematic information on mechanisms of sonation in birds in general, and the Pipridae specifically. Further, these results provide the first evidence that acoustically similar avian sonations, such as brief, broad frequency snaps, can be produced by diverse kinematic means, both among and within species. The use of high-speed video recordings in the field in a comparative manner documents the diversity of kinematic mechanisms used to sonate, and uncovers a hidden, sexually selected radiation of

  12. Developmental and diurnal expression of the synaptosomal-associated protein 25 (Snap25) in the rat pineal gland.

    PubMed

    Karlsen, Anna S; Rath, Martin F; Rohde, Kristian; Toft, Trine; Møller, Morten

    2013-06-01

    Snap25 (synaptosomal-associated protein) is a 25 kDa protein, belonging to the SNARE-family (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) of proteins, essential for synaptic and secretory vesicle exocytosis. Snap25 has by immunohistochemistry been demonstrated in the rat pineal gland but the biological importance of this is unknown. In this study, we demonstrate a high expression of mRNA encoding Snap25 in all parts of the rat pineal complex, the superficial-, and deep-pineal gland, as well as in the pineal stalk. Snap25 showed a low pineal expression during embryonic stages with a strong increase in expression levels just after birth. The expression showed no day/night variations. Neither removal of the sympathetic input to the pineal gland by superior cervical ganglionectomy nor bilateral decentralization of the superior cervical ganglia significantly affected the expression of Snap25 in the gland. The pineal expression levels of Snap25 were not changed following intraperitoneal injection of isoproterenol. The strong expression of Snap25 in the pineal gland suggests the presence of secretory granules and microvesicles in the rat pinealocyte supporting the concept of a vesicular release. At the transcriptional level, this Snap25-based release mechanism does not exhibit any diurnal rhythmicity and is regulated independently of the sympathetic nervous input to the gland.

  13. Multi-environment selection of small sieve snap beans reduces production constraints in East Africa and subtropical regions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Common bean rust caused by Uromyces appendiculatus, and heat stress lower the yield and quality of snap beans (Phaseolus vulgaris L.) in East Africa. Four snap bean breeding lines previously selected for broad-spectrum rust resistance (involving Ur-4 and Ur-11 rust genes) and heat tolerance followin...

  14. A Novel Site of Action for α-SNAP in the SNARE Conformational Cycle Controlling Membrane Fusion

    PubMed Central

    Barszczewski, Marcin; Chua, John J.; Stein, Alexander; Winter, Ulrike; Heintzmann, Rainer; Zilly, Felipe E.; Fasshauer, Dirk; Lang, Thorsten

    2008-01-01

    Regulated exocytosis in neurons and neuroendocrine cells requires the formation of a stable soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of synaptobrevin-2/vesicle-associated membrane protein 2, synaptosome-associated protein of 25 kDa (SNAP-25), and syntaxin 1. This complex is subsequently disassembled by the concerted action of α-SNAP and the ATPases associated with different cellular activities-ATPase N-ethylmaleimide-sensitive factor (NSF). We report that NSF inhibition causes accumulation of α-SNAP in clusters on plasma membranes. Clustering is mediated by the binding of α-SNAP to uncomplexed syntaxin, because cleavage of syntaxin with botulinum neurotoxin C1 or competition by using antibodies against syntaxin SNARE motif abolishes clustering. Binding of α-SNAP potently inhibits Ca2+-dependent exocytosis of secretory granules and SNARE-mediated liposome fusion. Membrane clustering and inhibition of both exocytosis and liposome fusion are counteracted by NSF but not when an α-SNAP mutant defective in NSF activation is used. We conclude that α-SNAP inhibits exocytosis by binding to the syntaxin SNARE motif and in turn prevents SNARE assembly, revealing an unexpected site of action for α-SNAP in the SNARE cycle that drives exocytotic membrane fusion. PMID:18094056

  15. A novel site of action for alpha-SNAP in the SNARE conformational cycle controlling membrane fusion.

    PubMed

    Barszczewski, Marcin; Chua, John J; Stein, Alexander; Winter, Ulrike; Heintzmann, Rainer; Zilly, Felipe E; Fasshauer, Dirk; Lang, Thorsten; Jahn, Reinhard

    2008-03-01

    Regulated exocytosis in neurons and neuroendocrine cells requires the formation of a stable soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of synaptobrevin-2/vesicle-associated membrane protein 2, synaptosome-associated protein of 25 kDa (SNAP-25), and syntaxin 1. This complex is subsequently disassembled by the concerted action of alpha-SNAP and the ATPases associated with different cellular activities-ATPase N-ethylmaleimide-sensitive factor (NSF). We report that NSF inhibition causes accumulation of alpha-SNAP in clusters on plasma membranes. Clustering is mediated by the binding of alpha-SNAP to uncomplexed syntaxin, because cleavage of syntaxin with botulinum neurotoxin C1 or competition by using antibodies against syntaxin SNARE motif abolishes clustering. Binding of alpha-SNAP potently inhibits Ca(2+)-dependent exocytosis of secretory granules and SNARE-mediated liposome fusion. Membrane clustering and inhibition of both exocytosis and liposome fusion are counteracted by NSF but not when an alpha-SNAP mutant defective in NSF activation is used. We conclude that alpha-SNAP inhibits exocytosis by binding to the syntaxin SNARE motif and in turn prevents SNARE assembly, revealing an unexpected site of action for alpha-SNAP in the SNARE cycle that drives exocytotic membrane fusion.

  16. Photochemical oxidants potentiate yield losses in snap beans attributable to sulfur dioxide

    SciTech Connect

    Heggestad, H.E.; Bennett, J.H.

    1981-08-28

    Field-grown snap beans (Phaseolus vulgaris) were given recurring midday exposures to sulfur dioxide in open-top field chambers containing ambient photochemical oxidants. There was a linear correlation (correlation coefficient = -.99) between increasing concentrations of sulfur dioxide and the yields of snap beans. Synergism was indicated for the mixtures of ambient ozone plus sulfur dioxide, leading to threefold greater yield losses in nonfiltered air than in charcoal-filtered air (to remove the ozone). Even the lowest sulfur dioxide dose in nonfiltered air reduced the yields of Astro, a cultivar that exhibited no visible pollutant-induced foliar injury. 16 referances, 1 figure, 1 table.

  17. The snap-back effect of an RC-IGBT and its simulations

    NASA Astrophysics Data System (ADS)

    Wenliang, Zhang; Xiaoli, Tian; Jingfei, Tan; Yangjun, Zhu

    2013-07-01

    The RC-IGBT (reverse conducting insulated gate bipolar transistor) is a new kind of power semiconductor device which has many advantages such as smaller chip size, higher power density, lower manufacturing cost, softer turn off behavior, and better reliability. However, its performance has a number of drawbacks, such as the snap-back effect. In this paper, an introduction about the snap-back effect of the RC-IGBT is given firstly. Then the physical explanations are presented with two simplified models. After that, some numerical simulations are carried out to verify the correctness of the models.

  18. Identification of exocytotic membrane proteins, syntaxin-1 and SNAP-25, in Entamoeba histolytica from hamster liver.

    PubMed

    Ventura-Juárez, Javier; Salinas, Eva; Campos-Rodríguez, Rafael; Kouri, Juan B; Quintanar, Luis

    2007-06-01

    Entamoeba histolytica is a protozoan parasite causing dysentery and in some cases liver abscesses. These effects have been attributed to cytolytic substances released by exocytosis. In this study, the presence of the proteins syntaxin-1 and SNAP-25, which are assumed to be involved in exocytosis, were examined by immunohistochemistry, immunoelectron microscopy and western blot analysis. Syntaxin-1 and SNAP-25 were expressed in the vesicular, vacuolar and plasma membranes of E. histolytica trophozoites. It can be concluded that these proteins might be involved in exocytosis processes.

  19. Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD+ analogues

    PubMed Central

    Wallrodt, Sarah; Simpson, Edward L

    2017-01-01

    ADP-ribosyl transferases with diphtheria toxin homology (ARTDs) catalyse the covalent addition of ADP-ribose onto different acceptors forming mono- or poly(ADP-ribos)ylated proteins. Out of the 18 members identified, only four are known to synthesise the complex poly(ADP-ribose) biopolymer. The investigation of this posttranslational modification is important due to its involvement in cancer and other diseases. Lately, metabolic labelling approaches comprising different reporter-modified NAD+ building blocks have stimulated and enriched proteomic studies and imaging applications of ADP-ribosylation processes. Herein, we compare the substrate scope and applicability of different NAD+ analogues for the investigation of the polymer-synthesising enzymes ARTD1, ARTD2, ARTD5 and ARTD6. By varying the site and size of the NAD+ modification, suitable probes were identified for each enzyme. This report provides guidelines for choosing analogues for studying poly(ADP-ribose)-synthesising enzymes. PMID:28382184

  20. Immunoaffinity fractionation of the poly(ADP-ribosyl)ated domains of chromatin.

    PubMed Central

    Malik, N; Miwa, M; Sugimura, T; Thraves, P; Smulson, M

    1983-01-01

    Antibody to poly(ADP-ribose) has been covalently coupled to Sepharose and utilized to isolate selectively oligonucleosomes undergoing the poly(ADP-ribosyl)ation reaction from the bulk of chromatin. Approximately 12% of the unfractionated oligonucleosomes were bound to the immunoaffinity column and these represented essentially 100% of the original poly(ADP-ribosyl)ated nucleosomal species in the unfractionated chromatin. Poly(ADP-ribosyl)ated chromatin was not bound by preimmune IgG columns. KSCN eluted the modified nucleosomes in the form of nucleoprotein complexes. The eluted chromatin components were shown to contain poly(ADP-ribosyl)ated histones as well as automodified poly(ADP-ribose) polymerase. By using [3H]lysine- and [3H]arginine-labeled chromatin, it was shown that the poly-(ADP-ribosyl)ated histones, attached to stretches of oligonucleosomes bound to the column, had a 6-fold enrichment of the modification compared to histones of the unfractionated chromatin. This indicated that non-poly(ADP-ribosyl)ated nucleosomes, connected and proximal to the modified regions, were copurified by this procedure. This allowed characterization of the oligonucleosomal DNA around poly(ADP-ribosyl)ated chromatin domains to be compared with the unbound bulk chromatin. The data indicated that immunofractionated poly(ADP-ribosyl)ated oligonucleosomal DNA contained significant amounts of internal single-strand breaks compared with bulk chromatin. The bound nucleo-protein complexes were found to be enzymatically active for poly(ADP-ribose) polymerase after elution from the antibody column. In contrast, the unbound nucleosomes, representing 90% of the unfractionated chromatin, were totally inactive in the poly(ADP-ribosyl)ation reaction. Images PMID:6573670

  1. NAD-dependent ADP-ribosylation of the human antimicrobial and immune-modulatory peptide LL-37 by ADP-ribosyltransferase-1.

    PubMed

    Picchianti, Monica; Russo, Carla; Castagnini, Marta; Biagini, Massimiliano; Soldaini, Elisabetta; Balducci, Enrico

    2015-04-01

    LL-37 is a cationic peptide belonging to the cathelicidin family that has antimicrobial and immune-modulatory properties. Here we show that the mammalian mono-ADP-ribosyltransferase-1 (ART1), which selectively transfers the ADP-ribose moiety from NAD to arginine residues, ADP-ribosylates LL-37 in vitro. The incorporation of ADP-ribose was first observed by Western blot analysis and then confirmed by MALDI-TOF. Mass-spectrometry showed that up to four of the five arginine residues present in LL-37 could be ADP-ribosylated on the same peptide when incubated at a high NAD concentration in the presence of ART1. The attachment of negatively charged ADP-ribose moieties considerably alters the positive charge of the arginine residues thus reducing the cationicity of LL-37. The cationic nature of LL-37 is key for its ability to interact with cell membranes or negatively charged biomolecules, such as DNA, RNA, F-actin and glycosaminoglycans. Thus, the ADP-ribosylation of LL-37 is expected to have the potential to modulate LL-37 biological activities in several physiological and pathological settings.

  2. Structures of the human poly (ADP-ribose) glycohydrolase catalytic domain confirm catalytic mechanism and explain inhibition by ADP-HPD derivatives.

    PubMed

    Tucker, Julie A; Bennett, Neil; Brassington, Claire; Durant, Stephen T; Hassall, Giles; Holdgate, Geoff; McAlister, Mark; Nissink, J Willem M; Truman, Caroline; Watson, Martin

    2012-01-01

    Poly(ADP-ribose) glycohydrolase (PARG) is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers, thereby reversing the effects of poly(ADP-ribose) polymerases. PARG deficiency leads to cell death whilst PARG depletion causes sensitisation to certain DNA damaging agents, implicating PARG as a potential therapeutic target in several disease areas. Efforts to develop small molecule inhibitors of PARG activity have until recently been hampered by a lack of structural information on PARG. We have used a combination of bio-informatic and experimental approaches to engineer a crystallisable, catalytically active fragment of human PARG (hPARG). Here, we present high-resolution structures of the catalytic domain of hPARG in unliganded form and in complex with three inhibitors: ADP-ribose (ADPR), adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) and 8-n-octyl-amino-ADP-HPD. Our structures confirm conservation of overall fold amongst mammalian PARG glycohydrolase domains, whilst revealing additional flexible regions in the catalytic site. These new structures rationalise a body of published mutational data and the reported structure-activity relationship for ADP-HPD based PARG inhibitors. In addition, we have developed and used biochemical, isothermal titration calorimetry and surface plasmon resonance assays to characterise the binding of inhibitors to our PARG protein, thus providing a starting point for the design of new inhibitors.

  3. The role of ADP-ribosylation in regulating DNA interstrand crosslink repair

    PubMed Central

    Gunn, Alasdair R.; Banos-Pinero, Benito; Paschke, Peggy; Sanchez-Pulido, Luis; Ariza, Antonio; Day, Joseph; Emrich, Mehera; Leys, David; Ponting, Chris P.

    2016-01-01

    ABSTRACT ADP-ribosylation by ADP-ribosyltransferases (ARTs) has a well-established role in DNA strand break repair by promoting enrichment of repair factors at damage sites through ADP-ribose interaction domains. Here, we exploit the simple eukaryote Dictyostelium to uncover a role for ADP-ribosylation in regulating DNA interstrand crosslink repair and redundancy of this pathway with non-homologous end-joining (NHEJ). In silico searches were used to identify a protein that contains a permutated macrodomain (which we call aprataxin/APLF-and-PNKP-like protein; APL). Structural analysis reveals that this permutated macrodomain retains features associated with ADP-ribose interactions and that APL is capable of binding poly(ADP-ribose) through this macrodomain. APL is enriched in chromatin in response to cisplatin treatment, an agent that induces DNA interstrand crosslinks (ICLs). This is dependent on the macrodomain of APL and the ART Adprt2, indicating a role for ADP-ribosylation in the cellular response to cisplatin. Although adprt2− cells are sensitive to cisplatin, ADP-ribosylation is evident in these cells owing to redundant signalling by the double-strand break (DSB)-responsive ART Adprt1a, promoting NHEJ-mediated repair. These data implicate ADP-ribosylation in DNA ICL repair and identify that NHEJ can function to resolve this form of DNA damage in the absence of Adprt2. PMID:27587838

  4. The rise and fall of poly(ADP-ribose): An enzymatic perspective.

    PubMed

    Pascal, John M; Ellenberger, Tom

    2015-08-01

    Human cells respond to DNA damage with an acute and transient burst in production of poly(ADP-ribose), a posttranslational modification that expedites damage repair and plays a pivotal role in cell fate decisions. Poly(ADP-ribose) polymerases (PARPs) and glycohydrolase (PARG) are the key set of enzymes that orchestrate the rise and fall in cellular levels of poly(ADP-ribose). In this perspective, we focus on recent structural and mechanistic insights into the enzymes involved in poly(ADP-ribose) production and turnover, and we highlight important questions that remain to be answered.

  5. The Rise and Fall of Poly (ADP-ribose). An Enzymatic Perspective

    PubMed Central

    Pascal, John M.; Ellenberger, Tom

    2015-01-01

    Human cells respond to DNA damage with an acute and transient burst in production of poly(ADP-ribose), a posttranslational modification that expedites damage repair and plays a pivotal role in cell fate decisions. Poly(ADP-ribose) polymerases (PARPs) and glycohydrolase (PARG) are the key set of enzymes that orchestrate the rise and fall in cellular levels of poly(ADP-ribose). In this perspective, we focus on recent structural and mechanistic insights into the enzymes involved in poly(ADP-ribose) production and turnover, and we highlight important questions that remain to be answered. PMID:25963443

  6. The actin-ADP-ribosylating Clostridium botulinum C2 toxin.

    PubMed

    Aktories, Klaus; Barth, Holger

    2004-04-01

    Clostridium botulinum C2 toxin is the prototype of actin-ADP-ribosylating toxins. The toxin consists of the enzyme component C2I and the separated binding/translocation component C2II. C2II is proteolytically activated to form heptamers, which bind the enzyme component. After endocytosis of the receptor-toxin complex, the enzyme component enters the cytosol from an acidic endosomal compartment to modify G-actin at arginine177. Recent data indicate that chaperons are involved in the translocation process of the toxin.

  7. Molecular Bases of Catalysis and ADP-Ribose Preference of Human Mn2+-Dependent ADP-Ribose/CDP-Alcohol Diphosphatase and Conversion by Mutagenesis to a Preferential Cyclic ADP-Ribose Phosphohydrolase

    PubMed Central

    Cabezas, Alicia; Ribeiro, João Meireles; Rodrigues, Joaquim Rui; López-Villamizar, Iralis; Fernández, Ascensión; Canales, José; Pinto, Rosa María; Costas, María Jesús; Cameselle, José Carlos

    2015-01-01

    Among metallo-dependent phosphatases, ADP-ribose/CDP-alcohol diphosphatases form a protein family (ADPRibase-Mn-like) mainly restricted, in eukaryotes, to vertebrates and plants, with preferential expression, at least in rodents, in immune cells. Rat and zebrafish ADPRibase-Mn, the only biochemically studied, are phosphohydrolases of ADP-ribose and, somewhat less efficiently, of CDP-alcohols and 2´,3´-cAMP. Furthermore, the rat but not the zebrafish enzyme displays a unique phosphohydrolytic activity on cyclic ADP-ribose. The molecular basis of such specificity is unknown. Human ADPRibase-Mn showed similar activities, including cyclic ADP-ribose phosphohydrolase, which seems thus common to mammalian ADPRibase-Mn. Substrate docking on a homology model of human ADPRibase-Mn suggested possible interactions of ADP-ribose with seven residues located, with one exception (Cys253), either within the metallo-dependent phosphatases signature (Gln27, Asn110, His111), or in unique structural regions of the ADPRibase-Mn family: s2s3 (Phe37 and Arg43) and h7h8 (Phe210), around the active site entrance. Mutants were constructed, and kinetic parameters for ADP-ribose, CDP-choline, 2´,3´-cAMP and cyclic ADP-ribose were determined. Phe37 was needed for ADP-ribose preference without catalytic effect, as indicated by the increased ADP-ribose Km and unchanged kcat of F37A-ADPRibase-Mn, while the Km values for the other substrates were little affected. Arg43 was essential for catalysis as indicated by the drastic efficiency loss shown by R43A-ADPRibase-Mn. Unexpectedly, Cys253 was hindering for cADPR phosphohydrolase, as indicated by the specific tenfold gain of efficiency of C253A-ADPRibase-Mn with cyclic ADP-ribose. This allowed the design of a triple mutant (F37A+L196F+C253A) for which cyclic ADP-ribose was the best substrate, with a catalytic efficiency of 3.5´104 M-1s-1 versus 4´103 M-1s-1 of the wild type. PMID:25692488

  8. Molecular bases of catalysis and ADP-ribose preference of human Mn2+-dependent ADP-ribose/CDP-alcohol diphosphatase and conversion by mutagenesis to a preferential cyclic ADP-ribose phosphohydrolase.

    PubMed

    Cabezas, Alicia; Ribeiro, João Meireles; Rodrigues, Joaquim Rui; López-Villamizar, Iralis; Fernández, Ascensión; Canales, José; Pinto, Rosa María; Costas, María Jesús; Cameselle, José Carlos

    2015-01-01

    Among metallo-dependent phosphatases, ADP-ribose/CDP-alcohol diphosphatases form a protein family (ADPRibase-Mn-like) mainly restricted, in eukaryotes, to vertebrates and plants, with preferential expression, at least in rodents, in immune cells. Rat and zebrafish ADPRibase-Mn, the only biochemically studied, are phosphohydrolases of ADP-ribose and, somewhat less efficiently, of CDP-alcohols and 2´,3´-cAMP. Furthermore, the rat but not the zebrafish enzyme displays a unique phosphohydrolytic activity on cyclic ADP-ribose. The molecular basis of such specificity is unknown. Human ADPRibase-Mn showed similar activities, including cyclic ADP-ribose phosphohydrolase, which seems thus common to mammalian ADPRibase-Mn. Substrate docking on a homology model of human ADPRibase-Mn suggested possible interactions of ADP-ribose with seven residues located, with one exception (Cys253), either within the metallo-dependent phosphatases signature (Gln27, Asn110, His111), or in unique structural regions of the ADPRibase-Mn family: s2s3 (Phe37 and Arg43) and h7h8 (Phe210), around the active site entrance. Mutants were constructed, and kinetic parameters for ADP-ribose, CDP-choline, 2´,3´-cAMP and cyclic ADP-ribose were determined. Phe37 was needed for ADP-ribose preference without catalytic effect, as indicated by the increased ADP-ribose Km and unchanged kcat of F37A-ADPRibase-Mn, while the Km values for the other substrates were little affected. Arg43 was essential for catalysis as indicated by the drastic efficiency loss shown by R43A-ADPRibase-Mn. Unexpectedly, Cys253 was hindering for cADPR phosphohydrolase, as indicated by the specific tenfold gain of efficiency of C253A-ADPRibase-Mn with cyclic ADP-ribose. This allowed the design of a triple mutant (F37A+L196F+C253A) for which cyclic ADP-ribose was the best substrate, with a catalytic efficiency of 3.5´104 M-1s-1 versus 4´103 M-1s-1 of the wild type.

  9. Innovative, wearable snap connector technology for improved device networking in electronic garments

    NASA Astrophysics Data System (ADS)

    Kostrzewski, Andrew A.; Lee, Kang S.; Gans, Eric; Winterhalter, Carole A.; Jannson, Tomasz P.

    2007-04-01

    This paper discusses Physical Optics Corporation's (POC) wearable snap connector technology that provides for the transfer of data and power throughout an electronic garment (e-garment). These connectors resemble a standard garment button and can be mated blindly with only one hand. Fully compatible with military clothing, their application allows for the networking of multiple electronic devices and an intuitive method for adding/removing existing components from the system. The attached flexible cabling also permits the rugged snap connectors to be fed throughout the standard webbing found in military garments permitting placement in any location within the uniform. Variations of the snap electronics/geometry allow for integration with USB 2.0 devices, RF antennas, and are capable of transferring high bandwidth data streams such as the 221 Mbps required for VGA video. With the trend towards providing military officers with numerous electronic devices (i.e., heads up displays (HMD), GPS receiver, PDA, etc), POC's snap connector technology will greatly improve cable management resulting in a less cumbersome uniform. In addition, with electronic garments gaining widespread adoption in the commercial marketplace, POC's technology is finding applications in such areas as sporting good manufacturers and video game technology.

  10. Surgical Treatment of Snapping Scapula Syndrome Due to Malunion of Rib Fractures.

    PubMed

    Ten Duis, Kaj; IJpma, Frank F A

    2017-02-01

    This report describes a case of snapping scapula syndrome (SSS) caused by malunited rib fractures. Abrasion of the deformed ribs was performed with good results. SSS as a cause of shoulder pain after thoracic trauma has to be considered and can be treated by a surgical abrasion technique.

  11. Frequency doubling of copper lasers using temperature-tuned ADP

    SciTech Connect

    Molander, W.A.

    1994-03-01

    The ability to generate high average power uv at 255 nm by frequency doubling the green line (510.6 nm) of copper lasers would greatly extend the utility of copper lasers. Material processing and microlithography are two areas of interest. The frequency-doubled copper laser could replace the KrF excimer laser, which has a similar wavelength (248 nm), in some applications. The frequency-doubled copper laser has a narrow linewidth and excellent beam quality at a competitive cost. Other attractive features are high reliability, low operating costs, and the absence of toxic gases. This paper will report recent progress in high-efficiency, high-average-power harmonic generation of the copper laser green line using noncritical phase matching in ADP. Frequency doubling of the yellow line (578.2 nm) and sum-frequency mixing of the two lines are also of interest. These processes, however, cannot be phase-matched in ADP and, therefore, will not be discussed here. The results reported and the issues identified here would be important in these other processes and also in many other frequency conversion schemes in the uv such as 4{omega} conversion of Nd{sup 3+}:YAG lasers.

  12. Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells

    SciTech Connect

    Fahrer, Joerg; Wagner, Silvia; Buerkle, Alexander; Koenigsrainer, Alfred

    2009-08-14

    Rapamycin is an immunosuppressive drug, which inhibits the mammalian target of rapamycin (mTOR) kinase activity inducing changes in cell proliferation. Synthesis of poly(ADP-ribose) (PAR) is an immediate cellular response to genotoxic stress catalyzed mostly by poly(ADP-ribose) polymerase 1 (PARP-1), which is also controlled by signaling pathways. Therefore, we investigated whether rapamycin affects PAR production. Strikingly, rapamycin inhibited PAR synthesis in living fibroblasts in a dose-dependent manner as monitored by immunofluorescence. PARP-1 activity was then assayed in vitro, revealing that down-regulation of cellular PAR production by rapamycin was apparently not due to competitive PARP-1 inhibition. Further studies showed that rapamycin did not influence the cellular NAD pool and the activation of PARP-1 in extracts of pretreated fibroblasts. Collectively, our data suggest that inhibition of cellular PAR synthesis by rapamycin is mediated by formation of a detergent-sensitive complex in living cells, and that rapamycin may have a potential as therapeutic PARP inhibitor.

  13. Metabolic roles of poly(ADP-ribose) polymerases.

    PubMed

    Vida, András; Márton, Judit; Mikó, Edit; Bai, Péter

    2017-03-01

    Poly(ADP-ribosyl)ation (PARylation) is an evolutionarily conserved reaction that had been associated with numerous cellular processes such as DNA repair, protein turnover, inflammatory regulation, aging or metabolic regulation. The metabolic regulatory tasks of poly(ADP-ribose) polymerases (PARPs) are complex, it is based on the regulation of metabolic transcription factors (e.g. SIRT1, nuclear receptors, SREBPs) and certain cellular energy sensors. PARP over-activation can cause damage to mitochondrial terminal oxidation, while the inhibition of PARP-1 or PARP-2 can induce mitochondrial oxidation by enhancing the mitotropic tone of gene transcription and signal transduction. These PARP-mediated processes impact on higher order metabolic regulation that modulates lipid metabolism, circadian oscillations and insulin secretion and signaling. PARP-1, PARP-2 and PARP-7 are related to metabolic diseases such as diabetes, alcoholic and non-alcoholic fatty liver disease (AFLD, NAFLD), or on a broader perspective to Warburg metabolism in cancer or the metabolic diseases accompanying aging.

  14. Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites.

    PubMed

    Neuvonen, Maarit; Ahola, Tero

    2009-01-09

    Macro domain is a highly conserved protein domain found in both eukaryotes and prokaryotes. Macro domains are also encoded by a set of positive-strand RNA viruses that replicate in the cytoplasm of animal cells, including coronaviruses and alphaviruses. The functions of the macro domain are poorly understood, but it has been suggested to be an ADP-ribose-binding module. We have here characterized three novel human macro domain proteins that were found to reside either in the cytoplasm and nucleus [macro domain protein 2 (MDO2) and ganglioside-induced differentiation-associated protein 2] or in mitochondria [macro domain protein 1 (MDO1)], and compared them with viral macro domains from Semliki Forest virus, hepatitis E virus, and severe acute respiratory syndrome coronavirus, and with a yeast macro protein, Poa1p. MDO2 specifically bound monomeric ADP-ribose with a high affinity (K(d)=0.15 microM), but did not bind poly(ADP-ribose) efficiently. MDO2 also hydrolyzed ADP-ribose-1'' phosphate, resembling Poa1p in all these properties. Ganglioside-induced differentiation-associated protein 2 did not show affinity for ADP-ribose or its derivatives, but instead bound poly(A). MDO1 was generally active in these reactions, including poly(A) binding. Individual point mutations in MDO1 abolished monomeric ADP-ribose binding, but not poly(ADP-ribose) binding; in poly(ADP-ribose) binding assays, the monomer did not compete against polymer binding. The viral macro proteins bound poly(ADP-ribose) and poly(A), but had a low affinity for monomeric ADP-ribose. Thus, the viral proteins do not closely resemble any of the human proteins in their biochemical functions. The differential activity profiles of the human proteins implicate them in different cellular pathways, some of which may involve RNA rather than ADP-ribose derivatives.

  15. How Much Does the Supplemental Nutrition Assistance Program Reduce Food Insecurity?

    PubMed Central

    Ratcliffe, Caroline; McKernan, Signe-Mary; Zhang, Sisi

    2014-01-01

    Nearly 15% of all U.S. households and 40% of near-poor households were food insecure in 2009. The Supplemental Nutrition Assistance Program (SNAP) is the cornerstone of federal food assistance programs and serves as the first line of defense against food-related hardship. This paper measures the effectiveness of SNAP in reducing food insecurity using an instrumental variables approach to control for selection. Our results suggest that receipt of SNAP benefits reduces the likelihood of being food insecure by roughly 30% and reduces the likelihood of being very food insecure by 20%. PMID:25197100

  16. A technique for optimal temperature estimation for modeling sunrise/sunset thermal snap disturbance torque

    NASA Technical Reports Server (NTRS)

    Zimbelman, D. F.; Dennehy, C. J.; Welch, R. V.; Born, G. H.

    1990-01-01

    A predictive temperature estimation technique which can be used to drive a model of the Sunrise/Sunset thermal 'snap' disturbance torque experienced by low Earth orbiting spacecraft is described. The twice per orbit impulsive disturbance torque is attributed to vehicle passage in and out of the Earth's shadow cone (umbra), during which large flexible appendages undergo rapidly changing thermal conditions. Flexible members, in particular solar arrays, experience rapid cooling during umbra entrance (Sunset) and rapid heating during exit (Sunrise). The thermal 'snap' phenomena has been observed during normal on-orbit operations of both the LANDSAT-4 satellite and the Communications Technology Satellite (CTS). Thermal 'snap' has also been predicted to be a dominant source of error for the TOPEX satellite. The fundamental equations used to model the Sunrise/Sunset thermal 'snap' disturbance torque for a typical solar array like structure will be described. For this derivation the array is assumed to be a thin, cantilevered beam. The time varying thermal gradient is shown to be the driving force behind predicting the thermal 'snap' disturbance torque and therefore motivates the need for accurate estimates of temperature. The development of a technique to optimally estimate appendage surface temperature is highlighted. The objective analysis method used is structured on the Gauss-Markov Theorem and provides an optimal temperature estimate at a prescribed location given data from a distributed thermal sensor network. The optimally estimated surface temperatures could then be used to compute the thermal gradient across the body. The estimation technique is demonstrated using a typical satellite solar array.

  17. Gas-bubble snap-off under pressure driven flow in constricted noncircular capillaries

    SciTech Connect

    Kovscek, A.R.; Radke, C.J.

    1996-04-01

    A model for snap-off of a gas thread in a constricted cornered pore is developed. The time for wetting liquid to accumulate at a pore throat into an unstable collar is examined, as for the resulting pore-spanning lens to be displaced from the pore so that snap-off is the time may repeat. A comer-flow hydrodynamic analysis for the accumulation rate of wetting liquid due to both gradients in interfacial curvature and in applied liquid-phase pressure reveals that wetting-phase pressure gradients significantly increase the frequency of liquid accumulation for snap-off as compared to liquid rearrangement driven only by differences in pore-wall curvature. For moderate and large pressure gradients, the frequency of accumulation increases linearly with pressure gradient because of the increased rate of wetting liquid flow along pore comers. Pore topology is important to the theory, for pores with relatively small throats connected to large bodies demonstrate excellent ability to snapoff gas threads even when the initial capillary pressure is high or equivalently when the liquid saturation is low. A macroscopic momentum balance across the lens resulting from snap-off reveals that lens displacement rates are not linear with the imposed pressure drop. Instead, the frequency of lens displacement scales with powers between 0.5 and 0.6 for pores with dimensionless constriction radii between 0.15 and 0.40. Statistical percolation arguments are employed to form a generation rate expression and connect pore-level foam generation events to macroscopic pressure gradients in porous media. The rate of foam generation by capillary snap-off increases linearly with the liquid-phase pressure gradient and according to a power-law relationship with respect to the imposed gas-phase pressure gradient.

  18. An experimental framework for improved selection of binding proteins using SNAP display.

    PubMed

    Houlihan, Gillian; Gatti-Lafranconi, Pietro; Kaltenbach, Miriam; Lowe, David; Hollfelder, Florian

    2014-03-01

    Display technologies (e.g. phage and ribosome display) are powerful tools for selecting and evolving protein binders against various target molecules. SNAP display is a DNA display technology that is conducted entirely in vitro: DNA encoding a library of variants is encapsulated in water-in-oil droplets wherein in vitro protein expression and covalent coupling to the encoding DNA occurs. Here, we explore critical factors for the successful performance of SNAP display based on a set of experiments designed to measure and quantify to what extent they affect selection efficiency. We find that, in SNAP display, the reconstituted cell free expression system PURExpress led to 1.5-fold more active protein and achieved 3.5-fold greater DNA recovery in model selections compared to the RTS 100 Escherichia coli lysate based expression system. We report on the influence parameters including droplet occupancy, valency and selection stringency have on recovery and enrichment. An improved procedure involving bivalent display and stringent selection against a model target, Her2, led to a 10(7)-fold enrichment of a DARPin (H10-2-G3, known to bind Her2 with picomolar affinity) over a non-binding DARPin after three rounds of selection. Furthermore, when spiked into a mixture of DARPins with different affinities, DARPin H10-2-G3 outcompeted all other variants demonstrating SNAP display's ability to efficiently resolve clones with affinities in the nano- to picomolar range. These data establish SNAP display as an in vitro protein engineering tool for isolating protein binders and provide a framework for troubleshooting affinity selections.

  19. Snapping Sharks, Maddening Mindreaders, and Interactive Images: Teaching Correlation.

    ERIC Educational Resources Information Center

    Mitchell, Mark L.

