WorldWideScience

Sample records for program atp proposal

  1. Program Proposal

    Science.gov (United States)

    Baskas, Richard S.

    2012-01-01

    A study was conducted to determine if a deficiency, or learning gap, existed in a particular working environment. To determine if an assessment was to be conducted, a program proposal would need to be developed to explore this situation. In order for a particular environment to react and grow with other environments, it must be able to take on…

  2. Using alternative transient program and electromagnetic transients programs (ATP/EMTP in lightning overvoltages analysis

    Directory of Open Access Journals (Sweden)

    Mrvić Jovan

    2016-01-01

    Full Text Available The goal of this paper is to introduce a procedure for risk assessment of insulation failure due to storm surges. The simulations were carried out in ATP / EMTP software, which allowed the use of the Monte Carlo method for the statistical analysis of insulation coordination. The paper gives a detailed account of modelling of all the elements relevant to the analysis. At the same time, the capabilities of the programming language MODELS (allows the creation and implementation of new complex components within the ATP software are discussed.

  3. Non conventional transient analysis of modelling and control systems using ATP program; Analise transitoria de sistemas de controle e modelagem de sistemas nao convencionais no programa ATP

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Marco Polo [FURNAS Centrais Eletricas S.A., Rio de Janeiro, RJ (Brazil); Fonseca, Claudio S. [Marte Engenharia Ltda (Brazil); Carvalho, Dourival S.; Dube, Laurent

    1995-12-31

    The digital program called Alternative Transients Program (ATP) which is generally used to simulate electromagnets transients in electric power systems presents two basic alternatives for the simulation of control and modelling of non conventional elements. The main objective of this work is to present the potential utilization of one routine of such program, called MODELS, compared to another routine, called TACS. A case study is presented 4 figs., 6 refs.

  4. Molecular basis of multidrug transport by ATP-binding cassette transporters : A proposed two-cylinder engine model

    NARCIS (Netherlands)

    van Veen, HW; Higgins, CF; Konings, WN

    ATP-binding cassette multidrug transporters are probably present in all living cells, and are able to export a variety of structurally unrelated compounds at the expense of ATP hydrolysis. The elevated expression of these proteins in multidrug resistant cells interferes with the drug-based control

  5. Prevalence of the metabolic syndrome using the Third Report of the National Cholesterol Educational Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) and the modified ATP III definitions for Japanese and Mongolians.

    Science.gov (United States)

    Enkhmaa, Byambaa; Shiwaku, Kuninori; Anuurad, Erdembileg; Nogi, Akiko; Kitajima, Keiko; Yamasaki, Masayuki; Oyunsuren, Tsendsuren; Yamane, Yosuke

    2005-02-01

    A clustering of insulin resistance, hypertension, and dyslipidemia has been labeled as metabolic syndrome. Asians have a lower frequency of obesity than do Caucasians but have an increasing tendency toward metabolic syndrome. We conducted a cross-sectional study of individuals aged 30-60 years. We analyzed the health data of 596 Japanese and Mongolians for metabolic syndrome based on the Third Report of the National Cholesterol Educational Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) definition and the three modified ATP III definitions. The prevalence of metabolic syndrome using ATP III criteria was 6% for the Japanese and 12% for the Mongolians, a remarkable lower prevalence relative to the reported prevalence in the United States. With the exception of visceral obesity, the prevalences of individual metabolic abnormalities within each of the two Asian groups were similar to each other and to reported rates of prevalence in the United States. A universal metabolic syndrome definition is inappropriate for comparisons of metabolic syndrome among Asian ethnic groups. We believe that the ATP III index for visceral obesity should be adjusted for Asian populations.

  6. Federal Aviation Administration retained savings program proposal

    Energy Technology Data Exchange (ETDEWEB)

    Hostick, D.J.; Larson, L.L. [Pacific Northwest National Lab., Richland, WA (United States); Hostick, C.J. [IBP, Inc., Pasco, WA (United States)

    1998-03-01

    Federal legislation allows federal agencies to retain up to 50% of the savings associated with implementing energy efficiency and water conservation measures and practices. Given budget pressures to reduce expenditures, the use of retained savings to fund additional projects represents a source of funds outside of the traditional budget cycle. The Southwest Region Federal Aviation Administration (FAA) has tasked Pacific Northwest National Laboratory (PNNL) to develop a model retained savings program for Southwest Region FAA use and as a prototype for consideration by the FAA. PNNL recommends the following steps be taken in developing a Southwest Region FAA retained savings program: Establish a retained savings mechanism. Determine the level at which the retained savings should be consolidated into a fund. The preliminary recommendation is to establish a revolving efficiency loan fund at the regional level. Such a mechanism allows some consolidation of savings to fund larger projects, while maintaining a sense of facility ownership in that the funds will remain within the region.

  7. TEACHING ADMINISTRATION: PROPOSAL OF THE PROGRAM CONTENT

    Directory of Open Access Journals (Sweden)

    Eduardo Ribeiro Rodrigues

    2016-08-01

    Full Text Available The National Curriculum Guidelines established by MEC (Brazilian Ministry of Education, define the specific areas of vocational training content that should be included in the curricular organization of undergraduate courses in Brazil, without suggesting or detailing which content should be offered in each area. In this sense, this study aims at proposing the course syllabus for the financial area for the undergraduate courses of Management. To achieve this goal, the curriculum matrices and the teaching plans of the financial discipline of the undergraduate courses on Management with the highest grades in ENADE were analyzed. Based on this survey, seven disciplines were elaborated with the professional qualification contents of the area, with 560 hours/class in total, distributed in the curriculum matrix, according to their goals: presentation of corporate finance and personal finance, short and long-term financial decisions, financial economic analysis, financial planning, and financial strategies.

  8. The reliability of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF) definitions in diagnosing metabolic syndrome (MetS) among Gaza Strip Palestinians.

    Science.gov (United States)

    Sirdah, Mahmoud M; Abu Ghali, Asmaa S; Al Laham, Nahed A

    2012-01-01

    Metabolic syndrome (MetS) which is a multifaceted syndrome, has been demonstrated as a common precursor for developing cardiovascular diseases and/or type 2 diabetes mellitus. Different diagnostic definitions for MetS have been proposed and recommended. We set up to evaluate the reliabilities of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF) definitions in diagnosing MetS among Gaza Strip Palestinians. This cross sectional study involved a randomly selected two hundred and thirty apparently healthy adults from the Gaza Strip. Anthropometric measurements, blood pressure, fasting plasma glucose, lipid profile, and questionnaire interviews were performed. The overall prevalence of MetS in our Gaza Strip cohort was 23.0% and 39.5% according to NCEP/ATP III and IDF definitions respectively (pIII showed an increased prevalence of MetS with age, and body mass index (BMI), however they revealed different prevalence trends with sex. Except for BMI, there were no significant differences in the general and metabolic related characteristics between subjects with MetS of IDF and NCEP/ATP III definitions. Independently of the definition used, MetS is highly prevalent in Gaza Strip population, with a steady increase in MetS prevalence through age and BMI. The IDF definition tends to give higher values for MetS prevalence, and therefore could be more appropriate for diagnosing MetS in Gaza Strip cohort. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  9. Proposal for Supply Chain Concentration in the Traditional MBA Program

    Science.gov (United States)

    Ramaswamy, K. V.

    2012-01-01

    The purpose of this proposal is to develop and implement a concentration in Supply Chain Management in the existing traditional MBA program effective fall 2012. Houston is the hub for many multinational oil and energy companies, large healthcare systems, wholesale/retail businesses, engineering and construction companies, and is a major city along…

  10. ATP as a biological hydrotrope.

    Science.gov (United States)

    Patel, Avinash; Malinovska, Liliana; Saha, Shambaditya; Wang, Jie; Alberti, Simon; Krishnan, Yamuna; Hyman, Anthony A

    2017-05-19

    Hydrotropes are small molecules that solubilize hydrophobic molecules in aqueous solutions. Typically, hydrotropes are amphiphilic molecules and differ from classical surfactants in that they have low cooperativity of aggregation and work at molar concentrations. Here, we show that adenosine triphosphate (ATP) has properties of a biological hydrotrope. It can both prevent the formation of and dissolve previously formed protein aggregates. This chemical property is manifested at physiological concentrations between 5 and 10 millimolar. Therefore, in addition to being an energy source for biological reactions, for which micromolar concentrations are sufficient, we propose that millimolar concentrations of ATP may act to keep proteins soluble. This may in part explain why ATP is maintained in such high concentrations in cells. Copyright © 2017, American Association for the Advancement of Science.

  11. Cost estimate for a proposed GDF Suez LNG testing program

    Energy Technology Data Exchange (ETDEWEB)

    Blanchat, Thomas K.; Brady, Patrick Dennis; Jernigan, Dann A.; Luketa, Anay Josephine; Nissen, Mark R.; Lopez, Carlos; Vermillion, Nancy; Hightower, Marion Michael

    2014-02-01

    At the request of GDF Suez, a Rough Order of Magnitude (ROM) cost estimate was prepared for the design, construction, testing, and data analysis for an experimental series of large-scale (Liquefied Natural Gas) LNG spills on land and water that would result in the largest pool fires and vapor dispersion events ever conducted. Due to the expected cost of this large, multi-year program, the authors utilized Sandia's structured cost estimating methodology. This methodology insures that the efforts identified can be performed for the cost proposed at a plus or minus 30 percent confidence. The scale of the LNG spill, fire, and vapor dispersion tests proposed by GDF could produce hazard distances and testing safety issues that need to be fully explored. Based on our evaluations, Sandia can utilize much of our existing fire testing infrastructure for the large fire tests and some small dispersion tests (with some modifications) in Albuquerque, but we propose to develop a new dispersion testing site at our remote test area in Nevada because of the large hazard distances. While this might impact some testing logistics, the safety aspects warrant this approach. In addition, we have included a proposal to study cryogenic liquid spills on water and subsequent vaporization in the presence of waves. Sandia is working with DOE on applications that provide infrastructure pertinent to wave production. We present an approach to conduct repeatable wave/spill interaction testing that could utilize such infrastructure.

  12. Proposal for a unified selection to medical residency programs.

    Science.gov (United States)

    Toffoli, Sônia Ferreira Lopes; Ferreira Filho, Olavo Franco; Andrade, Dalton Francisco de

    2013-01-01

    This paper proposes the unification of entrance exams to medical residency programs (MRP) in Brazil. Problems related to MRP and its interface with public health problems in Brazil are highlighted and how this proposal are able to help solving these problems. The proposal is to create a database to be applied in MRP unified exams. Some advantages of using the Item Response Theory (IRT) in this database are highlighted. The MRP entrance exams are developed and applied decentralized where each school is responsible for its examination. These exams quality are questionable. Reviews about items quality, validity and reliability of appliances are not common disclosed. Evaluation is important in every education system bringing on required changes and control of teaching and learning. The proposal of MRP entrance exams unification, besides offering high quality exams to institutions participants, could be as an extra source to rate medical school and cause improvements, provide studies with a database and allow a regional mobility. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  13. R&D Proposal for the National Muon Acccelerator Program

    Energy Technology Data Exchange (ETDEWEB)

    2010-02-01

    This document contains a description of a multi-year national R&D program aimed at completing a Design Feasibility Study (DFS) for a Muon Collider and, with international participation, a Reference Design Report (RDR) for a muon-based Neutrino Factory. It also includes the supporting component development and experimental efforts that will inform the design studies and permit an initial down-selection of candidate technologies for the ionization cooling and acceleration systems. We intend to carry out this plan with participants from the host national laboratory (Fermilab), those from collaborating U.S. national laboratories (ANL, BNL, Jlab, LBNL, and SNAL), and those from a number of other U.S. laboratories, universities, and SBIR companies. The R&D program that we propose will provide the HEP community with detailed information on future facilities based on intense beams of muons - the Muon Collider and the Neutrino Factory. We believe that these facilities offer the promise of extraordinary physics capabilities. The Muon Collider presents a powerful option to explore the energy frontier and the Neutrino Factory gives the opportunity to perform the most sensitive neutrino oscillation experiments possible, while also opening expanded avenues for the study of new physics in the neutrino sector. The synergy between the two facilities presents the opportunity for an extremely broad physics program and a unique pathway in accelerator facilities. Our work will give clear answers to the questions of expected capabilities and performance of these muon-based facilities, and will provide defensible ranges for their cost. This information, together with the physics insights gained from the next-generation neutrino and LHC experiments, will allow the HEP community to make well-informed decisions regarding the optimal choice of new facilities. We believe that this work is a critical part of any broad strategic program in accelerator R&D and, as the P5 panel has recently

  14. R&D PROPOSAL FOR THE NATIONAL MUON ACCELERATOR PROGRAM

    Energy Technology Data Exchange (ETDEWEB)

    Muon Accelerator Program; Zisman, Michael S.; Geer, Stephen

    2010-02-24

    This document contains a description of a multi-year national R&D program aimed at completing a Design Feasibility Study (DFS) for a Muon Collider and, with international participation, a Reference Design Report (RDR) for a muon-based Neutrino Factory. It also includes the supporting component development and experimental efforts that will inform the design studies and permit an initial down-selection of candidate technologies for the ionization cooling and acceleration systems. We intend to carry out this plan with participants from the host national laboratory (Fermilab), those from collaborating U.S. national laboratories (ANL, BNL, Jlab, LBNL, and SNAL), and those from a number of other U.S. laboratories, universities, and SBIR companies. The R&D program that we propose will provide the HEP community with detailed information on future facilities based on intense beams of muons--the Muon Collider and the Neutrino Factory. We believe that these facilities offer the promise of extraordinary physics capabilities. The Muon Collider presents a powerful option to explore the energy frontier and the Neutrino Factory gives the opportunity to perform the most sensitive neutrino oscillation experiments possible, while also opening expanded avenues for the study of new physics in the neutrino sector. The synergy between the two facilities presents the opportunity for an extremely broad physics program and a unique pathway in accelerator facilities. Our work will give clear answers to the questions of expected capabilities and performance of these muon-based facilities, and will provide defensible ranges for their cost. This information, together with the physics insights gained from the next-generation neutrino and LHC experiments, will allow the HEP community to make well-informed decisions regarding the optimal choice of new facilities. We believe that this work is a critical part of any broad strategic program in accelerator R&D and, as the P5 panel has recently

  15. A proposed application programming interface for a physical volume repository

    Science.gov (United States)

    Jones, Merritt; Williams, Joel; Wrenn, Richard

    1996-01-01

    The IEEE Storage System Standards Working Group (SSSWG) has developed the Reference Model for Open Storage Systems Interconnection, Mass Storage System Reference Model Version 5. This document, provides the framework for a series of standards for application and user interfaces to open storage systems. More recently, the SSSWG has been developing Application Programming Interfaces (APIs) for the individual components defined by the model. The API for the Physical Volume Repository is the most fully developed, but work is being done on APIs for the Physical Volume Library and for the Mover also. The SSSWG meets every other month, and meetings are open to all interested parties. The Physical Volume Repository (PVR) is responsible for managing the storage of removable media cartridges and for mounting and dismounting these cartridges onto drives. This document describes a model which defines a Physical Volume Repository, and gives a brief summary of the Application Programming Interface (API) which the IEEE Storage Systems Standards Working Group (SSSWG) is proposing as the standard interface for the PVR.

  16. Journey in guidelines for lipid management: From adult treatment panel (ATP-I to ATP-III and what to expect in ATP-IV

    Directory of Open Access Journals (Sweden)

    P G Talwalkar

    2013-01-01

    Full Text Available Adult Treatment Panel (ATP, an expert panel to supervise cholesterol management was set up under the aegis of National Cholesterol Education Program (NCEP in 1985. Since then NCEP-ATP has been revising and framing guidelines to enable clinician to deliver better treatment to cardiovascular patients and to educate general people. As a result, considerable reduction in cardiovascular related deaths has been observed in recent times. All three ATP guidelines viz. ATP-I, ATP-II and ATP-III have targeted low density lipoprotein as their primary goal. The ATP-III guideline was updated in the light of evidences from 5-major clinical trials and was released in 2004. It added therapeutic lifestyle changes, concept of risk equivalents, Framingham CHD-risk score non-high density lipoprotein cholesterol (non-HDL-C as secondary target and gave strong emphasis on metabolic risk factors. The earlier treat-to-target paradigm faced fierce criticism from clinicians across the globe because of insufficient proof of safety and benefits of treating patients with respect to an individual′s low density lipoprotein (LDL level. Further, demonstration of non-HDL-C and total cholesterol/HDL-C ratio as strong predictors of overall cardiovascular risk foresees new guidelines. A tailored-treatment approach was suggested instead of LDL-C target based treatment approach which was soundly based on direct clinical trials evidences and proposes treatment based on individual′s overall 5- to 10-year cardiovascular risk irrespective of LDL-C level, leading to lower number of people on high dose/s of statins. Recent report of the Cholesterol Treatment Trialist′s Collaborators meta-analysis strongly supported primary prevention of LDL with statins in low risk individuals and showed that its benefits completely outweighed its known hazards. Markers other than LDL-C like apolipoprotein B, non-HDL-C and total cholesterol/HDL-C ratio would take precedence in the risk assessment and

  17. Journey in guidelines for lipid management: From adult treatment panel (ATP)-I to ATP-III and what to expect in ATP-IV.

    Science.gov (United States)

    Talwalkar, P G; Sreenivas, C G; Gulati, Ashish; Baxi, Hemang

    2013-07-01

    Adult Treatment Panel (ATP), an expert panel to supervise cholesterol management was set up under the aegis of National Cholesterol Education Program (NCEP) in 1985. Since then NCEP-ATP has been revising and framing guidelines to enable clinician to deliver better treatment to cardiovascular patients and to educate general people. As a result, considerable reduction in cardiovascular related deaths has been observed in recent times. All three ATP guidelines viz. ATP-I, ATP-II and ATP-III have targeted low density lipoprotein as their primary goal. The ATP-III guideline was updated in the light of evidences from 5-major clinical trials and was released in 2004. It added therapeutic lifestyle changes, concept of risk equivalents, Framingham CHD-risk score non-high density lipoprotein cholesterol (non-HDL-C) as secondary target and gave strong emphasis on metabolic risk factors. The earlier treat-to-target paradigm faced fierce criticism from clinicians across the globe because of insufficient proof of safety and benefits of treating patients with respect to an individual's low density lipoprotein (LDL) level. Further, demonstration of non-HDL-C and total cholesterol/HDL-C ratio as strong predictors of overall cardiovascular risk foresees new guidelines. A tailored-treatment approach was suggested instead of LDL-C target based treatment approach which was soundly based on direct clinical trials evidences and proposes treatment based on individual's overall 5- to 10-year cardiovascular risk irrespective of LDL-C level, leading to lower number of people on high dose/s of statins. Recent report of the Cholesterol Treatment Trialist's Collaborators meta-analysis strongly supported primary prevention of LDL with statins in low risk individuals and showed that its benefits completely outweighed its known hazards. Markers other than LDL-C like apolipoprotein B, non-HDL-C and total cholesterol/HDL-C ratio would take precedence in the risk assessment and strong emphasis would

  18. Muscle interstitial ATP and norepinephrine concentrations in the human leg during exercise and ATP infusion

    DEFF Research Database (Denmark)

    Mortensen, Stefan P.; Gonzalez-Alonso, Jose; Nielsen, Jens Jung

    2009-01-01

    ATP has been proposed to play multiple roles in local skeletal muscle blood flow regulation by inducing vasodilation and modulating sympathetic vasoconstrictor activity, but the mechanism remain unclear. Here we evaluated the effects of arterial ATP infusion and exercise on limb muscle interstitial...... local concentration. Key words: sympathetic nerve activity, vasodilation, endothelium, skeletal muscle....

  19. Technical Proposal Salton Sea Geothermal Power Pilot Plant Program

    Energy Technology Data Exchange (ETDEWEB)

    None

    1975-03-28

    The proposed Salton Sea Geothermal Power Pilot Plant Program comprises two phases. The objective of Phase 1 is to develop the technology for power generation from high-temperature, high-salinity geothermal brines existing in the Salton Sea known geothermal resources area. Phase 1 work will result in the following: (a) Completion of a preliminary design and cost estimate for a pilot geothermal brine utilization facility. (b) Design and construction of an Area Resource Test Facility (ARTF) in which developmental geothermal utilization concepts can be tested and evaluated. Program efforts will be divided into four sub-programs; Power Generation, Mineral Extraction, Reservoir Production, and the Area Resources Test Facility. The Power Generation Subprogram will include testing of scale and corrosion control methods, and critical power cycle components; power cycle selection based on an optimization of technical, environmental and economic analyses of candidate cycles; preliminary design of a pilot geothermal-electric generating station to be constructed in Phase 2 of this program. The Mineral Extraction Subprogram will involve the following: selection of an optimum mineral recovery process; recommendation of a brine clean-up process for well injection enhancement; engineering, construction and operation of mineral recovery and brine clean-up facilities; analysis of facility operating results from environmental, economical and technical point-of-view; preliminary design of mineral recovery and brine clean-up facilities of sufficient size to match the planned pilot power plant. The Reservoir Production Subprogram will include monitoring the operation and maintenance of brine production, handling and injection systems which were built with private funding in phase 0, and monitoring of the brine characteristics and potential subsidence effects during well production and injection. Based on the above, recommendations and specifications will be prepared for production and

  20. 78 FR 23818 - Urbanized Area Formula Program: Proposed Circular

    Science.gov (United States)

    2013-04-22

    ... inaccurate, and now interprets each provision to require their application at the UZA level. In other words... Program (5337) Rural Area Formula Program (5311) Transit Oriented Development Pilot Program (section 20005...

  1. Transcriptional organization of the large and the small ATP synthase operons, atpI/H/F/A and atpB/E, in Arabidopsis thaliana chloroplasts.

    Science.gov (United States)

    Malik Ghulam, Mustafa; Zghidi-Abouzid, Ouafa; Lambert, Emeline; Lerbs-Mache, Silva; Merendino, Livia

    2012-06-01

    The ATP synthase is a ubiquitous enzyme which is found in bacteria and eukaryotic organelles. It is essential in the photosynthetic and respiratory processes, by transforming the electrochemical proton gradient into ATP energy via proton transport across the membranes. In Escherichia coli, the atp genes coding for the subunits of the ATP synthase enzyme are grouped in the same transcriptional unit, while in higher plants the plastid atp genes are organized into a large (atpI/H/F/A) and a small (atpB/E) atp operon. By using the model plant Arabidopsis thaliana, we have investigated the strategy evolved in chloroplasts to overcome the physical separation of the atp gene clusters and to coordinate their transcription. We show that all the identified promoters in the two atp operons are PEP dependent and require sigma factors for specific recognition. Our results indicate that transcription of the two atp operons is initiated by at least one common factor, the essential SIG2 factor. Our data show that SIG3 and SIG6 also participate in transcription initiation of the large and the small atp operon, respectively. We propose that SIG2 might be the factor responsible for coordinating the basal transcription of the plastid atp genes and that SIG3 and SIG6 might serve to modulate plastid atp expression with respect to physiological and environmental conditions. However, we observe that in the sigma mutants (sig2, sig3 and sig6) the deficiency in the recognition of specific atp promoters is largely balanced by mRNA stabilization and/or by activation of otherwise silent promoters, indicating that the rate-limiting step for expression of the atp operons is mostly post-transcriptional.

  2. 78 FR 24431 - Notice of Submission of Proposed Information Collection to OMB; Housing Counseling Training Program

    Science.gov (United States)

    2013-04-25

    ... Training Program AGENCY: Office of the Chief Information Officer, HUD. ACTION: Notice. SUMMARY: The... lists the following information: Title of Proposed: Housing Counseling Training Program. OMB Approval... the information and proposed use: The Housing Counseling Training NOFA, which requests narrative...

  3. ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Masaki Nakano

    2017-08-01

    Full Text Available Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances, which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen receptor-related receptors are expected to raise cellular ATP levels via enhancing ATP production. Here, we show that esculetin functions as an ERR agonist, and its addition to culture media enhances glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels. Subsequently, we show the neuroprotective efficacies of KUSs, esculetin, and GSK4716 (an ERRγ agonist against cell death in Parkinson's disease models. In the surviving neurons, ATP levels and expression levels of α-synuclein and CHOP (an ER stress-mediated cell death executor were all rectified. We propose that maintenance of ATP levels, by inhibiting ATP consumption or enhancing ATP production, or both, would be a promising therapeutic strategy for Parkinson's disease.

  4. [Participatory evaluation in health programs: a proposal for the Adolescent Health Care Program].

    Science.gov (United States)

    Bursztyn, Ivani; Ribeiro, José Mendes

    2005-01-01

    This article presents a model for participatory evaluation of the Adolescent Health Program (PROSAD) in Brazil. The study focuses on the concept of participation, with a review of internationally validated planning methodologies (RAP, logFRAME, ZOPP, PCM) and the programmatic characteristics of PROSAD. The proposed model comprises 4 steps, involving the constitution of the analytical matrix, a self-evaluation workshop, a summary of results, and graphic representation. The model promotes participatory practice in health program management by using techniques that allow a workshop to be held in 70 minutes (mean time), producing results that are recognized and easily grasped by the local team.

  5. 76 FR 67200 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Science.gov (United States)

    2011-10-31

    ... HUMAN SERVICES National Institutes of Health Proposed National Toxicology Program (NTP) Review Process... the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS... Toxicology Program. BILLING CODE 4140-01-P ...

  6. 76 FR 3080 - Agency Information Collection Activities: Proposed Collection; Comment Request-Food Programs...

    Science.gov (United States)

    2011-01-19

    ...), and the Senior Farmers' Market Nutrition Program (SFMNP). Currently, the nutrition assistance programs... Food and Nutrition Service Agency Information Collection Activities: Proposed Collection; Comment Request--Food Programs Reporting System AGENCY: Food and Nutrition Service (FNS), USDA. ACTION: Notice...

  7. 78 FR 20612 - Agency Information Collection Activities: Proposed Collection; Comment Request-Food Programs...

    Science.gov (United States)

    2013-04-05

    ...) and the Senior Farmers' Market Nutrition Program (SFMNP). Currently, the nutrition assistance programs...; ] DEPARTMENT OF AGRICULTURE Food and Nutrition Service Agency Information Collection Activities: Proposed Collection; Comment Request--Food Programs Reporting System AGENCY: Food and Nutrition Service (FNS), USDA...

  8. Adenosine triphosphate (ATP) as a possible indicator of extraterrestrial biology

    Science.gov (United States)

    Chappelle, E. W.; Picciolo, G. L.

    1974-01-01

    The ubiquity of adenosine triphosphate (ATP) in terrestrial organisms provides the basis for proposing the assay of this vital metabolic intermediate for detecting extraterrestrial biological activity. If an organic carbon chemistry is present on the planets, the occurrence of ATP is possible either from biosynthetic or purely chemical reactions. However, ATP's relative complexity minimizes the probability of abiogenic synthesis. A sensitive technique for the quantitative detection of ATP was developed using the firefly bioluminescent reaction. The procedure was used successfully for the determination of the ATP content of soil and bacteria. This technique is also being investigated from the standpoint of its application in clinical medicine.

  9. 75 FR 5760 - Proposed Information Collection; Comment Request; Western Alaska Community Development Quota Program

    Science.gov (United States)

    2010-02-04

    ... National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Western Alaska Community Development Quota Program AGENCY: National Oceanic and Atmospheric Administration (NOAA... opportunity to comment on proposed and/or continuing information collections, as required by the Paperwork...

  10. 75 FR 60169 - Proposed Information Collection (Vetbiz Vendor Information Pages Verification Program) Activity...

    Science.gov (United States)

    2010-09-29

    ... AFFAIRS Proposed Information Collection (Vetbiz Vendor Information Pages Verification Program) Activity... use of other forms of information technology. Title: Vetbiz Vendor Information Pages Verification... collection. Abstract: Vetbiz Vendor Information Pages Verification Program is used to assist federal agencies...

  11. 77 FR 17458 - Proposed Information Collection; Comment Request; Observer Programs' Information that Can Be...

    Science.gov (United States)

    2012-03-26

    ... Programs' Information that Can Be Gathered Only Through Questions AGENCY: National Oceanic and Atmospheric... action and proposed management options; and (5) ensure that the observer programs can safely and...

  12. 75 FR 75693 - Rehabilitation Mortgage Insurance Underwriting Program Section 203(k); Notice of Proposed...

    Science.gov (United States)

    2010-12-06

    ... URBAN DEVELOPMENT Rehabilitation Mortgage Insurance Underwriting Program Section 203(k); Notice of... INFORMATION CONTACT: Arlene Nunes, Deputy Director, Home Mortgage Insurance Division, Office of Single Family... information: Title of Proposal: Rehabilitation Mortgage Insurance Underwriting Program Section 203(k). OMB...

  13. 76 FR 71037 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Science.gov (United States)

    2011-11-16

    ... HUMAN SERVICES Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens... Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS); National Institutes... (see ADDRESSES). Dated: November 8, 2011. John R. Bucher, Associate Director, National Toxicology...

  14. 78 FR 29331 - Proposed Information Collection; Comment Request; Western Alaska Community Development Quota Program

    Science.gov (United States)

    2013-05-20

    ... current information collection. The Western Alaska Community Development Quota (CDQ) Program is an... National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Western Alaska Community Development Quota Program AGENCY: National Oceanic and Atmospheric Administration (NOAA...

  15. Validation of a proposal for evaluating hospital infection control programs.

    Science.gov (United States)

    Silva, Cristiane Pavanello Rodrigues; Lacerda, Rúbia Aparecida

    2011-02-01

    To validate the construct and discriminant properties of a hospital infection prevention and control program. The program consisted of four indicators: technical-operational structure; operational prevention and control guidelines; epidemiological surveillance system; and prevention and control activities. These indicators, with previously validated content, were applied to 50 healthcare institutions in the city of São Paulo, Southeastern Brazil, in 2009. Descriptive statistics were used to characterize the hospitals and indicator scores, and Cronbach's α coefficient was used to evaluate the internal consistency. The discriminant validity was analyzed by comparing indicator scores between groups of hospitals: with versus without quality certification. The construct validity analysis was based on exploratory factor analysis with a tetrachoric correlation matrix. The indicators for the technical-operational structure and epidemiological surveillance presented almost 100% conformity in the whole sample. The indicators for the operational prevention and control guidelines and the prevention and control activities presented internal consistency ranging from 0.67 to 0.80. The discriminant validity of these indicators indicated higher and statistically significant mean conformity scores among the group of institutions with healthcare certification or accreditation processes. In the construct validation, two dimensions were identified for the operational prevention and control guidelines: recommendations for preventing hospital infection and recommendations for standardizing prophylaxis procedures, with good correlation between the analysis units that formed the guidelines. The same was found for the prevention and control activities: interfaces with treatment units and support units were identified. Validation of the measurement properties of the hospital infection prevention and control program indicators made it possible to develop a tool for evaluating these programs

  16. 77 FR 30305 - Notice of Proposed Information Collection; Comment Request Housing Counseling Program

    Science.gov (United States)

    2012-05-22

    ... URBAN DEVELOPMENT Notice of Proposed Information Collection; Comment Request Housing Counseling Program.... This Notice also lists the following information: Title of Proposal: Housing Counseling Program. OMB...: Nonprofit Housing Counseling organizations submit information to HUD through Grants.gov when applying for...

  17. 76 FR 22411 - Notice of Proposed Information Collection: Comment Request; Housing Counseling Program...

    Science.gov (United States)

    2011-04-21

    ... URBAN DEVELOPMENT Notice of Proposed Information Collection: Comment Request; Housing Counseling Program--Application for Approval as a Housing Counseling Agency AGENCY: Office of the Assistant Secretary for Housing... information: Title of Proposal: Housing Counseling Program--Application for Approval as a Housing Counseling...

  18. 75 FR 52393 - Proposed Data Collection; Comment Request: New Markets Tax Credit (NMTC) Program-Allocation...

    Science.gov (United States)

    2010-08-25

    ... Proposed Data Collection; Comment Request: New Markets Tax Credit (NMTC) Program--Allocation Application... the New Markets Tax Credit (NMTC) Program--Allocation Application (hereafter, the Application). DATES...: Direct all comments to Rosa Martinez, Acting NMTC Program Manager, Community Development Financial...

  19. 77 FR 39342 - Proposed Information Collection (Homeless Providers Grant and Per Diem Program) Activity; Comment...

    Science.gov (United States)

    2012-07-02

    .../or per diem for programs to assist homeless veterans' transition to independent living and to... AFFAIRS Proposed Information Collection (Homeless Providers Grant and Per Diem Program) Activity; Comment.... Titles a. Homeless Providers Grant and Per Diem Program, Capital Grant. Application, VA Form 10-0361-CG...

  20. 75 FR 60398 - California: Proposed Authorization of State Hazardous Waste Management Program Revision

    Science.gov (United States)

    2010-09-30

    ... AGENCY 40 CFR Part 271 California: Proposed Authorization of State Hazardous Waste Management Program... application for authorization for changes to its hazardous waste management program by November 1, 2010... waste management program. EPA continues to have independent enforcement authority under RCRA sections...

  1. 78 FR 77204 - Proposed Information Collection (VA National Veterans Sports Programs and Special Event Surveys...

    Science.gov (United States)

    2013-12-20

    ... AFFAIRS Proposed Information Collection (VA National Veterans Sports Programs and Special Event Surveys... solicits comments on the information needed to evaluate the National Veterans Sports Programs and Special... ``OMB Control No. 2900-NEW (VA National Veterans Sports Programs and Special Event Surveys)'' in any...

  2. Reformation or Reclassification? A Proposal of a Rating System for Youth Sport Programs

    Science.gov (United States)

    Wiersma, Lenny D.

    2005-01-01

    The vast diversity in goals and emphases of sport programs for children and the potential problems that exist when a child is enrolled in a program that does not best serve his/her needs accentuate the need for a rating system for youth sport programs. The current proposal of a youth sport rating scale would provide information for parents on the…

  3. 75 FR 23851 - Medicare Program; Proposed Changes to the Hospital Inpatient Prospective Payment Systems for...

    Science.gov (United States)

    2010-05-04

    ... medical education I-O Input-Output IOM Institute of Medicine IPF Inpatient psychiatric facility IPPS... Determinations 6. RHQDAPU Program Disaster Extensions and Waivers 7. Proposed Chart Validation Requirements for...

  4. 76 FR 44306 - Proposed Information Collection; Comment Request; Fisheries Finance Program Requirements

    Science.gov (United States)

    2011-07-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Fisheries Finance Program Requirements AGENCY: National Oceanic and Atmospheric Administration (NOAA), Commerce...

  5. 77 FR 50457 - Agency Information Collection Activities: Proposed Collection; Comment Request-WIC Program...

    Science.gov (United States)

    2012-08-21

    ... foods, nutrition education, and health care referrals to low income, nutritionally at risk pregnant... Food and Nutrition Service Agency Information Collection Activities: Proposed Collection; Comment Request--WIC Program Regulations--Reporting and Recordkeeping Burden AGENCY: Food and Nutrition Service...

  6. 75 FR 67948 - Proposed Information Collection; Comment Request; Marine Recreational Information Program (Marine...

    Science.gov (United States)

    2010-11-04

    ... Proposed Information Collection; Comment Request; Marine Recreational Information Program (Marine... renewal of an existing information collection. Marine recreational anglers are surveyed for catch and effort data, fish biology data, and angler socioeconomic characteristics. These data are required to...

  7. 75 FR 27789 - Proposed Collection; Comment Request; Application for the Pharmacology Research Associate Program

    Science.gov (United States)

    2010-05-18

    ... projects to be submitted to the Office of Management and Budget (OMB) for review and approval. Proposed... program is to develop leaders in pharmacological research for key positions in academic, industrial, and...

  8. 76 FR 38197 - Notice of Submission of Proposed Information Collection to OMB; Housing Counseling Program...

    Science.gov (United States)

    2011-06-29

    ... URBAN DEVELOPMENT Notice of Submission of Proposed Information Collection to OMB; Housing Counseling... provide oversight for agencies approved to participate in the Housing Counseling Program. Specifically... counseling aids tenants and homeowners in ] improving their housing conditions and in meeting the...

  9. 78 FR 17354 - Proposed Information Collection; Comment Request; Western Pacific Community Development Program...

    Science.gov (United States)

    2013-03-21

    ... Collection The collection of information of a community development plan involves no forms, and respondents... National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Western Pacific Community Development Program Process AGENCY: National Oceanic and Atmospheric Administration...

  10. 77 FR 43428 - Financial Management Service; Proposed Collection of Information: Minority Bank Deposit Program...

    Science.gov (United States)

    2012-07-24

    ... Fiscal Service Financial Management Service; Proposed Collection of Information: Minority Bank Deposit Program (MBDP) Certification Form for Admission AGENCY: Financial Management Service, Fiscal Service, Treasury. ACTION: Notice and Request for comments. SUMMARY: The Financial Management Service, as part of...

  11. Pilot program to assess proposed basic quality assurance requirements in the medical use of byproduct materials

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, E.; Nelson, K.; Meinhold, C.B. (Brookhaven National Lab., Upton, NY (United States))

    1991-10-01

    In January 1990, the Nuclear Regulatory Commission (NRC) proposed amendments to 10 CFR Part 35 that would require medical licensees using byproduct material to establish and implement a basic quality assurance program. A 60-day real-world trial of the proposed rules was initiated to obtain information beyond that generally found through standard public comment procedures. Volunteers from randomly selected institutions had opportunities to review the details of the proposed regulations and to implement these rules on a daily basis during the trial. The participating institutions were then asked to evaluate the proposed regulations based on their personal experiences. The pilot project sought to determine whether medical institutions could develop written quality assurance programs that would meet the eight performance-based objectives of proposed Section 35.35. In addition, the NRC wanted to learn from these volunteers if they had any recommendations on how the rule could be revised to minimized its cost and to clarify its objectives without decreasing its effectiveness. It was found that licensees could develop acceptable QA programs under a performance-based approach, that most licensee programs did meet the proposed objectives, and that most written QA plans would require consultations with NRC or Agreement State personnel before they would fully meet all objectives of proposed Section 35.35. This report describes the overall pilot program. The methodology used to select and assemble the group of participating licensees is presented. The various workshops and evaluation questionnaires are discussed, and detailed findings are presented. 7 refs.

  12. Dynamics of the metal binding domains and regulation of the human copper transporters ATP7B and ATP7A.

    Science.gov (United States)

    Yu, Corey H; Dolgova, Natalia V; Dmitriev, Oleg Y

    2017-04-01

    Copper transporters ATP7A and ATP7B regulate copper levels in the human cells and deliver copper to the biosynthetic pathways. ATP7A and ATP7B belong to the P-type ATPases and share much of the domain architecture and the mechanism of ATP hydrolysis with the other, well-studied, enzymes of this type. A unique structural feature of the copper ATPases is the chain of six cytosolic metal-binding domains (MBDs), which are believed to be involved in copper-dependent regulation of the activity and intracellular localization of these enzymes. Although the structures of all the MBDs have been solved, the mechanism of copper-dependent regulation of ATP7B and ATP7A, the roles of individual MBDs, and the relationship between the regulatory and catalytic copper binding are still unknown. We describe the structure and dynamics of the MBDs, review the current knowledge about their functional roles and propose a mechanism of regulation of ATP7B by copper-dependent changes in the dynamics and conformation of the MBD chain. Transient interactions between the MBDs, rather than transitions between distinct static conformations are likely to form the structural basis of regulation of the ATP-dependent copper transporters in human cells. © 2016 IUBMB Life, 69(4):226-235, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  13. 76 FR 24041 - Notice of Proposed Information Collection: Comment Request; HUD Housing Counseling Program-Agency...

    Science.gov (United States)

    2011-04-29

    ... Counseling Agencies and maintains a toll free housing counseling hotline, performance reviews help HUD ensure... URBAN DEVELOPMENT Notice of Proposed Information Collection: Comment Request; HUD Housing Counseling... information: Title of Proposal: HUD Housing Counseling Program--Agency Performance Review. OMB Control Number...

  14. 77 FR 50150 - Notice of Proposed Information Collection for Public Comment: Debt Resolution Program

    Science.gov (United States)

    2012-08-20

    ... URBAN DEVELOPMENT Notice of Proposed Information Collection for Public Comment: Debt Resolution Program... (OMB) for review, as required by the Paperwork Reduction Act. The Department is soliciting public... comments from members of the public and affected agencies concerning the proposed collection of information...

  15. 77 FR 29647 - Medicare Program; Solicitation for Proposals for the Medicare Graduate Nurse Education...

    Science.gov (United States)

    2012-05-18

    ... [CMS-5052-N2] Medicare Program; Solicitation for Proposals for the Medicare Graduate Nurse Education... participate in the Medicare Graduate Nurse Education (GNE) Demonstration. DATES: Proposals will be considered...--(A) 1 or more applicable schools of nursing; and (B) 2 or more applicable non- hospital community...

  16. 77 FR 39722 - Notice of Proposed Information Collection for Public Comment: Housing Choice Voucher Program...

    Science.gov (United States)

    2012-07-05

    ... sample. For the current OMB request, the research team proposes three main types of data collection: (1... Act. The Department is soliciting public comments on the subject proposal. This request is for the... accurate information on the costs of administering the HCV program across a national sample of high- [[Page...

  17. 75 FR 9120 - Energy Conservation Program: Public Meeting and Availability of the Notice of Proposed Rulemaking...

    Science.gov (United States)

    2010-03-01

    ...; ] DEPARTMENT OF ENERGY 10 CFR Part 431 RIN 1904-AB85 Energy Conservation Program: Public Meeting and Availability of the Notice of Proposed Rulemaking for Walk-In Coolers and Walk-In Freezers; Date Change AGENCY: Office of Energy Efficiency and Renewable Energy, Department of Energy. ACTION: Proposed rulemaking; date...

  18. Proposal for Indicators to Evaluate the Quality of a Postgraduate Program in Education

    Directory of Open Access Journals (Sweden)

    Edgar Oliver Cardoso Espinosa

    2011-11-01

    Full Text Available It is now imperative for those postgraduate programs oriented toward Education to meet the quality standards set by the National Postgraduate-Quality Program (PNPC, since this constitutes the Federal Government's main guideline for allocating resources. The present study aims to propose indicators that would allow assessment of postgraduate-program quality in Education by using the following criteria as a basis for analysis: efficacy, efficiency, importance, equity and relevance. It also indicates the status of these programs to the CONACYT, a minimal involvement, demonstrating the need to establish indicators that would serve as a guide for cataloguing programs according to their quality.

  19. 76 FR 53882 - Proposed Information Collection; Comment Request; Trade Fair Certification Program Application

    Science.gov (United States)

    2011-08-30

    ... International Trade Administration Proposed Information Collection; Comment Request; Trade Fair Certification... and instructions should be directed to Michael Thompson, Trade Fair Certification Program, U.S... . SUPPLEMENTARY INFORMATION: I. Abstract The Trade Fair Certification (TFC) Program is a service of the U.S...

  20. 77 FR 16319 - Proposed Renewal; Comment Request; Anti-Money Laundering Programs for Various Financial Institutions

    Science.gov (United States)

    2012-03-20

    ... Financial Crimes Enforcement Network Proposed Renewal; Comment Request; Anti-Money Laundering Programs for... develop and implement written anti-money laundering programs reasonably designed to prevent those financial institutions from being used to facilitate money laundering and the financing of terrorist...

  1. 76 FR 15052 - Proposed Information Collection (Time Record (Work-Study Program); Comment Request

    Science.gov (United States)

    2011-03-18

    ... AFFAIRS Proposed Information Collection (Time Record (Work-Study Program); Comment Request AGENCY... of automated collection techniques or the use of other forms of information technology. Title: Time Record (Work-Study Program)), VA Form 22-8690. OMB Control Number: 2900-0379. Type of Review: Extension...

  2. 77 FR 65244 - 60-Day Notice of Proposed Information Collection: Smart Traveler Enrollment Program

    Science.gov (United States)

    2012-10-25

    ... Notice of Proposed Information Collection: Smart Traveler Enrollment Program ACTION: Notice of request... 1995, we are requesting comments on this collection from all interested individuals and organizations...: Smart Traveler Enrollment Program (STEP) OMB Control Number: 1405-0152 Type of Request: Extension...

  3. 78 FR 1916 - 30-Day Notice of Proposed Information Collection: Smart Traveler Enrollment Program

    Science.gov (United States)

    2013-01-09

    ... Notice of Proposed Information Collection: Smart Traveler Enrollment Program ACTION: Notice of request... comments on this collection from all interested individuals and organizations. The purpose of this Notice... Information Collection: Smart Traveler Enrollment Program (STEP). OMB Control Number: 1405-0152. Type of...

  4. 78 FR 31999 - 30-Day Notice of Proposed Information Collection: Iran Democracy Program Grants Vetting

    Science.gov (United States)

    2013-05-28

    ... Notice of Proposed Information Collection: Iran Democracy Program Grants Vetting ACTION: Notice of...: Iran Program Grants Vetting. OMB Control Number: 1405-0176. Type of Request: Extension. ] Originating... conduct this vetting, the Department collects information from grantees and sub-grantees regarding the...

  5. 75 FR 25307 - 30-Day Notice of Proposed Information Collection: DS-4100, Iran Program Grants Vetting...

    Science.gov (United States)

    2010-05-07

    ... Notice of Proposed Information Collection: DS-4100, Iran Program Grants Vetting, Information Collection... Department conduct a vetting of potential Iran programs grantees and sub-grantees for counter-terrorism purposes. To conduct this vetting the Department envisions collecting information from grantees and sub...

  6. 78 FR 15798 - 60-Day Notice of Proposed Information Collection: Iran Democracy Program Grants Vetting

    Science.gov (United States)

    2013-03-12

    ... Notice of Proposed Information Collection: Iran Democracy Program Grants Vetting ACTION: Notice of... to conduct vetting of potential Iran ] program grantees and sub-grantees for counter-terrorism purposes. To conduct this vetting, the Department collects information from grantees and sub-grantees...

  7. 75 FR 2181 - 60-Day Notice of Proposed Information Collection: DS-4100, Iran Program Grants Vetting...

    Science.gov (United States)

    2010-01-14

    ... Notice of Proposed Information Collection: DS-4100, Iran Program Grants Vetting, Information Collection... Foreign Assets Control (OFAC) mandates that the Department conduct a vetting of potential Iran programs grantees and sub-grantees for counter-terrorism purposes. To conduct this vetting the Department envisions...

  8. 77 FR 24766 - Call for Proposals for a Micro Support Program on International Conflict Resolution and...

    Science.gov (United States)

    2012-04-25

    ... funding, and provide financial and report management oversight. Deadline: Friday, May 11, 2012 at 3 p.m... PEACE Call for Proposals for a Micro Support Program on International Conflict Resolution and... Support Program on International Conflict Resolution and Peacebuilding. The United States Institute of...

  9. 75 FR 78798 - Airport Improvement Program: Proposed Changes to Benefit Cost Analysis (BCA) Threshold

    Science.gov (United States)

    2010-12-16

    ... Federal Aviation Administration Airport Improvement Program: Proposed Changes to Benefit Cost Analysis... requiring benefit cost analyses (BCA) for capacity projects when applying for Airport Improvement Program... Friday, except Federal holidays. Privacy: We will post all comments we receive, without change, to http...

  10. 78 FR 5479 - Notice of Proposed Information Collection: Comment Request; Housing Counseling Training Program

    Science.gov (United States)

    2013-01-25

    ... Training Program AGENCY: Office of the Assistant Secretary for Housing, HUD. ACTION: Notice. SUMMARY: The.... This Notice also lists the following information: Title of Proposal: Housing Counseling Training Program. OMB Control Number, if applicable: 2502-0567. Description of the need for the information and...

  11. 75 FR 78939 - Senior Community Service Employment Program; Notice of Proposed Rulemaking, Additional Indicator...

    Science.gov (United States)

    2010-12-17

    ... Program; Notice of Proposed Rulemaking, Additional Indicator on Volunteer Work; Correction AGENCY... Service Employment Program (SCSEP), Additional Indicator on Volunteer Work that was published on November 23, 2010. The NPRM updates the SCSEP regulations to add an indicator to measure the number of exiting...

  12. 78 FR 32242 - Notice of Proposed Collection Requests; Comment Request; Program for International Student...

    Science.gov (United States)

    2013-05-29

    ... Notice of Proposed Collection Requests; Comment Request; Program for International Student Assessment...) for the Program for International Student Assessments (PISA 2015) Recruitment and Field Test, 1850... will include an assessment of students' financial literacy. From the sample of students that take the...

  13. Lightning Protection Performance Assessment of Transmission Line Based on ATP model Automatic Generation

    Directory of Open Access Journals (Sweden)

    Luo Hanwu

    2016-01-01

    Full Text Available This paper presents a novel method to solve the initial lightning breakdown current by combing ATP and MATLAB simulation software effectively, with the aims to evaluate the lightning protection performance of transmission line. Firstly, the executable ATP simulation model is generated automatically according to the required information such as power source parameters, tower parameters, overhead line parameters, grounding resistance and lightning current parameters, etc. through an interface program coded by MATLAB. Then, the data are extracted from the generated LIS files which can be obtained by executing the ATP simulation model, the occurrence of transmission lie breakdown can be determined by the relative data in LIS file. The lightning current amplitude should be reduced when the breakdown occurs, and vice the verse. Thus the initial lightning breakdown current of a transmission line with given parameters can be determined accurately by continuously changing the lightning current amplitude, which is realized by a loop computing algorithm that is coded by MATLAB software. The method proposed in this paper can generate the ATP simulation program automatically, and facilitates the lightning protection performance assessment of transmission line.

  14. Electric field driven torque in ATP synthase.

    Directory of Open Access Journals (Sweden)

    John H Miller

    Full Text Available FO-ATP synthase (FO is a rotary motor that converts potential energy from ions, usually protons, moving from high- to low-potential sides of a membrane into torque and rotary motion. Here we propose a mechanism whereby electric fields emanating from the proton entry and exit channels act on asymmetric charge distributions in the c-ring, due to protonated and deprotonated sites, and drive it to rotate. The model predicts a scaling between time-averaged torque and proton motive force, which can be hindered by mutations that adversely affect the channels. The torque created by the c-ring of FO drives the γ-subunit to rotate within the ATP-producing complex (F1 overcoming, with the aid of thermal fluctuations, an opposing torque that rises and falls with angular position. Using the analogy with thermal Brownian motion of a particle in a tilted washboard potential, we compute ATP production rates vs. proton motive force. The latter shows a minimum, needed to drive ATP production, which scales inversely with the number of proton binding sites on the c-ring.

  15. ATP release and purinergic signaling in NLRP3 inflammasome activation

    Directory of Open Access Journals (Sweden)

    Isabelle eCOUILLIN

    2013-01-01

    Full Text Available The NLRP3 inflammasome is a protein complex involved in IL-1β and IL-18 processing that senses pathogen- and danger-associated molecular patterns. One step- or two step- models have been proposed to explain the tight regulation of IL-1β production during inflammation. Moreover, cellular stimulation triggers ATP release and subsequent activation of purinergic receptors at the cell surface. Importantly some studies have reported roles for extracellular ATP (eATP, in NLRP3 inflammasome activation in response to PAMPs and DAMPs. In this mini review, we will discuss the link between active ATP release, purinergic signaling and NLRP3 inflammasome activation. We will focus on the role of autocrine or paracrine ATP export in particle-induced NLRP3 inflammasome activation and discuss how particle activators are competent to induce maturation and secretion of IL-1β through a process that involves, as a first event, extracellular release of endogenous ATP through hemichannel opening, and as a second event, signaling through purinergic receptors that trigger NLRP3 inflammasome activation. Finally, we will review the evidence for ATP as a key proinflammatory mediator released by dying cells. In particular we will discuss how cancer cells dying via autophagy trigger ATP-dependent NLRP3 inflammasome activation in the macrophages engulfing them, eliciting an immunogenic response against tumors.

  16. Striking a Balance between Program Requirements and GT Principles: Writing a compromised GT proposal

    Directory of Open Access Journals (Sweden)

    Sherry L. Xie, Ph.D. Candidate

    2009-06-01

    Full Text Available Glaser’s term “compromised GT proposal” (2001, p.114 refers to the type of Grounded Theory (GT proposal that is written in order to conform to the requirements of a standardized qualitative research proposal. A GT proposal needs only to supply information on the area of interest, the data source and a statement of method to the effect that the researcher begin to collect, code and analyse the data and let the theory emerge. Thus, the proposal may only occupy “a page or two” (Glaser, 2001, p. 111. Whilst being consistent with the methodology, a GT proposal sometimes has to give way to the format specified by a PhD program or committee even though the format was not defined for a GT proposal and in some areas, conflicts with GT principles; for example, the format may require a literature review. This short paper reports on my experience of writing a compromised GT proposal as a first-time GT researcher. It describes how both Glaser’s advice on writing compromised GT research proposals and the characteristics of the substantive area of the proposed research were used to satisfy program requirements while still maintaining GT fundamentals.

  17. Prevalence of metabolic syndrome with International Diabetes Federation Criteria and ATP III Program in patients 65 years of age or older.

    Science.gov (United States)

    De Luis, D A; Lopez Mongil, R; Gonzalez Sagrado, M; Lopez Trigo, J A; Mora, P F; Castrodeza Sanz, J

    2010-05-01

    The relationship between cardiovascular factors and death can vary with age, very few studies have examined metabolic syndrome in the elderly. The aim of this study is to assess the prevalence of the MS in a sample of elderly institutionalized patients (> 65 years) using ATPIII and IDF definitions. This was a cross-sectional survey covering a sample of representative of the institutionalized Spanish population aged above 65 years. The final sample study consisted of 862 patients, 556 females and 306 males. ATPIII and IDF definitions were used to classify the patients. Prevalence of MS was different according to the two definitions used. When the IDF definition was applied, total prevalence was 48.91% (CI 95%:43.47-50.25), while prevalence according to ATPIII criteria was 46.80% (CI = 43.47-50.25). a higher prevalence of MS was found in females as compared to males. Using IDF criteria, odds ratio was 1.9 (CI 95%:1.4-2.6) and 1.7 (CI 95%:1.2-2.2) according to ATPIII criteria. a steady decrease is seen in MS prevalence as the age of patients increases (the last two groups (85-94 ys and > 95 ys), both for the ATP III and the IDF definitions. A higher prevalence of MS in this elderly population as compared to general population was observed. A decrease of this prevalence above 95 years was detected.

  18. ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease.

    Science.gov (United States)

    Nakano, Masaki; Imamura, Hiromi; Sasaoka, Norio; Yamamoto, Masamichi; Uemura, Norihito; Shudo, Toshiyuki; Fuchigami, Tomohiro; Takahashi, Ryosuke; Kakizuka, Akira

    2017-08-01

    Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen receptor-related receptors) are expected to raise cellular ATP levels via enhancing ATP production. Here, we show that esculetin functions as an ERR agonist, and its addition to culture media enhances glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels. Subsequently, we show the neuroprotective efficacies of KUSs, esculetin, and GSK4716 (an ERRγ agonist) against cell death in Parkinson's disease models. In the surviving neurons, ATP levels and expression levels of α-synuclein and CHOP (an ER stress-mediated cell death executor) were all rectified. We propose that maintenance of ATP levels, by inhibiting ATP consumption or enhancing ATP production, or both, would be a promising therapeutic strategy for Parkinson's disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. The first two years of the Gemini Fast Turnaround Proposal Program

    Science.gov (United States)

    Andersen, Morten; Mason, Rachel; Geballe, Thomas R.; Chiboucas, Kristin; Salinas, Ricardo; Lundquist, Michael J.; scharwaechter, Julia; Schirmer, Mischa; silva, Karleyene

    2017-01-01

    Gemini Observatory has since February 2015 offered telescope time monthly through the Fast Turnaround observing route. A fast review process by the proposers themselves coupled with rapid scheduling allow the proposals to go from submission to part of the queue in a month and the observations are then active for 3 months, much faster than the traditional semester based proposal scheme.Both telescopes are included and around 10% of the available telescope time is allocated each month.Here we present the early results and lessons learned from the program. We discuss the over-subscription, the review process and the selection of proposals as well as the scheduling. The completion rates is further discussed. Finally we highlight some of the science results coming out of the program.

  20. 78 FR 59666 - Transmission Infrastructure Program; Proposed Transmission Infrastructure Program Updates and...

    Science.gov (United States)

    2013-09-27

    ... principle investment, all operating costs including overhead, and accrued interest by the end of the project... Programs Office into the process. The FRN also identifies the principles Western will continue using to... Contents I. Definitions II. Principles III. Project Evaluation Criteria IV. Project Life-Cycle Overview V...