    Understanding correlation coefficients is difficult for students. A free computer program that helps introductory psychology students distinguish between positive and negative correlation, and which also teaches them to understand the differences between correlation coefficients of different size is described in this paper. The program is…

  20. Multiple functions of the SNARE protein Snap29 in autophagy, endocytic, and exocytic trafficking during epithelial formation in Drosophila

    PubMed Central

    Morelli, Elena; Ginefra, Pierpaolo; Mastrodonato, Valeria; Beznoussenko, Galina V; Rusten, Tor Erik; Bilder, David; Stenmark, Harald; Mironov, Alexandre A; Vaccari, Thomas

    2015-01-01

    How autophagic degradation is linked to endosomal trafficking routes is little known. Here we screened a collection of uncharacterized Drosophila mutants affecting membrane transport to identify new genes that also have a role in autophagy. We isolated a loss of function mutant in Snap29 (Synaptosomal-associated protein 29 kDa), the gene encoding the Drosophila homolog of the human protein SNAP29 and have characterized its function in vivo. Snap29 contains 2 soluble NSF attachment protein receptor (SNARE) domains and a asparagine-proline-phenylalanine (NPF motif) at its N terminus and rescue experiments indicate that both SNARE domains are required for function, whereas the NPF motif is in part dispensable. We find that Snap29 interacts with SNARE proteins, localizes to multiple trafficking organelles, and is required for protein trafficking and for proper Golgi apparatus morphology. Developing tissue lacking Snap29 displays distinctive epithelial architecture defects and accumulates large amounts of autophagosomes, highlighting a major role of Snap29 in autophagy and secretion. Mutants for autophagy genes do not display epithelial architecture or secretion defects, suggesting that the these alterations of the Snap29 mutant are unlikely to be caused by the impairment of autophagy. In contrast, we find evidence of elevated levels of hop-Stat92E (hopscotch-signal transducer and activator of transcription protein at 92E) ligand, receptor, and associated signaling, which might underlie the epithelial defects. In summary, our findings support a role of Snap29 at key steps of membrane trafficking, and predict that signaling defects may contribute to the pathogenesis of cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma (CEDNIK), a human congenital syndrome due to loss of Snap29. PMID:25551675

  1. Evaluation of Fluorophores to Label SNAP-Tag Fused Proteins for Multicolor Single-Molecule Tracking Microscopy in Live Cells

    PubMed Central

    Bosch, Peter J.; Corrêa, Ivan R.; Sonntag, Michael H.; Ibach, Jenny; Brunsveld, Luc; Kanger, Johannes S.; Subramaniam, Vinod

    2014-01-01

    Single-molecule tracking has become a widely used technique for studying protein dynamics and their organization in the complex environment of the cell. In particular, the spatiotemporal distribution of membrane receptors is an active field of study due to its putative role in the regulation of signal transduction. The SNAP-tag is an intrinsically monovalent and highly specific genetic tag for attaching a fluorescent label to a protein of interest. Little information is currently available on the choice of optimal fluorescent dyes for single-molecule microscopy utilizing the SNAP-tag labeling system. We surveyed 6 green and 16 red excitable dyes for their suitability in single-molecule microscopy of SNAP-tag fusion proteins in live cells. We determined the nonspecific binding levels and photostability of these dye conjugates when bound to a SNAP-tag fused membrane protein in live cells. We found that only a limited subset of the dyes tested is suitable for single-molecule tracking microscopy. The results show that a careful choice of the dye to conjugate to the SNAP-substrate to label SNAP-tag fusion proteins is very important, as many dyes suffer from either rapid photobleaching or high nonspecific staining. These characteristics appear to be unpredictable, which motivated the need to perform the systematic survey presented here. We have developed a protocol for evaluating the best dyes, and for the conditions that we evaluated, we find that Dy 549 and CF 640 are the best choices tested for single-molecule tracking. Using an optimal dye pair, we also demonstrate the possibility of dual-color single-molecule imaging of SNAP-tag fusion proteins. This survey provides an overview of the photophysical and imaging properties of a range of SNAP-tag fluorescent substrates, enabling the selection of optimal dyes and conditions for single-molecule imaging of SNAP-tagged fusion proteins in eukaryotic cell lines. PMID:25140415

  2. Therapeutic effectiveness of botulinum neurotoxin A: potent blockade of autonomic transmission by targeted cleavage of only the pertinent SNAP-25.

    PubMed

    Lawrence, Gary W; Ovsepian, Saak V; Wang, Jiafu; Aoki, K Roger; Dolly, J Oliver

    2013-07-01

    In search of a basis for the impressive potency of an endoprotease that cleaves SNAP-25, botulinum neurotoxin type A (BoNT/A), in treating numerous diseases due to hyper-active autonomic nerves, truncation of its target and inhibition of neurotransmission were studied in rat sympathetic neurons. Tetrodotoxin-sensitive spontaneous cholinergic neurotransmission was blocked >80% by 1 pM BoNT/A despite cleaving <20% of the SNAP-25. A maximum cleavage of ∼60% SNAP-25 could be achieved with >1 nM BoNT/A, despite an absence of non-cleavable SNAP-25 in the detergent-solubilised neurons. In contrast, BoNT/E (100 nM) truncated nearly all the SNAP-25 in the intact cells, but was unable to block neurotransmission at low concentrations like BoNT/A. Chimeras created by inserting the acceptor-binding HC domain of BoNT/A into BoNT/E still cleaved all the SNAP-25, indicating ubiquitous expression of BoNT/A acceptors. Accordingly, SV2 and SNAP-25 were found to be co-expressed and broadly co-localised in neurons, but absent from non-neuronal cells. On the other hand, partial cleavage by the BoNT/A protease persisted upon replacing its HC with counterparts from BoNT/E or BoNT/B. Moreover, limited cleavage of SNAP-25 was conferred onto the protease from BoNT/E when fused to the N-terminus of BoNT/A. Thus, the BoNT/A protease is uniquely well-adapted for selectively inactivating the SNAP-25 directly involved in neurotransmission; this together with the toxin's acceptor and its target being localised on the peri-somatic boutons likely contribute to its exceptional therapeutic utility in the clinic.

  3. Multiple functions of the SNARE protein Snap29 in autophagy, endocytic, and exocytic trafficking during epithelial formation in Drosophila.

    PubMed

    Morelli, Elena; Ginefra, Pierpaolo; Mastrodonato, Valeria; Beznoussenko, Galina V; Rusten, Tor Erik; Bilder, David; Stenmark, Harald; Mironov, Alexandre A; Vaccari, Thomas

    2014-01-01

    How autophagic degradation is linked to endosomal trafficking routes is little known. Here we screened a collection of uncharacterized Drosophila mutants affecting membrane transport to identify new genes that also have a role in autophagy. We isolated a loss of function mutant in Snap29 (Synaptosomal-associated protein 29 kDa), the gene encoding the Drosophila homolog of the human protein SNAP29 and have characterized its function in vivo. Snap29 contains 2 soluble NSF attachment protein receptor (SNARE) domains and a asparagine-proline-phenylalanine (NPF motif) at its N terminus and rescue experiments indicate that both SNARE domains are required for function, whereas the NPF motif is in part dispensable. We find that Snap29 interacts with SNARE proteins, localizes to multiple trafficking organelles, and is required for protein trafficking and for proper Golgi apparatus morphology. Developing tissue lacking Snap29 displays distinctive epithelial architecture defects and accumulates large amounts of autophagosomes, highlighting a major role of Snap29 in autophagy and secretion. Mutants for autophagy genes do not display epithelial architecture or secretion defects, suggesting that the these alterations of the Snap29 mutant are unlikely to be caused by the impairment of autophagy. In contrast, we find evidence of elevated levels of hop-Stat92E (hopscotch-signal transducer and activator of transcription protein at 92E) ligand, receptor, and associated signaling, which might underlie the epithelial defects. In summary, our findings support a role of Snap29 at key steps of membrane trafficking, and predict that signaling defects may contribute to the pathogenesis of cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma (CEDNIK), a human congenital syndrome due to loss of Snap29.

  4. Involvement of gecko SNAP25b in spinal cord regeneration by promoting outgrowth and elongation of neurites.

    PubMed

    Wang, Yingjie; Dong, Yingying; Song, Honghua; Liu, Yan; Liu, Mei; Yuan, Ying; Ding, Fei; Gu, Xiaosong; Wang, Yongjun

    2012-12-01

    SNARE complex mediates cellular membrane fusion events essential for neurotransmitter release and synaptogenesis. SNAP25, a member of the SNARE proteins, plays critical roles during the development of the central nervous system via regulation by alternative splicing and protein kinase phosphorylation. To date, little information is available regarding the protein in the spinal cord regeneration, especially for the postnatal highly expressed isoform SNAP25b. In the present study, we characterized gecko SNAP25b, which shared high identity with those of other vertebrates. Expression of gecko SNAP25b was temporally upregulated in both neurons of spinal cord and forming ependymal tube following tail amputation, coinciding with the occurrence of regenerate re-innervation. Overexpression of gecko wild type SNAP25b in the SH-SY5Y and undifferentiated PC12 cells promoted the elongation and outgrowth of neurites, while mutant constructs at Serine(187) resulted in differential effects for which S187A had a promoting role. Knockdown of endogenous SNAP25b affected the formation of neurites, which could be rescued by overexpression of SNAP25b. FM1-43 staining revealed that transfection of S187E mutant construct reduced the recruitment of vesicles. In addition, transfection of gecko SNAP25b in the astrocyte, which is absent from neuronal specific VAMP2, was capable of enhancing process elongation, indicating a potential for various alternative protein combinations. Taken together, our data suggest that gecko SNAP25b is involved in spinal cord regeneration by promoting outgrowth and elongation of neurites in a more extensive protein binding manner.

  5. 78 FR 20411 - Supplemental Nutrition Assistance Program: Nutrition Education and Obesity Prevention Grant Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... demonstrated impact. Nutrition Education State Plans Prior regulation required that SNAP-Ed Plans include... Service 7 CFR Part 272 RIN 0584-AE07 Supplemental Nutrition Assistance Program: Nutrition Education and... education and obesity prevention programs. These programs will provide services for eligible...

  6. Supplemental nutrition assistance program participation and health: Evidence from low-income individuals in Tennessee

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigate the factors that contribute to participation in the Supplemental Nutrition Assistance Program (SNAP), and the effects of such participation on self-assessed health (SAH). An endogenous switching ordered probability model is developed with alternative error distributional assumptions, ...

  7. Molecular Toxicology of Chromatin: The Role of Poly (ADP-Ribose) in Gene Control

    DTIC Science & Technology

    1985-12-15

    mechanism is operative from NOD either directly ADY-ribosy- latintr "acceptor" proteins (%.g., hiatone), a reaction presumably catalyzed by the...24 Figures 1through 5. .. ............................. .. .. .. .. .........25-29’ 2. Mechanisms of’Poly(ADP-Ribose) Poiymerase Catalysis...Figures 1 through 3 .. ...................... ...........................46-48 3. Mechanism of inactivation of Poly(ADP-Ribose) Polymerase of Rat Liver

  8. Microtubule protein ADP-ribosylation in vitro leads to assembly inhibition and rapid depolymerization

    SciTech Connect

    Scaife, R.M. ); Wilson, L. ); Purich, D.L. )

    1992-01-14

    Bovine brain microtubule protein, containing both tubulin and microtubule-associated proteins, undergoes ADP-ribosylation in the presence of ({sup 14}C)NAD{sup +} and a turkey erythrocyte mono-ADP-ribosyltransferase in vitro. The modification reaction could be demonstrated in crude brain tissue extracts where selective ADP-ribosylation of both the {alpha} and {beta} chains of tubulin and of the high molecular weight microtubule-associated protein MAP-2 occurred. In experiments with purified microtubule protein, tubulin dimer, the high molecular weight microtubule-associated protein MAP-2, and another high molecular weight microtubule-associated protein which may be a MAP-1 species were heavily labeled. Tubulin and MAP-2 incorporated ({sup 14}C)ADP-ribose to an average extent of approximately 2.4 and 30 mol of ADP-ribose/mol of protein, respectively. Assembly of microtubule protein into microtubules in vitro was inhibited by ADP-ribosylation, and incubation of assembled steady-state microtubules with ADP-ribosyltransferase and NAD{sup +} resulted in rapid depolymerization of the microtubules. Thus, the eukaryotic enzyme can ADP-ribosylate tubulin and microtubule-associated proteins to much greater extents than previously observed with cholera and pertussis toxins, and the modification can significantly modulate microtubule assembly and disassembly.

  9. 45 CFR 95.625 - Increased FFP for certain ADP systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (FFP) Specific Conditions for Ffp § 95.625 Increased FFP for certain ADP systems. (a) General. FFP is available at enhanced matching rates for the development of individual or integrated systems and the... 45 Public Welfare 1 2010-10-01 2010-10-01 false Increased FFP for certain ADP systems....

  10. The NarE protein of Neisseria gonorrhoeae catalyzes ADP-ribosylation of several ADP-ribose acceptors despite an N-terminal deletion.

    PubMed

    Rodas, Paula I; Álamos-Musre, A Said; Álvarez, Francisca P; Escobar, Alejandro; Tapia, Cecilia V; Osorio, Eduardo; Otero, Carolina; Calderón, Iván L; Fuentes, Juan A; Gil, Fernando; Paredes-Sabja, Daniel; Christodoulides, Myron

    2016-09-01

    The ADP-ribosylating enzymes are encoded in many pathogenic bacteria in order to affect essential functions of the host. In this study, we show that Neisseria gonorrhoeae possess a locus that corresponds to the ADP-ribosyltransferase NarE, a previously characterized enzyme in N. meningitidis The 291 bp coding sequence of gonococcal narE shares 100% identity with part of the coding sequence of the meningococcal narE gene due to a frameshift previously described, thus leading to a 49-amino-acid deletion at the N-terminus of gonococcal NarE protein. However, we found a promoter region and a GTG start codon, which allowed expression of the protein as demonstrated by RT-PCR and western blot analyses. Using a gonococcal NarE-6xHis fusion protein, we demonstrated that the gonococcal enzyme underwent auto-ADP-ribosylation but to a lower extent than meningococcal NarE. We also observed that gonoccocal NarE exhibited ADP-ribosyltransferase activity using agmatine and cell-free host proteins as ADP-ribose acceptors, but its activity was inhibited by human β-defensins. Taken together, our results showed that NarE of Neisseria gonorrhoeae is a functional enzyme that possesses key features of bacterial ADP-ribosylating enzymes.

  11. Immunohistochemical study of Syntaxin-1 and SNAP-25 in the pituitaries of mouse, guinea pig and cat.

    PubMed

    Salinas, E; Quintanar, J L; Reig, J A

    1999-01-01

    In the present work we have investigated the presence of the membrane proteins Syntaxin-1 and synaptosomal-associated protein (SNAP-25) by immunohistochemistry in the different parts of the pituitary of mouse, guinea pig and cat. We have demonstrated Syntaxin-1 and SNAP-25 immunoreactivity in the adenohypophysis as well as in the neurohypophysis but not in intermediate lobe. The results suggest that Syntaxin-1 and SNAP-25 are involved in the hormonal secretary process of adenohypophysis as well as neurohypophysis of these animals.

  12. The Mitochondrial Fission Receptor MiD51 Requires ADP as a Cofactor

    PubMed Central

    Losón, Oliver C.; Liu, Raymond; Rome, Michael E.; Meng, Shuxia; Kaiser, Jens T.; Shan, Shu-ou; Chan, David C.

    2014-01-01

    SUMMARY Mitochondrial fission requires recruitment of dynamin-related protein 1 (Drp1) to the mitochondrial surface and activation of its GTP-dependent scission function. The Drp1 receptors MiD49 and MiD51 recruit Drp1 to facilitate mitochondrial fission, but their mechanism of action is poorly understood. Using X-ray crystallography, we demonstrate that MiD51 contains a nucleotidyl transferase domain that binds ADP with high affinity. MiD51 recruits Drp1 via a surface loop that functions independently of ADP binding. However, in the absence of nucleotide binding, the recruited Drp1 cannot be activated for fission. Purified MiD51 strongly inhibits Drp1 assembly and GTP hydrolysis in the absence of ADP. Addition of ADP relieves this inhibition and promotes Drp1 assembly into spirals with enhanced GTP hydrolysis. Our results reveal ADP as an essential cofactor for MiD51 during mitochondrial fission. PMID:24508339

  13. The mitochondrial fission receptor MiD51 requires ADP as a cofactor.

    PubMed

    Losón, Oliver C; Liu, Raymond; Rome, Michael E; Meng, Shuxia; Kaiser, Jens T; Shan, Shu-ou; Chan, David C

    2014-03-04

    Mitochondrial fission requires recruitment of dynamin-related protein 1 (Drp1) to the mitochondrial surface and activation of its GTP-dependent scission function. The Drp1 receptors MiD49 and MiD51 recruit Drp1 to facilitate mitochondrial fission, but their mechanism of action is poorly understood. Using X-ray crystallography, we demonstrate that MiD51 contains a nucleotidyl transferase domain that binds ADP with high affinity. MiD51 recruits Drp1 via a surface loop that functions independently of ADP binding. However, in the absence of nucleotide binding, the recruited Drp1 cannot be activated for fission. Purified MiD51 strongly inhibits Drp1 assembly and GTP hydrolysis in the absence of ADP. Addition of ADP relieves this inhibition and promotes Drp1 assembly into spirals with enhanced GTP hydrolysis. Our results reveal ADP as an essential cofactor for MiD51 during mitochondrial fission.

  14. The Sound of Silence: RNAi in Poly (ADP-Ribose) Research

    PubMed Central

    Blenn, Christian; Wyrsch, Philippe; Althaus, Felix R.

    2012-01-01

    Poly(ADP-ribosyl)-ation is a nonprotein posttranslational modification of proteins and plays an integral part in cell physiology and pathology. The metabolism of poly(ADP-ribose) (PAR) is regulated by its synthesis by poly(ADP-ribose) polymerases (PARPs) and on the catabolic side by poly(ADP-ribose) glycohydrolase (PARG). PARPs convert NAD+ molecules into PAR chains that interact covalently or noncovalently with target proteins and thereby modify their structure and functions. PAR synthesis is activated when PARP1 and PARP2 bind to DNA breaks and these two enzymes account for almost all PAR formation after genotoxic stress. PARG cleaves PAR molecules into free PAR and finally ADP-ribose (ADPR) moieties, both acting as messengers in cellular stress signaling. In this review, we discuss the potential of RNAi to manipulate the levels of PARPs and PARG, and consequently those of PAR and ADPR, and compare the results with those obtained after genetic or chemical disruption. PMID:24705085

  15. Characterization of the active site of ADP-ribosyl cyclase.

    PubMed

    Munshi, C; Thiel, D J; Mathews, I I; Aarhus, R; Walseth, T F; Lee, H C

    1999-10-22

    ADP-ribosyl cyclase synthesizes two Ca(2+) messengers by cyclizing NAD to produce cyclic ADP-ribose and exchanging nicotinic acid with the nicotinamide group of NADP to produce nicotinic acid adenine dinucleotide phosphate. Recombinant Aplysia cyclase was expressed in yeast and co-crystallized with a substrate, nicotinamide. x-ray crystallography showed that the nicotinamide was bound in a pocket formed in part by a conserved segment and was near the central cleft of the cyclase. Glu(98), Asn(107) and Trp(140) were within 3.5 A of the bound nicotinamide and appeared to coordinate it. Substituting Glu(98) with either Gln, Gly, Leu, or Asn reduced the cyclase activity by 16-222-fold, depending on the substitution. The mutant N107G exhibited only a 2-fold decrease in activity, while the activity of W140G was essentially eliminated. The base exchange activity of all mutants followed a similar pattern of reduction, suggesting that both reactions occur at the same active site. In addition to NAD, the wild-type cyclase also cyclizes nicotinamide guanine dinucleotide to cyclic GDP-ribose. All mutant enzymes had at least half of the GDP-ribosyl cyclase activity of the wild type, some even 2-3-fold higher, indicating that the three coordinating amino acids are responsible for positioning of the substrate but not absolutely critical for catalysis. To search for the catalytic residues, other amino acids in the binding pocket were mutagenized. E179G was totally devoid of GDP-ribosyl cyclase activity, and both its ADP-ribosyl cyclase and the base exchange activities were reduced by 10,000- and 18,000-fold, respectively. Substituting Glu(179) with either Asn, Leu, Asp, or Gln produced similar inactive enzymes, and so was the conversion of Trp(77) to Gly. However, both E179G and the double mutant E179G/W77G retained NAD-binding ability as shown by photoaffinity labeling with [(32)P]8-azido-NAD. These results indicate that both Glu(179) and Trp(77) are crucial for catalysis and

  16. Biochemical and molecular characterization of barley plastidial ADP-glucose transporter (HvBT1).

    PubMed

    Soliman, Atta; Ayele, Belay T; Daayf, Fouad

    2014-01-01

    In cereals, ADP-glucose transporter protein plays an important role in starch biosynthesis. It acts as a main gate for the transport of ADP-glucose, the main precursor for starch biosynthesis during grain filling, from the cytosol into the amyloplasts of endospermic cells. In this study, we have shed some light on the molecular and biochemical characteristics of barley plastidial ADP-glucose transporter, HvBT1. Phylogenetic analysis of several BT1 homologues revealed that BT1 homologues are divided into two distinct groups. The HvBT1 is assigned to the group that represents BT homologues from monocotyledonous species. Some members of this group mainly work as nucleotide sugar transporters. Southern blot analysis showed the presence of a single copy of HvBT1 in barley genome. Gene expression analysis indicated that HvBT1 is mainly expressed in endospermic cells during grain filling; however, low level of its expression was detected in the autotrophic tissues, suggesting the possible role of HvBT1 in autotrophic tissues. The cellular and subcellular localization of HvBT1 provided additional evidence that HvBT1 targets the amyloplast membrane of the endospermic cells. Biochemical characterization of HvBT1 using E. coli system revealed that HvBT1 is able to transport ADP-glucose into E. coli cells with an affinity of 614.5 µM and in counter exchange of ADP with an affinity of 334.7 µM. The study also showed that AMP is another possible exchange substrate. The effect of non-labeled ADP-glucose and ADP on the uptake rate of [α-32P] ADP-glucose indicated the substrate specificity of HvBT1 for ADP-glucose and ADP.

  17. Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes.

    PubMed

    Cantó, Carles; Sauve, Anthony A; Bai, Peter

    2013-12-01

    Poly(ADP-ribose) polymerases (PARPs) are NAD(+) dependent enzymes that were identified as DNA repair proteins, however, today it seems clear that PARPs are responsible for a plethora of biological functions. Sirtuins (SIRTs) are NAD(+)-dependent deacetylase enzymes involved in the same biological processes as PARPs raising the question whether PARP and SIRT enzymes may interact with each other in physiological and pathophysiological conditions. Hereby we review the current understanding of the SIRT-PARP interplay in regard to the biochemical nature of the interaction (competition for the common NAD(+) substrate, mutual posttranslational modifications and direct transcriptional effects) and the physiological or pathophysiological consequences of the interactions (metabolic events, oxidative stress response, genomic stability and aging). Finally, we give an overview of the possibilities of pharmacological intervention to modulate PARP and SIRT enzymes either directly, or through modulating NAD(+) homeostasis.

  18. Pharmacological inhibition of poly(ADP-ribose) polymerase inhibits angiogenesis

    SciTech Connect

    Rajesh, Mohanraj; Mukhopadhyay, Partha; Batkai, Sandor; Godlewski, Grzegorz; Hasko, Gyoergy; Liaudet, Lucas; Pacher, Pal . E-mail: pacher@mail.nih.gov

    2006-11-17

    Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which plays an important role in regulating cell death and cellular responses to DNA repair. Pharmacological inhibitors of PARP are being considered as treatment for cancer both in monotherapy as well as in combination with chemotherapeutic agents and radiation, and were also reported to be protective against untoward effects exerted by certain anticancer drugs. Here we show that pharmacological inhibition of PARP with 3-aminobenzamide or PJ-34 dose-dependently reduces VEGF-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells in vitro. These results suggest that treatment with PARP inhibitors may exert additional benefits in various cancers and retinopathies by decreasing angiogenesis.

  19. Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes

    PubMed Central

    Cantó, Carles; Sauve, Anthony A.; Bai, Peter

    2013-01-01

    Poly(ADP-ribose) polymerases (PARPs) are NAD+ dependent enzymes that were identified as DNA repair proteins, however, today it seems clear that PARPs are responsible for a plethora of biological functions. Sirtuins (SIRTs) are NAD+-dependent deacetylase enzymes involved in the same biological processes as PARPs raising the question whether PARP and SIRT enzymes may interact with each other in physiological and pathophysiological conditions. Hereby we review the current understanding of the SIRT-PARP interplay in regard to the biochemical nature of the interaction (competition for the common NAD+ substrate, mutual posttranslational modifications and direct transcriptional effects) and the physiological, or pathophysiological consequences of the interactions (metabolic events, oxidative stress response, genomic stability and ageing). Finally, we give an overview of the possibilities of pharmacological intervention to modulate PARP and SIRT enzymes either directly, or through modulating NAD+ homeostasis. PMID:23357756

  20. Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

    PubMed

    Vida, András; Abdul-Rahman, Omar; Mikó, Edit; Brunyánszki, Attila; Bai, Peter

    2016-01-01

    Poly(ADP-ribose) polymerases were originally described as DNA repair enzymes. PARP-1, PARP-2 and PARP-3 can be activated by DNA damage and the resulting activation of these enzymes that facilitate DNA repair, seems to be a prerequisite of successful aging. PARP activation helps to maintain genomic integrity through supporting DNA repair systems; however, in parallel these enzymes limit metabolic fitness and make the organism more prone for metabolic diseases. In addition, several other pathways (e.g., proteostasis, nutrient sensing, stem cell proliferation or cellular communication) all contributing to aging, were shown to be PARP mediated. In this review we aim to summarize our current knowledge on the role of PARPs in aging.

  1. Cholera toxin can catalyze ADP-ribosylation of cytoskeletal proteins

    SciTech Connect

    Kaslow, H.R.; Groppi, V.E.; Abood, M.E.; Bourne, H.R.

    1981-11-01

    Cholera toxin catalyzes transfer of radiolabel from (/sup 32/P)NAD/sup +/ to several peptides in particulate preparations of human foreskin fibroblasts. Resolution of these peptides by two-dimensional gel electrophoresis allowed identification of two peptides of M/sub r/ = 42,000 and 52,000 as peptide subunits of a regulatory component of adenylate cyclase. The radiolabeling of another group of peptides (M/sub r/ = 50,000 to 65,000) suggested that cholera toxin could catalyze ADP-ribosylation of cytoskeletal proteins. This suggestion was confirmed by showing that incubation with cholera toxin and (/sup 32/P)NAD/sup +/ caused radiolabeling of purified microtubule and intermediate filament proteins.

  2. Hubble Space Telescope faint object spectrograph Quasar Absorption System Snapshot Survey (AbSnap). 1: Astrometric optical positions and finding charts of 269 bright QSO

    NASA Technical Reports Server (NTRS)

    Bowen, David V.; Osmer, Samantha J.; Blades, J. Chris; Tytler, David; Cottrell, Lance; Fan, Xiao-Ming; Lanzetta, Kenneth M.

    1994-01-01

    We present finding charts and optical positions accurate to less than 1 arcsec for 269 bright (V less than or = 18.5) Quasi-Stellar Objects (QSOs). These objects were selected as candidates for the Hubble Space Telescope (HST) Quasar Absorption System Snapshot Survey (AbSnap), a program designed to use the Faint Object Spectrograph (FOS) to obtain short exposure ultraviolet (UV) spectra of bright QSOs. Many quasars were included because of their proximity to bright, low redshift galaxies and positions of these QSOs are measured accurately for the first time. Data were obtained using the digitized sky survey produced by the Space Telescope Science Institute's Guide Stars Selection System Astrometric Support Program.

  3. Testing Two Alternative Pathological Personality Measures in the Assessment of Psychopathy: An Examination of the Snap and DAPP-BQ.

    PubMed

    Pryor, Lauren R; Miller, Joshua D; Gaughan, Eric T

    2009-02-01

    The current study examined the interrelations between two measures of pathological personality, the Schedule for Nonadaptive and Adaptive Personality (SNAP; Clark, 1993) and the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ; Livesley, 1990), and their respective relations with psychopathy. Two hundred and twenty-nine undergraduate students completed the SNAP, DAPP-BQ, and two self-report psychopathy inventories, the Levenson Self-Report Psychopathy Scale (LSRP; Levenson, Kiehl, & Fitzpatrick, 1995) and the Psychopathic Personality Inventory-Revised (PPI-R; Lilienfeld & Widows, 2005). Results revealed good convergence between conceptually related SNAP and DAPP-BQ subscales. Both the SNAP and DAPP-BQ accounted for a substantial amount of variance in psychopathy scores although the DAPP-BQ accounted for a larger percentage of the variance and demonstrated greater incremental validity. Results suggest that both measures can be successfully used to assess traits associated with psychopathy.

  4. Sweet vs. Snap! Effective Dispositions in the Media Center

    ERIC Educational Resources Information Center

    Standard, April

    2011-01-01

    In "What Defines an Exemplary School Librarian," Jami Jones and Gail Bush make a strong argument that professional disposition is the key to a successful library media program. The authors emphasize the relevance of INTASC standards which specify that teachers must promote "positive social interaction and (develop) healthy and helping…

  5. SNAP/SMART: Technical Training for the Disadvantaged.

    ERIC Educational Resources Information Center

    Educational Computer Corp., Radnor, PA.

    This project was designed to develop and test unique curricula that demonstrate means of circumventing the customary training program reliance on reading and thus eliminate an artificial barrier to the training and employment of a large portion of the population. A number of specialized educational techniques and equipment were used in the…

  6. The galanin-3 receptor antagonist, SNAP 37889, suppresses alcohol drinking and morphine self-administration in mice.

    PubMed

    Scheller, Karlene J; Williams, Spencer J; Lawrence, Andrew J; Djouma, Elvan

    2017-03-05

    The neuropeptide, galanin, is widely expressed in the central and peripheral nervous systems and is involved in a range of different functions including nociception, neurogenesis, hormone release, reproduction, cognitive function and appetite. Given the overlap between galanin expression and reward circuitry in the brain, galanin has been targeted for alcohol use disorder (AUD) and opioid dependency. Furthermore, the galanin-3 receptor (GAL3) specifically regulates emotional states and plays a role in motivation, reward and drug-seeking behaviour. We have previously shown that the GAL3 antagonist, SNAP 37889, reduces ethanol self-administration and cue-induced re-instatement in alcohol-preferring (iP) rats with no alterations in locomotor activity or anxiety-like behaviour. The aim of this study was to investigate whether SNAP 37889 reduces binge drinking and/or self-administration of morphine in mice. Using the Scheduled High Alcohol Consumption (SHAC) procedure, SNAP 37889 (30 mg/kg) treated mice drank significantly less ethanol, sucrose and saccharin than vehicle treated mice. Using an operant paradigm, SNAP 37889 reduced morphine self-administration but failed to impact cue-induced relapse-like behaviour. SNAP 37889 had no significant effect on locomotor activity, motor co-ordination, anxiety, nor was SNAP 37889 itself positively reinforcing. Liver assays showed that there was no alteration in the rate of hepatic ethanol metabolism between SNAP 37889 and vehicle treated mice suggesting that the reduction in ethanol intake via SNAP 37889 is due to a central effect of GAL3 signalling. This study implicates the GAL3 receptor in consummatory drive which may have wider implications for the treatment of different addictions.

  7. Bespoke SnAP reagents for the synthesis of C-substituted spirocyclic and bicyclic saturated N-heterocycles.

    PubMed

    Geoghegan, Kimberly; Bode, Jeffrey W

    2015-04-17

    The precise placement of C-substituents on bicyclic and spirocyclic N-heterocycles is readily achieved by the combination of aldehydes and new SnAP reagents. The substituted SnAP reagents are readily prepared from simple starting materials and couple with a variety of aromatic and heteroaromatic aldehydes at room temperature under operationally simple conditions to deliver substituted morpholine and piperazine products.

  8. How the Venus flytrap actively snaps: hydrodynamic measurements at the cellular level

    NASA Astrophysics Data System (ADS)

    Colombani, Mathieu; Forterre, Yoel; GEP Team

    2012-11-01

    Although they lack muscle, plants have evolved a remarkable range of mechanisms to create rapid motion, from the rapid folding of sensitive plants to seed dispersal. Of these spectacular examples that have long fascinated scientists, the carnivorous plant Venus flytrap, whose leaves snap together in a fraction of second to capture insects, has long been a paradigm for study. Recently, we have shown that this motion involves a snap-buckling instability due to the shell-like geometry of the leaves of the trap. However, the origin of the movement that allows the plant to cross the instability threshold and actively bend remains largely unknown. In this study, we investigate this active motion using a micro-fluidic pressure probe that gives direct hydraulic and mechanical measurements at the cellular level (osmotic pressure, cell membrane permeability, cell wall elasticity). Our results challenge the role of osmotically-driven water flows usually put forward to explain Venus flytrap's active closure.

  9. MATERIALS COMPATIBILITY OF SNAP FUEL COMPONENTS DURING SHIPMENT IN 9975 PACKAGING

    SciTech Connect

    Vormelker, P

    2006-11-14

    Materials Science and Technology has evaluated materials compatibility for the SNAP (Systems for Nuclear Auxiliary Power) fuel for containment within a 9975 packaging assembly for a shipping period of one year. The evaluation included consideration for potential for water within the convenience can, corrosion from water, galvanic corrosion, tape degradation, and thermal expansion risk. Based on a review of existing literature and assumed conditions, corrosion and/or degradation of the 304 stainless steel (SS) Primary Containment Vessel (PCV) and the 304 stainless steel convenience cans containing the SNAP fuel is not significant to cause failure during the 1 year time shipping period in the 9975 packaging assembly. However, storage beyond the 1 year shipping period has not been validated.

  10. Poly(ADP-ribosylation) and neoplastic transformation: effect of PARP inhibitors.

    PubMed

    Donà, Francesca; Chiodi, Ilaria; Belgiovine, Cristina; Raineri, Tatiana; Ricotti, Roberta; Mondello, Chiara; Scovassi, Anna Ivana

    2013-01-01

    Poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribosylation) play essential roles in several biological processes, among which neoplastic transformation and telomere maintenance. In this paper, we review the poly(ADP-ribosylation) process together with the highly appealing use of PARP inhibitors for the treatment of cancer. In addition, we report our results concerning poly(ADP-ribosylation) in a cellular model system for neoplastic transformation developed in our laboratory. Here we show that PARP-1 and PARP-2 expression increases during neoplastic transformation, together with the basal levels of poly(ADP-ribosylation). Furthermore, we demonstrate a greater effect of the PARP inhibitor 3-aminobenzamide (3AB) on cellular viability in neoplastically transformed cells compared to normal fibroblasts and we show that prolonged 3AB administration to tumorigenic cells causes a decrease in telomere length. Taken together, our data support an active involvement of poly(ADP-ribosylation) in neoplastic transformation and telomere length maintenance and confirm the relevant role of poly(ADP-ribosylation) inhibition for the treatment of cancer.

  11. Proteome-wide identification of the endogenous ADP-ribosylome of mammalian cells and tissue

    PubMed Central

    Martello, Rita; Leutert, Mario; Jungmichel, Stephanie; Bilan, Vera; Larsen, Sara C.; Young, Clifford; Hottiger, Michael O.; Nielsen, Michael L.

    2016-01-01

    Although protein ADP-ribosylation is involved in diverse biological processes, it has remained a challenge to identify ADP-ribose acceptor sites. Here, we present an experimental workflow for sensitive and unbiased analysis of endogenous ADP-ribosylation sites, capable of detecting more than 900 modification sites in mammalian cells and mouse liver. In cells, we demonstrate that Lys residues, besides Glu, Asp and Arg residues, are the dominant in vivo targets of ADP-ribosylation during oxidative stress. In normal liver tissue, we find Arg residues to be the predominant modification site. The cellular distribution and biological processes that involve ADP-ribosylated proteins are different in cultured cells and liver tissue, in the latter of which the majority of sites were found to be in cytosolic and mitochondrial protein networks primarily associated with metabolism. Collectively, we describe a robust methodology for the assessment of the role of ADP-ribosylation and ADP-ribosyltransferases in physiological and pathological states. PMID:27686526

  12. SNAP23/25 and VAMP2 mediate exocytic event of transferrin receptor-containing recycling vesicles

    PubMed Central

    Kubo, Keiji; Kobayashi, Minako; Nozaki, Shohei; Yagi, Chikako; Hatsuzawa, Kiyotaka; Katoh, Yohei; Shin, Hye-Won; Takahashi, Senye; Nakayama, Kazuhisa

    2015-01-01

    ABSTRACT We recently showed that Rab11 is involved not only in formation of recycling vesicles containing the transferrin (Tfn)–transferrin receptor (TfnR) complex at perinuclear recycling endosomes but also in tethering of recycling vesicles to the plasma membrane (PM) in concert with the exocyst tethering complex. We here aimed at identifying SNARE proteins responsible for fusion of Tfn–TfnR-containing recycling vesicles with the PM, downstream of the exocyst. We showed that exocyst subunits, Sec6 and Sec8, can interact with SNAP23 and SNAP25, both of which are PM-localizing Qbc-SNAREs, and that depletion of SNAP23 and/or SNAP25 in HeLa cells suppresses fusion of Tfn–TfnR-containing vesicles with the PM, leading to accumulation of the vesicles at the cell periphery. We also found that VAMP2, an R-SNARE, is colocalized with endocytosed Tfn on punctate endosomal structures, and that its depletion in HeLa cells suppresses recycling vesicle exocytosis. These observations indicate that fusion of recycling vesicles with the PM downstream of the exocyst is mediated by SNAP23/25 and VAMP2, and provide novel insight into non-neuronal roles of VAMP2 and SNAP25. PMID:26092867

  13. The Association of SNAP25 Gene Polymorphisms in Attention Deficit/Hyperactivity Disorder: a Systematic Review and Meta-Analysis.

    PubMed

    Liu, Yun-Sheng; Dai, Xuan; Wu, Wei; Yuan, Fang-Fen; Gu, Xue; Chen, Jian-Guo; Zhu, Ling-Qiang; Wu, Jing

    2017-04-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most highly heritable psychiatric disorders in childhood. The risk gene mutation accounts for about 60 to 90 % cases. Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic plasma membrane protein which is expressed highly and specifically in the neuronal cells. A number of evidences have suggested the role of SNAP-25 in the etiology of ADHD. Notably, the animal model of coloboma mouse mutant bears a ∼2-cM deletion encompassing genes including SNAP25 and displays spontaneous hyperkinetic behavior. Previous investigators have reported association between SNPs in SNAP25 and ADHD, and controversial results were observed. In this study, we analyzed the possible association between six polymorphisms (rs3746544, rs363006, rs1051312, rs8636, rs362549, and rs362998) of SNAP25 and ADHD in a pooled sample of ten family-based studies and four case-control studies by using meta-analysis. The combined analysis results were significant only for rs3746544 (P = 0.010) with mild association (odds ratio (OR) = 1.14). And, the meta-analysis data for rs8636, rs362549, and rs362998 are the first time to be reported; however, no positive association was detected. In conclusion, we report some evidence supporting the association of SNAP25 to ADHD. Future research should emphasize genome-wide association studies in more specific subgroups and larger independent samples.

  14. Regulation of Ca2+ channels by SNAP-25 via recruitment of syntaxin-1 from plasma membrane clusters

    PubMed Central

    Toft-Bertelsen, Trine Lisberg; Ziomkiewicz, Iwona; Houy, Sébastien; Pinheiro, Paulo S.; Sørensen, Jakob B.

    2016-01-01

    SNAP-25 regulates Ca2+ channels, with potentially important consequences for diseases involving an aberrant SNAP-25 expression level. How this regulation is executed mechanistically remains unknown. We investigated this question in mouse adrenal chromaffin cells and found that SNAP-25 inhibits Ca2+ currents, with the B-isoform being more potent than the A-isoform, but not when syntaxin-1 is cleaved by botulinum neurotoxin C. In contrast, syntaxin-1 inhibits Ca2+ currents independently of SNAP-25. Further experiments using immunostaining showed that endogenous or exogenous SNAP-25 expression recruits syntaxin-1 from clusters on the plasma membrane, thereby increasing the immunoavailability of syntaxin-1 and leading indirectly to Ca2+ current inhibition. Expression of Munc18-1, which recruits syntaxin-1 within the exocytotic pathway, does not modulate Ca2+ channels, whereas overexpression of the syntaxin-binding protein Doc2B or ubMunc13-2 increases syntaxin-1 immunoavailability and concomitantly down-regulates Ca2+ currents. Similar findings were obtained upon chemical cholesterol depletion, leading directly to syntaxin-1 cluster dispersal and Ca2+ current inhibition. We conclude that clustering of syntaxin-1 allows the cell to maintain a high syntaxin-1 expression level without compromising Ca2+ influx, and recruitment of syntaxin-1 from clusters by SNAP-25 expression makes it available for regulating Ca2+ channels. This mechanism potentially allows the cell to regulate Ca2+ influx by expanding or contracting syntaxin-1 clusters. PMID:27605709

  15. Demonstration/Validation of the Snap Sampler Passive Ground Water Sampling Device

    DTIC Science & Technology

    2011-06-01

    sampling 5. Carefully selecting a sampling order that reduces sampler impacts on subsequent sampling events. 6.1.2 Baseline Characterization Prior to...sampling • Carefully selecting a sampling order that reduces sampler impacts on subsequent sampling events. 27 6.2.2 Baseline...Validation of the Snap Sampler Passive Ground Water Sampling Device June 2011 i COST & PERFORMANCE REPORT Project: ER-200630 TABLE OF CONTENTS

  16. Niobium tunnel junction fabrication using e-gun evaporation and SNAP

    NASA Astrophysics Data System (ADS)

    Kortlandt, J.; van der Zant, H. S. J.; Schellingerhout, A. J. G.; Mooij, J. E.

    1990-11-01

    We have fabricated high quality small area Nb-Al-Al 2O 3-Nb junctions with SNAP, making use of e-beam evaporation in a 10 -5 Pa diffusion pumped vacuum system. Nominal dimensions of the junctions are 8x8, 4x4 and 2x2 μm 2. We obtain typical current densities of 5-6 × 10 +2A/cm 2 and (critical current) x (subgap resistance) products of 40 mV.

  17. Variants in SNAP25 are targets of natural selection and influence verbal performances in women.

    PubMed

    Cagliani, Rachele; Riva, Stefania; Marino, Cecilia; Fumagalli, Matteo; D'Angelo, Maria Grazia; Riva, Valentina; Comi, Giacomo P; Pozzoli, Uberto; Forni, Diego; Cáceres, Mario; Bresolin, Nereo; Clerici, Mario; Sironi, Manuela

    2012-05-01

    Descriptions of genes that are adaptively evolving in humans and that carry polymorphisms with an effect on cognitive performances have been virtually absent. SNAP25 encodes a presynaptic protein with a role in regulation of neurotransmitter release. We analysed the intra-specific diversity along SNAP25 and identified a region in intron 1 that shows signatures of balancing selection in humans. The estimated TMRCA (time to the most recent common ancestor) of the SNAP25 haplotype phylogeny amounted to 2.08 million years. The balancing selection signature is not secondary to demographic events or to biased gene conversion, and encompasses rs363039. This SNP has previously been associated to cognitive performances with contrasting results in different populations. We analysed this variant in two Italian cohorts in different age ranges and observed a significant genotype effect for rs363039 on verbal performances in females alone. Post hoc analysis revealed that the effect is driven by differences between heterozygotes and both homozygous genotypes. Thus, heterozygote females for rs363039 display higher verbal performances compared to both homozygotes. This finding was replicated in a cohort of Italian subjects suffering from neuromuscular diseases that do not affect cognition. Heterozygote advantage is one of the possible reasons underlying the maintenance of genetic diversity in natural populations. The observation that heterozygotes for rs363039 display higher verbal abilities compared to homozygotes perfectly fits the underlying balancing selection model. Although caution should be used in inferring selective pressures from observed signatures, SNAP25 might represent the first description of an adaptively evolving gene with a role in cognition.

  18. Near-Optimal Control for Nonzero-Sum Differential Games of Continuous-Time Nonlinear Systems Using Single-Network ADP.

    PubMed

    Zhang, Huaguang; Cui, Lili; Luo, Yanhong

    2013-02-01

    In this paper, a near-optimal control scheme is proposed to solve the nonzero-sum differential games of continuous-time nonlinear systems. The single-network adaptive dynamic programming (ADP) is utilized to obtain the optimal control policies which make the cost functions reach the Nash equilibrium of nonzero-sum differential games, where only one critic network is used for each player instead of the action-critic dual network used in a typical ADP architecture. Furthermore, the novel weight tuning laws for critic neural networks are proposed, which not only ensure the Nash equilibrium to be reached but also guarantee the system to be stable. No initial stabilizing control policy is required for each player. Moreover, Lyapunov theory is utilized to demonstrate the uniform ultimate boundedness of the closed-loop system. Finally, a simulation example is given to verify the effectiveness of the proposed near-optimal control scheme.

  19. Validation of questionnaire on the Spiritual Needs Assessment for Patients (SNAP) questionnaire in Brazilian Portuguese

    PubMed Central

    de Araujo Toloi, Diego; Uema, Deise; Matsushita, Felipe; da Silva Andrade, Paulo Antonio; Branco, Tiago Pugliese; de Carvalho Chino, Fabiana Tomie Becker; Guerra, Raquel Bezerra; Pfiffer, Túlio Eduardo Flesch; Chiba, Toshio; Guindalini, Rodrigo Santa Cruz; Sulmasy, Daniel P; Riechelmann, Rachel P

    2016-01-01

    Summary Objectives Spirituality is related to the care and the quality of life of cancer patients. Thus, it is very important to assess their needs. The objective of this study was the translation and cultural adjustment of the Spiritual Needs Assessment for Patients (SNAP) questionnaire to the Brazilian Portuguese language. Methodology The translation and cultural adjustment of the SNAP questionnaire involved six stages: backtranslation, revision of backtranslation, translation to the original language and adjustments, pre-test on ten patients, and test and retest with 30 patients after three weeks. Adult patients, with a solid tumour and literate with a minimum of four years schooling were included. For analysis and consistency we used the calculation of the Cronbach alpha coefficient and the Pearson linear correlation. Results The final questionnaire had some language and content adjustments compared to the original version in English. The correlation analysis of each item with the total score of the questionnaire showed coefficients above 0.99. The calculation of the Cronbach alpha coefficient was 0.9. The calculation of the Pearson linear correlation with the test and retest of the questionnaire was equal to 0.95. Conclusion The SNAP questionnaire translated into Brazilian Portuguese is adequately reliable and consistent. This instrument allows adequate access to spiritual needs and can help patient care. PMID:28101137

  20. Disposition of low and high environmental concentrations of PCBs in snapping turtle tissues

    SciTech Connect

    Bryan, A.M.; Olafsson, P.G.; Stone, W.B.

    1987-06-01

    Snapping turtles, as a result of their ability to store high concentrations of PCBs in their fat, provide an excellent screen for the detection of trace toxic substances in water. Snapping turtles may also be of value in the monitoring of the disposition of environmental pollutants in the tissues of organisms living in a particular ecosystem. Many organochlorine compounds are only slowly metabolized by animals and consequently the parent compounds tend to persist in the tissues. Differences in the degree of dissolution of various polychlorinated hydrocarbons in blood may be attributed to differences in the relative solubility of these compounds in one or more of the blood components. It has been shown that binding of individual organochlorine compounds by lipoproteins and albumin involves slowly reversible hydrophobic interactions with a quasi steady state between adipose tissue, blood and remaining tissues. If such a dynamic equilibrium is involved, it might be anticipated that, under the impact of a multi-component pollutant such as an Aroclor, the biological system would respond in the same manner over a wide range of concentrations provided that the binding of each the congeners involved reversible interactions with the quasi steady state. The net result would be that the order of quantitative disposition of PCBs in the various tissues would be maintained as the concentration in each site increased. It is the objective of this study to determine if such a pharmacodynamic equilibrium is operative in snapping turtles subjected to widely differing degrees of PCB environment contamination.

  1. Atrazine and glyphosate dynamics in a lotic ecosystem: the common snapping turtle as a sentinel species.

    PubMed

    Douros, Derrick L; Gaines, Karen F; Novak, James M

    2015-03-01

    Atrazine and glyphosate are two of the most common pesticides used in the US Midwest that impact water quality via runoff, and the common snapping turtle (Chelydra serpentina) is an excellent indicator species to monitor these pesticides especially in lotic systems. The goals of this study were to (1) quantify atrazine, the atrazine metabolite diaminochlorotriazine (DACT), and glyphosate burdens in common snapping turtle tissue from individuals collected within the Embarras River in Illinois; (2) quantify atrazine, DACT, and glyphosate loads in water from the aquatic habitats in which common snapping turtles reside; and (3) investigate tissue loads based on turtle morphology and habitat choice. Concentrations of atrazine, DACT, and glyphosate in tissue did not show any relationship with lake habitat, carapace length, width, or mass. Both atrazine and glyphosate tissue samples varied as a function of site (river vs. lake), but DACT did not. Atrazine and glyphosate concentrations in water samples showed a linear effect on distance from the reservoir spillway and a deviation from linearity. Water column concentrations of all three contaminants varied across capture sites, but atrazine water concentration did not influence DACT water concentration nor did it exhibit a site interaction. Water atrazine and glyphosate concentrations were greater than tissue concentrations, whereas DACT water and tissue concentrations did not differ. This study showed that turtles are useful in long-term pesticide monitoring, and because DACT as a metabolite is less sensitive to variation, it should be considered as a preferred biomarker for pesticide runoff.

  2. Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes.

    PubMed

    de Wit, Heidi; Walter, Alexander M; Milosevic, Ira; Gulyás-Kovács, Attila; Riedel, Dietmar; Sørensen, Jakob B; Verhage, Matthijs

    2009-09-04

    Docking, the initial association of secretory vesicles with the plasma membrane, precedes formation of the SNARE complex, which drives membrane fusion. For many years, the molecular identity of the docked state, and especially the vesicular docking protein, has been unknown, as has the link to SNARE complex assembly. Here, using adrenal chromaffin cells, we identify the vesicular docking partner as synaptotagmin-1, the calcium sensor for exocytosis, and SNAP-25 as an essential plasma membrane docking factor, which, together with the previously known docking factors Munc18-1 and syntaxin, form the minimal docking machinery. Moreover, we show that the requirement for Munc18-1 in docking, but not fusion, can be overcome by stabilizing syntaxin/SNAP-25 acceptor complexes. These findings, together with cross-rescue, double-knockout, and electrophysiological data, lead us to propose that vesicles dock when synaptotagmin-1 binds to syntaxin/SNAP-25 acceptor complexes, whereas Munc18-1 is required for the downstream association of synaptobrevin to form fusogenic SNARE complexes.

  3. Dynamic Snap-Through of Thermally Buckled Structures by a Reduced Order Method

    NASA Technical Reports Server (NTRS)

    Przekop, Adam; Rizzi, Stephen A.

    2007-01-01

    The goal of this investigation is to further develop nonlinear modal numerical simulation methods for application to geometrically nonlinear response of structures exposed to combined high intensity random pressure fluctuations and thermal loadings. The study is conducted on a flat aluminum beam, which permits a comparison of results obtained by a reduced-order analysis with those obtained from a numerically intensive simulation in physical degrees-of-freedom. A uniformly distributed thermal loading is first applied to investigate the dynamic instability associated with thermal buckling. A uniformly distributed random loading is added to investigate the combined thermal-acoustic response. In the latter case, three types of response characteristics are considered, namely: (i) small amplitude vibration around one of the two stable buckling equilibrium positions, (ii) intermittent snap-through response between the two equilibrium positions, and (iii) persistent snap-through response between the two equilibrium positions. For the reduced-order analysis, four categories of modal basis functions are identified including those having symmetric transverse, anti-symmetric transverse, symmetric in-plane, and anti-symmetric in-plane displacements. The effect of basis selection on the quality of results is investigated for the dynamic thermal buckling and combined thermal-acoustic response. It is found that despite symmetric geometry, loading, and boundary conditions, the anti-symmetric transverse and symmetric in-plane modes must be included in the basis as they participate in the snap-through behavior.

  4. Dynamic Snap-Through of Thin-Walled Structures by a Reduced Order Method

    NASA Technical Reports Server (NTRS)

    Przekop, Adam; Rizzi, Stephen A.

    2006-01-01

    The goal of this investigation is to further develop nonlinear modal numerical simulation methods for application to geometrically nonlinear response of structures exposed to combined high intensity random pressure fluctuations and thermal loadings. The study is conducted on a flat aluminum beam, which permits a comparison of results obtained by a reduced-order analysis with those obtained from a numerically intensive simulation in physical degrees-of-freedom. A uniformly distributed thermal loading is first applied to investigate the dynamic instability associated with thermal buckling. A uniformly distributed random loading is added to investigate the combined thermal-acoustic response. In the latter case, three types of response characteristics are considered, namely: (i) small amplitude vibration around one of the two stable buckling equilibrium positions, (ii) intermittent snap-through response between the two equilibrium positions, and (iii) persistent snap-through response between the two equilibrium positions. For the reduced order analysis, four categories of modal basis functions are identified including those having symmetric transverse (ST), anti-symmetric transverse (AT), symmetric in-plane (SI), and anti-symmetric in-plane (AI) displacements. The effect of basis selection on the quality of results is investigated for the dynamic thermal buckling and combined thermal-acoustic response. It is found that despite symmetric geometry, loading, and boundary conditions, the AT and SI modes must be included in the basis as they participate in the snap-through behavior.

  5. IκB kinase phosphorylation of SNAP-23 controls platelet secretion.

    PubMed

    Karim, Zubair A; Zhang, Jinchao; Banerjee, Meenakshi; Chicka, Michael C; Al Hawas, Rania; Hamilton, Tara R; Roche, Paul A; Whiteheart, Sidney W

    2013-05-30

    Platelet secretion plays a key role in thrombosis, thus the platelet secretory machinery offers a unique target to modulate hemostasis. We report the regulation of platelet secretion via phosphorylation of SNAP-23 at Ser95. Phosphorylation of this t-soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) occurs upon activation of known elements of the platelet signaling cascades (ie, phospholipase C, [Ca(2+)]i, protein kinase C) and requires IκB kinase (IKK)-β. Other elements of the nuclear factor κB/IκB cascade (ie, IKK-α,-β,-γ/NEMO and CARMA/MALT1/Bcl10 complex) are present in anucleate platelets and IκB is phosphorylated upon activation, suggesting that this pathway is active in platelets and implying a nongenomic role for IKK. Inhibition of IKK-β, either pharmacologically (with BMS-345541, BAY11-7082, or TPCA-1) or by genetic manipulation (platelet factor 4 Cre:IKK-β(flox/flox)), blocked SNAP-23 phosphorylation, platelet secretion, and SNARE complex formation; but, had no effect on platelet morphology or other metrics of platelet activation. Consistently, SNAP-23 phosphorylation enhanced membrane fusion of SNARE-containing proteoliposomes. In vivo studies with IKK inhibitors or platelet-specific IKK-β knockout mice showed that blocking IKK-β activity significantly prolonged tail bleeding times, suggesting that currently available IKK inhibitors may affect hemostasis.

  6. Morphological study on the olfactory systems of the snapping turtle, Chelydra serpentina.

    PubMed

    Nakamuta, Nobuaki; Nakamuta, Shoko; Kato, Hideaki; Yamamoto, Yoshio

    2016-06-01

    In this study, the olfactory system of a semi-aquatic turtle, the snapping turtle, has been morphologically investigated by electron microscopy, immunohistochemistry, and lectin histochemistry. The nasal cavity of snapping turtle was divided into the upper and lower chambers, lined by the sensory epithelium containing ciliated and non-ciliated olfactory receptor neurons, respectively. Each neuron expressed both Gαolf, the α-subunit of G-proteins coupling to the odorant receptors, and Gαo, the α-subunit of G-proteins coupling to the type 2 vomeronasal receptors. The axons originating from the upper chamber epithelium projected to the ventral part of the olfactory bulb, while those from the lower chamber epithelium to the dorsal part of the olfactory bulb. Despite the identical expression of G-protein α-subunits in the olfactory receptor neurons, these two projections were clearly distinguished from each other by the differential expression of glycoconjugates. In conclusion, these data indicate the presence of two types of olfactory systems in the snapping turtle. Topographic arrangement of the upper and lower chambers and lack of the associated glands in the lower chamber epithelium suggest their possible involvement in the detection of odorants: upper chamber epithelium in the air and the lower chamber epithelium in the water.

  7. The Structural and Functional Implications of Linked SNARE Motifs in SNAP25

    PubMed Central

    Wang, Li; Bittner, Mary A.; Axelrod, Daniel

    2008-01-01

    We investigated the functional and structural implications of SNAP25 having two SNARE motifs (SN1 and SN2). A membrane-bound, intramolecular FRET probe was constructed to report on the folding of N-terminal SN1 and C-terminal SN2 in living cells. Membrane-bound constructs containing either or both SNARE motifs were also singly labeled with donor or acceptor fluorophores. Interaction of probes with other SNAREs was monitored by the formation of SDS-resistant complexes and by changes in FRET measured in vitro using spectroscopy and in the plasma membrane of living cells using TIRF microscopy. The probes formed the predicted SDS-resistant SNARE complexes. FRET measurements revealed that syntaxin induced a close association of the N-termini of SN1 and SN2. This association required that the SNARE motifs reside in the same molecule. Unexpectedly, the syntaxin-induced FRET was prevented by VAMP. Both full-length SNAP25 constructs and the combination of its separated, membrane-bound constituent chains supported secretion in permeabilized chromaffin cells that had been allowed to rundown. However, only full-length SNAP25 constructs enabled robust secretion from intact cells or permeabilized cells before rundown. The experiments suggest that the bidentate structure permits specific conformations in complexes with syntaxin and VAMP and facilitates the function of SN1 and SN2 in exocytosis. PMID:18596234

  8. Presence of SNAP-23 and syntaxin 4 in mouse and hamster peritoneal mast cells.

    PubMed

    Salinas, Eva; Rodríguez, Gonzalo; Quintanar, J Luis

    2007-01-01

    Mast cells (MCs) play a crucial role in inflammatory reactions. Their presence and number in the peritoneal cavity is important to overcome and enhance resistance to peritoneal infection. When MCs are activated they release a variety of biological mediators from their granules, such as histamine, that contribute to the appropriate and rapid local immune response. Granular content is released using a process of compound exocytosis, also termed degranulation. SNAP-23 and syntaxin 4 are plasma membrane proteins involved in degranulation of rat MCs. Their presence, however, has not been studied in MCs of other rodent species. The aim of the present study was to investigate using immunocytochemistry whether SNAP-23 and syntaxin 4 are present in peritoneal MCs of the mouse and hamster. In addition, the diameter, percentage and histamine content of these cells were also analyzed. Our results demonstrate that SNAP-23 and syntaxin 4 are present in the mouse and hamster peritoneal MCs, suggesting that proteins involved in the secretory process in MCs are conserved among species. Likewise, we conclude that peritoneal MCs of mouse and hamster are heterogeneous in size, percentage and histamine content.

  9. Development of NIR detectors and science driven requirements forSNAP

    SciTech Connect

    Brown, M.G.; Bebek, C.; Bernstein, G.; Bonissent, A.; Carithers,B.; Cole, D.; Figer, D.; Gerdes, D.; Gladney, L.; Lorenzon, W.; Kim, A.; Kushner, G.; Kuznetsova, N.; Linder, E.; McKee, S.; Miquel, R.; Mostek,N.; Mufson, S.; Schubnell, M.; Seshadri, S.; Shukla, H.; Smith, R.; Stebbins, A.; Stoughton, C.; Tarle, G.

    2006-05-23

    Precision near infrared (NIR) measurements are essential for the next generation of ground and space based instruments. The SuperNova Acceleration Probe (SNAP) will measure thousands of type Ia supernovae upto a redshift of 1.7. The highest redshift supernovae provide the most leverage for determining cosmological parameters, in particular the dark energy equation of state and its possible time evolution. Accurate NIR observations are needed to utilize the full potential of the highest redshift supernovae. Technological improvements in NIR detector fabrication have lead to high quantum efficiency, low noise detectors using a HgCdTe diode with a band-gap that is tuned to cutoff at 1:7 1m. The effects of detector quantum efficiency, read noise, and dark current on lightcurve signal to noise, lightcurve parameter errors, and distance modulus ?ts are simulated in the SNAP sim framework. Results show that improving quantum efficiency leads to the largest gains in photometric accuracy for type Ia supernovae. High quantum efficiency in the NIR reduces statistical errors and helps control systematic uncertainties at the levels necessary to achieve the primary SNAP science goals.

  10. [SNAP-25 and DTNBP1 as candidate genes for cognitive reserve in schizophrenia].

    PubMed

    Afimova, M V; Golimbet, V E; Monakhov, M V; Abramova, L I; Aksenova, E V; Kaleda, V G; Velikaia, N V

    2013-01-01

    Cognitive reserve (CR) postulates that individual differences in the cognitive processes or neural networks underlying task performance allow some people to cope better than others with brain damage. An aim of the study was to search for candidate genes for CR in schizophrenia. We propose that higher frequencies of low risk alleles is observed in healthy relatives of schizophrenic patients compared to patients and controls and in patients without neurocognitive deficit and with less severity of the disease compared to other patients and controls. Besides, frequencies of these alleles in patients should be similar to those in general population. Authors studied SNAP-25 and DTNBP1 genes. The polymorphism T1065G of SNAP-25 was genotyped in 278 patients with schizophrenia, 126 their relatives and 207 controls and the polymorphism P1763 of DTNBP1 was genotyped in 202 patients, 229 relatives and 262 controls. There was a trend towards the increase in the frequency of an G allele of SNAP-25 in siblings of patients. The frequency of this allele was higher in patients without neurocognitive deficit compared to patients with cognitive deficit (p=0.003) and controls (p=0.002). The allele was associated with index of cognitive functioning in patients (p=0.012) and controls (p=0.006) and with the severity of negative symptoms in patients (p=0.023). At the same time, the polymorphism T1065G was not associated with schizophrenia. Therefore, an allele G may be considered as a marker for higher CR.

  11. Support for Policies to Improve the Nutritional Impact of the Supplemental Nutrition Assistance Program in California.

    PubMed

    Leung, Cindy W; Ryan-Ibarra, Suzanne; Linares, Amanda; Induni, Marta; Sugerman, Sharon; Long, Michael W; Rimm, Eric B; Willett, Walter C

    2015-08-01

    The Supplemental Nutrition Assistance Program (SNAP) provides a vital buffer against hunger and poverty for 47.6 million Americans. Using 2013 California Dietary Practices Survey data, we assessed support for policies to strengthen the nutritional influence of SNAP. Among SNAP participants, support ranged from 74% to 93% for providing monetary incentives for fruits and vegetables, restricting purchases of sugary beverages, and providing more total benefits. Nonparticipants expressed similar levels of support. These approaches may alleviate the burden of diet-related disease in low-income populations.

  12. Implications of the Supplemental Nutrition Assistance Program Tax Exemption on Sugar-Sweetened Beverage Taxes.

    PubMed

    Pomeranz, Jennifer L

    2015-11-01

    US state and local governments are debating sugar-sweetened beverage excise taxes to support public health. A related issue is whether such taxes would apply to beverage purchases made by Supplemental Nutrition Assistance Program (SNAP) participants. Federal law proscribes states from collecting excise taxes on SNAP purchases, but the law is confined to taxes at the point of sale. I provide legal analysis and recommendations for policymakers to enact taxes that are not subject to the SNAP tax exemption to potentially deter consumption by all consumers.

  13. Maternal Rest/Nrsf Regulates Zebrafish Behavior through snap25a/b

    PubMed Central

    Moravec, Cara E.; Samuel, John; Weng, Wei; Wood, Ian C.

    2016-01-01

    During embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs throughout its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural-specific genes during early development. Here we show that in zebrafish, maternally supplied rest regulates expression of target genes during larval development and has lifelong impacts on behavior. Larvae deprived of maternal rest are hyperactive and show atypical spatial preferences. Adult male fish deprived of maternal rest present with atypical spatial preferences in a novel environment assay. Transcriptome sequencing revealed 158 genes that are repressed by maternal rest in blastula stage embryos. Furthermore, we found that maternal rest is required for target gene repression until at least 6 dpf. Importantly, disruption of the RE1 sites in either snap25a or snap25b resulted in behaviors that recapitulate the hyperactivity phenotype caused by absence of maternal rest. Both maternal rest mutants and snap25a RE1 site mutants have altered primary motor neuron architecture that may account for the enhanced locomotor activity. These results demonstrate that maternal rest represses snap25a/b to modulate larval behavior and that early Rest activity has lifelong behavioral impacts. SIGNIFICANCE STATEMENT Maternal factors deposited in the oocyte have well-established roles during embryonic development. We show that, in zebrafish, maternal rest (RE1-silencing transcription factor) regulates expression of target genes during larval development and has lifelong impacts on behavior. The Rest transcriptional repressor interacts with chromatin-modifying complexes to limit transcription of neural

  14. Review of Poly (ADP-ribose) Polymerase (PARP) Mechanisms of Action and Rationale for Targeting in Cancer and Other Diseases

    PubMed Central

    Morales, Julio C.; Li, Longshan; Fattah, Farjana J.; Dong, Ying; Bey, Erik A.; Patel, Malina; Gao, Jinming; Boothman, David A.

    2016-01-01

    Poly (ADP-ribose) polymerases (PARPs) are a family of related enzymes that share the ability to catalyze the transfer of ADP-ribose to target proteins. PARPs play an important role in various cellular processes, including modulation of chromatin structure, transcription, replication, recombination, and DNA repair. The role of PARP proteins in DNA repair is of particular interest, in view of the finding that certain tumors defective in homologous recombination mechanisms, may rely on PARP-mediated DNA repair for survival, and are sensitive to its inhibition. PARP inhibitors may also increase tumor sensitivity to DNA-damaging agents. Clinical trials of PARP inhibitors are investigating the utility of these approaches in cancer. The hyperactivation of PARP has also been shown to result in a specific programmed cell death pathway involving NAD+/ATP depletion, mu-calpain activation, loss of mitochondrial membrane potential, and the release of apoptosis inducing factor. Hyperactivation of the PARP pathway may be exploited to selectively kill cancer cells. Other PARP forms, including tankyrase 1 (PARP 5a), which plays an important role in enhancing telomere elongation by telomerase, have been found to be potential targets in cancer therapy. The PARP pathway and its inhibition thus offers a number of opportunities for therapeutic intervention in both cancer and other disease states. PMID:24579667

  15. Poly(ADP-ribose): Structure, Physicochemical Properties and Quantification In Vivo, with Special Reference to Poly(ADP-ribose) Binding Protein Modules.

    PubMed

    Miwa, Masanao; Ida, Chieri; Yamashita, Sachiko; Tanaka, Masakazu; Fujisawa, Junichi

    2016-01-01

    PolyADP-ribosylation is a unique posttranslational modification of proteins, involved in various cellular functions including stability of chromatin. PolyADP-ribosylation modifies acceptor proteins with a large negatively charged poly(ADP-ribose) (PAR) to greatly change the structure and function of the acceptor proteins. In addition various specific motifs of proteins were recently found to interact non-covalently with PAR thereby changing the spaciotemporal activity of protein-protein interaction in cells. However, the structure of PAR to which specific protein motifs should bind is not fully characterized. The present work will review the structure, physicochemical properties and quantification of PAR in vivo, with special reference to PAR binding protein modules.

  16. Oscillation of ADP-ribosyl cyclase activity during the cell cycle and function of cyclic ADP-ribose in a unicellular organism, Euglena gracilis.

    PubMed

    Masuda, W; Takenaka, S; Inageda, K; Nishina, H; Takahashi, K; Katada, T; Tsuyama, S; Inui, H; Miyatake, K; Nakano, Y

    1997-03-17

    In Euglena gracilis, the activity of ADP-ribosyl cyclase, which produces cyclic ADP-ribose, oscillated during the cell cycle in a synchronous culture induced by a light-dark cycle, and a marked increase in the activity was observed in the G2 phase. Similarly, the ADP-ribosyl cyclase activity rose extremely immediately before cell division started, when synchronous cell division was induced by adding cobalamin (which is an essential growth factor and participates in DNA synthesis in this organism) to its deficient culture. Further, cADPR in these cells showed a maximum level immediately before cell division started. A dose-dependent Ca2+ release was observed when microsomes were incubated with cADPR.

  17. Bradykinin activates ADP-ribosyl cyclase in neuroblastoma cells: intracellular concentration decrease in NAD and increase in cyclic ADP-ribose.

    PubMed

    Higashida, Haruhiro; Salmina, Alla; Hashii, Minako; Yokoyama, Shigeru; Zhang, Jia-Sheng; Noda, Mami; Zhong, Zen-Guo; Jin, Duo

    2006-09-04

    ADP-ribosyl cyclase activity in the crude membrane fraction of neuroblastomaxglioma NGPM1-27 hybrid cells was measured by monitoring [(3)H] cyclic ADP-ribose (cADPR) formation from [(3)H] NAD(+). Bradykinin (BK) at 100nM increased ADP-ribosyl cyclase activity by about 2.5-fold. Application of 300nM BK to living NGPM1-27 cells decreased NAD(+) to 78% of the prestimulation level at 30s. In contrast, intracellular cADPR concentrations were increased by 2-3-fold during the period from 30 to 120s after the same treatment. Our results suggest that cADPR is one of the second messengers downstream of B(2) BK receptors.