  1. Investment in selective social programs: a proposed methodological tool for the analysis of programs’ sustainability

    Directory of Open Access Journals (Sweden)

    Manuel Antonio Barahona Montero

    2014-08-01

    Full Text Available This paper proposes a methodology to evaluate sustainability of Selective Social Programs (SSP, based on the relationship between economic growth and human development posed by the United Nations Development Program (UNDP.  For such purposes, the Circle of Sustainability is developed, which is comprised of 12 pillars. Each pillar is evaluated based on its current status and impact.  Combining both results allows to assesses sustainability of these programs and identify areas of focus. Therefore, this methodology helps to better channel available efforts and resources.

  2. 77 FR 61776 - Notice of Submission of Proposed Information Collection to OMB Housing Counseling Program

    Science.gov (United States)

    2012-10-11

    ... URBAN DEVELOPMENT Notice of Submission of Proposed Information Collection to OMB Housing Counseling... September 17, 2012, at 77 FR 57103, HUD published Housing Counseling Program and reference to the NOFA charts were excluded. Nonprofit Housing Counseling organizations ] submit information to HUD through...

  3. 78 FR 70090 - 30-Day Notice of Proposed Information Collection: PEPFAR Program Expenditures

    Science.gov (United States)

    2013-11-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE 30-Day Notice of Proposed Information Collection: PEPFAR Program Expenditures ACTION: Notice of request for... to allow 30 days for public comment. DATES: Submit comments directly to the Office of Management and...

  4. 78 FR 23288 - Proposed Information Collection: State Water Resources Research Institute Program; Annual...

    Science.gov (United States)

    2013-04-18

    ... research into areas of water management, development, and conservation that have a regional or national... Geological Survey Proposed Information Collection: State Water Resources Research Institute Program; Annual... collection (IC) to renew approval of the paperwork requirements for ``National Institutes for Water Resources...

  5. Communicative Competence of the Fourth Year Students: Basis for Proposed English Language Program

    Science.gov (United States)

    Tuan, Vu Van

    2017-01-01

    This study on level of communicative competence covering linguistic/grammatical and discourse has aimed at constructing a proposed English language program for 5 key universities in Vietnam. The descriptive method utilized was scientifically employed with comparative techniques and correlational analysis. The researcher treated the surveyed data…

  6. 77 FR 10718 - Request for Proposals: 2012 Hazardous Fuels Woody Biomass Utilization Grant Program

    Science.gov (United States)

    2012-02-23

    ... Forest Service Request for Proposals: 2012 Hazardous Fuels Woody Biomass Utilization Grant Program AGENCY... applications for wood energy projects that require engineering services. The document contained incorrect dates... regulations, contact your appropriate Forest Service Regional Biomass Coordinator as listed in the addresses...

  7. 78 FR 59048 - 30-Day Notice of Proposed Information Collection: Family Self-Sufficiency Program (FSS)

    Science.gov (United States)

    2013-09-25

    ... URBAN DEVELOPMENT 30-Day Notice of Proposed Information Collection: Family Self- Sufficiency Program..., 2013. A. Overview of Information Collection Title of Information Collection: Family Self-Sufficiency... toward economic independence and self-sufficiency. Public Housing Agencies consult with local officials...

  8. 78 FR 67183 - Proposed Information Collection; Migratory Bird Harvest Information Program and Migratory Bird...

    Science.gov (United States)

    2013-11-08

    ... Fish and Wildlife Service Proposed Information Collection; Migratory Bird Harvest Information Program and Migratory Bird Surveys AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice; request for... Bird Treaty Act (16 U.S.C. 703-711) and the Fish and Wildlife Act of 1956 (16 U.S.C. 742d) designate...

  9. 77 FR 28854 - Proposed Information Collection; Comment Request; Coastal Zone Management Program Administration

    Science.gov (United States)

    2012-05-16

    ... importance of U.S. coastal areas, the U.S. Congress passed the Coastal Zone Management Act of 1972 (CZMA), 16... approve amendments or program changes; and report on the states' coastal nonpoint source pollution... National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Coastal...

  10. 76 FR 38198 - Notice of Submission of Proposed Information Collection to OMB Housing Counseling Program...

    Science.gov (United States)

    2011-06-29

    ... URBAN DEVELOPMENT Notice of Submission of Proposed Information Collection to OMB Housing Counseling Program- Application for Approval as a Housing Counseling Agency AGENCY: Office of the Chief Information... counseling services directly or through their affiliates or branches regarding home buying, homeownership and...

  11. 78 FR 5421 - Proposed Information Collection; Comment Request; NOAA's Teacher at Sea Program

    Science.gov (United States)

    2013-01-25

    ... National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; NOAA's Teacher at Sea Program AGENCY: National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION... Hammond, (301) 713-0353, or [email protected]noaa.gov . SUPPLEMENTARY INFORMATION: I. Abstract This...

  12. 77 FR 41191 - Proposed Collection; Comment Request: Effectiveness of the NIH Curriculum Supplements Programs

    Science.gov (United States)

    2012-07-12

    ... NIH Curriculum Supplements Programs SUMMARY: In compliance with the requirements of section 3506(c)(2... review and approval. Proposed Collection: Title: The Effectiveness of the NIH Curriculum Supplements... will attempt to assess customer demographics and their satisfaction with the NIH curriculum supplements...

  13. 78 FR 11870 - Proposed Information Collection Request; Comment Request; Renewable Fuels Standard (RFS2) Program

    Science.gov (United States)

    2013-02-20

    ... the proposed collection of information, including the validity of the methodology and assumptions used... Fuel Producer Co-products Report RFS0801: RFS2 Renewable Biomass Report RFS0901: RFS2 Production... of the RFS2 program and was not a feature of RFS1. For the new EMTS system, all parties who owned...

  14. A Proposal for a CA-Integrated English Language Teacher Education Program in Turkey

    Science.gov (United States)

    Sert, Olcay

    2010-01-01

    This study proposes a comprehensive framework for a Conversation Analysis (CA) informed English language teacher education program in Turkey. By reviewing recent studies in CA, Critical Reflective Practice, Teacher Language Awareness and language teacher education in general; the author calls for a more effective language teacher education program…

  15. 78 FR 12349 - Proposed Information Collection; Land and Water Conservation Fund State Assistance Program

    Science.gov (United States)

    2013-02-22

    ... National Park Service Proposed Information Collection; Land and Water Conservation Fund State Assistance... INFORMATION: I. Abstract The Land and Water Conservation Fund Act of 1965 (LWCF Act) (16 U.S.C. 460l-4 et seq... discussed in detail in the Land and Water Conservation Fund State Assistance Program Federal Financial...

  16. 78 FR 23775 - Notice of Proposed Information Collection; Comment Request: Tax Credit Assistance Program (TCAP)

    Science.gov (United States)

    2013-04-22

    ... URBAN DEVELOPMENT Notice of Proposed Information Collection; Comment Request: Tax Credit Assistance... Credit Assistance Program (TCAP). This is a revision of an already approved information collection. HUD... information collection requirement described below has been submitted to the Office of Management and Budget...

  17. Students' needs reflected in the efl program: a small-scale evaluation of the methodologies proposed in an english program

    OpenAIRE

    Mora Acosta Lisbeth; Ramos Holguín Bertha

    2009-01-01

    In order to evaluate if there were discrepancies or not among the methodology proposed in the English program, students’ needs and what the teacher was actually doing in her classes, 13 ninth graders were asked to answer two questionnaires and they were also observed while they were in their English classes at the Institución Educativa Departamental El Vino (Cundinamarca, Colombia). The English teacher was also interviewed and a self- assessment questionnaire was given to her. The analysis of...

  18. BA- proposal made in collaboration between students and clinical practitioner at the OT-program

    DEFF Research Database (Denmark)

    Hove, Anne

    2014-01-01

    Presentation 24 BA- proposal made in collaboration between students and clinical practitioner at the OT-program Anne Hove (Metropolitan University College, Denmark) At the OT education a key aim is to ensure the students develop their BA-projects in a concrete collaboration with the practice field...... developing a project proposal is a difficult task. We have therefore in the spring of 2014 piloted a new ways of addressing this challenge. We have given students and practitioners the opportunity to develop project proposals in collaboration. I will present the first experiences from the pilot. We will host....... This focus is strengthen through a process where clinical practitioners and students develop in collaboration project proposals to BA-projects. We strongly believe that students learn more with this type of BA-project. In the lecture, I will short describe the learning potential we see in this type of BA...

  19. Draft report: a selection methodology for LWR safety R and D programs and proposals

    Energy Technology Data Exchange (ETDEWEB)

    Husseiny, A. A.; Ritzman, R. L.

    1980-03-01

    The results of work done to develop a methodology for selecting LWR safety R and D programs and proposals is described. A critical survey of relevant decision analysis methods is provided including the specifics of multiattribute utility theory. This latter method forms the basis of the developed selection methodology. Details of the methodology and its use are provided along with a sample illustration of its application.

  20. 43 CFR 404.51 - Are proposed projects under the Rural Water Supply Program reviewed by the Administration?

    Science.gov (United States)

    2010-10-01

    ... Water Supply Program reviewed by the Administration? 404.51 Section 404.51 Public Lands: Interior... SUPPLY PROGRAM Feasibility Studies § 404.51 Are proposed projects under the Rural Water Supply Program... the Reclamation's Rural Water Supply Program. This includes review under Executive Order 12322 to...

  1. The relative influence of secondary versus primary prevention using the national cholesterol education program adult treatment panel II guidelines

    NARCIS (Netherlands)

    Goldman, L; Coxson, P; Hunink, MGM; Goldman, PA; Tosteson, ANA; Mittleman, M; Williams, L; Weinstein, MC

    OBJECTIVES This study was undertaken to project the population-wide effect of full implementation of the Adult Treatment Panel (ATP) II guidelines of the National Cholesterol Education Program (NCEP). BACKGROUND The ATP II has proposed guidelines for cholesterol reduction, but the long-term

  2. Making didactics proposals aimed at improving socioeducational programs for youngters at risk of social exclusion

    Directory of Open Access Journals (Sweden)

    María Violeta Álvarez Fernández

    2013-12-01

    Full Text Available Educators at Sograndio Juvenile Detention Center in Asturias were sure that they were able to offer new alternatives to improve their socio-educational intervention. That is the reason why they got involved in an action research training process aimed at making didactic proposals which tried to optimize the development of social competence programs for youngsters with criminal behavior. In order to do this, the Short Version of the Prosocial Thinking Program for Young People (Alba et al., 2005 was applied to nine inmates, eight males between 14 and 20 years old and a female of 16 years old. Theywere the basis and reflection of ourmethodological intervention. The teamtaking part in this intervention is formed by nine inmates and three external members (two coordinators and a woman psychologist. The investigation, mainly qualitative, includes different instruments (both qualitative and quantitative, such as: observation registries, discussion groups, questionnaires and notebooks. After the implementation of the program, positive changes must be highlighted in the emotional dimension, the resolution of problems, self-control and frustration tolerance. Besides, very high levels of satisfaction have been observed among youngsters, educators and external informants. It is important to have created a climate of professional compromise towards change and this way to have abandoned a passive attitude towards training, so that we were able to start an active search for practical answers, adjusted to our necessities and professional interests. Finally, we make several observations and intervention proposals that contribute to generate didactic knowledge thought and adapted for social education.

  3. Proposal to introduce Disaster Risk Management topics in Master programs in ESAN Graduate School of Business

    Directory of Open Access Journals (Sweden)

    CECILIA DEJO ESTEVES

    Full Text Available This paper aims to explain and present a proposal to introduce Disaster Risk Management (DRM topics into ESAN Graduate School of Business Master's programs. Although disasters have cost Peru more than USD 7,600 million in the past 2 decades the business sector, particularly Small and Medium Enterprises, have not developed preventive or continuity plans mainly because they are not familiar with DRM topics. Taking this into consideration, the paper presents a detailed academic/curricular proposal for DRM topics such as business continuity, business ethics, corporate social responsibility, and sustainable management. Additionally, it introduces the idea of promoting Disaster Risk Management (DRM topics to the Peruvian business community as a strategy to enhance the graduate education.

  4. Curricular renovation in the phonoaudiology program of the University of Cauca: a proposal for educational quality

    Directory of Open Access Journals (Sweden)

    Liliana María Pérez-Tenorio

    2010-09-01

    Full Text Available In Colombia, the Superior Education is going through a transformation process. These changes must be in coherence with the formulation of flexible policies among the diverse components of the curriculum and with the need for new forms of working and producing knowledge. The curricular renovation must ref lect an educational quality compromise and contribute to generate human development with high social impact. This article presents a proposal for Curricular Renovation, elaborated by faculty and students of the Phonoaudiology Program of the University of Cauca. This document contains aspects related to the pedagogic model, didactics, faculty-student relation, systems of evaluation and plan of studies. Furthermore, in this document the bases for the Route of Curricular Renovation are presented, consisting of the following phases: background, diagnosis and operational plan. These should facilitate the academic integration for adjusting the curricular processes to the needs of the academic program in a local, national and international context.

  5. Intertechnology Corporation proposed test and evaluation plan, commercial buildings. National Solar Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    None

    1976-09-01

    This report has three major parts. The first of these derives the requirements for the Test and Evaluation plan from the System Level Plan which is summarized in Section II. The second part contains the proposed plan to fill these requirements and includes hardware and software recommendations as well as procedures and management considerations. Primary emphasis has been given to the remote site because this is the area in which the commercial part of the demonstration is most unique. Finally, some pre-demonstration activities are described. The pilot program is intended to resolve a number of issues which arose in the course of the T and E plan. These relate to choice of scan frequencies, compression algorithms, etc. It is also intended to confirm performance and cost effectiveness of the site data collection package. The base line measurements of attitudes, etc. provide a reference mark against which one can measure the non-technical effectiveness of the demonstration program. (WDM)

  6. Identification of Barriers Towards Change and Proposal to Institutionalize Continuous Improvement Programs in Manufacturing Operations

    Directory of Open Access Journals (Sweden)

    Alvair Silveira Torres Jr.

    2011-06-01

    Full Text Available A multi case research unfolded into a study in a sample of Brazilian manufacturing companies concerning their Continuous Improvement (CI program in manufacturing operations. Stakeholders interviews and performance analyses were conducted. The study aims to analyze the existence or absence of the institutionalization of a CI culture in manufacturing operations, identify barriers and difficulties within the process and propose a model for change. As a result of the research, it was observed that despite the considerable motivation of staff, rapid gains of the company and superior results during the early phases of the CI program, time and again such results were either not upheld or faded out over time, delivering no significant mid-term or long term results, due to poor management of changes. This happened mainly as a result of lack of strategic alignment at all levels of the organization, translated in measureable activities and projects, coached and mentored by the middle and upper management throughout the implementation and maintenance of the program. The selected cases showed a declining in performance after two years of CI program start up. Learning, union and process ownership among participants by means of interactions, are necessary to absorb and incorporate changes, instead of merely "smart words" .

  7. Proposed Social Spending Innovation Research (SSIR) Program: Harnessing American Entrepreneurial Talent to Solve Major U.S. Social Problems

    Science.gov (United States)

    Coalition for Evidence-Based Policy, 2015

    2015-01-01

    The Social Spending Innovation Research (SSIR) proposal seeks to replicate, in social spending, the great success of the Small Business Innovation Research (SBIR) program in technology development. The SBIR program funds technology development by entrepreneurial small companies. The program has spawned breakthrough technologies in diverse areas…

  8. 77 FR 38375 - Advisory Circular (AC) 150/5345-53D, Airport Lighting Equipment Certification Program; Proposed...

    Science.gov (United States)

    2012-06-27

    ... Certification Program (ALECP) for acceptance of an organization as a third party certification body (third party... certification body (third party certifier) and how manufacturers may get equipment qualified under the program... Certification Program; Proposed Update and Opportunity to Comment AGENCY: Federal Aviation Administration (FAA...

  9. [The Articulator of Primary Health Care Program: an innovative proposal for qualification of Primary Health Care].

    Science.gov (United States)

    Doricci, Giovanna Cabral; Guanaes-Lorenzi, Carla; Pereira, Maria José Bistafa

    2017-06-01

    In 2009, the Secretary of State for Health of Sao Paulo created a Program with a view to qualify the primary care in the state. This proposal includes a new job function, namely the articulator of primary care. Due to the scarcity of information about the practice of these new professionals in the scientific literature, this article seeks to analyze how articulators interpret their function and how they describe their daily routines. Thirteen articulators were interviewed. The interviews were duly analyzed by qualitative delineation. The results describe three themes: 1)Roles of the articulator: technical communicator and political advisor; 2) Activities performed to comply with the expected roles, examples being diagnosis of the municipalities, negotiation of proposals, participation in meetings, visits to municipalities; and 3) Challenges of the role, which are configured as challenges to the health reform process, examples being the lack of physical and human resources, activities of professionals in the medical-centered model, among others. The conclusion drawn is that the Program has great potential to provide input for the development and enhancement of Primary Care. Nevertheless, there are a series of challenges to be overcome, namely challenges to the context per se.

  10. Seminar program for postgraduate specialty training in general practice: proposal for a 5-year thematic catalogue

    Science.gov (United States)

    Sommer, Susanne; Baum, Erika; Magez, Julia; Chenot, Jean-Francois; Weckmann, Gesine; Steinhäuser, Jost; Heim, Susanne; Schneider, Dagmar; Fuchs, Stephan

    2017-01-01

    Introduction: In different German regions, seminar programs have been conducted for General practice residents. In each region, selection and teaching of learning content is conducted in a different manner. So far, no structured, standardized curriculum has been implemented nationwide. We have investigated, if the development of a common 5-year program of learning topics is conceivable between the different university departments of General practice in Germany. Method: The seminar program working group of the DEGAM (German College of General Practitioners and Family Physicians) has conducted an online survey based on information gathered via preliminary telephone conference (n=7; physicians with postgraduate teaching experience) among all German university departments of General Practice and two non-university teaching institutions, identified via the internet. 884 topics were extracted from 14 Seminar programs. The topics were entered in a database, discussed and categorized: Practice management/practice work flow/standardized documentation forms/quality management (n=33 topics), common acute and chronic diseases, including disease management programs (n=29 topics), communication, neurological, psychological and psychiatric consultations (n=24 topics), common medical problems, including eye, ear, nose, throat, skin and pediatric problems (n=99 Topics) family physicians general approach, including epidemiology, shared decision making, test of time (n=42 Topics). These topics have been rated for priority and desirable number of teaching-units. Results: A catalogue of 111 topics was designed, encompassing 160 teaching units. There is a suggestion of wide topics collections plus an add-on catalogue. Conclusion: A proposal for a 5-year-thematic catalogue for postgraduate training of general practice residents in Germany has been developed. This newly developed curriculum has the potential to improve knowledge and skills that have not been covered during in-house and

  11. PROPOSAL FOR AN EXPERIMENT PROGRAM IN NEUTRINO PHYSICS AND PROTON DECAY IN THE HOMESTAKE LABORATORY.

    Energy Technology Data Exchange (ETDEWEB)

    DIWAN, M.; KETTELL, S.; LITTENBERG, W.; MARIANO, W.; PARSA, Z.; SAMIOS, N.; WHITE, S.; ET AL.

    2006-07-24

    This report is intended to describe first, the principal physics reasons for an ambitious experimental program in neutrino physics and proton decay based on construction of a series of massive water Cherenkov detectors located deep underground (4850 ft) in the Homestake Mine of the South Dakota Science and Technology Authority (SDSTA); and second, the engineering design of the underground chambers to house the Cherenkov detector modules; and third, the conceptual design of the water Cherenkov detectors themselves for this purpose. In this proposal we show the event rates and physics sensitivity for beams from both FNAL (1300 km distant from Homestake) and BNL (2540 km distant from Homestake). The program we propose will benefit with a beam from FNAL because of the high intensities currently available from the Main Injector with modest upgrades. The possibility of tuning the primary proton energy over a large range from 30 to 120 GeV also adds considerable flexibility to the program from FNAL. On the other hand the beam from BNL over the larger distance will produce very large matter effects, and consequently a hint of new physics (beyond CP violation) can be better tested with that configuration. In this proposal we focus on the CP violation physics. Included in this document are preliminary costs and time-to-completion estimates which have been exposed to acknowledged experts in their respective areas. This presentation is not, however, to be taken as a technical design report with the extensive documentation and contingency costs that a TDR usually entails. Nevertheless, some contingency factors have been included in the estimates given here. The essential ideas expressed here were first laid out in a letter of intent to the interim director of the Homestake Laboratory on July 26, 2001. Since that time, the prospect of a laboratory in the Homestake Mine has been realized, and the design of a long baseline neutrino experiment has been refined. The extrapolation

  12. ATP synthase in slow- and fast-growing mycobacteria is active in ATP synthesis and blocked in ATP hydrolysis direction.

    NARCIS (Netherlands)

    Haagsma, A.C.; Driessen, N.N.; Hahn, M.M.; Lill, H.; Bald, D.

    2010-01-01

    ATP synthase is a validated drug target for the treatment of tuberculosis, and ATP synthase inhibitors are promising candidate drugs for the treatment of infections caused by other slow-growing mycobacteria, such as Mycobacterium leprae and Mycobacterium ulcerans. ATP synthase is an essential enzyme

  13. ATP synthase from slow and fast growing mycobacteria is active in ATP synthesis and blocked in ATP hydrolysis direction.

    NARCIS (Netherlands)

    Haagsma, A.C.; Driessen, N.N.; Hahn, M.M.; Lill, H.; Bald, D.

    2010-01-01

    ATP synthase is a validated drug target for the treatment of tuberculosis, and ATP synthase inhibitors are promising candidate drugs for the treatment of infections caused by other slow-growing mycobacteria, such as Mycobacterium leprae and Mycobacterium ulcerans. ATP synthase is an essential enzyme

  14. [The Purpose of Medical Education: Proposal to Standardize a System of Credits for Medical Specializations Programs].

    Science.gov (United States)

    Cañar, Carlos Andrés Pineda

    2012-01-01

    This article analyzes the concept of an academic credit system and proposes a way to systematize medical specialization programs. The credit system is a way to recognize and standardize the total time that a student must devote to their training. Thus, a credit equal to a certain number of hours of classroom training and independent activities is proposed. An educational program is expressed in the number of credits needed for the whole training process to achieve the competencies expected. A review of the concept of competition in education is also performed. The introduction of the term and its relation to the need to measure performance in future professionals according to labor market needs is identified. A critical discussion about skills defining the different types of skills in the educational field is later discussed. Subsequently, the Colombian regulatory framework is presented concerning the powers, in particular, Decree 1295 of 2010, which defines one academic credit equal to 48 hours in a semester, of which 16 hours are classroom and 32 hours are independent study. A tor of the major milestones in the history of medical education is later made. The structure of credits and contact hours, independent of postgraduate psychiatry in the country is reviewed showing the heterogeneity in their approach. The proposal is presented, defining the types of classroom activities and how to calculate the hours of independent study by type of classroom activity. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  15. A Proposed Arctic Ocean Field Program During the International Polar Year 2007-2008

    Science.gov (United States)

    Persson, O. P.

    2004-05-01

    The Arctic Ocean represents a glaring void of measurements appropriate for monitoring and understanding the climate changes currently occurring in the Arctic region. We propose a field program in the central Arctic Ocean to develop and improve methods for the long-term monitoring of the Arctic atmosphere, ice, and ocean and the interactions among them, and to study physical processes crucial to the regional climate change. The approach will include developing and evaluating methods by which long-term satellite-, surface-, and ocean-based measurements of the thermodynamic and kinematic properties of the atmosphere, ice, and ocean can be integrated to measure key parameters with accuracies necessary to detect climatic change, to attribute responsibility to the processes causing this change, and to evaluate the role of anthropogenic sources in this change. Key measurements include the atmospheric circulation above and within the atmospheric boundary layer, cloud macro and microphysical properties, atmospheric aerosols and chemical constituents, all components of the energy budget of the pack ice including the oceanic heat flux, and the pack ice mass balance. Many of the techniques to be developed will likely use in-situ surface and ocean-based measurements to evaluate and improve the accuracy of the satellite-based measurements. These measurements will generally integrate existing technology, though some will require technological development as well. Many physical processes over the pack ice are different than those over the circumpolar land areas where SEARCH (Study of Environmental Arctic Change) intensive observing sites are being established. Observations at the land sites are largely influenced by processes forced by coastal gradients or by orography, and are much less influenced by the oceanic heat source omnipresent over the Arctic Ocean. The proposed pack ice field program will make measurements specific to processes important for climate models and that are

  16. ATP Release and Effects in Pancreas

    DEFF Research Database (Denmark)

    Novak, Ivana; Amstrup, Jan; Henriksen, Katrine Lütken

    2003-01-01

    ATP and other nucleotides are released from various cells, but the pathway and physiological stimulus for ATP release are often unclear. The focus of our studies is the understanding of ATP release and signaling in rat exocrine pancreas. In acinar suspension mechanical stimulation, hypotonic shock...

  17. Extracellular ATP induces albuminuria in pregnant rats

    NARCIS (Netherlands)

    Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.

    BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.

  18. A Proposal for a Standard Interface Between Monte Carlo Tools And One-Loop Programs

    Energy Technology Data Exchange (ETDEWEB)

    Binoth, T.; /Edinburgh U.; Boudjema, F.; /Annecy, LAPP; Dissertori, G.; Lazopoulos, A.; /Zurich, ETH; Denner, A.; /PSI, Villigen; Dittmaier, S.; /Freiburg U.; Frederix, R.; Greiner, N.; Hoeche, Stefan; /Zurich U.; Giele, W.; Skands, P.; Winter, J.; /Fermilab; Gleisberg, T.; /SLAC; Archibald, J.; Heinrich, G.; Krauss, F.; Maitre, D.; /Durham U., IPPP; Huber, M.; /Munich, Max Planck Inst.; Huston, J.; /Michigan State U.; Kauer, N.; /Royal Holloway, U. of London; Maltoni, F.; /Louvain U., CP3 /Milan Bicocca U. /INFN, Turin /Turin U. /Granada U., Theor. Phys. Astrophys. /CERN /NIKHEF, Amsterdam /Heidelberg U. /Oxford U., Theor. Phys.

    2011-11-11

    Many highly developed Monte Carlo tools for the evaluation of cross sections based on tree matrix elements exist and are used by experimental collaborations in high energy physics. As the evaluation of one-loop matrix elements has recently been undergoing enormous progress, the combination of one-loop matrix elements with existing Monte Carlo tools is on the horizon. This would lead to phenomenological predictions at the next-to-leading order level. This note summarises the discussion of the next-to-leading order multi-leg (NLM) working group on this issue which has been taking place during the workshop on Physics at TeV Colliders at Les Houches, France, in June 2009. The result is a proposal for a standard interface between Monte Carlo tools and one-loop matrix element programs.

  19. Academic stress in Chinese schools and a proposed preventive intervention program

    Directory of Open Access Journals (Sweden)

    Xu Zhao

    2015-12-01

    Full Text Available While American educators fret about the mediocre educational performance of American students in international contests (e.g. the Program for International Student Assessment and wonder why the Chinese education system produces such high-achieving students, educators, journalists, and public officials in China want to know what causes and how to prevent the high levels of academic stress that Chinese students, their families, and their school systems experience. So far, much of the blame for these toxic levels of stress has been directed to the Gaokao, the Chinese national college entrance exam that takes place in June each year. But to date, top-down Chinese educational reforms have been ineffective in reducing the problem. In this article, we build a case for strengthening bottom-up efforts at the school level in China and propose an evidence-based approach for addressing the challenge of academic stress experienced by Chinese students.

  20. EPA Proposes Revisions to its Risk Management Program to Improve Chemical Process Safety and Further Protect Communities and First Responders

    Science.gov (United States)

    WASHINGTON - The U.S. Environmental Protection Agency (EPA) is proposing to revise its Risk Management Program (RMP) regulations to improve chemical process safety, assist local emergency authorities in planning for and responding to accidents, and

  1. 76 FR 77581 - 60-Day Notice of Proposed Information Collection: Form DS-3097, Exchange Visitor Program Annual...

    Science.gov (United States)

    2011-12-13

    ... Notice of Proposed Information Collection: Form DS-3097, Exchange Visitor Program Annual Report, and OMB... of 1995. Title of Information Collection: Exchange Visitor Program Annual Report. OMB Control Number... the Student and Exchange Visitor Information System (SEVIS) and then printed and signed by a sponsor...

  2. 78 FR 52962 - 60-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

    Science.gov (United States)

    2013-08-27

    ... URBAN DEVELOPMENT 60-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing... Collection Title of Information Collection: Housing Finance Agency Risk- Sharing Program. OMB Approval Number... housing finance agencies (HFAs). Under this program, HUD provides full mortgage insurance on multifamily...

  3. 78 FR 65696 - 30-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

    Science.gov (United States)

    2013-11-01

    ... URBAN DEVELOPMENT 30-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing... Collection Title of Information Collection: Housing Finance Agency Risk- Sharing Program. OMB Approval Number... with State and local housing finance agencies (HFAs). Under this program, HUD provides full mortgage...

  4. 77 FR 69550 - Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program...

    Science.gov (United States)

    2012-11-19

    ... AFFAIRS Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program.... This notice solicits comments on information needed to determine patients' satisfaction with services... information technology. Title: Patient Satisfaction Survey Michael E. DeBakey Home Care Program, VA Form 10...

  5. 75 FR 62635 - Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program...

    Science.gov (United States)

    2010-10-12

    ... AFFAIRS Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program... needed to determine patients' satisfaction with services provided by or through the Michael E. DeBakey.... Title: Patient Satisfaction Survey Michael E. DeBakey Home Care Program, VA Form 10-0476. OMB Control...

  6. 78 FR 6851 - Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program...

    Science.gov (United States)

    2013-01-31

    ... AFFAIRS Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program....'' SUPPLEMENTARY INFORMATION: Title: Patient Satisfaction Survey Michael E. DeBakey Home Care Program, VA Form 10.... Abstract: VA Form 10-0476 will be used to gather feedback from patients regarding their satisfaction with...

  7. 76 FR 51943 - Proposed Information Collection; Comment Request; International Dolphin Conservation Program

    Science.gov (United States)

    2011-08-19

    ...; International Dolphin Conservation Program AGENCY: National Oceanic and Atmospheric Administration (NOAA... (NOAA) collects information to implement the International Dolphin Conservation Program Act (Act). The... ] nations in the International Dolphin Conservation Program that would otherwise be under embargo. The Act...

  8. Arabidopsis fructokinase-like protein associations are regulated by ATP.

    Science.gov (United States)

    Riggs, John W; Callis, Judy

    2017-05-10

    The Arabidopsis thaliana fructokinase-like proteins FLN1 and FLN2 are required for the differentiation of plastids into photosynthetically competent chloroplasts. However, their specific roles are unknown. FLN1 and FLN2 localize in a multisubunit prokaryotic-type polymerase (plastid-encoded RNA polymerase) complex that transcribes genes encoding components of photosynthesis-related assemblies. Despite sequence identity with fructokinases, which are members of the pfkB (phosphofructokinase B) family of enzymes, kinase activity of FLN1 and FLN2 has not been demonstrated. Homology modeling using pfkB X-ray structures, sequence comparisons, and mutational analyses suggests that FLN proteins may bind their substrates differently from other pfkB proteins. We provide evidence that purified recombinant FLN1 undergoes an ATP-mediated change in binding affinity with both itself and recombinant FLN2. The ATP-mediated change in the affinity of FLN1 for FLN2 is not affected by mutations in conserved active-site residues known to affect catalysis in active pfkB enzymes. In contrast, recombinant FLN2 hetero-oligomerizes independently of ATP concentration. At ATP concentrations that promote FLN1 homomeric interactions, the FLN1-FLN2 hetero-oligomer is the dominant form in vitro We further present evidence that FLN1 associates with a large protein complex in chloroplasts independently of ATP. Given that ATP levels fluctuate between light-dark cycles in the 1-5 mM range, we propose that changes in FLN1 and FLN2 interactions are biologically meaningful. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  9. Review of current Southern California edison load management programs and proposal for a new market-driven, mass-market, demand-response program

    Energy Technology Data Exchange (ETDEWEB)

    Weller, G.H.

    2002-01-01

    Utility load management programs, including direct load control and interruptible load programs, constitute a large installed base of controllable loads that are employed by utilities as system reliability resources. In response to energy supply shortfalls expected during the summer of 2001, the California Public Utilities Commission in spring 2001 authorized new utility load management programs as well as revisions to existing programs. This report provides an independent review of the designs of these new programs for a large utility (Southern California Edison) and suggests possible improvements to enhance the price responsiveness of the customer actions influenced by these programs. The report also proposes a new program to elicit a mass-market demand response to utility price signals.

  10. Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium

    Directory of Open Access Journals (Sweden)

    Hayoz Sébastien

    2012-05-01

    Full Text Available Abstract Background ATP is an extracellular signaling molecule with many ascribed functions in sensory systems, including the olfactory epithelium. The mechanism(s by which ATP is released in the olfactory epithelium has not been investigated. Quantitative luciferin-luciferase assays were used to monitor ATP release, and confocal imaging of the fluorescent ATP marker quinacrine was used to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory epithelial slices. Results Under control conditions, constitutive release of ATP occurs via exocytosis, hemichannels and ABC transporters and is inhibited by vesicular fusion inhibitor Clostridium difficile toxin A and hemichannel and ABC transporter inhibitor probenecid. Constitutive ATP release is negatively regulated by the ATP breakdown product ADP through activation of P2Y receptors, likely via the cAMP/PKA pathway. In vivo studies indicate that constitutive ATP may play a role in neuronal homeostasis as inhibition of exocytosis inhibited normal proliferation in the OE. ATP-evoked ATP release is also present in mouse neonatal OE, triggered by several ionotropic P2X purinergic receptor agonists (ATP, αβMeATP and Bz-ATP and a G protein-coupled P2Y receptor agonist (UTP. Calcium imaging of P2X2-transfected HEK293 “biosensor” cells confirmed the presence of evoked ATP release. Following purinergic receptor stimulation, ATP is released via calcium-dependent exocytosis, activated P2X1,7 receptors, activated P2X7 receptors that form a complex with pannexin channels, or ABC transporters. The ATP-evoked ATP release is inhibited by the purinergic receptor inhibitor PPADS, Clostridium difficile toxin A and two inhibitors of pannexin channels: probenecid and carbenoxolone. Conclusions The constitutive release of ATP might be involved in normal cell turn-over or modulation of odorant sensitivity in physiological conditions. Given the growth-promoting effects of ATP, ATP-evoked ATP

  11. ATP hydrolysis assists phosphate release and promotes reaction ordering in F1-ATPase

    Science.gov (United States)

    Li, Chun-Biu; Ueno, Hiroshi; Watanabe, Rikiya; Noji, Hiroyuki; Komatsuzaki, Tamiki

    2015-01-01

    F1-ATPase (F1) is a rotary motor protein that can efficiently convert chemical energy to mechanical work of rotation via fine coordination of its conformational motions and reaction sequences. Compared with reactant binding and product release, the ATP hydrolysis has relatively little contributions to the torque and chemical energy generation. To scrutinize possible roles of ATP hydrolysis, we investigate the detailed statistics of the catalytic dwells from high-speed single wild-type F1 observations. Here we report a small rotation during the catalytic dwell triggered by the ATP hydrolysis that is indiscernible in previous studies. Moreover, we find in freely rotating F1 that ATP hydrolysis is followed by the release of inorganic phosphate with low synthesis rates. Finally, we propose functional roles of the ATP hydrolysis as a key to kinetically unlock the subsequent phosphate release and promote the correct reaction ordering. PMID:26678797

  12. Effects of surface adsorption on catalytic activity of heavy meromyosin studied using a fluorescent ATP analogue.

    Science.gov (United States)

    Balaz, Martina; Sundberg, Mark; Persson, Malin; Kvassman, Jan; Månsson, Alf

    2007-06-19

    Biochemical studies in solution and with myosin motor fragments adsorbed to surfaces (in vitro motility assays) are invaluable for elucidation of actomyosin function. However, there is limited understanding of how surface adsorption affects motor properties, e.g., catalytic activity. Here we address this issue by comparing the catalytic activity of heavy meromyosin (HMM) in solution and adsorbed to standard motility assay surfaces [derivatized with trimethylchlorosilane (TMCS)]. For these studies we first characterized the interaction of HMM and actomyosin with the fluorescent ATP analogue adenosine 5'-triphosphate Alexa Fluor 647 2'- (or 3'-) O-(N-(2-aminoethyl)urethane) hexa(triethylammonium) salt (Alexa-ATP). The data suggest that Alexa-ATP is hydrolyzed by HMM in solution at a slightly higher rate than ATP but with a generally similar mechanism. Furthermore, Alexa-ATP is effective as a fuel for HMM-propelled actin filament sliding. The catalytic activity of HMM on TMCS surfaces was studied using (1) Alexa-ATP in total internal reflection fluorescence (TIRF) spectroscopy experiments and (2) Alexa-ATP and ATP in HPLC-aided ATPase measurements. The results support the hypothesis of different HMM configurations on the surface. However, a dominant proportion of the myosin heads were catalytically active, and their average steady-state hydrolysis rate was slightly higher (with Alexa-ATP) or markedly higher (with ATP) on the surface than in solution. The results are discussed in relation to the use of TMCS surfaces and Alexa-ATP for in vitro motility assays and single molecule studies. Furthermore, we propose a novel TIRF microscopy method to accurately determine the surface density of catalytically active myosin motors.

  13. 75 FR 43178 - Medicare Program; Solicitation for Proposals for the Medicare Imaging Demonstration

    Science.gov (United States)

    2010-07-23

    ... defined in Sec. 1834(e)(1)(B) of the Social Security Act (the Act): Diagnostic magnetic resonance imaging... Domestic Assistance Program No. 93.773, Medicare--Hospital Insurance; and Program No. 93.774, Medicare...

  14. An Application Programming Interface For Developing Distributed Algorithm Along With Proposed Meta Language Concept

    OpenAIRE

    Kishalay Bairagi

    2015-01-01

    Abstract In computer science an application programming interface API is an interface that defines the ways by which an application programming may request services from libraries.7 Libraries of a programming language are the list of all classes and interfaces along with their fields constructors and methods that are part of that language. For example java is an object oriented programming language which has a rich set of built-in classes and interfaces packaged in the API also known as java ...

  15. 78 FR 16862 - Notice of Submission of Proposed Information Collection to OMB: Emergency Shelter Grants Program...

    Science.gov (United States)

    2013-03-19

    ... requirements that Emergency Solutions Grants (ESG) program recipients will be expected to implement and retain. This submission is limited to the record keeping burden under the ESG entitlement program, formerly... HEARTH Act. To see the regulations for the new ESG program and applicable supplementary documents, visit...

  16. Abiogenic Photophosphorylation of ADP to ATP Sensitized by Flavoproteinoid Microspheres

    Science.gov (United States)

    Kolesnikov, Michael P.; Telegina, Taisiya A.; Lyudnikova, Tamara A.; Kritsky, Mikhail S.

    2008-06-01

    A model for abiogenic photophosphorylation of ADP by orthophosphate to yield ATP was studied. The model is based on the photochemical activity of flavoproteinoid microspheres that are formed by aggregation in an aqueous medium of products of thermal condensation of a glutamic acid, glycine and lysine mixture (8:3:1) and contain, along with amino acid polymers (proteinoids), abiogenic isoalloxazine (flavin) pigments. Irradiation of aqueous suspensions of microspheres with blue visible light or ultraviolet in the presence of ADP and orthophosphate resulted in ATP formation. The yield of ATP in aerated suspensions was 10 20% per one mol of starting ADP. Deaeration reduced the photophosphorylating activity of microspheres five to 10 times. Treatment of aerated microsphere suspensions with superoxide dismutase during irradiation partially suppressed ATP formation. Deaerated microspheres restored completely their photophosphorylating activity after addition of hydrogen peroxide to the suspension. The photophosphorylating activity of deaerated suspensions of flavoproteinoid microspheres was also recovered by introduction of Fe3+-cytochrome c, an electron acceptor alternative to oxygen. On the basis of the results obtained, a chemical mechanism of phosphorylation is proposed in which the free radical form of reduced flavin sensitizer left( {{text{FlH}}^ bullet } right) and ADP are involved.

  17. Genetic variation in ATP5O is associated with skeletal muscle ATP50 mRNA expression and glucose uptake in young twins.

    Directory of Open Access Journals (Sweden)

    Tina Rönn

    Full Text Available BACKGROUND: Impaired oxidative capacity of skeletal muscle mitochondria contribute to insulin resistance and type 2 diabetes (T2D. Furthermore, mRNA expression of genes involved in oxidative phosphorylation, including ATP5O, is reduced in skeletal muscle from T2D patients. Our aims were to investigate mechanisms regulating ATP5O expression in skeletal muscle and association with glucose metabolism, and the relationship between ATP5O single nucleotide polymorphisms (SNPs and risk of T2D. METHODOLOGY/PRINCIPAL FINDINGS: ATP5O mRNA expression was analyzed in skeletal muscle from young (n = 86 and elderly (n = 68 non-diabetic twins before and after a hyperinsulinemic euglycemic clamp. 11 SNPs from the ATP5O locus were genotyped in the twins and a T2D case-control cohort (n = 1466. DNA methylation of the ATP5O promoter was analyzed in twins (n = 22 using bisulfite sequencing. The mRNA level of ATP5O in skeletal muscle was reduced in elderly compared with young twins, both during basal and insulin-stimulated conditions (p<0.0005. The degree of DNA methylation around the transcription start of ATP5O was <1% in both young and elderly twins and not associated with mRNA expression (p = 0.32. The mRNA level of ATP5O in skeletal muscle was positively related to insulin-stimulated glucose uptake (regression coefficient = 6.6; p = 0.02. Furthermore, two SNPs were associated with both ATP5O mRNA expression (rs12482697: T/T versus T/G; p = 0.02 and rs11088262: A/A versus A/G; p = 0.004 and glucose uptake (rs11088262: A/A versus A/G; p = 0.002 and rs12482697: T/T versus T/G; p = 0.005 in the young twins. However, we could not detect any genetic association with T2D. CONCLUSIONS/SIGNIFICANCE: Genetic variation and age are associated with skeletal muscle ATP5O mRNA expression and glucose disposal rate, suggesting that combinations of genetic and non-genetic factors may cause the reduced expression of ATP5O in T2D muscle. These findings propose a role for ATP5O, in

  18. Plasma ATP concentration and venous oxygen content in the forearm during dynamic handgrip exercise

    Directory of Open Access Journals (Sweden)

    Askew Christopher D

    2009-12-01

    Full Text Available Abstract Background It has been proposed that adenosine triphosphate (ATP released from red blood cells (RBCs may contribute to the tight coupling between blood flow and oxygen demand in contracting skeletal muscle. To determine whether ATP may contribute to the vasodilatory response to exercise in the forearm, we measured arterialised and venous plasma ATP concentration and venous oxygen content in 10 healthy young males at rest, and at 30 and 180 seconds during dynamic handgrip exercise at 45% of maximum voluntary contraction (MVC. Results Venous plasma ATP concentration was elevated above rest after 30 seconds of exercise (P Conclusions Collectively these results indicate that ATP in the plasma originated from the muscle microcirculation, and are consistent with the notion that deoxygenation of the blood perfusing the muscle acts as a stimulus for ATP release. That ATP concentration was elevated just 30 seconds after the onset of exercise also suggests that ATP may be a contributing factor to the blood flow response in the transition from rest to steady state exercise.

  19. Report of an equity-focused health impact assessment of a proposed universal parenting program in Manitoba.

    Science.gov (United States)

    Cohen, Benita E; Ateah, Christine A; Chartier, Mariette J; Anderson DeCoteau, Marcia; Harris, Elizabeth; Serwonka, Karen

    2016-06-27

    To assess potential inequitable impacts of a proposed Teen Triple P Positive Parenting Program (Teen PPP) in Manitoba to achieve equity of access and outcomes for families of diverse backgrounds; recommend (if required) alternative actions to promote greater equity of access and outcomes for families participating in Teen PPP; and evaluate the influence of recommendations on implementation of the proposed program. An equity-focused health impact assessment (EfHIA) of the proposed Teen PPP was conducted, using a standard EfHIA framework. Methods used to assess potential Teen PPP impacts included: a literature review, key informant interviews and 14 community consultations. Evidence was analyzed, summarized and presented to the project Steering Committee (SC), along with draft recommendations for ensuring that equity is considered in Teen PPP planning and rollout. The SC prioritized 12 possible inequitable impacts of Teen PPP with potential to prevent certain parents/caregivers either from accessing the proposed program or benefitting adequately from the program, causing them to drop out prematurely. Recommendations for avoiding these impacts were finalized by the SC and presented to provincial government officials responsible for the proposed program. Follow-up interviews with these individuals indicated that the recommendations were well received and raised equity-related issues that will be considered in future program planning decisions. EfHIA is a proven planning tool for ensuring that health equity is considered in all policies, which is one of the necessary conditions for reducing inequities and closing the health equity gap throughout Canada within a generation.

  20. Glucose and the ATP paradox in yeast.

    NARCIS (Netherlands)

    Somsen, O.J.G.; Hoeben, M.A.; Esgalhado, M.E.L.M.; Snoep, J.L.; Visser, D.; van der Heijden, R.T.J.M.; Heijnen, J.J.; Westerhoff, H.V.

    2000-01-01

    A sustained decrease in the intracellular ATP concentration has been observed when extra glucose was added to yeast cells growing aerobically under glucose limitation. Because glucose degradation is the main source of ATP-derived free energy, this is a counter-intuitive phenomenon, which cannot be

  1. Optimisation of ATP determination in drinking water

    DEFF Research Database (Denmark)

    Corfitzen, Charlotte B.; Albrechtsen, Hans-Jørgen

    aliquots of standards increase quality control and ease daily operation. The medium (Lumin(PM) buffer, tap water or MilliQ water) for preparation of ATP-standard dilution significantly affected the rlu response of the ATP-standard dilutions (20% difference). The effect of dilution media and of sample...

  2. The Role of Light–Dark Regulation of the Chloroplast ATP Synthase

    Directory of Open Access Journals (Sweden)

    Kaori Kohzuma

    2017-07-01

    Full Text Available The chloroplast ATP synthase catalyzes the light-driven synthesis of ATP and is activated in the light and inactivated in the dark by redox-modulation through the thioredoxin system. It has been proposed that this down-regulation is important for preventing wasteful hydrolysis of ATP in the dark. To test this proposal, we compared the effects of extended dark exposure in Arabidopsis lines expressing the wild-type and mutant forms of ATP synthase that are redox regulated or constitutively active. In contrast to the predictions of the model, we observed that plants with wild-type redox regulation lost photosynthetic capacity rapidly in darkness, whereas those expressing redox-insensitive form were far more stable. To explain these results, we propose that in wild-type plants, down-regulation of ATP synthase inhibits ATP hydrolysis, leading to dissipation of thylakoid proton motive force (pmf and subsequent inhibition of protein transport across the thylakoid through the twin arginine transporter (Tat-dependent and Sec-dependent import pathways, resulting in the selective loss of specific protein complexes. By contrast, in mutants with a redox-insensitive ATP synthase, pmf is maintained by ATP hydrolysis, thus allowing protein transport to maintain photosynthetic activities for extended periods in the dark. Hence, a basal level of Tat-dependent, as well as, Sec-dependent import activity, in the dark helps replenishes certain components of the photosynthetic complexes and thereby aids in maintaining overall complex activity. However, the influence of a dark pmf on thylakoid protein import, by itself, could not explain all the effects we observed in this study. For example, we also observed in wild type plants a large transient buildup of thylakoid pmf and nonphotochemical exciton quenching upon sudden illumination of dark adapted plants. Therefore, we conclude that down-regulation of the ATP synthase is probably not related to preventing loss of ATP

  3. Striking a Balance between Program Requirements and GT Principles: Writing a compromised GT proposal

    OpenAIRE

    Sherry L. Xie, Ph.D. Candidate

    2009-01-01

    Glaser’s term “compromised GT proposal” (2001, p.114) refers to the type of Grounded Theory (GT) proposal that is written in order to conform to the requirements of a standardized qualitative research proposal. A GT proposal needs only to supply information on the area of interest, the data source and a statement of method to the effect that the researcher begin to collect, code and analyse the data and let the theory emerge. Thus, the proposal may only occupy “a page or two” (Glaser, 2001, p...

  4. 76 FR 13101 - Building Energy Codes Program: Presenting and Receiving Comments to DOE Proposed Changes to the...

    Science.gov (United States)

    2011-03-10

    ... CONTACT: Mr. Robert Dewey, U.S. Department of Energy, Energy Efficiency and Renewable Energy, Building... Part 430 Building Energy Codes Program: Presenting and Receiving Comments to DOE Proposed Changes to the International Green Construction Code (IgCC) AGENCY: Office of Energy Efficiency and Renewable...

  5. 78 FR 67385 - 30-Day Notice of Proposed Information Collection: FHA PowerSaver Pilot Program (Title I Property...

    Science.gov (United States)

    2013-11-12

    ... URBAN DEVELOPMENT 30-Day Notice of Proposed Information Collection: FHA PowerSaver Pilot Program (Title... with the Paperwork Reduction Act. The purpose of this notice is to allow for an additional 30 days of... information collection for a period of 60 days was published on August 9, 2013. A. Overview of Information...

  6. 78 FR 64145 - 30-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

    Science.gov (United States)

    2013-10-25

    ... URBAN DEVELOPMENT 30-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing..., 2013. A. Overview of Information Collection Title of Information Collection: Housing Finance Agency... Secretary to implement risk sharing with State and local housing finance agencies (HFAs). Under this program...

  7. 76 FR 624 - Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program...

    Science.gov (United States)

    2011-01-05

    ... AFFAIRS Proposed Information Collection (Patient Satisfaction Survey Michael E. DeBakey Home Care Program.... 2900-New (VA Form 10-0476).'' SUPPLEMENTARY INFORMATION: Title: Patient Satisfaction Survey Michael E... Review: New collection. Abstract: VA Form 10-0476 will be used to gather feedback from patients regarding...

  8. 76 FR 47180 - Pick-Sloan Missouri Basin Program-Eastern Division-2021 Power Marketing Initiative Proposal

    Science.gov (United States)

    2011-08-04

    ... Area Power Administration Pick-Sloan Missouri Basin Program--Eastern Division--2021 Power Marketing... marketing agency of the Department of Energy (DOE) published the proposed 2021 Power Marketing Initiative... Region. The meetings provided all firm power customers the opportunity to review current marketing plan...

  9. 77 FR 57103 - Notice of Submission of Proposed Information Collection to OMB Housing Counseling Program

    Science.gov (United States)

    2012-09-17

    ... URBAN DEVELOPMENT Notice of Submission of Proposed Information Collection to OMB Housing Counseling... comments on the subject proposal. Nonprofit Housing Counseling organizations submit information to HUD through Grants.gov when applying for grant funds to provide housing counseling assistance to eligible...

  10. 76 FR 25612 - National Organic Program; Proposed Amendments to the National List of Allowed and Prohibited...

    Science.gov (United States)

    2011-05-05

    ... treatment for dairy and breeder stock when organic system plan-approved ] preventive management does not...; ] DEPARTMENT OF AGRICULTURE Agricultural Marketing Service 7 CFR Part 205 RIN 0581-AD05 National Organic...: Agricultural Marketing Service, USDA. ACTION: Proposed rule. SUMMARY: This proposed rule would amend the U.S...

  11. 75 FR 71513 - Senior Community Service Employment Program; Notice of Proposed Rulemaking, Additional Indicator...

    Science.gov (United States)

    2010-11-23

    ... Rulemaking, Additional Indicator on Volunteer Work; Proposed Rule #0;#0;Federal Register / Vol. 75, No. 225... Rulemaking, Additional Indicator on Volunteer Work AGENCY: Employment and Training Administration, Labor... to the proposed additional indicator on http://www.regulations.gov without making any change to the...

  12. 76 FR 38618 - Proposed Information Collection; Comment Request; Coral Reef Conservation Program Survey

    Science.gov (United States)

    2011-07-01

    ... 6616, 14th and Constitution Avenue, NW., Washington, DC 20230 (or via the Internet at [email protected] allow CRCP staff to ensure programs are designed appropriately at the start, future program evaluation... expect to use face-to-face interviews in American Samoa, internet-based survey techniques in Hawaii and...

  13. 76 FR 43657 - Proposed Information Collection; Comment Request; Project 25 Compliance Assessment Program...

    Science.gov (United States)

    2011-07-21

    ... Compliance Assessment Program Laboratory Application for Assessment and Recognition AGENCY: National... (NIST) and the Department of Homeland Security (DHS) developed the Project 25 Compliance Assessment Program (P25 CAP) to improve public safety confidence in purchasing land mobile radio (LMR) equipment...

  14. 75 FR 32182 - Medicaid Program: Proposed Implementation of Section 614 of the Children's Health Insurance...

    Science.gov (United States)

    2010-06-07

    ... 614 of the Children's Health Insurance Program Reauthorization Act of 2009 (CHIPRA), Public Law 111-3... under the Children's Health Insurance Program under title XXI of the Social Security Act. In other... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND...

  15. 76 FR 60854 - Notice of Submission of Proposed Information Collection to OMB; Housing Choice Voucher Program...

    Science.gov (United States)

    2011-09-30

    ... performing and efficient PHAs and to use this information to develop a new administrative fee allocation... the overhead costs and other costs related to HCV program administration that cannot be captured by... to develop a new administrative fee allocation formula for the HCV program. The study is proceeding...

  16. 76 FR 4376 - Office of Justice Programs; Agency Information Collection Activities; Proposed Collection...

    Science.gov (United States)

    2011-01-25

    ...-effectiveness of the Forensic Casework DNA Backlog Programs over time and to diagnose performance problems in... Officials, and Forensic Laboratory personnel from agencies within the jurisdiction represented by the... diagnose program performance problems, but also to better understand whether the benefits of DNA collection...

  17. 77 FR 262 - Proposed Information Collection; Comment Request; Geographic Partnership Programs

    Science.gov (United States)

    2012-01-04

    ... updates and corrections to the elementary, secondary, and unified school district names and Federal Local... INFORMATION: I. Abstract The mission of the Geography Division within the Census Bureau is to plan, coordinate... statistical programs throughout the United States and its territories. The Geography Division manages programs...

  18. Metal-dependent regulation of ATP7A and ATP7B in fibroblast cultures

    DEFF Research Database (Denmark)

    Lenartowicz, Malgorzata; Moos, Torben; Ogórek, Mateusz

    2016-01-01

    Deficiency of one of the copper transporters ATP7A and ATP7B leads to the rare X-linked disorder Menkes Disease (MD) or the rare autosomal disorder Wilson disease (WD), respectively. In order to investigate whether the ATP7A and the ATP7B genes may be transcriptionally regulated, we measured...... the expression level of the two genes at various concentrations of iron, copper, and insulin. Treating fibroblasts from controls or from individuals with MD or WD for 3 and 10 days with iron chelators revealed that iron deficiency led to increased transcript levels of both ATP7A and ATP7B. Copper deficiency...... for the two genes were observed in response to iron deficiency, different responses were observed after changes in the access to copper. Mosaic fibroblast cultures from female carriers of MD treated with copper or copper chelator for 6-8 weeks led to clonal selection. Cells that express the normal ATP7A...

  19. Identification of a site of ATP requirement for signal processing in bacterial chemotaxis.

    Science.gov (United States)

    Smith, J M; Rowsell, E H; Shioi, J; Taylor, B L

    1988-06-01

    In Escherichia coli and Salmonella typhimurium, ATP is required for chemotaxis and for a normal probability of clockwise rotation of the flagellar motors, in addition to the requirement for S-adenosylmethionine (J. Shioi, R. J. Galloway, M. Niwano, R. E. Chinnock, and B. L. Taylor, J. Biol. Chem. 257:7969-7975, 1982). The site of the ATP requirement was investigated. The times required for S. typhimurium ST23 (hisF) to adapt to a step increase in serine, phenol, or benzoate were similar in cells depleted of ATP and in cells with normal levels of ATP. This established that ATP was not required for the chemotactic signal to cross the inner membrane or for adaptation to the transmembrane signal to occur. Depletion of ATP did not affect the probability of clockwise rotation in E. coli cheYZ scy strains that were defective in the cheY and cheZ genes and had a partially compensating mutation in the motor switch. Strain HCB326 (cheAWRBYZ tar tap tsr trg::Tn10), which was deficient in all chemotaxis components except the switch and motor, was transformed with the pCK63 plasmid (ptac-cheY+). Induction of cheY in the transformant increased the frequency of clockwise rotation, but except at the highest levels of CheY overproduction, clockwise rotation was abolished by depleting ATP. It is proposed that the CheY protein is normally in an inactive form and that ATP is required for formation of an active CheY* protein that binds to the switch on the flagellar motors and initiates clockwise rotation. Depletion of ATP partially inhibits feedback regulation of the cheB product, protein methylesterase, but this may reflect a second site of ATP action in chemotaxis.

  20. Lowest Price, Technically Acceptable Evaluation Criteria Used in the November 2014 Request for Proposal for the Program Executive Office Soldier Systems Engineering and Technical Assistance (SETA) Contract

    Science.gov (United States)

    2017-09-01

    USED IN THE NOVEMBER 2014 REQUEST FOR PROPOSAL FOR THE PROGRAM EXECUTIVE OFFICE SOLDIER SYSTEMS ENGINEERING AND TECHNICAL ASSISTANCE (SETA) CONTRACT...NOVEMBER 2014 REQUEST FOR PROPOSAL FOR THE PROGRAM EXECUTIVE OFFICE SOLDIER SYSTEMS ENGINEERING AND TECHNICAL ASSISTANCE (SETA) CONTRACT 5. FUNDING...evaluation process for replies received in response to a request for proposal (RFP) for systems engineering and technical assistance (SETA) support

  1. 76 FR 21372 - Medicare Program; Solicitation for Proposals for the Medicare Community-Based Care Transitions...

    Science.gov (United States)

    2011-04-15

    ... beneficiaries at high risk for readmission, including those with multiple chronic conditions, depression, or... proposal in the manner intended by the applicant (for example, collated, tabulated color copies). Hard...

  2. 77 FR 7604 - Notice Requesting Public Comment on Two Proposed Unemployment Insurance (UI) Program Performance...

    Science.gov (United States)

    2012-02-13

    ... Employment and Training Administration Notice Requesting Public Comment on Two Proposed Unemployment... Recovery Act of 2010 (IPERA) AGENCY: Employment and Training Administration (ETA), Labor. ACTION: Notice... Definition and Acceptable Level of Performance (ALP) Measure Definition: Combined percentage of UI benefits...

  3. 75 FR 26283 - Proposed Collection, Submission for OMB Review, Museums for America Grant Program Evaluation

    Science.gov (United States)

    2010-05-11

    ... burden of the proposed collection of information including the validity of the methodology and... Time per Respondent: Dependent on level of questioning: 475--15 minutes; 250--30 minutes: 175--50...

  4. 75 FR 46169 - Medicare Program; Proposed Changes to the Hospital Outpatient Prospective Payment System and CY...

    Science.gov (United States)

    2010-08-03

    ... OPPS Payments A. Proposed Recalibration of APC Relative Weights 1. Database Construction a. Database... occupational therapy, and speech-language pathology services, for which payment is made under a fee schedule...

  5. 78 FR 52008 - 30-Day Notice of Proposed Information Collection: Multifamily Housing Service Coordinator Program

    Science.gov (United States)

    2013-08-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT 30-Day Notice of Proposed Information Collection: Multifamily Housing Service..., 2012. A. Overview of Information Collection Title of Information Collection: Multifamily Housing...

  6. 76 FR 32971 - Proposed Priority for the Disability and Rehabilitation Research Projects and Centers Program

    Science.gov (United States)

    2011-06-07

    ... and Rehabilitation Research Project (DRRP)--Center on Knowledge Translation for Disability and... notice proposes a priority for a center on knowledge translation for disability and rehabilitation..., demonstration projects, training, and related activities, including international activities, to develop methods...

  7. Molecular devices for the regulation of chloroplast ATP synthase

    NARCIS (Netherlands)

    Hisabori, T.; Konno, H.; Ichimura, H.; Strotmann, H.; Bald, D.

    2002-01-01

    In chloroplasts, synthesis of ATP is energetically coupled with the utilization of a proton gradient formed by photosynthetic electron transport. The involved enzyme, the chloroplast ATP synthase, can potentially hydrolyze ATP when the magnitude of the transmembrane electrochemical potential

  8. Preoperative multidisciplinary program for bariatric surgery: a proposal for the Brazilian Public Health System

    Directory of Open Access Journals (Sweden)

    Elinton Adami CHAIM

    Full Text Available ABSTRACT BACKGROUND Bariatric surgery has become the gold standard treatment for morbid obesity, but access to surgery remains difficult and low compliance to postoperative follow-up is common. To improve outcomes, enable access and optimize follow-up, we developed a multidisciplinary preoperative approach for bariatric surgery. OBJECTIVE To determine the impact of this program in the outcomes of bariatric surgery in the Brazilian public health system. METHODS A prospective evaluation of the individuals who underwent a preoperative multidisciplinary program for bariatric surgery and comparison of their surgical outcomes with those observed in the prospectively collected historical database of the individuals who underwent surgery before the beginning of the program. RESULTS There were 176 individuals who underwent the multidisciplinary program and 226 who did not. Individuals who underwent the program had significantly lower occurrence of the following variables: hospital stay; wound dehiscence; wound infection; pulmonary complications; anastomotic leaks; pulmonary thromboembolism; sepsis; incisional hernias; eventrations; reoperations; and mortality. Both loss of follow-up and weight loss failure were also significantly lower in the program group. CONCLUSION The adoption of a comprehensive preoperative multidisciplinary approach led to significant improvements in the postoperative outcomes and also in the compliance to the postoperative follow-up. It represents a reproducible and potentially beneficial approach within the context of the Brazilian public health system.

  9. Kinetics of signaling-DNA-aptamer-ATP binding

    Science.gov (United States)

    Nakamura, Issei; Shi, An-Chang; Nutiu, Razvan; Yu, Jasmine M. Y.; Li, Yingfu

    2009-03-01

    DNA aptamers are molecular biosensors consisting of single functionalized DNA molecules, which can bind to specific targets or complementary DNA sequences. The binding kinetics of DNA aptamers is studied by fluorescence quenching at 23°C . A kinetic model for the binding reaction of DNA aptamer, antisense DNA, and ATP target is developed to describe experimental observations. The approach leads to a simple procedure to deduce relevant kinetic reactions and their rate constants. A comparison between theory and experiments indicates that the previously established bimolecular DNA-ATP binding does not provide a complete description of the experimental data. Side reactions such as trimolecular complexation are proposed. Rate constants of the model are determined by comparing the model predictions and experiments. Good agreements between the model and experiments have been obtained. Possible blocking reactions by the misfolded DNA aptamer are also discussed.

  10. Extracellular ATP Induces Calcium Signaling in Odontoblasts.

    Science.gov (United States)

    Lee, B M; Jo, H; Park, G; Kim, Y H; Park, C K; Jung, S J; Chung, G; Oh, S B

    2017-02-01

    Odontoblasts form dentin at the outermost surface of tooth pulp. An increasing level of evidence in recent years, along with their locational advantage, implicates odontoblasts as a secondary role as sensory or immune cells. Extracellular adenosine triphosphate (ATP) is a well-characterized signaling molecule in the neuronal and immune systems, and its potential involvement in interodontoblast communications was recently demonstrated. In an effort to elaborate the ATP-mediated signaling pathway in odontoblasts, the current study performed single-cell reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescent detection to investigate the expression of ATP receptors related to calcium signal in odontoblasts from incisal teeth of 8- to 10-wk-old rats, and demonstrated an in vitro response to ATP application via calcium imaging experiments. While whole tissue RT-PCR analysis detected P2Y2, P2Y4, and all 7 subtypes (P2X1 to P2X7) in tooth pulp, single-cell RT-PCR analysis of acutely isolated rat odontoblasts revealed P2Y2, P2Y4, P2X2, P2X4, P2X6, and P2X7 expression in only a subset (23% to 47%) of cells tested, with no evidence for P2X1, P2X3, and P2X5 expression. An increase of intracellular Ca(2+) concentration in response to 100μM ATP, which was repeated after pretreatment of thapsigargin or under the Ca(2+)-free condition, suggested function of both ionotropic and metabotropic ATP receptors in odontoblasts. The enhancement of ATP-induced calcium response by ivermectin and inhibition by 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD) confirmed a functional P2X4 subtype in odontoblasts. Positive calcium response to 2',3'-O-(benzoyl-4-benzoyl)-ATP (BzATP) and negative response to α,β-methylene ATP suggested P2X2, P2X4, and P2X7 as functional subunits in rat odontoblasts. Single-cell RT-PCR analysis of the cells with confirmed calcium response and immunofluorescent detection further corroborated the expression of P2X

  11. Proposed Revenues, Financial Strategy, and Program Costs for FY 1992 and 1993 : Technical Appendix, BPA Programs in Perspective.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1990-07-01

    Programs in Perspective is the Bonneville Power Administration's public involvement process (PIP) for engaging customers and other stakeholders in a regional dialog to set strategic direction and broad program plans for BPA effort. This planning leads into a biennial rate setting cycle and offers a more accessible and flexible opportunity for dialog on broad issues than is possible under the strict administrative procedures of ratemaking. The self-financed character of BPA has made this public process a necessary and valuable one to assure that those who pay BPA's rates have a clear understanding and a strong voice in the plans for use of the resulting revenues. During 1989, the previous PIP engaged the region in discussion of major strategic, issues focussing on major areas. In 1990, BPA seeks discussion of the directions and plans specifically for fiscal years 1992 and 1993. The steps taken for those years will lay the foundation for the years beyond. Thus, we have subtitled this year's process, Staying fit for the long run.'' We have consulted extensively with customers and others in the region in developing these plans. In dozens of program--specific meetings, BPA staff have talked and listened to what others think our plans ought to be. PIP now gives us a chance to review their sum total, along with projections for revenues and our overall financial position. 8 tabs., 8 figs.

  12. A proposal to establish master's in biomedical sciences degree programs in medical school environments.

    Science.gov (United States)

    Ingoglia, Nicholas A

    2009-04-01

    Most graduate schools associated with medical schools offer programs leading to the PhD degree but pay little attention to master's programs. This is unfortunate because many university graduates who are interested specifically in biomedical rather than pure science fields need further education before making decisions on whether to enter clinical, research, education, or business careers. Training for these students is done best in a medical school, rather than a graduate university, environment and by faculty who are engaged in research in the biomedical sciences. Students benefit from these programs by exploring career options they might not have previously considered while learning about disease-related subjects at the graduate level. Graduate faculty can also benefit by being compensated for their teaching with a portion of the tuition revenue, funds that can help run their laboratories and support other academic expenses. Faculty also may attract talented students to their labs and to their PhD programs by exposing them to a passion for research. The graduate school also benefits by collecting masters tuition revenue that can be used toward supporting PhD stipends. Six-year outcome data from the program at Newark show that, on completion of the program, most students enter educational, clinical, or research careers and that the graduate school has established a new and significant stream of revenue. Thus, the establishment of a master's program in biomedical sciences that helps students match their academic abilities with their career goals significantly benefits students as well as the graduate school and its faculty.

  13. School-based sleep education programs: A knowledge-to-action perspective regarding barriers, proposed solutions, and future directions.

    Science.gov (United States)

    Gruber, Reut

    2017-12-01

    Sleep is associated with an array of physical and mental health outcomes that are essential for healthy adjustment in children. Unfortunately, transfer of this knowledge into action has been slow and largely ineffective. There are only 15 published school-based sleep health promotion programs, and findings are mixed in terms of their impact on sleep behavior, knowledge and health outcomes. This paper applies a knowledge-to-action (KTA) framework to assess the strengths and weaknesses of such programs and to identify strategies that can be used to enhance the translation of empirical evidence in pediatric sleep to effective action. It is proposed that effectiveness of interventions may be increased by defining specific targets for change, identifying prospectively the gap between current sleep practice or knowledge and intervention goals, assessing and addressing barriers and facilitators for program implementation, adapting the program for local use, tailoring it to the developmental needs of the target users, using rigorous designs to evaluate outcomes and improving sustainability by engaging multiple stakeholders throughout the KTA process. Collectively it is proposed that integrating a KTA framework and related strategies will enhance the effectiveness of these programs in translating empirical evidence in pediatric sleep to effective and sustained action. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Metal-dependent regulation of ATP7A and ATP7B in fibroblast cultures

    Directory of Open Access Journals (Sweden)

    Lenartowicz Malgorzata

    2016-08-01

    Full Text Available Deficiency of one of the copper transporters ATP7A and ATP7B leads to the rare X-linked disorder Menkes Disease (MD or the rare autosomal disorder Wilson disease (WD, respectively. In order to investigate whether the ATP7A and the ATP7B genes may be transcriptionally regulated, we measured the expression level of the two genes at various concentrations of iron, copper and insulin. Treating fibroblasts from controls or from individuals with MD or WD for 3 and10 days with iron chelators revealed that iron deficiency led to increased transcript levels of both ATP7A and ATP7B. Copper deficiency obtained by treatment with the copper chelator led to a downregulation of ATP7A in the control fibroblasts, but surprisingly not in the WD fibroblasts. In contrast, the addition of copper led to an increased expression of ATP7A, but a decreased expression of ATP7B. Thus, whereas similar regulation patterns for the two genes were observed in response to iron deficiency, different responses were observed after changes in the access to copper. Mosaic fibroblast cultures from female carriers of MD treated with copper or copper chelator for 6-8 weeks led to clonal selection. Cells that express the normal ATP7A allele had a selective growth advantage at high copper concentrations, whereas more surprisingly, cells that express the mutant ATP7A allele had a selective growth advantage at low copper concentrations. Thus, although the transcription of ATP7A is regulated by copper, clonal growth selection in mosaic cell cultures is affected by the level of copper. Female carriers of MD are rarely affected probably due to a skewed inactivation of the X-chromosome bearing the ATP7A mutation.

  15. ATP oscillations mediate inductive action of FGF and Shh signalling on prechondrogenic condensation.

    Science.gov (United States)

    Kwon, Hyuck Joon

    2013-01-01

    Skeletal patterns are prefigured by prechondrogenic condensation. Morphogens such as fibroblast growth factor (FGF) and sonic hedgehog (Shh) specify the skeletal patterns in limb development. However, how morphogens regulate prechondrogenic condensation has remained unclear. Recently, it was demonstrated that synchronized Adenosine triphosphate (ATP) oscillations play a critical role in prechondrogenic condensation. Thus, the present study has focused on whether ATP oscillations mediate the actions of major developmental morphogens such as FGF and Shh on prechondrogenic condensation. It has been shown that both FGF and Shh signalling promoted cellular condensation but not chondrogenic differentiation and also induced ATP oscillations. In addition, blockage of FGF and Shh signalling prevented both ATP oscillations and prechondrogenic condensation. Furthermore, it was found that inhibition of ATP oscillations suppressed FGF/Shh-induced prechondrogenic condensation. These results indicate that ATP oscillations mediate the actions of FGF and Shh signalling on prechondrogenic condensation. This study proposes that morphogens organize skeletal patterns via ATP oscillations. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1.

    Science.gov (United States)

    Elnatan, Daniel; Betegon, Miguel; Liu, Yanxin; Ramelot, Theresa; Kennedy, Michael A; Agard, David A

    2017-07-25

    Hsp90 is a homodimeric ATP-dependent molecular chaperone that remodels its substrate 'client' proteins, facilitating their folding and activating them for biological function. Despite decades of research, the mechanism connecting ATP hydrolysis and chaperone function remains elusive. Particularly puzzling has been the apparent lack of cooperativity in hydrolysis of the ATP in each protomer. A crystal structure of the mitochondrial Hsp90, TRAP1, revealed that the catalytically active state is closed in a highly strained asymmetric conformation. This asymmetry, unobserved in other Hsp90 homologs, is due to buckling of one of the protomers and is most pronounced at the broadly conserved client-binding region. Here, we show that rather than being cooperative or independent, ATP hydrolysis on the two protomers is sequential and deterministic. Moreover, dimer asymmetry sets up differential hydrolysis rates for each protomer, such that the buckled conformation favors ATP hydrolysis. Remarkably, after the first hydrolysis, the dimer undergoes a flip in the asymmetry while remaining in a closed state for the second hydrolysis. From these results, we propose a model where direct coupling of ATP hydrolysis and conformational flipping rearranges client-binding sites, providing a paradigm of how energy from ATP hydrolysis can be used for client remodeling.

  17. 78 FR 25760 - Proposed Information Collection; Urban Park and Recreation Recovery Program Grants

    Science.gov (United States)

    2013-05-02

    ...--renovate or redesign existing close-to- home recreation facilities. Innovation--specific activities that... Rehabilitation or Innovation grants. Rehabilitation and Innovation proposals must be based on priorities...), narrative statements with a description and scope of the planning product(s) to be developed, a project...

  18. 78 FR 72600 - Proposed Priorities, Requirements, and Definitions-Charter Schools Program (CSP) Grants for...

    Science.gov (United States)

    2013-12-03

    ...) Grants for National Leadership Activities AGENCY: Office of Innovation and Improvement, Department of... Assistant Deputy Secretary for Innovation and Improvement proposes priorities, requirements, and definitions...-career-ready standards. Moreover, it is of great importance to ensure equitable access to and use of...

  19. 77 FR 3787 - Notice of Submission of Proposed Information Collection to OMB; Family Unification Program (FUP)

    Science.gov (United States)

    2012-01-25

    ... Vouchers available to eligible families to promote family reunification. Youths 18 to 21 who left foster... promote family reunification. Youths 18 to 21 who left foster care at age 16 or older are also eligible to... URBAN DEVELOPMENT Notice of Submission of Proposed Information Collection to OMB; Family Unification...

  20. 76 FR 11505 - Notice of Submission of Proposed Information Collection to OMB Family Unification Program (FUP)

    Science.gov (United States)

    2011-03-02

    ... Vouchers available to eligible families to promote family reunification. Youths 18 to 21 who left foster... family reunification. Youths 18 to 21 who left foster care at age 16 or older are also eligible to... URBAN DEVELOPMENT Notice of Submission of Proposed Information Collection to OMB Family Unification...

  1. 76 FR 35864 - Proposed Priority; Special Demonstration Programs-National Technical Assistance Projects To...

    Science.gov (United States)

    2011-06-20

    ... continuing education to State VR agencies and other entities that partner with State VR agencies. The purpose... Doc No: 2011-15293] DEPARTMENT OF EDUCATION [CFDA 84.235M] Proposed Priority; Special Demonstration... Disabilities AGENCY: Office of Special Education and Rehabilitative Services, Department of Education. ACTION...

  2. 78 FR 11622 - Request for Proposals: 2013 Hazardous Fuels Woody Biomass Utilization Grant Program

    Science.gov (United States)

    2013-02-19

    ... energy technology, what other technologies were considered, why the recommended renewable energy.... Total Points 15 d. Amount and type of fossil fuel offset in therms/year and increased system fuel use... Unit, located at the Forest Products Laboratory, requests proposals for wood energy projects that...

  3. 77 FR 56857 - Notice of Proposed Information Collection for Public Comment; Public Housing Mortgage Program and...

    Science.gov (United States)

    2012-09-14

    ... other assets, a proposal must be submitted to HUD. After approval and execution of any legal documents... [email protected] . Persons with hearing or speech impairments may access this number through TTY by...-402-4109, (this is not a toll-free number). Persons with hearing or speech impairments may access this...

  4. 78 FR 20296 - Proposed Information Collection; Comment Request; Marine Recreational Information Program Fishing...

    Science.gov (United States)

    2013-04-04

    ... information or copies of the information collection instrument(s) and instructions should be directed to Rob... Atlantic and Gulf coast states (except TX), HI and Puerto Rico. II. Method of Collection Information will... National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Marine...

  5. 75 FR 24962 - Notice of Proposed Information Collection for Public Comment: Disaster Assistance Program...

    Science.gov (United States)

    2010-05-06

    ... an important opportunity for HUD to learn about rent- setting strategies and case management services... strategies employed by participating public housing authorities (PHAs) for providing case management to help... URBAN DEVELOPMENT Notice of Proposed Information Collection for Public Comment: Disaster Assistance...

  6. 76 FR 68770 - Proposed Eligibility Criteria for the Centers of Excellence Program in Health Professions...

    Science.gov (United States)

    2011-11-07

    ... graduate degree in Behavioral or Mental Health from the school of discipline, the proposed graduation rate... students from all levels of the education pipeline to pursue health professions careers. Such schools are... Education for Under-Represented Minority Individuals AGENCY: Health Resources and Services Administration...

  7. 77 FR 16250 - Notice of Proposed Information Collection for Public Comment; Office of Native American Programs...

    Science.gov (United States)

    2012-03-20

    ... Native American, Alaska Native, and native Hawaiian communities, as funded by Indian Housing Block Grants...: Office of the Assistant Secretary for Public and Indian Housing, HUD. ACTION: Notice of proposed..., Departmental Reports Management Officer, QDAM, Department of Housing and Urban Development, 451 7th Street SW...

  8. 77 FR 21547 - Proposed Priorities; Disability and Rehabilitation Research Projects and Centers Program

    Science.gov (United States)

    2012-04-10

    ... research on persons with disabilities: What we know and where we need to go. American Journal of Physical... with disabilities. Journal of Womens Health. 19(10): 1869-76. ] Proposed Priority 2--Rehabilitation... children with autism and elderly adults with dementia (Van der Loos & Reinkensmeyer, 2008). There are a...

  9. Redox regulation of ATP sulfurylase in microalgae

    Czech Academy of Sciences Publication Activity Database

    Prioretti, L.; Lebrun, R.; Gontero, B.; Giordano, Mario

    2016-01-01

    Roč. 478, č. 4 (2016), s. 1555-1562 ISSN 0006-291X Institutional support: RVO:61388971 Keywords : ATP sulfurylase * cysteine * Sulfur metabolism Subject RIV: EE - Microbiology, Virology Impact factor: 2.466, year: 2016

  10. 76 FR 13648 - Proposed Collection; Comment Request; Process Evaluation of the NIH Roadmap Epigenomics Program

    Science.gov (United States)

    2011-03-14

    ... synthesized results across primary and secondary data sources will provide critical insights on... tracking and monitoring systems along with primary data to assess program process and progress, is non-experimental. The assessment is based on secondary source information, with primary source information...

  11. 76 FR 35232 - Notice of Proposed Information Collection for Public Comment; Housing Choice Voucher Program...

    Science.gov (United States)

    2011-06-16

    ... respond, including through the use of appropriate automated collection techniques or other forms of... collecting cost data: (1) Measuring the time that front line staff spend working on the program and translating that time into costs using the salaries and benefits of the staff doing the work and adjusting for...

  12. 76 FR 79650 - Proposed Information Collection; Comment Request; Survey of Income and Program Participation...

    Science.gov (United States)

    2011-12-22

    ... (or via the Internet at [email protected] ). FOR FURTHER INFORMATION CONTACT: Requests for additional... effect of tax and transfer programs on this distribution. They also need improved and expanded data on... estimate that each household contains 2.1 people, age 15 years or older, yielding approximately 94,500...

  13. 75 FR 21593 - Proposed Information Collection; Comment Request; Survey of Income and Program Participation...

    Science.gov (United States)

    2010-04-26

    ... 20230 (or via the Internet at [email protected] ). FOR FURTHER INFORMATION CONTACT: Requests for additional... effect of tax and transfer programs on this distribution. They also need improved and expanded data on... contains 2.1 people, yielding 88,267 person-level interviews in Wave 1 and subsequent waves. Interviews...

  14. 75 FR 22102 - Proposed Information Collection; Comment Request; Survey of Income and Program Participation...

    Science.gov (United States)

    2010-04-27

    ... 20230 (or via the Internet at [email protected] ). FOR FURTHER INFORMATION CONTACT: Requests for additional... effect of tax and transfer programs on this distribution. They also need improved and expanded data on... contains 2.1 people, yielding 88,267 person-level interviews in Wave 1 and subsequent waves. Interviews...

  15. 76 FR 24457 - Proposed Information Collection; Comment Request; Survey of Income and Program Participation...

    Science.gov (United States)

    2011-05-02

    ...., Washington, DC 20230 (or via the Internet at [email protected] ). FOR FURTHER INFORMATION CONTACT: Requests for... effect of tax and transfer programs on this distribution. They also need improved and expanded data on... estimate that each household contains 2.1 people, age 15 years or older, yielding approximately 94,500...

  16. 77 FR 16841 - Medicare Program; Solicitation for Proposals for the Medicare Graduate Nurse Education...

    Science.gov (United States)

    2012-03-22

    ... the Medicare Graduate Nurse Education Demonstration Program AGENCY: Centers for Medicare & Medicaid... to participate in the Medicare Graduate Nurse Education (GNE) Demonstration. The primary goal of the... has a written agreement in place with--(A) 1 or more applicable schools of nursing; and (B) 2 or more...

  17. 76 FR 63017 - Medicare Program; Proposed Changes to the Medicare Advantage and the Medicare Prescription Drug...

    Science.gov (United States)

    2011-10-11

    .... Medication Therapy Management Comprehensive Medication Reviews and Beneficiaries in LTC Settings (Sec. 423... Medication Therapy Management MTMP Medication Therapy Management Program ] NAIC National Association... gradually increasing coverage in the coverage gap for both generic drugs (beginning in 2011) and brand name...

  18. Health and weight control management among wrestlers. A proposed program for high school athletes.

    Science.gov (United States)

    Perriello, V A; Almquist, J; Conkwright, D; Cutter, D; Gregory, D; Pitrezzi, M J; Roemmich, J; Snyders, G

    1995-01-01

    Weight loss is a part of any competitive sport which matches participants of equal weight or sports where participating at lower weights or with a thinner body habitus is considered an advantage. For some wrestlers, weight loss is excessive and often accomplished by methods that lead to loss of lean body mass and total body water. There is convincing evidence that this excessive weight loss is unhealthy for all individuals who follow these practices. Even greater harm is experienced by high school wrestlers who have not yet completed their growth and development. These health consequences include growth retardation, decreased academic performance, altered endocrine or hormonal function and damage to many vital organs. "cycling" of weight results in decrease in strength, power and endurance which would effect adversely a wrestler's likelihood of success. The VHSL has begun an educational program to inform coaches, wrestlers and parents about the hazards inherent in these weight loss practices. History suggests that education alone will not alter the present practices of weight loss. Therefore a weight management program similar to ones initiated in other states is being pursued by the VHSL. The pilot program this year is scheduled to be followed next year by a more wide-spread voluntary program across the Commonwealth.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. 76 FR 7570 - Proposed Collection; Comment Request; National Institutes of Health Loan Repayment Programs

    Science.gov (United States)

    2011-02-10

    ... Application System (MIS/OAS). Request for Comments: Written comments and/or suggestions from the public and... participation in the program. Frequency of Response: Initial application and one- or two-year renewal application. Affected Public: Individuals or households, nonprofits, and businesses or other for-profit. Type...

  20. 77 FR 73493 - Notice of Proposed Information Collection: Comment Request Family Self-Sufficiency Program...

    Science.gov (United States)

    2012-12-10

    ... the program. A random assignment model is needed because participant self-selection into FSS limits... forms of information technology, e.g., permitting electronic submission of responses. This notice also.... FSS has operated since 1992 and serves voucher holders and residents of public housing. The FSS model...

  1. 75 FR 338 - Proposed Information Collection; Comment Request; NOAA Teacher at Sea Program

    Science.gov (United States)

    2010-01-05

    ... Information Collection; Comment Request; NOAA Teacher at Sea Program AGENCY: National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice. SUMMARY: The Department of Commerce, as part of its continuing... Hammond, (301) 713-0353, or [email protected]noaa.gov . SUPPLEMENTARY INFORMATION: I. Abstract NOAA...

  2. Academic Stress in Chinese Schools and a Proposed Preventive Intervention Program

    Science.gov (United States)

    Zhao, Xu; Selman, Robert L.; Haste, Helen

    2015-01-01

    While American educators fret about the mediocre educational performance of American students in international contests (e.g. the Program for International Student Assessment) and wonder why the Chinese education system produces such high-achieving students, educators, journalists, and public officials in China want to know what causes and how to…

  3. 76 FR 53844 - National Dairy Promotion and Research Program; Invitation To Submit Comments on Proposed...

    Science.gov (United States)

    2011-08-30

    ... pursuant to the Dairy Production Stabilization Act (Dairy Act) of 1983 [7 U.S.C. 4501- 4514], as amended... Dairy Production Stabilization Act of 1983 authorizes a national program for dairy product promotion... of milk production in the United States. The Dairy Order is administered by a 38-member Dairy Board...

  4. An Application Programming Interface For Developing Distributed Algorithm Along With Proposed Meta Language Concept

    Directory of Open Access Journals (Sweden)

    Kishalay Bairagi

    2015-08-01

    Full Text Available Abstract In computer science an application programming interface API is an interface that defines the ways by which an application programming may request services from libraries.7 Libraries of a programming language are the list of all classes and interfaces along with their fields constructors and methods that are part of that language. For example java is an object oriented programming language which has a rich set of built-in classes and interfaces packaged in the API also known as java API7. Therefore a programmer can easily borrow built-in classes or interfaces to use the fields constructors and methods of those classes and interfaces in his or her application and is able to be free from the hazards of thinking the implementation details of those functions and constructors and writing it down to the application he or she is developing. An API 7 also helps a programmer to write a short and compact code to save time of program and application development and to produce a quality code having readability and understandability than the code without having the application of API. Almost all the modern programming languages come up with the rich set of APIs. The basic difference between an API and library lies in the fact that while API reflects the expected behaviour library is an actual implementation of this set of rules. 7 On the other hand the relation with framework is based on several libraries implementing several APIs but instead of normal use of an API the access to the behaviour built into the framework is made possible by extending its contents with new classes and interfaces.7 This paper presents a component of framework4 where the API for the distributed algorithms has been plugged into the framework so that a programmer can get services from the built- in classes and interfaces for easily understandable compact and faster program development. Here a concept of meta language consisting of very simple constructs has been introduced

  5. The structural basis of a high affinity ATP binding ε subunit from a bacterial ATP synthase.

    Directory of Open Access Journals (Sweden)

    Alexander Krah

    Full Text Available The ε subunit from bacterial ATP synthases functions as an ATP sensor, preventing ATPase activity when the ATP concentration in bacterial cells crosses a certain threshold. The R103A/R115A double mutant of the ε subunit from thermophilic Bacillus PS3 has been shown to bind ATP two orders of magnitude stronger than the wild type protein. We use molecular dynamics simulations and free energy calculations to derive the structural basis of the high affinity ATP binding to the R103A/R115A double mutant. Our results suggest that the double mutant is stabilized by an enhanced hydrogen-bond network and fewer repulsive contacts in the ligand binding site. The inferred structural basis of the high affinity mutant may help to design novel nucleotide sensors based on the ε subunit from bacterial ATP synthases.

  6. atpE gene as a new useful specific molecular target to quantify Mycobacterium in environmental samples

    Science.gov (United States)

    2013-01-01

    Background The environment is the likely source of many pathogenic mycobacterial species but detection of mycobacteria by bacteriological tools is generally difficult and time-consuming. Consequently, several molecular targets based on the sequences of housekeeping genes, non-functional RNA and structural ribosomal RNAs have been proposed for the detection and identification of mycobacteria in clinical or environmental samples. While certain of these targets were proposed as specific for this genus, most are prone to false positive results in complex environmental samples that include related, but distinct, bacterial genera. Nowadays the increased number of sequenced genomes and the availability of software for genomic comparison provide tools to develop novel, mycobacteria-specific targets, and the associated molecular probes and primers. Consequently, we conducted an in silico search for proteins exclusive to Mycobacterium spp. genomes in order to design sensitive and specific molecular targets. Results Among the 3989 predicted proteins from M. tuberculosis H37Rv, only 11 proteins showed 80% to 100% of similarity with Mycobacterium spp. genomes, and less than 50% of similarity with genomes of closely related Corynebacterium, Nocardia and Rhodococcus genera. Based on DNA sequence alignments, we designed primer pairs and a probe that specifically detect the atpE gene of mycobacteria, as verified by quantitative real-time PCR on a collection of mycobacteria and non-mycobacterial species. The real-time PCR method we developed was successfully used to detect mycobacteria in tap water and lake samples. Conclusions The results indicate that this real-time PCR method targeting the atpE gene can serve for highly specific detection and precise quantification of Mycobacterium spp. in environmental samples. PMID:24299240

  7. ORGANIZATION AND PLANNING IN CHILDREN WITH ADHD: EVALUATION AND PROPOSAL OF A STIMULATION PROGRAM

    Directory of Open Access Journals (Sweden)

    Josefina Rubiales

    2011-12-01

    Full Text Available The Attention Deficit Hyperactivity Disorder (ADHD is a neurobiological disorder of a complex and heterogeneous origin characterized by a persistent pattern of inattention, hyperactivity and / or impulsivity. Is one of the most common neurobehavioral disorders in childhood and adolescence, and one of the main reasons for consultation because of difficulties in school performance, behavior problems, difficulties of living at home and with peers, involvement in self-esteem and aggressiveness. The primary deficit is associated with executive dysfunction, among which is the organization and planning. The aim of this study was to compare the performance in organization and planning of children with and without a diagnosis of ADHD and submit a stimulation proposal according to their needs. MATERIALS AND METHODS: The clinical sample comprised 16 children diagnosed with ADHD and the control sample of 32 children without a diagnosis, in both cases 8 to 14 years old and from the city of Mar del Plata (Argentina. The instruments used to evaluate the organization and planning has been the subtest Torres of Mexico Child Neuropsychological Battery (ENI, and cubes subtests Construction, Completion and Management Object Test Story Weschler Intelligence for children and adolescents. The proposed treatment includes 8 sessions of stimulation. RESULTS AND CONCLUSIONS: Children with ADHD have greater difficulty in planning and organizational skills than the children of the control sample, from which it establishes a estimulation proposal, whose originality and advantage is accentuated in the ecological validity the process.

  8. Lyndon B. Johnson Space Center (JSC) proposed dual-use technology investment program in intelligent robotics

    Science.gov (United States)

    Erickson, Jon D.

    1994-01-01

    This paper presents an overview of the proposed Lyndon B. Johnson Space Center (JSC) precompetitive, dual-use technology investment project in robotics. New robotic technology in advanced robots, which can recognize and respond to their environments and to spoken human supervision so as to perform a variety of combined mobility and manipulation tasks in various sectors, is an objective of this work. In the U.S. economy, such robots offer the benefits of improved global competitiveness in a critical industrial sector; improved productivity by the end users of these robots; a growing robotics industry that produces jobs and profits; lower cost health care delivery with quality improvements; and, as these 'intelligent' robots become acceptable throughout society, an increase in the standard of living for everyone. In space, such robots will provide improved safety, reliability, and productivity as Space Station evolves, and will enable human space exploration (by human/robot teams). The proposed effort consists of partnerships between manufacturers, universities, and JSC to develop working production prototypes of these robots by leveraging current development by both sides. Currently targeted applications are in the manufacturing, health care, services, and construction sectors of the U.S. economy and in the inspection, servicing, maintenance, and repair aspects of space exploration. But the focus is on the generic software architecture and standardized interfaces for custom modules tailored for the various applications allowing end users to customize a robot as PC users customize PC's. Production prototypes would be completed in 5 years under this proposal.

  9. Proposed framework for the Western Area Power Administration Environmental Risk Management Program

    Energy Technology Data Exchange (ETDEWEB)

    Glantz, C.S.; DiMassa, F.V.; Pelto, P.J.; Brothers, A.J. [Pacific Northwest Lab., Richland, WA (United States); Roybal, A.L. [Western Area Power Administration, Golden, CO (United States)

    1994-12-01

    The Western Area Power Administration (Western) views environmental protection and compliance as a top priority as it manages the construction, operation, and maintenance of its vast network of transmission lines, substations, and other facilities. A recent Department of Energy audit of Western`s environmental management activities recommends that Western adopt a formal environmental risk program. To accomplish this goal, Western, in conjunction with Pacific Northwest Laboratory, is in the process of developing a centrally coordinated environmental risk program. This report presents the results of this design effort, and indicates the direction in which Western`s environmental risk program is heading. Western`s environmental risk program will consist of three main components: risk communication, risk assessment, and risk management/decision making. Risk communication is defined as an exchange of information on the potential for threats to human health, public safety, or the environment. This information exchange provides a mechanism for public involvement, and also for the participation in the risk assessment and management process by diverse groups or offices within Western. The objective of risk assessment is to evaluate and rank the relative magnitude of risks associated with specific environmental issues that are facing Western. The evaluation and ranking is based on the best available scientific information and judgment and serves as input to the risk management process. Risk management takes risk information and combines it with relevant non-risk factors (e.g., legal mandates, public opinion, costs) to generate risk management options. A risk management tool, such as decision analysis, can be used to help make risk management choices.

  10. Academic stress in Chinese schools and a proposed preventive intervention program

    OpenAIRE

    Xu Zhao; Robert L. Selman; Helen Haste

    2015-01-01

    While American educators fret about the mediocre educational performance of American students in international contests (e.g. the Program for International Student Assessment) and wonder why the Chinese education system produces such high-achieving students, educators, journalists, and public officials in China want to know what causes and how to prevent the high levels of academic stress that Chinese students, their families, and their school systems experience. So far, much of the blame for...

  11. PROPOSAL FOR NEURAL-LINGUISTIC PROGRAMMING (N.L.P. INTHE ADMINISTRATIVE DEVELOPMENT OF LEADERSHIP SPORTS

    Directory of Open Access Journals (Sweden)

    Khalil Samira

    2010-08-01

    Full Text Available Neural-linguistic programming is an organised method to know the human self construction and dealing with it in fixed means and styles so as to decesisively affect the processes of perception, thinking, imaging, ideas,feeling and also in behavior, skills and the human body and mental performance (1 Neural-linguistic programming has a private nature because it is a group of mechanisms and practicaltechniques far from likeliness, so it enters in the circle of application and employment of the human abilities and possibilities. (9 Al Fiky (2001 points out that neural linguistic programming created the favourable environment to help individuals to get rid of their diseased fears and controlling in their negative reactions and thus improving communication with themselves and with others. He shows it took its way into the human life fields because itsways and strategies are used in the sectors of health, education, marketing and administration(2. The modern administration embarks on the human element that represents the most valuable elementsof administration and is the most effective on the productivity and with the increasing the effect of the human element in the efficacy of the administrative organizations, the need increased to consider the management of the human resources as an independent function of administrative functions that cancers the human element and onwhose efficiency, abilities, experience and zeal for work, the administration efficacy depends.

  12. Double-lock ratchet mechanism revealing the role of  SER-344 in FoF1 ATP synthase

    KAUST Repository

    Beke-Somfai, T.

    2011-03-07

    In a majority of living organisms, FoF1 ATP synthase performs the fundamental process of ATP synthesis. Despite the simple net reaction formula, ADP+Pi→ATP+H2O, the detailed step-by-step mechanism of the reaction yet remains to be resolved owing to the complexity of this multisubunit enzyme. Based on quantum mechanical computations using recent high resolution X-ray structures, we propose that during ATP synthesis the enzyme first prepares the inorganic phosphate for the γP-OADP bond-forming step via a double-proton transfer. At this step, the highly conserved αS344 side chain plays a catalytic role. The reaction thereafter progresses through another transition state (TS) having a planar ion configuration to finally form ATP. These two TSs are concluded crucial for ATP synthesis. Using stepwise scans and several models of the nucleotide-bound active site, some of the most important conformational changes were traced toward direction of synthesis. Interestingly, as the active site geometry progresses toward the ATP-favoring tight binding site, at both of these TSs, a dramatic increase in barrier heights is observed for the reverse direction, i.e., hydrolysis of ATP. This change could indicate a "ratchet" mechanism for the enzyme to ensure efficacy of ATP synthesis by shifting residue conformation and thus locking access to the crucial TSs.

  13. Extracellular ATP is internalized by macropinocytosis and induces intracellular ATP increase and drug resistance in cancer cells.

    Science.gov (United States)

    Qian, Yanrong; Wang, Xuan; Liu, Yi; Li, Yunsheng; Colvin, Robert A; Tong, Lingying; Wu, Shiyong; Chen, Xiaozhuo

    2014-09-01

    ATP plays central roles in cancer metabolism and the Warburg effect. Intratumoral ATP concentrations are up to 10(4) times higher than those of interstitial ATP in normal tissues. However, extracellular ATP is not known to enter cancer cells. Here we report that human A549 lung cancer cells internalized extracellular ATP by macropinocytosis as demonstrated by colocalization of a nonhydrolyzable fluorescent ATP and a macropinocytosis tracer high-molecular-weight dextran, as well as by a macropinocytosis inhibitor study. Extracellular ATP also induced increase of intracellular ATP levels, without involving transcription and translation at significant levels, and cancer cells' resistance to ATP-competitor anticancer drugs, likely through the mechanism of ATP internalization. These findings, described for the first time, have profound implications in ATP-sharing among cancer cells in tumors and highlight a novel anticancer target. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. The thermodynamic efficiency of ATP synthesis in oxidative phosphorylation.

    Science.gov (United States)

    Nath, Sunil

    2016-12-01

    As the chief energy source of eukaryotic cells, it is important to determine the thermodynamic efficiency of ATP synthesis in oxidative phosphorylation (OX PHOS). Previous estimates of the thermodynamic efficiency of this vital process have ranged from Lehninger's original back-of-the-envelope calculation of 38% to the often quoted value of 55-60% in current textbooks of biochemistry, to high values of 90% from recent information theoretic considerations, and reports of realizations of close to ideal 100% efficiencies by single molecule experiments. Hence this problem has been reinvestigated from first principles. The overall thermodynamic efficiency of ATP synthesis in the mitochondrial energy transduction OX PHOS process has been found to lie between 40 and 41% from four different approaches based on a) estimation using structural and biochemical data, b) fundamental nonequilibrium thermodynamic analysis, c) novel insights arising from Nath's torsional mechanism of energy transduction and ATP synthesis, and d) the overall balance of cellular energetics. The torsional mechanism also offers an explanation for the observation of a thermodynamic efficiency approaching 100% in some experiments. Applications of the unique, molecular machine mode of functioning of F 1 F O -ATP synthase involving direct inter-conversion of chemical and mechanical energies in the design and fabrication of novel, man-made mechanochemical devices have been envisaged, and some new ways to exorcise Maxwell's demon have been proposed. It is hoped that analysis of the fundamental problem of energy transduction in OX PHOS from a fresh perspective will catalyze new avenues of research in this interdisciplinary field. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Facility Location Evaluation for Satsop Integrating transmission : Draft Supplement to the Environmental Statement, Fiscal Year 1976 Proposed Program.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1975-02-26

    Alternatives were discussed for the proposed construction of a substation near Satsop and two 500-kV transmission lines from the proposed Satsop Substation approximately 24 miles west of Olympia, one running from Satsop to Paul Substation and one running from Satsop to Olympia Substation. Depending on the final route location chosen, between approximately 62 and 73 miles of 500-kV transmission line between the proposed Satsop Substation and Olympia and Paul Substations over existing, parallel, and new right-of-way would be required. Between 15 and 31 miles of new access road would also be required. Land use affected would include clearing from 560 to 1180 acres of timber. Depending upon the route location chosen, between 1/4 and 4 acres of agricultural land would be removed from production, and between 4 and 37 acres temporarily disrupted. In addition, approximately 30 acres of land would be required for the substation. Other impacts would include the removal of wildlife habitat associated with the above mentioned right-of-way requirements. Disturbance to wildlife during construction would occur. Some erosion and sedimentation would occur. Visual impacts would result from clearing rights-of-way through heavily forested areas. Noise and other disturbances to residents will occur, primarily during construction. The alternatives considered include: (1) nonconstruction, and (2) six alternative route locations for the proposed transmission lines. Generation alternatives to all transmission construction, including alternative methods of electrical transmission and generation, transmission construction, disposal of slash and limiting the consumption of electricity are discussed in BPA's General Construction and Maintenance Program Statement and the Annual Proposed Program Statement.

  16. A Training Program to Enhance Postgraduate Students' Research Skills in Preparing a Research Proposal in the Field of Curriculum and Instruction Methods of Arabic Language

    Science.gov (United States)

    Alfakih, Ahmed Hassan

    2017-01-01

    The study examined the impact of a training program on enhancing postgraduate students' research skills in preparing a research proposal. The nature of the skills required to prepare a research proposal were first determined using a questionnaire. A training program for improving such skills was then constructed and seven postgraduate students in…

  17. ATP8B1 and ATP11C: Two Lipid Flippases Important for Hepatocyte Function

    NARCIS (Netherlands)

    Naik, Jyoti; de Waart, Dirk R.; Utsunomiya, Karina; Duijst, Suzanne; Mok, Kam Ho; Oude Elferink, Ronald P. J.; Bosma, Piter J.; Paulusma, Coen C.

    2015-01-01

    P4 ATPases are lipid flippases and transport phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes. Lipid flipping is important for the biogenesis of transport vesicles. Recently it was shown that loss of the P4 ATPases ATP8B1 and ATP11C are associated with severe

  18. ATP-consuming and ATP-generating enzymes secreted by pancreas

    DEFF Research Database (Denmark)

    Yegutkin, Gennady G; Samburski, Sergei S; Jalkanen, Sirpa

    2006-01-01

    Pancreatic acini release ATP in response to various stimuli, including cholecystokinin octapeptide (CCK-8), as we show in the present study. There were indications that pancreatic juice also contains enzymes that could hydrolyze ATP during its passage through the ductal system. The aim of this st......Pancreatic acini release ATP in response to various stimuli, including cholecystokinin octapeptide (CCK-8), as we show in the present study. There were indications that pancreatic juice also contains enzymes that could hydrolyze ATP during its passage through the ductal system. The aim...... of this study was to determine which ATP-degrading and possibly ATP-generating enzymes were present in pancreatic secretion. For this purpose, pancreatic juice was collected from anesthetized rats stimulated with infusion of CCK-8. Purine-converting activities in juice samples were assayed by TLC using either...... [gamma-(32)P]ATP or (14)C/(3)H-labeled and unlabeled nucleotides as appropriate substrates. Data show that the juice contains the enzyme ecto-nucleoside triphosphate diphosphohydrolase that can hydrolyze both [(14)C]ATP and [(3)H]ADP about equally well, i.e. CD39. Reverse-phase high-performance liquid...

  19. ATP: The crucial component of secretory vesicles.

    Science.gov (United States)

    Estévez-Herrera, Judith; Domínguez, Natalia; Pardo, Marta R; González-Santana, Ayoze; Westhead, Edward W; Borges, Ricardo; Machado, José David

    2016-07-12

    The colligative properties of ATP and catecholamines demonstrated in vitro are thought to be responsible for the extraordinary accumulation of solutes inside chromaffin cell secretory vesicles, although this has yet to be demonstrated in living cells. Because functional cells cannot be deprived of ATP, we have knocked down the expression of the vesicular nucleotide carrier, the VNUT, to show that a reduction in vesicular ATP is accompanied by a drastic fall in the quantal release of catecholamines. This phenomenon is particularly evident in newly synthesized vesicles, which we show are the first to be released. Surprisingly, we find that inhibiting VNUT expression also reduces the frequency of exocytosis, whereas the overexpression of VNUT drastically increases the quantal size of exocytotic events. To our knowledge, our data provide the first demonstration that ATP, in addition to serving as an energy source and purinergic transmitter, is an essential element in the concentration of catecholamines in secretory vesicles. In this way, cells can use ATP to accumulate neurotransmitters and other secreted substances at high concentrations, supporting quantal transmission.

  20. Cost-Benefit Comparison of Two Proposed Overseas Programs for Reducing Chronic Hepatitis B Infection among Refugees: Is Screening Essential?

    Science.gov (United States)

    Jazwa, Amelia; Coleman, Margaret S.; Gazmararian, Julie; Wingate, La’Marcus T.; Maskery, Brian; Mitchell, Tarissa; Weinberg, Michelle

    2015-01-01

    Background Refugees are at an increased risk of chronic Hepatitis B Virus (HBV) infection because many of their countries of origin, as well as host countries, have intermediate-to-high prevalence rates. Refugees arriving to the US are also at risk of serious sequelae from chronic HBV infection because they are not routinely screened for the virus overseas or in domestic post-arrival exams, and may live in the US for years without awareness of their infection status. Methods A cohort of 26,548 refugees who arrived in Minnesota and Georgia during 2005–2010 was evaluated to determine the prevalence of chronic HBV infection. This prevalence information was then used in a cost-benefit analysis comparing two variations of a proposed overseas program to prevent or ameliorate the effects of HBV infection, titled ‘Screen, then vaccinate or initiate management’ (SVIM) and ‘Vaccinate only’ (VO). The analyses were performed in 2013. All values were converted to US 2012 dollars. Results The estimated six year period-prevalence of chronic HBV infection was 6.8% in the overall refugee population arriving to Minnesota and Georgia and 7.1% in those ≥ 6 years of age. The SVIM program variation was more cost beneficial than VO. While the up-front costs of SVIM were higher than VO ($154,084 vs. $73,758; n=58,538 refugees), the SVIM proposal displayed a positive net benefit, ranging from $24 million to $130 million after only 5 years since program initiation, depending on domestic post-arrival screening rates in the VO proposal. Conclusions Chronic HBV infection remains an important health problem in refugees resettling to the United States. An overseas screening policy for chronic HBV infection is more cost-beneficial than a ‘Vaccination only’ policy. The major benefit drivers for the screening policy are earlier medical management of chronic HBV infection and averted lost societal contributions from premature death. PMID:25595868

  1. Guide for the preparation of proposals for the Pre-Freshman Engineering Program: PREP - 1984 (for minorities and women)

    Energy Technology Data Exchange (ETDEWEB)

    None

    1983-08-01

    The Pre-Freshman Engineering Program (PREP) for minorities and women (formerly PREFACE) will provide funds to colleges and universities for projects aimed at seeking out minority group individuals and women during junior high school and high school years (7th grade through 12th grade) and providing them with enrichment experiences. These experiences shall consist of activities to identify, motivate and prepare students for engineering studies. Emphasis is on the individuals identified, regardless of where they may decide to matriculate for undergraduate studies. Work experience is believed to contribute to the success of these projects because it exposes students to the real world of work of the professional engineer. However, no DOE funds may be used directly to support such work experiences. Eligible organizations, limitations of funding, preparation and submission of proposals, evaluation and selection of proposals, and the final report are discussed.

  2. A Proposed Return-to-Sport Program for Patients With Midportion Achilles Tendinopathy: Rationale and Implementation.

    Science.gov (United States)

    Silbernagel, Karin Grävare; Crossley, Kay M

    2015-11-01

    Synopsis Achilles tendinopathy is a common overuse injury in athletes involved in running and jumping activities and sports. The intervention with the highest level of evidence is exercise therapy, and it is recommended that all patients initially be treated with exercise for at least 3 months prior to considering other treatment options. Recovery from Achilles tendinopathy can take up to a year, and there is a high propensity for recurrence, especially during the return-to-sport phase. The extent of the tendon injury, the age and sex of the athlete, the magnitude of pain/symptoms, the extent of impairments, and the demands of the sport all need to be considered when planning for return to sport. This clinical commentary describes an approach to return to sport for patients with midportion Achilles tendinopathy. The aim of the return-to-sport program is to facilitate the decision-making process in returning an athlete with midportion Achilles tendinopathy back to full sport participation and to minimize the chances for recurrence of the injury. J Orthop Sports Phys Ther 2015;45(11):876-886. Epub 21 Sep 2015. doi:10.2519/jospt.2015.5885.

  3. A proposed Russian-American NEPST program utilizing Russian launch and support systems

    Science.gov (United States)

    Ponomarev-Stepnoi, N. N.; Usov, Veniamin; Yefremov, Gennadi L.; Degtiariev, Yuri G.; Belousov, Stanislav Y.; Ogloblin, Boris G.; Bocharov, Anatoli F.

    1995-01-01

    This paper summarizes the research efforts on investigating the possibility of launching the Nuclear Electric Propulsion Space Test Program (NEPSTP) spacecraft, designed by the Applied Physics Laboratory (APL) of Johns Hopkins University, with the Russian ``Proton'' launch vehicle from the Baikonur launch site (Ponomarev-Stepnoi 1994). The NEPSTP spacecraft is designed to demonstrate a payload transportation to GEO using the TOPAZ II space nuclear power system and nuclear electric propulsion of different types (including those developed in the US, Great Britain and Russia) capable of providing spacecraft injection to GEO. The spacecraft's onboard instrumentation includes sensors to measure neutron and gamma radiation around the spacecraft, as well as positron fields surrounding the reactor, and neutral particles and the plasma resulting from operation of nuclear electric propulsion, powered by the nuclear power source. The analysis under study was prepared by the scientists from the Scientific Industrial Association (SIA) of ``Machine Building,'' RRC ``Kurchatov Institute,'' and the Central Design Bureau of Machine Building (CDBMB), on request and support of ``INERTEK'' Joint Stock Company.

  4. Guidelines for a Comprehensive Care Program to Ostomized Patients and Families: a Nursing proposal

    Directory of Open Access Journals (Sweden)

    Paula Alvarenga de Figueiredo

    2016-01-01

    Full Text Available Objectives: describe care needs and demands that mark the discursive practices of ostomized clients and family members and discuss guidelines for a comprehensive care program to ostomized clients and their families, organized by macrosociological categories. Method: Creative and Sensitive, involving 17 ostomized subjects and family members at a municipal outpatient clinic. The ethical aspects were complied with. A characterization form was used, as well as Creativity and Sensitivity Dynamics: "speaking map", "body-knowledge" and "calendar". Critical Discourse Analysis was applied. Results: the health needs and care demands of the ostomized patients and their family members, in their multiple dimensions, were constituted in the home and community, outpatient and social context, implying new orientations for nursing care. The unveiling of the data brought elements that constituted guidelines, in a macrosociological approach, to achieve the expanded integrality of nursing care. Conclusion: the ostomized clients are unique in their genre/peculiar from Latin sui generis, calling for strategies that respond to and distinguish their specificities. Elaborating a Public Health Policy that improves and reorganizes the care demands, taking into account these individual biopsychosocial and spiritual aspects, is a possible and irrevocable target in the attempt to achieve better conditions of health and wellbeing.

  5. Employability of Engineering Graduates from 2013 to 2015 as Basis for a Proposed Student Development Program

    Directory of Open Access Journals (Sweden)

    Nemy H. Chavez

    2017-02-01

    Full Text Available This study aims to determine the employability of Mechanical, Industrial and Electronics Engineering graduates which also explores the relevance of curriculum and work-related behavior to the job placement of the graduate-respondents. Descriptive type of research was utilized in the study. Findings showed that engineering graduates of the academic institution under study are highly employable and gainfully employed locally while enjoying the benefits of regular status and handling professional, technical or supervisory positions where they find their present jobs within 1 to 6 months. Relevance of the engineering program to graduates’ present work assignment is one of the common reasons in accepting and staying on the job while communication skill is the most common useful ability of the engineering graduates in their job placement and leadership, hard work and professional integrity are the work – related values identified with very much contribution in meeting the demands of their present employment. Curriculum is also considered relevant for Mechanical and Industrial Engineering graduates but only slightly relevant for Electronics Engineering Graduates.

  6. Guidelines for a Comprehensive Care Program to Ostomized Patients and Families: a Nursing proposal.

    Science.gov (United States)

    de Figueiredo, Paula Alvarenga; Alvim, Neide Aparecida Titonelli

    2016-01-01

    describe care needs and demands that mark the discursive practices of ostomized clients and family members and discuss guidelines for a comprehensive care program to ostomized clients and their families, organized by macrosociological categories. Creative and Sensitive, involving 17 ostomized subjects and family members at a municipal outpatient clinic. The ethical aspects were complied with. A characterization form was used, as well as Creativity and Sensitivity Dynamics: "speaking map", "body-knowledge" and "calendar". Critical Discourse Analysis was applied. the health needs and care demands of the ostomized patients and their family members, in their multiple dimensions, were constituted in the home and community, outpatient and social context, implying new orientations for nursing care. The unveiling of the data brought elements that constituted guidelines, in a macrosociological approach, to achieve the expanded integrality of nursing care. the ostomized clients are unique in their genre/peculiar from Latin sui generis, calling for strategies that respond to and distinguish their specificities. Elaborating a Public Health Policy that improves and reorganizes the care demands, taking into account these individual biopsychosocial and spiritual aspects, is a possible and irrevocable target in the attempt to achieve better conditions of health and wellbeing.

  7. Guidelines for a Comprehensive Care Program to Ostomized Patients and Families: a Nursing proposal1

    Science.gov (United States)

    de Figueiredo, Paula Alvarenga; Alvim, Neide Aparecida Titonelli

    2016-01-01

    Objectives: describe care needs and demands that mark the discursive practices of ostomized clients and family members and discuss guidelines for a comprehensive care program to ostomized clients and their families, organized by macrosociological categories. Method: Creative and Sensitive, involving 17 ostomized subjects and family members at a municipal outpatient clinic. The ethical aspects were complied with. A characterization form was used, as well as Creativity and Sensitivity Dynamics: "speaking map", "body-knowledge" and "calendar". Critical Discourse Analysis was applied. Results: the health needs and care demands of the ostomized patients and their family members, in their multiple dimensions, were constituted in the home and community, outpatient and social context, implying new orientations for nursing care. The unveiling of the data brought elements that constituted guidelines, in a macrosociological approach, to achieve the expanded integrality of nursing care. Conclusion: the ostomized clients are unique in their genre/peculiar from Latin sui generis, calling for strategies that respond to and distinguish their specificities. Elaborating a Public Health Policy that improves and reorganizes the care demands, taking into account these individual biopsychosocial and spiritual aspects, is a possible and irrevocable target in the attempt to achieve better conditions of health and wellbeing. PMID:27192418

  8. A Response to Proposed Budget Cuts Affecting Children's Mental Health: Protecting Policies and Programs That Promote Collective Efficacy.