  18. Dynamics of nonlinear snap--through chains with application to energy harvesting and wave propagation

    NASA Astrophysics Data System (ADS)

    Panigrahi, Smruti Ranjan

    There is much current research interest in nonlinear structures, smart materials, and metamaterials, that incorporate bistable, or snap-through, structural elements. Various applications include energy harvesting, energy dissipation, vibration absorption, vibration isolation, targeted energy transfer, bandgap design and metamaterials. In this dissertation, we explore snap-through structures with nonlinearity and negative linear stiffness. We start with a study of a simple Duffing oscillator with snap-through orbits around the separatrix. Multi-degree-of-freedom snap-through structures are known to convert the low-frequency inputs into high-frequency oscillations, and are called twinkling oscillators. A generalized two-degree-of-freedom (2-DOF) snap-through oscillator is shown to have rich bifurcation structure. The steady-state bifurcation analysis uncovered two unique bifurcations "star" and "eclipse" bifurcations, named due to their structures. The 2-DOF twinkler exhibits transient chaos in the snap-through regime. A fractal basin boundary study provides insight into the regions in the parameter space where the total energy level is predictable in an unsymmetric twinkler. Due to its capacity to convert low frequency to high-frequency oscillations, the snap-through oscillators can be used to harvest energy from low-frequency vibration sources. This idea has led us to explore the energy harvesting capacity of twinkling oscillators. Using magnets and linear springs we built (in collaboration with researchers at Duke university) novel experimental twinkling oscillators (SDOF and 2-DOF) for energy harvesting. When the magnets exhibit high-frequency oscillations through the inducting coil, a current is generated in the coil. This experiment shows promising results both for the SDOF and the 2-DOF twinkling energy generators by validating the frequency up-conversion and generating power from the low-frequency input oscillations. The experimental twinkling oscillator

  19. Unidirectional growth of pure and L-lysine added ADP crystals from aqueous solution

    NASA Astrophysics Data System (ADS)

    Salarian, Samaneh; Dizaji, Hamid Rezagholipour

    2014-01-01

    Pure and L-lysine added ammonium dihydrogen phosphate (ADP) crystals were grown in the <001> direction by Sankaranarayanan-Ramasamy (S-R) method. The grown crystals were characterized by X-Ray diffractometry (XRD), UV-Vis spectroscopy, Fourier Transform Infrared (FT-IR) and Vicker's Microhardness analysis. XRD spectrum of each of the grown crystals proved its crystallinity. The crystals showed good transparency in the entire visible region. FT-IR spectra of the specimens revealed the presence of functional groups in them. The hardness of the pure and L-lysine added ADP crystals were measured and that of the added one was found higher. Meanwhile, it was found that the ADP crystals (pure and L-lysine added) grown by S-R method had higher hardness compared to ADP crystal grown by conventional method.

  20. An affinity matrix for the purification of poly(ADP-ribose) glycohydrolase.

    PubMed Central

    Thomassin, H; Jacobson, M K; Guay, J; Verreault, A; Aboul-ela, N; Menard, L; Poirier, G G

    1990-01-01

    The preparation of quantities of poly(ADP-ribose) glycohydrolase sufficient for detailed structural and enzymatic characterizations has been difficult due to the very low tissue content of the enzyme and its lability in late stages of purification. To date, the only purification of this enzyme to apparent homogeneity has involved a procedure requiring 6 column chromatographic steps. Described here is the preparation of an affinity matrix which consists of ADP-ribose polymers bound to dihydroxyboronyl sepharose. An application is described for the purification of poly(ADP-ribose) glycohydrolase from calf thymus in which a single rapid affinity step was used to replace 3 column chromatographic steps yielding enzyme of greater than 90% purity with a 3 fold increase in yield. This matrix should also prove useful for other studies of ADP-ribose polymer metabolism and related clinical conditions. Images PMID:2395636

  1. ADP-ribosylation of membrane components by pertussis and cholera toxin

    SciTech Connect

    Ribeiro-Neto, F.A.P.; Mattera, F.; Hildebrandt, J.D.; Codina, J.; Field, J.B.; Birnbaumer, L.; Sekura, R.D.

    1985-01-01

    Pertussis and cholera toxins are important tools to investigate functional and structural aspects of the stimulatory (N/sub s/) and inhibitory (N/sub i/) regulatory components of adenylyl cyclase. Cholera toxin acts on N/sub s/ by ADP-ribosylating its ..cap alpha../sub s/ subunit; pertussis toxin acts on N/sub i/ by ADP-ribosylating its ..cap alpha..; subunit. By using (/sup 32/P)NAD/sup +/ and determining the transfer of its (/sup 32/P)ADP-ribose moiety to membrane components, it is possible to obtain information on N/sub s/ and N/sub i/. A set of protocols is presented that can be used to study simultaneously and comparatively the susceptibility of N/sub s/ and N/sub i/ to be ADP-ribosylated by cholera and pertussis toxin.

  2. Poly(ADP-ribose)polymerase inhibition decreases angiogenesis

    SciTech Connect

    Rajesh, Mohanraj; Mukhopadhyay, Partha; Godlewski, Grzegorz; Batkai, Sandor; Hasko, Gyoergy; Liaudet, Lucas; Pacher, Pal . E-mail: pacher@mail.nih.gov

    2006-12-01

    Inhibitors of poly(ADP-ribose)polymerase (PARP), a nuclear enzyme involved in regulating cell death and cellular responses to DNA repair, show considerable promise in the treatment of cancer both in monotherapy as well as in combination with chemotherapeutic agents and radiation. We have recently demonstrated that PARP inhibition with 3-aminobenzamide or PJ-34 reduced vascular endothelial growth factor (VEGF)-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Here, we show dose-dependent reduction of VEGF- and basic fibroblast growth factor (bFGF)-induced proliferation, migration, and tube formation of HUVECs in vitro by two potent PARP inhibitors 5-aminoisoquinolinone-hydrochloride (5-AIQ) and 1,5-isoquinolinediol (IQD). Moreover, PARP inhibitors prevented the sprouting of rat aortic ring explants in an ex vivo assay of angiogenesis. These results establish the novel concept that PARP inhibitors have antiangiogenic effects, which may have tremendous clinical implications for the treatment of various cancers, tumor metastases, and certain retinopathies.

  3. Serine ADP-Ribosylation Depends on HPF1.

    PubMed

    Bonfiglio, Juan José; Fontana, Pietro; Zhang, Qi; Colby, Thomas; Gibbs-Seymour, Ian; Atanassov, Ilian; Bartlett, Edward; Zaja, Roko; Ahel, Ivan; Matic, Ivan

    2017-03-02

    ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. However, the biochemical basis underlying this serine modification remained unknown. Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. Quantitative proteomics revealed that serine ADPr does not occur in cells lacking HPF1. Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability.

  4. Multiple forms of ADP-glucose pyrophosphorylase from tomato fruit

    NASA Technical Reports Server (NTRS)

    Chen, B. Y.; Janes, H. W.

    1997-01-01

    ADP-glucose pyrophosphorylase (AGP) was purified from tomato (Lycopersicon esculentum Mill.) fruit to apparent homogeneity. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis the enzyme migrated as two close bands with molecular weights of 50,000 and 51,000. Two-dimensional polyacrylamide gel electrophoresis analysis of the purified enzyme, however, revealed at least five major protein spots that could be distinguished by their slight differences in net charge and molecular weight. Whereas all of the spots were recognized by the antiserum raised against tomato fruit AGP holoenzyme, only three of them reacted strongly with antiserum raised against the potato tuber AGP large subunit, and the other two spots (with lower molecular weights) reacted specifically with antisera raised against spinach leaf AGP holoenzyme and the potato tuber AGP small subunit. The results suggest the existence of at least three isoforms of the AGP large subunit and two isoforms of the small subunit in tomato fruit in vivo. The native molecular mass of the enzyme determined by gel filtration was 220 +/- 10 kD, indicating a tetrameric structure for AGP from tomato fruit. The purified enzyme is very sensitive to 3-phosphoglycerate/inorganic phosphate regulation.

  5. Pseudomonas aeruginosa Exopolyphosphatase Is Also a Polyphosphate: ADP Phosphotransferase.

    PubMed

    Beassoni, Paola R; Gallarato, Lucas A; Boetsch, Cristhian; Garrido, Mónica N; Lisa, Angela T

    2015-01-01

    Pseudomonas aeruginosa exopolyphosphatase (paPpx; EC 3.6.1.11) catalyzes the hydrolysis of polyphosphates (polyP), producing polyPn-1 plus inorganic phosphate (Pi). In a recent work we have shown that paPpx is involved in the pathogenesis of P. aeruginosa. The present study was aimed at performing the biochemical characterization of this enzyme. We found some properties that were already described for E. coli Ppx (ecPpx) but we also discovered new and original characteristics of paPpx: (i) the peptide that connects subdomains II and III is essential for enzyme activity; (ii) NH4 (+) is an activator of the enzyme and may function at concentrations lower than those of K(+); (iii) Zn(2+) is also an activator of paPpx and may substitute Mg(2+) in the catalytic site; and (iv) paPpx also has phosphotransferase activity, dependent on Mg(2+) and capable of producing ATP regardless of the presence or absence of K(+) or NH4 (+) ions. In addition, we detected that the active site responsible for the phosphatase activity is also responsible for the phosphotransferase activity. Through the combination of molecular modeling and docking techniques, we propose a model of the paPpx N-terminal domain in complex with a polyP chain of 7 residues long and a molecule of ADP to explain the phosphotransferase activity.

  6. Distribution of protein poly(ADP-ribosyl)ation systems across all domains of life

    PubMed Central

    Perina, Dragutin; Mikoč, Andreja; Ahel, Josip; Ćetković, Helena; Žaja, Roko; Ahel, Ivan

    2014-01-01

    Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved in regulation of many cellular pathways. Poly(ADP-ribose) (PAR) consists of chains of repeating ADP-ribose nucleotide units and is synthesized by the family of enzymes called poly(ADP-ribose) polymerases (PARPs). This modification can be removed by the hydrolytic action of poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3 (ARH3). Hydrolytic activity of macrodomain proteins (MacroD1, MacroD2 and TARG1) is responsible for the removal of terminal ADP-ribose unit and for complete reversion of protein ADP-ribosylation. Poly(ADP-ribosyl)ation is widely utilized in eukaryotes and PARPs are present in representatives from all six major eukaryotic supergroups, with only a small number of eukaryotic species that do not possess PARP genes. The last common ancestor of all eukaryotes possessed at least five types of PARP proteins that include both mono and poly(ADP-ribosyl) transferases. Distribution of PARGs strictly follows the distribution of PARP proteins in eukaryotic species. At least one of the macrodomain proteins that hydrolyse terminal ADP-ribose is also always present. Therefore, we can presume that the last common ancestor of all eukaryotes possessed a fully functional and reversible PAR metabolism and that PAR signalling provided the conditions essential for survival of the ancestral eukaryote in its ancient environment. PARP proteins are far less prevalent in bacteria and were probably gained through horizontal gene transfer. Only eleven bacterial species possess all proteins essential for a functional PAR metabolism, although it is not known whether PAR metabolism is truly functional in bacteria. Several dsDNA viruses also possess PARP homologues, while no PARP proteins have been identified in any archaeal genome. Our analysis of the distribution of enzymes involved in PAR metabolism provides insight into the evolution of these important signalling systems, as well as

  7. Loss of a membrane trafficking protein αSNAP induces non-canonical autophagy in human epithelia

    PubMed Central

    Naydenov, Nayden G.; Harris, Gianni; Morales, Victor; Ivanov, Andrei I.

    2012-01-01

    Autophagy is a catabolic process that sequesters intracellular proteins and organelles within membrane vesicles called autophagosomes with their subsequent delivery to lyzosomes for degradation. This process involves multiple fusions of autophagosomal membranes with different vesicular compartments; however, the role of vesicle fusion in autophagosomal biogenesis remains poorly understood. This study addresses the role of a key vesicle fusion regulator, soluble N-ethylmaleimide-sensitive factor attachment protein α (αSNAP), in autophagy. Small interfering RNA-mediated downregulation of αSNAP expression in cultured epithelial cells stimulated the autophagic flux, which was manifested by increased conjugation of microtubule-associated protein light chain 3 (LC3-II) and accumulation of LC3-positive autophagosomes. This enhanced autophagy developed via a non-canonical mechanism that did not require beclin1-p150-dependent nucleation, but involved Atg5 and Atg7-mediated elongation of autophagosomal membranes. Induction of autophagy in αSNAP-depleted cells was accompanied by decreased mTOR signaling but appeared to be independent of αSNAP-binding partners, N-ethylmaleimide-sensitive factor and BNIP1. Loss of αSNAP caused fragmentation of the Golgi and downregulation of the Golgi-specific GTP exchange factors, GBF1, BIG1 and BIG2. Pharmacological disruption of the Golgi and genetic inhibition of GBF1 recreated the effects of αSNAP depletion on the autophagic flux. Our study revealed a novel role for αSNAP as a negative regulator of autophagy that acts by enhancing mTOR signaling and regulating the integrity of the Golgi complex. PMID:23187805

  8. Improved Hemocompatibility of Multilumen Catheters via Nitric Oxide (NO) Release from S-Nitroso-N-acetylpenicillamine (SNAP) Composite Filled Lumen.

    PubMed

    Brisbois, Elizabeth J; Kim, Maria; Wang, Xuewei; Mohammed, Azmath; Major, Terry C; Wu, Jianfeng; Brownstein, Jessica; Xi, Chuanwu; Handa, Hitesh; Bartlett, Robert H; Meyerhoff, Mark E

    2016-11-02

    Blood-contacting devices, such as intravascular catheters, suffer from challenges related to thrombus formation and infection. Nitric oxide (NO) is an endogenous antiplatelet and antimicrobial agent. Exogenous release of NO from various polymer matrices has been shown to reduce thrombosis and infection of/on implantable medical devices. However, the clinical applications of such materials have been hindered due to factors such as NO donor leaching and thermal instability. In this study, a novel approach is demonstrated in which one lumen of commercial dual lumen catheters is dedicated to the NO release chemistry, allowing the other lumen to be available for clinical vascular access. A composite consisting of poly(ethylene glycol) (PEG) and S-nitroso-N-acetylpenicillamine (SNAP) is used to fill the NO-releasing lumen of commercial 7 French silicone catheters. Physiological levels of NO are released from the SNAP-PEG catheters for up to 14 d, as measured by chemiluminescence NO analyzer (in PBS buffer at 37 °C). PEG facilitates the NO release from SNAP within the lumen by increasing the water absorption and slowly dissolving the solid SNAP-PEG composite. In a CDC biofilm bioreactor, the SNAP-PEG catheters are found to reduce >97% bacterial adhesion as compared to the PEG controls for single bacterial species including E. coli and S. aureus. SNAP-PEG and PEG control catheters were implanted in rabbit veins for 7 h (single lumen) and 11 d (dual lumen) to evaluate their hemocompatibility properties. Significant reductions in thrombus formation on the SNAP-PEG vs PEG controls were observed, with ca. 85% reduction for 7 h single lumen catheters and ca. 55% reduction for 11 d dual lumen catheters.

  9. ADP stimulates the respiratory burst without activation of ERK and AKT in rat alveolar macrophages.

    PubMed

    Gozal, E; Forman, H J; Torres, M

    2001-09-01

    Alveolar macrophages (AM) are the first line of defense against infection in the lungs. We previously showed that the production of superoxide and hydrogen peroxide, i.e., the respiratory burst, is stimulated by adenine nucleotides (ADP > ATP) in rat AM through signaling pathways involving calcium and protein kinase C. Here, we further show that ADP induces a rapid increase in the tyrosine phosphorylation of several proteins that was reduced by the tyrosine kinase inhibitor genistein, which also inhibited the respiratory burst. Interestingly, ADP did not trigger the activation of the mitogen-activated protein kinases ERK1 and ERK2, or that of protein kinase B/AKT, a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway. This is in contrast to another stimulus of the respiratory burst, zymosan-activated serum (ZAS), which activates both the ERK and PI3K pathways. Thus, this study demonstrates that the receptor for ADP in rat AM is not coupled to the ERK and AKT pathways and, that neither the ERK pathway nor AKT is essential to induce the activation of the NAPDH oxidase by ADP in rat AM while tyrosine kinases appeared to be required. The rate and amount of hydrogen peroxide released by the ADP-stimulated respiratory burst was similar to that produced by ZAS stimulation. The absence of ERK activation after ADP stimulation therefore suggests that hydrogen peroxide is not sufficient to activate the ERK pathway in rat AM. Nonetheless, as hydrogen peroxide was necessary for ERK activation by ZAS, this indicates that, in contrast to ADP, ZAS stimulates a pathway that is targeted by hydrogen peroxide and leads to ERK activation.

  10. Quantitative site-specific ADP-ribosylation profiling of DNA-dependent PARPs.

    PubMed

    Gagné, Jean-Philippe; Ethier, Chantal; Defoy, Daniel; Bourassa, Sylvie; Langelier, Marie-France; Riccio, Amanda A; Pascal, John M; Moon, Kyung-Mee; Foster, Leonard J; Ning, Zhibin; Figeys, Daniel; Droit, Arnaud; Poirier, Guy G

    2015-06-01

    An important feature of poly(ADP-ribose) polymerases (PARPs) is their ability to readily undergo automodification upon activation. Although a growing number of substrates were found to be poly(ADP-ribosyl)ated, including histones and several DNA damage response factors, PARPs themselves are still considered as the main acceptors of poly(ADP-ribose). By monitoring spectral counts of specific hydroxamic acid signatures generated after the conversion of the ADP-ribose modification onto peptides by hydroxylamine hydrolysis, we undertook a thorough mass spectrometry mapping of the glutamate and aspartate ADP-ribosylation sites onto automodified PARP-1, PARP-2 and PARP-3. Thousands of hydroxamic acid-conjugated peptides were identified with high confidence and ranked based on their spectral count. This semi-quantitative approach allowed us to locate the preferentially targeted residues in DNA-dependent PARPs. In contrast to what has been reported in the literature, automodification of PARP-1 is not predominantly targeted towards its BRCT domain. Our results show that interdomain linker regions that connect the BRCT to the WGR module and the WGR to the PRD domain undergo prominent ADP-ribosylation during PARP-1 automodification. We also found that PARP-1 efficiently automodifies the D-loop structure within its own catalytic fold. Interestingly, additional major ADP-ribosylation sites were identified in functional domains of PARP-1, including all three zinc fingers. Similar to PARP-1, specific residues located within the catalytic sites of PARP-2 and PARP-3 are major targets of automodification following their DNA-dependent activation. Together our results suggest that poly(ADP-ribosyl)ation hot spots make a dominant contribution to the overall automodification process.

  11. Poly(ADP-ribose) polymerases covalently modify strand break termini in DNA fragments in vitro

    PubMed Central

    Talhaoui, Ibtissam; Lebedeva, Natalia A.; Zarkovic, Gabriella; Saint-Pierre, Christine; Kutuzov, Mikhail M.; Sukhanova, Maria V.; Matkarimov, Bakhyt T.; Gasparutto, Didier; Saparbaev, Murat K.; Lavrik, Olga I.; Ishchenko, Alexander A.

    2016-01-01

    Poly(ADP-ribose) polymerases (PARPs/ARTDs) use nicotinamide adenine dinucleotide (NAD+) to catalyse the synthesis of a long branched poly(ADP-ribose) polymer (PAR) attached to the acceptor amino acid residues of nuclear proteins. PARPs act on single- and double-stranded DNA breaks by recruiting DNA repair factors. Here, in in vitro biochemical experiments, we found that the mammalian PARP1 and PARP2 proteins can directly ADP-ribosylate the termini of DNA oligonucleotides. PARP1 preferentially catalysed covalent attachment of ADP-ribose units to the ends of recessed DNA duplexes containing 3′-cordycepin, 5′- and 3′-phosphate and also to 5′-phosphate of a single-stranded oligonucleotide. PARP2 preferentially ADP-ribosylated the nicked/gapped DNA duplexes containing 5′-phosphate at the double-stranded termini. PAR glycohydrolase (PARG) restored native DNA structure by hydrolysing PAR-DNA adducts generated by PARP1 and PARP2. Biochemical and mass spectrometry analyses of the adducts suggested that PARPs utilise DNA termini as an alternative to 2′-hydroxyl of ADP-ribose and protein acceptor residues to catalyse PAR chain initiation either via the 2′,1″-O-glycosidic ribose-ribose bond or via phosphodiester bond formation between C1′ of ADP-ribose and the phosphate of a terminal deoxyribonucleotide. This new type of post-replicative modification of DNA provides novel insights into the molecular mechanisms underlying biological phenomena of ADP-ribosylation mediated by PARPs. PMID:27471034

  12. Poly (ADP-ribose) Polymerase 1 Protein Expression in Normal and Neoplastic Prostatic Tissue

    PubMed Central

    Salemi, M.; Galia, A.; Fraggetta, F.; La Corte, C.; Pepe, P.; La Vignera, S.; Improta, G.; Bosco, P.; Calogero, A.E.

    2013-01-01

    A genetic background has been implicated in the development of prostate cancer. Protein microarrays have enabled the identification of proteins, some of which associated with apoptosis, that may play a role in the development of such a tumor. Inhibition of apoptosis is a co-factor that contributes to the onset and progression of prostate cancer, though the molecular mechanisms are not entirely understood. Poly (ADP-ribose) polymerase 1 (PARP-1) gene is required for translocation of the apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Hence, it is involved in programmed cell death. Different PARP-1 gene expression has been observed in various tumors such as glioblastoma, lung, ovarian, endometrial, and skin cancers. We evaluated the expression of PARP-1 protein in prostatic cancer and normal prostate tissues by immunohistochemistry in 40 men with prostate cancer and in 37 normal men. Positive nuclear PARP-1 staining was found in all samples (normal prostate and prostate cancer tissues). No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted significantly higher in patients with prostate carcinoma compared with controls (P<0.001). PARP-1 over-expression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor similarly to what reported in other cancers. PMID:23807292

  13. Pierisins and CARP-1: ADP-ribosylation of DNA by ARTCs in butterflies and shellfish.

    PubMed

    Nakano, Tsuyoshi; Takahashi-Nakaguchi, Azusa; Yamamoto, Masafumi; Watanabe, Masahiko

    2015-01-01

    The cabbage butterfly, Pieris rapae, and related species possess a previously unknown ADP-ribosylating toxin, guanine specific ADP-ribosyltransferase. This enzyme toxin, known as pierisin, consists of enzymatic N-terminal domain and receptor-binding C-terminal domain, or typical AB-toxin structure. Pierisin efficiently transfers an ADP-ribosyl moiety to the N(2) position of the guanine base of dsDNA. Receptors for pierisin are suggested to be the neutral glycosphingolipids, globotriaosylceramide (Gb3), and globotetraosylceramide (Gb4). This DNA-modifying toxin exhibits strong cytotoxicity and induces apoptosis in various human cell lines, which can be blocked by Bcl-2. Pierisin also produces detrimental effects on the eggs and larvae of the non-habitual parasitoids. In contrast, a natural parasitoid of the cabbage butterfly, Cotesia glomerata, was resistant to this toxin. The physiological role of pierisin in the butterfly is suggested to be a defense factor against parasitization by wasps. Other type of DNA ADP-ribosyltransferase is present in certain kinds of edible clams. For example, the CARP-1 protein found in Meretrix lamarckii consists of an enzymatic domain without a possible receptor-binding domain. Pierisin and CARP-1 are almost fully non-homologous at the amino acid sequence level, but other ADP-ribosyltransferases homologous to pierisin are present in different biological species such as eubacterium Streptomyces. Possible diverse physiological roles of the DNA ADP-ribosyltransferases are discussed.

  14. Regulation of NFAT by poly(ADP-ribose) polymerase activity in T cells.

    PubMed

    Valdor, Rut; Schreiber, Valérie; Saenz, Luis; Martínez, Teresa; Muñoz-Suano, Alba; Dominguez-Villar, Margarita; Ramírez, Pablo; Parrilla, Pascual; Aguado, Enrique; García-Cózar, Francisco; Yélamos, José

    2008-04-01

    The nuclear factor of activated T cells (NFAT) family of transcription factors is pivotal for T lymphocyte functionality. All relevant NFAT activation events upon T cells stimulation such as nuclear translocation, DNA binding, and transcriptional activity have been shown to be dictated by its phosphorylation state. Here, we provide evidence for a novel post-translational modification that regulates NFAT. Indeed, NFATc1 and NFATc2 are poly(ADP-ribosyl)ated by poly-ADP-ribose polymerase-1 (PARP-1). Moreover, we have also found a physical interaction between PARP-1 and both NFATc1 and NFATc2. Interestingly, PARP is activated during T cell stimulation in the absence of DNA damage, leading to ADP-ribose polymers formation and transfer to nuclear acceptor proteins. Our data suggest that poly(ADP-ribosyl)ation modulates the activation of NFAT in T cells, as PARP inhibition causes an increase in NFAT-dependent transactivation and a delay in NFAT nuclear export. Poly(ADP-ribosyl)ation will expedited NFAT export from the nucleus directly or by priming/facilitating NFAT phosphorylation. Altogether, these data point to PARP-1 and poly(ADP-ribosyl)ation as a novel regulatory mechanism of NFAT at nuclear level, suggesting a potential use of PARP as a new therapeutic target in the modulation of NFAT.

  15. A Kinetic Assay of Mitochondrial ATP-ADP Exchange Rate in Permeabilized Cells

    PubMed Central

    Kawamata, Hibiki; Starkov, Anatoly A; Manfredi, Giovanni; Chinopoulos, Christos

    2010-01-01

    We have previously described a method to measure ADP-ATP exchange rates in isolated mitochondria by recording the changes in free extramitochondrial [Mg2+] reported by a Mg2+-sensitive fluorescent indicator, exploiting the differential affinity of ADP and ATP to Mg2+. In this manuscript we describe a modification of this method suited for following ADP-ATP exchange rates in environments with competing reactions that interconvert adenine nucleotides, such as in permeabilized cells that harbor phosphorylases and kinases, ion pumps exhibiting substantial ATPase activity and myosin ATPase activity. Here we report that addition of BeF3− and Na3VO4 to media containing digitonin-permeabilized cells inhibit all ATP-ADP utilizing reactions, except the ANT-mediated mitochondrial ATP-ADP exchange. An advantage of this assay is that mitochondria that may have been also permeabilized by digitonin do not contribute to ATP consumption by the exposed F1Fo-ATPase, due to its sensitivity to BeF3− and Na3VO4. With this assay, ADP-ATP exchange rate mediated by the ANT in permeabilized cells is measured for the entire range of mitochondrial membrane potential titrated by stepwise additions of an uncoupler, and expressed as a function of citrate synthase activity per total amount of protein. PMID:20691655

  16. Protein Poly(ADP-ribosyl)ation Regulates Arabidopsis Immune Gene Expression and Defense Responses

    PubMed Central

    Feng, Baomin; Liu, Chenglong; de Oliveira, Marcos V. V.; Intorne, Aline C.; Li, Bo; Babilonia, Kevin; de Souza Filho, Gonçalo A.; Shan, Libo; He, Ping

    2015-01-01

    Perception of microbe-associated molecular patterns (MAMPs) elicits transcriptional reprogramming in hosts and activates defense to pathogen attacks. The molecular mechanisms underlying plant pattern-triggered immunity remain elusive. A genetic screen identified Arabidopsis poly(ADP-ribose) glycohydrolase 1 (atparg1) mutant with elevated immune gene expression upon multiple MAMP and pathogen treatments. Poly(ADP-ribose) glycohydrolase (PARG) is predicted to remove poly(ADP-ribose) polymers on acceptor proteins modified by poly(ADP-ribose) polymerases (PARPs) with three PARPs and two PARGs in Arabidopsis genome. AtPARP1 and AtPARP2 possess poly(ADP-ribose) polymerase activity, and the activity of AtPARP2 was enhanced by MAMP treatment. AtPARG1, but not AtPARG2, carries glycohydrolase activity in vivo and in vitro. Importantly, mutation (G450R) in atparg1 blocks its activity and the corresponding residue is highly conserved and essential for human HsPARG activity. Consistently, mutant atparp1atparp2 plants exhibited compromised immune gene activation and enhanced susceptibility to pathogen infections. Our study indicates that protein poly(ADP-ribosyl)ation plays critical roles in plant immune gene expression and defense to pathogen attacks. PMID:25569773

  17. Protein poly(ADP-ribosyl)ation regulates arabidopsis immune gene expression and defense responses.

    PubMed

    Feng, Baomin; Liu, Chenglong; de Oliveira, Marcos V V; Intorne, Aline C; Li, Bo; Babilonia, Kevin; de Souza Filho, Gonçalo A; Shan, Libo; He, Ping

    2015-01-01

    Perception of microbe-associated molecular patterns (MAMPs) elicits transcriptional reprogramming in hosts and activates defense to pathogen attacks. The molecular mechanisms underlying plant pattern-triggered immunity remain elusive. A genetic screen identified Arabidopsis poly(ADP-ribose) glycohydrolase 1 (atparg1) mutant with elevated immune gene expression upon multiple MAMP and pathogen treatments. Poly(ADP-ribose) glycohydrolase (PARG) is predicted to remove poly(ADP-ribose) polymers on acceptor proteins modified by poly(ADP-ribose) polymerases (PARPs) with three PARPs and two PARGs in Arabidopsis genome. AtPARP1 and AtPARP2 possess poly(ADP-ribose) polymerase activity, and the activity of AtPARP2 was enhanced by MAMP treatment. AtPARG1, but not AtPARG2, carries glycohydrolase activity in vivo and in vitro. Importantly, mutation (G450R) in atparg1 blocks its activity and the corresponding residue is highly conserved and essential for human HsPARG activity. Consistently, mutant atparp1atparp2 plants exhibited compromised immune gene activation and enhanced susceptibility to pathogen infections. Our study indicates that protein poly(ADP-ribosyl)ation plays critical roles in plant immune gene expression and defense to pathogen attacks.

  18. Biosynthesis Pathway of ADP-l-glycero-β-d-manno-Heptose in Escherichia coli

    PubMed Central

    Kneidinger, Bernd; Marolda, Cristina; Graninger, Michael; Zamyatina, Alla; McArthur, Fiona; Kosma, Paul; Valvano, Miguel A.; Messner, Paul

    2002-01-01

    The steps involved in the biosynthesis of the ADP-l-glycero-β-d-manno-heptose (ADP-l-β-d-heptose) precursor of the inner core lipopolysaccharide (LPS) have not been completely elucidated. In this work, we have purified the enzymes involved in catalyzing the intermediate steps leading to the synthesis of ADP-d-β-d-heptose and have biochemically characterized the reaction products by high-performance anion-exchange chromatography. We have also constructed a deletion in a novel gene, gmhB (formerly yaeD), which results in the formation of an altered LPS core. This mutation confirms that the GmhB protein is required for the formation of ADP-d-β-d-heptose. Our results demonstrate that the synthesis of ADP-d-β-d-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional d-β-d-heptose 7-phosphate kinase/d-β-d-heptose 1-phosphate adenylyltransferase), and GmhB (d,d-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate. A previously characterized epimerase, formerly named WaaD (RfaD) and now renamed HldD, completes the pathway to form the ADP-l-β-d-heptose precursor utilized in the assembly of inner core LPS. PMID:11751812

  19. A kinetic assay of mitochondrial ADP-ATP exchange rate in permeabilized cells.

    PubMed

    Kawamata, Hibiki; Starkov, Anatoly A; Manfredi, Giovanni; Chinopoulos, Christos

    2010-12-01

    We previously described a method to measure ADP-ATP exchange rates in isolated mitochondria by recording the changes in free extramitochondrial [Mg(2+)] reported by an Mg(2+)-sensitive fluorescent indicator, exploiting the differential affinity of ADP and ATP to Mg(2+). In the current article, we describe a modification of this method suited for following ADP-ATP exchange rates in environments with competing reactions that interconvert adenine nucleotides such as in permeabilized cells that harbor phosphorylases and kinases, ion pumps exhibiting substantial ATPase activity, and myosin ATPase activity. Here we report that the addition of BeF(3)(-) and sodium orthovanadate (Na(3)VO(4)) to medium containing digitonin-permeabilized cells inhibits all ADP-ATP-using reactions except the adenine nucleotide translocase (ANT)-mediated mitochondrial ADP-ATP exchange. An advantage of this assay is that mitochondria that may have been also permeabilized by digitonin do not contribute to ATP consumption by the exposed F(1)F(o)-ATPase due to its sensitivity to BeF(3)(-) and Na(3)VO(4). With this assay, ADP-ATP exchange rate mediated by the ANT in permeabilized cells is measured for the entire range of mitochondrial membrane potential titrated by stepwise additions of an uncoupler and expressed as a function of citrate synthase activity per total amount of protein.

  20. Vault-poly-ADP-ribose polymerase in the Octopus vulgaris brain: a regulatory factor of actin polymerization dynamic.

    PubMed

    De Maio, Anna; Natale, Emiliana; Rotondo, Sergio; Di Cosmo, Anna; Faraone-Mennella, Maria Rosaria

    2013-09-01

    Our previous behavioural, biochemical and immunohistochemical analyses conducted in selected regions (supra/sub oesophageal masses) of the Octopus vulgaris brain detected a cytoplasmic poly-ADP-ribose polymerase (more than 90% of total enzyme activity). The protein was identified as the vault-free form of vault-poly-ADP-ribose polymerase. The present research extends and integrates the biochemical characterization of poly-ADP-ribosylation system, namely, reaction product, i.e., poly-ADP-ribose, and acceptor proteins, in the O. vulgaris brain. Immunochemical analyses evidenced that the sole poly-ADP-ribose acceptor was the octopus cytoskeleton 50-kDa actin. It was present in both free, endogenously poly-ADP-ribosylated form (70kDa) and in complex with V-poly-ADP-ribose polymerase and poly-ADP-ribose (260kDa). The components of this complex, alkali and high salt sensitive, were purified and characterized. The kind and the length of poly-ADP-ribose corresponded to linear chains of 30-35 ADP-ribose units, in accordance with the features of the polymer synthesized by the known vault-poly-ADP-ribose polymerase. In vitro experiments showed that V-poly-ADP-ribose polymerase activity of brain cytoplasmic fraction containing endogenous actin increased upon the addition of commercial actin and was highly reduced by ATP. Anti-actin immunoblot of the mixture in the presence and absence of ATP showed that the poly-ADP-ribosylation of octopus actin is a dynamic process balanced by the ATP-dependent polymerization of the cytoskeleton protein, a fundamental mechanism for synaptic plasticity.

  1. A versatile snap chip for high-density sub-nanoliter chip-to-chip reagent transfer

    NASA Astrophysics Data System (ADS)

    Li, Huiyan; Munzar, Jeffrey D.; Ng, Andy; Juncker, David

    2015-07-01

    The coordinated delivery of minute amounts of different reagents is important for microfluidics and microarrays, but is dependent on advanced equipment such as microarrayers. Previously, we developed the snap chip for the direct transfer of reagents, thus realizing fluidic operations by only manipulating microscope slides. However, owing to the misalignment between arrays spotted on different slides, millimeter spacing was needed between spots and the array density was limited. In this work, we have developed a novel double transfer method and have transferred 625 spots cm-2, corresponding to >10000 spots for a standard microscope slide. A user-friendly snapping system was manufactured to make liquid handling straightforward. Misalignment, which for direct transfer ranged from 150-250 μm, was reduced to <40 μm for double transfer. The snap chip was used to quantify 50 proteins in 16 samples simultaneously, yielding limits of detection in the pg/mL range for 35 proteins. The versatility of the snap chip is illustrated with a 4-plex homogenous enzyme inhibition assay analyzing 128 conditions with precise timing. The versatility and high density of the snap chip with double transfer allows for the development of high throughput reagent transfer protocols compatible with a variety of applications.