    Science.gov (United States)

    Hoagwood, Kimberly Eaton; Atkins, Marc; Horwitz, Sarah; Kutash, Krista; Olin, S Serene; Burns, Barbara; Peth-Pierce, Robin; Kuppinger, Anne; Burton, Geraldine; Shorter, Priscilla; Kelleher, Kelly J

    2017-11-01

    Children stand to lose if the federal government follows through on threats to cut funding for critical safety-net programs that have long supported families and communities. Although cuts directly targeting children's mental health are a great concern, cuts to policies that support health, housing, education, and family income are equally disturbing. These less publicized proposed cuts affect children indirectly, but they have direct effects on their families and communities. The importance of these services is supported by an extensive body of social learning research that promotes collective efficacy-neighbors positively influencing each other-shown to have positive long-term effects on children's development and adult outcomes. In this article, the authors describe two federal programs that by virtue of their impact on families and communities are likely to promote collective efficacy and positively affect children's mental health; both programs are facing severe cutbacks. They suggest that states adopt a cross-system approach to promote policies and programs in general medical health, mental health, housing, education, welfare and social services, and juvenile justice systems as a viable strategy to strengthen families and communities and promote collective efficacy. The overall goal is to advance a comprehensive national mental health policy for children that enhances collaboration across systems and strengthens families and communities, which is especially critical for children living in marginalized communities.

  9. A Proposal for a Three Detector Short-Baseline Neutrino Oscillation Program in the Fermilab Booster Neutrino Beam

    CERN Document Server

    Antonello, M.; Bellini, V.; Benetti, P.; Bertolucci, S.; Bilokon, H.; Boffelli, F.; Bonesini, M.; Bremer, J.; Calligarich, E.; Centro, S.; Cocco, A.G.; Dermenev, A.; Falcone, A.; Farnese, C.; Fava, A.; Ferrari, A.; Gibin, D.; Gninenko, S.; Golubev, N.; Guglielmi, A.; Ivashkin, A.; Kirsanov, M.; Kisiel, J.; Kose, U.; Mammoliti, F.; Mannocchi, G.; Menegolli, A.; Meng, G.; Mladenov, D.; Montanari, C.; Nessi, M.; Nicoletto, M.; Noto, F.; Picchi, P.; Pietropaolo, F.; Plonski, P.; Potenza, R.; Rappoldi, A.; Raselli, G.L.; Rossella, M.; Rubbia, C.; Sala, P.; Scaramelli, A.; Sobczyk, J.; Spanu, M.; Stefan, D.; Sulej, R.; Sutera, C.M.; Torti, M.; Tortorici, F.; Varanini, F.; Ventura, S.; Vignoli, C.; Wachala, T.; Zani, A.; Adams, C.; Andreopoulos, C.; Ankowski, A.M.; Asaadi, J.; Bagby, L.; Baller, B.; Barros, N.; Bass, M.; Bishai, M.; Bitadze, A.; Bugel, L.; Camilleri, L.; Cavanna, F.; Chen, H.; Chi, C.; Church, E.; Cianci, D.; Collin, G.H.; Conrad, J.M.; De Geronimo, G.; Dharmapalan, R.; Djurcic, Z.; Ereditato, A.; Esquivel, J.; Evans, J.; Fleming, B.T.; Foreman, W.M.; Freestone, J.; Gamble, T.; Garvey, G.; Genty, V.; Goldi, D.; Gramellini, E.; Greenlee, H.; Guenette, R.; Hackenburg, A.; Hanni, R.; Ho, J.; Howell, J.; James, C.; Jen, C.M.; Jones, B.J.P.; Kalousis, L.N.; Karagiorgi, G.; Ketchum, W.; Klein, J.; Klinger, J.; Kreslo, I.; Kudryavtsev, V.A.; Lissauer, D.; Livesly, P.; Louis, W.C.; Luthi, M.; Mariani, C.; Mavrokoridis, K.; McCauley, N.; McConkey, N.; Mercer, I.; Miao, T.; Mills, G.B.; Montanari, D.; Moon, J.; Moss, Z.; Mufson, S.; Norris, B.; Nowak, J.; Pal, S.; Palamara, O.; Pater, J.; Pavlovic, Z.; Perkin, J.; Pulliam, G.; Qian, X.; Qiuguang, L.; Radeka, V.; Rameika, R.; Ratoff, P.N.; Richardson, M.; von Rohr, C.Rudolf; Russell, B.; Schmitz, D.W.; Shaevitz, M.H.; Sippach, B.; Soderberg, M.; Soldner-Rembold, S.; Spitz, J.; Spooner, N.; Strauss, T.; Szelc, A.M.; Taylor, C.E.; Terao, K.; Thiesse, M.; Thompson, L.; Thomson, M.; Thorn, C.; Toups, M.; Touramanis, C.; Van de Water, R.G.; Weber, M.; Whittington, D.; Wongjirad, T.; Yu, B.; Zeller, G.P.; Zennamo, J.; Acciarri, R.; An, R.; Barr, G.; Blake, A.; Bolton, T.; Bromberg, C.; Caratelli, D.; Carls, B.; Convery, M.; Dytmam, S.; Eberly, B.; Gollapinni, S.; Graham, M.; Grosso, R.; Hen, O.; Hewes, J.; Horton-Smith, G.; Johnson, R.A.; Joshi, J.; Jostlein, H.; Kaleko, D.; Kirby, B.; Kirby, M.; Kobilarcik, T.; Li, Y.; Littlejohn, B.; Lockwitz, S.; Lundberg, B.; Marchionni, A.; Marshall, J.; McDonald, K.; Meddage, V.; Miceli, T.; Mooney, M.; Moulai, M.H.; Murrells, R.; Naples, D.; Nienaber, P.; Paolone, V.; Papavassiliou, V.; Pate, S.; Pordes, S.; Raaf, J.L.; Rebel, B.; Rochester, L.; Schukraft, A.; Seligman, W.; St. John, J.; Tagg, N.; Tsai, Y.; Usher, T.; Wolbers, S.; Woodruff, K.; Xu, M.; Yang, T.; Zhang, C.; Badgett, W.; Biery, K.; Brice, S.J.; Dixon, S.; Geynisman, M.; Moore, C.; Snider, E.; Wilson, P.

    2015-01-01

    A Short-Baseline Neutrino (SBN) physics program of three LAr-TPC detectors located along the Booster Neutrino Beam (BNB) at Fermilab is presented. This new SBN Program will deliver a rich and compelling physics opportunity, including the ability to resolve a class of experimental anomalies in neutrino physics and to perform the most sensitive search to date for sterile neutrinos at the eV mass-scale through both appearance and disappearance oscillation channels. Using data sets of 6.6e20 protons on target (P.O.T.) in the LAr1-ND and ICARUS T600 detectors plus 13.2e20 P.O.T. in the MicroBooNE detector, we estimate that a search for muon neutrino to electron neutrino appearance can be performed with ~5 sigma sensitivity for the LSND allowed (99% C.L.) parameter region. In this proposal for the SBN Program, we describe the physics analysis, the conceptual design of the LAr1-ND detector, the design and refurbishment of the T600 detector, the necessary infrastructure required to execute the program, and a possible...

  10. Voltage Dependence of ATP Secretion in Mammalian Taste Cells

    Science.gov (United States)

    Romanov, Roman A.; Rogachevskaja, Olga A.; Khokhlov, Alexander A.; Kolesnikov, Stanislav S.

    2008-01-01

    Mammalian type II taste cells release the afferent neurotransmitter adenosine triphosphate (ATP) through ATP-permeable ion channels, most likely to be connexin (Cx) and/or pannexin hemichannels. Here, we show that ion channels responsible for voltage-gated (VG) outward currents in type II cells are ATP permeable and demonstrate a strong correlation between the magnitude of the VG current and the intensity of ATP release. These findings suggest that slowly deactivating ion channels transporting the VG outward currents can also mediate ATP secretion in type II cells. In line with this inference, we studied a dependence of ATP secretion on membrane voltage with a cellular ATP sensor using different pulse protocols. These were designed on the basis of predictions of a model of voltage-dependent transient ATP efflux. Consistently with curves that were simulated for ATP release mediated by ATP-permeable channels deactivating slowly, the bell-like and Langmuir isotherm–like potential dependencies were characteristic of ATP secretion obtained for prolonged and short electrical stimulations of taste cells, respectively. These observations strongly support the idea that ATP is primarily released via slowly deactivating channels. Depolarizing voltage pulses produced negligible Ca2+ transients in the cytoplasm of cells releasing ATP, suggesting that ATP secretion is mainly governed by membrane voltage under our recording conditions. With the proviso that natural connexons and pannexons are kinetically similar to exogenously expressed hemichannels, our findings suggest that VG ATP release in type II cells is primarily mediated by Cx hemichannels. PMID:19029378

  11. Heterotrimeric G Protein-Regulated Ca2+ Influx and PIN2 Asymmetric Distribution Are Involved in Arabidopsis thaliana Roots' Avoidance Response to Extracellular ATP

    Directory of Open Access Journals (Sweden)

    Ruojia Zhu

    2017-09-01

    Full Text Available Extracellular ATP (eATP has been reported to be involved in plant growth as a primary messenger in the apoplast. Here, roots of Arabidopsis thaliana seedlings growing in jointed medium bent upon contact with ATP-containing medium to keep away from eATP, showing a marked avoidance response. Roots responded similarly to ADP and bz-ATP but did not respond to AMP and GTP. The eATP avoidance response was reduced in loss-of-function mutants of heterotrimeric G protein α subunit (Gα (gpa1-1 and gpa1-2 and enhanced in Gα-over-expression (OE lines (wGα and cGα. Ethylenebis(oxyethylenenitrilo tetraacetic acid (EGTA and Gd3+ remarkably suppressed eATP-induced root bending. ATP-stimulated Ca2+ influx was impaired in Gα null mutants and increased in its OE lines. DR5-GFP and PIN2 were asymmetrically distributed in ATP-stimulated root tips, this effect was strongly suppressed by EGTA and diminished in Gα null mutants. In addition, some eATP-induced genes' expression was also impaired in Gα null mutants. Based on these results, we propose that heterotrimeric Gα-regulated Ca2+ influx and PIN2 distribution may be key signaling events in eATP sensing and avoidance response in Arabidopsis thaliana roots.

  12. Tracking protons from respiratory chain complexes to ATP synthase c-subunit: The critical role of serine and threonine residues.

    Science.gov (United States)

    Panfoli, Isabella; Ponassi, Marco; Ravera, Silvia; Calzia, Daniela; Beitia, Maider; Morelli, Alessandro; Rosano, Camillo

    2017-01-22

    F1Fo-ATP synthase is a multisubunit enzyme responsible for the synthesis of ATP. Among its multiple subunits (8 in E. coli, 17 in yeast S. cerevisiae, 16 in vertebrates), two subunits a and c are known to play a central role controlling the H(+) flow through the inner mitochondrial membrane which allows the subsequent synthesis of ATP, but the pathway followed by H(+) within the two proteins is still a matter of debate. In fact, even though the structure of ATP synthase is now well defined, the molecular mechanisms determining the function of both F1 and FO domains are still largely unknown. In this study, we propose a pathway for proton migration along the ATP synthase by hydrogen-bonded chain mechanism, with a key role of serine and threonine residues, by X-ray diffraction data on the subunit a of E. coli Fo. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Overlapping ATP2C1 and ASTE1 Genes in Human Genome: Implications for SPCA1 Expression?

    Directory of Open Access Journals (Sweden)

    Massimo Micaroni

    2013-01-01

    Full Text Available The ATP2C1 gene encodes for the secretory pathway calcium (Ca2+-ATPase pump (SPCA1, which localizes along the secretory pathway, mainly in the trans-Golgi. The loss of one ATP2C1 allele causes Hailey-Hailey disease in humans but not mice. Examining differences in genomic organization between mouse and human we speculate that the overlap between ATP2C1 and ASTE1 genes only in humans could explain this different response to ATP2C1 dysregulation. We propose that ASTE1, overlapping with ATP2C1 in humans, affects alternative splicing, and potentially protein expression of the latter. If dysregulated, the composition of the SPCA1 isoform pool could diverge from the physiological status, affecting cytosolic Ca2+-signaling, and in turn perturbing cell division, leading to cell death or to neoplastic transformation.

  14. Extracellular ATP is a key modulator of alveolar bone loss in periodontitis.

    Science.gov (United States)

    Binderman, Itzhak; Gadban, Nasir; Yaffe, Avinoam

    2017-09-01

    Periodontal diseases are initiated by pathogenic bacterial biofilm activity that induces a host inflammatory cells immune response, degradation of dento gingival fibrous tissue and its detachment from root cementum. It is well accepted, that osteoclastic alveolar bone loss is governed exclusively through secretion of proinflammatory cytokines. Nevertheless, our findings suggest that once degradation of collagen fibers by MMPs occurs, a drop of cellular strains cause immediate release of ATP from marginal gingival fibroblasts, cell deformation and influx of Ca+2. Increased extracellular ATP (eATP) by interacting with P2×7 purinoreceptors, present on fibroblasts and osteoblasts, induces generation of receptor activator of nuclear factor kB ligand (RANKL) that further activates osteoclastic alveolar bone resorption and bone loss. In addition, increased eATP levels may amplify inflammation by promoting leukocyte recruitment and NALP3-inflammasome activation via P2×7. Then, the inflammatory cells secrete cytokines, interleukin IL-1, TNF and RANKL that further trigger alveolar bone resorption. Moreover, eATP can be secreted from periodontal bacteria that may further contribute to inflammation and bone loss in periodontitis. It seems therefore, that eATP is a key modulator that initiates the pathway of alveolar bone resorption and bone loss in patients with periodontal disease. In conclusion, we propose that strain release in gingival fibroblasts aligned on collagen fibers, due to activity of MMP, activates release of ATP that triggers the pathway of alveolar bone resorption in periodontitis. We predict that by controlling the eATP interaction with its cellular purinoreceptors will reduce significantly bone loss in periodontitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Imaging exocytosis of ATP-containing vesicles with TIRF microscopy in lung epithelial A549 cells.

    Science.gov (United States)

    Akopova, Irina; Tatur, Sabina; Grygorczyk, Mariusz; Luchowski, Rafał; Gryczynski, Ignacy; Gryczynski, Zygmunt; Borejdo, Julian; Grygorczyk, Ryszard

    2012-03-01

    Nucleotide release constitutes the first step of the purinergic signaling cascade, but its underlying mechanisms remain incompletely understood. In alveolar A549 cells much of the experimental data is consistent with Ca(2+)-regulated vesicular exocytosis, but definitive evidence for such a release mechanism is missing, and alternative pathways have been proposed. In this study, we examined ATP secretion from A549 cells by total internal reflection fluorescence microscopy to directly visualize ATP-loaded vesicles and their fusion with the plasma membrane. A549 cells were labeled with quinacrine or Bodipy-ATP, fluorescent markers of intracellular ATP storage sites, and time-lapse imaging of vesicles present in the evanescent field was undertaken. Under basal conditions, individual vesicles showed occasional quasi-instantaneous loss of fluorescence, as expected from spontaneous vesicle fusion with the plasma membrane and dispersal of its fluorescent cargo. Hypo-osmotic stress stimulation (osmolality reduction from 316 to 160 mOsm) resulted in a transient, several-fold increment of exocytotic event frequency. Lowering the temperature from 37°C to 20°C dramatically diminished the fraction of vesicles that underwent exocytosis during the 2-min stimulation, from ~40% to ≤1%, respectively. Parallel ATP efflux experiments with luciferase bioluminescence assay revealed that pharmacological interference with vesicular transport (brefeldin, monensin), or disruption of the cytoskeleton (nocodazole, cytochalasin), significantly suppressed ATP release (by up to ~80%), whereas it was completely blocked by N-ethylmaleimide. Collectively, our data demonstrate that regulated exocytosis of ATP-loaded vesicles likely constitutes a major pathway of hypotonic stress-induced ATP secretion from A549 cells.

  16. Molecular Events Involved in a Single Cycle of Ligand Transfer from an ATP Binding Cassette Transporter, LolCDE, to a Molecular Chaperone, LolA*

    OpenAIRE

    Taniguchi, Naohiro; Tokuda, Hajime

    2008-01-01

    An ATP binding cassette transporter LolCDE complex releases lipoproteins from the inner membrane of Escherichia coli in an ATP-dependent manner, leading to the formation of a complex between a lipoprotein and a periplasmic chaperone, LolA. LolA is proposed to undergo a conformational change upon the lipoprotein binding. The lipoprotein is then transferred from the LolA-lipoprotein complex to the outer membrane via LolB. Unlike most ATP binding cassette transporters med...

  17. Distinct Conformation of ATP Molecule in Solution and on Protein.

    Science.gov (United States)

    Kobayashi, Eri; Yura, Kei; Nagai, Yoshinori

    2013-01-01

    Adenosine triphosphate (ATP) is a versatile molecule used mainly for energy and a phosphate source. The hydrolysis of γ phosphate initiates the reactions and these reactions almost always start when ATP binds to protein. Therefore, there should be a mechanism to prevent spontaneous hydrolysis reaction and a mechanism to lead ATP to a pure energy source or to a phosphate source. To address these questions, we extensively analyzed the effect of protein to ATP conformation based on the sampling of the ATP solution conformations obtained from molecular dynamics simulation and the sampling of ATP structures bound to protein found in a protein structure database. The comparison revealed mainly the following three points; 1) The ribose ring in ATP molecule, which puckers in many ways in solution, tends to assume either C2' exo or C2' endo when it binds to protein. 2) The adenine ring in ATP molecule, which takes open-book motion with the two ring structures, has two distinct structures when ATP binds to protein. 3) The glycosyl-bond and the bond between phosphate and the ribose have unique torsion angles, when ATP binds to protein. The combination of torsion angles found in protein-bound forms is under-represented in ATP molecule in water. These findings suggest that ATP-binding protein exerts forces on ATP molecule to assume a conformation that is rarely found in solution, and that this conformation change should be a trigger for the reactions on ATP molecule.

  18. H Scan/AHP decision process planning for evaluating and ranking of proposals submitted to the DOE hydrogen program

    Energy Technology Data Exchange (ETDEWEB)

    Szoka de Valladares, M.R. [National Renwable Energy Lab., Washington, DC (United States); Mack, S. [Energtics, Washington, DC (United States)

    1995-09-01

    The DOE Hydrogen Program needs to develop criteria as part of a systematic evaluation process for proposal identification, evaluation and selection. The H Scan component of this process provides a framework in which a project proposer can fully describe their candidate technology system and its components. The H Scan complements traditional methods of capturing cost and technical information. It consists of a special set of survey forms designed to elicit information so expert reviewers can assess the proposal relative to DOE specified selection criteria. The Analytic Hierarchy Process (AHP) component of the decision process assembles the management defined evaluation and selection criteria into a coherent multi-level decision construct by which projects can be evaluated in pair-wise comparisons. The AHP model will reflect management`s objectives and it will assist in the ranking of individual projects based on the extent to which each contributes to management`s objectives. This paper contains a detailed description of the products and activities associated with the planning and evaluation process: The objectives or criteria; the H Scan; and The Analytic Hierarchy Process (AHP).

  19. Proposing a New Approach for Supplier Selection Based on Kraljic’s Model Using FMEA and Integer Linear Programming

    Directory of Open Access Journals (Sweden)

    S. Mohammad Arabzad

    2012-06-01

    Full Text Available In recent years, numerous methods have been proposed to deal with supplier evaluation and selection problem, but a point which has been usually neglected by researchers is the role of purchasing items. The aim of this paper is to propose an integrated approach to select suppliers and allocate orders on the basis of the nature of the purchasing items which means that this issue plays an important role in supplier selection and order allocation. Therefore, items are first categorized according to the Kraljic’s model by the use of FMEA technique. Then, suppliers are categorized and evaluated in four phases with respect to different types of purchasing items (Strategic, Bottleneck, Leverage and Routine. Finally, an integer linear programming is utilized to allocate purchasing orders to suppliers. Furthermore, an empirical example is conducted to illustrate the stage of proposed approach. Results imply that ranking of suppliers and allocation of purchasing items based on the nature of purchasing items will create more capabilities in managing purchasing items and suppliers .

  20. Regulation of Pannexin 1 Surface Expression by Extracellular ATP: Potential Implications for Nervous System Function in Health and Disease

    Directory of Open Access Journals (Sweden)

    Leigh A. Swayne

    2017-08-01

    Full Text Available Pannexin 1 (Panx1 channels are widely recognized for their role in ATP release, and as follows, their function is closely tied to that of ATP-activated P2X7 purinergic receptors (P2X7Rs. Our recent work has shown that extracellular ATP induces clustering of Panx1 with P2X7Rs and their subsequent internalization through a non-canonical cholesterol-dependent mechanism. In other words, we have demonstrated that extracellular ATP levels can regulate the cell surface expression of Panx1. Here we discuss two situations in which we hypothesize that ATP modulation of Panx1 surface expression could be relevant for central nervous system function. The first scenario involves the development of new neurons in the ventricular zone. We propose that ATP-induced Panx1 endocytosis could play an important role in regulating the balance of cell proliferation, survival, and differentiation within this neurogenic niche in the healthy brain. The second scenario relates to the spinal cord, in which we posit that an impairment of ATP-induced Panx1 endocytosis could contribute to pathological neuroplasticity. Together, the discussion of these hypotheses serves to highlight important outstanding questions regarding the interplay between extracellular ATP, Panx1, and P2X7Rs in the nervous system in health and disease.

  1. A simplified ATP method for the rapid control of cell viability in a freeze-dried BCG vaccine.

    Science.gov (United States)

    Ugarova, Natalia N; Lomakina, Galina Yu; Modestova, Yulia; Chernikov, Sergey V; Vinokurova, Natalia V; Оtrashevskaya, Elena V; Gorbachev, Vyacheslav Y

    2016-11-01

    We propose a simple and cost-effective ATP method for controlling the specific activity of a freeze-dried BCG vaccine. A freeze-dried BCG vaccine is reconstituted with 1ml saline and incubated for 15min at room temperature and then for 1h at 37°C. The vaccine is then treated with apyrase to remove extracellular ATP. After that, the cells are lysed with DMSO and the ATP content in the lysate is measured by the bioluminescence method. To implement the method, we developed a kit that requires no time-consuming preparation before the analysis. We demonstrated the linear relationship between the experimental values of the specific activity (106CFU/mg) and intracellular ATP content (ATP, pmol/mg) for different batches of the studied BCG vaccines; the proportionality coefficient was К=0.36±0.02. We proposed a formula for calculating the specific activity from the measured content of intracellular ATP (ATP, pmol/mg). The comparison of the measured and calculated values of the specific activity (106CFU/mg) shows that these values are similar; their differences fall within the allowable range of deviations for the specific activity values of the BCG vaccine. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: results from a postpartum survey

    Science.gov (United States)

    2012-01-01

    Background In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. Methods A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Results Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian

  3. Two mutations in mitochondrial ATP6 gene of ATP synthase, related to human cancer, affect ROS, calcium homeostasis and mitochondrial permeability transition in yeast.

    Science.gov (United States)

    Niedzwiecka, Katarzyna; Tisi, Renata; Penna, Sara; Lichocka, Malgorzata; Plochocka, Danuta; Kucharczyk, Roza

    2018-01-01

    The relevance of mitochondrial DNA (mtDNA) mutations in cancer process is still unknown. Since the mutagenesis of mitochondrial genome in mammals is not possible yet, we have exploited budding yeast S. cerevisiae as a model to study the effects of tumor-associated mutations in the mitochondrial MTATP6 gene, encoding subunit 6 of ATP synthase, on the energy metabolism. We previously reported that four mutations in this gene have a limited impact on the production of cellular energy. Here we show that two mutations, Atp6-P163S and Atp6-K90E (human MTATP6-P136S and MTATP6-K64E, found in prostate and thyroid cancer samples, respectively), increase sensitivity of yeast cells both to compounds inducing oxidative stress and to high concentrations of calcium ions in the medium, when Om45p, the component of porin complex in outer mitochondrial membrane (OM), was fused to GFP. In OM45-GFP background, these mutations affect the activation of yeast permeability transition pore (yPTP, also called YMUC, yeast mitochondrial unspecific channel) upon calcium induction. Moreover, we show that calcium addition to isolated mitochondria heavily induced the formation of ATP synthase dimers and oligomers, recently proposed to form the core of PTP, which was slower in the mutants. We show the genetic evidence for involvement of mitochondrial ATP synthase in calcium homeostasis and permeability transition in yeast. This paper is a first to show, although in yeast model organism, that mitochondrial ATP synthase mutations, which accumulate during carcinogenesis process, may be significant for cancer cell escape from apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Implementation of the parametric variation method in an EMTP program

    DEFF Research Database (Denmark)

    Holdyk, Andrzej; Holbøll, Joachim

    2013-01-01

    The paper presents an algorithm for- and shows the implementation of a method to perform parametric variation studies using electromagnetic transients programs applied to an offshore wind farm. Those kind of studies are used to investigate the sensitivity of a given phenomena to variation...... of parameters in an electric system. The proposed method allows varying any parameter of a circuit, including the simulation settings and exploits the specific structure of the ATP-EMTP software. In the implementation of the method, Matlab software is used to control the execution of the ATP solver. Two...

  5. Control of respiration and ATP synthesis in mammalian mitochondria and cells.

    Science.gov (United States)

    Brown, G C

    1992-05-15

    We have seen that there is no simple answer to the question 'what controls respiration?' The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that

  6. Kinetics of extracellular ATP in mastoparan 7-activated human erythrocytes

    Science.gov (United States)

    Denis, María Florencia Leal; Incicco, J. Jeremías; Espelt, María Victoria; Verstraeten, Sandra V.; Pignataro, Omar P.; Lazarowski, Eduardo R.; Schwarzbaum, Pablo J.

    2014-01-01

    SUMMARY Background The peptide mastoparan 7 (MST7) stimulated ATP release in human erythrocytes. We explored intra- and extracellular processes governing the time-dependent accumulation of extracellular ATP (i.e., ATPe kinetics). Methods Human erythrocytes were treated with MST7 in the presence or absence of two blockers of pannexin 1. ATPe concentration was monitored by luciferin-luciferase based real-time luminometry. Results Exposure of human erythrocytes to MST7 led to an acute increase in [ATPe], followed by a slower increase phase. ATPe kinetics reflected a strong activation of ATP efflux and a low rate of ATPe hydrolysis by ectoATPase activity. Enhancement of [ATPe] by MST7 required adhesion of erythrocytes to poly-D-lysin-coated coverslips, and correlated with a 31% increase of cAMP and 10% cell swelling. However, when MST7 was dissolved in a hyperosmotic medium to block cell swelling, ATPe accumulation was inhibited by 49%. Erythrocytes pre-exposure to 10 μM of either carbenoxolone or probenecid, two blockers of pannexin 1, exhibited a partial reduction of ATP efflux. Erythrocytes from pannexin 1 knockout mice exhibited similar ATPe kinetics as those of wild type mice erythrocytes exposed to pannexin 1 blockers. Conclusions MST7 induced release of ATP required either cell adhesion or strong activation of cAMP synthesis. Part of this release required cell swelling. Kinetic analysis and a data driven model suggested that ATP efflux is mediated by two ATP conduits displaying different kinetics, with one conduit being fully blocked by pannexin 1 blockers. General Significance Kinetic analysis of extracellular ATP accumulation from human erythrocytes and potential effects on microcirculation. PMID:23742824

  7. Highly Divergent Mitochondrial ATP Synthase Complexes in Tetrahymena thermophila

    NARCIS (Netherlands)

    Nina, Praveen Balabaskaran; Dudkina, Natalya V.; Kane, Lesley A.; van Eyk, Jennifer E.; Boekema, Egbert J.; Mather, Michael W.; Vaidya, Akhil B.; Eisen, Jonathan A.

    The F-type ATP synthase complex is a rotary nano-motor driven by proton motive force to synthesize ATP. Its F(1) sector catalyzes ATP synthesis, whereas the F(o) sector conducts the protons and provides a stator for the rotary action of the complex. Components of both F(1) and F(o) sectors are

  8. ATP release, generation and hydrolysis in exocrine pancreatic duct cells

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena; Yegutkin, G.G.; Novak, Ivana

    2015-01-01

    Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, ou...

  9. Limitations of ATP as a measure of microbial biomass | Stuart ...

    African Journals Online (AJOL)

    Estimates of the total living biomass of micro-organisms on decomposing kelp detritus, calculated indirectly from the concentration of ATP, were compared with those obtained directly from cell numbers and volumes. Large overestimates in biomass were obtained from ATP x 250, and C:ATP ratios varied considerably with ...

  10. H+/ATP ratio during ATP hydrolysis by mitochondria: modification of the chemiosmotic theory.

    Science.gov (United States)

    Brand, M D; Lehninger, A L

    1977-01-01

    The stoichiometry of H+ ejection by mitochondria during hydrolysis of a small pulse of ATP (the H+/ATP ratio) has been reexamined in the light of our recent observation that the stoichiometry of H+ ejection during mitochondrial electron transport (the H+/site ratio) was previously underestimated. We show that earlier estimates of the H+/ATP ratio in intact mitochondria were based upon an invalid correction for scaler H+ production and describe a modified method for determination of this ratio which utilizes mersalyl or N-ethylmaleimide to prevent complicating transmembrane movements of phosphate and H+. This method gives a value for the H+/ATP ratio of 2.0 without the need for questionable corrections, compared with a value of 3.0 for the H+/site ratio also obtained by pulse methods. A modified version of the chemiosmotic theory is presented, in which 3 H+ are ejected per pair of electrons traversing each energy-conserving site of the respiratory chain. Of these, 2 H+ return to the matrix through the ATPase to form ATP from ADP and phosphate, and 1 H+ returns through the combined action of the phosphate and adenine nucleotide exchange carriers of the inner membrane to allow the energy-requiring influx of Pi and ADP3- and efflux of ATP4-. Thus, up to one-third of the energy input into synthesis of extramitochondrial ATP may be required for transport work. Since other methods suggest that the H+/site significantly exceeds 3.0, an alternative possibility is that 4 h+ are ejected per site, followed by return of 3 H+ through the ATPase and 1 H+ through the operation of the proton-coupled membrane transport systems. PMID:17116

  11. Clotrimazole potentiates the inhibitory effects of ATP on the key glycolytic enzyme 6-phosphofructo-1-kinase.

    Science.gov (United States)

    Marcondes, Mariah Celestino; Sola-Penna, Mauro; Zancan, Patricia

    2010-05-01

    Clotrimazole (CTZ) has been proposed as a potential anti-neoplastic agent, which inhibits glucose metabolism. The present work aimed to evaluate the effects of CTZ on the kinetic mechanism of 6-phosphofructo-1-kinase (PFK). We show that CTZ promotes a dose-dependent inhibition of PFK, presenting a K(i) of 28 +/- 2 microM. Inhibition occurs through the dissociation of the enzyme tetramers, as demonstrated through fluorescence spectroscopy and gel filtration chromatography. Moreover, the affinities of the enzyme for ATP and fructose-6-phosphate are reduced 50% and 30%, respectively. Furthermore, the affinity of PFK for ATP at the inhibitory site becomes 2-fold higher. Altogether, the results presented here suggest that PFK inhibition by CTZ involves a decrease in the affinity of PFK for its substrates at the catalytic site with the concomitant potentiation of the inhibitory properties of ATP. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Multiple phosphorylation sites in the beta subunit of thylakoid ATP synthase.

    Science.gov (United States)

    del Riego, Guillermo; Casano, Leonardo M; Martín, Mercedes; Sabater, Bartolomé

    2006-07-01

    Proteomic analyses of the beta subunit of the plastid ATP synthase of barley (Hordeum vulgare L.) revealed that mature protein was not carboxy terminus processed and suggested the correction of the 274 codon (GAT to AAT) in the data bank that was confirmed by DNA sequencing. Six isoforms of the ATP synthase beta subunit with pI ranging from 4.95 to 5.14 were resolved by two-dimensional electrophoresis (2-DE). Mass spectrometry analyses indicated that the six isoforms differ in their phosphorylation degree, which was confirmed by the disappearance of more acidic forms after incubation with the protein phosphatase calcineurin. Six Ser and/or Thr were detected as phosphorylated, among them the conserved Thr-179 that is also phosphorylated in the beta subunit of human mitochondria. The results are discussed in relation with the proposed regulation of the ATP synthase by phosphorylation and 14-3-3 proteins.

  13. Nitration of specific tyrosines in FoF1 ATP synthase and activity loss in aging.

    Science.gov (United States)

    Haynes, Virginia; Traaseth, Nathaniel J; Elfering, Sarah; Fujisawa, Yasuko; Giulivi, Cecilia

    2010-05-01

    It has been reported that C-nitration of proteins occurs under nitrative/oxidative stress; however, its role in pathophysiological situations is not fully understood. In this study, we determined that nitration of Tyr(345) and Tyr(368) in the beta-subunit of the mitochondrial F(o)F(1)-ATPase is a major target for nitrative stress in rat liver under in vivo conditions. The chemical characteristics of these Tyr make them suitable for a facilitated nitration (solvent accessibility, consensus sequence, and pK(a)). Moreover, beta-subunit nitration increased significantly with the age of the rats (from 4 to 80 weeks old) and correlated with decreased ATP hydrolysis and synthesis rates. Although its affinity for ATP binding was unchanged, maximal ATPase activity decreased between young and old rats by a factor of two. These changes directly impacted the available ATP concentration in vivo, and it was expected that they would affect multiple cellular ATP-dependent processes. For instance, at least 50% of available [ATP] in the liver of older rats would have to be committed to sustain maximal Na(+)-K(+)-ATPase activity, whereas only 30% would be required for young rats. If this requirement was not fulfilled, the osmoregulation and Na(+)-nutrient cotransport in liver of older rats would be compromised. On the basis of our studies, we propose that targeted nitration of the beta-subunit is an early marker for nitrative stress and aging.

  14. Yeast Mitochondrial Interactosome Model: Metabolon Membrane Proteins Complex Involved in the Channeling of ADP/ATP

    Directory of Open Access Journals (Sweden)

    Benjamin Clémençon

    2012-02-01

    Full Text Available The existence of a mitochondrial interactosome (MI has been currently well established in mammalian cells but the exact composition of this super-complex is not precisely known, and its organization seems to be different from that in yeast. One major difference is the absence of mitochondrial creatine kinase (MtCK in yeast, unlike that described in the organization model of MI, especially in cardiac, skeletal muscle and brain cells. The aim of this review is to provide a detailed description of different partner proteins involved in the synergistic ADP/ATP transport across the mitochondrial membranes in the yeast Saccharomyces cerevisiae and to propose a new mitochondrial interactosome model. The ADP/ATP (Aacp and inorganic phosphate (PiC carriers as well as the VDAC (or mitochondrial porin catalyze the import and export of ADP, ATP and Pi across the mitochondrial membranes. Aacp and PiC, which appear to be associated with the ATP synthase, consist of two nanomotors (F0, F1 under specific conditions and form ATP synthasome. Identification and characterization of such a complex were described for the first time by Pedersen and co-workers in 2003.

  15. Nullius in verba: The University of Minnesota Social and Administrative Pharmacy Program proposed Guidelines for Formulary Evaluations

    Directory of Open Access Journals (Sweden)

    Paul C Langley

    2016-07-01

    Full Text Available The University of Minnesota Social and Administrative Pharmacy Program proposed Guidelines for Formulary Evaluations (GFE are designed to focus on the credibility of clinical and cost-outcomes claims in formulary decision making. The last few years have witnessed increasing concern over the credibility of trial based efficacy claims, with a surprisingly high proportion of claims falling short. At the same time cost-outcomes claims, where comparative clinical claims are a key input, have been presented where the claims made are not open to experimental or observational assessment. This follows from standards recommended for modeled and simulated claims. In the absence of cost-outcomes claims being presented in an evaluable form, it is impossible not only to replicate the claim or to judge whether or not it is credible. Claims for product value based on such claims are unacceptable. The guidelines proposed here are designed to overcome these limitations and support an evidence base that is both credible and replicable for formulary decisions. This is achieved by focusing on short-term modeled or simulated claims for cost-effectiveness. The requirement for modeled or simulated claims that are evaluable within a time frame that is meaningful for formulary decisions marks a major departure from format submissions already in play, not only in the US but in other developed economies. Rather than subscribing to the gold standard of long term or lifetime cost-per-QALY claims a short-term time horizon of no more than 2-years is recommended. This allows products to be provisionally placed on formulary but subject to a protocol that supports an evaluation to be reported back to a formulary committee as part of ongoing disease area or therapeutic class reviews. The place of the product and its contracted price can then be reviewed. Conflict of Interest None Type: Commentary

  16. Universal proposal strategies of anti-HPV vaccination for adolescents: comparative analysis between school-based and clinic immunization programs.

    Science.gov (United States)

    Desiante, F; Russo, C; Giorgino, A; Caputi, G; Battista, T; Cipriani, R; Conversano, M

    2017-09-01

    A promising approach to increase teenager's adherence to immunization against HPV is the administration of vaccinations within the school facilities. The Local Health Unit of Taranto experienced two different vaccine strategy proposals in the twelve-year-olds: the first one was the usual active call strategy in the outpatient clinic, while the second one provided the involvement of the schools in the area. The aim of the study is to evaluate the results of the proposed vaccination strategies in both sexes and in towns of different sizes in order to identify an effective path for achieving vaccine coverage improvement. To estimate the number of anti-HPV vaccine doses administered in adolescents of the 2003 cohort, we used the computerized vaccination system data of the Apulia Region. Then, once analyzed, the data for anti-HPV vaccine were broken down by gender, vaccine strategy and size of the town of residence. Analyses performed by using STATA SE 14. The multiple logistic regression points out that, females (OR = 3.2; p HPV vaccine cycle in adolescents. The comparative assessment of anti-HPV coverage strategies, suggests that school vaccination has resulted in significantly better outcomes than outpatient clinic one, for all the groups considered (overall 72.3% vs 55.6%). The involvement of school institutes can define a winning organizational model to get a wider adolescent's adherence to immunization programs, especially in bigger towns. The school vaccination strategy could improve anti-HPV vaccine adherence also in males, who perceives a lower HPV-related diseases risk than females.

  17. NCEP-ATP III and IDF criteria for metabolic syndrome predict type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Eva Sulistiowati

    2016-05-01

    Full Text Available Background Subjects with metabolic syndrome (MetS have a greater risk for acquiring type 2 diabetes mellitus (type 2 DM. The MetS criteria usually used are those of the National Cholesterol Education Program Expert Panel (NCEP and Adult Treatment Panel III (ATP III and of the International Diabetes Federation (IDF. This study aimed to evaluate the modified NCEP-ATP III and IDF criteria as predictor of type 2 DM among subjects with MetS.   Methods A cohort study was conducted among 4240 subjects with MetS. MetS was determined according to the modified NCEP-ATP III and IDF criteria. The study followed up 3324 non-diabetic subjects of the cohort study of non-communicable disease (NCD risk factors (NCD study during a 2-year period. Type 2 DM was determined from the diagnosis by health personnel or from fasting blood glucose of ≥126 mg/dL or blood glucose of ≥200 mg/dL, 2 hours after 75g glucose loading.   Results The MetS prevalence based on modified NCEP ATP III and IDF criteria in non-DM subjects was 17.1% and 15.6%, respectively. The risk for DM in subjects with MetS using modified NCEP ATP III and IDF criteria was 4.7 (CI 95%: 3.4-6.5 and 4.1 (CI 95%: 3.0-5.7, respectively.   Conclusions Both MetS criteria can be used as predictors of the occurrence of DM type 2, but the modified NCEP-ATP III is more properly applied than the IDF criteria in subjects with MetS. Screening programs and routine monitoring of MetS components are required for early detection of type 2 DM.

  18. Facility Location Evaluation for Bonneville Dam Integrating Transmission, Study Area 77-2 : Draft Supplement to the Environmental Statement, Fiscal Year 1977 Proposed Program.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1976-01-22

    The overall construction and maintenance program in general, the Pacific Northwest Environment in which it operates, and the environmental impacts that typically occur from transmission line construction and maintenance activities are described. A framework for evaluation of specific proposals is provided. The need for a specific new transmission facility proposed as part of the Annual Proposed Program is identified and the probable environmental impact of constructing the facility in accordance with a general proposed system plan and alternative plans is outlined. This expands the facility planning supplement to include alternative locations for the proposed new facility and environmental impacts associated with each alternative location. This supplement was prepared after public and agency review of the final planning supplement had been completed and reconnaissance studies were made.

  19. ATP and astrocytes play a prominent role in the control of the respiratory pattern generator in the lamprey.

    Science.gov (United States)

    Cinelli, Elenia; Iovino, Ludovica; Mutolo, Donatella

    2017-12-01

    The paratrigeminal respiratory group (pTRG) is responsible for the respiratory pattern generation in the lamprey. The role of ATP and astrocytes, known to control respiratory activity in mammals, was investigated in the lamprey respiratory network. ATP microinjected into the pTRG induces a biphasic response consisting of marked increases in respiratory frequency mediated by P2X receptors followed by a decrease in the respiratory motor output due to the ATP metabolite adenosine. We provide evidence that astrocytes are involved in the genesis of the normal respiratory pattern, ATP-induced responses and acidification-induced increases of the respiratory activity. The function of astrocytes in rhythmic networks appears to be phylogenetically conserved. The role of ATP and astrocytes in respiratory rhythm modulation has been recently investigated in neonatal rodents. However, no information on the role of ATP and astrocytes within the respiratory network of the lamprey is available, particularly within the paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator. To address these issues, the present study was carried out on isolated brainstems of the adult lamprey. Bath application of ATP caused marked increases in respiratory frequency followed by decreases in the respiratory motor output, mediated by the ATP metabolite adenosine at the level of the pTRG. Bath applications and microinjections of agonists and antagonists of purinergic receptors showed that ATP increased respiratory activity through an action on pTRG P2X receptors. To disclose the respiratory role of astrocytes, we used bath application of the gliotoxin aminoadipic acid, which dramatically depressed the respiratory motor output that, however, promptly recovered following glutamine application. Furthermore, the excitatory responses to ATP-γ-S (a non-hydrolysable ATP analogue), but not to substance P, microinjected into the pTRG, were abolished. Finally, we also

  20. ATP synthases from archaea: the beauty of a molecular motor.

    Science.gov (United States)

    Grüber, Gerhard; Manimekalai, Malathy Sony Subramanian; Mayer, Florian; Müller, Volker

    2014-06-01

    Archaea live under different environmental conditions, such as high salinity, extreme pHs and cold or hot temperatures. How energy is conserved under such harsh environmental conditions is a major question in cellular bioenergetics of archaea. The key enzymes in energy conservation are the archaeal A1AO ATP synthases, a class of ATP synthases distinct from the F1FO ATP synthase ATP synthase found in bacteria, mitochondria and chloroplasts and the V1VO ATPases of eukaryotes. A1AO ATP synthases have distinct structural features such as a collar-like structure, an extended central stalk, and two peripheral stalks possibly stabilizing the A1AO ATP synthase during rotation in ATP synthesis/hydrolysis at high temperatures as well as to provide the storage of transient elastic energy during ion-pumping and ATP synthesis/-hydrolysis. High resolution structures of individual subunits and subcomplexes have been obtained in recent years that shed new light on the function and mechanism of this unique class of ATP synthases. An outstanding feature of archaeal A1AO ATP synthases is their diversity in size of rotor subunits and the coupling ion used for ATP synthesis with H(+), Na(+) or even H(+) and Na(+) using enzymes. The evolution of the H(+) binding site to a Na(+) binding site and its implications for the energy metabolism and physiology of the cell are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Environmental considerations for inclusion in program opportunity notices, requests for proposals, and environmental reports: fossil energy demonstration plants

    Energy Technology Data Exchange (ETDEWEB)

    Salk, M.S.; Baird, J.N.; Barnthouse, L.W.; Berry, L.G.; Roop, R.D.; Sanders, F.S.

    1978-01-01

    This document was prepared for the Department of Energy, Division of Coal Conversion, for use in developing Program Opportunity Notices (PON), Requests for Proposals (RFP), and Environmental Reports (ER). Environmental considerations to be addressed by Offerors and Contractors are divided into three parts that correspond to the separate stages of project development: (1) the Offeror's response to the PON or RFP; (2) the Contractor's performance of baseline data collection and environmental impact assessment that results in an Environmental Report (ER) for use by DOE in the preparation of an Environmental Impact Statement (EIS); and (3) the Contractor's continuance of environmental monitoring and assessment during construction and operation. Environmental analysis and environmental protection are an integral part of the Offeror's or Contractor's performance under contract to DOE. Consideration should be given to the health and socioeconomic status of man as well as to the physical and biological environment. The Offeror's or Contractor's consideration of and commitment to avoiding adverse environmental impacts must be demonstrated at every stage of the process from planning through construction and operation.

  2. Complex processing patterns of mRNAs of the large ATP synthase operon in Arabidopsis chloroplasts.

    Directory of Open Access Journals (Sweden)

    Mustafa Malik Ghulam

    Full Text Available Chloroplasts are photosynthetic cell organelles which have evolved from endosymbiosis of the cyanobacterial ancestor. In chloroplasts, genes are still organized into transcriptional units as in bacteria but the corresponding poly-cistronic mRNAs undergo complex processing events, including inter-genic cleavage and 5' and 3' end-definition. The current model for processing proposes that the 3' end of the upstream cistron transcripts and the 5' end of the downstream cistron transcripts are defined by the same RNA-binding protein and overlap at the level of the protein-binding site. We have investigated the processing mechanisms that operate within the large ATP synthase (atp operon, in Arabidopsis thaliana chloroplasts. This operon is transcribed by the plastid-encoded RNA polymerase starting from two promoters, which are upstream and within the operon, respectively, and harbors four potential sites for RNA-binding proteins. In order to study the functional significance of the promoters and the protein-binding sites for the maturation processes, we have performed a detailed mapping of the atp transcript ends. Our data indicate that in contrast to maize, atpI and atpH transcripts with overlapping ends are very rare in Arabidopsis. In addition, atpA mRNAs, which overlap with atpF mRNAs, are even truncated at the 3' end, thus representing degradation products. We observe, instead, that the 5' ends of nascent poly-cistronic atp transcripts are defined at the first protein-binding site which follows either one of the two transcription initiation sites, while the 3' ends are defined at the subsequent protein-binding sites or at hairpin structures that are encountered by the progressing RNA polymerase. We conclude that the overlapping mechanisms of mRNA protection have only a limited role in obtaining stable processed atp mRNAs in Arabidopsis. Our findings suggest that during evolution of different plant species as maize and Arabidopsis, chloroplasts

  3. NASA ATP Force Measurement Technology Capability Strategic Plan

    Science.gov (United States)

    Rhew, Ray D.

    2008-01-01

    The Aeronautics Test Program (ATP) within the National Aeronautics and Space Administration (NASA) Aeronautics Research Mission Directorate (ARMD) initiated a strategic planning effort to re-vitalize the force measurement capability within NASA. The team responsible for developing the plan included members from three NASA Centers (Langley, Ames and Glenn) as well as members from the Air Force s Arnold Engineering and Development Center (AEDC). After visiting and discussing force measurement needs and current capabilities at each participating facility as well as selected force measurement companies, a strategic plan was developed to guide future NASA investments. This paper will provide the details of the strategic plan and include asset management, organization and technology research and development investment priorities as well as efforts to date.

  4. Bioanalytical Applications of Real-Time ATP Imaging Via Bioluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Gruenhagen, Jason Alan [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    The research discussed within involves the development of novel applications of real-time imaging of adenosine 5'-triphosphate (ATP). ATP was detected via bioluminescence and the firefly luciferase-catalyzed reaction of ATP and luciferin. The use of a microscope and an imaging detector allowed for spatially resolved quantitation of ATP release. Employing this method, applications in both biological and chemical systems were developed. First, the mechanism by which the compound 48/80 induces release of ATP from human umbilical vein endothelial cells (HUVECs) was investigated. Numerous enzyme activators and inhibitors were utilized to probe the second messenger systems involved in release. Compound 48/80 activated a G{sub q}-type protein to initiate ATP release from HUVECs. Ca2+ imaging along with ATP imaging revealed that activation of phospholipase C and induction of intracellular Ca2+ signaling were necessary for release of ATP. Furthermore, activation of protein kinase C inhibited the activity of phospholipase C and thus decreased the magnitude of ATP release. This novel release mechanism was compared to the existing theories of extracellular release of ATP. Bioluminescence imaging was also employed to examine the role of ATP in the field of neuroscience. The central nervous system (CNS) was dissected from the freshwater snail Lymnaea stagnalis. Electrophysiological experiments demonstrated that the neurons of the Lymnaea were not damaged by any of the components of the imaging solution. ATP was continuously released by the ganglia of the CNS for over eight hours and varied from ganglion to ganglion and within individual ganglia. Addition of the neurotransmitters K+ and serotonin increased release of ATP in certain regions of the Lymnaea CNS. Finally, the ATP imaging technique was investigated for the study of drug release systems. MCM-41-type mesoporous nanospheres were loaded with ATP and end-capped with mercaptoethanol

  5. A taste for ATP: neurotransmission in taste buds

    Science.gov (United States)

    Kinnamon, Sue C.; Finger, Thomas E.

    2013-01-01

    Not only is ATP a ubiquitous source of energy but it is also used widely as an intercellular signal. For example, keratinocytes release ATP in response to numerous external stimuli including pressure, heat, and chemical insult. The released ATP activates purinergic receptors on nerve fibers to generate nociceptive signals. The importance of an ATP signal in epithelial-to-neuronal signaling is nowhere more evident than in the taste system. The receptor cells of taste buds release ATP in response to appropriate stimulation by tastants and the released ATP then activates P2X2 and P2X3 receptors on the taste nerves. Genetic ablation of the relevant P2X receptors leaves an animal without the ability to taste any primary taste quality. Of interest is that release of ATP by taste receptor cells occurs in a non-vesicular fashion, apparently via gated membrane channels. Further, in keeping with the crucial role of ATP as a neurotransmitter in this system, a subset of taste cells expresses a specific ectoATPase, NTPDase2, necessary to clear extracellular ATP which otherwise will desensitize the P2X receptors on the taste nerves. The unique utilization of ATP as a key neurotransmitter in the taste system may reflect the epithelial rather than neuronal origins of the receptor cells. PMID:24385952

  6. Electron transfer precedes ATP hydrolysis during nitrogenase catalysis

    Science.gov (United States)

    Duval, Simon; Danyal, Karamatullah; Shaw, Sudipta; Lytle, Anna K.; Dean, Dennis R.; Hoffman, Brian M.; Antony, Edwin; Seefeldt, Lance C.

    2013-01-01

    The biological reduction of N2 to NH3 catalyzed by Mo-dependent nitrogenase requires at least eight rounds of a complex cycle of events associated with ATP-driven electron transfer (ET) from the Fe protein to the catalytic MoFe protein, with each ET coupled to the hydrolysis of two ATP molecules. Although steps within this cycle have been studied for decades, the nature of the coupling between ATP hydrolysis and ET, in particular the order of ET and ATP hydrolysis, has been elusive. Here, we have measured first-order rate constants for each key step in the reaction sequence, including direct measurement of the ATP hydrolysis rate constant: kATP = 70 s−1, 25 °C. Comparison of the rate constants establishes that the reaction sequence involves four sequential steps: (i) conformationally gated ET (kET = 140 s−1, 25 °C), (ii) ATP hydrolysis (kATP = 70 s−1, 25 °C), (iii) Phosphate release (kPi = 16 s−1, 25 °C), and (iv) Fe protein dissociation from the MoFe protein (kdiss = 6 s−1, 25 °C). These findings allow completion of the thermodynamic cycle undergone by the Fe protein, showing that the energy of ATP binding and protein–protein association drive ET, with subsequent ATP hydrolysis and Pi release causing dissociation of the complex between the Feox(ADP)2 protein and the reduced MoFe protein. PMID:24062462

  7. Evaluation and Proposed Refinement of the Sampling Design for the Long Term Resource Monitoring Program's Fish Component

    National Research Council Canada - National Science Library

    Ickes, Brian

    2002-01-01

    ... if the sampling design adequately addresses program goals and objectives. Periodic evaluations also permit assessment of a program's ability to provide adequate and useful information for changing management and science needs...

  8. Monitoring of endoscope reprocessing with an adenosine triphosphate (ATP bioluminescence method

    Directory of Open Access Journals (Sweden)

    Parohl, Nina

    2017-03-01

    Full Text Available Background: The arising challenges over endoscope reprocessing quality proposes to look for possibilities to measure and control the process of endoscope reprocessing.Aim: The goal of this study was to evaluate the feasibility of monitoring endoscope reprocessing with an adenosine triphosphate (ATP based bioluminescence system.Methods: 60 samples of eight gastroscopes have been assessed from routine clinical use in a major university hospital in Germany. Endoscopes have been assessed with an ATP system and microbial cultures at different timepoints during the reprocessing. Findings: After the bedside flush the mean ATP level in relative light units (RLU was 19,437 RLU, after the manual cleaning 667 RLU and after the automated endoscope reprocessor (AER 227 RLU. After the manual cleaning the mean total viable count (TVC per endoscope was 15.3 CFU/10 ml, and after the AER 5.7 CFU/10 ml. Our results show that there are reprocessing cycles which are not able to clean a patient used endoscope.Conclusion: Our data suggest that monitoring of flexible endoscope with ATP can identify a number of different influence factors, like the endoscope condition and the endoscopic procedure, or especially the quality of the bedside flush and manual cleaning before the AER. More process control is one option to identify and improve influence factors to finally increase the overall reprocessing quality, best of all by different methods. ATP measurement seems to be a valid technique that allows an immediate repeat of the manual cleaning if the ATP results after manual cleaning exceed the established cutoff of 200 RLU.

  9. Stoichiometry of vectorial H+ movements coupled to electron transport and to ATP synthesis in mitochondria

    Science.gov (United States)

    Alexandre, Adolfo; Reynafarje, Baltazar; Lehninger, Albert L.

    1978-01-01

    In order to verify more directly our earlier measurements showing that, on the average, close to four vectorial H+ are rejected per pair of electrons passing each of the three energy-conserving sites of the mitochondrial electron transport chain, direct tests of the H+/2e- ratio for sites 2 and 3 were carried out in the presence of permeant charge-compensating cations. Site 2 was examined by utilizing succinate as electron donor and ferricyanide as electron acceptor from mitochondrial cytochrome c; the directly measured H+/2e- ratio was close to 4. Energy-conserving site 3 was isolated for study with ferrocyanide or ascorbate plus tetramethylphenylenediamine as electron donors to cytochrome c and with oxygen as electron acceptor. The directly measured H+/2e- ratio for site 3 was close to 4. The H+/ATP ratio (number of vectorial H+ ejected per ATP hydrolyzed) was determined with a new method in which the steady-state rates of both H+ ejection and ATP hydrolysis were measured in the presence of K+ + valinomycin. The H+/ATP ratio was found to approach 3.0. A proton cycle for oxidative phosphorylation is proposed, in which four electrochemical H+ equivalents are ejected per pair of electrons passing each energy-conserving site; three of the H+ equivalents pass inward to derive ATP synthesis from ADP and phosphate and the fourth H+ is used to bring about the energy-requiring electrogenic expulsion of ATP4- in exchange for extramitochondrial ADP3-, via the H+/H2PO4- symporter. PMID:31621

  10. Understanding structure, function, and mutations in the mitochondrial ATP synthase

    Directory of Open Access Journals (Sweden)

    Ting Xu

    2015-03-01

    Full Text Available The mitochondrial ATP synthase is a multimeric enzyme complex with an overall molecular weight of about 600,000 Da. The ATP synthase is a molecular motor composed of two separable parts: F1 and Fo. The F1 portion contains the catalytic sites for ATP synthesis and protrudes into the mitochondrial matrix. Fo forms a proton turbine that is embedded in the inner membrane and connected to the rotor of F1. The flux of protons flowing down a potential gradient powers the rotation of the rotor driving the synthesis of ATP. Thus, the flow of protons though Fo is coupled to the synthesis of ATP. This review will discuss the structure/function relationship in the ATP synthase as determined by biochemical, crystallographic, and genetic studies. An emphasis will be placed on linking the structure/function relationship with understanding how disease causing mutations or putative single nucleotide polymorphisms (SNPs in genes encoding the subunits of the ATP synthase, will affect the function of the enzyme and the health of the individual. The review will start by summarizing the current understanding of the subunit composition of the enzyme and the role of the subunits followed by a discussion on known mutations and their effect on the activity of the ATP synthase. The review will conclude with a summary of mutations in genes encoding subunits of the ATP synthase that are known to be responsible for human disease, and a brief discussion on SNPs.

  11. MRT letter: Expression of ATP sensor protein in Caenorhabditis elegans.

    Science.gov (United States)

    Kishikawa, Jun-ichi; Fujikawa, Makoto; Imamura, Hiromi; Yasuda, Kayo; Noji, Hiroyuki; Ishii, Naoaki; Mitani, Shohei; Yokoyama, Ken

    2012-01-01

    Adenosine 5'-triphosphate (ATP) is the major energy currency and is involved in many biological processes. The ATP-monitoring system for cells in animals can be helpful to study the relationship between energy metabolism and biological processes. The fluorescent ATP biosensor ATeam (ATP indicator based on Epsilon subunit for Analytical Measurements), which has been reported to monitor ATP levels in cultured cells on the basis of fluorescence resonance energy transfer (FRET), was introduced into nematodes by microinjection and UV-irradiation method. To confirm whether ATeam functions as an ATP sensor in nematode cells, the authors measured FRET of ATeam in cells of transgenic nematode. The ATeam was expressed in target cells in nematode. In vulva cells, ATP levels in the cytosol were higher than those in mitochondria. ATeam also sensed ATP level change in cultured cells from the transgenic nematode. These experiments indicated that ATeam is available for detection of changes in ATP levels in nematode cells. Copyright © 2011 Wiley Periodicals, Inc.

  12. Teaching Education and Socio-educational Action: Developing an Implementation Proposal of the Program Community Teachers (PCT

    Directory of Open Access Journals (Sweden)

    Paulette Barberousse-Alfonso

    2017-12-01

    Full Text Available From a critical and transformative approach, this essay presents inputs and relevant conclusions obtained during the first stage of the project Construyendo una propuesta de implementación del Programa Maestros Comunitarios (PMC, Code number 0166-15 DEB-UNA (UNA, DEB, s. f., conducted in 2016. Considering our perspective as researchers and professors at División de Educación Básica, the paper addresses a current topic within the socio-educative field to face challenges of contemporary educational models in formal and non-formal areas of elementary education in the Costa Rican context. Our purpose is that students and teachers of the career program Pedagogía con énfasis en I y II ciclos de la Educación General Básica have an overview of the national, social, and educational reality in an attempt to involve them in applying pedagogical actions towards finding a solution to school dropouts at Escuela Finca Guararí, Heredia, Costa Rica. The essay describes the experience of teaching education students and their socio-educational action with the focus on the systematization of the experience in the initial stage of the project. Furthermore, the paper connects with emerging strategic knowledge areas at División de Educación Básica (DEB, such as social and community pedagogy in the context of the National University (UNA of Costa Rica. It takes over a route already traced at DEB, which proposes more flexible and alternative pedagogic formats to promote educational equity and diversity issues. The paper describes the project background and a theoretical framework, as well as aspects that have been shared by the protagonist actors along the process: students-teachers, host teachers, supervisor professors, school children, and their parents at Escuela Finca Guararí. Conclusions address main results and facts during 2016 in order to show the viability of the project, which is conducted from a public university. Finally, the article also

  13. Human MSH2 (hMSH2) protein controls ATP processing by hMSH2-hMSH6.

    Science.gov (United States)

    Heinen, Christopher D; Cyr, Jennifer L; Cook, Christopher; Punja, Nidhi; Sakato, Miho; Forties, Robert A; Lopez, Juana Martin; Hingorani, Manju M; Fishel, Richard

    2011-11-18

    The mechanics of hMSH2-hMSH6 ATP binding and hydrolysis are critical to several proposed mechanisms for mismatch repair (MMR), which in turn rely on the detailed coordination of ATP processing between the individual hMSH2 and hMSH6 subunits. Here we show that hMSH2-hMSH6 is strictly controlled by hMSH2 and magnesium in a complex with ADP (hMSH2(magnesium-ADP)-hMSH6). Destabilization of magnesium results in ADP release from hMSH2 that allows high affinity ATP binding by hMSH6, which then enhances ATP binding by hMSH2. Both subunits must be ATP-bound to efficiently form a stable hMSH2-hMSH6 hydrolysis-independent sliding clamp required for MMR. In the presence of magnesium, the ATP-bound sliding clamps remain on the DNA for ∼8 min. These results suggest a precise stepwise kinetic mechanism for hMSH2-hMSH6 functions that appears to mimic G protein switches, severely constrains models for MMR, and may partially explain the MSH2 allele frequency in Lynch syndrome or hereditary nonpolyposis colorectal cancer.

  14. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

    Directory of Open Access Journals (Sweden)

    Quadros Edward V

    2009-05-01

    Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

  15. Rational design of substrate binding pockets in polyphosphate kinase for use in cost-effective ATP-dependent cascade reactions.

    Science.gov (United States)

    Cao, Hao; Nie, Kaili; Li, Chengcheng; Xu, Haijun; Wang, Fang; Tan, Tianwei; Liu, Luo

    2017-07-01

    Adenosine-5'-triphosphate (ATP) is the energy equivalent of the living system. Polyphosphate (polyP) is the ancient energy storage equivalent of organisms. Polyphosphate kinases (PPKs) catalyze the polyP formation or ATP formation, to store energy or to regenerate ATP, respectively. However, most PPKs are active only in the presence of long polyPs, which are more difficult and more expensive to generate than the short polyPs. We investigated the PPK preference towards polyPs by site-directed mutagenesis and computational simulation, to understand the mechanism and further design enzymes for effective ATP regeneration using short polyPs for in vitro cascade reactions, which are highly desired for research and applications. The results suggest that the short polyPs inhibit PPK by blocking the ADP-binding pocket. Structural comparison between PPK (Corynebacterium glutamicum) and PPK (Sinorhizobium meliloti) indicates that three amino acid residues, i.e., lysine, glutamate, and threonine, are involved in the activity towards short polyP by fixing the adenosine group of ADP in between the subunits of the dimer, while the terminal phosphate group of ADP still offers an active site, which presents a binding pocket for ADP. A proposed triple mutant PPK (SMc02148-KET) demonstrates significant activity towards short polyP to form ATP from ADP. The obtained high glutathione titer (38.79 mM) and glucose-6-phosphate titer (87.35 mM) in cascade reactions with ATP regeneration using the triple mutant PPK (SMc02148-KET) reveal that the tailored PPK establishes the effective ATP regeneration system for ATP-dependent reactions.

  16. Modelling the ATP production in mitochondria

    CERN Document Server

    Saa, Alberto

    2012-01-01

    We revisit here the mathematical model for ATP production in mitochondria introduced recently by Bertram, Pedersen, Luciani, and Sherman (BPLS) as a simplification of the more complete but intricate Magnus and Keizer's model. We correct some inaccuracies in the BPLS original approximations and then analyze some of the dynamical properties of the model. We infer from exhaustive numerical explorations that the enhanced BPLS equations have a unique attractor fixed point for physiologically acceptable ranges of mitochondrial variables and respiration inputs. We determine, in the stationary regime, the dependence of the mitochondrial variables on the respiration inputs, namely the cytosolic concentration of calcium ${\\rm Ca}_{\\rm c}$ and the substrate fructose 1,6-bisphosphate FBP. The same effect of calcium saturation reported for the original BPLS model is observed here. We find out, however, an interesting non-stationary effect: the inertia of the model tends to increase considerably for high concentrations of ...

  17. Targeting ATP7A to increase the sensitivity of neuroblastoma cells to retinoid therapy.

    Science.gov (United States)

    Cheung, B B; Marshall, G M

    2011-09-01

    Following the discovery that defective retinoid signaling directly contributes to tumorigenesis, and, that retinoids have an anti-cancer effect in vitro and in vivo, retinoids have become part of the routine care in children with neuroblastoma at the stage of minimal residual disease. However, many patients still relapse following retinoid therapy, demonstrating the need for more effective retinoids and better assays to predict retinoid sensitivity in cancer cells. Recent evidence suggests that the copper metabolism gene, ATP7A, is retinoid-regulated and an important component of the retinoic acid receptor β (RARβ) anticancer effect in neuroblastoma cells. To highlight and further develop the concept of using ATP7A as a target in retinoid therapy, and combination therapy with copper chelators in neuroblastoma, the current literature and abstracts related to the clinical application of retinoids, the function of ATP7A and the clinical application of copper chelators are summarized. We propose that strategies targeting the copper export protein, ATP7A, in combination therapy with retinoids and copper depletion therapy, may have great therapeutic potential in the clinical treatment of neuroblastoma and other malignancies.

  18. A novel ATP1A2 gene mutation in an Irish familial hemiplegic migraine kindred.

    LENUS (Irish Health Repository)

    Fernandez, Desiree M

    2012-02-03

    OBJECTIVE: We studied a large Irish Caucasian pedigree with familial hemiplegic migraine (FHM) with the aim of finding the causative gene mutation. BACKGROUND: FHM is a rare autosomal-dominant subtype of migraine with aura, which is linked to 4 loci on chromosomes 19p13, 1q23, 2q24, and 1q31. The mutations responsible for hemiplegic migraine have been described in the CACNA1A gene (chromosome 19p13), ATP1A2 gene (chromosome 1q23), and SCN1A gene (chromosome 2q24). METHODS: We performed linkage analyses in this family for chromosome 1q23 and performed mutation analysis of the ATP1A2 gene. RESULTS: Linkage to the FHM2 locus on chromosome 1 was demonstrated. Mutation screening of the ATP1A2 gene revealed a G to C substitution in exon 22 resulting in a novel protein variant, D999H, which co-segregates with FHM within this pedigree and is absent in 50 unaffected individuals. This residue is also highly conserved across species. CONCLUSIONS: We propose that D999H is a novel FHM ATP1A2 mutation.

  19. Role of Erythrocyte-released ATP in the Regulation of Microvascular Oxygen Supply in Skeletal Muscle

    Science.gov (United States)

    Ellsworth, Mary L.; Ellis, Christopher G.; Sprague, Randy S.

    2015-01-01

    In a 1914 book entitled The Respiratory Function of the Blood, Joseph Barcroft stated that “the cell takes what it needs and leaves the rest.” He postulated that there must be both a “call for oxygen” and a “mechanism by which the call elicits a response…” In the past century, intensive investigation has provided significant insights into the hemodynamic and biophysical mechanisms involved in supplying oxygen to skeletal muscle. However, the identification of the mechanism by which tissue oxygen needs are sensed and the affector responsible for altering the upstream vasculature to enable the need to be appropriately met has been a challenge. In 1995, Ellsworth et al proposed that the oxygen carrying erythrocyte, by virtue of its capacity to release the vasoactive mediator ATP in response to a decrease in oxygen saturation, could serve both roles. Several in vitro and in situ studies have established that exposure of erythrocytes to reduced oxygen tension induces the release of ATP which does result in a conducted arteriolar vasodilation with a sufficiently rapid time course to make the mechanism physiologically relevant. The components of the signaling pathway for the controlled release of ATP from erythrocytes in response to exposure to low oxygen tension have been determined. In addition, the implications of defective ATP release on human pathological conditions have been explored. This review provides a perspective on oxygen supply and the role that such a mechanism plays in meeting the oxygen needs of skeletal muscle. PMID:26336065

  20. Mevalonate 5-diphosphate mediates ATP binding to the mevalonate diphosphate decarboxylase from the bacterial pathogen Enterococcus faecalis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chun-Liang; Mermoud, James C.; Paul, Lake N.; Steussy, Calvin Nicklaus; Stauffacher, Cynthia V. (Purdue)

    2017-10-12

    The mevalonate pathway produces isopentenyl diphosphate (IPP), a building block for polyisoprenoid synthesis, and is a crucial pathway for growth of the human bacterial pathogen Enterococcus faecalis. The final enzyme in this pathway, mevalonate diphosphate decarboxylase (MDD), acts on mevalonate diphosphate (MVAPP) to produce IPP while consuming ATP. This essential enzyme has been suggested as a therapeutic target for the treatment of drug-resistant bacterial infections. Here, we report functional and structural studies on the mevalonate diphosphate decarboxylase from E. faecalis (MDDEF). The MDDEF crystal structure in complex with ATP (MDDEF–ATP) revealed that the phosphate-binding loop (amino acids 97–105) is not involved in ATP binding and that the phosphate tail of ATP in this structure is in an outward-facing position pointing away from the active site. This suggested that binding of MDDEF to MVAPP is necessary to guide ATP into a catalytically favorable position. Enzymology experiments show that the MDDEF performs a sequential ordered bi-substrate reaction with MVAPP as the first substrate, consistent with the isothermal titration calorimetry (ITC) experiments. On the basis of ITC results, we propose that this initial prerequisite binding of MVAPP enhances ATP binding. In summary, our findings reveal a substrate-induced substrate-binding event that occurs during the MDDEF-catalyzed reaction. The disengagement of the phosphate-binding loop concomitant with the alternative ATP-binding configuration may provide the structural basis for antimicrobial design against these pathogenic enterococci.

  1. Proposed Rule and Related Materials for Heavy-Duty Highway Program: Revisions for Emergency Vehicles and SCR Maintenance

    Science.gov (United States)

    May 23, 2012, Notice of Proposed Rulemaking with revisions related to emissions controls on diesel-powered emergency vehicles and revisions related to scheduled maintenance intervals for diesel engines and vehicles using Selective Catalytic Reduction (SCR)

  2. 76 FR 70156 - Proposed 5-Year Outer Continental Shelf (OCS) Oil and Gas Leasing Program for 2012-2017

    Science.gov (United States)

    2011-11-10

    ...-4010), Room 3120, 381 Elden Street, Herndon, Virginia 20170. Please label your comments and the....gov for public review and comment: (1) Economic Analysis for the OCS 5-Year Program 2012-2017: Theory...

  3. Exon duplications in the ATP7A gene

    DEFF Research Database (Denmark)

    Mogensen, Mie; Skjørringe, Tina; Kodama, Hiroko

    2011-01-01

    BACKGROUND: Menkes disease (MD) is an X-linked, fatal neurodegenerative disorder of copper metabolism, caused by mutations in the ATP7A gene. Thirty-three Menkes patients in whom no mutation had been detected with standard diagnostic tools were screened for exon duplications in the ATP7A gene. ME...

  4. K ATP channels in pig and human intracranial arteries

    DEFF Research Database (Denmark)

    Ploug, Kenneth Beri; Sørensen, Mette Aaskov; Strøbech, Lotte

    2008-01-01

    Clinical trials suggest that synthetic ATP-sensitive K(+) (K(ATP)) channel openers may cause headache and migraine by dilating cerebral and meningeal arteries. We studied the mRNA expression profile of K(ATP) channel subunits in the pig and human middle meningeal artery (MMA) and in the pig middle...... cerebral artery (MCA). We determined the order of potency of four K(ATP) channel openers when applied to isolated pig MMA and MCA, and we examined the potential inhibitory effects of the Kir6.1 subunit specific K(ATP) channel blocker PNU-37883A on K(ATP) channel opener-induced relaxation of the isolated...... pig MMA and MCA. Using conventional RT-PCR, we detected the mRNA transcripts of the K(ATP) channel subunits Kir6.1 and SUR2B in all the examined pig and human intracranial arteries. Application of K(ATP) channel openers to isolated pig MMA and MCA in myographs caused a concentration...

  5. Cellular ATP release in the lung and airway

    Directory of Open Access Journals (Sweden)

    Satoru Ito

    2016-11-01

    Full Text Available Adenosine triphosphate (ATP is a universal energy source synthesized by mitochondrial oxidative phosphorylation and cytosolic glycolysis and transported by the vesicular nucleotide transporter for storage in secretory vesicles. Extracellular ATP regulates physiological functions and homeostasis of the respiratory system and is associated with pathogenesis of respiratory diseases. Thus, modulation of ATP and purinergic signaling may be a novel therapeutic approach to pulmonary disease. ATP is released from alveolar epithelial cells, airway epithelial cells, airway smooth muscle cells, fibroblasts and endothelial cells in response to various chemical and mechanical stimuli. In addition to conductive pathways such as connexins and pannexins, vesicular exocytosis is involved in the mechanisms of ATP release from the cells. Imaging approaches enable us to visualize ATP release from not only cultured cells but also lung tissue ex vivo. Extracellular vesicles, exosomes and membrane-derived microvesicles, containing cytoplasmic proteins, mRNA and microRNA, represent important mediators of cell-to-cell communication and the intercellular microenvironment. However, it is not known whether extracellular vesicles contain ATP as an intercellular messenger. Future studies are necessary to elucidate the mechanisms of cellular ATP release and purinergic signaling in the respiratory system.

  6. Renal epithelial cells can release ATP by vesicular fusion

    Directory of Open Access Journals (Sweden)

    Randi G Bjaelde

    2013-09-01

    Full Text Available Renal epithelial cells have the ability to release nucleotides as paracrine factors. In the intercalated cells of the collecting duct, ATP is released by connexin30 (cx30, which is selectively expressed in this cell type. However, ATP is released by virtually all renal epithelia and the aim of the present study was to identify possible alternative nucleotide release pathways in a renal epithelial cell model. We used MDCK (type1 cells to screen for various potential ATP release pathways. In these cells, inhibition of the vesicular H+-ATPases (bafilomycin reduced both the spontaneous and hypotonically (80%-induced nucleotide release. Interference with vesicular fusion using N-ethylamide markedly reduced the spontaneous nucleotide release, as did interference with trafficking from the endoplasmic reticulum to the Golgi apparatus (brefeldin A1 and vesicular transport (nocodazole. These findings were substantiated using a siRNA directed against SNAP-23, which significantly reduced spontaneous ATP release. Inhibition of pannexin and connexins did not affect the spontaneous ATP release in this cell type, which consists of ∼90% principal cells. TIRF-microscopy of either fluorescently-labeled ATP (MANT-ATP or quinacrine-loaded vesicles, revealed that spontaneous release of single vesicles could be promoted by either hypoosmolality (50% or ionomycin. This vesicular release decreased the overall cellular fluorescence by 5.8% and 7.6% respectively. In summary, this study supports the notion that spontaneous and induced ATP release can occur via exocytosis in renal epithelial cells.

  7. The Role of ATP in the Regulation of NCAM Function

    DEFF Research Database (Denmark)

    Hübschmann, Martin; Skladchikova, Galina

    2008-01-01

    Extracellular ATP is an abundant signaling molecule that has a number of functions in the nervous system. It is released by both neurons and glial cells, activates purinergic receptors and acts as a trophic factor as well as a neurotransmitter. In this review, we summarize the evidence for a dire...... shedding, possibly affecting the structural plasticity associated with learning and memory.......Extracellular ATP is an abundant signaling molecule that has a number of functions in the nervous system. It is released by both neurons and glial cells, activates purinergic receptors and acts as a trophic factor as well as a neurotransmitter. In this review, we summarize the evidence for a direct...... ATP-NCAM interaction and discuss its functional implications. The ectodomain of NCAM contains the ATP binding Walker motif A and has intrinsic ATPase activity, which could modulate NCAM-dependent signaling processes. NCAM interacts directly with and signals through FGFR. The NCAM binding site to ATP...

  8. Dexamethasone Enhances ATP-Induced Inflammatory Responses in Endothelial Cells

    Science.gov (United States)

    Ding, Yi; Gao, Zhan-Guo; Jacobson, Kenneth A.

    2010-01-01

    The purinergic nucleotide ATP is released from stressed cells and is implicated in vascular inflammation. Glucocorticoids are essential to stress responses and are used therapeutically, yet little information is available that describes the effects of glucocorticoids on ATP-induced inflammation. In a human microvascular endothelial cell line, extracellular ATP-induced interleukin (IL)-6 secretion in a dose- and time-dependent manner. When cells were pretreated with dexamethasone, a prototypic glucocorticoid, ATP-induced IL-6 production was enhanced in a time- and dose-dependent manner. Mifepristone, a glucocorticoid receptor antagonist, blocked these effects. ATP-induced IL-6 release was significantly inhibited by a phospholipase C inhibitor [1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U73122)] (63.2 ± 3%, p dexamethasone induced mRNA expression of the purinergic P2Y2 receptor (P2Y2R) 1.8- ± 0.1-fold and, when stimulated with ATP, enhanced Ca2+ release and augmented IL-6 mRNA expression. Silencing of the P2Y2R by its small interfering RNA decreased ATP-induced IL-6 production by 81 ± 1% (p Dexamethasone enhanced the transcription rate of P2Y2R mRNA and induced a dose-related increase in the activity of the P2Y2R promoter. Furthermore, dexamethasone-enhanced ATP induction of adhesion molecule transcription and augmented the release of IL-8. Dexamethasone leads to an unanticipated enhancement of endothelial inflammatory mediator production by extracellular ATP via a P2Y2R-dependent mechanism. These data define a novel positive feedback loop of glucocorticoids and ATP-induced endothelial inflammation. PMID:20826566

  9. Expression of ATP7B in normal human liver

    Directory of Open Access Journals (Sweden)

    D Fanni

    2009-06-01

    Full Text Available ATP7B is a copper transporting P-type ATPase, also known as Wilson disease protein, which plays a key role in copper distribution inside cells. Recent experimental data in cell culture have shown that ATP7B putatively serves a dual function in hepatocytes: when localized to the Golgi apparatus, it has a biosynthetic role, delivering copper atoms to apoceruloplasmin; when the hepatocytes are under copper stress, ATP7B translocates to the biliary pole to transport excess copper out of the cell and into the bile canaliculus for subsequent excretion from the body via the bile. The above data on ATP7B localization have been mainly obtained in tumor cell systems in vitro. The aim of the present work was to assess the presence and localization of the Wilson disease protein in the human liver. We tested immunoreactivity for ATP7B in 10 human liver biopsies, in which no significant pathological lesion was found using a polyclonal antiserum specific for ATP7B. In the normal liver, immunoreactivity for ATP7B was observed in hepatocytes and in biliary cells. In the hepatocytes, immunoreactivity for ATP7B was observed close to the plasma membrane, both at the sinusoidal and at the biliary pole. In the biliary cells, ATP7B was localized close to the cell membrane, mainly concentrated at the basal pole of the cells. The data suggest that, in human liver, ATP7B is localized to the plasma membrane of both hepatocytes and biliary epithelial cells.

  10. Nanomolar ambient ATP decelerates P2X3 receptor kinetics.

    Science.gov (United States)

    Grote, Alexander; Hans, Michael; Boldogkoi, Zsolt; Zimmer, Andreas; Steinhäuser, Christian; Jabs, Ronald

    2008-12-01

    Homomeric P2X receptors differ in their electrophysiological and pharmacological profiles. The rapidly activating and desensitizing P2X3 receptors are known for their involvement in pain signalling pathways. Modulatory effects on P2X3 receptors have been reported for low concentrations of ATP ([ATP]). This includes both, enhancement and reduction of receptor currents. The first has been reported to be mediated by activation of ectoprotein kinases and high affinity desensitization (HAD), respectively. Both processes influence receptor current amplitudes. Here we describe a new phenomenon, the modulatory influence of ambient low [ATP] on P2X3 receptor kinetics. First, we studied in HEK cells whether persistent ATP affects current decay. To this end, P2X3 receptor mediated currents, elicited by pressure application of saturating [ATP], were analyzed after pre-application of low [ATP]. Second, UV-flash photolysis of ATP was employed to investigate whether submicromolar [ATP] affects receptor activation. Finally we confirmed the action of nanomolar [ATP] on native P2X3 receptors of neurons freshly isolated from rat dorsal root ganglia. We found that persistent low [ATP] caused pronounced deceleration of receptor current activation and decay. This priming effect indicates a mechanism different from HAD. It could be explained by a pre-opening receptor isomerization, induced by the occupation of a high affinity binding site already at the resting state. The observed modulation of the receptor kinetics could be considered as a physiological fine tuning mechanism of the nociceptive system, driven by the actual ambient agonist concentration.

  11. The National School Lunch Program: Ideas, proposals, policies, and politics shaping students' experiences with school lunch in the United States, 1946 - present

    OpenAIRE

    Gosliner, Wendi Anne

    2013-01-01

    AbstractThe National School Lunch Program:Ideas, proposals, policies, and politics shaping students' experiences with school lunch in the United States, 1946 - presentBy Wendi Anne GoslinerDoctor of Public HealthUniversity of California, BerkeleyProfessor Ann Keller, ChairOn an average school day in 2012, The National School Lunch Program (NSLP) supported the provision of lunch meals to almost 2/3 of school-age youth in the United States. Recent spikes in childhood obesity rates and the emerg...

  12. A proposed emergency management program for acute care facilities in response to a highly virulent infectious disease.

    Science.gov (United States)

    Petinaux, Bruno; Ferguson, Brandy; Walker, Milena; Lee, Yeo-Jin; Little, Gary; Parenti, David; Simon, Gary

    2016-01-01

    To address the organizational complexities associated with a highly virulent infectious disease (HVID) hazard, such as Ebola Virus Disease (EVD), an acute care facility should institute an emergency management program rooted in the fundamentals of mitigation, preparedness, response, and recovery. This program must address all known facets of the care of a patient with HVID, from unannounced arrival to discharge. The implementation of such a program not only serves to mitigate the risks from an unrecognized exposure but also serves to prepare the organization and its staff to provide for a safe response, and ensure a full recovery. Much of this program is based on education, training, and infection control measures along with resourcing for appropriate personal protective equipment which is instrumental in ensuring an organized and safe response of the acute care facility in the service to the community. This emergency management program approach can serve as a model in the care of not only current HVIDs such as EVD but also future presentations in our healthcare setting.

  13. Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue

    Directory of Open Access Journals (Sweden)

    Ip Virginia

    2010-09-01

    Full Text Available Abstract Background ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg or drug vehicle twice weekly for 8 weeks. Results In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H. High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals. Conclusions In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non

  14. 78 FR 55084 - Proposed Collection; 60-day Comment Request; Data Collection To Understand How NIH Programs Apply...

    Science.gov (United States)

    2013-09-09

    ... are employed to increase organizational effectiveness. The Office of Management and Budget (OMB) and..., change management, organizational assessment and intervention, organizational design, process improvement... proposed projects to be submitted to the Office of Management and Budget (OMB) for review and approval...

  15. 78 FR 70958 - 30-Day Notice of Proposed Information Collection: Recordkeeping for HUD's Continuum of Care Program

    Science.gov (United States)

    2013-11-27

    ... URBAN DEVELOPMENT 30-Day Notice of Proposed Information Collection: Recordkeeping for HUD's Continuum of... allow for an additional 30 days of public comment. DATES: Comments Due Date: December 27, 2013... solicited public comment on the information collection for a period of 60 days was published on March 25...

  16. 76 FR 12104 - Pick-Sloan Missouri Basin Program-Eastern Division-2021 Power Marketing Initiative Proposal

    Science.gov (United States)

    2011-03-04

    ... Power Marketing Initiative (2021 PMI). Western's Firm Electric Service (FES) contracts associated with... plan, with amendments, to key marketing plan principles. This Federal Register notice initiates Western... 2021 PMI proposal. Key Marketing Plan principles discussed with firm power customers included: Contract...

  17. 76 FR 70828 - Proposed Information Collection (Mentor-Protégé Program Application and Reports) Activity...

    Science.gov (United States)

    2011-11-15

    ...://www.Regulations.gov ; or to Arita Tillman, Office of Acquisition and Logistics (049P1), Department of... information will have practical utility; (2) the accuracy of (OM)'s estimate of the burden of the proposed collection of information; (3) ways to enhance the quality, utility, and clarity of the information to be...

  18. Facility Location Evaluation for Haymill Service Study Area : Draft Supplement to the Environmental Statement, Fiscal Year 1977 Proposed Program.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1976-03-05

    This document expands the facility planning supplement to include alternative locations for the proposed new facility and environmental impacts associated with each alternative location. This supplement is prepared after public and agency review of the final planning supplement has been completed and reconnaissance studies have been made.

  19. Environmental Impact Analysis Process. Draft Environmental Impact Statement Proposed Central Radar System Over-the-Horizon Backscatter Radar Program

    Science.gov (United States)

    1986-08-01

    depression, feelings of inadequacy, headaches, hypersensitivity to sensory stimulation, and psychosomatic symptoms (disturbances of digestion and...Fence I 325 442 Proposed CRS Operations Existing Building18.000 Gal Underground Propane Tank 10" Water i . 8" Sewer 1 302 E 329 5" High Temperature

  20. 78 FR 9935 - Notice of Submission of Proposed Information Collection to OMB; Family Self-Sufficiency Program...

    Science.gov (United States)

    2013-02-12

    ... of Management and Budget (OMB) for review, as required by the Paperwork Reduction Act. The Department... program and illustrate strategies that assist participants to obtain greater economic independence. While..., which include: Getting a first job; getting a higher paying job; self-employment/small business...

  1. 77 FR 6585 - Proposed Information Collection Request (ICR) for the Impact Evaluation of the YouthBuild Program...

    Science.gov (United States)

    2012-02-08

    ..., from low-income families or in foster care and who are offenders, migrants, disabled or children of... emotional development. The evaluation represents an important opportunity for DOL and CNCS to add to the growing body of knowledge about the impacts of ``second chance'' programs for youth who have dropped out...

  2. 76 FR 27363 - Proposed Information Collection Request (ICR) for the Impact Evaluation of the YouthBuild Program...

    Science.gov (United States)

    2011-05-11

    ...-income communities: available housing, and youth education, employment and criminal behavior. The program... from school and work, be incarcerated, be unmarried, and have children outside of marriage. The... impacts on employment, earnings, and job characteristics? What are YouthBuild's impacts on crime and...

  3. Mental Health Awareness and Services in Armenian-American Schools: A Grant Proposal for a Teacher Training Program

    Science.gov (United States)

    Tanielian, Aline Zarig

    2012-01-01

    School-based mental health programs in America provide students with psychological services that have been found to increase students' academic and social success and overall well-being. Furthermore, teacher involvement in students' psychological well-being via awareness, psychoeducation, and/or rendering help and resources has been found to be a…

  4. Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP Binding: Requirement for Establishing Chronic Persistent Infection

    Energy Technology Data Exchange (ETDEWEB)

    Drumm, J.; Mi, K; Bilder, P; Sun, M; Lim, J; Bielefeldt-Ohmann, H; Basaraba, R; So, M; Zhu, G; et. al.

    2009-01-01

    Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

  5. Adenosine Triphosphate (ATP Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway

    Directory of Open Access Journals (Sweden)

    Zhengchang Liu

    2013-03-01

    Full Text Available Intracellular communication from the mitochondria to the nucleus is achieved via the retrograde response. In budding yeast, the retrograde response, also known as the RTG pathway, is regulated positively by Rtg1, Rtg2, Rtg3 and Grr1 and negatively by Mks1, Lst8 and two 14-3-3 proteins, Bmh1/2. Activation of retrograde signaling leads to activation of Rtg1/3, two basic helix-loop-helix leucine zipper transcription factors. Rtg1/3 activation requires Rtg2, a cytoplasmic protein with an N-terminal adenosine triphosphate (ATP binding domain belonging to the actin/Hsp70/sugar kinase superfamily. The critical regulatory step of the retrograde response is the interaction between Rtg2 and Mks1. Rtg2 binds to and inactivates Mks1, allowing for activation of Rtg1/3 and the RTG pathway. When the pathway is inactive, Mks1 has dissociated from Rtg2 and bound to Bmh1/2, preventing activation of Rtg1/3. What signals association or disassociation of Mks1 and Rtg2 is unknown. Here, we show that ATP at physiological concentrations dissociates Mks1 from Rtg2 in a highly cooperative fashion. We report that ATP-mediated dissociation of Mks1 from Rtg2 is conserved in two other fungal species, K. lactis and K. waltii. Activation of Rtg1/3 upregulates expression of genes encoding enzymes catalyzing the first three reactions of the Krebs cycle, which is coupled to ATP synthesis through oxidative phosphorylation. Therefore, we propose that the retrograde response is an ATP homeostasis pathway coupling ATP production with ATP-mediated repression of the retrograde response by releasing Mks1 from Rtg2.

  6. Environmental Impact Analysis Process. Final Environmental Impact Statement. Part 2. Proposed High Frequency Active Auroral Research Program.

    Science.gov (United States)

    1993-07-01

    which I will identify by page number. Nikola Tesla , built huge facilities early in this century to study electricity and the earth’s ability to...I believe you have left out some critical points which the public will want to have answers to before construction and operation begin. Like Tesla ...based on the proposed tax laws), then it would be helpful to have a BTU equivalent for the facility and its components as well. 11-4 Like Tesla , the

  7. Electromagnetic interference impact of the proposed emitters for the High Frequency Active Auroral Research Program (HAARP). Interim report

    Energy Technology Data Exchange (ETDEWEB)

    Robertshaw, G.A.; Snyder, A.L.; Weiner, M.M.

    1993-05-14

    The proposed HAARP emitters at the Gakona (Alaska) preferred site and at the Clear AFS (Alaska) alternative site are the Ionospheric Research Instrument (IRI), the Incoherent Scatter Radar (ISR), and the Vertical Incidence Sounder(VIS). The electromagnetic interference (EMI) impact of those emitters on receiving systems in the vicinity of the sites is estimated in this study. The results are intended for use as an input to the Air Force Environmental Impact Statement as part of the Environmental Impact Analysis Process.

  8. Facility Location Evaluation for Satsop Integrating Transmission : Final Supplement to the Environmental Statement, Fiscal Year 1976 Proposed Program.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1976-06-08

    Proposed is the construction of a substation near Satsop and two 500-kV transmission lines from the proposed Satsop Substation approximately 24 miles west of Olympia, one running from Satsop to Paul Substation and one running from Satsop to Olympia Substation. Approximately 74 miles of 500-kV transmission line between the proposed Satsop Substation and Olympia and Paul Substations over existing, parallel, and new right-of-way would be required. Between 15 and 31 miles of new access road would also be required. Land use affected would include clearing from 560 to 1180 acres of timber. Approximately one acre of agricultural land would be removed from production and 37 acres temporarily disrupted. In addition approximately 30 acres of land would be required for the substation. Other impacts would include the removal of wildlife habitat associated with the above mentioned right-of-way requirements. Disturbance to wildlife during construction would occur. Some erosion and sedimentation would occur. Visual impacts would result from clearing rights-of-way through heavily forested areas. Noise and other disturbances to residents will occur, primarily during construction.

  9. Proposed program for and present status of the Geological Survey's investigation of domestic resources of radioactive raw materials

    Science.gov (United States)

    Bulter, A.P.; Killeen, P.L.; Page, G.B.; Rubey, W.W.

    1983-01-01

    This interim report is designed to show the present status of the Geological Survey's information and the parts of a comprehensive program necessary to improve our information about the raw material resources of uranium and thorium. Rarely in geologic work has it been necessary. to determine so completely a nation's resources of useful minerals in so brief a span of time. Ordinarily, information on mineral resources Is accumulated during a long period of years. However, uranium and thorium were suddenly thrust from a position of subsidiary economic interest into one of great strategic importance. Information concerning their occurrence must, therefore, be obtained as rapidly as reliable methods of investigation will permit. Accordingly the program must be at once comprehensive and carried out over an area more extensive than is usual in the search for and appraisal of most other mineral resources.

  10. Electromagnetic field generation by ATP-induced reverse electron transfer.

    Science.gov (United States)

    Steele, Richard H

    2003-03-01

    This paper describes a mechanism to explain low-level light emission in biology. A biological analog of the electrical circuitry, modeled on the parallel plate capacitor, traversed by a helical structure, required to generate electromagnetic radiation in the optical spectral range, is described. The charge carrier required for the emissions is determined to be an accelerating electron driven by an ATP-induced reverse electron transfer. The radial velocity component, the emission trajectory, of the moving charges traversing helical protein structures in a cyclotron-type mechanism is proposed to be imposed by the ferromagnetic field components of the iron in the iron-sulfur proteins. The redox systems NADH, riboflavin, and chlorophyll were examined with their long-wavelength absorption maxima determining the energetic parameters for the calculations. Potentials calculated from the axial velocity components for the riboflavin and NADH systems were found to equal the standard redox potentials of these systems as measured electrochemically and enzymatically. The mechanics for the three systems determined the magnetic moments, the angular momenta, and the orbital magnetic fluxes to be adiabatic invariant parameters. The De Broglie dual wave-particle equation, the fundamental equation of wave mechanics, and the key idea of quantum mechanics, establishes the wavelengths for accelerating electrons which, divided into a given radial velocity, gives its respective emission frequency. Electrons propelled through helical structures, traversed by biologically available electric and magnetic fields, make accessible to the internal environment the optical spectral frequency range that the solar spectrum provides to the external environment.

  11. Compartmentation of ATP:citrate lyase in plants.

    Science.gov (United States)

    Rangasamy, D; Ratledge, C

    2000-04-01

    Extracts prepared from young leaves of Pea (Pisum sativum), tobacco (Nicotiana tabacum), rape (Brassica napus), and spinach (Spinacia oleracea) all contained ATP:citrate lyase (ACL) activity, which was most active in rape leaflets (130 nmol min(-1) g fresh weight). In rape and spinach, ACL activity was predominantly localized in the plastids (between about 78% and 90% of the total activity), whereas in pea and tobacco, distribution was mainly cytosolic (about 85% and 78%, respectively, of the total). These distributions were calculated from the relative distributions of plastid and cytosol marker enzymes. Cross-reactivity between plant and rat ACL antibody was carried out by immunoblot analysis and, in rape and spinach, showed that a 120-kD protein, presumably indicating homomeric ACL proteins, was present in both cytosolic and plastidic fractions. In pea, two cross-reacting proteins were detected, the major material being in the cytosol fraction. Therefore, ACL occurs both in the cytosol and plastids of higher plants, but the distribution of activity changes according to the species. The plastidic ACL is proposed to function for the supply of acetyl-coenzyme A for lipid biosynthesis de novo, whereas the cytosolic ACL may provide acetyl-coenzyme A for the mevalonate pathway or fatty acid elongation.

  12. The need of a weight management control program in judo: a proposal based on the successful case of wrestling

    Directory of Open Access Journals (Sweden)

    Sterkowicz Stanislaw

    2010-05-01

    Full Text Available Abstract Judo competitions are divided into weight classes. However, most athletes reduce their body weight in a few days before competition in order to obtain a competitive advantage over lighter opponents. To achieve fast weight reduction, athletes use a number of aggressive nutritional strategies so many of them place themselves at a high health-injury risk. In collegiate wrestling, a similar problem has been observed and three wrestlers died in 1997 due to rapid weight loss regimes. After these deaths, the National Collegiate Athletic Association had implemented a successful weight management program which was proven to improve weight management behavior. No similar program has ever been discussed by judo federations even though judo competitors present a comparable inappropriate pattern of weight control. In view of this, the basis for a weight control program is provided in this manuscript, as follows: competition should begin within 1 hour after weigh-in, at the latest; each athlete is allowed to be weighed-in only once; rapid weight loss as well as artificial rehydration (i.e., saline infusion methods are prohibited during the entire competition day; athletes should pass the hydration test to get their weigh-in validated; an individual minimum competitive weight (male athletes competing at no less than 7% and females at no less than 12% of body fat should be determined at the beginning of each season; athletes are not allowed to compete in any weight class that requires weight reductions greater than 1.5% of body weight per week. In parallel, educational programs should aim at increasing the athletes', coaches' and parents' awareness about the risks of aggressive nutritional strategies as well as healthier ways to properly manage body weight.

  13. The need of a weight management control program in judo: a proposal based on the successful case of wrestling

    Science.gov (United States)

    2010-01-01

    Judo competitions are divided into weight classes. However, most athletes reduce their body weight in a few days before competition in order to obtain a competitive advantage over lighter opponents. To achieve fast weight reduction, athletes use a number of aggressive nutritional strategies so many of them place themselves at a high health-injury risk. In collegiate wrestling, a similar problem has been observed and three wrestlers died in 1997 due to rapid weight loss regimes. After these deaths, the National Collegiate Athletic Association had implemented a successful weight management program which was proven to improve weight management behavior. No similar program has ever been discussed by judo federations even though judo competitors present a comparable inappropriate pattern of weight control. In view of this, the basis for a weight control program is provided in this manuscript, as follows: competition should begin within 1 hour after weigh-in, at the latest; each athlete is allowed to be weighed-in only once; rapid weight loss as well as artificial rehydration (i.e., saline infusion) methods are prohibited during the entire competition day; athletes should pass the hydration test to get their weigh-in validated; an individual minimum competitive weight (male athletes competing at no less than 7% and females at no less than 12% of body fat) should be determined at the beginning of each season; athletes are not allowed to compete in any weight class that requires weight reductions greater than 1.5% of body weight per week. In parallel, educational programs should aim at increasing the athletes', coaches' and parents' awareness about the risks of aggressive nutritional strategies as well as healthier ways to properly manage body weight. PMID:20441594

  14. Evaluation of the proposed pilot groundwater pump and treat demonstration for the Paducah Gaseous Diffusion Plant. Environmental Restoration Program

    Energy Technology Data Exchange (ETDEWEB)

    Bodenstein, G.W.; Bonczek, R.R.; Early, T.O.; Hale, T.B.; Huff, D.D.; Nickelson, M.D.; Rightmire, C.T.

    1992-11-01

    This report contains the evaluation and recommendations of a Groundwater Corrective Actions Review Team. The primary goal is to evaluate the technical merit of and the need to implement a proposed groundwater pump-and-treat demonstration project for the Northwest contaminant plume at Paducah, Kentucky. A key distinction recognized by the review team is that the proposed project is intended to be a full-scale hydraulic containment of contaminants migrating from the sources of the plume, not plume remediation. The key questions incorporated into this plan are whether (1) dense, nonaqueous-phase liquids (DNAPLS) are present in the Regional Gravel Aquifer (RGA) at the source of the plume and (2) {sup 99}Tc removal must be included as part of any groundwater treatment process. The first question cannot be answered until the contaminant sources are better defined; the second question requires further risk assessment and/or a policy decision by DOE. Technical evaluation by the review team suggests that the recommended course of action be to modify the proposed work plan to include accurate identification of the sources of contaminants and vertical distribution of contaminants within the Northwest plume before a decision is made on the preferred source-control option. If DNAPLs are not present in the RGA, removal or containment of the sources is recommended. If DNAPLs are present, then hydraulic containment will be required. Finally, the review team recognizes that it is necessary to initiate a more comprehensive analysis of sitewide remediation needs to create links between action taken for the Northwest plume and action taken for other contamination sites at PGPD.

  15. The two-hit hypothesis for neuroinflammation: role of exogenous ATP in modulating inflammation in the brain

    Directory of Open Access Journals (Sweden)

    Bernd L. Fiebich

    2014-09-01

    Full Text Available Brain inflammation is a common occurrence following responses to varied insults such as bacterial infections, stroke, traumatic brain injury and neurodegenerative disorders. A common mediator for these varied inflammatory responses is prostaglandin E2 (PGE2, produced by the enzymatic activity of cyclooxygenases (COX 1 and 2. Previous attempts to reduce neuronal inflammation through COX inhibition, by use of nonsteroidal anti-inflammatory drugs (NSAIDs, have met with limited success. We are proposing the two-hit model for neuronal injury – an initial localized inflammation mediated by PGE2 (first hit and the simultaneous release of adenosine triphosphate (ATP by injured cells (second hit, which significantly enhances the inflammatory response through increased synthesis of PGE2. Several evidences on the role of exogenous ATP in inflammation have been reported, including contrary instances where extracellular ATP reduces inflammatory events. In this review, we will examine the current literature on the role of P2 receptors, to which ATP binds, in modulating inflammatory reactions during neurodegeneration. Targeting the P2 receptors, therefore, provides a therapeutic alternative to reduce inflammation in the brain. P2 receptor-based anti-inflammatory drugs (PBAIDs will retain the activities of essential COX enzymes, yet will significantly reduce neuroinflammation by decreasing the enhanced production of PGE2 by extracellular ATP.

  16. COMPARATIVE ANALYSIS OF THE MAIN UNIT-LINKED INVESTMENT PROGRAMS PROPOSED BY THE ROMANIAN LIFE INSURANCE COMPANIES

    Directory of Open Access Journals (Sweden)

    CIUMAS Cristina

    2017-06-01

    Full Text Available An important component of the activity carried out by the insurance companies is the investment of the premiums paid by policyholders in various types of assets, in order to obtain higher yields than those guaranteed by the insurance contracts, while providing the necessary liquidity for the payment of insurance claims in case of occurrence of the assumed risks. This research contributes to the existing literature regarding the study of investment alternatives, with an exclusive focus on the investment in unit-linked life insurance. A special place in this study is the comparative analysis of the main unit-linked investment programs offered by Romanian insurance companies.

  17. Draft Supplement to the Environmental Statement Fiscal Year 1975 Proposed Program : Facility Location Evaluation for Richland Area Electrical Service.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1974-01-01

    The proposal involves the construction of 35.2 miles of 230-kV and 3.6 miles of 115-kV transmission line as well as the associated construction of three new substation facilities. A total of 697 acres of the new easement required for the proposed transmission facilities would occur entirely within the Atomic Energy Commission's Hanford Reservation where land uses and public access are already restricted for safety reasons. The removal of vegetative cover in the reservation during construction operations will increase an already high potential for wind erosion. An additional 5 miles of new right-of-way easement will be required outside of the Hanford Reservation crossing primarily sagebrush rangeland with some irrigated cropland being removed from production. Depending upon actual sites selected for the three new substation facilities a total of up to approximately 60 acres of sagebrush rangeland would be permanently removed from production. Disturbance of game in the immediate vicinity of the transmission facilities will occur during construction, as will some soil erosion primarily during and immediately after construction, siltation in nearby streams, disturbance of nearby residents from noise and dust during construction and some degration of AM reception immediately adjacent to the right-of-way. 15 figs.

  18. Therapeutic Patient Education in Cancer Pain Management: from Practice to Research: Proposals and Strategy of the French EFFADOL Program.

    Science.gov (United States)

    Prevost, Virginie; Clarisse, Bénédicte; Heutte, Natacha; Leconte, Alexandra; Bisson, Cécile; Bignon, Rachel; Cauchin, Sonia; Feuillet, Maryline; Gehanne, Sylvie; Gicquère, Maud; Grach, Marie-Christine; Guillaumé, Cyril; Le Gal, Christine; Le Garrec, Joelle; Lecaer, Franck; Lepleux, Isabelle; Millet, Anne-Laure; Ropartz, Marie-Claude; Roux, Nathalie; Hieng, Virith Sep; Van Delook, Carole; Le Chevalier, Aline; Delorme, Claire

    2017-08-13

    In the field of cancer pain, therapeutic patient education (TPE) allows patients to develop skills to better manage their pain. In the Lower Normandy region of France, the management of pain is based on networking, thus allowing proximity and accessibility for all concerned. We have thus designed and initiated a broad five-stage research program that includes the following: (1) training for caregivers in TPE; (2) identifying the educational expectations of patients and their relatives with regard to cancer pain; (3) the design of a TPE program; (4) the evaluation of its quality; and (5) the evaluation of its effectiveness by comparative randomization. This article presents this approach and more particularly the research phases (stages 2, 4, 5) for which the objectives, the methodology, and the expected results are justified. Among the key points, particular attention is paid to the evaluation of the educational dimension that provides patients with self-efficacy to participate actively in the management of their pain, their perception of changes in relation to it and its impact. The choice of a specific assessment criterion (subscale 9 of the Brief Pain Inventory) and of the step-wedge design are thus argued. This approach, which is based on a partnership between health care professionals and researchers, aims to demonstrate the benefits provided by TPE to patients in order to enable them to better manage their pain on a daily basis.

  19. Distinct neurological disorders with ATP1A3 mutations

    Science.gov (United States)

    Heinzen, Erin L.; Arzimanoglou, Alexis; Brashear, Allison; Clapcote, Steven J.; Gurrieri, Fiorella; Goldstein, David B.; Jóhannesson, Sigurður H.; Mikati, Mohamad A.; Neville, Brian; Nicole, Sophie; Ozelius, Laurie J.; Poulsen, Hanne; Schyns, Tsveta; Sweadner, Kathleen J.; van den Maagdenberg, Arn; Vilsen, Bente

    2014-01-01

    Genetic research has shown that mutations that modify the protein-coding sequence of ATP1A3, the gene encoding the α3 subunit of Na+/K+-ATPase, cause both rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. These discoveries link two clinically distinct neurological diseases to the same gene, however, ATP1A3 mutations are, with one exception, disease-specific. Although the exact mechanism of how these mutations lead to disease is still unknown, much knowledge has been gained about functional consequences of ATP1A3 mutations using a range of in vitro and animal model systems, and the role of Na+/K+-ATPases in the brain. Researchers and clinicians are attempting to further characterise neurological manifestations associated with mutations in ATP1A3, and to build on the existing molecular knowledge to understand how specific mutations can lead to different diseases. PMID:24739246

  20. A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase.

    Science.gov (United States)

    Ahmad, Zulfiqar; Hassan, Sherif S; Azim, Sofiya

    2017-11-20

    For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phytochemicals is based on tradition or word of mouth with few evidence-based studies. Moreover, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become pertinent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of dietary phytochemicals are known to inhibit ATP synthase. Structural modifications of phytochemicals have been shown to increase the inhibitory potency and extent of inhibition. Sitedirected mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can result in selective binding and inhibition of microbial ATP synthase. In this review, the therapeutic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective targeting of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. FIBROBLAST CYTOSKELETAL REMODELING INDUCED BY TISSUE STRETCH INVOLVES ATP SIGNALING

    OpenAIRE

    Langevin, HM; Fujita, T.; Bouffard, NA; Takano, T; Koptiuch, C; Badger, GJ; Nedergaard, M

    2013-01-01

    Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 minutes, returning to baseline at 60 min...

  2. Development and Validation of the Guide for Effective Nutrition Interventions and Education (GENIE): A Tool for Assessing the Quality of Proposed Nutrition Education Programs.

    Science.gov (United States)

    Hand, Rosa K; Abram, Jenica K; Brown, Katie; Ziegler, Paula J; Parrott, J Scott; Steiber, Alison L

    2015-01-01

    To develop and validate the Guide for Effective Nutrition Interventions and Education (GENIE), a checklist of research-based quality indicators for nutrition education programs. A prospective test of criterion validity and inter-rater reliability of a new tool comparing expert assessments and trained reviewer GENIE scores of the same nutrition education proposals. Ten nutrition education experts; 13 volunteer reviewers. GENIE's face, content, and criterion validity and inter-rater reliability compared using expert assessments and reviewer objective and subjective scores. Reviewer scores compared using Spearman correlation. Inter-rater reliability tested using intra-class correlation (ICC), Cronbach alpha, and ANOVA. Criterion validity tested using independent t test and point bi-serial correlation to compare reviewer with expert scores. Correlation found between total objective and total subjective scores. Agreement found between reviewers across proposals and categories considering subjective scores (F = 7.21, P validity and reliability of GENIE as a tool for nutrition education practitioners, researchers, and program funding agencies to accurately assess the quality of a variety of nutrition program plans. Copyright © 2015 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  3. Proposed 'grant-and-access' program with price caps could stimulate development of drugs for very rare diseases.

    Science.gov (United States)

    Valverde, Ana M; Reed, Shelby D; Schulman, Kevin A

    2012-11-01

    The 1983 Orphan Drug Act created incentives for the development of orphan drugs. Despite its successes, including a substantial increase in new drugs, approved orphan drugs still treat fewer than 5 percent of registered rare diseases. In addition, concerns have arisen about the high prices of many of these therapies, which can cost hundreds of thousands of dollars per patient each year. In this article, we propose a new "grant-and-access pathway," in which drug developers could opt to compete for federal grants to subsidize the costs of clinical testing. In return for the grant funding, companies would no longer claim orphan drug tax credits and would agree to price caps for marketed products based on the duration and costs associated with drug development, expected market size, and target rate of return. We identify scenarios in which such a policy could provide a net benefit to society.

  4. A Proposal for the Education based on the Information Technology in Technical High Schools, Linking Together Web Programming and Microcontroller

    Science.gov (United States)

    Shinozaki, Kenichi; Yanaru, Torao

    Recently, IT (Information Technology) have rapidly revolved and penetrated into the usual human life, with such as the household appliances and the mobile devices. Considering this strong change of social environment, what technology is introduced to satisfy the present educational needs and how to develop the teaching system is very important. Then in this paper, we describe the developed web-teaching material that links Xport, an embedded device server, with the control system using microcontroller technology. In the classes, we have implemented the lessons that utilize this system in the following subjects : programming technology, hardware technology, electronic circuit and practical training. Furthermore, because of high availability of the developed system through internet, it is also useful for the education on science and technical arts in general high schools or in junior high schools as well as in technical high schools.

  5. Analysis of Combined Data from Heterogeneous Study Designs: A Methodological Proposal from the Patient Navigation Research program

    Science.gov (United States)

    Roetzheim, Richard G.; Freund, Karen M.; Corle, Don K.; Murray, David M.; Snyder, Frederick R.; Kronman, Andrea C.; Jean-Pierre, Pascal; Raich, Peter C.; Holden, Alan E. C.; Darnell, Julie S.; Warren-Mears, Victoria; Patierno, Steven; Design, PNRP; Committee, Analysis

    2013-01-01

    Background The Patient Navigation Research Program (PNRP) is a cooperative effort of nine research projects, each employing its own unique study design. To evaluate projects such as PNRP, it is desirable to perform a pooled analysis to increase power relative to the individual projects. There is no agreed upon prospective methodology, however, for analyzing combined data arising from different study designs. Expert opinions were thus solicited from members of the PNRP Design and Analysis Committee Purpose To review possible methodologies for analyzing combined data arising from heterogeneous study designs. Methods The Design and Analysis Committee critically reviewed the pros and cons of five potential methods for analyzing combined PNRP project data. Conclusions were based on simple consensus. The five approaches reviewed included: 1) Analyzing and reporting each project separately, 2) Combining data from all projects and performing an individual-level analysis, 3) Pooling data from projects having similar study designs, 4) Analyzing pooled data using a prospective meta analytic technique, 5) Analyzing pooled data utilizing a novel simulated group randomized design. Results Methodologies varied in their ability to incorporate data from all PNRP projects, to appropriately account for differing study designs, and in their impact from differing project sample sizes. Limitations The conclusions reached were based on expert opinion and not derived from actual analyses performed. Conclusions The ability to analyze pooled data arising from differing study designs may provide pertinent information to inform programmatic, budgetary, and policy perspectives. Multi-site community-based research may not lend itself well to the more stringent explanatory and pragmatic standards of a randomized controlled trial design. Given our growing interest in community-based population research, the challenges inherent in the analysis of heterogeneous study design are likely to become

  6. [ATP pool and bioluminescence in psychrophilic bacteria Photobacterium phosphoreum].

    Science.gov (United States)

    Alekserova, L É; Alenina, K A; Efremenko, E N; Mazhul', M M; Piskunova, N F; Ismailov, A D

    2014-01-01

    Bioluminescence activity and ATP pool were investigated in the culture of psychrophilic bacteria Photobacterium phosphoreum collected-from the exponential and stationary growth phases, as well as immobilized in polyvinyl alcohol (PVA) cryogel. In liquid culture, ATP pool remained at an almost a constant level throughout the luminescence cycle (over 100 h). The ATP pool in the stationary-phase and PVA-immobilizedl cells remained constant throughout their incubation in the medium (over 200 h) and in 3% NaCl solution (over 100 h): Quantitative assessment of integral photon yield and ATP pool indicated that bioluminescence decay in growing or stationary cells was not caused by limitation by the energy substrates of the luciferase reaction. Kinetic and quantitative parameters of emission activity and ATP pool excluded the possibility of formation of the aldehyde substrate for luciferase via reduction of the relevant fatty acids in NADPH and ATP-dependent reductase reaction and its oxidation in the monooxygenase reaction. Our results indicate that the aliphatic aldehyde is not utilized in the process of light emission.