  2. A versatile snap chip for high-density sub-nanoliter chip-to-chip reagent transfer

    PubMed Central

    Li, Huiyan; Munzar, Jeffrey D.; Ng, Andy; Juncker, David

    2015-01-01

    The coordinated delivery of minute amounts of different reagents is important for microfluidics and microarrays, but is dependent on advanced equipment such as microarrayers. Previously, we developed the snap chip for the direct transfer of reagents, thus realizing fluidic operations by only manipulating microscope slides. However, owing to the misalignment between arrays spotted on different slides, millimeter spacing was needed between spots and the array density was limited. In this work, we have developed a novel double transfer method and have transferred 625 spots cm−2, corresponding to >10000 spots for a standard microscope slide. A user-friendly snapping system was manufactured to make liquid handling straightforward. Misalignment, which for direct transfer ranged from 150–250 μm, was reduced to <40 μm for double transfer. The snap chip was used to quantify 50 proteins in 16 samples simultaneously, yielding limits of detection in the pg/mL range for 35 proteins. The versatility of the snap chip is illustrated with a 4-plex homogenous enzyme inhibition assay analyzing 128 conditions with precise timing. The versatility and high density of the snap chip with double transfer allows for the development of high throughput reagent transfer protocols compatible with a variety of applications. PMID:26148566

  3. Molecular and morphological characterization of a haemogregarine in the alligator snapping turtle, Macrochelys temminckii (Testudines: Chelydridae).

    PubMed

    Alhaboubi, Amer Rasool; Pollard, Dana A; Holman, Patricia J

    2017-01-01

    A severely underweight alligator snapping turtle Macrochelys temminckii Troost in Harlan, 1835, was found near Tyler, Texas, and taken to the Caldwell Zoo. Blood films were submitted to Texas A&M University, College Station, Texas, for morphological and molecular identification of haemogregarine-like inclusions in the red blood cells. Intraerythrocytic Haemogregarina sp. forms were found on microscopic examination at a parasitemia of <1 %. The morphology and morphometric data for the forms indicate similarity to Haemogregarina macrochelysi n. sp. Telford et al., 2009, previously reported in alligator snapping turtles in Florida and Georgia, but two characteristic stage forms were not shared between H. macrochelysi n. sp. and the parasite found in this report. The haemogregarine 18S ribosomal RNA gene (1555-bp fragment) was amplified and cloned, and five clones sequenced. The sequences were deposited in the NCBI GenBank database. All five showed ∼96 % identity to Haemogregarina balli Paterson and Desser, 1976, Hepatozoon sp., and Hemolivia stellata Petit et al., 1990. A 774-bp segment shared 98-99 % identity with the corresponding Haemogregarina sp. rDNA sequence (KR006985) from Caspian turtles (Mauremys caspica McDowell, 1964) in Iran. A neighbor-joining phylogenetic tree generated from aligned sequences from the clones, 26 hematozoa, Adelina dimidiata Schneider, 1875, and Cryptosporidium serpentis Levine, 1980, revealed the cloned sequences clustered on their own branch within the Haemogregarina spp. clade. No genetic data are available for H. macrochelysi n. sp. at this time, so it remains unclear if this parasite in a Texas alligator snapping turtle is conspecific with H. macrochelysi n. sp.

  4. The impact of long-term participation in the supplemental nutrition assistance program on child obesity.

    PubMed

    Schmeiser, Maximilian D

    2012-04-01

    Participation in the Supplemental Nutrition Assistance Program (SNAP) reached an all-time high of 40.2 million persons in March 2010, which means the program affects a substantial fraction of Americans. A significant body of research has emerged suggesting that participation in SNAP increases the probability of being obese for adult women and has little effect on the probability for adult men. However, studies addressing the effects of participation on children have produced mixed results. This paper examines the effect of long-term SNAP participation on the Body Mass Index (BMI) percentile and probability of being overweight or obese for children ages 5-18 using data from the National Longitudinal Survey of Youth 1979 Children and Young Adults data set. An instrumental variables identification strategy that exploits exogenous variation in state-level program parameters, as well as state and federal expansions of the Earned Income Tax Credit (EITC), is used to address the endogeneity between SNAP participation and obesity. SNAP participation is found to significantly reduce BMI percentile and the probability of being overweight or obese for boys and girls ages 5-11 and boys ages 12-18. For girls ages 12-18, SNAP participation appears to have no significant effect on these outcomes.

  5. NaK loop testing of thermoelectric converter modules (SNAP program)

    NASA Technical Reports Server (NTRS)

    Johnson, J. L.

    1973-01-01

    The history of testing of compact tubular modules in flowing NaK loops is summarized. Test procedures, data handling, and instrument calibration are discussed. Also included is descriptive information of the test facilities, operational problems encountered, and some recommendations for testing.

  6. 78 FR 51136 - Request for Information: Supplemental Nutrition Assistance Program (SNAP) Enhancing Retail Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    .... (2) ``Staple foods'' do not include accessory food items, such as coffee, tea, cocoa, carbonated and... limited to, coffee, tea, cocoa, carbonated and un-carbonated drinks, candy, condiments, and spices shall... be purchased with food stamp benefits. USDA FNS Policy: ``Accessory food items include coffee,...

  7. 78 FR 64468 - Request for Information: Supplemental Nutrition Assistance Program (SNAP) Enhancing Retail Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-29

    ... items, such as coffee, tea, cocoa, carbonated and un-carbonated drinks, candy, condiments, and spices. 7... items including, but not limited to, coffee, tea, cocoa, carbonated and un-carbonated drinks, candy... include coffee, tea, cocoa, carbonated and un-carbonated drinks, candy, condiments and spices. All...

  8. 76 FR 25413 - Supplemental Nutrition Assistance Program (SNAP): Eligibility, Certification, and Employment and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ... include simple 401(k) plans and traditional 401(k) plans. Simple 401(k) plans are for small businesses... individuals rather than employers. Simple retirement account IRAs are only available to small businesses. SEPs are sponsored by small business employers and allow the employer to add funds to the account...

  9. SNAP 19 Viking Program. Bimonthly technical progress report, December 1980-January 1981

    SciTech Connect

    Not Available

    1981-03-11

    Monitoring of power systems performance data for Pioneer 10 and Pioneer Saturn spacecrafts continued. Net power output for either system during mid-January of 1981 was 112 watts. Power degradation has, for several years, been stable between 4 and 5 watts per year. Viking 1 Lander data acquisition has been resumed following the conclusion of Saturn encounter activities. Figures show the Mars Lander performance history of Viking 1. These data include both the minimum and maximum data for each of the SOL days plotted to show the range of performance experienced on the Martian surface.

  10. Long-Term Nitric Oxide Release and Elevated Temperature Stability with S-Nitroso-N-acetylpenicillamine (SNAP)-Doped Elast-eon E2As Polymer

    PubMed Central

    Brisbois, Elizabeth J.; Handa, Hitesh; Major, Terry C.; Bartlett, Robert H.; Meyerhoff, Mark E.

    2013-01-01

    Nitric oxide (NO) is known to be a potent inhibitor of platelet activation and adhesion. Healthy endothelial cells that line the inner walls of all blood vessels exhibit a NO flux of 0.5~4×10−10 mol cm−2 min−1 that helps prevent thrombosis. Materials with a NO flux that is equivalent to this level are expected to exhibit similar anti-thrombotic properties. In this study, five biomedical grade polymers doped with S-nitroso-N-acetylpenicillamine (SNAP) were investigated for their potential to control the release of NO from the SNAP within the polymers, and further control the release of SNAP itself. SNAP in the Elast-eon E2As polymer creates an inexpensive, homogeneous coating that can locally deliver NO (via thermal and photochemical reactions) as well slowly release SNAP. Furthermore, SNAP is surprisingly stable in the E2As polymer, retaining 82% of the initial SNAP after 2 months storage at 37°C. The E2As polymer containing SNAP was coated on the walls of extracorporeal circuits (ECC) and exposed to 4 h blood flow in a rabbit model of extracorporeal circulation to examine the effects on platelet count, platelet function, clot area, and fibrinogen adsorption. After 4 h, platelet count was preserved at 100±7% of baseline for the SNAP/E2As coated loops, compared to 60±6% for E2As control circuits (n=4). The SNAP/E2As coating also reduced the thrombus area when compared to the control (2.3±0.6 and 3.4±1.1 pixels/cm2, respectively). The results suggest that the new SNAP/E2As coating has potential to improve the thromboresistance of intravascular catheters, grafts, and other blood contacting medical devices, and exhibits excellent storage stability compared to previously reported NO release polymeric materials. PMID:23777908

  11. Radionuclide measurement proficiency testing for SNAP using NPL waste drum standards.

    PubMed

    Miller, T J

    2010-12-01

    AWE has participated in two rounds of radionuclide measurement proficiency testing using 200 l waste drum standards prepared by the National Physical Laboratory (NPL). The results achieved, using the SNAP (spectral non-destructive assay platform) system, were generally within a few per cent of the true activities and gave confidence in the ability to allocate wastes to the correct categories in accordance with national legislation. This is important for reasons of public safety and also for minimisation of the amount of RSA (Radioactive Substances Act) Exempt material categorised as LLW (low level waste) as the UK's LLW storage capacity diminishes.

  12. Epileptogenesis and epileptic maturation in phosphorylation site-specific SNAP-25 mutant mice.

    PubMed

    Watanabe, Shigeru; Yamamori, Saori; Otsuka, Shintaro; Saito, Masanori; Suzuki, Eiji; Kataoka, Masakazu; Miyaoka, Hitoshi; Takahashi, Masami

    2015-09-01

    Snap25(S187A/S187A) mouse is a knock-in mouse with a single amino acid substitution at a protein kinase C-dependent phosphorylation site of the synaptosomal-associated protein of 25 kDa (SNAP-25), which is a target-soluble NSF attachment protein receptor (t-SNARE) protein essential for neurotransmitter release. Snap25(S187A/S187A) mice exhibit several distinct phenotypes, including reductions in dopamine and serotonin release in the brain, anxiety-like behavior, and cognitive dysfunctions. Homozygous mice show spontaneous epileptic convulsions, and about 15% of the mice die around three weeks after birth. The remaining mice survive for almost two years and exhibit spontaneous recurrent seizures throughout their lifetime. Here, we conducted long-term continuous video electroencephalogram recording of the mice and analyzed the process of epileptogenesis and epileptic maturation in detail. Spikes and slow-wave discharges (SWDs) were observed in the cerebral cortex and thalamus before epileptic convulsions began. SWDs showed several properties similar to those observed in absence seizures including (1) lack of in the hippocampus, (2) movement arrest during SWDs, and (3) inhibition by ethosuximide. Multiple generalized seizures occurred in all homozygous mice around three weeks after birth. However, seizure generation stopped within several days, and a seizure-free latent period began. Following a spike-free quiet period, the number of spikes increased gradually, and epileptic seizures reappeared. Subsequently, spontaneous seizures occurred cyclically throughout the life of the mice, and several progressive changes in seizure frequency, seizure duration, seizure cycle interval, seizure waveform, and the number and waveform of epileptic discharges during slow-wave sleep occurred with different time courses over 10 weeks. Anxiety-related behaviors appeared suddenly within three days after epileptic seizures began and were delayed markedly by oral administration of

  13. Characterization of microsatellite DNA markers for the alligator snapping turtle, Macrochelys temminckii: Primer note

    USGS Publications Warehouse

    Hackler, J.C.; Van Den Bussche, Ronald A.; Leslie, David M.

    2007-01-01

    Two trinucleotide and seven tetranucleotide microsatellite loci were isolated from an alligator snapping turtle Macrochelys temminckii. To assess the degree of variability in these nine microsatellite loci, we genotyped 174 individuals collected from eight river drainage basins in the southeastern USA. These markers revealed a moderate degree of allelic diversity (six to 16 alleles per locus) and observed heterozygosity (0.166-0.686). These polymorphic microsatellite loci provide powerful tools for population genetic studies for a species that is afforded some level of conservation protection in every state in which it occurs. ?? 2006 The Authors.

  14. Elastoviscoplastic snap-through behavior of shallow arches subjected to thermomechanical loads

    NASA Technical Reports Server (NTRS)

    Simitses, George J.; Song, Yuzhao; Sheinman, Izhak

    1991-01-01

    The problem of snap-through buckling of clamped shallow arches under thermomechanical loads is investigated. The analysis is based on nonlinear kinematic relations and nonlinear rate-dependent unified constitutive equations. A finite element approach is employed to predict the, in general, inelastic buckling behavior. The construction material is alloy B1900 + Hf, which is commonly utilized in high-temperature environments. The effect of several parameters is assessed. These parameters include the rise parameter and temperature. Comparison between elastic and elastoviscoplastic responses is also presented.

  15. Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition

    PubMed Central

    Beck, Florian; Geiger, Jörg; Gambaryan, Stepan; Solari, Fiorella A.; Dell’Aica, Margherita; Loroch, Stefan; Mattheij, Nadine J.; Mindukshev, Igor; Pötz, Oliver; Jurk, Kerstin; Burkhart, Julia M.; Fufezan, Christian; Heemskerk, Johan W. M.; Walter, Ulrich

    2017-01-01

    Adenosine diphosphate (ADP) enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein–coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades, leading to integrin αIIbβ3 activation, a process antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful antiplatelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (1) critical hubs in platelet signaling toward aggregation and (2) novel molecular targets for antiplatelet treatment strategies. We applied quantitative temporal phosphoproteomics to study ADP-mediated signaling at unprecedented molecular resolution. Furthermore, to mimic the antagonistic efficacy of endothelial-derived prostacyclin, we determined how Iloprost reverses ADP-mediated signaling events. We provide temporal profiles of 4797 phosphopeptides, 608 of which showed significant regulation. Regulated proteins are implicated in well-known activating functions such as degranulation and cytoskeletal reorganization, but also in less well-understood pathways, involving ubiquitin ligases and GTPase exchange factors/GTPase-activating proteins (GEF/GAP). Our data demonstrate that ADP-triggered phosphorylation occurs predominantly within the first 10 seconds, with many short rather than sustained changes. For a set of phosphorylation sites (eg, PDE3ASer312, CALDAG-GEFISer587, ENSASer109), we demonstrate an inverse regulation by ADP and Iloprost, suggesting that these are central modulators of platelet homeostasis. This study demonstrates an extensive spectrum of human platelet protein phosphorylation in response to ADP and Iloprost, which inversely overlap and represent major activating and inhibitory pathways. PMID:28060719

  16. Overview on poly(ADP-ribose) immuno-biomedicine and future prospects

    PubMed Central

    KANAI, Yoshiyuki

    2016-01-01

    Poly(ADP-ribose), identified in 1966 independently by three groups Strassbourg, Kyoto and Tokyo, is synthesized by poly(ADP-ribose) polymerases (PARP) from NAD+ as a substrate in the presence of Mg2+. The structure was unique in that it has ribose-ribose linkage. In the early-1970s, however, its function in vivo/in vitro was still controversial and the antibody against it was desired to help clear its significance. Thereupon, the author tried to produce antibody against poly(ADP-ribose) in rabbits and succeeded in it for the first time in the world. Eventually, this success has led to the following two groundbreaking papers in Nature: “Naturally-occurring antibody against poly(ADP-ribose) in patients with autoimmune disease SLE”, and “Induction of anti-poly(ADP-ribose) antibody by immunization with synthetic double-stranded RNA, poly(A)·poly(U)”. On the way to the publication of the first paper, a reviewer gave me a friendly comment that there is “heteroclitic” fashion as a mechanism of the production of natural antibody. This comment was really a God-send for me, and became a train of power for publication of another paper, as described above. Accordingly, I thought this, I would say, episode is worth describing herein. Because of its importance in biomedical phenomena, a certain number of articles related to “heteroclitic” have become to be introduced in this review, although they were not always directly related to immuno-biological works on poly(ADP-ribose). Also, I tried to speculate on the future prospects of poly(ADP-ribose), product of PARP, as an immuno-regulatory molecule, including either induced or naturally-occurring antibodies, in view of “heteroclitic”. PMID:27477457

  17. Negative feedback of extracellular ADP on ATP release in goldfish hepatocytes: a theoretical study.

    PubMed

    Chara, Osvaldo; Pafundo, Diego E; Schwarzbaum, Pablo J

    2010-06-21

    A mathematical model was built to account for the kinetic of extracellular ATP (ATPe) and extracellular ADP (ADPe) concentrations from goldfish hepatocytes exposed to hypotonicity. The model was based on previous experimental results on the time course of ATPe accumulation, ectoATPase activity, and cell viability [Pafundo et al., 2008]. The kinetic of ATPe is controlled by a lytic ATP flux, a non-lytic ATP flux, and ecto-ATPase activity, whereas ADPe kinetic is governed by a lytic ADP flux and both ecto-ATPase and ecto-ADPase activities. Non-lytic ATPe efflux was included as a diffusion equation modulated by ATPe activation (positive feedback) and ADPe inhibition (negative feedback). The model yielded physically meaningful and stable steady-state solutions, was able to fit the experimental time evolution of ATPe and simulated the concomitant kinetic of ADPe. According to the model during the first minute of hypotonicity the concentration of ATPe is mainly governed by both lytic and non-lytic ATP efflux, with almost no contribution from ecto-ATPase activity. Later on, ecto-ATPase activity becomes important in defining the time dependent decay of ATPe levels. ADPe inhibition of the non-lytic ATP efflux was strong, whereas ATPe activation was minimal. Finally, the model was able to predict the consequences of partial inhibition of ecto-ATPase activity on the ATPe kinetic, thus emulating the exposure of goldfish cells to hypotonic medium in the presence of the ATP analog AMP-PCP. The model predicts this analog to both inhibit ectoATPase activity and increase non-lytic ATP release.

  18. Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo-glycohydrolase activities

    PubMed Central

    Barkauskaite, Eva; Brassington, Amy; Tan, Edwin S.; Warwicker, Jim; Dunstan, Mark S.; Banos, Benito; Lafite, Pierre; Ahel, Marijan; Mitchison, Timothy J.; Ahel, Ivan; Leys, David

    2013-01-01

    Poly-ADP-ribosylation is a post-translational modification that regulates processes involved in genome stability. Breakdown of the poly(ADP-ribose) (PAR) polymer is catalysed by poly(ADP-ribose) glycohydrolase (PARG), whose endo-glycohydrolase activity generates PAR fragments. Here we present the crystal structure of PARG incorporating the PAR substrate. The two terminal ADP-ribose units of the polymeric substrate are bound in exo-mode. Biochemical and modelling studies reveal that PARG acts predominantly as an exo-glycohydrolase. This preference is linked to Phe902 (human numbering), which is responsible for low-affinity binding of the substrate in endo-mode. Our data reveal the mechanism of poly-ADP-ribosylation reversal, with ADP-ribose as the dominant product, and suggest that the release of apoptotic PAR fragments occurs at unusual PAR/PARG ratios. PMID:23917065

  19. Crystal structures of the ATP-binding and ADP-release dwells of the V1 rotary motor

    PubMed Central

    Suzuki, Kano; Mizutani, Kenji; Maruyama, Shintaro; Shimono, Kazumi; Imai, Fabiana L.; Muneyuki, Eiro; Kakinuma, Yoshimi; Ishizuka-Katsura, Yoshiko; Shirouzu, Mikako; Yokoyama, Shigeyuki; Yamato, Ichiro; Murata, Takeshi

    2016-01-01

    V1-ATPases are highly conserved ATP-driven rotary molecular motors found in various membrane systems. We recently reported the crystal structures for the Enterococcus hirae A3B3DF (V1) complex, corresponding to the catalytic dwell state waiting for ATP hydrolysis. Here we present the crystal structures for two other dwell states obtained by soaking nucleotide-free V1 crystals in ADP. In the presence of 20 μM ADP, two ADP molecules bind to two of three binding sites and cooperatively induce conformational changes of the third site to an ATP-binding mode, corresponding to the ATP-binding dwell. In the presence of 2 mM ADP, all nucleotide-binding sites are occupied by ADP to induce conformational changes corresponding to the ADP-release dwell. Based on these and previous findings, we propose a V1-ATPase rotational mechanism model. PMID:27807367

  20. Snapping turtles (Chelydra serpentina) as biomonitors of lead contamination of the Big River in Missouri`s Old Lead Belt

    SciTech Connect

    Overmann, S.R.; Krajicek, J.J.

    1995-04-01

    The usefulness of common snapping turtles (Chelydra serpentina) as biomonitors of lead (Pb) contamination of aquatic ecosystems was assessed. Thirty-seven snapping turtles were collected from three sites on the Big River, an Ozarkian stream contaminated with Pb mine tailings. Morphometric measurements, tissue Pb concentrations (muscle, blood, bone, carapace, brain, and liver), {delta}-aminolevulinic acid dehydratase ({delta}-ALAD) activity, hematocrit, hemoglobin, plasma glucose, osmolality, and chloride ion content were measured. The data showed no effects of Pb contamination on capture success or morphological measurements. Tissue Pb concentrations were related to capture location. Hematocrit, plasma osmolality, plasma glucose, and plasma chloride ion content were not significantly different with respect to capture location. The {delta}-ALAD activity levels were decreased in turtles taken from contaminated sites. Lead levels in the Big River do not appear to be adversely affecting the snapping turtles of the river. Chelydra serpentina is a useful species for biomonitoring of Pb-contaminated aquatic environments.

  1. Arginine-specific mono(ADP-ribosyl)transferase activity on the surface of human polymorphonuclear neutrophil leucocytes.

    PubMed Central

    Donnelly, L E; Rendell, N B; Murray, S; Allport, J R; Lo, G; Kefalas, P; Taylor, G W; MacDermot, J

    1996-01-01

    An Arg-specific mono(ADP-ribosyl)transferase activity on the surface of human polymorphonuclear neutrophil leucocytes (PMNs) was confirmed by the use of diethylamino-(benzylidineamino)guanidine (DEA-BAG) as an ADP-ribose acceptor. Two separate HPLC systems were used to separate ADP-ribosyl-DEA-BAG from reaction mixtures, and its presence was confirmed by electrospray mass spectrometry. ADP-ribosyl-DEA-BAG was produced in the presence of PMNs, but not in their absence. Incubation of DEA-BAG with ADP-ribose (0.1-10 mM) did not yield ADP-ribosyl-DEA-BAG, which indicates that ADP-ribosyl-DEA-BAG formed in the presence of PMNs was not simply a product of a reaction between DEA-BAG and free ADP-ribose, due possibly to the hydrolysis of NAD+ by an NAD+ glycohydrolase. The assay of mono(ADP-ribosyl)transferase with agmatine as a substrate was modified for intact PMNs, and the activity was found to be approx. 50-fold lower than that in rabbit cardiac membranes. The Km of the enzyme for NAD+ was 100.1 30.4 microM and the Vmax 1.4 0.2 pmol of ADP-ribosylagmatine/h per 10(6) cells. The enzyme is likely to be linked to the cell surface via a glycosylphosphatidylinositol anchor, since incubation of intact PMNs with phosphoinositol-specific phospholipase C (PI-PLC) led to a 98% decrease in mono(ADP-ribosyl)transferase activity in the cells. Cell surface proteins were labelled after exposure of intact PMNs to [32P]NAD+. Their molecular masses were 79, 67, 46, 36 and 26 kDa. The time course for labelling was non-linear under these conditions over a period of 4 h. The labelled products were identified as mono(ADP-ribosyl)ated proteins by hydrolysis with snake venom phosphodiesterase to yield 5'-AMP. PMID:8615841

  2. Detection of the interaction between SNAP25 and rabphilin in neuroendocrine PC12 cells using the FLIM/FRET technique.

    PubMed

    Lee, Jiung-De; Chang, Yu-Fen; Kao, Fu-Jen; Kao, Lung-Sen; Lin, Chung-Chih; Lu, Ai-Chu; Shyu, Bai-Chuang; Chiou, Shih-Hwa; Yang, De-Ming

    2008-01-01

    Exocytosis has been proposed to contain four sequential steps, namely docking, priming, fusion, and recycling, and to be regulated by various proteins-protein interactions. Synaptosomal-associated protein of 25 kDa (SNAP25) has recently been found to bind rabphilin, the Rab3A specific binding protein, in vitro. However, it is still unclear whether SNAP25 and rabphilin interact during exocytosis within cells in vivo. This problem was addressed by the integration of fluorescence resonance energy transfer (FRET) with high sensitivity fluorescence lifetime imaging microscopy (FLIM) to observe this protein-protein interaction. Enhanced green fluorescence protein-labeled SNAP25 (donor) and red fluorescence protein-labeled rabphilin (acceptor) were expressed in neuroendocrine PC12 cells as a FRET pair and ATP stimulation was carried out for various durations. With 10 s stimulation, a 0.17-ns left shift of the lifetime peak was found when compared with donor only. Analysis of the lifetime image further suggested that the lifetime recovered to a similar level as the donor only in a time dependent manner. Four-dimensional (4D) images by FLIM provided useful information indicating that the interaction of SNAP25 and rabphilin occurred particularly within optical sections near cell membrane. Together the results suggest that SNAP25 bound rabphilin loosely at docking step before exocytosis and the binding became tighter at the very start of exocytosis. Finally, these two proteins dissociated after stimulation. To our knowledge, this is the first report to demonstrate the interaction of SNAP25 and rabphilin in situ using the FLIM-FRET technique within neuroendocrine cells.

  3. The Schedule for Nonadaptive and Adaptive Personality for Youth (SNAP-Y): A New Measure for Assessing Adolescent Personality and Personality Pathology

    ERIC Educational Resources Information Center

    Linde, Jennifer A.; Stringer, Deborah; Simms, Leonard J.; Clark, Lee Anna

    2013-01-01

    The Schedule for Nonadaptive and Adaptive Personality-Youth Version (SNAP-Y) is a new, reliable self-report questionnaire that assesses 15 personality traits relevant to both normal-range personality and the alternative "DSM"-5 model for personality disorder. Community adolescents, 12 to 18 years old (N = 364), completed the SNAP-Y; 347…

  4. 75 FR 21050 - V-GPO, Inc., Valesc Holdings, Inc., Venture Stores, Inc., Vertigo Theme Parks, Inc. (f/k/a Snap2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-22

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION V-GPO, Inc., Valesc Holdings, Inc., Venture Stores, Inc., Vertigo Theme Parks, Inc. (f/k/a Snap2... concerning the securities of Vertigo Theme Parks, Inc. (f/k/a Snap2 Corp.) because it has not filed...

  5. The Q-soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor (Q-SNARE) SNAP-47 Regulates Trafficking of Selected Vesicle-associated Membrane Proteins (VAMPs)*

    PubMed Central

    Kuster, Aurelia; Nola, Sebastien; Dingli, Florent; Vacca, Barbara; Gauchy, Christian; Beaujouan, Jean-Claude; Nunez, Marcela; Moncion, Thomas; Loew, Damarys; Formstecher, Etienne; Galli, Thierry; Proux-Gillardeaux, Veronique

    2015-01-01

    SNAREs constitute the core machinery of intracellular membrane fusion, but vesicular SNAREs localize to specific compartments via largely unknown mechanisms. Here, we identified an interaction between VAMP7 and SNAP-47 using a proteomics approach. We found that SNAP-47 mainly localized to cytoplasm, the endoplasmic reticulum (ER), and ERGIC and could also shuttle between the cytoplasm and the nucleus. SNAP-47 preferentially interacted with the trans-Golgi network VAMP4 and post-Golgi VAMP7 and -8. SNAP-47 also interacted with ER and Golgi syntaxin 5 and with syntaxin 1 in the absence of Munc18a, when syntaxin 1 is retained in the ER. A C-terminally truncated SNAP-47 was impaired in interaction with VAMPs and affected their subcellular distribution. SNAP-47 silencing further shifted the subcellular localization of VAMP4 from the Golgi apparatus to the ER. WT and mutant SNAP-47 overexpression impaired VAMP7 exocytic activity. We conclude that SNAP-47 plays a role in the proper localization and function of a subset of VAMPs likely via regulation of their transport through the early secretory pathway. PMID:26359495

  6. Site-specific ADP-ribosylation of histone H2B in response to DNA double strand breaks

    PubMed Central

    Rakhimova, Alina; Ura, Seiji; Hsu, Duen-Wei; Wang, Hong-Yu; Pears, Catherine J.; Lakin, Nicholas D.

    2017-01-01

    ADP-ribosyltransferases (ARTs) modify proteins with single units or polymers of ADP-ribose to regulate DNA repair. However, the substrates for these enzymes are ill-defined. For example, although histones are modified by ARTs, the sites on these proteins ADP-ribosylated following DNA damage and the ARTs that catalyse these events are unknown. This, in part, is due to the lack of a eukaryotic model that contains ARTs, in addition to histone genes that can be manipulated to assess ADP-ribosylation events in vivo. Here we exploit the model Dictyostelium to identify site-specific histone ADP-ribosylation events in vivo and define the ARTs that mediate these modifications. Dictyostelium histones are modified in response to DNA double strand breaks (DSBs) in vivo by the ARTs Adprt1a and Adprt2. Adprt1a is a mono-ART that modifies H2BE18 in vitro, although disruption of this site allows ADP-ribosylation at H2BE19. Although redundancy between H2BE18 and H2BE19 ADP-ribosylation is also apparent following DSBs in vivo, by generating a strain with mutations at E18/E19 in the h2b locus we demonstrate these are the principal sites modified by Adprt1a/Adprt2. This identifies DNA damage induced histone mono-ADP-ribosylation sites by specific ARTs in vivo, providing a unique platform to assess how histone ADP-ribosylation regulates DNA repair. PMID:28252050

  7. Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease

    PubMed Central

    Sharifi, Reza; Morra, Rosa; Denise Appel, C; Tallis, Michael; Chioza, Barry; Jankevicius, Gytis; Simpson, Michael A; Matic, Ivan; Ozkan, Ege; Golia, Barbara; Schellenberg, Matthew J; Weston, Ria; Williams, Jason G; Rossi, Marianna N; Galehdari, Hamid; Krahn, Juno; Wan, Alexander; Trembath, Richard C; Crosby, Andrew H; Ahel, Dragana; Hay, Ron; Ladurner, Andreas G; Timinszky, Gyula; Williams, R Scott; Ahel, Ivan

    2013-01-01

    Adenosine diphosphate (ADP)-ribosylation is a post-translational protein modification implicated in the regulation of a range of cellular processes. A family of proteins that catalyse ADP-ribosylation reactions are the poly(ADP-ribose) (PAR) polymerases (PARPs). PARPs covalently attach an ADP-ribose nucleotide to target proteins and some PARP family members can subsequently add additional ADP-ribose units to generate a PAR chain. The hydrolysis of PAR chains is catalysed by PAR glycohydrolase (PARG). PARG is unable to cleave the mono(ADP-ribose) unit directly linked to the protein and although the enzymatic activity that catalyses this reaction has been detected in mammalian cell extracts, the protein(s) responsible remain unknown. Here, we report the homozygous mutation of the c6orf130 gene in patients with severe neurodegeneration, and identify C6orf130 as a PARP-interacting protein that removes mono(ADP-ribosyl)ation on glutamate amino acid residues in PARP-modified proteins. X-ray structures and biochemical analysis of C6orf130 suggest a mechanism of catalytic reversal involving a transient C6orf130 lysyl-(ADP-ribose) intermediate. Furthermore, depletion of C6orf130 protein in cells leads to proliferation and DNA repair defects. Collectively, our data suggest that C6orf130 enzymatic activity has a role in the turnover and recycling of protein ADP-ribosylation, and we have implicated the importance of this protein in supporting normal cellular function in humans. PMID:23481255

  8. The ARTT motif and a unified structural understanding of substraterecognition in ADP ribosylating bacterial toxins and eukaryotic ADPribosyltransferases

    SciTech Connect

    Han, S.; Tainer, J.A.

    2001-08-01

    ADP-ribosylation is a widely occurring and biologically critical covalent chemical modification process in pathogenic mechanisms, intracellular signaling systems, DNA repair, and cell division. The reaction is catalyzed by ADP-ribosyltransferases, which transfer the ADP-ribose moiety of NAD to a target protein with nicotinamide release. A family of bacterial toxins and eukaryotic enzymes has been termed the mono-ADP-ribosyltransferases, in distinction to the poly-ADP-ribosyltransferases, which catalyze the addition of multiple ADP-ribose groups to the carboxyl terminus of eukaryotic nucleoproteins. Despite the limited primary sequence homology among the different ADP-ribosyltransferases, a central cleft bearing NAD-binding pocket formed by the two perpendicular b-sheet core has been remarkably conserved between bacterial toxins and eukaryotic mono- and poly-ADP-ribosyltransferases. The majority of bacterial toxins and eukaryotic mono-ADP-ribosyltransferases are characterized by conserved His and catalytic Glu residues. In contrast, Diphtheria toxin, Pseudomonas exotoxin A, and eukaryotic poly-ADP-ribosyltransferases are characterized by conserved Arg and catalytic Glu residues. The NAD-binding core of a binary toxin and a C3-like toxin family identified an ARTT motif (ADP-ribosylating turn-turn motif) that is implicated in substrate specificity and recognition by structural and mutagenic studies. Here we apply structure-based sequence alignment and comparative structural analyses of all known structures of ADP-ribosyltransfeases to suggest that this ARTT motif is functionally important in many ADP-ribosylating enzymes that bear a NAD binding cleft as characterized by conserved Arg and catalytic Glu residues. Overall, structure-based sequence analysis reveals common core structures and conserved active sites of ADP-ribosyltransferases to support similar NAD binding mechanisms but differing mechanisms of target protein binding via sequence variations within the ARTT

  9. Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness

    PubMed Central

    Sequeira, Vasco; Najafi, Aref; McConnell, Mark; Fowler, Ewan D; Bollen, Ilse A E; Wüst, Rob C I; dos Remedios, Cris; Helmes, Michiel; White, Ed; Stienen, Ger J M; Tardiff, Jil; Kuster, Diederik W D; van der Velden, Jolanda

    2015-01-01

    Abstract Heart failure (HF) with diastolic dysfunction has been attributed to increased myocardial stiffness that limits proper filling of the ventricle. Altered cross-bridge interaction may significantly contribute to high diastolic stiffness, but this has not been shown thus far. Cross-bridge interactions are dependent on cytosolic [Ca2+] and the regeneration of ATP from ADP. Depletion of myocardial energy reserve is a hallmark of HF leading to ADP accumulation and disturbed Ca2+ handling. Here, we investigated if ADP elevation in concert with increased diastolic [Ca2+] promotes diastolic cross-bridge formation and force generation and thereby increases diastolic stiffness. ADP dose-dependently increased force production in the absence of Ca2+ in membrane-permeabilized cardiomyocytes from human hearts. Moreover, physiological levels of ADP increased actomyosin force generation in the presence of Ca2+ both in human and rat membrane-permeabilized cardiomyocytes. Diastolic stress measured at physiological lattice spacing and 37°C in the presence of pathological levels of ADP and diastolic [Ca2+] revealed a 76 ± 1% contribution of cross-bridge interaction to total diastolic stress in rat membrane-permeabilized cardiomyocytes. Inhibition of creatine kinase (CK), which increases cytosolic ADP, in enzyme-isolated intact rat cardiomyocytes impaired diastolic re-lengthening associated with diastolic Ca2+ overload. In isolated Langendorff-perfused rat hearts, CK inhibition increased ventricular stiffness only in the presence of diastolic [Ca2+]. We propose that elevations of intracellular ADP in specific types of cardiac disease, including those where myocardial energy reserve is limited, contribute to diastolic dysfunction by recruiting cross-bridges, even at low Ca2+, and thereby increase myocardial stiffness. Key points Diastolic dysfunction in heart failure patients is evident from stiffening of the passive properties of the ventricular wall. Increased actomyosin

  10. 7 CFR 281.8 - Transfer of program administration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Transfer of program administration. 281.8 Section 281.8 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE FOOD STAMP AND FOOD DISTRIBUTION PROGRAM ADMINISTRATION OF SNAP ON...