  7. Histone deacetylase inhibitors promote the expression of ATP2A3 gene in breast cancer cell lines.

    Science.gov (United States)

    Contreras-Leal, Erika; Hernández-Oliveras, Andrés; Flores-Peredo, Lucía; Zarain-Herzberg, Ángel; Santiago-García, Juan

    2016-10-01

    Recent studies have shown that expression of Sarco(endo)plasmic Reticulum Ca(2+) -ATPase 2 (SERCA2) is decreased in oral cancer; whereas expression of SERCA3 is considerably decreased or absent in human colon, gastric, breast, and lung cancers. The ATP2A2 and ATP2A3 genes encode SERCA2 and SERCA3 isoforms, respectively. Promoter methylation on CpG islands was responsible for the repression of ATP2A2 gene in human oral cancer samples. On the other hand, histone deacetylase inhibitors (HDACi) up-regulate ATP2A3 expression in gastric, colon, and lung cancer cells in culture, however, the molecular mechanism is unknown. In this study, we investigate whether HDACi and DNA methylation regulate ATP2A2 and ATP2A3 expression in human breast cancer cell lines. Results show a marked induction of SERCA3a and pan-SERCA3 mRNA expression in human MCF-7 and MDA-MB-231 cells treated with sodium butyrate (NaB) or trichostatin A (TSA); whereas SERCA2b mRNA expression did not change significantly. ChIP assays show that NaB or TSA treatment of MDA-MB-231 cells increases H3K9 acetylation on ATP2A3 promoter. NaB also decreases H3K9 trimethylation; suggesting that these modifications stimulate ATP2A3 gene expression, through a chromatin remodeling mechanism. In contrast, NaB or TSA do not increase H3K9-acetylation of ATP2A2 proximal promoter. In addition, treatment with 5-aza-2'-deoxycytidine did not affect SERCA2b and SERCA3a expression, suggesting that promoter methylation status does not alter their expression in these cell lines. We propose that alteration of SERCA2b/SERCA3a isoform expression ratio could affect calcium management within the cell, and thus, the cellular pathways regulated by calcium could be compromised, such as cellular proliferation or apoptosis. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  8. An ATP synthase harboring an atypical γ-subunit is involved in ATP synthesis in tomato fruit chromoplasts

    DEFF Research Database (Denmark)

    Pateraki, Irini; Renato, Marta; Azcõn-Bieto, Joaquín

    2013-01-01

    Chromoplasts are non-photosynthetic plastids specialized in the synthesis and accumulation of carotenoids. During fruit ripening, chloroplasts differentiate into photosynthetically inactive chromoplasts in a process characterized by the degradation of the thylakoid membranes, and by the active...... synthesis and accumulation of carotenoids. This transition renders chromoplasts unable to photochemically synthesize ATP, and therefore these organelles need to obtain the ATP required for anabolic processes through alternative sources. It is widely accepted that the ATP used for biosynthetic processes...... the involvement of a plastidial ATP synthase harboring an atypical γ-subunit induced during ripening, which lacks the regulatory dithiol domain present in plant and algae chloroplast γ-subunits. Silencing of this atypical γ-subunit during fruit ripening impairs the capacity of isolated chromoplast to synthesize...

  9. ATP binding and hydrolysis by Saccharomyces cerevisiae Msh2-Msh3 are differentially modulated by mismatch and double-strand break repair DNA substrates.

    Science.gov (United States)

    Kumar, Charanya; Eichmiller, Robin; Wang, Bangchen; Williams, Gregory M; Bianco, Piero R; Surtees, Jennifer A

    2014-06-01

    In Saccharomyces cerevisiae, Msh2-Msh3-mediated mismatch repair (MMR) recognizes and targets insertion/deletion loops for repair. Msh2-Msh3 is also required for 3' non-homologous tail removal (3'NHTR) in double-strand break repair. In both pathways, Msh2-Msh3 binds double-strand/single-strand junctions and initiates repair in an ATP-dependent manner. However, we recently demonstrated that the two pathways have distinct requirements with respect to Msh2-Msh3 activities. We identified a set of aromatic residues in the nucleotide binding pocket (FLY motif) of Msh3 that, when mutated, disrupted MMR, but left 3'NHTR largely intact. One of these mutations, msh3Y942A, was predicted to disrupt the nucleotide sandwich and allow altered positioning of ATP within the pocket. To develop a mechanistic understanding of the differential requirements for ATP binding and/or hydrolysis in the two pathways, we characterized Msh2-Msh3 and Msh2-msh3Y942A ATP binding and hydrolysis activities in the presence of MMR and 3'NHTR DNA substrates. We observed distinct, substrate-dependent ATP hydrolysis and nucleotide turnover by Msh2-Msh3, indicating that the MMR and 3'NHTR DNA substrates differentially modify the ATP binding/hydrolysis activities of Msh2-Msh3. Msh2-msh3Y942A retained the ability to bind DNA and ATP but exhibited altered ATP hydrolysis and nucleotide turnover. We propose that both ATP and structure-specific repair substrates cooperate to direct Msh2-Msh3-mediated repair and suggest an explanation for the msh3Y942A separation-of-function phenotype. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained.

    Science.gov (United States)

    Cai, Shi-Ying; Gautam, Samir; Nguyen, Trong; Soroka, Carol J; Rahner, Christoph; Boyer, James L

    2009-03-01

    Progressive familial intrahepatic cholestasis 1 (PFIC1) results from mutations in ATP8B1, a putative aminophospholipid flippase. Conflicting hypotheses have been proposed for the pathogenesis of PFIC1. The aim of this study was to determine whether ATP8B1 deficiency produces cholestasis by altering the activity of the farnesoid X receptor (FXR) or by impairing the structure of the canalicular membrane. ATP8B1/Atp8b1 was knocked down in human and rat hepatocytes and Caco2 cells using adenoviral and oligonucleotide small interfering RNAs. ATP8B1 messenger RNA and protein expression was greatly reduced in human and rat cells. In contrast, FXR expression and several FXR-dependent membrane transporters (bile salt export pump [BSEP], multidrug resistance-associated protein [MRP] 2) were unchanged at messenger RNA or protein levels in ATP8B1-deficient cells, whereas Mrp3 and Mrp4 were up-regulated in rat hepatocytes. FXR activity remained intact in these cells, as evidenced by 6alpha-ethyl chenodeoxycholic acid-mediated induction of small heterodimer partner, BSEP, and multidrug-resistant protein (MDR) 3/Mdr2. Fluorescent substrate excretion assays indicate that Bsep function was significantly reduced in Atp8b1-deficient rat hepatocytes, although Bsep remained localized to the canalicular membrane. Exposure to the hydrophobic bile acid CDCA resulted in focal areas of canalicular membrane disruption by electron microscopy and luminal accumulation of NBD-phosphatidylserine, consistent with the function of Atp8b1 as an aminophospholipid flippase. ATP8B1 deficiency predisposes to cholestasis by favoring bile acid-induced injury in the canalicular membrane but does not directly affect FXR expression, which may occur in PFIC1 as a secondary phenomenon associated with cholestasis.

  11. ATP binding and hydrolysis by Saccharomyces cerevisiae Msh2-Msh3 are differentially modulated by Mismatch and Double-strand Break Repair DNA substrates

    Science.gov (United States)

    Kumar, Charanya; Eichmiller, Robin; Wang, Bangchen; Williams, Gregory M.; Bianco, Piero R.; Surtees, Jennifer A.

    2014-01-01

    In Saccharomyces cerevisiae, Msh2-Msh3-mediated mismatch repair (MMR) recognizes and targets insertion/deletion loops for repair. Msh2-Msh3 is also required for 3′ non-homologous tail removal (3′NHTR) in double-strand break repair. In both pathways, Msh2-Msh3 binds double-strand/single-strand junctions and initiates repair in an ATP-dependent manner. However, we recently demonstrated that the two pathways have distinct requirements with respect to Msh2-Msh3 activities. We identified a set of aromatic residues in the nucleotide binding pocket (FLY motif) of Msh3 that, when mutated, disrupted MMR, but left 3′ NHTR largely intact. One of these mutations, msh3Y942A, was predicted to disrupt the nucleotide sandwich and allow altered positioning of ATP within the pocket. To develop a mechanistic understanding of the differential requirements for ATP binding and/or hydrolysis in the two pathways, we characterized Msh2-Msh3 and Msh2-msh3Y942A ATP binding and hydrolysis activities in the presence of MMR and 3′ NHTR DNA substrates. We observed distinct, substrate-dependent ATP hydrolysis and nucleotide turnover by Msh2-Msh3, indicating that the MMR and 3′ NHTR DNA substrates differentially modify the ATP binding/hydrolysis activities of Msh2-Msh3. Msh2-msh3Y942A retained the ability to bind DNA and ATP but exhibited altered ATP hydrolysis and nucleotide turnover. We propose that both ATP and structure-specific repair substrates cooperate to direct Msh2-Msh3-mediated repair and suggest an explanation for the msh3Y942A separation-of-function phenotype. PMID:24746922

  12. Facility Location Evaluation for Ellensburg Service Study Area 78-2 : Draft Environmental Supplement, Fiscal Year 1978 Proposed Program.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1977-03-21

    Construction of transmission facilities to provide for increasing electrical loads in the Ellensburg Service Area is proposed. The alternatives considered include nonconstruction and 3 alternative route locations for the transmission lines. The alternatives involve the construction of between 2 and 4 miles of new 115-kV transmission line and the addition of a new 115-12.5-kV substation. Depending on the final route location chosen, between 2 and 3 acres of new right-of-way would be required for the line. In all cases, approximately 2 acres would be required for a new substation. Only one alternative would require access road construction and that would be limited to 1/2 mile. Vegetation removal would be limited to less than 4 total acres for the line and substation. Minimal erosion and sedimentation would occur. Disturbances to agricultural lands would occur. Disturbances to agricultural lands would be minor and short-term. Visual impacts would occur, as well as noise and other minor disturbances during construction. 18 references, 13 figures, 9 tables.

  13. Death Valley Lower Carbonate Aquifer Monitoring Program Wells Down gradient of the Proposed Yucca Mountain Nuclear Waste Repository

    Energy Technology Data Exchange (ETDEWEB)

    Inyo County

    2006-07-26

    Inyo County has participated in oversight activities associated with the Yucca Mountain Nuclear Waste Repository since 1987. The overall goal of these studies are the evaluation of far-field issues related to potential transport, by ground water, or radionuclides into Inyo County, including Death Valley, and the evaluation of a connection between the Lower Carbonate Aquifer (LCA) and the biosphere. Our oversight and completed Cooperative Agreement research, and a number of other investigators research indicate that there is groundwater flow between the alluvial and carbonate aquifers both at Yucca Mountain and in Inyo County. In addition to the potential of radionuclide transport through the LCA, Czarnecki (1997), with the US Geological Survey, research indicate potential radionuclide transport through the shallower Tertiary-age aquifer materials with ultimate discharge into the Franklin Lake Playa in Inyo County. The specific purpose of this Cooperative Agreement drilling program was to acquire geological, subsurface geology, and hydrologic data to: (1) establish the existence of inter-basin flow between the Amargosa Basin and Death Valley Basin; (2) characterize groundwater flow paths in the LCA through Southern Funeral Mountain Range, and (3) Evaluation the hydraulic connection between the Yucca Mountain repository and the major springs in Death Valley through the LCA.

  14. Extracellular ATP in the lymphohematopoietic system: P2Z purinoceptors and membrane permeabilization

    Directory of Open Access Journals (Sweden)

    Persechini P.M.

    1998-01-01

    Full Text Available The effects of extracellular nucleosides and nucleotides on many organs and systems have been recognized for almost 50 years. The effects of extracellular ATP (ATPo, UTPo, ADPo, and other agonists are mediated by P2 purinoceptors. One of the most dramatic effects of ATPo is the permeabilization of plasma membranes to low molecular mass solutes of up to 900 Da. This effect is evident in several cells of the lymphohematopoietic system and is supposed to be mediated by P2Z, an ATP4--activated purinoceptor. Here, we review some basic information concerning P2 purinoceptors and focus our attention on P2Z-associated phenomena displayed by macrophages. Using fluorescent dye uptake, measurement of free intracellular Ca2+ concentration and electrophysiological recordings, we elucidate some of the events that follow the application of ATP to the extracellular surface of macrophages. We propose a regulatory mechanism for the P2Z-associated permeabilization pore. The presence of P2 purinoceptors in cells of the lymphohematopoietic system makes them potential candidates to mediate immunoregulatory events

  15. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    Science.gov (United States)

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)+ ratio. PMID:24554722

  16. TRPA1 and TRPV4 activation in human odontoblasts stimulates ATP release.

    Science.gov (United States)

    Egbuniwe, O; Grover, S; Duggal, A K; Mavroudis, A; Yazdi, M; Renton, T; Di Silvio, L; Grant, A D

    2014-09-01

    The mechanism of pain in dentine hypersensitivity is poorly understood but proposed to result from the activation of dental sensory neurons in response to dentinal fluid movements. Odontoblasts have been suggested to contribute to thermal and mechanosensation in the tooth via expression of transient receptor potential (TRP) channels. However, a mechanism by which odontoblasts could modulate neuronal activity has not been demonstrated. In this study, we investigated functional TRP channel expression in human odontoblast-like cells and measured ATP release in response to TRP channel activation. Human immortalized dental pulp cells were driven toward an odontoblast phenotype by culture in conditioned media. Functional expression of TRP channels was determined with reverse transcription polymerase chain reaction and ratiometric calcium imaging with Fura-2. ATP release was measured using a luciferin-luciferase assay. Expression of mRNA for TRPA1, TRPV1, and TRPV4 but not TRPM8 was detected in odontoblasts by reverse transcription polymerase chain reaction. Expression of TRPV4 protein was detected by Western blotting and immunocytochemistry. The TRPA1 agonists allyl isothiocyanate and cinnamaldehyde and the TRPV4 agonist GSK1016790A caused a concentration-dependent increase in intracellular Ca(2+) concentration that was inhibited by the selective antagonists HC030031, AP18, and HC067047, respectively. In contrast, exposure to the TRPV1 agonist capsaicin or the TRPM8 agonist icilin had no effect on intracellular Ca(2+) concentration. Treatment with allyl isothiocyanate, cinnamaldehyde, or GSK1016790A caused an increase in ATP concentration in culture medium that was abolished by preincubation with TRP channel antagonists. These data demonstrate that activation of TRPA1 and TRPV4 channels in human odontoblast-like cells can stimulate ATP release. We were unable to confirm the presence of thermosensitive TRPV1 and TRPM8 that has previously been reported in odontoblasts.

  17. Sympathetic nerve-derived ATP regulates renal medullary blood flow via vasa recta pericytes

    Directory of Open Access Journals (Sweden)

    Scott S Wildman

    2013-10-01

    Full Text Available Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta, and therefore may be able to regulate medullary blood flow (MBF. Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesise that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is

  18. Cervical anterior transpedicular screw fixation (ATPS)--Part II. Accuracy of manual insertion and pull-out strength of ATPS.

    Science.gov (United States)

    Koller, Heiko; Acosta, Frank; Tauber, Mark; Fox, Michael; Martin, Hudelmaier; Forstner, Rosmarie; Augat, Peter; Penzkofer, Rainer; Pirich, Christian; Kässmann, H; Resch, Herbert; Hitzl, Wolfgang

    2008-04-01

    Reconstruction after multilevel decompression of the cervical spine, especially in the weakened osteoporotic, neoplastic or infectious spine often requires circumferential stabilization and fusion. To avoid the additional posterior surgery in these cases while increasing rigidity of anterior-only screw-plate constructs, the authors introduce the concept of anterior transpedicular screw (ATPS) fixation. We demonstrated its morphological feasibility as well as its indications in a previous study in Part I of our project. Consequently, the objectives of the current study were to assess the ex vivo accuracy of placing ATPS into the cervical vertebra as well as the biomechanical performance of ATPS in comparison to traditional vertebral body screws (VBS) in terms of pull-out strength (POS). Twenty-three ATPS were inserted alternately to two screws into the pedicles and vertebral bodies, respectively, of six cadaveric specimens from C3-T1. For insertion of ATPS, a manual fluoroscopically assisted technique was used. Pre- and post insertional CT-scans were used to assess accuracy of ATPS insertion in the axial and sagittal planes. A newly designed grading system and accuracy score were used to delineate accuracy of ATPS insertion. Following insertion of screws, 23 ATPS and 22 VBS were subjected to pull-out testing (POT). The bone mineral density (BMD) of each specimen was assessed prior to POT. Statistical analysis showed that the incidence of correctly placed screws and non-critical pedicles breaches in axial plane was 78.3%, and 95.7% in sagittal plane. Hence, according to our definition of "critical" pedicle breach that exposes neurovascular structures at risk, 21.7% (n = 5) of all ATPS inserted showed a critical pedicle breach in axial plane. Notably, no critical pedicle perforation occurred at the C6 to T1 levels. Pull-out testing of ATPS and VBS revealed that pull-out resistance of ATPS was 2.5-fold that of VBS. Mean POS of 23 ATPS with a mean BMD of 0.566 g/cm(2

  19. ATP11C targets basolateral bile salt transporter proteins in mouse central hepatocytes

    NARCIS (Netherlands)

    de Waart, Dirk R.; Naik, Jyoti; Utsunomiya, Karina S.; Duijst, Suzanne; Ho-Mok, Kam; Bolier, A. Ruth; Hiralall, Johan; Bull, Laura N.; Bosma, Piter J.; Oude Elferink, Ronald P. J.; Paulusma, Coen C.

    2016-01-01

    ATP11C is a homolog of ATP8B1, both of which catalyze the transport of phospholipids in biological membranes. Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis type1 in humans, which is characterized by a canalicular cholestasis. Mice deficient in ATP11C are characterized by a

  20. Phylogenetic analysis of the thylakoid ATP/ADP carrier reveals new insights into its function restricted to green plants

    Directory of Open Access Journals (Sweden)

    Cornelia eSpetea

    2012-01-01

    Full Text Available ATP is the common energy currency of cellular metabolism in all living organisms. Most of them synthesize ATP in the cytosol or on the mitochondrial inner membrane, whereas land plants, algae and cyanobacteria also produce it on the thylakoid membrane during the light-dependent reactions of photosynthesis. From the site of synthesis, ATP is transported to the site of utilization via intracellular membranes transporters. One major type of ATP transporter is represented by the mitochondrial ADP/ATP carrier family. Here we review a recently characterized member, namely the thylakoid ATP/ADP carrier from Arabidopsis thaliana (AtTAAC. Thus far, no orthologues of this carrier have been characterized in other organisms, although similar sequences can be recognized in many sequenced genomes. Protein Sequence database searches and phylogenetic analyses indicate the absence of TAAC in cyanobacteria and its appearance early in the evolution of photosynthetic eukaryotes. The TAAC clade is composed of carriers found in land plants and some green algae, but no proteins from other photosynthetic taxa, such as red algae, brown algae and diatoms. This implies that TAAC-like sequences arose only once before the divergence of green algae and land plants. Based on these findings, it is proposed that TAAC may have evolved in response to the need of a new activity in higher photosynthetic eukaryotes. This activity may provide the energy to drive reactions during biogenesis and turnover of photosynthetic complexes, which are heterogenously distributed in a thylakoid membrane system composed of appressed and non-appressed regions.

  1. KREBER`S ADVENTURES: COMPUTER GAME ABOUT THE ATP FORMATION

    Directory of Open Access Journals (Sweden)

    F. J. Baêta

    2015-08-01

    Full Text Available Introduction: Biochemistry, as well as other subjects related to molecular area, have several abstract and difficult concepts to be understood, therefore, many educational innovations have been developed, highlighting the digital games. The digital games feature a playful and motivational character that encourages students during the concepts learning, with a different way to learning the concepts studied. Objectives: The objective of this study was the development of a computer game focused on the concepts of ATP formation, including the glycolytic pathway, Krebs cycle and Electron Transport Chain, as well as aspects related to the regulation, and evaluate the usability of it, as well as some evidence of its educational potential. Material and methods: The development of the game followed the following steps: definition of the subject; understanding of game developer (it was chosen the GameMaker; storyboard creation of the game; prototyping, implementation and usability testing. For the evaluation, inspection usability was performed (without involving end users and subsequently the cognitive route and the usability questionnaire (the latter two with students of the discipline of Biochemistry. Results: The game approached the energy metabolism in three phases: the glycolytic pathway, Krebs cycle and electron transport chain. Each phase has a different purpose, with some questions about the ways. To complete the game, you must correctly answer the questions, avoid the obstacles and achieve the goals of each phase. After usability testing, it found that users could, in a playful manner, actively interact with the content addressed and, through the difficulties presented in the game, had the opportunity to expand and review their knowledge. Conclusions: The game was identified as a motivating and innovative proposal for  teaching, and it had good usability for undergraduate students. The ludic worked as a pedagogical practice encourages student

  2. Facility Location Evaluation for Shelton-Kitsap 230-kV Line, Study Area 75-4. Draft supplement to the Environmental Statement Fiscal Year 1976 Proposed Program.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1974-10-22

    This report discusses alternative route locations for the proposed construction of a 31.6-mile, 230-kV transmission line from Shelton, Washington, to Kitsap Substation near Port Orchard, Washington. The new line would replace an existing 115-kV wood-pole line for 28.8 miles and has the potential to replace or parallel for 2.8 miles. Approximately 22.6 miles of commercial Christmas trees growing on the existing right-of-way will be removed during the construction of this facility. Depending on the alternative chosen, for the last 2.8 miles, increased right-of-way width could require from 9 to 24 acres of additional tree cover, primarily Douglas-fir. Alternatives considered are: (1) nonconstruction, and (2) replacement of existing 115-kV wood-pole line with replacement and parallel alternatives for the last 2.8 miles. Generation alternatives to all transmission construction, including alternative methods of electrical transmission and generation, transmission construction, disposal of slash and limiting the consumption of electricity, are discussed in BPA's General Construction and Maintenance Program Statement and the Annual Proposed Program Environmental Statement.

  3. ATP hydrolyzing salivary enzymes of caterpillars suppress plant defenses.

    Directory of Open Access Journals (Sweden)

    Shuang Wu

    Full Text Available The oral secretions of herbivores are important recognition cues that can be used by plants to mediate induced defenses. In this study, a degradation of adenosine-5'-triphosphate (ATP in tomato leaves was detected after treatment with Helicoverpa zea saliva. Correspondingly, a high level of ATPase activity in saliva was detected and three ATP hydrolyzing enzymes: apyrase, ATP synthase and ATPase 13A1 were identified in salivary glands. To determine the functions of these proteins in mediating defenses, they were cloned from H. zea and expressed in Escherichia coli. By applying the purified expressed apyrase, ATP synthase or ATPase 13A1 to wounded tomato leaves, it was determined that these ATP hydrolyzing enzymes suppressed the defensive genes regulated by the jasmonic acid and ethylene pathways in tomato plant. Suppression of glandular trichome production was also observed after treatment. Blood-feeding arthropods employ 5'-nucleotidase family of apyrases to circumvent host responses and the H. zea apyrase, is also a member of this family. The comparatively high degree of sequence similarity of the H. zea salivary apyrase with mosquito apyrases suggests a broader evolutionary role for salivary apyrases than previously envisioned.

  4. Fibroblast cytoskeletal remodeling induced by tissue stretch involves ATP signaling.

    Science.gov (United States)

    Langevin, Helene M; Fujita, Takumi; Bouffard, Nicole A; Takano, Takahiro; Koptiuch, Cathryn; Badger, Gary J; Nedergaard, Maiken

    2013-09-01

    Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 min, returning to baseline at 60 min. No increase in ATP was observed in tissue incubated without stretch or tissue stretched in the presence of the Rho kinase inhibitor Y27632. The increase in fibroblast cross sectional area in response to tissue stretch was blocked by both suramin (a purinergic receptor blocker) and apyrase (an enzyme that selectively degrades extracellular ATP). Furthermore, connexin channel blockers (octanol and carbenoxolone), but not VRAC (fluoxetine) or pannexin (probenecid) channel blockers, inhibited fibroblast expansion. Together, these results support a mechanism in which extracellular ATP signaling via connexin hemichannels mediate the active change in fibroblast shape that occurs in response to a static increase in tissue length. Copyright © 2013 Wiley Periodicals, Inc.

  5. Phenomenological analysis of ATP dependence of motor protein

    CERN Document Server

    Zhang, Yunxin

    2011-01-01

    In this study, through phenomenological comparison of the velocity-force data of processive motor proteins, including conventional kinesin, cytoplasmic dynein and myosin V, we found that, the ratio between motor velocities of two different ATP concentrations is almost invariant for any substall, superstall or negative external loads. Therefore, the velocity of motor can be well approximated by a Michaelis-Menten like formula $V=\\atp k(F)L/(\\atp +K_M)$, with $L$ the step size, and $k(F)$ the external load $F$ dependent rate of one mechanochemical cycle of motor motion in saturated ATP solution. The difference of Michaelis-Menten constant $K_M$ for substall, superstall and negative external load indicates, the ATP molecule affinity of motor head for these three cases are different, though the expression of $k(F)$ as a function of $F$ might be unchanged for any external load $F$. Verifications of this Michaelis-Menten like formula has also been done by fitting to the recent experimental data.

  6. [ATP content in cryopreserved sperm of Siberian white cranes Grus leucogeranus (Aves: Gruiformes)].

    Science.gov (United States)

    Maksudov, G Iu; Erokhin, A S; Nesterenko, O N; Panchenko, V G

    2002-01-01

    ATP contents were studied in the native and cryoconserved sperm of Siberian white cranes Grus leucogeranus using bioluminescence analysis. The ATP content in freshly obtained spermatozoa was 12.7 nmol/10(8) cells. No ATP was found in the seminal plasma. In the process of freezing-thawing, the ATP concentration in the spermatozoa decreased by 30%. The differences in the dynamics of ATP content during cryoconservation of sperm of white cranes and other birds and mammals are discussed.

  7. ATP level and caffeine efficiency on cytokinesis inhibition in plants.

    Science.gov (United States)

    López-Sáez, J F; Mingo, R; González-Fernández, A

    1982-06-01

    Plant cytokinesis appears to be a topographically organized process of exocytosis. Golgi vesicles which contain cell wall precursors are translocated during telophase, by interzonal microtubules, to the equatorial region of the mitotic apparatus where they fuse with each other giving rise to the new cell wall. Caffeine inhibits cytokinesis by hindering Golgi vesicle coalescence. The present results demonstrate that treatments which increase the cellular ATP level (adenosine, cycloheximide and anisomycin) counteract caffein-induced cytokinesis inhibition in meristem cells of onion root tips (Allium cepa L.), while treatments which decrease ATP level potentiate this caffeine effect (dinitrophenol, fluoroacetate, low oxygen tensions, etc.). We postulate that caffeine, in competition with the cellular ATP level, blocks cell plate formation by inhibiting a certain ATPase activity required for membrane fusion of Golgi vesicles.

  8. ATP measurements for monitoring microbial drinking water quality

    DEFF Research Database (Denmark)

    Vang, Óluva Karin

    Current standard methods for surveillance of microbial drinking water quality are culture based, which are laborious and time-consuming, where results not are available before one to three days after sampling. This means that the water may have been consumed before results on deteriorated water....... The overall aim of this PhD study was to investigate various methodological features of the ATP assay for a potential implementation on a sensor platform as a real-time parameter for continuous on-line monitoring of microbial drinking water quality. Commercial reagents are commonly used to determine ATP......, microbial quality in distributed water, detection of aftergrowth, biofilm formation etc. This PhD project demonstrated that ATP levels are relatively low and fairly stable in drinking water without chlorine residual despite different sampling locations, different drinking water systems and time of year...

  9. ATP economy of force maintenance in human tibialis anterior muscle

    DEFF Research Database (Denmark)

    Nakagawa, Yoshinao; Ratkevicius, Aivaras; Mizuno, Masao

    2005-01-01

    PURPOSE: The aim of this study was investigate ATP economy of force maintenance in the human tibialis anterior muscle during 60 s of anaerobic voluntary contraction at 50% of maximum voluntary contraction (MVC). METHODS: ATP turnover rate was evaluated using P magnetic resonance spectroscopy (P......) of the total ankle dorsiflexor muscle volume, which was 267 +/- 10 cm. Relative cross-sectional areas occupied by Type I, IIA, and IIB fibers in the tibialis anterior were 69.3 +/- 2.2, 27.4 +/- 2.76, and 3.2 +/- 1.0%, respectively. ATP economy of force maintenance did not change significantly during the 60-s...... contraction. It averaged at 4.81 +/- 0.42 N.s.micromol-1, and correlated with the relative cross-sectional area of the muscle occupied by Type I fiber (r = 0.73, P economy compared with those maintaining the force (3...

  10. Mechanism of ATP turnover inhibition in the EJC

    Science.gov (United States)

    Nielsen, Klaus H.; Chamieh, Hala; Andersen, Christian B.F.; Fredslund, Folmer; Hamborg, Kristiane; Le Hir, Hervé; Andersen, Gregers R.

    2009-01-01

    The exon junction complex (EJC) is deposited onto spliced mRNAs and is involved in many aspects of mRNA function. We have recently reconstituted and solved the crystal structure of the EJC core made of MAGOH, Y14, the most conserved portion of MLN51, and the DEAD-box ATPase eIF4AIII bound to RNA in the presence of an ATP analog. The heterodimer MAGOH/Y14 inhibits ATP turnover by eIF4AIII, thereby trapping the EJC core onto RNA, but the exact mechanism behind this remains unclear. Here, we present the crystal structure of the EJC core bound to ADP-AIF3, the first structure of a DEAD-box helicase in the transition-mimicking state during ATP hydrolysis. It reveals a dissociative transition state geometry and suggests that the locking of the EJC onto the RNA by MAGOH/Y14 is not caused by preventing ATP hydrolysis. We further show that ATP can be hydrolyzed inside the EJC, demonstrating that MAGOH/Y14 acts by locking the conformation of the EJC, so that the release of inorganic phosphate, ADP, and RNA is prevented. Unifying features of ATP hydrolysis are revealed by comparison of our structure with the EJC–ADPNP structure and other helicases. The reconstitution of a transition state mimicking complex is not limited to the EJC and eIF4AIII as we were also able to reconstitute the complex Dbp5–RNA–ADP–AlF3, suggesting that the use of ADP–AlF3 may be a valuable tool for examining DEAD-box ATPases in general. PMID:19033377

  11. The evidence for association of ATP2B2 polymorphisms with autism in Chinese Han population.

    Directory of Open Access Journals (Sweden)

    Wen Yang

    Full Text Available BACKGROUND: Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca(2+ from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population. METHODS: We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT program was used to perform association test for SNPs and haplotype analyses. RESULTS: This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013. While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = -2.482, p = 0.013; Z = -2.591, p = 0.0096. Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180-rs3774179 showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = -2.037, p = 0.042; Global p = 0.03. As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = -2.206, p = 0.027; Global p = 0.04, while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032. These results were still significant after using the permutation method to obtain empirical p values. CONCLUSIONS: Our research suggested that ATP2B2

  12. A goal programming approach for a joint design of macroeconomic and environmental policies: a methodological proposal and an application to the Spanish economy.

    Science.gov (United States)

    André, Francisco J; Cardenete, M Alejandro; Romero, Carlos

    2009-05-01

    The economic policy needs to pay increasingly more attention to the environmental issues, which requires the development of methodologies able to incorporate environmental, as well as macroeconomic, goals in the design of public policies. Starting from this observation, this article proposes a methodology based upon a Simonian satisficing logic made operational with the help of goal programming (GP) models, to address the joint design of macroeconomic and environmental policies. The methodology is applied to the Spanish economy, where a joint policy is elicited, taking into consideration macroeconomic goals (economic growth, inflation, unemployment, public deficit) and environmental goals (CO(2), NO( x ) and SO( x ) emissions) within the context of a computable general equilibrium model. The results show how the government can "fine-tune" its policy according to different criteria using GP models. The resulting policies aggregate the environmental and the economic goals in different ways: maximum aggregate performance, maximum balance and a lexicographic hierarchy of the goals.

  13. Fast monitoring of indoor bioaerosol concentrations with ATP bioluminescence assay using an electrostatic rod-type sampler.

    Directory of Open Access Journals (Sweden)

    Ji-Woon Park

    Full Text Available A culture-based colony counting method is the most widely used analytical technique for monitoring bioaerosols in both indoor and outdoor environments. However, this method requires several days for colony formation. In this study, our goal was fast monitoring (Sampling: 3 min, Detection: < 1 min of indoor bioaerosol concentrations with ATP bioluminescence assay using a bioaerosol sampler. For this purpose, a novel hand-held electrostatic rod-type sampler (110 mm wide, 115 mm long, and 200 mm tall was developed and used with a commercial luminometer, which employs the Adenosine triphosphate (ATP bioluminescence method. The sampler consisted of a wire-rod type charger and a cylindrical collector, and was operated with an applied voltage of 4.5 kV and a sampling flow rate of 150.7 lpm. Its performance was tested using Staphylococcus epidermidis which was aerosolized with an atomizer. Bioaerosol concentrations were measured using ATP bioluminescence method with our sampler and compared with the culture-based method using Andersen cascade impactor under controlled laboratory conditions. Indoor bioaerosol concentrations were also measured using both methods in various indoor environments. A linear correlation was obtained between both methods in lab-tests and field-tests. Our proposed sampler with ATP bioluminescence method may be effective for fast monitoring of indoor bioaerosol concentrations.

  14. Increased degradation of ATP is driven by memory regulatory T cells in kidney transplantation tolerance.

    Science.gov (United States)

    Durand, Maxim; Dubois, Florian; Dejou, Cécile; Durand, Eugénie; Danger, Richard; Chesneau, Mélanie; Brosseau, Carole; Guerif, Pierrick; Soulillou, Jean-Paul; Degauque, Nicolas; Eliaou, Jean-François; Giral, Magali; Bonnefoy, Nathalie; Brouard, Sophie

    2018-02-15

    Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process. The conserved proportion of memory Tregs leads to the establishment of a pro-tolerogenic balance in operationally tolerant patients. Memory Tregs in tolerant patients display normal capacity to degrade extracellular ATP/ADP. In contrast, memory Tregs from patients with stable graft function do not have this ability. Finally, in vitro, immunosuppressive drugs may favor the lower proportion of memory Tregs in stable patients, but they have no effect on CD39-dependent ATP degradation and do not explain memory Treg lack of extracellular ATP/ADP degradation ability. Thus, intrinsic active regulatory mechanisms may act long after immunosuppressive drug arrest in operationally tolerant patients and may contribute to kidney allograft tolerance via the maintenance of CD39 Treg function. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  15. Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Alexey Bogdanov

    2017-01-01

    Full Text Available Breast cancer is the first in incidence and the second in death among all solid tumors occurring in women. The identification of molecular genetic abnormalities in breast cancer is important to improve the results of treatment. In the present study, we analyzed microarray data of breast cancer expression profiling (NCBI GEO database, accession GSE65194, focusing on Na+/K+-ATPase coding genes. We found overexpression of the ATP1A1 and down-regulation of the ATP1A2. We expect that our research could help to improve the understanding of predictive and prognostic features of breast cancer.

  16. Implementation proposal of a water conservation and reuse program at the TRANSPETRO; Proposta de implementacao de um programa de conservacao e reuso de agua na TRANSPETRO

    Energy Technology Data Exchange (ETDEWEB)

    Martini, Andrea Dietrich; Alves, Anibal Jose Constantino; Melo Neto, Joao Evangelista de [TRANSPETRO - PETROBRAS Transporte S.A., Rio de Janeiro, RJ (Brazil)

    2008-07-01

    The great amount of water that is used by industries and the ascendant preoccupation about the quantity and quality of water resources in Brazil and in the world are important justifications to start thinking of more efficient proposals for water application. Between the alternatives for water consume reduction in industry there is the reuse as the principle of those. A study of PricewaterhouseCoopers about this matter at the main national industries identified that 48% have reuse goals. The present work intends to show a methodology and the justifications to implement a conservation and water reuse program at the Terminals of PETROBRAS Transporte S.A. - TRANSPETRO. Therefore are presented the many possible applications for reuse water at TRANSPETRO and the stages to the implementation of this kind of project. The methodology presented, based on FIESP Proposal, has as the objective both water consumed reduction and water discharged reduction. Then it must be realized an identification of several water consumed sources and water discharged sources, focusing on the many reuse possible. (author)

  17. Bioluminometric assay of ATP in mouse brain: Determinant factors ...

    Indian Academy of Sciences (India)

    Firefly luciferase bioluminescence (FLB) is a highly sensitive and specific method for the analysis of adenosine-5-triphosphate (ATP) in biological samples. Earlier attempts to modify the FLB test for enhanced sensitivity have been typically based on in vitro cell systems. This study reports an optimized FLB procedure for the ...

  18. Electrochemical Investigation of the Interaction between Catecholamines and ATP.

    Science.gov (United States)

    Taleat, Zahra; Estévez-Herrera, Judith; Machado, José D; Dunevall, Johan; Ewing, Andrew G; Borges, Ricardo

    2018-02-06

    The study of the colligative properties of adenosine 5'-triphosphate (ATP) and catecholamines has received the attention of scientists for decades, as they could explain the capabilities of secretory vesicles (SVs) to accumulate neurotransmitters. In this Article, we have applied electrochemical methods to detect such interactions in vitro, at the acidic pH of SVs (pH 5.5) and examined the effect of compounds having structural similarities that correlate with functional groups of ATP (adenosine, phosphoric acid and sodium phosphate salts) and catecholamines (catechol). Chronoamperometry and fast scan cyclic voltammetry (FSCV) provide evidence compatible with an interaction of the catechol and adenine rings. This interaction is also reinforced by an electrostatic interaction between the phosphate group of ATP and the protonated ammonium group of catecholamines. Furthermore, chronoamperometry data suggest that the presence of ATP subtlety reduces the apparent diffusion coefficient of epinephrine in aqueous media that adds an additional factor leading to a slower rate of catecholamine exocytosis. This adds another plausible mechanism to regulate individual exocytosis events to alter communication.

  19. Carbon and energy metabolism of atp mutants of Escherichia coli

    DEFF Research Database (Denmark)

    Jensen, Peter Ruhdal; Michelsen, Ole

    1992-01-01

    The membrane-bound H+-ATPase plays a key role in free-energy transduction of biological systems. We report how the carbon and energy metabolism of Escherichia coli changes in response to deletion of the atp operon that encodes this enzyme. Compared with the isogenic wild-type strain, the growth...

  20. Two-step ATP-driven opening of cohesin head.

    Science.gov (United States)

    Marcos-Alcalde, Íñigo; Mendieta-Moreno, Jesús I; Puisac, Beatriz; Gil-Rodríguez, María Concepción; Hernández-Marcos, María; Soler-Polo, Diego; Ramos, Feliciano J; Ortega, José; Pié, Juan; Mendieta, Jesús; Gómez-Puertas, Paulino

    2017-06-12

    The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the "head" structure, formed of the ATPase domains of Smc1A and Smc3 and Rad21. We investigate the mechanisms of the cohesin ring opening using techniques of free molecular dynamics (MD), steered MD and quantum mechanics/molecular mechanics MD (QM/MM MD). The study allows the thorough analysis of the opening events at the atomic scale: i) ATP hydrolysis at the Smc1A site, evaluating the role of the carboxy-terminal domain of Rad21 in the process; ii) the activation of the Smc3 site potentially mediated by the movement of specific amino acids; and iii) opening of the head domains after the two ATP hydrolysis events. Our study suggests that the cohesin ring opening is triggered by a sequential activation of the ATP sites in which ATP hydrolysis at the Smc1A site induces ATPase activity at the Smc3 site. Our analysis also provides an explanation for the effect of pathogenic variants related to cohesinopathies and cancer.

  1. Diversity and regulation of ATP sulfurylase in photosynthetic organisms

    Directory of Open Access Journals (Sweden)

    Laura ePrioretti

    2014-11-01

    Full Text Available ATP sulfurylase (ATPS catalyzes the first committed step in the sulfate assimilation pathway, the activation of sulfate prior to its reduction. ATPS has been studied in only a few model organisms and even in these cases to a much smaller extent than the sulfate reduction and cysteine synthesis enzymes. This is possibly because the latter were considered of greater regulatory importance for sulfate assimilation. Recent evidences (reported in this paper challenge this view and suggest that ATPSes may have a crucial regulatory role in sulfate assimilation, at least in algae.In the ensuing text, we summarize the current knowledge on ATPS, with special attention to the processes that control its activity and gene(s expression. Special attention is given to algae ATPSes. The focus on algae is the consequence of the fact that a comprehensive investigation of ATPSes revealed that the algal enzymes, especially those that are most likely involved in the pathway of sulfate reduction to cysteine, possess features that are not present in other organisms. For instance, algae ATPSes show a great diversity of isoforms and a high content of cysteine residues, whose positions are often conserved. It is interesting that, at least with respect to the number of cysteines, the ATPSes of eukaryotic algae are closer to the marine cyanobacteria of the genera Synechococcus and Prochlorococcus and are more distant from freshwater cyanobacteria. These characteristics might have evolved in parallel with the radiation of algae in the oceans and the increase of sulfate concentration in seawater.

  2. Familial Hemiplegic Migraine With ATP1A2 Mutations

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-05-01

    Full Text Available Three children with prolonged hemiplegia following severe unilateral headache and having mutations in ATP1A2 are reported from UCLA School of Medicine, Los Angeles, CA; University Children’s Hospital, Zurich, Switzerland; and Wake Forest University School of Medicine, Winston-Salem, NC.

  3. Distinct neurological disorders with ATP1A3 mutations

    NARCIS (Netherlands)

    Heinzen, E.L.; Arzimanoglou, A.; Brashear, A.; Clapcote, S.J.; Gurrieri, F.; Goldstein, D.B; Johannesson, S.H.; Mikati, M.A.; Neville, B.; Nicole, S.; Ozelius, L.J.; Poulsen, H.; Schyns, T.; Sweadner, K.J.; Maagdenberg, A. van den; Vilsen, B.; Koenderink, J.B.

    2014-01-01

    Genetic research has shown that mutations that modify the protein-coding sequence of ATP1A3, the gene encoding the alpha3 subunit of Na(+)/K(+)-ATPase, cause both rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. These discoveries link two clinically distinct neurological

  4. Animation Model to Conceptualize ATP Generation: A Mitochondrial Oxidative Phosphorylation

    Science.gov (United States)

    Jena, Ananta Kumar

    2015-01-01

    Adenosine triphosphate (ATP) is the molecular unit of intracellular energy and it is the product of oxidative phosphorylation of cellular respiration uses in cellular processes. The study explores the growth of the misconception levels amongst the learners and evaluates the effectiveness of animation model over traditional methods. The data…

  5. Hair bundles are specialized for ATP delivery via creatine kinase.

    NARCIS (Netherlands)

    Shin, J.B.; Streijger, F.; Beynon, A.J.; Peters, T.; Gadzala, L.; McMillen, D.; Bystrom, C.; Zee, C.E.E.M. van der; Wallimann, T.; Gillespie, P.G.

    2007-01-01

    When stimulated strongly, a hair cell's mechanically sensitive hair bundle may consume ATP too rapidly for replenishment by diffusion. To provide a broad view of the bundle's protein complement, including those proteins participating in energy metabolism, we used shotgun mass spectrometry methods to

  6. Treatment of heterotopic ossification through remote ATP hydrolysis.

    Science.gov (United States)

    Peterson, Jonathan R; De La Rosa, Sara; Eboda, Oluwatobi; Cilwa, Katherine E; Agarwal, Shailesh; Buchman, Steven R; Cederna, Paul S; Xi, Chuanwu; Morris, Michael D; Herndon, David N; Xiao, Wenzhong; Tompkins, Ronald G; Krebsbach, Paul H; Wang, Stewart C; Levi, Benjamin

    2014-09-24

    Heterotopic ossification (HO) is the pathologic development of ectopic bone in soft tissues because of a local or systemic inflammatory insult, such as burn injury or trauma. In HO, mesenchymal stem cells (MSCs) are inappropriately activated to undergo osteogenic differentiation. Through the correlation of in vitro assays and in vivo studies (dorsal scald burn with Achilles tenotomy), we have shown that burn injury enhances the osteogenic potential of MSCs and causes ectopic endochondral heterotopic bone formation and functional contractures through bone morphogenetic protein-mediated canonical SMAD signaling. We further demonstrated a prevention strategy for HO through adenosine triphosphate (ATP) hydrolysis at the burn site using apyrase. Burn site apyrase treatment decreased ATP, increased adenosine 3',5'-monophosphate, and decreased phosphorylation of SMAD1/5/8 in MSCs in vitro. This ATP hydrolysis also decreased HO formation and mitigated functional impairment in vivo. Similarly, selective inhibition of SMAD1/5/8 phosphorylation with LDN-193189 decreased HO formation and increased range of motion at the injury site in our burn model in vivo. Our results suggest that burn injury-exacerbated HO formation can be treated through therapeutics that target burn site ATP hydrolysis and modulation of SMAD1/5/8 phosphorylation. Copyright © 2014, American Association for the Advancement of Science.

  7. Clipboard: New paradigm for ATP synthesis and consumption

    Indian Academy of Sciences (India)

    2011-03-14

    Mar 14, 2011 ... Home; Journals; Journal of Biosciences; Volume 36; Issue 1. Clipboard: New paradigm for ATP synthesis and consumption. C Channakeshava. Volume 36 Issue 1 March 2011 pp 3-4. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/jbsc/036/01/0003-0004 ...

  8. Differential expression of ATP-dependent RNA helicase gene in ...

    African Journals Online (AJOL)

    AJL

    2012-02-07

    Feb 7, 2012 ... lysogeny broth (LB) medium at 4°C was induced for VBNC state; activated genes were detected using. mRNA differential display .... 191 amino acids. This cDNA sequence had a homology of 95 to 100% to the nucleotide of adenosine tripho- sphate (ATP)-dependent RNA helicase rh1B gene in different ...

  9. Cyclodextrin-based microcapsules as bioreactors for ATP biosynthesis.

    Science.gov (United States)

    Li, Jian-Hu; Wang, Yi-Fu; Ha, Wei; Liu, Yan; Ding, Li-Sheng; Li, Bang-Jing; Zhang, Sheng

    2013-09-09

    A biomimetic energy converter was fabricated via the assembly of CF0F1-ATPase on lipid-coated hollow nanocapsules composed of α-cyclodextrins/chitosan-graft-poly(ethylene glycol) methacrylate. Upon entrapped GOD into these capsules, the addition of glucose could trigger proton-motive force and then drive the rotation of ATPase to synthesize ATP.

  10. Activated sludge optimization using ATP in pulp and paper industry.

    Science.gov (United States)

    Bäckman, Göran; Gytel, Ulla

    2015-01-01

    The activated sludge process is an old technology, but still the most commonly used one for treatment of wastewater. Despite the wide spread usage the technology still suffers from instability (Tandoi et al. 2006) and high operating cost. Activated sludge processes often carry a large solids inventory. Managing the total inventory without interference is the key component of the optimization process described in this paper. Use of nutrients is common in pulp and paper effluent treatment. Feeding enough nutrients to support the biomass growth is a delicate balance. Overfeeding or underfeeding of nutrients can result in higher costs. Detrimental substances and toxic components in effluents entering a biological treatment system can cause severe, long lasting disturbances (Hynninen & Ingman 1998; Bergeron & Pelletier 2004). A LumiKem test kit is used to measure biological activity with adenosine triphosphate (ATP) in a pulp and paper mill. ATP data are integrated with other standardized mill parameters. Measurements of active volatile suspended solids based on ATP can be used to quantify the living biomass in the activated sludge process and to ensure that sufficient biomass is present in order to degrade the wastewater constituents entering the process. Information about active biomass will assist in optimizing sludge inventories and feeding of nutrients allowing the living biomass to re-populate to create optimal efficiency. ATP measurements can also be used to alert operators if any components toxic to bacteria are present in wastewater. The bio stress index represents the stress level experienced by the microbiological population. This parameter is very useful in monitoring toxicity in and around bioreactors. Results from the wastewater process optimization and ATP measurements showed that treatment cost could be reduced by approximately 20-30% with fewer disturbances and sustained biological activity compared to the reference period. This was mainly achieved by

  11. Concentration Gradient Effects of Sodium and Lithium Ions and Deuterium Isotope Effects on the Activities of H+-ATP Synthase from Chloroplasts

    Science.gov (United States)

    Chen, M.-F.; Wang, J.-D.; Su, T.-M.

    2009-01-01

    We explored the concentration gradient effects of the sodium and lithium ions and the deuterium isotope's effects on the activities of H+-ATP synthase from chloroplasts (CF0F1). We found that the sodium concentration gradient can drive the ATP synthesis reaction of CF0F1. In contrast, the lithium ion can be an efficient enzyme-inhibitor by blocking the entrance channel of the ion translocation pathway in CF0. In the presence of sodium or lithium ions and with the application of a membrane potential, unexpected enzyme behaviors of CF0F1 were evident. To account for these observations, we propose that both of the sodium and lithium ions could undergo localized hydrolysis reactions in the chemical environment of the ion channel of CF0. The protons generated locally could proceed to complete the ion translocation process in the ATP synthesis reaction of CF0F1. Experimental and theoretical deuterium isotope effects of the localized hydrolysis on the activities of CF0F1, and the energetics of these related reactions, support this proposed mechanism. Our experimental observations could be understood in the framework of the well-established ion translocation models for the H+-ATP synthase from Escherichia coli, and the Na+-ATP synthase from Propionigenium modestum and Ilyobacter tartaricus. PMID:19289072

  12. Extracellular ATP inhibits root gravitropism at concentrations that inhibit polar auxin transport

    Science.gov (United States)

    Tang, Wenqiang; Brady, Shari R.; Sun, Yu; Muday, Gloria K.; Roux, Stanley J.

    2003-01-01

    Raising the level of extracellular ATP to mM concentrations similar to those found inside cells can block gravitropism of Arabidopsis roots. When plants are grown in Murashige and Skoog medium supplied with 1 mM ATP, their roots grow horizontally instead of growing straight down. Medium with 2 mM ATP induces root curling, and 3 mM ATP stimulates lateral root growth. When plants are transferred to medium containing exogenous ATP, the gravity response is reduced or in some cases completely blocked by ATP. Equivalent concentrations of ADP or inorganic phosphate have slight but usually statistically insignificant effects, suggesting the specificity of ATP in these responses. The ATP effects may be attributable to the disturbance of auxin distribution in roots by exogenously applied ATP, because extracellular ATP can alter the pattern of auxin-induced gene expression in DR5-beta-glucuronidase transgenic plants and increase the response sensitivity of plant roots to exogenously added auxin. The presence of extracellular ATP also decreases basipetal auxin transport in a dose-dependent fashion in both maize (Zea mays) and Arabidopsis roots and increases the retention of [(3)H]indole-3-acetic acid in root tips of maize. Taken together, these results suggest that the inhibitory effects of extracellular ATP on auxin distribution may happen at the level of auxin export. The potential role of the trans-plasma membrane ATP gradient in auxin export and plant root gravitropism is discussed.

  13. How Native and Alien Metal Cations Bind ATP: Implications for Lithium as a Therapeutic Agent

    Science.gov (United States)

    Dudev, Todor; Grauffel, Cédric; Lim, Carmay

    2017-02-01

    Adenosine triphosphate (ATP), the major energy currency of the cell, exists in solution mostly as ATP-Mg. Recent experiments suggest that Mg2+ interacts with the highly charged ATP triphosphate group and Li+ can co-bind with the native Mg2+ to form ATP-Mg-Li and modulate the neuronal purine receptor response. However, it is unclear how the negatively charged ATP triphosphate group binds Mg2+ and Li+ (i.e. which phosphate group(s) bind Mg2+/Li+) and how the ATP solution conformation depends on the type of metal cation and the metal-binding mode. Here, we reveal the preferred ATP-binding mode of Mg2+/Li+ alone and combined: Mg2+ prefers to bind ATP tridentately to each of the three phosphate groups, but Li+ prefers to bind bidentately to the terminal two phosphates. We show that the solution ATP conformation depends on the cation and its binding site/mode, but it does not change significantly when Li+ binds to Mg2+-loaded ATP. Hence, ATP-Mg-Li, like Mg2+-ATP, can fit in the ATP-binding site of the host enzyme/receptor, activating specific signaling pathways.

  14. Description of Professional Master's Athletic Training Programs

    Science.gov (United States)

    Bowman, Thomas G.; Pitney, William A.; Mazerolle, Stephanie M.; Dodge, Thomas M.

    2015-01-01

    Context: Professional master's (PM) athletic training programs (ATPs) are becoming more popular as the profession debates what the entry-level degree should be for athletic training. More information is needed related to the potential benefits of PM ATPs. Objective: Describe the Commission on Accreditation of Athletic Training Education (CAATE)…

  15. Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis

    Directory of Open Access Journals (Sweden)

    Jonathon eTelianidis

    2013-08-01

    Full Text Available Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer’s, Parkinson’s and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-Type ATPases (copper-ATPases, ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration.

  16. On Local Coupling of Electron Transport and ATP-Synthesis System in Mitochondria. Theory and Experiment.

    Science.gov (United States)

    Eremeev, S A; Yaguzhinsky, L S

    2015-05-01

    A brief description of the principal directions for searching and investigating the model of local coupling between respiration and phosphorylation proposed by R. Williams is given in this paper. We found conditions where it was possible to reveal typical functional special features of the mitochondrial phosphorylating system. According to the theory, such special features should be observed experimentally if the mitochondrial phosphorylating system operated in the state of a supercomplex. It was proved that the phosphorylating system is able to operate in two states: P. Mitchell state and R. Williams state. It was demonstrated that in the ATP synthesis reaction, ATP-synthase (F1F0) was able to use thermodynamic potential of Bronsted acids as a source of energy. It was shown using a double-inhibitor titration technique that when the phosphorylating system operated in the supercomplex state, the electron transfer system and ATP-synthesis system were docked rigidly. A model system of chemical synthesis of membrane-bound proton fraction (Bronsted acids), carrying a free energy excess, was developed on the model of bilayer lipid membrane. Catalysts selectively accelerating proton detachment of this fraction were also found. The formation of a Bronsted acids fraction carrying free energy excess was recorded during the operation of proton pumps on mitochondrial and mitoplastic membranes. In the experimental part of the work, a brief description is given of studies on new uncouplers that transfer the phosphorylation system from the local coupling state to the state of transmembrane proton transfer. Thus, they accelerated the respiration of mitochondria and decreased the ADP/O parameter.

  17. Environmental Assessment for Selection and Operation of the Proposed Field Research Centers for the Natural and Accelerated Bioremediation Research (NABIR) Program

    Energy Technology Data Exchange (ETDEWEB)

    N/A

    2000-04-18

    The US Department of Energy (DOE) Office of Biological and Environmental Research (OBER), within the Office of Science (SC), proposes to add a Field Research Center (FRC) component to the existing Natural and Accelerated Bioremediation Research (NABIR) Program. The NABIR Program is a ten-year fundamental research program designed to increase the understanding of fundamental biogeochemical processes that would allow the use of bioremediation approaches for cleaning up DOE's contaminated legacy waste sites. An FRC would be integrated with the existing and future laboratory and field research and would provide a means of examining the fundamental biogeochemical processes that influence bioremediation under controlled small-scale field conditions. The NABIR Program would continue to perform fundamental research that might lead to promising bioremediation technologies that could be demonstrated by other means in the future. For over 50 years, DOE and its predecessor agencies have been responsible for the research, design, and production of nuclear weapons, as well as other energy-related research and development efforts. DOE's weapons production and research activities generated hazardous, mixed, and radioactive waste products. Past disposal practices have led to the contamination of soils, sediments, and groundwater with complex and exotic mixtures of compounds. This contamination and its associated costs and risks represents a major concern to DOE and the public. The high costs, long duration, and technical challenges associated with remediating the subsurface contamination at DOE sites present a significant need for fundamental research in the biological, chemical, and physical sciences that will contribute to new and cost-effective solutions. One possible low-cost approach for remediating the subsurface contamination of DOE sites is through the use of a technology known as bioremediation. Bioremediation has been defined as the use of microorganisms to

  18. PROPUESTA PARA EL DESARROLLO DE INSTRUMENTOS DE AUTOEVALUACIÓN PARA PROGRAMAS EDUCATIVOS A DISTANCIA (PROPOSAL FOR THE DEVELOPMENT OF SELF-ASSESSMENT INSTRUMENTS FOR DISTANCE EDUCATION PROGRAMS

    Directory of Open Access Journals (Sweden)

    García Martínez Verónica

    2011-08-01

    Full Text Available Resumen:El presente trabajo expone la etapa inicial de un proyecto conjunto entre la Universidad Juárez Autónoma de Tabasco (UJAT y la Universidad Autónoma de Chiapas (UNACH, México; se trata de una estrategia diseñada para elaborar mecanismos que permitan a los programas virtuales autoevaluarse. La propuesta surge como resultado de la aplicación de un modelo de autoevaluación de programas a distancia diseñado por la Asociación Nacional de Universidades e Instituciones de Educación Superior (ANUIES y tomado como referencia para instrumentar en la UJAT, un ejercicio de autodiagnóstico durante el periodo 2008-2009. Los resultados mostraron la necesidad de pensar en mecanismos de evaluación situados en el contexto regional. La propuesta descansa, principalmente, en la revisión documental y en el panel de expertos elegidos mediante el método Delphi y Método combinado TZ. La estrategia metodológica consta de cuatro etapas: a revisión de modelos de evaluación; b la selección de expertos de dos universidades de los Estados de Tabasco y Chiapas que cuentan desde hace más de diez años con programas virtuales; c el diseño de instrumentos de auto diagnóstico y d la calificación de los instrumentos por los expertos. El reporte describe tres de las cuatro etapas del estudio. El promedio del índice de expertos en la autoevaluación fue similar en las dos universidades; se concluye, por lo tanto, que los expertos comparten un nivel de conocimiento afín, en especial en el diseño de materiales u objetos de aprendizaje, no así en indicadores de calidad estimados para la educación virtual.Abstract: The present study describes the initial stage of a joint project between the Universidad Juárez Autónoma de Tabasco (UJAT y the Universidad Autónoma de Chiapas (UNACH México. This is a strategy designed to develop mechanisms to let the distance learning programs to self - assessment. The proposal is the result of applying a self

  19. Geophysical Characterization by the SAGE Program of a Newly Proposed, Low Temperature-EGS Prospect in the Central Rio Grande Rift, New Mexico

    Science.gov (United States)

    Jiracek, G. R.; Zablowski, P.; Castro, B.; Le Pape, F.; Biagini, B.; Kennedy, M.; Feucht, D. W.; Pellerin, L.; Bedrosian, P. A.; Hasterok, D. P.; Biehler, S.; McPhee, D. K.; Ferguson, J. F.