  11. Snap-Cards: A Dynamic Data Construct of Rapid Information Gathering and Integration for C2 Effectiveness in Homeland Security

    DTIC Science & Technology

    2004-03-24

    adapted. III.4 Wild card and wild matches. Wild card and wild card matches should be allowed and activated in the snap-card system construct...air is presenting). Only a few designated filed of a card can be set wild. Not every filed of a card can be set wild. A wild card match slot in AAP...may be matched with several different snap cards. A wild card is kind of different from the incomplete card where some card entries (fields

  12. Snap-lock bags with red band: A study of manufacturing characteristics, thermal and chemical properties.

    PubMed

    Sim, Yvonne Hui Ying; Koh, Alaric C W; Lim, Shing Min; Yew, Sok Yee

    2015-10-01

    Drug packaging is commonly submitted to the Forensic Chemistry and Physics Laboratory of the Health Sciences Authority, Singapore, for examination. The drugs seized are often packaged in plastic bags. These bags are examined for linkages to provide law enforcement with useful associations between the traffickers and drug abusers. The plastic bags submitted may include snap-lock bags, some with a red band located above the snap-lock closure and some without. Current techniques for examination involve looking at the physical characteristics (dimensions, thickness and polarising patterns) and manufacturing marks of these bags. In cases where manufacturing marks on the main body of the bags are poor or absent, the manufacturing characteristics present on the red band can be examined. A study involving approximately 1000 bags was conducted to better understand the variations in the manufacturing characteristics of the red band. This understanding is crucial in helping to determine associations/eliminations between bags. Two instrumental techniques, namely differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) were explored to evaluate the effectiveness of examining the chemical composition to discriminate the bags.

  13. Effect of dichlorodiphenyltrichloroethane on sex determination of the common snapping turtle (Chelydra serpentina serpentina).

    PubMed

    Portelli, M J; de Solla, S R; Brooks, R J; Bishop, C A

    1999-07-01

    Recent evidence indicates that 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane (DDT) and some of its metabolites alter reproductive and endocrine function in wildlife. Exposure to such endocrine-disrupting compounds during embryonic development can affect sexual differentiation. The authors tested the hypothesis that dichlorodiphenyltrichloroethane (p,p'-DDE) causes feminization of the common snapping turtle (Chelydra s. serpentina), a species with temperature-dependent sex determination, during embryonic development. Eggs from eight clutches (total eggs tested=237) were incubated at a male-producing temperature (26 degrees C). At stage 14 of embryonic development, p,p'-DDE was applied topically at four concentrations and estrogen (estradiol-17 beta) was applied as a positive control. Although application of estrogen did induce female development at this temperature, application of p,p'-DDE did not affect sex determination at the exposure levels used. Residue analysis indicated that the amount of p,p'-DDE detected in the eggs 72 h after application was considerably less than the concentrations applied. However, the amounts that penetrated the shells were comparable to levels which have been found in moderately contaminated sites in the Great Lakes. These results indicate that p, p'-DDE, at levels that exist in the environment in the Great Lakes, does not cause the feminization of snapping turtles during embryonic development.

  14. Diatoms on the carapace of common snapping turtles: Luticola spp. dominate despite spatial variation in assemblages

    PubMed Central

    Wu, Shelly C.; Bergey, Elizabeth A.

    2017-01-01

    Filamentous algae are often visible on the carapaces of freshwater turtles and these algae are dominated by a few species with varying geographic distributions. Compared to filamentous algae, little is known about the much more speciose microalgae on turtles. Our objectives were to compare the diatom flora on a single turtle species (the common snapping turtle, Chelydra serpentina) across part of its range to examine spatial patterns and determine whether specific diatom taxa were consistently associated with turtles (as occurs in the filamentous alga Basicladia spp.). Using preserved turtle specimens from museums, we systematically sampled diatoms on the carapaces of 25 snapping turtles across five states. The diverse diatom assemblages formed two groups–the southern Oklahoma group and the northern Illinois/Wisconsin/New York group, with Arkansas not differing from either group. Of the six diatom species found in all five states, four species are widespread, whereas Luticola cf. goeppertiana and L. cf. mutica are undescribed species, known only from turtles in our study. L. cf. goeppertiana comprised 83% of the diatom abundance on Oklahoma turtles and was relatively more abundant on southern turtles (Oklahoma and Arkansas) than on northern turtles (where mean abundance/state was > 10%). L. cf. mutica was the most abundant species (40%) on New York turtles. Some Luticola species are apparently turtle associates and results support a pattern of spatial variation in Luticola species, similar to that in Basicladia. Using museum specimens is an efficient and effective method to study the distribution of micro-epibionts. PMID:28192469

  15. A dielectric elastomer actuator coupled with water: snap-through instability and giant deformation

    NASA Astrophysics Data System (ADS)

    Godaba, Hareesh; Foo, Choon Chiang; Zhang, Zhi Qian; Khoo, Boo Cheong; Zhu, Jian

    2015-04-01

    A dielectric elastomer actuator is one class of soft actuators which can deform in response to voltage. Dielectric elastomer actuators coupled with liquid have recently been developed as soft pumps, soft lenses, Braille displays, etc. In this paper, we conduct experiments to investigate the performance of a dielectric elastomer actuator which is coupled with water. The membrane is subject to a constant water pressure, which is found to significantly affect the electromechanical behaviour of the membrane. When the pressure is small, the membrane suffers electrical breakdown before snap-through instability, and achieves a small voltage-induced deformation. When the pressure is higher to make the membrane near the verge of the instability, the membrane can achieve a giant voltage-induced deformation, with an area strain of 1165%. When the pressure is large, the membrane suffers pressure-induced snap-through instability and may collapse due to a large amount of liquid enclosed by the membrane. Theoretical analyses are conducted to interpret these experimental observations.

  16. Building the Case for SNAP: Creation of Multi-Band, Simulated Images With Shapelets

    NASA Technical Reports Server (NTRS)

    Ferry, Matthew A.

    2005-01-01

    Dark energy has simultaneously been the most elusive and most important phenomenon in the shaping of the universe. A case for a proposed space-telescope called SNAP (SuperNova Acceleration Probe) is being built, a crucial component of which is image simulations. One method for this is "Shapelets," developed at Caltech. Shapelets form an orthonormal basis and are uniquely able to represent realistic space images and create new images based on real ones. Previously, simulations were created using the Hubble Deep Field (HDF) as a basis Set in one band. In this project, image simulations are created.using the 4 bands of the Hubble Ultra Deep Field (UDF) as a basis set. This provides a better basis for simulations because (1) the survey is deeper, (2) they have a higher resolution, and (3) this is a step closer to simulating the 9 bands of SNAP. Image simulations are achieved by detecting sources in the UDF, decomposing them into shapelets, tweaking their parameters in realistic ways, and recomposing them into new images. Morphological tests were also run to verify the realism of the simulations. They have a wide variety of uses, including the ability to create weak gravitational lensing simulations.

  17. SNAP-, CLIP- and Halo-tag labelling of budding yeast cells.

    PubMed

    Stagge, Franziska; Mitronova, Gyuzel Y; Belov, Vladimir N; Wurm, Christian A; Jakobs, Stefan

    2013-01-01

    Fluorescence microscopy of the localization and the spatial and temporal dynamics of specifically labelled proteins is an indispensable tool in cell biology. Besides fluorescent proteins as tags, tag-mediated labelling utilizing self-labelling proteins as the SNAP-, CLIP-, or the Halo-tag are widely used, flexible labelling systems relying on exogenously supplied fluorophores. Unfortunately, labelling of live budding yeast cells proved to be challenging with these approaches because of the limited accessibility of the cell interior to the dyes. In this study we developed a fast and reliable electroporation-based labelling protocol for living budding yeast cells expressing SNAP-, CLIP-, or Halo-tagged fusion proteins. For the Halo-tag, we demonstrate that it is crucial to use the 6'-carboxy isomers and not the 5'-carboxy isomers of important dyes to ensure cell viability. We report on a simple rule for the analysis of ¹H NMR spectra to discriminate between 6'- and 5'-carboxy isomers of fluorescein and rhodamine derivatives. We demonstrate the usability of the labelling protocol by imaging yeast cells with STED super-resolution microscopy and dual colour live cell microscopy. The large number of available fluorophores for these self-labelling proteins and the simplicity of the protocol described here expands the available toolbox for the model organism Saccharomyces cerevisiae.

  18. Effects of environmental contaminants on snapping turtles of a tidal wetland

    USGS Publications Warehouse

    Albers, P.H.; Sileo, L.; Mulhern, B.M.

    1986-01-01

    Snapping turtles (Chelydra serpentina) were collected from a brackish-water and a nearly freshwater area in the contaminated Hackensack Meadowlands of New Jersey and an uncontaminated freshwater area in Maryland to determine the effects of environmental contaminants on a resident wetland species. No turtles were observed or caught in the Meadowlands at two trapping sites that were the most heavily contaminated by metals. Snapping turtles from the brackish-water area had an unusually low lipid content of body fat and reduced growth compared to turtles from the fresh-water areas in New Jersey and Maryland. Despite the serious metal contamination of the Hackensack Meadowlands, the metal content of kidneys and livers from New Jersey turtles was low and not greatly different from that of the Maryland turtles. Organochlorine pesticide concentrations in body fat were generally low at all three study areas. Polychlorinated biphenyls (PCBs) concentrations in fat were highest in male turtles from the New Jersey brackish-water area. Analysis of blood for amino-levulinic acid dehydratase, albumin, glucose, hemoglobin, osmolality, packed cell volume, total protein, triglycerides, and uric acid failed to reveal any differences among groups that would indicate physiological impairment related to contaminants.

  19. Towards Lego Snapping; Integration of Carbon Nanotubes and Few-Layer Graphene

    NASA Astrophysics Data System (ADS)

    Nasseri, Mohsen; Boland, Mathias; Farrokhi, M. Javad; Strachan, Douglas

    Integration of semiconducting, conducting, and insulating nanomaterials into precisely aligned complicated systems is one of the main challenges to the ultimate size scaling of electronic devices, which is a key goal in nanoscience and nanotechnology. This integration could be made more effective through controlled alignment of the crystallographic lattices of the nanoscale components. Of the vast number of materials of atomically-thin materials, two of the sp2 bonded carbon structures, graphene and carbon nanotubes, are ideal candidates for this type of application since they are built from the same backbone carbon lattice. Here we report carbon nanotube and graphene hybrid nanostructures fabricated through their catalytic synthesis and etching. The growth formations we have investigated through various high-resolution microscopy techniques provide evidence of lego-snapped interfaces between nanotubes and graphene into device-relevant orientations. We will finish with a discussion of the various size and energy regimes relevant to these lego-snapped interfaces and their implications on developing these integrated formations.

  20. Critical Windows of Cardiovascular Susceptibility to Developmental Hypoxia in Common Snapping Turtle (Chelydra serpentina) Embryos.

    PubMed

    Tate, Kevin B; Kohl, Zachary F; Eme, John; Rhen, Turk; Crossley, Dane A

    2015-01-01

    Environmental conditions fluctuate dramatically in some reptilian nests. However, critical windows of environmental sensitivity for cardiovascular development have not been identified. Continuous developmental hypoxia has been shown to alter cardiovascular form and function in embryonic snapping turtles (Chelydra serpentina), and we used this species to identify critical periods during which hypoxia modifies the cardiovascular phenotype. We hypothesized that incubation in 10% O2 during specific developmental periods would have differential effects on the cardiovascular system versus overall somatic growth. Two critical windows were identified with 10% O2 from 50% to 70% of incubation, resulting in relative heart enlargement, either via preservation of or preferential growth of this tissue, while exposure to 10% O2 from 20% to 70% of incubation resulted in a reduction in arterial pressure. The deleterious or advantageous aspects of these embryonic phenotypes in posthatching snapping turtles have yet to be explored. However, identification of these critical windows has provided insight into how the developmental environment alters the phenotype of reptiles and will also be pivotal in understanding its impact on the fitness of egg-laying reptiles.

  1. IJS procedure for RELAP5 to TRACE input model conversion using SNAP

    SciTech Connect

    Prosek, A.; Berar, O. A.

    2012-07-01

    The TRAC/RELAP Advanced Computational Engine (TRACE) advanced, best-estimate reactor systems code developed by the U.S. Nuclear Regulatory Commission comes with a graphical user interface called Symbolic Nuclear Analysis Package (SNAP). Much of efforts have been done in the past to develop the RELAP5 input decks. The purpose of this study is to demonstrate the Institut 'Josef Stefan' (IJS) conversion procedure from RELAP5 to TRACE input model of BETHSY facility. The IJS conversion procedure consists of eleven steps and is based on the use of SNAP. For calculations of the selected BETHSY 6.2TC test the RELAP5/MOD3.3 Patch 4 and TRACE V5.0 Patch 1 were used. The selected BETHSY 6.2TC test was 15.24 cm equivalent diameter horizontal cold leg break in the reference pressurized water reactor without high pressure and low pressure safety injection. The application of the IJS procedure for conversion of BETHSY input model showed that it is important to perform the steps in proper sequence. The overall calculated results obtained with TRACE using the converted RELAP5 model were close to experimental data and comparable to RELAP5/MOD3.3 calculations. Therefore it can be concluded, that proposed IJS conversion procedure was successfully demonstrated on the BETHSY integral test facility input model. (authors)

  2. Histone ADP-Ribosylation Facilitates Gene Transcription by Directly Remodeling Nucleosomes

    PubMed Central

    Martinez-Zamudio, Ricardo

    2012-01-01

    The packaging of DNA into nucleosomes imposes obstacles on gene transcription, and histone-modifying and nucleosome-remodeling complexes work in concert to alleviate these obstacles so as to facilitate transcription. Emerging evidence shows that chromatin-associated poly(ADP-ribose) polymerase 1 (PARP-1) and its enzymatic activity facilitate inflammatory gene transcription and modulate the inflammatory response in animal models. However, the molecular mechanisms by which PARP-1 enzymatic activity facilitates transcription are not well understood. Here we show that through an intracellular signaling pathway, lipopolysaccharide (LPS) stimulation induces PARP-1 enzymatic activity and the ADP-ribosylation of histones at transcriptionally active and accessible chromatin regions in macrophages. In vitro DNase I footprinting and restriction endonuclease accessibility assays reveal that histone ADP-ribosylation directly destabilizes histone-DNA interactions in the nucleosome and increases the site accessibility of the nucleosomal DNA to nucleases. Consistent with this, LPS stimulation-induced ADP-ribosylation at the nucleosome-occupied promoters of il-1β, mip-2, and csf2 facilitates NF-κB recruitment and the transcription of these genes in macrophages. Therefore, our data suggest that PARP-1 enzymatic activity facilitates gene transcription through increasing promoter accessibility by histone ADP-ribosylation. PMID:22547677

  3. Drosophila Poly(ADP-Ribose) Glycohydrolase Mediates Chromatin Structure and SIR2-Dependent Silencing

    PubMed Central

    Tulin, Alexei; Naumova, Natalia M.; Menon, Ammini K.; Spradling, Allan C.

    2006-01-01

    Protein ADP ribosylation catalyzed by cellular poly(ADP-ribose) polymerases (PARPs) and tankyrases modulates chromatin structure, telomere elongation, DNA repair, and the transcription of genes involved in stress resistance, hormone responses, and immunity. Using Drosophila genetic tools, we characterize the expression and function of poly(ADP-ribose) glycohydrolase (PARG), the primary enzyme responsible for degrading protein-bound ADP-ribose moieties. Strongly increasing or decreasing PARG levels mimics the effects of Parp mutation, supporting PARG's postulated roles in vivo both in removing ADP-ribose adducts and in facilitating multiple activity cycles by individual PARP molecules. PARP is largely absent from euchromatin in PARG mutants, but accumulates in large nuclear bodies that may be involved in protein recycling. Reducing the level of either PARG or the silencing protein SIR2 weakens copia transcriptional repression. In the absence of PARG, SIR2 is mislocalized and hypermodified. We propose that PARP and PARG promote chromatin silencing at least in part by regulating the localization and function of SIR2 and possibly other nuclear proteins. PMID:16219773

  4. Inhibiting poly(ADP-ribose) polymerase: a potential therapy against oligodendrocyte death

    PubMed Central

    Veto, Sara; Acs, Peter; Bauer, Jan; Lassmann, Hans; Berente, Zoltan; Setalo, Gyorgy; Borgulya, Gabor; Sumegi, Balazs; Komoly, Samuel; Gallyas, Ferenc; Illes, Zsolt

    2010-01-01

    Oligodendrocyte loss and demyelination are major pathological hallmarks of multiple sclerosis. In pattern III lesions, inflammation is minor in the early stages, and oligodendrocyte apoptosis prevails, which appears to be mediated at least in part through mitochondrial injury. Here, we demonstrate poly(ADP-ribose) polymerase activation and apoptosis inducing factor nuclear translocation within apoptotic oligodendrocytes in such multiple sclerosis lesions. The same morphological and molecular pathology was observed in an experimental model of primary demyelination, induced by the mitochondrial toxin cuprizone. Inhibition of poly(ADP-ribose) polymerase in this model attenuated oligodendrocyte depletion and decreased demyelination. Poly(ADP-ribose) polymerase inhibition suppressed c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation, increased the activation of the cytoprotective phosphatidylinositol-3 kinase-Akt pathway and prevented caspase-independent apoptosis inducing factor-mediated apoptosis. Our data indicate that poly(ADP-ribose) polymerase activation plays a crucial role in the pathogenesis of pattern III multiple sclerosis lesions. Since poly(ADP-ribose) polymerase inhibition was also effective in the inflammatory model of multiple sclerosis, it may target all subtypes of multiple sclerosis, either by preventing oligodendrocyte death or attenuating inflammation. PMID:20157013

  5. Measurement of ADP-ATP exchange in relation to mitochondrial transmembrane potential and oxygen consumption.

    PubMed

    Chinopoulos, Christos; Kiss, Gergely; Kawamata, Hibiki; Starkov, Anatoly A

    2014-01-01

    We have previously described a fluorometric method to measure ADP-ATP exchange rates in mitochondria of permeabilized cells, in which several enzymes that consume substantial amounts of ATP and other competing reactions interconverting adenine nucleotides are present. This method relies on recording changes in free extramitochondrial Mg(2+) with the Mg(2+)-sensitive fluorescent indicator Magnesium Green (MgGr)™, exploiting the differential affinity of ADP and ATP for Mg(2+). In particular, cells are permeabilized with digitonin in the presence of BeF3(-) and Na3VO4, inhibiting all ATP- and ADP-utilizing reactions but mitochondrial exchange of ATP with ADP catalyzed by the adenine nucleotide translocase. The rate of ATP appearing in the medium upon the addition of ADP to energized mitochondria is then calculated from the rate of change in free extramitochondrial Mg(2+) using standard binding equations. Here, we describe a variant of this method involving an improved calibration step. This step minimizes errors that may be introduced during the conversion of the MgGr™ signal into free extramitochondrial [Mg(2+)] and ATP. Furthermore, we describe an approach for combining this methodology with the measurement of mitochondrial membrane potential and oxygen consumption in the same sample. The method described herein is useful for the study of malignant cells, which are known to thrive in hypoxic environments and to harbor mitochondria with profound functional alterations.

  6. A Novel Kinetic Assay of Mitochondrial ATP-ADP Exchange Rate Mediated by the ANT

    PubMed Central

    Chinopoulos, Christos; Vajda, Szilvia; Csanády, László; Mándi, Miklós; Mathe, Katalin; Adam-Vizi, Vera

    2009-01-01

    A novel method exploiting the differential affinity of ADP and ATP to Mg2+ was developed to measure mitochondrial ADP-ATP exchange rate. The rate of ATP appearing in the medium after addition of ADP to energized mitochondria, is calculated from the measured rate of change in free extramitochondrial [Mg2+] reported by the membrane-impermeable 5K+ salt of the Mg2+-sensitive fluorescent indicator, Magnesium Green, using standard binding equations. The assay is designed such that the adenine nucleotide translocase (ANT) is the sole mediator of changes in [Mg2+] in the extramitochondrial volume, as a result of ADP-ATP exchange. We also provide data on the dependence of ATP efflux rate within the 6.8–7.8 matrix pH range as a function of membrane potential. Finally, by comparing the ATP-ADP steady-state exchange rate to the amount of the ANT in rat brain synaptic, brain nonsynaptic, heart and liver mitochondria, we provide molecular turnover numbers for the known ANT isotypes. PMID:19289073

  7. AdpC is a Prevotella intermedia 17 leucine-rich repeat internalin-like protein.

    PubMed

    Iyer, Divya; Anaya-Bergman, Cecilia; Jones, Kevin; Yanamandra, Sai; Sengupta, Dipanwita; Miyazaki, Hiroshi; Lewis, Janina P

    2010-06-01

    The oral bacterium Prevotella intermedia attaches to and invades gingival epithelial cells, fibroblasts, and endothelial cells. Several genes encoding proteins that mediate both the adhesion and invasion processes are carried on the genome of this bacterium. Here, we characterized one such protein, AdpC, belonging to the leucine-rich repeat (LRR) protein family. Bioinformatics analysis revealed that this protein shares similarity with the Treponema pallidum LRR (LRR(TP)) family of proteins and contains six LRRs. Despite the absence of a signal peptide, this protein is localized on the bacterial outer membrane, indicating that it is transported through an atypical secretion mechanism. The recombinant form of this protein (rAdpC) was shown to bind fibrinogen. In addition, the heterologous host strain Escherichia coli BL21 expressing rAdpC (V2846) invaded fibroblast NIH 3T3 cells at a 40-fold-higher frequency than control E. coli BL21 cells expressing a sham P. intermedia 17 protein. Although similar results were obtained by using human umbilical vein endothelial cells (HUVECs), only a 3-fold-increased invasion of V2846 into oral epithelial HN4 cells was observed. Thus, AdpC-mediated invasion is cell specific. This work demonstrated that AdpC is an important invasin protein of P. intermedia 17.

  8. Growth of cerium(III)-doped ADP crystals and characterization studies

    NASA Astrophysics Data System (ADS)

    Vanchinathan, K.; Muthu, K.; Bhagavannarayana, G.; Meenakshisundaram, SP.

    2012-09-01

    Single crystals of Ce(III)-doped ammonium dihydrogen phosphate (ADP) are grown by conventional slow evaporation of aqueous solution and Sankaranarayanan-Ramasamy (SR) technique. High-resolution X-ray diffraction (HRXRD) studies reveal that the crystalline perfection is substantially better in the case of SR-grown crystal. Morphological changes are observed in the doped specimen. Doping has some influence on the DRS spectra and the band gap energy is estimated by Kubelka-Munk algorithm. Lattice parameters are determined by single crystal XRD analysis. The powder X-ray diffraction and FT-IR analyses indicate that the crystal undergoes considerable stress as a result of doping. The incorporation of Ce(III) into the crystalline matrix of ADP is confirmed by energy dispersive X-ray spectroscopy (EDS). Thermal studies reveal no decomposition up to the melting point and no significant changes are observed as a result of foreign ion incorporation in ADP crystalline matrix.

  9. Poly(ADP-ribosyl)ation as a new posttranslational modification of YB-1.

    PubMed

    Alemasova, Elizaveta E; Pestryakov, Pavel E; Sukhanova, Maria V; Kretov, Dmitry A; Moor, Nina A; Curmi, Patrick A; Ovchinnikov, Lev P; Lavrik, Olga I

    2015-12-01

    Multifunctional Y-box binding protein 1 (YB-1) is actively studied as one of the components of cellular response to genotoxic stress. However, the precise role of YB-1 in the process of DNA repair is still obscure. In the present work we report for the first time new posttranslational modification of YB-1 - poly(ADP-ribosyl)ation, catalyzed by one of the main regulatory enzymes of DNA repair - poly(ADP-ribose)polymerase 1 (PARP1) in the presence of model DNA substrate carrying multiple DNA lesions. Therefore, poly(ADP-ribosyl)ation of YB-1 catalyzed with PARP1, can be stimulated by damaged DNA. The observed property of YB-1 underlines its ability to participate in the DNA repair by its involvement in the regulatory cascades of DNA repair.

  10. The expanding role of poly(ADP-ribose) metabolism: current challenges and new perspectives.

    PubMed

    Gagné, Jean-Philippe; Hendzel, Michael J; Droit, Arnaud; Poirier, Guy G

    2006-04-01

    Recent discoveries have resulted in significant breakthroughs in the understanding of PARPs and PARG functions within a broad range of cellular processes. The novel and sometimes unexpected pathways that are regulated by poly(ADP-ribosylation) bring new questions and hypotheses, some of them being contentious. In this review, we highlight current areas of investigation such as the clinical potential of PARP and PARG inhibitors and the important mitotic regulatory functions of poly(ADP-ribose) in cell-cycle progression, a recent discovery that has broadened our knowledge regarding poly(ADP-ribose) functions. A special emphasis is placed on recent advances in relation to PARG that are stimulating new directions in future research. Noticeably, the existence of various PARG isoforms characterized by distinct cellular localizations and nucleocytoplasmic shuttling properties challenges our current comprehension of pADPr metabolism. Observations and suppositions towards functionally important regulatory elements in the N-terminal portion of PARG are also discussed.

  11. Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens

    PubMed Central

    Rack, Johannes Gregor Matthias; Morra, Rosa; Barkauskaite, Eva; Kraehenbuehl, Rolf; Ariza, Antonio; Qu, Yue; Ortmayer, Mary; Leidecker, Orsolya; Cameron, David R.; Matic, Ivan; Peleg, Anton Y.; Leys, David; Traven, Ana; Ahel, Ivan

    2015-01-01

    Summary Sirtuins are an ancient family of NAD+-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. In our model organisms, Staphylococcus aureus and Streptococcus pyogenes, the activity is dependent on prior lipoylation of the target protein and can be reversed by a sirtuin-associated macrodomain protein. Together, our data describe a sirtuin-dependent reversible protein ADP-ribosylation system and establish a crosstalk between lipoylation and mono-ADP-ribosylation. We propose that these posttranslational modifications modulate microbial virulence by regulating the response to host-derived reactive oxygen species. PMID:26166706

  12. ADP-2Ho as a Phasing Tool for Nucleotide-Containing Proteins

    SciTech Connect

    Ku,S.; Smith, G.; Howell, P.

    2007-01-01

    Trivalent holmium ions were shown to isomorphously replace magnesium ions to form an ADP-2Ho complex in the nucleotide-binding domain of Bacillus subtilis 5-methylthioribose (MTR) kinase. This nucleotide-holmium complex provided sufficient phasing power to allow SAD and SIRAS phasing of this previously unknown structure using the L{sub III} absorption edge of holmium. The structure of ADP-2Ho reveals that the two Ho ions are approximately 4 {angstrom} apart and are likely to share their ligands: the phosphoryl O atoms of ADP and a water molecule. The structure determination of MTR kinase using data collected using Cu K X-radiation was also attempted. Although the heavy-atom substructure determination was successful, interpretation of the map was more challenging. The isomorphous substitution of holmium for magnesium in the MTR kinase-nucleotide complex suggests that this could be a useful phasing tool for other metal-dependent nucleotide-containing proteins.

  13. Detection and Quantification of ADP-Ribosylated RhoA/B by Monoclonal Antibody

    PubMed Central

    Rohrbeck, Astrid; Fühner, Viola; Schröder, Anke; Hagemann, Sandra; Vu, Xuan-Khang; Berndt, Sarah; Hust, Michael; Pich, Andreas; Just, Ingo

    2016-01-01

    Clostridium botulinum exoenzyme C3 is the prototype of C3-like ADP-ribosyltransferases that modify the GTPases RhoA, B, and C. C3 catalyzes the transfer of an ADP-ribose moiety from the co-substrate nicotinamide adenine dinucleotide (NAD) to asparagine-41 of Rho-GTPases. Although C3 does not possess cell-binding/-translocation domains, C3 is able to efficiently enter intact cells, including neuronal and macrophage-like cells. Conventionally, the detection of C3 uptake into cells is carried out via the gel-shift assay of modified RhoA. Since this gel-shift assay does not always provide clear, evaluable results an additional method to confirm the ADP-ribosylation of RhoA is necessary. Therefore, a new monoclonal antibody has been generated that specifically detects ADP-ribosylated RhoA/B, but not RhoC, in Western blot and immunohistochemical assay. The scFv antibody fragment was selected by phage display using the human naive antibody gene libraries HAL9/10. Subsequently, the antibody was produced as scFv-Fc and was found to be as sensitive as a commercially available RhoA antibody providing reproducible and specific results. We demonstrate that this specific antibody can be successfully applied for the analysis of ADP-ribosylated RhoA/B in C3-treated Chinese hamster ovary (CHO) and HT22 cells. Moreover, ADP-ribosylation of RhoA was detected within 10 min in C3-treated CHO wild-type cells, indicative of C3 cell entry. PMID:27043630

  14. Detection and Quantification of ADP-Ribosylated RhoA/B by Monoclonal Antibody.

    PubMed

    Rohrbeck, Astrid; Fühner, Viola; Schröder, Anke; Hagemann, Sandra; Vu, Xuan-Khang; Berndt, Sarah; Hust, Michael; Pich, Andreas; Just, Ingo

    2016-04-01

    Clostridium botulinum exoenzyme C3 is the prototype of C3-like ADP-ribosyltransferases that modify the GTPases RhoA, B, and C. C3 catalyzes the transfer of an ADP-ribose moiety from the co-substrate nicotinamide adenine dinucleotide (NAD) to asparagine-41 of Rho-GTPases. Although C3 does not possess cell-binding/-translocation domains, C3 is able to efficiently enter intact cells, including neuronal and macrophage-like cells. Conventionally, the detection of C3 uptake into cells is carried out via the gel-shift assay of modified RhoA. Since this gel-shift assay does not always provide clear, evaluable results an additional method to confirm the ADP-ribosylation of RhoA is necessary. Therefore, a new monoclonal antibody has been generated that specifically detects ADP-ribosylated RhoA/B, but not RhoC, in Western blot and immunohistochemical assay. The scFv antibody fragment was selected by phage display using the human naive antibody gene libraries HAL9/10. Subsequently, the antibody was produced as scFv-Fc and was found to be as sensitive as a commercially available RhoA antibody providing reproducible and specific results. We demonstrate that this specific antibody can be successfully applied for the analysis of ADP-ribosylated RhoA/B in C3-treated Chinese hamster ovary (CHO) and HT22 cells. Moreover, ADP-ribosylation of RhoA was detected within 10 min in C3-treated CHO wild-type cells, indicative of C3 cell entry.

  15. Host Cell Poly(ADP-Ribose) Glycohydrolase Is Crucial for Trypanosoma cruzi Infection Cycle

    PubMed Central

    Vilchez Larrea, Salomé C.; Schlesinger, Mariana; Kevorkian, María L.; Flawiá, Mirtha M.; Alonso, Guillermo D.; Fernández Villamil, Silvia H.

    2013-01-01

    Trypanosoma cruzi, etiological agent of Chagas’ disease, has a complex life cycle which involves the invasion of mammalian host cells, differentiation and intracellular replication. Here we report the first insights into the biological role of a poly(ADP-ribose) glycohydrolase in a trypanosomatid (TcPARG). In silico analysis of the TcPARG gene pointed out the conservation of key residues involved in the catalytic process and, by Western blot, we demonstrated that it is expressed in a life stage-dependant manner. Indirect immunofluorescence assays and electron microscopy using an anti-TcPARG antibody showed that this enzyme is localized in the nucleus independently of the presence of DNA damage or cell cycle stage. The addition of poly(ADP-ribose) glycohydrolase inhibitors ADP-HPD (adenosine diphosphate (hydroxymethyl) pyrrolidinediol) or DEA (6,9-diamino-2-ethoxyacridine lactate monohydrate) to the culture media, both at a 1 µM concentration, reduced in vitro epimastigote growth by 35% and 37% respectively, when compared to control cultures. We also showed that ADP-HPD 1 µM can lead to an alteration in the progression of the cell cycle in hydroxyurea synchronized cultures of T. cruzi epimastigotes. Outstandingly, here we demonstrate that the lack of poly(ADP-ribose) glycohydrolase activity in Vero and A549 host cells, achieved by chemical inhibition or iRNA, produces the reduction of the percentage of infected cells as well as the number of amastigotes per cell and trypomastigotes released, leading to a nearly complete abrogation of the infection process. We conclude that both, T. cruzi and the host, poly(ADP-ribose) glycohydrolase activities are important players in the life cycle of Trypanosoma cruzi, emerging as a promising therapeutic target for the treatment of Chagas’ disease. PMID:23776710

  16. Host cell poly(ADP-ribose) glycohydrolase is crucial for Trypanosoma cruzi infection cycle.

    PubMed

    Vilchez Larrea, Salomé C; Schlesinger, Mariana; Kevorkian, María L; Flawiá, Mirtha M; Alonso, Guillermo D; Fernández Villamil, Silvia H

    2013-01-01

    Trypanosoma cruzi, etiological agent of Chagas' disease, has a complex life cycle which involves the invasion of mammalian host cells, differentiation and intracellular replication. Here we report the first insights into the biological role of a poly(ADP-ribose) glycohydrolase in a trypanosomatid (TcPARG). In silico analysis of the TcPARG gene pointed out the conservation of key residues involved in the catalytic process and, by Western blot, we demonstrated that it is expressed in a life stage-dependant manner. Indirect immunofluorescence assays and electron microscopy using an anti-TcPARG antibody showed that this enzyme is localized in the nucleus independently of the presence of DNA damage or cell cycle stage. The addition of poly(ADP-ribose) glycohydrolase inhibitors ADP-HPD (adenosine diphosphate (hydroxymethyl) pyrrolidinediol) or DEA (6,9-diamino-2-ethoxyacridine lactate monohydrate) to the culture media, both at a 1 µM concentration, reduced in vitro epimastigote growth by 35% and 37% respectively, when compared to control cultures. We also showed that ADP-HPD 1 µM can lead to an alteration in the progression of the cell cycle in hydroxyurea synchronized cultures of T. cruzi epimastigotes. Outstandingly, here we demonstrate that the lack of poly(ADP-ribose) glycohydrolase activity in Vero and A549 host cells, achieved by chemical inhibition or iRNA, produces the reduction of the percentage of infected cells as well as the number of amastigotes per cell and trypomastigotes released, leading to a nearly complete abrogation of the infection process. We conclude that both, T. cruzi and the host, poly(ADP-ribose) glycohydrolase activities are important players in the life cycle of Trypanosoma cruzi, emerging as a promising therapeutic target for the treatment of Chagas' disease.

  17. Purification and properties of poly(ADP-ribose)polymerase from Crithidia fasciculata. Automodification and poly(ADP-ribosyl)ation of DNA topoisomerase I.