    2011-12-01

    In 2011 the SAGE (Summer of Applied Geophysical Experience) program began initial field evaluation of a recently proposed geothermal prospect located approximately 20 km northwest of Santa Fe, New Mexico. New magnetotelluric (MT) and gravity measurements in the Caja del Rio volcanic field have been combined with previous industry seismic results and SAGE MT, gravity, and seismic data to define parameters important for potential low temperature and EGS development. A thick, 2.0-2.5 km-deep, water-saturated, electrically conductive section overlies resistive basement, presumably Paleozoic limestone on top of Precambrian granite. Therefore, by projecting a measured 58oC/km near-surface temperature gradient, the area would easily meet the criterion for high grade EGS of impermeable basement rock at >200oC at less than 4 km depth. MT-derived depth estimates of a ubiquitous, highly conductive midcrustal conductor along with thermal conductivity values, and estimates of radiogenic heat flow allowed thermal modeling of the entire upper crust. This relies on recent evidence that the midcrustal conductor depth is a good proxy for the depth to the 500oC isotherm in active tectonic areas. The resulting thermal calculations yield a surface heat flow of 80 mW/m2 for a 2 km-deep sedimentary column and a 14 km-deep conductor. Forced, westward flowing groundwater convection over a basement high has been proposed for the thermal anomaly. Our initial geophysical results do not provide strong evidence for this. Rather, we favor the possibility that deeply penetrating, permeable fault conduits provide pathways for ascending warm water beneath the volcanic field. This is supported by high 3He/4He ratios measured in groundwater samples. The Caja del Rio area appears to be the most attractive geothermal prospect in the central Rio Grande rift outside of the near-by, world-class Valles caldera geothermal area.

  20. Evaluation of change in canine diagnosis protocol adopted by the visceral leishmaniasis control program in Brazil and a new proposal for diagnosis.

    Directory of Open Access Journals (Sweden)

    Wendel Coura-Vital

    Full Text Available The techniques used for diagnosis of canine visceral leishmaniasis (CVL in Brazil ELISA and IFAT have been extensively questioned because of the accuracy of these tests. A recent change in the diagnosis protocol excluded IFAT and included the Dual-Path Platform (DPP. We evaluated the prevalence and incidence rates of Leishmania spp. before and after the change in the protocol. In addition, based on our results, we propose a new alternative that is less expensive for the screening and confirmation of CVL. Plasma samples were obtained from a serobank from dogs evaluated in a cross-sectional study (1,226 dogs and in a cohort study of susceptible animals (n = 447, followed for 26 months. Serology testing was performed using ELISA, IFAT, and DPP. The incidence and prevalence of CVL were determined by using the protocol of the Visceral Leishmaniasis Control and Surveillance Program until 2012 (ELISA and IFAT using filter paper and the protocol used after 2012 (DPP and ELISA using plasma. The prevalence was 6.2% and the incidence was 2.8 per 1,000 dog-months for the protocol used until 2012. For the new diagnosis protocol for CVL resulted in an incidence of 5.4 per 1,000 dog-months and a prevalence of 8.1%. Our results showed that the prevalence and incidence of infection were far greater than suggested by the previously used protocol and that the magnitude of infection in endemic areas has been underestimated. As tests are performed sequentially and euthanasia of dogs is carried out when the serological results are positive in both tests, the sequence does not affect the number of animals to be eliminated by the Control Program. Then we suggest to municipalities with a large demand of exams to use ELISA for screening and DPP for confirmation, since this allows easier performance and reduced cost.

  1. Inhibition of the ATP Synthase Eliminates the Intrinsic Resistance of Staphylococcus aureus towards Polymyxins

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Nøhr-Meldgaard, Katrine; Bojer, Martin Saxtorph

    2017-01-01

    Staphylococcus aureus is intrinsically resistant to polymyxins (polymyxin B and colistin), an important class of cationic antimicrobial peptides used in treatment of Gram-negative bacterial infections. To understand the mechanisms underlying intrinsic polymyxin resistance in S. aureus, we screened......G or the subunits of the ATP synthase (atpA, atpB, atpG, or atpH), which during respiration is the main source of energy. Inactivation of atpA also conferred hypersusceptibility to colistin and the aminoglycoside gentamicin, whereas susceptibilities to nisin, gallidermin, bacitracin, vancomycin, ciprofloxacin......, linezolid, daptomycin, and oxacillin were unchanged. ATP synthase activity is known to be inhibited by oligomycin A, and the presence of this compound increased polymyxin B-mediated killing of S. aureus Our results demonstrate that the ATP synthase contributes to intrinsic resistance of S. aureus towards...

  2. Studies towards the synthesis of ATP analogs as potential glutamine synthetase inhibitors

    CSIR Research Space (South Africa)

    Salisu, S

    2011-05-01

    Full Text Available In research directed at the development of adenine triphosphate (ATP) analogs as potential glutamine synthetase (GS) inhibitors, adenine and allopurinol derivatives have been synthesized either as novel ATP analogs or as scaffolds...

  3. Dynamic Regulation of Cell Volume and Extracellular ATP of Human Erythrocytes.

    Directory of Open Access Journals (Sweden)

    M Florencia Leal Denis

    Full Text Available The peptide mastoparan 7 (MST7 triggered in human erythrocytes (rbcs the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe, interacting with P (purinergic receptors, can affect cell volume (Vr, we explored the dynamic regulation between Vr and ATPe.We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors.In rbcs 10 μM MST7 promoted acute, strongly correlated changes in [ATPe] and Vr. Whereas MST7 induced increases of 10% in Vr and 190 nM in [ATPe], blocking swelling in a hyperosmotic medium + MST7 reduced [ATPe] by 40%. Pre-incubation of rbcs with 10 μM of either carbenoxolone or probenecid, two inhibitors of the ATP conduit pannexin 1, reduced [ATPe] by 40-50% and swelling by 40-60%, while in the presence of 80 U/mL apyrase, an ATPe scavenger, cell swelling was prevented. While exposure to 10 μM NF110, a blocker of ATP-P2X receptors mediating sodium influx, reduced [ATPe] by 48%, and swelling by 80%, incubation of cells in sodium free medium reduced swelling by 92%.Results were analyzed by means of a mathematical model where ATPe kinetics and Vr kinetics were mutually regulated. Model dependent fit to experimental data showed that, upon MST7 exposure, ATP efflux required a fast 1960-fold increase of ATP permeability, mediated by two kinetically different conduits, both of which were activated by swelling and inactivated by time. Both experimental and theoretical results suggest that, following MST7 exposure, ATP is released via two conduits, one of which is mediated by pannexin 1. The accumulated ATPe activates P2X receptors, followed by sodium influx, resulting in cell swelling, which in turn further activates ATP release. Thus swelling and P2X receptors constitute essential components of a positive feedback loop underlying ATP-induced ATP release of rbcs.

  4. Visualization and Measurement of ATP Levels in Living Cells Replicating Hepatitis C Virus Genome RNA

    OpenAIRE

    Tomomi Ando; Hiromi Imamura; Ryosuke Suzuki; Hideki Aizaki; Toshiki Watanabe; Takaji Wakita; Tetsuro Suzuki

    2012-01-01

    Adenosine 5'-triphosphate (ATP) is the primary energy currency of all living organisms and participates in a variety of cellular processes. Although ATP requirements during viral lifecycles have been examined in a number of studies, a method by which ATP production can be monitored in real-time, and by which ATP can be quantified in individual cells and subcellular compartments, is lacking, thereby hindering studies aimed at elucidating the precise mechanisms by which viral replication energi...

  5. A functional 12T-insertion polymorphism in the ATP1A1 promoter confers decreased susceptibility to hypertension in a male Sardinian population.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Identification of susceptibility genes for essential hypertension in humans has been a challenge due to its multifactorial pathogenesis complicated by gene-gene and gene-environment interactions, developmental programing and sex specific differences. These concurrent features make identification of causal hypertension susceptibility genes with a single approach difficult, thus requiring multiple lines of evidence involving genetic, biochemical and biological experimentation to establish causal functional mutations. Here we report experimental evidence encompassing genetic, biochemical and in vivo modeling that altogether support ATP1A1 as a hypertension susceptibility gene in males in Sardinia, Italy. ATP1A1 encodes the α1Na,K-ATPase isoform, the sole sodium pump in vascular endothelial and renal tubular epithelial cells. DNA-sequencing detected a 12-nucleotide long thymidine (12T insertion(ins/deletion(del polymorphism within a poly-T sequence (38T vs 26T in the ATP1A1 5'-regulatory region associated with hypertension in a male Sardinian population. The 12T-insertion allele confers decreased susceptibility to hypertension (P = 0.035; OR = 0.50 [0.28-0.93] accounting for 12.1 mmHg decrease in systolic BP (P = 0.02 and 6.6 mmHg in diastolic BP (P = 0.046. The ATP1A1 promoter containing the 12T-insertion exhibited decreased transcriptional activity in in vitro reporter-assay systems, indicating decreased α1Na,K-ATPase expression with the 12T-insertion, compared with the 12T-deletion ATP1A1 promoter. To test the effects of decreased α1Na,K-ATPase expression on blood pressure, we measured blood pressure by radiotelemetry in three month-old, highly inbred heterozygous knockout ATP1A1+/- male mice with resultant 58% reduction in ATP1A1 protein levels. Male ATP1A1+/- mice showed significantly lower blood pressure (P < 0.03 than age-matched male wild-type littermate controls. Concordantly, lower ATP1A1 expression is expected to lower Na

  6. The dynamic equilibrium between ATP synthesis and ATP consumption is lower in isolated mitochondria from myotubes established from type 2 diabetic subjects compared to lean control

    DEFF Research Database (Denmark)

    Minet, Ariane D; Gaster, Michael

    2011-01-01

    selects the mitochondria based on an antibody recognizing the mitochondrial outer membrane and not by size through gradient centrifugation. The dynamic equilibrium between ATP synthesis and ATP consumption is 35% lower in isolated mitochondria from myotubes established from type 2 diabetic subjects...... or not in the mitochondria of diabetic skeletal muscle from subjects with type 2 diabetes. ATP synthesis was measured on mitochondria isolated from cultured myotubes established from lean (11/9), obese (9/11) and subjects with type 2 diabetes (9/11) (female/male, n=20 in each group), precultured under normophysiological...... compared to lean control. The ATP synthesis rate without ATP consumption was not different between groups and there were no significant gender differences. The mitochondrial dysfunction in type 2 diabetes in vivo is partly based on a primarily impaired ATP synthesis....

  7. Wilson Disease Protein ATP7B Utilizes Lysosomal Exocytosis to Maintain Copper Homeostasis

    NARCIS (Netherlands)

    Polishchuk, Elena V.; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C. D.; Chan, Jefferson; Chang, Christopher J.; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S.

    2014-01-01

    Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we

  8. A comparative study of ATPase subunit 9 (Atp9) gene between ...

    African Journals Online (AJOL)

    ATPase subunit 9 gene (Atp9) is an important functional gene in mitochondria, and is closely related with energy supply. RNA editing of atp9 gene was associated with male sterility in plants. In this study, the atp9 gene in soybeans was cloned from a soybean cytoplasmic male sterile line NJCMS2A and its maintainer line ...

  9. Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction

    DEFF Research Database (Denmark)

    Kringelbach, Tina M.; Aslan, Derya; Novak, Ivana

    2015-01-01

    effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP...

  10. A rapid and convenient method for preparing salt-free (. gamma. -/sup 32/P)ATP

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, J.L.; Avruch, J.

    1981-09-15

    (..gamma..-/sup 32/P)ATP is prepared by an existing enzymatic method that yields approximately 95% incorporation of /sup 32/P into ATP. A rapid and convenient method for purifying the (..gamma..-/sup 32/P)ATP which results in a product free of both salt and buffer is reported.

  11. ATP Release from Human Airway Epithelial Cells Exposed to Staphylococcus aureus Alpha-Toxin

    Directory of Open Access Journals (Sweden)

    Romina Baaske

    2016-12-01

    Full Text Available Airway epithelial cells reduce cytosolic ATP content in response to treatment with S. aureus alpha-toxin (hemolysin A, Hla. This study was undertaken to investigate whether this is due to attenuated ATP generation or to release of ATP from the cytosol and extracellular ATP degradation by ecto-enzymes. Exposure of cells to rHla did result in mitochondrial calcium uptake and a moderate decline in mitochondrial membrane potential, indicating that ATP regeneration may have been attenuated. In addition, ATP may have left the cells through transmembrane pores formed by the toxin or through endogenous release channels (e.g., pannexins activated by cellular stress imposed on the cells by toxin exposure. Exposure of cells to an alpha-toxin mutant (H35L, which attaches to the host cell membrane but does not form transmembrane pores, did not induce ATP release from the cells. The Hla-mediated ATP-release was completely blocked by IB201, a cyclodextrin-inhibitor of the alpha-toxin pore, but was not at all affected by inhibitors of pannexin channels. These results indicate that, while exposure of cells to rHla may somewhat reduce ATP production and cellular ATP content, a portion of the remaining ATP is released to the extracellular space and degraded by ecto-enzymes. The release of ATP from the cells may occur directly through the transmembrane pores formed by alpha-toxin.

  12. P2Y Receptor Modulation of ATP Release in the Urothelium

    Directory of Open Access Journals (Sweden)

    Kylie J. Mansfield

    2014-01-01

    Full Text Available The release of ATP from the urothelium in response to stretch during filling demonstrates the importance of the purinergic system for the physiological functioning of the bladder. This study examined the effect of P2 receptor agonists on ATP release from two urothelial cell lines (RT4 and UROtsa cells. Hypotonic Krebs was used as a stretch stimulus. Incubation of urothelial cells with high concentrations of the P2Y agonist ADP induced ATP release to a level that was 40-fold greater than hypotonic-stimulated ATP release (P < 0.0011, ADP EC50 1.8 µM. Similarly, an increase in ATP release was also observed with the P2Y agonist, UTP, up to a maximum of 70% of the hypotonic response (EC50 0.62 µM. Selective P2 receptor agonists, αβ-methylene-ATP, ATP-γ-S, and 2-methylthio-ADP had minimal effects on ATP release. ADP-stimulated ATP release was significantly inhibited by suramin (100 µM, P = 0.002. RT4 urothelial cells break down nucleotides (100 µM including ATP, ADP, and UTP to liberate phosphate. Phosphate liberation was also demonstrated from endogenous nucleotides with approximately 10% of the released ATP broken down during the incubation. These studies demonstrate a role for P2Y receptor activation in stimulation of ATP release and emphasize the complexity of urothelial P2 receptor signalling.

  13. Glycolysis and ATP degradation in cod ( Gadus morhua ) at subzero temperatures in relation to thaw rigor

    DEFF Research Database (Denmark)

    Cappeln, Gertrud; Jessen, Flemming

    2001-01-01

    Glycolysis was shown to occur during freezing of cod of decrease in glycogen and an increase in lactate. In addition, the ATP content decreased during freezing. Synthesis of ATP was measured as degradation of glycogen. During storage at -9 and - 12 degreesC it was found that degradation of ATP...

  14. Quantum-mechanical analysis of amino acid residues function in the proton transport during F0F1-ATP synthase catalytic cycle

    Science.gov (United States)

    Ivontsin, L. A.; Mashkovtseva, E. V.; Nartsissov, Ya R.

    2017-11-01

    Implications of quantum-mechanical approach to the description of proton transport in biological systems are a tempting subject for an overlapping of fundamental physics and biology. The model of proton transport through the integrated membrane enzyme FoF1-ATP synthase responsible for ATP synthesis was developed. The estimation of the mathematical expectation of the proton transfer time through the half-channel was performed. Observed set of proton pathways through the inlet half-channel showed the nanosecond timescale highly dependable of some amino acid residues. There were proposed two types of crucial amino acids: critically localized (His245) and being a part of energy conserving system (Asp119).

  15. Ionotropic ATP receptors in neuronal-glial communication.

    Science.gov (United States)

    Lalo, Ulyana; Verkhratsky, Alexei; Pankratov, Yuri

    2011-04-01

    In the central nervous system ATP is released from both neurones and astroglial cells acting as a homo- and heterocellular neurotransmitter. Glial cells express numerous purinoceptors of both ionotropic (P2X) and metabotropic (P2Y) varieties. Astroglial P2X receptors can be activated by ongoing synaptic transmission and can mediate fast local signalling through elevation in cytoplasmic Ca(2+) and Na(+) concentrations. These ionic signals can be translated into various physiological messages by numerous pathways, including release of gliotransmitters, metabolic support of neurones and regulation of activity of postsynaptic glutamate and GABA receptors. Ionotropic purinoceptors represent a novel pathway of glia-driven modulation of synaptic signalling that involves the release of ATP from neurones and astrocytes followed by activation of P2X receptors which can regulate synaptic activity by variety of mechanisms expressed in both neuronal and glial compartments. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Students' Interdisciplinary Reasoning about "High-Energy Bonds" and ATP

    CERN Document Server

    Dreyfus, Benjamin W; Sawtelle, Vashti; Svoboda, Julia; Turpen, Chandra; Redish, Edward F

    2012-01-01

    Students' sometimes contradictory ideas about ATP (adenosine triphosphate) and the nature of chemical bonds have been studied in the biology and chemistry education literatures, but these topics are rarely part of the introductory physics curriculum. We present qualitative data from an introductory physics course for undergraduate biology majors that seeks to build greater interdisciplinary coherence and therefore includes these topics. In these data, students grapple with the apparent contradiction between the energy released when the phosphate bond in ATP is broken and the idea that an energy input is required to break a bond. We see that students' perceptions of how each scientific discipline bounds the system of interest can influence how they justify their reasoning about a topic that crosses disciplines. This has consequences for a vision of interdisciplinary education that respects disciplinary perspectives while bringing them into interaction in ways that demonstrate consistency amongst the perspectiv...

  17. Students' interdisciplinary reasoning about "high-energy bonds" and ATP

    Science.gov (United States)

    Dreyfus, Benjamin W.; Geller, Benjamin D.; Sawtelle, Vashti; Svoboda, Julia; Turpen, Chandra; Redish, Edward F.

    2013-01-01

    Students' sometimes contradictory ideas about ATP (adenosine triphosphate) and the nature of chemical bonds have been studied in the biology and chemistry education literatures, but these topics are rarely part of the introductory physics curriculum. We present qualitative data from an introductory physics course for undergraduate biology majors that seeks to build greater interdisciplinary coherence and therefore includes these topics. In these data, students grapple with the apparent contradiction between the energy released when the phosphate bond in ATP is broken and the idea that an energy input is required to break a bond. We see that students' perceptions of how each scientific discipline bounds the system of interest can influence how they justify their reasoning about a topic that crosses disciplines. This has consequences for a vision of interdisciplinary education that respects disciplinary perspectives while bringing them into interaction in ways that demonstrate consistency amongst the perspectives.

  18. Motor pathway excitability in ATP13A2 mutation carriers

    DEFF Research Database (Denmark)

    Zittel, S; Kroeger, J; van der Vegt, J P M

    2012-01-01

    OBJECTIVE: To describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS). METHODS: Five members of a Chilean family...... with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval...... intracortical inhibition (SICI), intracortical facilitation (ICF), short latency afferent inhibition (SAI) as markers of intracortical intrahemispheric inhibition/facilitation and the ipsilateral silent period (iSP) and paired-pulse interhemispheric inhibition (IHI) to probe interhemispheric motor interactions...

  19. Structure and mechanism of ATP-dependent phospholipid transporters

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager; Bailly, Aurélien

    2015-01-01

    , despite differences in overall architecture, both appear to operate by an alternating access mechanism and during transport they might allow access of phospholipids to the internal part of the transmembrane domain. The latter feature is obvious for ABC transporters, but phospholipids and other hydrophobic......Background ATP-binding cassette (ABC) transporters and P4-ATPases are two large and seemingly unrelated families of primary active pumps involved in moving phospholipids from one leaflet of a biological membrane to the other. Scope of review This review aims to identify common mechanistic features...... in the way phospholipid flipping is carried out by two evolutionarily unrelated families of transporters. Major conclusions Both protein families hydrolyze ATP, although they employ different mechanisms to use it, and have a comparable size with twelve transmembrane segments in the functional unit. Further...

  20. Decipher the mechanisms of protein conformational changes induced by nucleotide binding through free-energy landscape analysis: ATP binding to Hsp70.

    Directory of Open Access Journals (Sweden)

    Adrien Nicolaï

    Full Text Available ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD of Hsp70 propagates a signal to its substrate-binding domain (SBD. Unbiased MD simulations were performed for Hsp70-DnaK chaperone in nucleotide-free, ADP-bound and ATP-bound states. The simulations revealed that the SBD does not interact with the NBD for DnaK in its nucleotide-free and ADP-bound states whereas the docking of the SBD was found in the ATP-bound state. The docked state induced by ATP binding found in MD is an intermediate state between the initial nucleotide-free and final ATP-bound states of Hsp70. The analysis of the FEL projected along the amino-acid sequence permitted to identify a subset of 27 protein internal coordinates corresponding to a network of 91 key residues involved in the conformational change induced by ATP binding. Among the 91 residues, 26 are identified for the first time, whereas the others were shown relevant for the allosteric communication of Hsp70 s in several experiments and bioinformatics analysis. The FEL analysis revealed also the origin of the ATP-induced structural modifications of the SBD recently measured by Electron Paramagnetic Resonance. The pathway between the nucleotide-free and the intermediate state of DnaK was extracted by applying principal component analysis to the subset of internal coordinates describing the transition. The methodology proposed is general and could be applied to analyze allosteric communication in

  1. Competitive fluorescence anisotropy/polarization assay for ATP using aptamer as affinity ligand and dye-labeled ATP as fluorescence tracer.

    Science.gov (United States)

    Li, Yapiao; Sun, Linlin; Zhao, Qiang

    2017-11-01

    We developed an aptamer-based competitive fluorescence anisotropy (FA)/fluorescence polarization (FP) assay for adenosine triphosphate (ATP). Different from the traditional fluorescence polarization immunoassays for small molecules, here DNA aptamer against ATP was used as affinity ligand, and tetramethylrhodamine (TMR) labeled ATP served as fluorescent tracer. The binding between TMR-labeled ATP and aptamer gave large FA due to molecular volume increase and restricted rotation of the dye-labeled ATP. When ATP was added in solution, ATP competitively displaced the TMR-labeled ATP from aptamer affinity complex, causing decrease of FA of TMR-labeled ATP. The buffer containing MgCl 2 and incubation at low temperature were preferred for large FA change in the FA assay. The FA change was further enhanced in this competitive FA assay by increasing the molecular weight of aptamer through extension of aptamer sequences or conjugating streptavidin protein on aptamer. This method allowed for the detection of ATP in the range from 0.5μM to 1mM, generating the maximum FA change about 0.187 (corresponding maximum FP change about 0.242). The detection of ATP spiked in diluted urine or serum sample was achieved, showing capability for analysis in complex sample matrix. This assay also enabled the detection of the analogues of ATP, e.g. adenosine, adenosine monophosphate (AMP), and adenosine diphosphate (ADP) with similar sensitivity. This aptamer-based competitive FA assay takes advantages of aptamer in ease of synthesis, good thermal stability, and facile modulating the molecular mass of aptamer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Alternative mitochondrial functions in cell physiopathology: beyond ATP production

    Directory of Open Access Journals (Sweden)

    Kowaltowski A.J.

    2000-01-01

    Full Text Available It is well known that mitochondria are the main site for ATP generation within most tissues. However, mitochondria also participate in a surprising number of alternative activities, including intracellular Ca2+ regulation, thermogenesis and the control of apoptosis. In addition, mitochondria are the main cellular generators of reactive oxygen species, and may trigger necrotic cell death under conditions of oxidative stress. This review concentrates on these alternative mitochondrial functions, and their role in cell physiopathology.

  3. Creatine kinase-mediated ATP supply fuels actin-based events in phagocytosis.

    Directory of Open Access Journals (Sweden)

    Jan W P Kuiper

    2008-03-01

    Full Text Available Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by actin polymerization and myosin motor activity. How this actomyosin dynamics is dependent upon systems that provide access to ATP at phagosome microdomains has not been determined. We analyzed the role of brain-type creatine kinase (CK-B, an enzyme involved in high-energy phosphoryl transfer. We demonstrate that endogenous CK-B in macrophages is mobilized from the cytosolic pool and coaccumulates with F-actin at nascent phagosomes. Live cell imaging with XFP-tagged CK-B and beta-actin revealed the transient and specific nature of this partitioning process. Overexpression of a catalytic dead CK-B or CK-specific cyclocreatine inhibition caused a significant reduction of actin accumulation in the phagocytic cup area, and reduced complement receptor-mediated, but not Fc-gammaR-mediated, ingestion capacity of macrophages. Finally, we found that inhibition of CK-B affected phagocytosis already at the stage of particle adhesion, most likely via effects on actin polymerization behavior. We propose that CK-B activity in macrophages contributes to complement-induced F-actin assembly events in early phagocytosis by providing local ATP supply.

  4. Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition

    Science.gov (United States)

    Park, Dohyun; Jeong, Heeyoon; Lee, Mi Nam; Koh, Ara; Kwon, Ohman; Yang, Yong Ryoul; Noh, Jungeun; Suh, Pann-Ghill; Park, Hwangseo; Ryu, Sung Ho

    2016-01-01

    Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway. We found that inhibition of mTOR activity and presence of ULK1 are required for autophagy induction by resveratrol. In line with this mTOR dependency, we found that resveratrol suppresses the viability of MCF7 cells but not of SW620 cells, which are mTOR inhibitor sensitive and insensitive cancer cells, respectively. We also found that resveratrol-induced cancer cell suppression occurred ULK1 dependently. For the mechanism of action of resveratrol on mTOR inhibition, we demonstrate that resveratrol directly inhibits mTOR. We found that resveratrol inhibits mTOR by docking onto the ATP-binding pocket of mTOR (i.e., it competes with ATP). We propose mTOR as a novel direct target of resveratrol, and inhibition of mTOR is necessary for autophagy induction. PMID:26902888

  5. ATP Synthase: The Right Size Base Model for Nanomotors in Nanomedicine

    Directory of Open Access Journals (Sweden)

    Zulfiqar Ahmad

    2014-01-01

    Full Text Available Nanomedicine results from nanotechnology where molecular scale minute precise nanomotors can be used to treat disease conditions. Many such biological nanomotors are found and operate in living systems which could be used for therapeutic purposes. The question is how to build nanomachines that are compatible with living systems and can safely operate inside the body? Here we propose that it is of paramount importance to have a workable base model for the development of nanomotors in nanomedicine usage. The base model must placate not only the basic requirements of size, number, and speed but also must have the provisions of molecular modulations. Universal occurrence and catalytic site molecular modulation capabilities are of vital importance for being a perfect base model. In this review we will provide a detailed discussion on ATP synthase as one of the most suitable base models in the development of nanomotors. We will also describe how the capabilities of molecular modulation can improve catalytic and motor function of the enzyme to generate a catalytically improved and controllable ATP synthase which in turn will help in building a superior nanomotor. For comparison, several other biological nanomotors will be described as well as their applications for nanotechnology.

  6. Nucleotide-induced asymmetry within ATPase activator ring drives σ54-RNAP interaction and ATP hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Sysoeva, Tatyana A.; Chowdhury, Saikat; Guo, Liang; Nixon, B. Tracy [IIT; (Penn)

    2013-12-10

    It is largely unknown how the typical homomeric ring geometry of ATPases associated with various cellular activities enables them to perform mechanical work. Small-angle solution X-ray scattering, crystallography, and electron microscopy (EM) reconstructions revealed that partial ATP occupancy caused the heptameric closed ring of the bacterial enhancer-binding protein (bEBP) NtrC1 to rearrange into a hexameric split ring of striking asymmetry. The highly conserved and functionally crucial GAFTGA loops responsible for interacting with σ54–RNA polymerase formed a spiral staircase. We propose that splitting of the ensemble directs ATP hydrolysis within the oligomer, and the ring's asymmetry guides interaction between ATPase and the complex of σ54 and promoter DNA. Similarity between the structure of the transcriptional activator NtrC1 and those of distantly related helicases Rho and E1 reveals a general mechanism in homomeric ATPases whereby complex allostery within the ring geometry forms asymmetric functional states that allow these biological motors to exert directional forces on their target macromolecules.

  7. Human ATP-binding cassette (ABC transporter family

    Directory of Open Access Journals (Sweden)

    Vasiliou Vasilis

    2009-04-01

    Full Text Available Abstract There exist four fundamentally different classes of membrane-bound transport proteins: ion channels; transporters; aquaporins; and ATP-powered pumps. ATP-binding cassette (ABC transporters are an example of ATP-dependent pumps. ABC transporters are ubiquitous membrane-bound proteins, present in all prokaryotes, as well as plants, fungi, yeast and animals. These pumps can move substrates in (influx or out (efflux of cells. In mammals, ABC transporters are expressed predominantly in the liver, intestine, blood-brain barrier, blood-testis barrier, placenta and kidney. ABC proteins transport a number of endogenous substrates, including inorganic anions, metal ions, peptides, amino acids, sugars and a large number of hydrophobic compounds and metabolites across the plasma membrane, and also across intracellular membranes. The human genome contains 49 ABC genes, arranged in eight subfamilies and named via divergent evolution. That ABC genes are important is underscored by the fact that mutations in at least I I of these genes are already known to cause severe inherited diseases (eg cystic fibrosis and X-linked adrenoleukodystrophy [X-ALD]. ABC transporters also participate in the movement of most drugs and their metabolites across cell surface and cellular organelle membranes; thus, defects in these genes can be important in terms of cancer therapy, pharmacokinetics and innumerable pharmacogenetic disorders.

  8. Persister formation in Staphylococcus aureus is associated with ATP depletion

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian P.; Rowe, Sarah E.; Gandt, Autumn Brown; Nuxoll, Austin S.; Donegan, Niles P.; Zalis, Eliza A.; Clair, Geremy; Adkins, Joshua N.; Cheung, Ambrose L.; Lewis, Kim

    2016-04-18

    Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic bacterial infection and antibiotic treatment failure. In Escherichia coli, toxin/antitoxin (TA) modules are responsible for persister formation. The mechanism of persister formation in Gram positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting TA modules in S. aureus did not affect the level of persisters. Here we show that S. aureus persisters are produced due to a stochastic entrance to stationary phase accompanied by a drop in intracellular ATP. Cells expressing stationary state markers are present throughout the growth phase, increasing in frequency with cell density. Cell sorting revealed that expression of stationary markers was associated with a 100-1000 fold increased likelihood of survival to antibiotic challenge. We find that the antibiotic tolerance of these cells is due to a drop in intracellular ATP. The ATP level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotic treatment.

  9. ATP-regenerating system in the cilia of Paramecium caudatum.

    Science.gov (United States)

    Noguchi, M; Sawada, T; Akazawa, T

    2001-03-01

    The energy supply for eukaryotic ciliary and flagellar movement is thought to be maintained by ATP-regenerating enzymes such as adenylate kinase, creatine kinase and arginine kinase. In this study, the energy-supplying system for the ciliary movement of Paramecium caudatum was examined. Arginine kinase and adenylate kinase activities were detected in the cilia. To demonstrate that phosphoarginine satisfactorily supplies high-energy phosphate compounds into the narrow ciliary space, we prepared an intact ciliated cortical sheet from live Paramecium caudatum. These cortical sheets, with an intact ciliary membrane, produced a half-closed system in which each cilium was covered with a ciliary membrane with an opening to the cell body. Ciliary beating on the intact cortical sheets was induced by perfusing not only ATP but also ADP. Addition of phosphoarginine (0.2 mmol l(-1)) increased the beat frequency. A further increase in beat frequency was observed in 0.4 mmol l(-1) phosphoarginine, and this was enhanced when the cilia were reactivated with relatively low concentrations of ATP. We have demonstrated that phosphoarginine supplies energy as a 'phosphagen' for ciliary beating in Paramecium caudatum, suggesting that phosphoarginine functions not only as a reservoir of energy but also as a transporter of energy in these continuously energy-consuming circumstances. http://www.biologists.com/JEB/movies/jeb3123.html

  10. [Environmental Hazards Assessment Program annual report, June 1992--June 1993]. Needs assessment for the proposed masters degree program in environmental science at the Medical University of South Carolina: EHAP Volume 1, No. 2

    Energy Technology Data Exchange (ETDEWEB)

    Hoomani, J.

    1993-05-01

    There will be a critical shortage of professionals who are educated to deal with environmental problems by 1997. This was the major finding of a 1992 study conducted by the Oak Ridge Associated Universities, Incorporated and the Pacific Northwest Laboratory (Publication Number PAL-8171, CU-700). The study was done to determine the manpower needs of the Office of Environmental Restoration and Waste Management in the US Department of Energy (DOE). Although the focus of the study was the 19 sites of the DOE complex, including the Savannah River Site in South Carolina, the study documented that such shortages will affect other major agencies and organizations including the US Department of Interior, the US Department of Defense, the Environmental Protection Agency, state and local governmental agencies, private agencies, and manufacturing enterprises throughout the State of South Carolina and the National. The Oak Ridge Study also documented that a variety of professional positions requiring environmental expertise are difficult to fill because traditional educational programs in physical science, engineering, health science, public policy, and administration have not adequately responded to the unique nature of these emerging specialities. This lack of educational preparation has necessitated extensive on-site training of new employees before they can become productive members of the environmental work force. Unique educational initiatives such as the Environmental Studies program proposed here are vital to address the long-term demand for environmental professionals.

  11. ATP release and extracellular nucleotidase activity in erythrocytes and coronary circulation of rainbow trout

    DEFF Research Database (Denmark)

    Jensen, Frank B; Agnisola, Claudio; Novak, Ivana

    2009-01-01

    The present study tested the hypothesis that rainbow trout erythrocytes release ATP upon deoxygenation, a mechanism that enables mammalian erythrocytes to produce local vasodilation. We also investigated ATP release and ectonucleotidase activity in the coronary circulation of the isolated trout......-perfused coronary circulation, [ATP] increased as the perfusate moved through the vessels in the presence of ARL 67156. When ATP was added to the inflowing saline, most ATP disappeared during passage of the coronary bed when ARL 67156 was absent but not when it was present. We conclude that rainbow trout...

  12. Program of scientific investigations and development of solid-oxide fuel cells (SOFC) in VNIITF. Proposals on scientific and technical collaboration and SOFC commercialization

    Energy Technology Data Exchange (ETDEWEB)

    Kleschev, Yu.N.; Chukharev, V.F.

    1996-04-01

    This paper describes proposals on scientific and technical collaborations pertaining to solid oxide fuel cell commercialization. Topics included for discussion are: materials research and manufacture; market estimation and cost; directions of collaboration; and project of proposals on joint enterprise creation.

  13. ICD programming

    OpenAIRE

    Biffi, Mauro

    2014-01-01

    Background: Appropriate ICD programming is the key to prevent inappropriate shock delivery, that is closely associated to a negative patients' outcome. Methods: Review of the literature on ICD therapy to generate ICD programmings that can be applied to the broad population of ICD and CRT-D carriers. Results: Arrhythmia detection should occur with a detection time ranging 9″–12″ in the VF zone, and 15″–60″ in the VT zone. Discriminator should be applied at least up to 200 bpm. ATP therap...

  14. Synthesis of the investment program proposals submitted by RTE to CRE's approval; Synthese des propositions de programme d'investissement soumises par RTE a l'approbation de la CRE

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    Conformably to the French law from February 10, 2000, the French commission of electricity regulation (CRE) must proceed to the examination of the proposals submitted by the electricity transportation network (RTE) for the approval of its 2002 investments program devoted to the power grid. The main lines of the proposals submitted by RTE are described in this document: 1 - strategy of grid development (methodology, interconnections), 2 - methods of evaluation and selection of regional projects (replacement and development projects), 3 - main projects retained (main transportation network and interconnections, regional networks, remote control and safety systems), 4 - program financing plan. (J.S.)

  15. Pharmacological and molecular comparison of K(ATP) channels in rat basilar and middle cerebral arteries

    DEFF Research Database (Denmark)

    Ploug, Kenneth Beri; Edvinsson, Lars; Olesen, Jes

    2006-01-01

    ATP-sensitive potassium (K(ATP)) channels play an important role in the regulation of cerebral vascular tone. In vitro studies using synthetic K(ATP) channel openers suggest that the pharmacological profiles differ between rat basilar arteries and rat middle cerebral arteries. To address this issue......, we studied the possible involvement of endothelial K(ATP) channels by pressurized arteriography after luminal administration of synthetic K(ATP) channel openers to rat basilar and middle cerebral arteries. Furthermore, we examined the mRNA and protein expression profile of K(ATP) channels to rat...... basilar and middle cerebral arteries using quantitative real-time PCR (Polymerase Chain Reaction) and Western blotting, respectively. In the perfusion system, we found no significant responses after luminal application of three K(ATP) channel openers to rat basilar and middle cerebral arteries...

  16. ATP Modifies the Proteome of Extracellular Vesicles Released by Microglia and Influences Their Action on Astrocytes

    Directory of Open Access Journals (Sweden)

    Francesco Drago

    2017-12-01

    Full Text Available Extracellular ATP is among molecules promoting microglia activation and inducing the release of extracellular vesicles (EVs, which are potent mediators of intercellular communication between microglia and the microenvironment. We previously showed that EVs produced under ATP stimulation (ATP-EVs propagate a robust inflammatory reaction among astrocytes and microglia in vitro and in mice with subclinical neuroinflammation (Verderio et al., 2012. However, the proteome of EVs released upon ATP stimulation has not yet been elucidated. In this study we applied a label free proteomic approach to characterize the proteome of EVs released constitutively and during microglia activation with ATP. We show that ATP drives sorting in EVs of a set of proteins implicated in cell adhesion/extracellular matrix organization, autophagy-lysosomal pathway and cellular metabolism, that may influence the response of recipient astrocytes to EVs. These data provide new clues to molecular mechanisms involved in microglia response to ATP and in microglia signaling to the environment via EVs.

  17. Prevalence of the metabolic syndrome in Pudong New Area of Shanghai using three proposed definitions among Chinese adults

    Directory of Open Access Journals (Sweden)

    Jiang Qing-wu

    2010-05-01

    Full Text Available Abstract Background The prevalence of metabolic syndrome (MS has been increasing in China in recent years. The aim of this study is to estimate and compare the prevalence of MS among Chinese adults in Shanghai, one of the most economic developed areas in China, using definitions proposed by World Health Organization (WHO, National Cholesterol Education Program Adult Treatment Panel (modified ATP III and International Diabetes Federation (IDF. Methods This cross-sectional study included 5,584 adults at age 20-79 randomly selected from Pudong New Area of Shanghai, China, through a three-stage sampling. All participants were interviewed in-person between April and July of 2008 to collect information on demographic and lifestyle characteristics. At the interview, anthropometry and blood pressure were measured and bio-specimens were collected. Results The prevalence estimates for the MS increased with age for each definition in men and women, but the estimates varied greatly between the definitions and by sex. The prevalence of the MS was higher in men (20.2% than in women (18.7% using WHO definition but this sex difference was reversed when using the modified ATP III (28.4% for men vs. 35.1% for women and the IDF (15.9% for men vs. 26.7% for women criteria. The most common metabolic disorder in this population was dyslipidaemia, regardless of the definition used. Substantial agreement, estimated using the kappa statistic, was found between the modified ATP III and IDF definition, whereas the lowest agreement was observed between the WHO and ATP III criteria. Conclusions The MS is highly prevalent among Chinese adults in Pudong New Area of Shanghai and the most prevalent component was dyslipidemia. These findings underscore the importance of prevention and control efforts for the MS in this area and the need for a unified predictive definition for the syndrome for use by clinical practitioners and public health agencies.

  18. Evaluation of ATP measurements to detect microbial ingress by wastewater and surface water in drinking water.

    Science.gov (United States)

    Vang, Óluva K; Corfitzen, Charlotte B; Smith, Christian; Albrechtsen, Hans-Jørgen

    2014-11-01

    Fast and reliable methods are required for monitoring of microbial drinking water quality in order to protect public health. Adenosine triphosphate (ATP) was investigated as a potential real-time parameter for detecting microbial ingress in drinking water contaminated with wastewater or surface water. To investigate the ability of the ATP assay in detecting different contamination types, the contaminant was diluted with non-chlorinated drinking water. Wastewater, diluted at 10(4) in drinking water, was detected with the ATP assay, as well as 10(2) to 10(3) times diluted surface water. To improve the performance of the ATP assay in detecting microbial ingress in drinking water, different approaches were investigated, i.e. quantifying microbial ATP or applying reagents of different sensitivities to reduce measurement variations; however, none of these approaches contributed significantly in this respect. Compared to traditional microbiological methods, the ATP assay could detect wastewater and surface water in drinking water to a higher degree than total direct counts (TDCs), while both heterotrophic plate counts (HPC 22 °C and HPC 37 °C) and Colilert-18 (Escherichia coli and coliforms) were more sensitive than the ATP measurements, though with much longer response times. Continuous sampling combined with ATP measurements displays definite monitoring potential for microbial drinking water quality, since microbial ingress in drinking water can be detected in real-time with ATP measurements. The ability of the ATP assay to detect microbial ingress is influenced by both the ATP load from the contaminant itself and the ATP concentration in the specific drinking water. Consequently, a low ATP concentration of the specific drinking water facilitates a better detection of a potential contamination of the water supply with the ATP assay. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Local release of ATP into the arterial inflow and venous drainage of human skeletal muscle: insight from ATP determination with the intravascular microdialysis technique

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Thaning, Pia; Nyberg, Michael Permin

    2011-01-01

    is released into plasma, we measured plasma [ATP] with the intravascular microdialysis technique at rest and during dynamic exercise (normoxia and hypoxia), passive exercise, thigh compressions and arterial ATP, tyramine and ACh infusion in a total of 16 healthy young men. Femoral arterial and venous...

  20. 3'-O-(5-fluoro-2,4-dinitrophenyl)ADP ether and ATP ether. Affinity reagents for labeling ATPases.

    Science.gov (United States)

    Chuan, H; Wang, J H

    1988-09-15

    The affinity reagents 3'-O-(5-fluoro-2,4-dinitrophenyl)ADP ether (FDNP-ADP) and 3'-O-(5-fluoro-2,4-dinitrophenyl)ATP ether (FDNP-ATP) were synthesized and characterized. FDNP[14C]ADP was found to label the active site of mitochondrial F1-ATPase slowly at room temperature but with high specificity. F1 was effectively protected from the labeling reagent by ATP or ADP. An average number of 1.3 covalent label per F1 is sufficient for 100% inhibition of the ATPase. About 73% of the radioactive label was found covalently attached to beta subunits, 9% on alpha, practically none on gamma, delta, and epsilon. Cleavage of the labeled enzyme by pepsin and sequencing of the major radioactive peptide showed that the labeled amino acid residue in beta subunit was Lys beta 162. These results show that Lys beta 162 is indeed at the active site of F1 as assumed in the recently proposed models (Fry, D. C., Kuby, S. A., and Mildvan, A. S. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 907-911; Duncan, I. M., Parsonage, D., and Senior, A. E. (1986) FEBS Lett. 208, 1-6).

  1. The Role of Platelet-Derived ADP and ATP in Promoting Pancreatic Cancer Cell Survival and Gemcitabine Resistance

    Directory of Open Access Journals (Sweden)

    Omar Elaskalani

    2017-10-01

    Full Text Available Platelets have been demonstrated to be vital in cancer epithelial-mesenchymal transition (EMT, an important step in metastasis. Markers of EMT are associated with chemotherapy resistance. However, the association between the development of chemoresistance, EMT, and the contribution of platelets to the process, is still unclear. Here we report that platelets regulate the expression of (1 human equilibrative nucleoside transporter 1 (hENT1 and (2 cytidine deaminase (CDD, markers of gemcitabine resistance in pancreatic cancer. Human ENT1 (hENT1 is known to enable cellular uptake of gemcitabine while CDD deactivates gemcitabine. Knockdown experiments demonstrate that Slug, a mesenchymal transcriptional factor known to be upregulated during EMT, regulates the expression of hENT1 and CDD. Furthermore, we demonstrate that platelet-derived ADP and ATP regulate Slug and CDD expression in pancreatic cancer cells. Finally, we demonstrate that pancreatic cancer cells express the purinergic receptor P2Y12, an ADP receptor found mainly on platelets. Thus ticagrelor, a P2Y12 inhibitor, was used to examine the potential therapeutic effect of an ADP receptor antagonist on cancer cells. Our data indicate that ticagrelor negated the survival signals initiated in cancer cells by platelet-derived ADP and ATP. In conclusion, our results demonstrate a novel role of platelets in modulating chemoresistance in pancreatic cancer. Moreover, we propose ADP/ATP receptors as additional potential drug targets for treatment of pancreatic cancer.

  2. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension

    DEFF Research Database (Denmark)

    Beuschlein, Felix; Boulkroun, Sheerazed; Osswald, Andrea

    2013-01-01

    Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na+/K+ ATPase α...... subunit) and ATP2B3 (encoding a Ca2+ ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced...... affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation...

  3. Splice Site Mutations in the ATP7A Gene

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Tümer, Zeynep; Møller, Lisbeth Birk

    2011-01-01

    Menkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12...... mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mutations were collected from the literature. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation...

  4. Real-Time Monitoring of ATP-Responsive Drug Release Using Mesoporous-Silica-Coated Multicolor Upconversion Nanoparticles.

    Science.gov (United States)

    Lai, Jinping; Shah, Birju P; Zhang, Yixiao; Yang, Letao; Lee, Ki-Bum

    2015-05-26

    Stimuli-responsive drug delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with integrated real-time monitoring capabilities is still in its nascent stage because of the limitations of imaging modalities. In this paper, we describe the development of a polypeptide-wrapped mesoporous-silica-coated multicolor upconversion nanoparticle (UCNP@MSN) as an adenosine triphosphate (ATP)-responsive drug delivery system (DDS) for long-term tracking and real-time monitoring of drug release. Our UCNP@MSN with multiple emission peaks in UV-NIR wavelength range was functionalized with zinc-dipicolylamine analogue (TDPA-Zn(2+)) on its exterior surface and loaded with small-molecule drugs like chemotherapeutics in interior mesopores. The drugs remained entrapped within the UCNP-MSNs when the nanoparticles were wrapped with a compact branched polypeptide, poly(Asp-Lys)-b-Asp, because of multivalent interactions between Asp moieties present in the polypeptide and the TDPA-Zn(2+) complex present on the surface of UCNP-MSNs. This led to luminescence resonance energy transfer (LRET) from the UCNPs to the entrapped drugs, which typically have absorption in UV-visible range, ultimately resulting in quenching of UCNP emission in UV-visible range while retaining their strong NIR emission. Addition of ATP led to a competitive displacement of the surface bound polypeptide by ATP due to its higher affinity to TDPA-Zn(2+), which led to the release of the entrapped drugs and subsequent elimination of LRET. Monitoring of such ATP-triggered ratiometric changes in LRET allowed us to monitor the release of the entrapped drugs in real-time. Given these results, we envision that our proposed UCNP@MSN-polypeptide hybrid nanoparticle has great potential for stimuli-responsive drug delivery as well as for monitoring biochemical changes taking place in live cancer

  5. Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain

    Science.gov (United States)

    Masuda, Takahiro; Ozono, Yui; Mikuriya, Satsuki; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Iwatsuki, Ken; Uneyama, Hisayuki; Ichikawa, Reiko; Salter, Michael W.; Tsuda, Makoto; Inoue, Kazuhide

    2016-01-01

    Activation of purinergic receptors in the spinal cord by extracellular ATP is essential for neuropathic hypersensitivity after peripheral nerve injury (PNI). However, the cell type responsible for releasing ATP within the spinal cord after PNI is unknown. Here we show that PNI increases expression of vesicular nucleotide transporter (VNUT) in the spinal cord. Extracellular ATP content ([ATP]e) within the spinal cord was increased after PNI, and this increase was suppressed by exocytotic inhibitors. Mice lacking VNUT did not show PNI-induced increase in [ATP]e and had attenuated hypersensitivity. These phenotypes were recapitulated in mice with specific deletion of VNUT in spinal dorsal horn (SDH) neurons, but not in mice lacking VNUT in primary sensory neurons, microglia or astrocytes. Conversely, ectopic VNUT expression in SDH neurons of VNUT-deficient mice restored PNI-induced increase in [ATP]e and pain. Thus, VNUT is necessary for exocytotic ATP release from SDH neurons which contributes to neuropathic pain. PMID:27515581

  6. Modeling the effects of hypoxia on ATP turnover in exercising muscle

    Science.gov (United States)

    Arthur, P. G.; Hogan, M. C.; Bebout, D. E.; Wagner, P. D.; Hochachka, P. W.

    1992-01-01

    Most models of metabolic control concentrate on the regulation of ATP production and largely ignore the regulation of ATP demand. We describe a model, based on the results of Hogan et al. (J. Appl. Physiol. 73: 728-736, 1992), that incorporates the effects of ATP demand. The model is developed from the premise that a unique set of intracellular conditions can be measured at each level of ATP turnover and that this relationship is best described by energetic state. Current concepts suggest that cells are capable of maintaining oxygen consumption in the face of declines in the concentration of oxygen through compensatory changes in cellular metabolites. We show that these compensatory changes can cause significant declines in ATP demand and result in a decline in oxygen consumption and ATP turnover. Furthermore we find that hypoxia does not directly affect the rate of anaerobic ATP synthesis and associated lactate production. Rather, lactate production appears to be related to energetic state, whatever the PO2. The model is used to describe the interaction between ATP demand and ATP supply in determining final ATP turnover.

  7. Mitochondrial calcium signaling mediates rhythmic extracellular ATP accumulation in suprachiasmatic nucleus astrocytes.

    Science.gov (United States)

    Burkeen, Jeff F; Womac, Alisa D; Earnest, David J; Zoran, Mark J

    2011-06-08

    The master circadian pacemaker located within the suprachiasmatic nuclei (SCN) controls neural and neuroendocrine rhythms in the mammalian brain. Astrocytes are abundant in the SCN, and this cell type displays circadian rhythms in clock gene expression and extracellular accumulation of ATP. Still, the intracellular signaling pathways that link the SCN clockworks to circadian rhythms in extracellular ATP accumulation remain unclear. Because ATP release from astrocytes is a calcium-dependent process, we investigated the relationship between intracellular Ca(2+) and ATP accumulation and have demonstrated that intracellular Ca(2+) levels fluctuate in an antiphase relationship with rhythmic ATP accumulation in rat SCN2.2 cell cultures. Furthermore, mitochondrial Ca(2+) levels were rhythmic and maximal in precise antiphase with the peak in cytosolic Ca(2+). In contrast, our finding that peak mitochondrial Ca(2+) occurred during maximal extracellular ATP accumulation suggests a link between these cellular rhythms. Inhibition of the mitochondrial Ca(2+) uniporter disrupted the rhythmic production and extracellular accumulation of ATP. ATP, calcium, and the biological clock affect cell division and have been implicated in cell death processes. Nonetheless, rhythmic extracellular ATP accumulation was not disrupted by cell cycle arrest and was not correlated with caspase activity in SCN2.2 cell cultures. Together, these results demonstrate that mitochondrial Ca(2+) mediates SCN2.2 rhythms in extracellular ATP accumulation and suggest a role for circadian gliotransmission in SCN clock function.

  8. ATP sensing in living plant cells reveals tissue gradients and stress dynamics of energy physiology.

    Science.gov (United States)

    De Col, Valentina; Fuchs, Philippe; Nietzel, Thomas; Elsässer, Marlene; Voon, Chia Pao; Candeo, Alessia; Seeliger, Ingo; Fricker, Mark D; Grefen, Christopher; Møller, Ian Max; Bassi, Andrea; Lim, Boon Leong; Zancani, Marco; Meyer, Andreas J; Costa, Alex; Wagner, Stephan; Schwarzländer, Markus

    2017-07-18

    Growth and development of plants is ultimately driven by light energy captured through photosynthesis. ATP acts as universal cellular energy cofactor fuelling all life processes, including gene expression, metabolism, and transport. Despite a mechanistic understanding of ATP biochemistry, ATP dynamics in the living plant have been largely elusive. Here, we establish MgATP2- measurement in living plants using the fluorescent protein biosensor ATeam1.03-nD/nA. We generate Arabidopsis sensor lines and investigate the sensor in vitro under conditions appropriate for the plant cytosol. We establish an assay for ATP fluxes in isolated mitochondria, and demonstrate that the sensor responds rapidly and reliably to MgATP2- changes in planta. A MgATP2- map of the Arabidopsis seedling highlights different MgATP2- concentrations between tissues and within individual cell types, such as root hairs. Progression of hypoxia reveals substantial plasticity of ATP homeostasis in seedlings, demonstrating that ATP dynamics can be monitored in the living plant.

  9. Glucose Triggers ATP Secretion from Bacteria in a Growth-Phase-Dependent Manner

    Science.gov (United States)

    Hironaka, Ippei; Iwase, Tadayuki; Sugimoto, Shinya; Okuda, Ken-ichi; Tajima, Akiko; Yanaga, Katsuhiko

    2013-01-01

    ATP modulates immune cell functions, and ATP derived from gut commensal bacteria promotes the differentiation of T helper 17 (Th17) cells in the intestinal lamina propria. We recently reported that Enterococcus gallinarum, isolated from mice and humans, secretes ATP. We have since found and characterized several ATP-secreting bacteria. Of the tested enterococci, Enterococcus mundtii secreted the greatest amount of ATP (>2 μM/108 cells) after overnight culture. Glucose, not amino acids and vitamins, was essential for ATP secretion from E. mundtii. Analyses of energy-deprived cells demonstrated that glycolysis is the most important pathway for bacterial ATP secretion. Furthermore, exponential-phase E. mundtii and Enterococcus faecalis cells secrete ATP more efficiently than stationary-phase cells. Other bacteria, including Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, also secrete ATP in exponential but not stationary phase. These results suggest that various gut bacteria, including commensals and pathogens, might secrete ATP at any growth phase and modulate immune cell function. PMID:23354720

  10. Evidence for Extracellular ATP as a Stress Signal in a Single-Celled Organism.

    Science.gov (United States)

    Sivaramakrishnan, Venketesh; Fountain, Samuel J

    2015-08-01

    ATP is omnipresent in biology and acts as an extracellular signaling molecule in mammals. Information regarding the signaling function of extracellular ATP in single-celled eukaryotes is lacking. Here, we explore the role of extracellular ATP in cell volume recovery during osmotic swelling in the amoeba Dictyostelium. Release of micromolar ATP could be detected during cell swelling and regulatory cell volume decrease (RVD) phases during hypotonic challenge. Scavenging ATP with apyrase caused profound cell swelling and loss of RVD. Apyrase-induced swelling could be rescued by 100 μM βγ-imidoATP. N-Ethylmalemide (NEM), an inhibitor of vesicular exocytosis, caused heightened cell swelling, loss of RVD, and inhibition of ATP release. Amoebas with impaired contractile vacuole (CV) fusion (drainin knockout [KO] cells) displayed increased swelling but intact ATP release. One hundred micromolar Gd(3+) caused cell swelling while blocking any recovery by βγ-imidoATP. ATP release was 4-fold higher in the presence of Gd(3+). Cell swelling was associated with an increase in intracellular nitric oxide (NO), with NO-scavenging agents causing cell swelling. Swelling-induced NO production was inhibited by both apyrase and Gd(3+), while NO donors rescued apyrase- and Gd(3+)-induced swelling. These data suggest extracellular ATP released during cell swelling is an important signal that elicits RVD. Though the cell surface receptor for ATP in Dictyostelium remains elusive, we suggest ATP operates through a Gd(3+)-sensitive receptor that is coupled with intracellular NO production. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Silencing of atp6v1c1 prevents breast cancer growth and bone metastasis.