    PubMed

    Podestá, Dolores; García-Herreros, María I; Cannata, Joaquín J B; Stoppani, Andrés O M; Fernández Villamil, Silvia H

    2004-06-01

    Poly(ADP-ribose)polymerase has been purified more than 160000-fold from Crithidia fasciculata. This is the first PARP isolated to apparent homogeneity from trypanosomatids. The purified enzyme absolutely required DNA for catalytic activity and histones enhanced it 2.5-fold, when the DNA:histone ratio was 1:1.3. The enzyme required no magnesium or any other metal ion cofactor. The apparent molecular mass of 111 kDa, determined by gel filtration would correspond to a dimer of two identical 55-kDa subunits. Activity was inhibited by nicotinamide, 3-aminobenzamide, theophylline, thymidine, xanthine and hypoxanthine but not by adenosine. The enzyme was localized to the cell nucleus. Our findings suggest that covalent poly(ADP-ribosyl)ation of PARP itself or DNA topoisomerase I resulted in the inhibition of their activities and provide an initial biochemical characterization of this covalent post-translational modification in trypanosomatids.

  18. Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose

    PubMed Central

    Tsuzuki, Takayoshi; Takano, Satoshi; Sakaguchi, Natsumi; Kudoh, Takashi; Murayama, Takashi; Sakurai, Takashi; Hashii, Minako; Higashida, Haruhiro; Weber, Karin; Guse, Andreas H.; Kameda, Tomoshi; Hirokawa, Takatsugu; Kumaki, Yasuhiro; Arisawa, Mitsuhiro; Potter, Barry V. L.; Shuto, Satoshi

    2016-01-01

    Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, 3), designed as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca2+-mobilizing second messenger, in which the key N1-β-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative 8 and the 4-thioribosylamine 7 via equilibrium in 7 between the α-anomer (7α) and the β-anomer (7β) during the reaction course. cADPtR is, unlike cADPR, chemically and biologically stable, while it effectively mobilizes intracellular Ca2+ like cADPR in various biological systems, such as sea urchin homogenate, NG108-15 neuronal cells, and Jurkat T-lymphocytes. Thus, cADPtR is a stable equivalent of cADPR, which can be useful as a biological tool for investigating cADPR-mediated Ca2+-mobilizing pathways. PMID:27200225

  19. Regulatory Control of Breast Tumor Cell Poly (ADP-Ribose) Polymerase

    DTIC Science & Technology

    2004-08-01

    The proteins were transferred to a nitrocellulose membrane and PARP was detected using anti-human PARP monoclonal antibody. Since PARP is a basic...to check if this modification is due to poly(ADP-ribosyl)ation of the protein , the membrane was stripped off and re-probed with anti-PAR polyclonal...detect any poly(ADP- ribosyl)ated proteins corresponding to the molecular weight of PARP (116 kDa) (Figure 18 ), we initiated experiment to test possible

  20. [The action of ADP ribose on the mechanical and bioelectrical activity of the frog heart].

    PubMed

    Sosulina, L Iu; Sukhova, G S; Chudnyĭ, M N; Ashmarin, I P

    1999-04-01

    In the frog isolated heart, cyclic perfusion of ADP-ribose induced a dose-dependent decrease in the heart rate and the contraction force, a decrease in the AP duration as well as in the rate of rise in the sinus node. It also shortened the atrial AP and exerted no significant effect upon multicellular ventricular preparations. In conditions of systemic administration in unanesthetised frogs, the ADP-ribose induced a reversible increase in the heart rate due, probably, to a sympathetic effect.

  1. Poly(ADP-ribosyl)ation is recognized by ECT2 during mitosis.

    PubMed

    Li, Mo; Bian, Chunjing; Yu, Xiaochun

    2014-01-01

    Poly(ADP-ribosyl)ation is an unique posttranslational modification and required for spindle assembly and function during mitosis. However, the molecular mechanism of poly(ADP-ribose) (PAR) in mitosis remains elusive. Here, we show the evidence that PAR is recognized by ECT2, a key guanine nucleotide exchange factor in mitosis. The BRCT domain of ECT2 directly binds to PAR both in vitro and in vivo. We further found that α-tubulin is PARylated during mitosis. PARylation of α-tubulin is recognized by ECT2 and recruits ECT2 to mitotic spindle for completing mitosis. Taken together, our study reveals a novel mechanism by which PAR regulates mitosis.

  2. ADP Regulates the Structure and Function of the Protein KaiC

    DTIC Science & Technology

    2016-08-11

    AFRL-AFOSR-VA-TR-2016-0294 ADP Regulates the Structure and Function of the Protein KaiC Andy LiWang UNIVERSITY OF CALIFORNIA MERCED 5200 N LAKE RD...REPORT TYPE Final Performance 3. DATES COVERED (From - To) 01 Aug 2013 to 31 Jul 2017 4. TITLE AND SUBTITLE ADP Regulates the Structure and Function of...LiWang lab exploited this in vitro clock system to gain an atomic -resolution understanding of a circadian clock. The rationale is that fundamental

  3. Inhibition of ADP-ribosyltransferase activity of cholera toxin by MDL 12330A and chlorpromazine.

    PubMed

    Bitonti, A J

    1984-04-30

    ADP-ribosylation by cholera toxin of the guanine nucleotide binding regulatory protein (Gs) of rat liver membrane adenylate cyclase was inhibited by 0.1-1 mM MDL 12330A or 0.1-1 mM chlorpromazine. Basal as well as cholera toxin activated adenylate cyclase activity in liver membranes was also inhibited by the two drugs. NAD glycohydrolase activity and self-ADP-ribosylation of cholera toxin were also inhibited by MDL 12330A and chlorpromazine. These effects of MDL 12330A and chlorpromazine may be related to their effects on cholera toxin-induced fluid secretion in vivo.

  4. Different mechanics of snap-trapping in the two closely related carnivorous plants Dionaea muscipula and Aldrovanda vesiculosa.

    PubMed

    Poppinga, Simon; Joyeux, Marc

    2011-10-01

    The carnivorous aquatic waterwheel plant (Aldrovanda vesiculosa L.) and the closely related terrestrial venus flytrap (Dionaea muscipula Sol. ex J. Ellis) both feature elaborate snap-traps, which shut after reception of an external mechanical stimulus by prey animals. Traditionally, Aldrovanda is considered as a miniature, aquatic Dionaea, an assumption which was already established by Charles Darwin. However, videos of snapping traps from both species suggest completely different closure mechanisms. Indeed, the well-described snapping mechanism in Dionaea comprises abrupt curvature inversion of the two trap lobes, while the closing movement in Aldrovanda involves deformation of the trap midrib but not of the lobes, which do not change curvature. In this paper, we present detailed mechanical models for these plants, which are based on the theory of thin solid membranes and explain this difference by showing that the fast snapping of Aldrovanda is due to kinematic amplification of the bending deformation of the midrib, while that of Dionaea unambiguously relies on the buckling instability that affects the two lobes.

  5. Field assessment of a snap bean ozone bioindicator system under elevated ozone and carbon dioxide in a free air system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ozone-sensitive (S156) and -tolerant (R123 and R331) genotypes of snap bean (Phaseolus vulgaris L.) were tested as a plant bioindicator system for detecting O3 effects at current and future levels of tropospheric O3 and atmospheric CO2 under field conditions. Plants were exposed to reciprocal combi...

  6. Construct and Criterion Validities of the Service Need Assessment Profile (SNAP): A Measure of Support for People with Disabilities

    ERIC Educational Resources Information Center

    Guscia, Roma; Harries, Julia; Kirby, Neil; Nettelbeck, Ted; Taplin, John

    2006-01-01

    Background: The "Service Need Assessment Profile" (SNAP) measures individual functional needs in areas of daily living. It produces a support profile, detailing the time allocations for staff support to assist in each area of need. The "Supports Intensity Scale" (SIS) is a support needs assessment scale designed to provide an…

  7. Synaptosomal Protein of 25 kDa (Snap25) Polymorphisms Associated with Glycemic Parameters in Type 2 Diabetes Patients

    PubMed Central

    Costa, Andrea S.; Alokail, Majed S.; Zanzottera, Milena; Alenad, Amal M.; Mohammed, Abdul Khader; Clerici, Mario; Guerini, Franca R.

    2016-01-01

    A possible role of Snap25 polymorphisms in type 2 diabetes mellitus (T2DM) was evaluated by analyzing three SNPs within intron 1 in a region known to affect the gene expression in vitro. Genomic DNA from 1019 Saudi individuals (489 confirmed T2DM and 530 controls) was genotyped for SNPs rs363039, rs363043, and rs363050 in Snap25 using the TaqMan Genotyping Assay. Significantly higher levels of fasting glucose and HbA1c were detected in T2DM patients carrying the rs363050 (AG/GG) genotypes compared to the (AA) genotype (f = 4.41, df = 1, and p = 0.03 and f = 5.31, df = 1, and p = 0.03, resp.). In these same patients, insulin levels were significantly decreased compared to the (AA) individuals (f = 7.29, df = 1, and p = 0.009). Significant associations were detected between rs363050 (AG/GG) genotypes and increasing fasting glucose levels (p = 0.01 and OR: 1.05), HbA1c levels (OR: 5.06 and p = 0.02), and lower insulinemia (p = 0.03 and OR: 0.95) in T2DM patients. The minor Snap25 rs363050 (G) allele, which results in a reduced expression of Snap25, is associated with altered glycemic parameters in T2DM possibly because of reduced functionality in the exocytotic machinery leading to suboptimal release of insulin. PMID:26779543

  8. Snapping knee caused by a popliteomeniscal fascicle tear of the lateral meniscus in a professional Taekwondo athlete.

    PubMed

    Park, Jong-Hoon; Ro, Kyung-Han; Lee, Dae-Hee

    2012-07-01

    A 19-year-old male professional Taekwondo athlete presented with a 2-year history of pain-free snapping of his right knee. He reported that his right knee joint gave way during games and training and that he could induce pain-free snapping between the proximal-to-fibular head and the lateral knee joint line. None of these physical findings suggested a meniscal pathology or ligamentous instability. Routine radiographs were normal. Magnetic resonance imaging of his right knee joint showed that the shape of the lateral meniscus was normal, and no lateral meniscus tears existed. On arthroscopic examination, popliteal hiatus view showed a posterosuperior popliteomeniscal fascicle tear between the posterior horn of the lateral meniscus and the posterior joint capsule just posteromedial to the popliteus tendon. With medial traction by probing, this popliteomeniscal tear made visible the significant subluxation of the posterior horn of the lateral meniscus to the center or anterior half of the tibial plateau. Based on the diagnosis of a posterosuperior popliteomeniscal tear of the right knee, Fast-Fix (Smith & Nephew, Andover, Massachusetts) was used for the direct repair of the peripheral portion of the lateral meniscus and joint capsule, targeting the popliteomeniscal junction. At 24 months postoperatively, the patient was performing athletic exercises relevant to his profession and was taking part in Taekwondo games, with no pain or recurrence of snapping. To the authors' knowledge, this is the first report of snapping of the lateral aspect of the knee due to a popliteomeniscal fascicle tear.

  9. Different mechanics of snap-trapping in the two closely related carnivorous plants Dionaea muscipula and Aldrovanda vesiculosa

    NASA Astrophysics Data System (ADS)

    Poppinga, Simon; Joyeux, Marc

    2011-10-01

    The carnivorous aquatic waterwheel plant (Aldrovanda vesiculosa L.) and the closely related terrestrial venus flytrap (Dionaea muscipula Sol. ex J. Ellis) both feature elaborate snap-traps, which shut after reception of an external mechanical stimulus by prey animals. Traditionally, Aldrovanda is considered as a miniature, aquatic Dionaea, an assumption which was already established by Charles Darwin. However, videos of snapping traps from both species suggest completely different closure mechanisms. Indeed, the well-described snapping mechanism in Dionaea comprises abrupt curvature inversion of the two trap lobes, while the closing movement in Aldrovanda involves deformation of the trap midrib but not of the lobes, which do not change curvature. In this paper, we present detailed mechanical models for these plants, which are based on the theory of thin solid membranes and explain this difference by showing that the fast snapping of Aldrovanda is due to kinematic amplification of the bending deformation of the midrib, while that of Dionaea unambiguously relies on the buckling instability that affects the two lobes.

  10. Reproductive physiology in eastern snapping turtles (Chelydra serpentina) exposed to runoff from a concentrated animal feeding operation

    EPA Science Inventory

    The eastern snapping turtle (Chelydra serpentina) is widely distributed throughout the eastern and central U.S. and may be a useful model organism to study land use impacts on water quality. We compared the reproductive condition of C. serpentina from a pond impacted by runoff fr...

  11. Fluorescent Probe Encapsulated in SNAP-Tag Protein Cavity To Eliminate Nonspecific Fluorescence and Increase Detection Sensitivity.

    PubMed

    Zeng, Yan-Syun; Gao, Ruo-Cing; Wu, Ting-Wei; Cho, Chien; Tan, Kui-Thong

    2016-08-17

    Despite the promising improvements made recently on fluorescence probes for the detection of enzymes and reactive small molecules, two fundamental problems remain: weaker fluorescence of many dyes in aqueous buffers and strong nonspecific signals in samples containing high protein levels. In this paper, we introduce a novel fluorescent probe encapsulated in protein cavity (FPEPC) concept as demonstrated by SNAP-tag protein and three environment-sensitive fluorescence probes to overcome these two problems. The probes were constructed by following the current probe design for enzymes and reactive small molecules but with an additional benzylguanine moiety for selective SNAP-tag conjugation. The SNAP-tag conjugated probes achieved quantitative nitroreductase and hydrogen sulfide detection in blood plasma, whereas analyte concentrations were overestimated up to 700-fold when bare fluorescent probes were employed for detection. Furthermore, detection sensitivity was increased dramatically, as our probes displayed 390-fold fluorescence enhancement upon SNAP-tag conjugation, in stark contrast to the weak fluorescence of the free probes in aqueous solutions. Compared with the conventional approaches where fluorescent probes are encapsulated into polymers and nanoparticles, our simple and general approach successfully overcame many key issues such as dye leakage, long preparation steps, inconsistent dye-host ratios, difficulty in constructing in situ in a complex medium, and limited application to detect only small metabolites.

  12. 77 FR 16988 - Protection of Stratospheric Ozone: Amendment to HFO-1234yf SNAP Rule for Motor Vehicle Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-23

    ... procedure, Air pollution control, Reporting and recordkeeping requirements, Stratospheric ozone layer. Dated... AGENCY 40 CFR Part 82 RIN 2060-AR20 Protection of Stratospheric Ozone: Amendment to HFO-1234yf SNAP Rule... substitute for ozone- depleting substances (ODSs) in the motor vehicle air conditioning end- use within...

  13. 77 FR 17344 - Protection of Stratospheric Ozone: Amendment to HFO-1234yf SNAP Rule for Motor Vehicle Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-26

    ... control, Incorporation by reference, Reporting and recordkeeping requirements, Stratospheric ozone layer... AGENCY 40 CFR Part 82 RIN-2060-AR20 Protection of Stratospheric Ozone: Amendment to HFO-1234yf SNAP Rule...-tetrafluoroprop-1-ene), a substitute for ozone-depleting substances (ODSs) in the motor vehicle air...

  14. Rapid isolation and single-molecule analysis of ribonucleoproteins from cell lysate by SNAP-SiMPull

    PubMed Central

    Rodgers, Margaret L.; Paulson, Joshua; Hoskins, Aaron A.

    2015-01-01

    Large macromolecular complexes such as the spliceosomal small nuclear ribonucleoproteins (snRNPs) play a variety of roles within the cell. Despite their biological importance, biochemical studies of snRNPs and other machines are often thwarted by practical difficulties in the isolation of sufficient amounts of material. Studies of the snRNPs as well as other macromolecular machines would be greatly facilitated by new approaches that enable their isolation and biochemical characterization. One such approach is single-molecule pull-down (SiMPull) that combines in situ immunopurification of complexes from cell lysates with subsequent single-molecule fluorescence microscopy experiments. We report the development of a new method, called SNAP-SiMPull, that can readily be applied to studies of splicing factors and snRNPs isolated from whole-cell lysates. SNAP-SiMPull overcomes many of the limitations imposed by conventional SiMPull strategies that rely on fluorescent proteins. We have used SNAP-SiMPull to study the yeast branchpoint bridging protein (BBP) as well as the U1 and U6 snRNPs. SNAP-SiMPull will likely find broad use for rapidly isolating complex cellular machines for single-molecule fluorescence colocalization experiments. PMID:25805862

  15. 77 FR 48461 - Supplemental Nutrition Assistance Program: Farm Bill of 2008 Retailer Sanctions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ...; ] DEPARTMENT OF AGRICULTURE Food and Nutrition Service 7 CFR Parts 278 and 279 RIN 0584-AD88 Supplemental Nutrition Assistance Program: Farm Bill of 2008 Retailer Sanctions AGENCY: Food and Nutrition Service (FNS... Nutrition Assistance Program (SNAP) (formerly the Food Stamp Program) retailer sanction regulations...

  16. The role of ADP in the modulation of the calcium-efflux pathway in rat brain mitochondria.

    PubMed Central

    Vitorica, J; Satrústegui, J

    1985-01-01

    The role of ADP in the regulation of Ca2+ efflux in rat brain mitochondria was investigated. ADP was shown to inhibit Ruthenium-Red-insensitive H+- and Na+-dependent Ca2+-efflux rates if Pi was present, but had no effect in the absence of Pi. The primary effect of ADP is an inhibition of Pi efflux, and therefore it allows the formation of a matrix Ca2+-Pi complex at concentrations above 0.2 mM-Pi and 25 nmol of Ca2+/mg of protein, which maintains a constant free matrix Ca2+ concentration. ADP inhibition of Pi and Ca2+ efflux is nucleotide-specific, since in the presence of oligomycin and an inhibitor of adenylate kinase ATP does not substitute for ADP, is dependent on the amount of ADP present, and requires ADP concentrations in excess of the concentrations of translocase binding sites. Brain mitochondria incubated with 0.2 mM-Pi and ADP showed Ca2+-efflux rates dependent on Ca2+ loads at Ca2+ concentrations below those required for the formation of a Pi-Ca2+ complex, and behaved as perfect cytosolic buffers exclusively at high Ca2+ loads. The possible role of brain mitochondrial Ca2+ in the regulation of the tricarboxylic acid-cycle enzymes and in buffering cytosolic Ca2+ is discussed. PMID:3977831

  17. Extensive diversity and inter-genepool introgression in a world-wide collection of indeterminate snap bean accessions.

    PubMed

    Blair, Matthew W; Chaves, Alejandro; Tofiño, Adriana; Calderón, Juan Felipe; Palacio, Juan Diego

    2010-05-01

    Common bean can be grown as a grain crop (dry beans) or as a fresh vegetable (snap beans/green beans), both items being important in nutritional terms for providing essential minerals and vitamins to the diet. Snap beans are thought to be derived predominantly from dry beans of the Andean genepool and to be of a recent European origin; however, the existence of Mesoamerican genepool characteristics especially in traditional indeterminate growth habit snap beans indicates a wider origin. The objective of this study was to evaluate genetic diversity within a set of 120 indeterminate (pole type) snap beans and 7 control genotypes representing each genepool using amplified fragment length polymorphism (AFLP) and simple sequence repeat or microsatellite (SSR) markers. The genotypes were predominantly from Asia, Europe and the United States but included some varieties from Latin America and Africa. AFLP polymorphism ranged from 53.2 to 67.7% while SSR polymorphism averaged 95.3% for the 32 fluorescent and 11 non-fluorescent markers evaluated and total expected heterozygosity was higher for SSR markers (0.521) than for AFLP markers (0.209). Both marker systems grouped the genotypes into two genepools with Andean and Mesoamerican controls, respectively, with the Mesoamerican group being predominant in terms of the number of genotypes assigned to this genepool. Phaseolin alleles were not tightly associated with genepool assignment indicating that introgression of this locus had occurred between the genepools, especially with phaseolin "S" in the Andean group (23.5%) and phaseolins "T" and "C" in the Mesoamerican group (12.2 and 8.2%, respectively). The implications of these results on the origin of pole type snap beans and on breeding strategies for this horticultural crop are discussed.

  18. The pioneering spirit of Takashi Sugimura: his studies of the biochemistry of poly(ADP-ribosylation) and of cancer.

    PubMed

    Masutani, Mitsuko

    2012-03-01

    Takashi Sugimura has accomplished many scientific achievements in the field of biochemistry and in cancer research. Sugimura's group identified the novel polymer poly(ADP-ribose) in parallel to P. Mandel's and O. Hayaishi's groups and demonstrated the presence of the enzyme poly(ADP-ribose) polymerase (PARP). He also discovered the cognate catabolic enzyme, poly(ADP-ribose) glycohydrolase (PARG) and further elucidated the biology of poly(ADP-ribose). The astonishing discovery of pierisin, an apoptogenic peptide that ADP-ribosyaltes DNA, profoundly illuminates his scientific character and curiosity as well. Sugimura's work in cancer research shows an extraordinarily wide range, which includes the establishment of new methods in chemical carcinogenesis, the identification of various environmental mutagens/carcinogens and new tumour promoters. He also established the concept that cancer is a disease of DNA and contributed to the development of the concept of the multi-step model of carcinogenesis.

  19. The efficient elimination of solid tumor cells by EGFR-specific and HER2-specific scFv-SNAP fusion proteins conjugated to benzylguanine-modified auristatin F.

    PubMed

    Woitok, Mira; Klose, Diana; Niesen, Judith; Richter, Wolfgang; Abbas, Muhammad; Stein, Christoph; Fendel, Rolf; Bialon, Magdalena; Püttmann, Christiane; Fischer, Rainer; Barth, Stefan; Kolberg, Katharina

    2016-10-28

    Antibody-drug conjugates (ADCs) combine the potency of cytotoxic drugs with the specificity of monoclonal antibodies (mAbs). Most ADCs are currently generated by the nonspecific conjugation of drug-linker reagents to certain amino acid residues in mAbs, resulting in a heterogeneous product. To overcome this limitation and prepare ADCs with a defined stoichiometry, we use SNAP-tag technology as an alternative conjugation strategy. This allows the site-specific conjugation of O(6)-benzylguanine (BG)-modified small molecules to SNAP-tag fusion proteins. To demonstrate the suitability of this system for the preparation of novel recombinant ADCs, here we conjugated SNAP-tagged single chain antibody fragments (scFvs) to a BG-modified version of auristatin F (AURIF). We used two scFv-SNAP fusion proteins targeting members of the epidermal growth factor receptor (EGFR) family that are frequently overexpressed in breast cancer. The conjugation of BG-AURIF to EGFR-specific 425(scFv)-SNAP and HER2-specific αHER2(scFv)-SNAP resulted in two potent recombinant ADCs that specifically killed breast cancer cell lines by inducing apoptosis when applied at nanomolar concentrations. These data confirm that SNAP-tag technology is a promising tool for the generation of novel recombinant ADCs.

  20. The surprising dynamics of a chain on a pulley: lift off and snapping.

    PubMed

    Brun, P-T; Audoly, Basile; Goriely, Alain; Vella, Dominic

    2016-06-01

    The motion of weights attached to a chain or string moving on a frictionless pulley is a classic problem of introductory physics used to understand the relationship between force and acceleration. Here, we consider the dynamics of the chain when one of the weights is removed and, thus, one end is pulled with constant acceleration. This simple change has dramatic consequences for the ensuing motion: at a finite time, the chain 'lifts off' from the pulley, and the free end subsequently accelerates faster than the end that is pulled. Eventually, the chain undergoes a dramatic reversal of curvature reminiscent of the crack or snap, of a whip. We combine experiments, numerical simulations and theoretical arguments to explain key aspects of this dynamical problem.

  1. Amplifying the response of soft actuators by harnessing snap-through instabilities

    PubMed Central

    Overvelde, Johannes T. B.; Kloek, Tamara; D’haen, Jonas J. A.; Bertoldi, Katia

    2015-01-01

    Soft, inflatable segments are the active elements responsible for the actuation of soft machines and robots. Although current designs of fluidic actuators achieve motion with large amplitudes, they require large amounts of supplied volume, limiting their speed and compactness. To circumvent these limitations, here we embrace instabilities and show that they can be exploited to amplify the response of the system. By combining experimental and numerical tools we design and construct fluidic actuators in which snap-through instabilities are harnessed to generate large motion, high forces, and fast actuation at constant volume. Our study opens avenues for the design of the next generation of soft actuators and robots in which small amounts of volume are sufficient to achieve significant ranges of motion. PMID:26283372

  2. Integrating competing dimensional models of personality: linking the SNAP, TCI, and NEO using Item Response Theory.

    PubMed

    Stepp, Stephanie D; Yu, Lan; Miller, Joshua D; Hallquist, Michael N; Trull, Timothy J; Pilkonis, Paul A

    2012-04-01

    Mounting evidence suggests that several inventories assessing both normal personality and personality disorders measure common dimensional personality traits (i.e., Antagonism, Constraint, Emotional Instability, Extraversion, and Unconventionality), albeit providing unique information along the underlying trait continuum. We used Widiger and Simonsen's (2005) pantheoretical integrative model of dimensional personality assessment as a guide to create item pools. We then used Item Response Theory (IRT) to compare the assessment of these five personality traits across three established dimensional measures of personality: the Schedule for Nonadaptive and Adaptive Personality (SNAP), the Temperament and Character Inventory (TCI), and the Revised NEO Personality Inventory (NEO PI-R). We found that items from each inventory map onto these five common personality traits in predictable ways. The IRT analyses, however, documented considerable variability in the item and test information derived from each inventory. Our findings support the notion that the integration of multiple perspectives will provide greater information about personality while minimizing the weaknesses of any single instrument.

  3. Effects of Management Practices on Meloidogyne incognita and Snap Bean Yield

    PubMed Central

    Smittle, D. A.; Johnson, A. W.

    1982-01-01

    Phenamiphos applied at 6.7 kg ai/ha through a solid set or a center pivot irrigation system with 28 mm of water effectively controlled root-knot nematodes, Meloidogyne incognita, and resulted in greater snap bean growth and yields irrespective of growing season, tillage method, or cover crop system. The percentage yield increases attributed to this method of M. incognita control over nontreated controls were 45% in the spring crop, and 90% and 409% in the fall crops following winter rye and fallow, respectively. Root galling was not affected by tillage systems or cover crop, but disk tillage resulted in over 50% reduction in bean yield compared with yields from the subsoil-bed tillage system. PMID:19295676

  4. Binding of calcium ions and SNAP-25 to the hexa EF-hand protein secretagogin

    PubMed Central

    Rogstam, Annika; Linse, Sara; Lindqvist, Anders; James, Peter; Wagner, Ludwig; Berggård, Tord

    2006-01-01

    Secretagogin is a hexa EF-hand protein, which has been identified as a novel potential tumour marker. In the present study, we show that secretagogin binds four Ca2+ ions (log K1=7.1±0.4, log K2=4.7±0.6, log K3=3.6±0.7 and log K4=4.6±0.6 in physiological salt buffers) with a [Ca2+]0.5 of approx. 25 μM. The tertiary structure of secretagogin changes significantly upon Ca2+ binding, but not upon Mg2+ binding, and the amount of exposed hydrophobic surface in secretagogin increases upon Ca2+ binding, but not upon Mg2+ binding. These properties suggest that secretagogin belongs to the ‘sensor’ family of Ca2+-binding proteins. However, in contrast with the prototypical Ca2+ sensor calmodulin, which interacts with a very large number of proteins, secretagogin is significantly less promiscuous. Only one secretagogin-interacting protein was reproducibly identified from insulinoma cell lysates and from bovine and mouse brain homogenates. This protein was identified as SNAP-25 (25 kDa synaptosome-associated protein), a protein involved in Ca2+-induced exocytosis in neurons and in neuroendocrine cells. Kd was determined to be 1.2×10−7 M in the presence of Ca2+ and 1.5×10−6 M in the absence of Ca2+. The comparatively low Ca2+ affinity for secretagogin and the fact that it undergoes Ca2+-induced conformational changes and interacts with SNAP-25 raise the possibility that secretagogin may link Ca2+ signalling to exocytotic processes. PMID:16939418

  5. Disposition of toxic PCB congeners in snapping turtle eggs: expressed as toxic equivalents of TCDD

    SciTech Connect

    Bryan, A.M.; Stone, W.B.; Olafsson, P.G.

    1987-11-01

    Studies of snapping turtles, taken from the region of the Upper Hudson River, in New York State, revealed exceedingly high levels of PCBs in the adipose tissue. There is evidence to suggest that large reserves of fat provide protection against chlorinated hydrocarbon toxicity. Such storage may protect snapping turtle eggs from disposition of toxic PCB congeners and account for the apparent absence of reports regarding detrimental effects on the hatchability of eggs from turtles living in the vicinity of the upper Hudson River. The present study was undertaken to determine if indeed these eggs are protected against disposition of toxic PCB congeners by the presence of large reserves of fat. Although tissue volumes play an important role in determining the initial site of disposition, the major factor controlling the elimination of these compounds involves metabolism. For simple halogenated benzenes as well as for more complex halogenated biphenyls, oxidative metabolism catalyzed by P-448, occurs primarily at the site of two adjacent unsubstituted carbon atoms via arene oxide formation leading to the formation of water soluble metabolites. Toxicological studies have demonstrated that the most toxic PCB congeners, isosteriomers of tetrachlorodibenzo-p-dioxin (TCDD), require no metabolic activation. These compounds have chlorine atoms in the meta and para positions of both rings. It may be concluded that the structures of PCB congeners and isomers which favor induction of cytochrome P-448 are also those which are toxic and resist metabolism. It is the objective of the present study to determine if the heavy fat bodies of the female turtle provide a sufficiently large sink to retain the toxic congeners and prevent their incorporation into the eggs.

  6. Probing Dark Energy via Weak Gravitational Lensing with the Supernova Acceleration Probe (SNAP)

    SciTech Connect

    Albert, J.; Aldering, G.; Allam, S.; Althouse, W.; Amanullah, R.; Annis, J.; Astier, P.; Aumeunier, M.; Bailey, S.; Baltay, C.; Barrelet, E.; Basa, S.; Bebek, C.; Bergstom, L.; Bernstein, G.; Bester, M.; Besuner, B.; Bigelow, B.; Blandford, R.; Bohlin, R.; Bonissent, A.; /Caltech /LBL, Berkeley /Fermilab /SLAC /Stockholm U. /Paris, IN2P3 /Marseille, CPPM /Marseille, Lab. Astrophys. /Yale U. /Pennsylvania U. /UC, Berkeley /Michigan U. /Baltimore, Space Telescope Sci. /Indiana U. /Caltech, JPL /Australian Natl. U., Canberra /American Astron. Society /Chicago U. /Cambridge U. /Saclay /Lyon, IPN

    2005-08-08

    SNAP is a candidate for the Joint Dark Energy Mission (JDEM) that seeks to place constraints on the dark energy using two distinct methods. The first, Type Ia SN, is discussed in a separate white paper. The second method is weak gravitational lensing, which relies on the coherent distortions in the shapes of background galaxies by foreground mass structures. The excellent spatial resolution and photometric accuracy afforded by a 2-meter space-based observatory are crucial for achieving the high surface density of resolved galaxies, the tight control of systematic errors in the telescope's Point Spread Function (PSF), and the exquisite redshift accuracy and depth required by this project. These are achieved by the elimination of atmospheric distortion and much of the thermal and gravity loads on the telescope. The SN and WL methods for probing dark energy are highly complementary and the error contours from the two methods are largely orthogonal. The nominal SNAP weak lensing survey covers 1000 square degrees per year of operation in six optical and three near infrared filters (NIR) spanning the range 350 nm to 1.7 {micro}m. This survey will reach a depth of 26.6 AB magnitude in each of the nine filters and allow for approximately 100 resolved galaxies per square arcminute, {approx} 3 times that available from the best ground-based surveys. Photometric redshifts will be measured with statistical accuracy that enables scientific applications for even the faint, high redshift end of the sample. Ongoing work aims to meet the requirements on systematics in galaxy shape measurement, photometric redshift biases, and theoretical predictions.

  7. Effects of ethylenediurea on snap bean at a range of ozone concentrations

    SciTech Connect

    Miller, J.E.; Pursley, W.A.; Heagle, A.S.

    1994-09-01

    Ethylenediurea (EDU) [N-[2-(2-Oxo-1-imidazolidinyl) ethyl]-N{prime}-phenylurea] often protects plants from visible foliar injury due ozone{sub 3}. A few studies have indicated that EDU can suppress plant growth and yield. Because of the potential value of EDU as a research and assessment tool, controlled field experiments with snap bean Phaseolus vulgaris L. ({open_quotes}BBL-290{close_quotes}) were performed to test the effectiveness of different EDU application rates used in open-top chambers in each of two experiments [charcoal-filtered (CF) air, nonfiltered (NF) air, and nominal O{sub 3} additions of 0.025 and 0.05 or 0.03 and 0.06 {mu}LL{sup -1}O{sub 3} to NF air]. Ethylenediurea was added biweekly to the potting medium . The EDU treatment concentration were 0, 14, 28, 56, and 120 and 0, 8, 16, and 32 mg EDU (active) L{sup -1} of potting medium in experiments one and two, respectively. Ethylenediurea provided some protection against O{sub 3}-induced foliar injury and growth suppression in both experiments. Measurements of net carbon exchange rate (NCER) and carbohydrate status of the tissues reflected the protective effects of EDU. In the first experiment EDU caused visible foliar injury at some growth stages and suppressed growth. In the second experiment, visible foliar injury was not caused by EDU at any concentration, but pod biomass (yield) was suppressed by EDU in CF chambers. The differences may have been due to environmental conditions (i.e., hot and dry during the first experiment and cooler during the second). Ethylenediurea also affected biomass partitioning in the plants grown in CF air (relative biomass was increased in leaves and decreased in pods). The results indicate that although EDU does protect or partially protect snap bean against O{sub 3} injury, it may also affect physiology and growth. 27 refs., 6 tabs.

  8. Proteolysis of SNAP-25 isoforms by botulinum neurotoxin types A, C, and E: domains and amino acid residues controlling the formation of enzyme-substrate complexes and cleavage.

    PubMed

    Vaidyanathan, V V; Yoshino, K; Jahnz, M; Dörries, C; Bade, S; Nauenburg, S; Niemann, H; Binz, T

    1999-01-01

    Tetanus toxin and the seven serologically distinct botulinal neurotoxins (BoNT/A to BoNT/G) abrogate synaptic transmission at nerve endings through the action of their light chains (L chains), which proteolytically cleave VAMP (vesicle-associated membrane protein)/synaptobrevin, SNAP-25 (synaptosome-associated protein of 25 kDa), or syntaxin. BoNT/C was reported to proteolyze both syntaxin and SNAP-25. Here, we demonstrate that cleavage of SNAP-25 occurs between Arg198 and Ala199, depends on the presence of regions Asn93 to Glu145 and Ile156 to Met202, and requires about 1,000-fold higher L chain concentrations in comparison with BoNT/A and BoNT/E. Analyses of the BoNT/A and BoNT/E cleavage sites revealed that changes in the carboxyl-terminal residues, in contrast with changes in the amino-terminal residues, drastically impair proteolysis. A proteolytically inactive BoNT/A L chain mutant failed to bind to VAMP/synaptobrevin and syntaxin, but formed a stable complex (KD = 1.9 x 10(-7) M) with SNAP-25. The minimal essential domain of SNAP-25 required for cleavage by BoNT/A involves the segment Met146-Gln197, and binding was optimal only with full-length SNAP-25. Proteolysis by BoNT/E required the presence of the domain Ile156-Asp186. Murine SNAP-23 was cleaved by BoNT/E and, to a reduced extent, by BoNT/A, whereas human SNAP-23 was resistant to all clostridial L chains. Lys185Asp or Pro182Arg mutations of human SNAP-23 induced susceptibility toward BoNT/E or toward both BoNT/A and BoNT/E, respectively.

  9. Ezrin/radixin/moesin proteins are high affinity targets for ADP-ribosylation by Pseudomonas aeruginosa ExoS.

    PubMed

    Maresso, Anthony W; Baldwin, Michael R; Barbieri, Joseph T

    2004-09-10

    Pseudomonas aeruginosa ExoS is a bifunctional type III-secreted cytotoxin. The N terminus (amino acids 96-233) encodes a GTPase-activating protein activity, whereas the C terminus (amino acids 234-453) encodes a factor-activating ExoS-dependent ADP-ribosyltransferase activity. The GTPase-activating protein activity inactivates the Rho GTPases Rho, Rac, and Cdc42 in cultured cells and in vitro, whereas the ADP-ribosylation by ExoS is poly-substrate-specific and includes Ras as an early target for ADP-ribosylation. Infection of HeLa cells with P. aeruginosa producing a GTPase-activating protein-deficient form of ExoS rounded cells, indicating the ADP-ribosyltransferase domain alone is sufficient to elicit cytoskeletal changes. Examination of substrates modified by type III-delivered ExoS identified a 70-kDa protein as an early and predominant target for ADP-ribosylation. Matrix-assisted laser desorption ionization mass spectroscopy identified this protein as moesin, a member of the ezrin/radixin/moesin (ERM) family of proteins. ExoS ADP-ribosylated recombinant moesin at a linear velocity that was 5-fold faster and with a K(m) that was 2 orders of magnitude lower than Ras. Moesin homologs ezrin and radixin were also ADP-ribosylated, indicating the ERMs collectively represent high affinity targets of ExoS. Type III delivered ExoS ADP-ribosylated moesin and ezrin (and/or radixin) in cultured HeLa cells. The ERM proteins contribute to cytoskeleton dynamics, and the ability of ExoS to ADP-ribosylate the ERM proteins links ADP-ribosylation with the cytoskeletal changes associated with ExoS intoxication.

  10. Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair.

    PubMed

    Marbaix, Alexandre Y; Noël, Gaëtane; Detroux, Aline M; Vertommen, Didier; Van Schaftingen, Emile; Linster, Carole L

    2011-12-02

    The reduced forms of NAD and NADP, two major nucleotides playing a central role in metabolism, are continuously damaged by enzymatic or heat-dependent hydration. We report the molecular identification of the eukaryotic dehydratase that repairs these nucleotides and show that this enzyme (Carkd in mammals, YKL151C in yeast) catalyzes the dehydration of the S form of NADHX and NADPHX, at the expense of ATP, which is converted to ADP. Surprisingly, the Escherichia coli homolog, YjeF, a bidomain protein, catalyzes a similar reaction, but using ADP instead of ATP. The latter reaction is ascribable to the C-terminal domain of YjeF. This represents an unprecedented example of orthologous enzymes using either ADP or ATP as phosphoryl donor. We also show that eukaryotic proteins homologous to the N-terminal domain of YjeF (apolipoprotein A-1-binding protein (AIBP) in mammals, YNL200C in yeast) catalyze the epimerization of the S and R forms of NAD(P)HX, thereby allowing, in conjunction with the energy-dependent dehydratase, the repair of both epimers of NAD(P)HX. Both enzymes are very widespread in eukaryotes, prokaryotes, and archaea, which together with the ADP dependence of the dehydratase in some species indicates the ancient origin of this repair system.

  11. Aero-Propulsion Technology (APT) Task V Low Noise ADP Engine Definition Study

    NASA Technical Reports Server (NTRS)

    Holcombe, V.

    2003-01-01

    A study was conducted to identify and evaluate noise reduction technologies for advanced ducted prop propulsion systems that would allow increased capacity operation and result in an economically competitive commercial transport. The study investigated the aero/acoustic/structural advancements in fan and nacelle technology required to match or exceed the fuel burned and economic benefits of a constrained diameter large Advanced Ducted Propeller (ADP) compared to an unconstrained ADP propulsion system with a noise goal of 5 to 10 EPNDB reduction relative to FAR 36 Stage 3 at each of the three measuring stations namely, takeoff (cutback), approach and sideline. A second generation ADP was selected to operate within the maximum nacelle diameter constrain of 160 deg to allow installation under the wing. The impact of fan and nacelle technologies of the second generation ADP on fuel burn and direct operating costs for a typical 3000 nm mission was evaluated through use of a large, twin engine commercial airplane simulation model. The major emphasis of this study focused on fan blade aero/acoustic and structural technology evaluations and advanced nacelle designs. Results of this study have identified the testing required to verify the interactive performance of these components, along with noise characteristics, by wind tunnel testing utilizing and advanced interaction rig.

  12. 45 CFR 95.625 - Increased FFP for certain ADP systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Increased FFP for certain ADP systems. 95.625 Section 95.625 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GENERAL... associated computer equipment that support the administration of State plans for Titles IV-D, IV-E,...

  13. 7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Processing Services means: (1) Services to operate ADP equipment, either by private sources, or by employees...) Services provided by private sources or by employees of the State agency or by State and local... operate the system; a description of system performance requirements; and a description of the...

  14. 7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Processing Services means: (1) Services to operate ADP equipment, either by private sources, or by employees...) Services provided by private sources or by employees of the State agency or by State and local... operate the system; a description of system performance requirements; and a description of the...

  15. 7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Processing Services means: (1) Services to operate ADP equipment, either by private sources, or by employees...) Services provided by private sources or by employees of the State agency or by State and local... operate the system; a description of system performance requirements; and a description of the...

  16. Poly(ADP-ribose) protects vascular smooth muscle cells from oxidative DNA damage

    PubMed Central

    Zhang, Chao; Luo, Tao; Cui, Shijun; Gu, Yongquan; Bian, Chunjing; Chen, Yibin; Yu, Xiaochun; Wang, Zhonggao

    2015-01-01

    Vascular smooth muscle cells (VSMCs) undergo death during atherosclerosis, a widespread cardiovascular disease. Recent studies suggest that oxidative damage occurs in VSMCs and induces atherosclerosis. Here, we analyzed oxidative damage repair in VSMCs and found that VSMCs are hypersensitive to oxidative damage. Further analysis showed that oxidative damage repair in VSMCs is suppressed by a low level of poly (ADP-ribosyl)ation (PARylation), a key post-translational modification in oxidative damage repair. The low level of PARylation is not caused by the lack of PARP-1, the major poly(ADP-ribose) polymerase activated by oxidative damage. Instead, the expression of poly(ADP-ribose) glycohydrolase, PARG, the enzyme hydrolyzing poly(ADP-ribose), is significantly higher in VSMCs than that in the control cells. Using PARG inhibitor to suppress PARG activity facilitates oxidative damage-induced PARylation as well as DNA damage repair. Thus, our study demonstrates a novel molecular mechanism for oxidative damage-induced VSMCs death. This study also identifies the use of PARG inhibitors as a potential treatment for atherosclerosis. [BMB Reports 2015; 48(6): 354-359] PMID:25748172

  17. 10 CFR 95.49 - Security of automatic data processing (ADP) systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Security of automatic data processing (ADP) systems. 95.49 Section 95.49 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Control of Information § 95.49 Security...

  18. 10 CFR 95.49 - Security of automatic data processing (ADP) systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Security of automatic data processing (ADP) systems. 95.49 Section 95.49 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Control of Information § 95.49 Security...

  19. Automated Data Processing Equipment for the Fleet Marine Force (ADPE-FMF).

    DTIC Science & Technology

    1982-06-01

    Systems Management Officer ( ISMO )--------------------------------------38 2. Information Systems Coordinator (ISC)-------39 3. Staff Officers...Management Officer ( ISMO ) of the First Marine Amphibious Force (IMAF), then spent the bulk of their time interviewing individual unit Information...interviews, the IMAF ISMO and his ADP personnel were interviewed. Interviews were taped for later review. E. FOLLOW-ON STUDY For the following four

  20. 48 CFR 245.608-72 - Screening excess automatic data processing equipment (ADPE).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Screening excess automatic data processing equipment (ADPE). 245.608-72 Section 245.608-72 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT GOVERNMENT PROPERTY Reporting, Redistribution, and Disposal...

  1. Improved Triacylglycerol Production in Acinetobacter baylyi ADP1 by Metabolic Engineering

    PubMed Central

    2011-01-01

    Background Triacylglycerols are used in various purposes including food applications, cosmetics, oleochemicals and biofuels. Currently the main sources for triacylglycerol are vegetable oils, and microbial triacylglycerol has been suggested as an alternative for these. Due to the low production rates and yields of microbial processes, the role of metabolic engineering has become more significant. As a robust model organism for genetic and metabolic studies, and for the natural capability to produce triacylglycerol, Acinetobacter baylyi ADP1 serves as an excellent organism for modelling the effects of metabolic engineering for energy molecule biosynthesis. Results Beneficial gene deletions regarding triacylglycerol production were screened by computational means exploiting the metabolic model of ADP1. Four deletions, acr1, poxB, dgkA, and a triacylglycerol lipase were chosen to be studied experimentally both separately and concurrently by constructing a knock-out strain (MT) with three of the deletions. Improvements in triacylglycerol production were observed: the strain MT produced 5.6 fold more triacylglycerol (mg/g cell dry weight) compared to the wild type strain, and the proportion of triacylglycerol in total lipids was increased by 8-fold. Conclusions In silico predictions of beneficial gene deletions were verified experimentally. The chosen single and multiple gene deletions affected beneficially the natural triacylglycerol metabolism of A. baylyi ADP1. This study demonstrates the importance of single gene deletions in triacylglycerol metabolism, and proposes Acinetobacter sp. ADP1 as a model system for bioenergetic studies regarding metabolic engineering. PMID:21592360

  2. Guidelines for developing NASA (National Aeronautics and Space Administration) ADP security risk management plans

    NASA Technical Reports Server (NTRS)

    Tompkins, F. G.

    1983-01-01

    This report presents guidance to NASA Computer security officials for developing ADP security risk management plans. The six components of the risk management process are identified and discussed. Guidance is presented on how to manage security risks that have been identified during a risk analysis performed at a data processing facility or during the security evaluation of an application system.

  3. Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion.

    PubMed

    Szabó, C; Dawson, V L

    1998-07-01

    Oxidative and nitrosative stress can trigger DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). This enzyme has also been termed poly(ADP-ribose) polymerase (PARP) or poly(ADP-ribose) transferase (pADPRT). Rapid activation of the enzyme depletes the intracellular concentration of its substrate, nicotinamide adenine dinucleotide, thus slowing the rate of glycolysis, electron transport and subsequently ATP formation. This process can result in cell dysfunction and cell death. In this article, Csaba Szabó and Valina Dawson overview the impact of pharmacological inhibition or genetic inactivation of PARS on the course of oxidant-induced cell death in vitro, and in inflammation and reperfusion injury in vivo. A major trigger for DNA damage in pathophysiological conditions is peroxynitrite, a cytotoxic oxidant formed by the reaction between the free radicals nitric oxide and superoxide. The pharmacological inhibition of poly(ADP-ribose) synthetase is a novel approach for the experimental therapy of various forms of inflammation and shock, stroke, myocardial and intestinal ischaemia-reperfusion, and diabetes mellitus.

  4. Poly(ADP-ribose) metabolism in brain and its role in ischemia pathology.

    PubMed

    Strosznajder, Robert Piotr; Czubowicz, Kinga; Jesko, Henryk; Strosznajder, Joanna Benigna

    2010-06-01

    The biological roles of poly(ADP-ribose) polymers (PAR) and poly(ADP-ribosyl)ation of proteins in the central nervous system are diverse. The homeostasis of PAR orchestrated by poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) is crucial for cell physiology and pathology. Both enzymes are ubiquitously distributed in neurons and glia; however, they are segregated at the subcellular level. PARP-1 serves as a "nick sensor" for single- or double-stranded breaks in DNA and is involved in long and short patch base-excision repair, while PARG breaks down PAR. The stimulation of PARP-1 and PAR formation can activate proinflammatory transcription factors, including nuclear factor kappa B. However, hyperactivation of PARP-1 can result in depletion of NAD/ATP, and in PAR-dependent mitochondrial pore formation leading to release of apoptosis inducing factor and cell death. The role of PAR as a death signaling molecule in brain ischemia-reperfusion and inflammation as well as the effect of gender and aging is presented in this review. Modulating the PAR level through pharmacological or genetic intervention on PARP-1/PARG activity and gene expression should be a valuable way for neuroprotective strategy.

  5. Does inhibition of poly(ADP-ribose) polymerase prevent energy overconsumption under microgravity?

    NASA Astrophysics Data System (ADS)

    Dobrota, C.; Piso, M. I.; Keul, A.

    When plants are exposed to a stress signal they expend a lot of energy and exhibit enhanced respiration rates This is partially due to a breakdown in the NAD pool caused by the enhanced activity PARP which uses NAD as a substrate to synthesize polymers of ADP-ribose Stress-induced depletion of NAD results in a similar depletion of energy since ATP molecules are required to resynthesize the depleted NAD It seems that plants with lowered poly ADP ribosyl ation activity appear tolerant to multiple stresses Inhibiting PARP activity prevents energy overconsumption under stress allowing normal mitochondrial respiration We intend to study if the microgravity is perceived by plants as a stress factor and if experimental inhibition of poly ADP-ribose polymerase may improve the energetic level of the cells References DeBlock M Verduyn C De Brouwer D and Cornelissen M 2005 Poly ADP-ribose polymerase in plants affects energy homeostasis cell death and stress tolerance The Plant Journal 41 95--106 Huang S Greenway H Colmerm T D and Millar A H 2005 Protein synthesis by rice coleoptiles during prolonged anoxia Implications for glycolysis growth and energy utilization Annals of Botany 96 703--715 Mittler R Vanderauwera S Gollery M and Van Breusegem F 2005 Reactive oxygen gene network of plants Trends in Plant Science 9 10 490-498

  6. Ectocellular in vitro and in vivo metabolism of cADP-ribose in cerebellum.

    PubMed Central

    De Flora, A; Guida, L; Franco, L; Zocchi, E; Pestarino, M; Usai, C; Marchetti, C; Fedele, E; Fontana, G; Raiteri, M

    1996-01-01

    CD38, a type II transmembrane glycoprotein predominantly expressed in blood cells, is a bifunctional ectoenzyme directly involved in the metabolism of cADP-ribose (cADPR). This is a potent Ca2+ mobilizer in several types of cells. The relationship between the ectocellular site of cADPR production and its intracellular calcium-related functions is poorly understood. Cultured rat cerebellar granule cells showed both enzymic activities of CD38, ADP-ribosyl cyclase and cADPR hydrolase, at a ratio of 16 to 1 respectively, and were immunostained by the anti-(human CD38) monoclonal antibody IB4. In these cells externally added cADPR and beta-NAD+ (the precursor of cADPR), but not alpha-NAD+ or ADP-ribose, enhanced the peak of the depolarization-induced rise in intracellular Ca2+ concentration. This effect was inhibited by 1 microM ryanodine, suggesting a potentiation of calcium-induced calcium release by cADPR. CD38 ectoenzyme activities, ADP-ribosyl cyclase and cADPR hydrolase, were also demonstrated in vivo by microdialysis of adult rat cerebellum, where IB4 bound to granule neurons selectively. Trace amounts (11.5 +/- 3.8 nM) of NAD+ were detected by microdialysis sampling and sensitive assays in the basal interstitial fluid of the cerebellum. These results provide a link between ectocellular cADPR turnover and intracellular calcium mobilization in cerebellum. PMID:8973582

  7. 7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... review of proposed contracts. Those standards include a requirement for maximum practical open and free... Processing Services means: (1) Services to operate ADP equipment, either by private sources, or by employees...) Services provided by private sources or by employees of the State agency or by State and...

  8. VERO cells harbor a poly-ADP-ribose belt partnering their epithelial adhesion belt.

    PubMed

    Lafon-Hughes, Laura; Vilchez Larrea, Salomé C; Kun, Alejandra; Fernández Villamil, Silvia H

    2014-01-01

    Poly-ADP-ribose (PAR) is a polymer of up to 400 ADP-ribose units synthesized by poly-ADP-ribose-polymerases (PARPs) and degraded by poly-ADP-ribose-glycohydrolase (PARG). Nuclear PAR modulates chromatin compaction, affecting nuclear functions (gene expression, DNA repair). Diverse defined PARP cytoplasmic allocation patterns contrast with the yet still imprecise PAR distribution and still unclear functions. Based on previous evidence from other models, we hypothesized that PAR could be present in epithelial cells where cadherin-based adherens junctions are linked with the actin cytoskeleton (constituting the adhesion belt). In the present work, we have examined through immunofluorescence and confocal microscopy, the subcellular localization of PAR in an epithelial monkey kidney cell line (VERO). PAR was distinguished colocalizing with actin and vinculin in the epithelial belt, a location that has not been previously reported. Actin filaments disruption with cytochalasin D was paralleled by PAR belt disruption. Conversely, PARP inhibitors 3-aminobenzamide, PJ34 or XAV 939, affected PAR belt synthesis, actin distribution, cell shape and adhesion. Extracellular calcium chelation displayed similar effects. Our results demonstrate the existence of PAR in a novel subcellular localization. An initial interpretation of all the available evidence points towards TNKS-1 as the most probable PAR belt architect, although TNKS-2 involvement cannot be discarded. Forthcoming research will test this hypothesis as well as explore the existence of the PAR belt in other epithelial cells and deepen into its functional implications.

  9. VERO cells harbor a poly-ADP-ribose belt partnering their epithelial adhesion belt

    PubMed Central

    Vilchez Larrea, Salomé C.; Kun, Alejandra

    2014-01-01

    Poly-ADP-ribose (PAR) is a polymer of up to 400 ADP-ribose units synthesized by poly-ADP-ribose-polymerases (PARPs) and degraded by poly-ADP-ribose-glycohydrolase (PARG). Nuclear PAR modulates chromatin compaction, affecting nuclear functions (gene expression, DNA repair). Diverse defined PARP cytoplasmic allocation patterns contrast with the yet still imprecise PAR distribution and still unclear functions. Based on previous evidence from other models, we hypothesized that PAR could be present in epithelial cells where cadherin-based adherens junctions are linked with the actin cytoskeleton (constituting the adhesion belt). In the present work, we have examined through immunofluorescence and confocal microscopy, the subcellular localization of PAR in an epithelial monkey kidney cell line (VERO). PAR was distinguished colocalizing with actin and vinculin in the epithelial belt, a location that has not been previously reported. Actin filaments disruption with cytochalasin D was paralleled by PAR belt disruption. Conversely, PARP inhibitors 3-aminobenzamide, PJ34 or XAV 939, affected PAR belt synthesis, actin distribution, cell shape and adhesion. Extracellular calcium chelation displayed similar effects. Our results demonstrate the existence of PAR in a novel subcellular localization. An initial interpretation of all the available evidence points towards TNKS-1 as the most probable PAR belt architect, although TNKS-2 involvement cannot be discarded. Forthcoming research will test this hypothesis as well as explore the existence of the PAR belt in other epithelial cells and deepen into its functional implications. PMID:25332845

  10. Further evidence for poly-ADP-ribosylated histones as DNA suppressors

    SciTech Connect

    Yu, F.L.; Geronimo, I.H.; Bender, W.; Meginniss, K.E.

    1986-05-01

    For many years histones have been considered to be the gene suppressors in eukaryotic cells. Recently, the authors have found strong evidence indicating that poly-ADP-ribosylated histones, rather than histones, are the potent inhibitors of DNA-dependent RNA synthesis. They now report additional evidence for this concept: 1) using histone inhibitor isolated directly from nuclei, the authors are able to confirm their earlier findings that the inhibitor substances are sensitive to pronase, snake venom phosphodiesterase digestion and 0.1N KOH hydrolysis, and are resistant to DNase I and RNase A digestion, 2) the O.D. 260/O.D.280 ratio of the histone inhibitor is between pure protein and nuclei acid, suggesting the inhibitor substance is a nucleoprotein hybrid. This result directly supports the fact that the isolated histone inhibitor is radioactive poly (ADP-ribose) labeled, 3) commercial histones show big differences in inhibitor activity. The authors believe this reflects the variation in poly-ADP-ribosylation among commercial histones, and 4) 0.1N KOH hydrolysis eliminates the poly (ADP-ribose) radioactivity from the acceptor proteins as well as histone inhibitor activity. Yet, on gel, the inhibitor shows identical histone bands and stain intensity before and after hydrolysis, indicating the histones per se are qualitatively and quantitatively unaffected by alkaline treatment. This result strongly suggests that histones themselves are not capable of inhibiting DNA-dependent RNA synthesis.

  11. Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae

    SciTech Connect

    Jorgensen, Rene; Purdy, Alexandra E.; Fieldhouse, Robert J.; Kimber, Matthew S.; Bartlett, Douglas H.; Merrill, A. Rod

    2008-07-15

    The ADP-ribosyltransferases are a class of enzymes that display activity in a variety of bacterial pathogens responsible for causing diseases in plants and animals, including those affecting mankind, such as diphtheria, cholera, and whooping cough. We report the characterization of a novel toxin from Vibrio cholerae, which we call cholix toxin. The toxin is active against mammalian cells (IC50 = 4.6 {+-} 0.4 ng/ml) and crustaceans (Artemia nauplii LD50 = 10 {+-} 2 {mu}g/ml). Here we show that this toxin is the third member of the diphthamide-specific class of ADP-ribose transferases and that it possesses specific ADP-ribose transferase activity against ribosomal eukaryotic elongation factor 2. We also describe the high resolution crystal structures of the multidomain toxin and its catalytic domain at 2.1- and 1.25-{angstrom} resolution, respectively. The new structural data show that cholix toxin possesses the necessary molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm, and inhibition of protein synthesis by specific modification of elongation factor 2. The crystal structures also provide important insight into the structural basis for activation of toxin ADP-ribosyltransferase activity. These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment.

  12. Three-Dimensional Structures Reveal Multiple ADP/ATP Binding Modes

    SciTech Connect

    C Simmons; C Magee; D Smith; L Lauman; J Chaput; J Allen

    2011-12-31

    The creation of synthetic enzymes with predefined functions represents a major challenge in future synthetic biology applications. Here, we describe six structures of de novo proteins that have been determined using protein crystallography to address how simple enzymes perform catalysis. Three structures are of a protein, DX, selected for its stability and ability to tightly bind ATP. Despite the addition of ATP to the crystallization conditions, the presence of a bound but distorted ATP was found only under excess ATP conditions, with ADP being present under equimolar conditions or when crystallized for a prolonged period of time. A bound ADP cofactor was evident when Asp was substituted for Val at residue 65, but ATP in a linear configuration is present when Phe was substituted for Tyr at residue 43. These new structures complement previously determined structures of DX and the protein with the Phe 43 to Tyr substitution [Simmons, C. R., et al. (2009) ACS Chem. Biol. 4, 649-658] and together demonstrate the multiple ADP/ATP binding modes from which a model emerges in which the DX protein binds ATP in a configuration that represents a transitional state for the catalysis of ATP to ADP through a slow, metal-free reaction capable of multiple turnovers. This unusual observation suggests that design-free methods can be used to generate novel protein scaffolds that are tailor-made for catalysis.

  13. Evidence that mono-ADP-ribosylation of CtBP1/BARS regulates lipid storage.

    PubMed

    Bartz, René; Seemann, Joachim; Zehmer, John K; Serrero, Ginette; Chapman, Kent D; Anderson, Richard G W; Liu, Pingsheng

    2007-08-01

    Mono-ADP-ribosylation is emerging as an important posttranslational modification that modulates a variety of cell signaling pathways. Here, we present evidence that mono-ADP-ribosylation of the transcriptional corepressor C terminal binding protein, brefeldin A (BFA)-induced ADP-ribosylated substrate (CtBP1/BARS) regulates neutral lipid storage in droplets that are surrounded by a monolayer of phospholipid and associated proteins. CtBP1/BARS is an NAD-binding protein that becomes ribosylated when cells are exposed to BFA. Both endogenous lipid droplets and droplets enlarged by oleate treatment are lost after 12-h exposure to BFA. Lipid loss requires new protein synthesis, and it is blocked by multiple ribosylation inhibitors, but it is not stimulated by disruption of the Golgi apparatus or the endoplasmic reticulum unfolded protein response. Small interfering RNA knockdown of CtBP1/BARS mimics the effect of BFA, and mouse embryonic fibroblasts derived from embryos that are deficient in CtBP1/BARS seem to be defective in lipid accumulation. We conclude that mono-ADP-ribosylation of CtBP1/BARS inactivates its repressor function, which leads to the activation of genes that regulate neutral lipid storage.

  14. Cyclic ADP-ribose as a universal calcium signal molecule in the nervous system.

    PubMed

    Higashida, Haruhiro; Salmina, Alla B; Olovyannikova, Raissa Ya; Hashii, Minako; Yokoyama, Shigeru; Koizumi, Keita; Jin, Duo; Liu, Hong-Xiang; Lopatina, Olga; Amina, Sarwat; Islam, Mohammad Saharul; Huang, Jian-Jun; Noda, Mami

    2007-01-01

    beta-NAD(+) is as abundant as ATP in neuronal cells. beta-NAD(+) functions not only as a coenzyme but also as a substrate. beta-NAD(+)-utilizing enzymes are involved in signal transduction. We focus on ADP-ribosyl cyclase/CD38 which synthesizes cyclic ADP-ribose (cADPR), a universal Ca(2+) mobilizer from intracellular stores, from beta-NAD(+). cADPR acts through activation/modulation of ryanodine receptor Ca(2+) releasing Ca(2+) channels. cADPR synthesis in neuronal cells is stimulated or modulated via different pathways and various factors. Subtype-specific coupling of various neurotransmitter receptors with ADP-ribosyl cyclase confirms the involvement of the enzyme in signal transduction in neurons and glial cells. Moreover, cADPR/CD38 is critical in oxytocin release from the hypothalamic cell dendrites and nerve terminals in the posterior pituitary. Therefore, it is possible that pharmacological manipulation of intracellular cADPR levels through ADP-ribosyl cyclase activity or synthetic cADPR analogues may provide new therapeutic opportunities for treatment of neurodevelopmental disorders.

  15. Poly(ADP-ribosyl)ation of a herpes simplex virus immediate early polypeptide

    SciTech Connect

    Preston, C.M.; Notarianni, E.L.

    1983-12-01

    In vitro poly(ADP-ribosyl)ation of the herpes simplex virus type 1 (HSV-1) immediate early polypeptide Vmw175 is reported. The phenomenon was most clearly observed by use of the temperature-sensitive mutant tsK, which overproduces Vmw175 at the nonpermissive temperature (NPT) and has a mutation in the coding sequences for this polypeptide. Nuclei prepared from cells which were infected with tsK at NPT and subsequently downshifted to the permissive temperature incorporated (/sup 32/P)NAD into Vmw175. This reaction did not occur when nuclei were prepared from cells constantly maintained at NPT, showing that only functional Vmw175 can be radiolabeled with (/sup 32/P)NAD. The identity of the acceptor protein was confirmed by demonstrating the expected electrophoretic mobility differences between the HSV-1 and HSV-2 counterparts of Vmw175. The use of suitable inhibitors demonstrated that the reaction represented mono- or poly(ADP-ribosyl)ation, and further analysis showed the presence of long poly(ADP-ribose) chains attached to Vmw175. Poly(ADP-ribosyl)ation may be important as a cause or result of the regulation of viral transcription by Vmw175. Radiolabeling of another virus-specified polypeptide (approximate molecular weight 38,000), thought to be a structural component of the input virus, is also reported.

  16. O6-alkylguanine-DNA transferase (SNAP) as capture module for site-specific covalent bioconjugation of targeting protein on nanoparticles

    NASA Astrophysics Data System (ADS)

    Mazzucchelli, Serena; Colombo, Miriam; Galbiati, Elisabetta; Corsi, Fabio; Montenegro, Josè M.; Parak, Wolfgang J.; Prosperi, Davide

    2013-02-01

    A bimodular genetic fusion comprising a delivery module (scFv) and a capture module (SNAP) is proposed as a novel strategy for the biologically mediated site-specific covalent conjugation of targeting proteins to nanoparticles. ScFv800E6, an scFv mutant selective for HER2 antigen overexpressed in breast cancer cells was chosen as targeting ligand. The fusion protein SNAP-scFv was irreversibly immobilized on magnetofluorescent nanoparticles through the recognition between SNAP module and pegylated O6-alkylguanine derivative. The targeting efficiency of the resulting nanoparticle against HER2-positive breast cancer cells was assessed by flow cytometry and immunofluorescence.

  17. The Pool of ADP and ATP Regulates Anaerobic Product Formation in Resting Cells of Lactococcus lactis

    PubMed Central

    Palmfeldt, Johan; Paese, Marco; Hahn-Hägerdal, Bärbel; van Niel, Ed W. J.

    2004-01-01

    Lactococcus lactis grows homofermentatively on glucose, while its growth on maltose under anaerobic conditions results in mixed acid product formation in which formate, acetate, and ethanol are formed in addition to lactate. Maltose was used as a carbon source to study mixed acid product formation as a function of the growth rate. In batch and nitrogen-limited chemostat cultures mixed acid product formation was shown to be linked to the growth rate, and homolactic fermentation occurred only in resting cells. Two of the four lactococcal strains investigated with maltose, L. lactis 65.1 and MG1363, showed more pronounced mixed acid product formation during growth than L. lactis ATCC 19435 or IL-1403. In resting cell experiments all four strains exhibited homolactic fermentation. In resting cells the intracellular concentrations of ADP, ATP, and fructose 1,6-bisphosphate were increased and the concentration of Pi was decreased compared with the concentrations in growing cells. Addition of an ionophore (monensin or valinomycin) to resting cultures of L. lactis 65.1 induced mixed acid product formation concomitant with decreases in the ADP, ATP, and fructose 1,6-bisphosphate concentrations. ADP and ATP were shown to inhibit glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and alcohol dehydrogenase in vitro. Alcohol dehydrogenase was the most sensitive enzyme and was totally inhibited at an adenine nucleotide concentration of 16 mM, which is close to the sum of the intracellular concentrations of ADP and ATP of resting cells. This inhibition of alcohol dehydrogenase might be partially responsible for the homolactic behavior of resting cells. A hypothesis regarding the level of the ATP-ADP pool as a regulating mechanism for the glycolytic flux and product formation in L. lactis is discussed. PMID:15345435

  18. The ADP/ATP Carrier and Its Relationship to Oxidative Phosphorylation in Ancestral Protist Trypanosoma brucei

    PubMed Central

    Gnipová, Anna; Šubrtová, Karolína; Panicucci, Brian; Horváth, Anton; Lukeš, Julius

    2015-01-01

    The highly conserved ADP/ATP carrier (AAC) is a key energetic link between the mitochondrial (mt) and cytosolic compartments of all aerobic eukaryotic cells, as it exchanges the ATP generated inside the organelle for the cytosolic ADP. Trypanosoma brucei, a parasitic protist of medical and veterinary importance, possesses a single functional AAC protein (TbAAC) that is related to the human and yeast ADP/ATP carriers. However, unlike previous studies performed with these model organisms, this study showed that TbAAC is most likely not a stable component of either the respiratory supercomplex III+IV or the ATP synthasome but rather functions as a physically separate entity in this highly diverged eukaryote. Therefore, TbAAC RNA interference (RNAi) ablation in the insect stage of T. brucei does not impair the activity or arrangement of the respiratory chain complexes. Nevertheless, RNAi silencing of TbAAC caused a severe growth defect that coincides with a significant reduction of mt ATP synthesis by both substrate and oxidative phosphorylation. Furthermore, TbAAC downregulation resulted in a decreased level of cytosolic ATP, a higher mt membrane potential, an elevated amount of reactive oxygen species, and a reduced consumption of oxygen in the mitochondria. Interestingly, while TbAAC has previously been demonstrated to serve as the sole ADP/ATP carrier for ADP influx into the mitochondria, our data suggest that a second carrier for ATP influx may be present and active in the T. brucei mitochondrion. Overall, this study provides more insight into the delicate balance of the functional relationship between TbAAC and the oxidative phosphorylation (OXPHOS) pathway in an early diverged eukaryote. PMID:25616281

  19. NADP/sup +/ enhances cholera and pertussis toxin-catalyzed ADP-ribosylation of membrane proteins

    SciTech Connect

    Kawai, Y.; Whitsel, C.; Arinze, I.J.

    1986-05-01

    Cholera or pertussis toxin-catalyzed (/sup 32/P)ADP-ribosylation is frequently used to estimate the concentration of the stimulatory (Ns) or inhibitory (Ni) guanine nucleotide regulatory proteins which modulate the activity of adenylate cyclase. With this assay, however, the degradation of the substrate, NAD/sup +/, by endogenous enzymes such as NAD/sup +/-glycohydrolase (NADase) present in the test membranes can influence the results. In this study the authors show that both cholera and pertussis toxin-catalyzed (/sup 32/P)ADP-ribosylation of liver membrane proteins is markedly enhanced by NADP/sup +/. The effect is concentration dependent; with 20 ..mu..M (/sup 32/P)NAD/sup +/ as substrate maximal enhancement is obtained at 0.5-1.0 mM NADP/sup +/. The enhancement of (/sup 32/P)ADP-ribosylation by NADP/sup +/ was much greater than that by other known effectors such as Mg/sup 2 +/, phosphate or isoniazid. The effect of NADP/sup +/ on ADP-ribosylation may occur by inhibition of the degradation of NAD/sup +/ probably by acting as an alternate substrate for NADase. Among inhibitors tested (NADP/sup +/, isoniazid, imidazole, nicotinamide, L-Arg-methyl-ester and HgCl/sub 2/) to suppress NADase activity, NADP/sup +/ was the most effective and, 10 mM, inhibited activity of the enzyme by about 90%. In membranes which contain substantial activities of NADase the inclusion of NADP/sup +/ in the assay is necessary to obtain maximal ADP-ribosylation.

  20. Caloric Beverage Intake Among Adult Supplemental Nutrition Assistance Program Participants

    PubMed Central

    2014-01-01

    Objectives. We compared sugar-sweetened beverage (SSB), alcohol, and other caloric beverage (juice and milk) consumption of Supplemental Nutrition Assistance Program (SNAP) participants with that of low-income nonparticipants. Methods. We used 1 day of dietary intake data from the 2005–2008 National Health and Nutrition Examination Survey for 4594 adults aged 20 years and older with household income at or below 250% of the federal poverty line. We used bivariate and multivariate methods to compare the probability of consuming and the amount of calories consumed for each beverage type across 3 groups: current SNAP participants, former participants, and nonparticipants. We used instrumental variable methods to control for unobservable differences in participant groups. Results. After controlling for observable characteristics, SNAP participants were no more likely to consume SSBs than were nonparticipants. Instrumental variable estimates showed that current participants consumed fewer calories from SSBs than did similar nonparticipants. We found no differences in alcoholic beverage consumption, which cannot be purchased with SNAP benefits. Conclusions. SNAP participants are not unique in their consumption of SSBs or alcoholic beverages. Purchase restrictions may have little effect on SSB consumption. PMID:25033141