    Science.gov (United States)

    Feng, Shengmei; Zhu, Guochun; McConnell, Matthew; Deng, Lianfu; Zhao, Qiang; Wu, Mengrui; Zhou, Qi; Wang, Jinshen; Qi, Jin; Li, Yi-Ping; Chen, Wei

    2013-01-01

    Previous studies have shown that Atp6v1c1, a regulator of the assembly of the V0 and V1 domains of the V-ATPase complex, is up-regulated in metastatic oral tumors. Despite these studies, the function of Atp6v1c1 in tumor growth and metastasis is still unknown. Atp6v1c1's expression in metastatic oral squamous cell carcinoma indicates that Atp6v1c1 has an important function in cancer growth and metastasis. We hypothesized that elevated expression of Atp6v1c1 is essential to cancer growth and metastasis and that Atp6v1c1 promotes cancer growth and metastasis through activation of V-ATPase activity. To test this hypothesis, a Lentivirus-mediated RNAi knockdown approach was used to study the function of Atp6v1c1 in mouse 4T1 mammary tumor cell proliferation and migration in vitro and cancer growth and metastasis in vivo. Our data revealed that silencing of Atp6v1c1 in 4T1 cancer cells inhibited lysosomal acidification and severely impaired 4T1 cell growth, migration, and invasion through Matrigel in vitro. We also show that Atp6v1c1 knockdown with Lenti-c1s3, a lentivirus targeting Atp6v1c1 for shRNA mediated knockdown, can significantly inhibit 4T1 xenograft tumor growth, metastasis, and osteolytic lesions in vivo. Our study demonstrates that Atp6v1c1 may promote breast cancer growth and bone metastasis through regulation of lysosomal V-ATPase activity, indicating that Atp6v1c1 may be a viable target for breast cancer therapy and silencing of Atp6v1c1 may be an innovative therapeutic approach for the treatment and prevention of breast cancer growth and metastasis.

  12. Activation of ATP/UTP-selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle

    DEFF Research Database (Denmark)

    Yegutkin, G.G.; Gonzalez-Alonso, J.; Rosenmeier, Jaya Birgitte

    2008-01-01

    and sympatholytic effects of exogenous ATP in the skeletal muscle vasculature are largely mediated via ATP itself rather than its dephosphorylated metabolites, most likely via binding to endothelial ATP/UTP-selective P2Y(2) receptors. These data are consistent with a role of ATP in skeletal muscle hyperaemia...

  13. A divergent ADP/ATP carrier in the hydrogenosomes of Trichomonas gallinae argues for an independent origin of these organelles.

    NARCIS (Netherlands)

    Tjaden, J.; Haferkamp, I.; Boxma, B.; Tielens, A.G.; Huynen, M.A.; Hackstein, J.H.P.

    2004-01-01

    The evolution of mitochondrial ADP and ATP exchanging proteins (AACs) highlights a key event in the evolution of the eukaryotic cell, as ATP exporting carriers were indispensable in establishing the role of mitochondria as ATP-generating cellular organelles. Hydrogenosomes, i.e. ATP- and

  14. A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2

    Directory of Open Access Journals (Sweden)

    Nico Mauri

    2017-08-01

    Full Text Available Spongy degeneration with cerebellar ataxia (SDCA is a genetically heterogeneous neurodegenerative disorder with autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. Using a combined linkage and homozygosity mapping approach we identified an ∼10.6 Mb critical interval on chromosome 5 in a Malinois family with four puppies affected by cerebellar dysfunction. Visual inspection of the 10.6 Mb interval in whole-genome sequencing data from one affected puppy revealed a 227 bp SINE insertion into the ATP1B2 gene encoding the β2 subunit of the Na+/K+-ATPase holoenzyme (ATP1B2:c.130_131insLT796559.1:g.50_276. The SINE insertion caused aberrant RNA splicing. Immunohistochemistry suggested a reduction of ATP1B2 protein expression in the central nervous system of affected puppies. Atp1b2 knockout mice had previously been reported to show clinical and neurohistopathological findings similar to the affected Malinois puppies. Therefore, we consider ATP1B2:c.130_131ins227 the most likely candidate causative variant for a second subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia subtype 2 (SDCA2. Our study further elucidates the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population in Malinois and the other varieties of the Belgian Shepherd breed. ATP1B2 thus represents another candidate gene for human inherited cerebellar ataxias, and SDCA2-affected Malinois puppies may serve as a naturally occurring animal model for this disorder.

  15. A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2).

    Science.gov (United States)

    Mauri, Nico; Kleiter, Miriam; Dietschi, Elisabeth; Leschnik, Michael; Högler, Sandra; Wiedmer, Michaela; Dietrich, Joëlle; Henke, Diana; Steffen, Frank; Schuller, Simone; Gurtner, Corinne; Stokar-Regenscheit, Nadine; O'Toole, Donal; Bilzer, Thomas; Herden, Christiane; Oevermann, Anna; Jagannathan, Vidhya; Leeb, Tosso

    2017-08-07

    Spongy degeneration with cerebellar ataxia (SDCA) is a genetically heterogeneous neurodegenerative disorder with autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. Using a combined linkage and homozygosity mapping approach we identified an ∼10.6 Mb critical interval on chromosome 5 in a Malinois family with four puppies affected by cerebellar dysfunction. Visual inspection of the 10.6 Mb interval in whole-genome sequencing data from one affected puppy revealed a 227 bp SINE insertion into the ATP1B2 gene encoding the β2 subunit of the Na+/K+-ATPase holoenzyme (ATP1B2:c.130_131insLT796559.1:g.50_276). The SINE insertion caused aberrant RNA splicing. Immunohistochemistry suggested a reduction of ATP1B2 protein expression in the central nervous system of affected puppies. Atp1b2 knockout mice had previously been reported to show clinical and neurohistopathological findings similar to the affected Malinois puppies. Therefore, we consider ATP1B2:c.130_131ins227 the most likely candidate causative variant for a second subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia subtype 2 (SDCA2). Our study further elucidates the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population in Malinois and the other varieties of the Belgian Shepherd breed. ATP1B2 thus represents another candidate gene for human inherited cerebellar ataxias, and SDCA2-affected Malinois puppies may serve as a naturally occurring animal model for this disorder. Copyright © 2017 Mauri et al.

  16. Medicaid program; third party liability for medical assistance; FFP rates for skilled professional medical personnel and supporting staff; and sources of state share of financial participation--HCFA. Proposed rules.

    Science.gov (United States)

    1984-06-04

    These proposed regulations would--(1) Broaden the scope of services for which a State must collect from third parties the cost of medical assistance furnished to Medicaid recipients, remove the specific requirements for the terms of cooperative agreements for third party collections, and revise the methods of paying claims involving third party liability; (2) Clarify criteria used in determining whether skilled professional medical personnel and supporting staff involved in the administration of the Medicaid program quality for 75 percent Federal matching; and (3) Clarify policy to permit public and private donations to be used as a State's share of financial participation in the entire Medicaid program, instead of only for training expenditures. The proposed amendments would clarify policy and reduce program expenditures.

  17. The Wright Institute Sanctuary Project: Development and Proposed Evaluation of a Graduate Training Program Providing Clinical Services to Asylum Seekers in the Bay Area

    Science.gov (United States)

    Padilla, Brenda Lisa

    2012-01-01

    This study highlights the development of a graduate training program at The Wright Institute in Berkeley, CA, which provides assessment services for undocumented immigrants seeking asylum. This program focuses on the needs of a general asylum seeking population, with a specific relevance to some of the populations that may be served in the…

  18. Thesis Proposal

    DEFF Research Database (Denmark)

    Sloth, Erik

    2010-01-01

    Strukturen i Thesis proposal er følgende: Først præsenteres mine konkrete empiriske forskningsprojekter som skal munde ud i afhandlingens artikler. Jeg præsenterer herefter de teoretiske overvejelser omkring oplevelsesbegrebet og forbrugerkulturteori som danner baggrund for at jeg er nået frem til...

  19. Intracellular ATP concentration contributes to the cytotoxic and cytoprotective effects of adenosine.

    Directory of Open Access Journals (Sweden)

    Shujue Li

    Full Text Available Extracellular adenosine (ADE interacts with cells by two pathways: by activating cell surface receptors at nanomolar/micromolar concentrations; and by interfering with the homeostasis of the intracellular nucleotide pool at millimolar concentrations. Ade shows both cytotoxic and cytoprotective effects; however, the underlying mechanisms remain unclear. In the present study, the effects of adenosine-mediated ATP on cell viability were investigated. Adenosine treatment was found to be cytoprotective in the low intracellular ATP state, but cytotoxic under the normal ATP state. Adenosine-mediated cytotoxicity and cytoprotection rely on adenosine-derived ATP formation, but not via the adenosine receptor pathway. Ade enhanced proteasome inhibition-induced cell death mediated by ATP generation. These data provide a new pathway by which adenosine exerts dual biological effects on cell viability, suggesting an important role for adenosine as an ATP precursor besides the adenosine receptor pathway.

  20. Facile conversion of ATP-binding RNA aptamer to quencher-free molecular aptamer beacon.

    Science.gov (United States)

    Park, Yoojin; Nim-Anussornkul, Duangrat; Vilaivan, Tirayut; Morii, Takashi; Kim, Byeang Hyean

    2018-01-15

    We have developed RNA-based quencher-free molecular aptamer beacons (RNA-based QF-MABs) for the detection of ATP, taking advantage of the conformational changes associated with ATP binding to the ATP-binding RNA aptamer. The RNA aptamer, with its well-defined structure, was readily converted to the fluorescence sensors by incorporating a fluorophore into the loop region of the hairpin structure. These RNA-based QF-MABs exhibited fluorescence signals in the presence of ATP relative to their low background signals in the absence of ATP. The fluorescence emission intensity increased upon formation of a RNA-based QF-MAB·ATP complex. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  2. Stimulation of acetoin production in metabolically engineered Lactococcus lactis by increasing ATP demand

    DEFF Research Database (Denmark)

    Liu, Jianming; Kandasamy, Vijayalakshmi; Würtz, Anders

    2016-01-01

    Having a sufficient supply of energy, usually in the form of ATP, is essential for all living organisms. In this study, however, we demonstrate that it can be beneficial to reduce ATP availability when the objective is microbial production. By introducing the ATP hydrolyzing F1-ATPase into a Lact......Having a sufficient supply of energy, usually in the form of ATP, is essential for all living organisms. In this study, however, we demonstrate that it can be beneficial to reduce ATP availability when the objective is microbial production. By introducing the ATP hydrolyzing F1-ATPase...... mM (32 g/L) of glucose into 146.5 mM (12.9 g/L) acetoin with a yield of 83 % of the theoretical maximum. To further demonstrate the potential of the cell factory developed, we complemented it with the lactose plasmid pLP712, which allowed for growth and acetoin production from a dairy waste stream...

  3. K-ATP channel expression and pharmacological in vivo and in vitro studies of the K-ATP channel blocker PNU-37883A in rat middle meningeal arteries

    DEFF Research Database (Denmark)

    Ploug, K.B.; Boni, L.J.; Baun, M.

    2008-01-01

    intracranial arteries, including the middle meningeal artery (MMA). We studied the K-ATP channel expression profile in rat MMA and examined the potential inhibitory effects of the K-ATP channel blocker PNU-37883A on K-ATP channel opener-induced relaxation of the rat MMA, using the three K-ATP channel openers...... levcromakalim, pinacidil and P-1075. Experimental approach: mRNA and protein expression of K-ATP channel subunits in the rat MMA were studied by quantitative real-time PCR and western blotting, respectively. The in vivo and in vitro effects of the K-ATP channel drugs on rat MMA were studied in the genuine...... closed cranial window model and in myograph baths, respectively. Key results: Expression studies indicate that inwardly rectifying K+ (Kir)6.1/sulphonylurea receptor (SUR) 2B is the major K-ATP channel complex in rat MMA. PNU-37883A (0.5 mg kg(-1)) significantly inhibited the in vivo dilatory effect...

  4. The cotton ATP synthase δ1 subunit is required to maintain a higher ATP/ADP ratio that facilitates rapid fibre cell elongation.

    Science.gov (United States)

    Pang, Y; Wang, H; Song, W-Q; Zhu, Y-X

    2010-11-01

    The δ subunit of mitochondrial ATP synthase serves as a linker between the F(0) and F(1) sectors. Here, through microarray and quantitative RT-PCR, we found that the δ1 subunit was significantly up-regulated during cotton fibre cell elongation. Both the relative level and duration of GhATPδ1 transcripts correlated positively with the final length of different cotton germplasms. Elongating fibre cells had a significantly elevated ATP/ADP ratio, suggesting that a higher energy input is probably required for primary fibre cell wall formation and elongation. We obtained a putative full-length GhATPδ1 cDNA that shows 37% sequence identity to the Saccharomyces cerevisiae ATP16 at the deduced amino acid level. An almost wild-type growth rate was restored in atp16Δ cells that expressed GhATPδ1, with a resultant ATP/ADP ratio similar to that found in wild-type cells, indicating that the cotton gene was functional in yeast. Mitochondria prepared from 10 dpa wild-type fibre cells showed significantly higher ATP synthase activity in comparison to ovule samples from wild type and leaf samples. Exogenous application of piceatannol (PA) or oligomycin (OM), inhibitors of ATP synthase F(1) or F(0) subunits, respectively, in ovule culture media resulted in much shorter fibre cells and a significantly lower ATP/ADP ratio. Our data suggest that GhATPδ1 is important for activity of mitochondrial ATP synthase and is probably related to cotton fibre elongation. © 2010 German Botanical Society and The Royal Botanical Society of The Netherlands.

  5. Extracellular ATP acts as a damage-associated molecular pattern (DAMP) signal in plants

    OpenAIRE

    Tanaka, Kiwamu; Choi, Jeongmin; Cao, Yangrong; Stacey, Gary

    2014-01-01

    As sessile organisms, plants have evolved effective mechanisms to protect themselves from environmental stresses. Damaged (i.e., wounded) plants recognize a variety of endogenous molecules as danger signals, referred to as damage-associated molecular patterns (DAMPs). ATP is among the molecules that are released by cell damage, and recent evidence suggests that ATP can serve as a DAMP. Although little studied in plants, extracellular ATP is well known for its signaling role in animals, includ...

  6. The National Shipbuilding Program. Preliminary Impact Analysis of Proposed Revisions of National Ambient Air Quality Standard for Ozone and Particulate Matter

    National Research Council Canada - National Science Library

    1997-01-01

    ...) and particulate matter (PM). The analysis was performed to provide information to the U.S. ship building and ship repair industry, so that companies in that industry could determine whether to submit comments on these EPA proposals...

  7. [Environmental Hazards Assessment Program annual report, June 1992--June 1993]. Proposal for a new program leading to the Master of Science degree in environmental studies to be offered jointly by the Medical University of South Carolina and the University of Charleston, South Carolina

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-01

    The Medical University of South Carolina (MUSC) and the University of Charleston, South Carolina (UCSC) propose to offer the degree of Master of Science in Environmental Studies. The proposed starting date is August 1994. The purpose of this interdisciplinary program is to offer nationally and internationally recognized graduate level training in the areas of environmental policy, science, and health risk assessment. Special emphasis will be placed on human health. Included in this proposal are a needs assessment for environmental science professionals along with employment projections and salary expectations. The Environmental Science program is described and its relationship to other programs within MUSC and UCSC, as well as its relation to similar programs at other institutions are examined. Enrollment is discussed, admission requirements and standards outlined, and the curriculum is described. Academic and physical resources are examined and estimated costs are given.

  8. Treatment with Oral ATP decreases alternating hemiplegia of childhood with de novo ATP1A3 Mutation.

    Science.gov (United States)

    Ju, Jun; Hirose, Shinichi; Shi, Xiu-Yu; Ishii, Atsushi; Hu, Lin-Yan; Zou, Li-Ping

    2016-05-04

    Alternating hemiplegia of childhood is an intractable neurological disorder characterized by recurrent episodes of alternating hemiplegia accompanied by other paroxysmal symptoms. Recent research has identified mutations in the ATP1A3 gene as the underlying cause. Adenosine-5'-triphosphate has a vasodilatory effect, can enhance muscle strength and physical performance, and was hypothesized to improve the symptoms of paroxysmal hemiplegia. A 7-year-old boy with alternating hemiplegia of childhood who was positive for a de novo ATP1A3 mutation was treated with adenosine- 5'- triphosphate supplementation orally as an innovative therapy for 2 years. Outcome was evaluated through the follow-up of improvement of hemiplegic episodes and psychomotor development. Side effects and safety were monitored in regularity. With the dosage of adenosine-5'-triphosphate administration increased, the patient showed significantly less frequency and shorter duration of hemiplegic episodes. Treatment with adenosine-5'-triphosphate was correlated with a marked amelioration of alternating hemiplegia of childhood episodes, and psychomotor development has improved. The maximum dose of oral administration of adenosine-5'-triphosphate reached 25 mg/kg per day. Adenosine-5'-triphosphate therapy was well tolerated without complaint of discomfort and side effects. The 2-year follow-up outcome of adenosine-5'-triphosphate therapy for alternating hemiplegia of childhood was successful.

  9. CgII cleaves DNA using a mechanism distinct from other ATP-dependent restriction endonucleases.

    Science.gov (United States)

    Toliusis, Paulius; Zaremba, Mindaugas; Silanskas, Arunas; Szczelkun, Mark D; Siksnys, Virginijus

    2017-08-21

    The restriction endonuclease CglI from Corynebacterium glutamicum recognizes an asymmetric 5'-GCCGC-3' site and cleaves the DNA 7 and 6/7 nucleotides downstream on the top and bottom DNA strands, respectively, in an NTP-hydrolysis dependent reaction. CglI is composed of two different proteins: an endonuclease (R.CglI) and a DEAD-family helicase-like ATPase (H.CglI). These subunits form a heterotetrameric complex with R2H2 stoichiometry. However, the R2H2·CglI complex has only one nuclease active site sufficient to cut one DNA strand suggesting that two complexes are required to introduce a double strand break. Here, we report studies to evaluate the DNA cleavage mechanism of CglI. Using one- and two-site circular DNA substrates we show that CglI does not require two sites on the same DNA for optimal catalytic activity. However, one-site linear DNA is a poor substrate, supporting a mechanism where CglI complexes must communicate along the one-dimensional DNA contour before cleavage is activated. Based on experimental data, we propose that adenosine triphosphate (ATP) hydrolysis by CglI produces translocation on DNA preferentially in a downstream direction from the target, although upstream translocation is also possible. Our results are consistent with a mechanism of CglI action that is distinct from that of other ATP-dependent restriction-modification enzymes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Dual role of PKA in phenotypic modulation of vascular smooth muscle cells by extracellular ATP.

    Science.gov (United States)

    Hogarth, D Kyle; Sandbo, Nathan; Taurin, Sebastien; Kolenko, Vladimir; Miano, Joseph M; Dulin, Nickolai O

    2004-08-01

    Extracellular ATP is released from activated platelets and endothelial cells and stimulates proliferation of vascular smooth muscle cells (VSMC). We found that ATP stimulates a profound but transient activation of protein kinase A (PKA) via purinergic P2Y receptors. The specific inhibition of PKA by adenovirus-mediated transduction of the PKA inhibitor (PKI) attenuates VSMC proliferation in response to ATP, suggesting a positive role for transient PKA activation in VSMC proliferation. By contrast, isoproterenol and forskolin, which stimulate a more sustained PKA activation, inhibit VSMC growth as expected. On the other hand, the activity of serum response factor (SRF) and the SRF-dependent expression of smooth muscle (SM) genes, such as SM-alpha-actin and SM22, are extremely sensitive to regulation by PKA, and even transient PKA activation by ATP is sufficient for their downregulation. Analysis of the dose responses of PKA activation, VSMC proliferation, SRF activity, and SM gene expression to ATP, with or without PKI overexpression, suggests the following model for the phenotypic modulation of VSMC by ATP, in which the transient PKA activation plays a critical role. At low micromolar doses, ATP elicits a negligible effect on DNA synthesis but induces profound SRF activity and SM gene expression, thus promoting the contractile VSMC phenotype. At high micromolar doses, ATP inhibits SRF activity and SM gene expression and promotes VSMC growth in a manner dependent on transient PKA activation. Transformation of VSMC by high doses of ATP can be prevented and even reversed by inhibition of PKA activity.

  11. Extracellular ATP acts as a damage-associated molecular pattern (DAMP) signal in plants.

    Science.gov (United States)

    Tanaka, Kiwamu; Choi, Jeongmin; Cao, Yangrong; Stacey, Gary

    2014-01-01

    As sessile organisms, plants have evolved effective mechanisms to protect themselves from environmental stresses. Damaged (i.e., wounded) plants recognize a variety of endogenous molecules as danger signals, referred to as damage-associated molecular patterns (DAMPs). ATP is among the molecules that are released by cell damage, and recent evidence suggests that ATP can serve as a DAMP. Although little studied in plants, extracellular ATP is well known for its signaling roles in animals, including acting as a DAMP during the inflammatory response and wound healing. If ATP acts outside the cell, then it is reasonable to expect that it is recognized by a plasma membrane-localized receptor. Recently, DORN1, a lectin receptor kinase, was shown to recognize extracellular ATP in Arabidopsis. DORN1 is the founding member of a new purinoceptor subfamily, P2K (P2 receptor kinase), which is plant-specific. P2K1 (DORN1) is required for ATP-induced cellular responses (e.g., cytosolic Ca(2+) elevation, MAPK phosphorylation, and gene expression). Genetic analysis of loss-of-function mutants and overexpression lines showed that P2K1 participates in the plant wound response, consistent with the role of ATP as a DAMP. In this review, we summarize past research on the roles and mechanisms of extracellular ATP signaling in plants, and discuss the direction of future research on extracellular ATP as a DAMP signal.

  12. ATP release and extracellular nucleotidase activity in erythrocytes and coronary circulation of rainbow trout

    DEFF Research Database (Denmark)

    Jensen, Frank Bo; Agnisola, Claudio; Novak, Ivana

    2009-01-01

    The present study tested the hypothesis that rainbow trout erythrocytes release ATP upon deoxygenation, a mechanism that enables mammalian erythrocytes to produce local vasodilation. We also investigated ATP release and ectonucleotidase activity in the coronary circulation of the isolated trout...... heart. Erythrocytes suspended in an albumin-containing saline and equilibrated at physiological Pco2 showed negligible hemolysis (... in its absence, revealing the presence of ectonucleotidase activity. The induction of either a slow (minutes) or a fast (seconds) decrease in hemoglobin O2 saturation did not lead to additional ATP release. An elevation of Pco2 was also without influence on erythrocyte ATP release. In the saline...

  13. The current child and adolescent health screening system: an assessment and proposal for an early and periodic check-up program

    Directory of Open Access Journals (Sweden)

    Baik-Lin Eun

    2010-03-01

    Full Text Available Purpose : Recent changes in the population structure of Korea, such as rapid decline in birth rate and exponential increase in old-aged people, prompted us to prepare a new health improvement program in children and adolescents. Methods : We reviewed current health screenings applied for children and adolescents in Korea and other developed countries. We collected and reviewed population-based data focused on mortality and morbidity, and other health-related statistical data. We generated problem lists in current systems and developed new principles. Results : Current health screening programs for children and adolescents were usually based on laboratory tests, such as blood tests, urinalysis, and radiologic tests. Almost all of these programs lacked evidence based on population data or controlled studies. In most developed countries, laboratory tests are used only very selectively, and they usually focus on primary prevention of diseases and health improvement using anticipatory guidance. In Korea, statistics on mortality and morbidity reveal that diseases related to lifestyle, such as obesity and metabolic syndrome, are increasing in all generations. Conclusion : We recommend a periodic health screening program with anticipatory guidance, which is focused on growth and developmental surveillance in infants and children. We no longer recommend old programs that are based on laboratory and radiologic examinations. School health screening programs should also be changed to meet current health issues, such as developing a healthier lifestyle to minimize risk behaviors&#8212;for example, good mental health, balanced nutrition, and more exercise.

  14. Molecular dynamics simulation studies of GLUT4: substrate-free and substrate-induced dynamics and ATP-mediated glucose transport inhibition.

    Science.gov (United States)

    Mohan, Suma; Sheena, Aswathy; Poulose, Ninu; Anilkumar, Gopalakrishnapillai

    2010-12-03

    Glucose transporter 4 (GLUT4) is an insulin facilitated glucose transporter that plays an important role in maintaining blood glucose homeostasis. GLUT4 is sequestered into intracellular vesicles in unstimulated cells and translocated to the plasma membrane by various stimuli. Understanding the structural details of GLUT4 will provide insights into the mechanism of glucose transport and its regulation. To date, a crystal structure for GLUT4 is not available. However, earlier work from our laboratory proposed a well validated homology model for GLUT4 based on the experimental data available on GLUT1 and the crystal structure data obtained from the glycerol 3-phosphate transporter. In the present study, the dynamic behavior of GLUT4 in a membrane environment was analyzed using three forms of GLUT4 (apo, substrate and ATP-substrate bound states). Apo form simulation analysis revealed an extracellular open conformation of GLUT4 in the membrane favoring easy exofacial binding of substrate. Simulation studies with the substrate bound form proposed a stable state of GLUT4 with glucose, which can be a substrate-occluded state of the transporter. Principal component analysis suggested a clockwise movement for the domains in the apo form, whereas ATP substrate-bound form induced an anti-clockwise rotation. Simulation studies suggested distinct conformational changes for the GLUT4 domains in the ATP substrate-bound form and favor a constricted behavior for the transport channel. Various inter-domain hydrogen bonds and switching of a salt-bridge network from E345-R350-E409 to E345-R169-E409 contributed to this ATP-mediated channel constriction favoring substrate occlusion and prevention of its release into cytoplasm. These data are consistent with the biochemical studies, suggesting an inhibitory role for ATP in GLUT-mediated glucose transport. In the absence of a crystal structure for any glucose transporter, this study provides mechanistic details of the conformational

  15. Modeling Dr. Dynasaur 2.0 Coverage and Finance Proposals: Effects of the Expansion of Vermont's Dr. Dynasaur Program to All Individuals Through Age 25.

    Science.gov (United States)

    Dick, Andrew W; Price, Carter C; Woods, Dulani; Freund, Deborah Anne; McNamara, Martin; Schramm, Steven P; Berkman, Elrycc; Dehner, Tom

    2017-01-01

    The authors assessed an expansion of Vermont's Dr. Dynasaur program that would cover all residents age 25 and younger. The current Dr. Dynasaur program combines Vermont's Medicaid program and Child Health Insurance Program for children ages 0 through 18 to provide a seamless insurance program for those with family incomes below 317 percent of the federal poverty level. The authors used RAND's COMPARE-VT microsimulation model with Vermont-specific demographic, economic, and actuarial data to estimate the effects on health insurance coverage, costs, and premiums. They also identified the new revenues required to fund the program expansion and explored three alternative financing strategies to raise those funds: (1) an increase in the Vermont income tax, (2) a Vermont payroll tax, and (3) a Vermont business enterprise tax. The authors found that enrollment would increase by more than 260 percent under the 100-percent enrollment scenario and by nearly 200 percent under the 70-percent enrollment scenario by 2019. Not surprisingly, the children and young adults who move off employer-sponsored insurance (ESI) and into Dr. Dynasaur 2.0 have considerably lower expected health care costs than those who remain on ESI, increasing the per-person premiums by nearly $1,000 for those remaining enrolled in ESI. Annual health care expenditures per person for children and young adults in 2019 are estimated at $4,325 with Medicare prices. The combination of increased reimbursement rates, large increases in enrollment, and relatively low Dr. Dynasaur premiums (no more than $720 per year) will require significant new tax revenues to meet program obligations.

  16. Draft Supplement to the Environmental Statement Fiscal Year 1976 Proposed Program : Facility Location Evaluation for Pebble Springs-Marion 500-KV Line Study Area 75-B.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1974-10-22

    Proposed is construction of an approximately 160 mile long, 500-kV, double-circuit transmission line from the proposed Pebble Springs Substation located southeast of Arlington, Oregon, to the existing Marion Substation, 11 miles west of Maupin, Oregon. Development is also proposed of a major switching complex, Pebble Springs Substation, near Arlington, Oregon. Depending on the final route chosen, from 45 to 71 miles of parallel, 9 to 42 miles of new, and 74 miles of existing right-of-way will be required. New access road requirements will range from 45 to 90 miles. Land use affected by the proposed facilities includes 800 to 855 acres of forestland removed from timber production. In addition, 50 miles of cropland, primarily wheat, and approximately 35 miles of grassland will be crossed. Disturbance to wildlife during construction will occur and habitat associated with the above land uses will be eliminated. Soil erosion and siltation, primarily during and immediately after construction will also occur. Visual impacts will occur near several highways, lakes, rivers, and recreation areas. Disturbances to nearby residents will occur during construction. An additional 45 acres of rangeland will be required for the proposed Pebble Springs Substation.

  17. PROPUESTA DE REESTRUCTURACIÓN DEL PROGRAMA DE FÍSICA Y QUÍMICA PARA ENSEÑANZA MEDIA (PROPOSAL FOR THE RESTRUCTURING OF THE PHYSICS AND CHEMISTRY STUDY PROGRAM IN SECONDARY EDUCATION

    Directory of Open Access Journals (Sweden)

    Herrera Vargas Leonardo

    2009-08-01

    Full Text Available Resumen:Este artículo presenta una propuesta de reestructuración del programa de Física y Química para la enseñanza media, la cual puede ser consultada en la tesis titulada “Evolución de los programas de enseñanza media en el área de Física y de Química propuestos por el Ministerio de Educación Pública-Costa Rica, para elciclo diversificado. Período 1980-2005”. En la propuesta para el programa de Física se realizó una comparación entre los contenidos del programa de ciencias sétimo año y el programa de Física de décimo y undécimo año.Para el caso de Quími ca la comparación se realizó entre los contenidos del programa de ciencias octavo año y el de Química de décimo y undécimo año. Dicha propuesta es producto de la triangulación que se llevó a cabo entre la revisión de los programas de enseñanza, las entrevistas realizadas a los asesores y profesores en ejercicio durante el periodo de estudio y el análisis de contenido.Abstract:This article presents a proposal for restructuring the program in Physics and Chemistry for secondary education, which can be found in the thesis entitled "Evolution of secondary education programs in the area of Physics and Chemistry proposed by the Ministry of Public Education-Costa Rica for the diversified cycle. Period 1980-2005. ". The proposal for the program of Physics a comparison was made between the contents of the science program for seventh grade and the program of physics for tenth and eleventh grades. I n the case of Chemistry a comparison was made between the content of the science program for the eighth grade and the program of Chemistry for the tenth and eleventh grades. The proposal is the result of triangulation, which took place between the revision of educational programs, interviews with counselors and in service teachers during the study and analysis of content.

  18. Immodest Proposals

    DEFF Research Database (Denmark)

    Bardzell, Jeffrey; Bardzell, Shaowen; Hansen, Lone Koefoed

    2015-01-01

    This paper offers theoretical support for research through design (RtD) by arguing that to legitimize and make use of research through design as research, HCI researchers need to explore and clarify how RtD objects contribute to knowledge. One way to pursue this goal is to leverage knowledge-prod...... fiction Menstruation Machine by Sputniko!, the paper explores how design objects coproduce knowledge, by working through complex design problem spaces in non-reductive ways, proposing new connections and distinctions, and embodying design ideas and processes across time and minds....

  19. Heterogeneity of ATP-sensitive K+ Channels in Cardiac Myocytes

    Science.gov (United States)

    Hong, Miyoun; Bao, Li; Kefaloyianni, Eirini; Agullo-Pascual, Esperanza; Chkourko, Halina; Foster, Monique; Taskin, Eylem; Zhandre, Marine; Reid, Dylan A.; Rothenberg, Eli; Delmar, Mario; Coetzee, William A.

    2012-01-01

    Ventricular ATP-sensitive potassium (KATP) channels link intracellular energy metabolism to membrane excitability and contractility. Our recent proteomics experiments identified plakoglobin and plakophilin-2 (PKP2) as putative KATP channel-associated proteins. We investigated whether the association of KATP channel subunits with junctional proteins translates to heterogeneous subcellular distribution within a cardiac myocyte. Co-immunoprecipitation experiments confirmed physical interaction between KATP channels and PKP2 and plakoglobin in rat heart. Immunolocalization experiments demonstrated that KATP channel subunits (Kir6.2 and SUR2A) are expressed at a higher density at the intercalated disk in mouse and rat hearts, where they co-localized with PKP2 and plakoglobin. Super-resolution microscopy demonstrate that KATP channels are clustered within nanometer distances from junctional proteins. The local KATP channel density, recorded in excised inside-out patches, was larger at the cell end when compared with local currents recorded from the cell center. The KATP channel unitary conductance, block by MgATP and activation by MgADP, did not differ between these two locations. Whole cell KATP channel current density (activated by metabolic inhibition) was ∼40% smaller in myocytes from mice haploinsufficient for PKP2. Experiments with excised patches demonstrated that the regional heterogeneity of KATP channels was absent in the PKP2 deficient mice, but the KATP channel unitary conductance and nucleotide sensitivities remained unaltered. Our data demonstrate heterogeneity of KATP channel distribution within a cardiac myocyte. The higher KATP channel density at the intercalated disk implies a possible role at the intercellular junctions during cardiac ischemia. PMID:23066018

  20. Mechanism of artemisinin resistance for malaria PfATP6 L263 mutations and discovering potential antimalarials: An integrated computational approach

    Science.gov (United States)

    Nagasundaram, N.; George Priya Doss, C.; Chakraborty, Chiranjib; Karthick, V.; Thirumal Kumar, D.; Balaji, V.; Siva, R.; Lu, Aiping; Ge, Zhang; Zhu, Hailong

    2016-07-01

    Artemisinin resistance in Plasmodium falciparum threatens global efforts in the elimination or eradication of malaria. Several studies have associated mutations in the PfATP6 gene in conjunction with artemisinin resistance, but the underlying molecular mechanism of the resistance remains unexplored. Associated mutations act as a biomarker to measure the artemisinin efficacy. In the proposed work, we have analyzed the binding affinity and efficacy between PfATP6 and artemisinin in the presence of L263D, L263E and L263K mutations. Furthermore, we performed virtual screening to identify potential compounds to inhibit the PfATP6 mutant proteins. In this study, we observed that artemisinin binding affinity with PfATP6 gets affected by L263D, L263E and L263K mutations. This in silico elucidation of artemisinin resistance enhanced the identification of novel compounds (CID: 10595058 and 10625452) which showed good binding affinity and efficacy with L263D, L263E and L263K mutant proteins in molecular docking and molecular dynamics simulations studies. Owing to the high propensity of the parasite to drug resistance the need for new antimalarial drugs will persist until the malarial parasites are eventually eradicated. The two compounds identified in this study can be tested in in vitro and in vivo experiments as possible candidates for the designing of new potential antimalarial drugs.

  1. Draft Supplement to the Environmental Statement Fiscal Year 1976 Proposed Program : Facility Location Evaluation for Hangman Creek Area Service Study Area 76-8.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1975-04-15

    Proposed construction of a substation near Hangmen Creek, south of Spokane, Washington. Summary of environmental impacts and adverse environmental effects: approximately 3 acres of grass and shrubs would be removed for the proposed substation. Depending upon the final site selected, a few trees could be removed. Some siltation to Hangman Creek would occur. Other impacts would include the removal of wildlife habitat associated with the above mentioned substation site requirements. Disturbance to wildlife during construction would occur. Some erosion and sedimentation would occur along with a certian degree of visual impact. 2 figs., 2 tabs.

  2. Draft Supplement to the Environmental Statement Fiscal Year 1976 Proposed Program : Facility Location Evaluation for Horse Heaven Hills Area Service (Horse Heaven Substation) Study Area 75-7.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1974-10-22

    The proposed plan of service consists of the construction of a new substation near Patterson, Washington. Land requirements for the new substation would be approximately 20 to 22 acres of land depending on the final site location chosen. Access road requirements range from 100 feet for alternative site 4 to 2000 feet for alternative site 2. The proposed facility would remove the land from potential irrigation development and could interfere with irrigation practices on adjacent land. Disturbance to wildlife and elimination of habitat associated with the above land requirements would occur. Soil erosion would result from site and access road grading. This facility would be visible from Washington Highway 14.

  3. Cervical anterior transpedicular screw fixation (ATPS)—Part II. Accuracy of manual insertion and pull-out strength of ATPS

    National Research Council Canada - National Science Library

    Koller, Heiko; Acosta, Frank; Tauber, Mark; Fox, Michael; Martin, Hudelmaier; Forstner, Rosmarie; Augat, Peter; Penzkofer, Rainer; Pirich, Christian; Kässmann, H; Resch, Herbert; Hitzl, Wolfgang

    2008-01-01

    .... To avoid the additional posterior surgery in these cases while increasing rigidity of anterior-only screw-plate constructs, the authors introduce the concept of anterior transpedicular screw (ATPS) fixation...

  4. Cultured senescent myoblasts derived from human vastus lateralis exhibit normal mitochondrial ATP synthesis capacities with correlating concomitant ROS production while whole cell ATP production is decreased

    DEFF Research Database (Denmark)

    Minet, Ariane D; Gaster, Michael

    2012-01-01

    satellite cells at early and late passage numbers. We show that cultured muscle satellite cells undergoing senescence express a reduced mitochondrial mass, decreased whole cell ATP level, normal to increased mitochondrial ATP production under ATP utilization, increased mitochondrial membrane potential......The free radical theory of aging says that increased oxidative stress and mitochondrial dysfunction are associated with old age. In the present study we have investigated the effects of cellular senescence on muscle energetic by comparing mitochondrial content and function in cultured muscle...... and increased superoxide/mitochondrial mass and hydrogen peroxide/mitochondrial mass ratios. Moreover, the increased ROS production correlates with the corresponding mitochondrial ATP production. Thus, myotubes differentiated from human myoblasts undergoing senescence have a reduced mitochondrial content...

  5. Visualization and measurement of ATP levels in living cells replicating hepatitis C virus genome RNA.

    Directory of Open Access Journals (Sweden)

    Tomomi Ando

    Full Text Available Adenosine 5'-triphosphate (ATP is the primary energy currency of all living organisms and participates in a variety of cellular processes. Although ATP requirements during viral lifecycles have been examined in a number of studies, a method by which ATP production can be monitored in real-time, and by which ATP can be quantified in individual cells and subcellular compartments, is lacking, thereby hindering studies aimed at elucidating the precise mechanisms by which viral replication energized by ATP is controlled. In this study, we investigated the fluctuation and distribution of ATP in cells during RNA replication of the hepatitis C virus (HCV, a member of the Flaviviridae family. We demonstrated that cells involved in viral RNA replication actively consumed ATP, thereby reducing cytoplasmic ATP levels. Subsequently, a method to measure ATP levels at putative subcellular sites of HCV RNA replication in living cells was developed by introducing a recently-established Förster resonance energy transfer (FRET-based ATP indicator, called ATeam, into the NS5A coding region of the HCV replicon. Using this method, we were able to observe the formation of ATP-enriched dot-like structures, which co-localize with non-structural viral proteins, within the cytoplasm of HCV-replicating cells but not in non-replicating cells. The obtained FRET signals allowed us to estimate ATP concentrations within HCV replicating cells as ∼5 mM at possible replicating sites and ∼1 mM at peripheral sites that did not appear to be involved in HCV replication. In contrast, cytoplasmic ATP levels in non-replicating Huh-7 cells were estimated as ∼2 mM. To our knowledge, this is the first study to demonstrate changes in ATP concentration within cells during replication of the HCV genome and increased ATP levels at distinct sites within replicating cells. ATeam may be a powerful tool for the study of energy metabolism during replication of the viral genome.

  6. Mesurements of intracellular ATP provide new insight into the regulation of glycolysis in the yeast Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Ytting, Cecilie Karkov; Fuglsang, Anja Thoe; Hiltunen, J. Kalervo

    2012-01-01

    Glycolysis in the yeast Saccharomyces cerevisiae exhibits temporal oscillation under anaerobic or semianaerobic conditions. Previous evidence indicated that at least two membrane-bound ATPases, the mitochondrial F0F1 ATPase and the plasma membrane P-type ATPase (Pma1p), were important in regulating...... of the temporal behaviour of intracellular ATP in a yeast strain with oscillating glycolysis showed that, in addition to oscillation in intracellular ATP, there is an overall slow decrease in intracellular ATP because the ATP consumption rate exceeds the ATP production in glycolysis. Measurements of the temporal...... activity is under strict control. In the absence of glucose ATPase activity is switched off, and the intracellular ATP concentration is high. When glucose is added to the cells the ATP concentration starts to decrease, because ATP consumption exceeds ATP production by glycolysis. Finally, when glucose...

  7. Global gene profiling of aging lungs in Atp8b1 mutant mice.

    Science.gov (United States)

    Soundararajan, Ramani; Stearns, Timothy M; Czachor, Alexander; Fukumoto, Jutaro; Turn, Christina; Westermann-Clark, Emma; Breitzig, Mason; Tan, Lee; Lockey, Richard F; King, Benjamin L; Kolliputi, Narasaiah

    2016-09-29

    Recent studies implicate cardiolipin oxidation in several age-related diseases. Atp8b1 encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in Atp8b1 gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between Atp8b1 mutation and age-related gene alteration is unknown. Therefore, we investigated how Atp8b1 mutation alters age-related genes. We performed Affymetrix gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months, 14 M, n=6) C57BL/6 and Atp8b1 mutant mice. In addition, Ingenuity Pathway Analysis (IPA) was performed. Differentially expressed genes were validated by quantitative real-time PCR (qRT-PCR). Global transcriptome analysis revealed 532 differentially expressed genes in Atp8b1 lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes in Atp8b1 lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase in Adamts2 and Mmp13 transcripts in aged Atp8b1 lungs was validated by qRT-PCR. Similarly, the decrease in Col1a1 and increase in Cxcr6 transcripts was confirmed in both Atp8b1 mutant and C57BL/6 lungs. Based on transcriptome profiling, our study indicates that Atp8b1 mutant mice may be susceptible to age-related lung diseases.

  8. Glyoxylate lowers metabolic ATP in human platelets without altering adenylate energy charge or aggregation.

    Science.gov (United States)

    Dangelmaier, Carol A; Holmsen, Holm

    2014-01-01

    Human blood platelets adhere to exposed collagen at the site of vascular injury, initiating a signaling cascade leading to fibrinogen activation, secretion of granules and aggregation, thus producing a stable thrombus. All these steps require metabolic ATP. In this study we have labeled the metabolic pool of ATP with nucleotides, treated platelets with various inhibitors and have monitored their ability to be activated. Incubating platelets with glyoxylate dramatically reduced the ATP level without a change in the adenylate energy charge (AEC). This reduction of ATP did not affect ADP-induced primary or secondary aggregation, whereas glyoxal, methyl glyoxal, or the combination of antimycin plus deoxyglucose reduced both ATP and AEC and inhibited aggregation. The reduction of ATP by glyoxylate was almost quantitatively matched by an increase in hypoxanthine without elevation of ADP. AMP, IMP or inosine, acetoacetate, aspartate, or glutamate had no effect on glyoxylate-induced breakdown of ATP, while pyruvate stopped the ATP reduction fast and efficiently. Glyoxylate also lowered the citrate content. The glyoxylate-induced breakdown of ATP coincided with an increase in fructose-1,6-bisphosphate, indicating that the phosphofructokinase reaction was the main ATP-consuming step. Glyoxylate was a substrate for lactate dehydrogenase although with a Km almost 100 times higher than pyruvate. We suggest that glyoxylate primarily competes with pyruvate in the pyruvate dehydrogenase reaction, thus lowering the citrate concentration, which in turn activates phosphofructokinase. Clearly, lowering of ATP in the cytosol by more than 50% does not affect platelet aggregation provided that the AEC is not reduced.

  9. ATP Binding and Hydrolysis Properties of ABCB10 and Their Regulation by Glutathione

    Science.gov (United States)

    Qiu, Wei; Liesa, Marc; Carpenter, Elizabeth P.; Shirihai, Orian S.

    2015-01-01

    ABCB10 (ATP binding cassette sub-family B10) is a mitochondrial inner-membrane ABC transporter. ABCB10 has been shown to protect the heart from the impact of ROS during ischemia-reperfusion and to allow for proper hemoglobin synthesis during erythroid development. ABC transporters are proteins that increase ATP binding and hydrolysis activity in the presence of the transported substrate. However, molecular entities transported by ABCB10 and its regulatory mechanisms are currently unknown. Here we characterized ATP binding and hydrolysis properties of ABCB10 by using the 8-azido-ATP photolabeling technique. This technique can identify potential ABCB10 regulators, transported substrates and amino-acidic residues required for ATP binding and hydrolysis. We confirmed that Gly497 and Lys498 in the Walker A motif, Glu624 in the Walker B motif and Gly602 in the C-Loop motif of ABCB10 are required for proper ATP binding and hydrolysis activity, as their mutation changed ABCB10 8-Azido-ATP photo-labeling. In addition, we show that the potential ABCB10 transported entity and heme precursor delta-aminolevulinic acid (dALA) does not alter 8-azido-ATP photo-labeling. In contrast, oxidized glutathione (GSSG) stimulates ATP hydrolysis without affecting ATP binding, whereas reduced glutathione (GSH) inhibits ATP binding and hydrolysis. Indeed, we detectABCB10 glutathionylation in Cys547 and show that it is one of the exposed cysteine residues within ABCB10 structure. In all, we characterize essential residues for ABCB10 ATPase activity and we provide evidence that supports the exclusion of dALA as a potential substrate directly transported by ABCB10. Last, we show the first molecular mechanism by which mitochondrial oxidative status, through GSH/GSSG, can regulate ABCB10. PMID:26053025

  10. Program Directors' Perceptions of Programmatic Attributes Contributing to Athletic Training Student Persistence

    Science.gov (United States)

    Bowman, Thomas G.; Dodge, Thomas M.; Mazerolle, Stephanie M.

    2015-01-01

    Context: Graduates of athletic training programs (ATPs) have identified factors contributing to their persistence through professional education. However, program directors have yet to elaborate on programmatic attributes that might contribute to athletic training student retention in their respective ATPs. Objective: To determine program…

  11. Draft Supplement to the Environmental Statement, Fiscal Year 1976 Proposed Program : Facility Location Evaluation for Ashe-Pebble Springs 500-KV Line, Study Area 75-3A.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1975-03-07

    Proposed is construction of an approximately 80-mile long, 500-kV single-circuit transmission line from Ashe Substation in the northeastern portion of the AEC Hanford Reservation to a proposed Pebble Springs Substation near Arlington, Oregon. In the eastern sector of the proposed facility from 49 to 58 miles of new right-of-way would be required depending on the final route chosen and approximately 15 miles of new access road. Land uses which could be affected by the proposed facility include 12 to 26 miles of wheatland, 4 to 10 miles of irrigated cropland, and 22 to 34 miles of rangeland crossed. The western sector would require approximately 25 miles of new right-of-way and 9 to 16 miles of new access road. Disturbance to wildlife during construction will occur, and habitat associated with the above rangeland and agricultural land will be eliminated. Soil erosion and siltation, primarily during and immediately after construction, will also occur. Visual impacts will occur primarily near several highways, recreation areas, and at river crossings particularly the Columbia River where extremely tall towers may be required. Disturbance to nearby residents will occur during construction.

  12. Draft Supplement to the Environmental Statement Fiscal Year 1976 Proposed Program : Facility Location Evaluation for Cheney-Four Lakes Area Service Study Area 76-7.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1975-04-15

    Proposed is construction of approximately 26 miles of 230-kV transmission line from the Four Mounds Area west of Spokane to either Cheney or Four Lakes Substation. Proposed also is construction of a new substation in the Four Mounds area. Depending upon final route location chosen, between 20 and 27 miles of new right-of-way would be required between the proposed Greenwood Substation and either Cheney or Four Lakes Substation. Between 25 and 41 miles of access road would also be required. Depending upon the final route selected, the amount of impact upon forest land would range from zero to 97 acres permanently removed. The amount of land temporarily disrupted for rangeland and cropland would be 8 to 13 acres and 30 to 40 acres, respectively. In addition, between approximately 4 and 8 acres of rangeland would be removed due to construction of the proposed new substation. Other impacts would include the removal of wildlife habitat associated with the above mentioned right-of-way requirements. Disturbance to wildlife during construction would occur. Some erosion and sedimentation would occur. Visual impacts would result from clearing rights-of-way through heavily forested areas. Noise and other disturbances to residents will occur, primarily during construction.

  13. Proposal for an advanced heat source assembly for the Isotope Brayton Power System. Volume 1. Technical program and statement of work

    Energy Technology Data Exchange (ETDEWEB)

    1974-12-09

    The technical program plan for evaluating the performance and safety of a radioisotope-fueled Brayton power system for space vehicles is presented with schedules for evaluating heat source design and safety, for specifying power system requirements, and for the development and operation of a ground demonstration system. (LCL)

  14. The Off-Site Plowshare and Vela Uniform Programs: Assessing Potential Environmental Liabilities through an Examination of Proposed Nuclear Projects,High Explosive Experiments, and High Explosive Construction Activities Volume 1 of 3

    Energy Technology Data Exchange (ETDEWEB)

    Beck Colleen M,Edwards Susan R.,King Maureen L.

    2011-09-01

    This document presents the results of nearly six years (2002-2008) of historical research and field studies concerned with evaluating potential environmental liabilities associated with U.S. Atomic Energy Commission projects from the Plowshare and Vela Uniform Programs. The Plowshare Program's primary purpose was to develop peaceful uses for nuclear explosives. The Vela Uniform Program focused on improving the capability of detecting, monitoring and identifying underground nuclear detonations. As a result of the Project Chariot site restoration efforts in the early 1990s, there were concerns that there might be other project locations with potential environmental liabilities. The Desert Research Institute conducted archival research to identify projects, an analysis of project field activities, and completed field studies at locations where substantial fieldwork had been undertaken for the projects. Although the Plowshare and Vela Uniform nuclear projects are well known, the projects that are included in this research are relatively unknown. They are proposed nuclear projects that were not executed, proposed and executed high explosive experiments, and proposed and executed high explosive construction activities off the Nevada Test Site. The research identified 170 Plowshare and Vela Uniform off-site projects and many of these had little or no field activity associated with them. However, there were 27 projects that merited further investigation and field studies were conducted at 15 locations.

  15. The Off-Site Plowshare and Vela Uniform Programs: Assessing Potential Environmental Liabilities through an Examination of Proposed Nuclear Projects,High Explosive Experiments, and High Explosive Construction Activities Volume 2 of 3

    Energy Technology Data Exchange (ETDEWEB)

    Beck Colleen M.,Edwards Susan R.,King Maureen L.

    2011-09-01

    This document presents the results of nearly six years (2002-2008) of historical research and field studies concerned with evaluating potential environmental liabilities associated with U.S. Atomic Energy Commission projects from the Plowshare and Vela Uniform Programs. The Plowshare Program's primary purpose was to develop peaceful uses for nuclear explosives. The Vela Uniform Program focused on improving the capability of detecting, monitoring and identifying underground nuclear detonations. As a result of the Project Chariot site restoration efforts in the early 1990s, there were concerns that there might be other project locations with potential environmental liabilities. The Desert Research Institute conducted archival research to identify projects, an analysis of project field activities, and completed field studies at locations where substantial fieldwork had been undertaken for the projects. Although the Plowshare and Vela Uniform nuclear projects are well known, the projects that are included in this research are relatively unknown. They are proposed nuclear projects that were not executed, proposed and executed high explosive experiments, and proposed and executed high explosive construction activities off the Nevada Test Site. The research identified 170 Plowshare and Vela Uniform off-site projects and many of these had little or no field activity associated with them. However, there were 27 projects that merited further investigation and field studies were conducted at 15 locations.

  16. The Off-Site Plowshare and Vela Uniform Programs: Assessing Potential Environmental Liabilities through an Examination of Proposed Nuclear Projects,High Explosive Experiments, and High Explosive Construction Activities Volume 3 of 3

    Energy Technology Data Exchange (ETDEWEB)

    Beck Colleen M.,Edwards Susan R.,King Maureen L.

    2011-09-01

    This document presents the results of nearly six years (2002-2008) of historical research and field studies concerned with evaluating potential environmental liabilities associated with U.S. Atomic Energy Commission projects from the Plowshare and Vela Uniform Programs. The Plowshare Program's primary purpose was to develop peaceful uses for nuclear explosives. The Vela Uniform Program focused on improving the capability of detecting, monitoring and identifying underground nuclear detonations. As a result of the Project Chariot site restoration efforts in the early 1990s, there were concerns that there might be other project locations with potential environmental liabilities. The Desert Research Institute conducted archival research to identify projects, an analysis of project field activities, and completed field studies at locations where substantial fieldwork had been undertaken for the projects. Although the Plowshare and Vela Uniform nuclear projects are well known, the projects that are included in this research are relatively unknown. They are proposed nuclear projects that were not executed, proposed and executed high explosive experiments, and proposed and executed high explosive construction activities off the Nevada Test Site. The research identified 170 Plowshare and Vela Uniform off-site projects and many of these had little or no field activity associated with them. However, there were 27 projects that merited further investigation and field studies were conducted at 15 locations.

  17. Development of an ATP measurement method suitable for xenobiotic treatment activated sludge biomass.

    Science.gov (United States)

    Nguyen, Lan Huong; Chong, Nyuk-Min

    2015-09-01

    Activated sludge consumes a large amount of energy to degrade a xenobiotic organic compound. By tracking the energy inventory of activated sludge biomass during the sludge's degradation of a xenobiotic, any disadvantageous effect on the sludge's performance caused by energy deficiency can be observed. The purpose of this study was to develop a reliable and accurate method for measuring the ATP contents of activated sludge cells that were to degrade a xenobiotic organic. Cell disruption and cellular ATP extraction were performed by a protocol with which xenobiotic degrading activated sludge biomass was washed with SDS, treated by Tris and TCA, and followed by bead blasting. The suspension of disrupted cells was filtered before the filtrate was injected into HPLC that was set at optimal conditions to measure the ATP concentration therein. This extraction protocol and HPLC measurement of ATP was evaluated for its linearity, limits of detection, and reproducibility. Evaluation test results reported a R(2) of 0.999 of linear fit of ATP concentration versus activated sludge concentration, a LOD=0.00045mg/L, a LOQ=0.0015mg/L for HPLC measurement of ATP, a MDL=0.46mg/g SS for ATP extraction protocol, and a recovery efficiency of 96.4±2%. This method of ATP measurement was simple, rapid, reliable, and was unburdened of some limitations other methods may have. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels.

    NARCIS (Netherlands)

    Carrasco, A.J.; Dzeja, P.P.; Alekseev, A.E.; Pucar, D.; Zingman, L.V.; Abraham, M.R.; Hodgson, D.M.; Bienengraeber, M.; Puceat, M.; Janssen, E.E.W.; Wieringa, B.; Terzic, A.

    2001-01-01

    Transduction of energetic signals into membrane electrical events governs vital cellular functions, ranging from hormone secretion and cytoprotection to appetite control and hair growth. Central to the regulation of such diverse cellular processes are the metabolism sensing ATP-sensitive K+ (K(ATP))

  19. Energy metabolic state in hypothermically stored boar spermatozoa using a revised protocol for efficient ATP extraction

    NARCIS (Netherlands)

    Nguyen, Quynh Thu; Wallner, Ulrike; Schmicke, Marion; Waberski, Dagmar; Henning, Heiko

    2016-01-01

    Mammalian spermatozoa utilize ATP as the energy source for key functions on the route to fertilization. ATP and its precursor nucleotides ADP and AMP are determined in many sperm physiology studies, mostly by bioluminescence assays. Assay results vary widely, mainly due to different efficiency in

  20. A futile cycle, formed between two ATP-dependant γ-glutamyl cycle ...

    Indian Academy of Sciences (India)

    Thus, in cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without production of glutathione and is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion observed in these cells. The model is also compatible with the ...

  1. Cloning and characterization of ATP synthase CF1 α gene from ...

    African Journals Online (AJOL)

    ATP synthase CF1 α subunit protein is a key enzyme for energy metabolism in plant kingdom, and plays an important role in multiple cell processes. In this study, the complete atpA gene (accession no. JN247444) was cloned from sweet potato (Ipomoea batatas L. Lam) by reverse transcriptasepolymerase chain reaction ...

  2. Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Feng; Stanevich, Vitali; Wlodarchak, Nathan; Sengupta, Rituparna; Jiang, Li; Satyshur, Kenneth A.; Xing, Yongna

    2013-10-08

    Proper activation of protein phosphatase 2A (PP2A) catalytic subunit is central for the complex PP2A regulation and is crucial for broad aspects of cellular function. The crystal structure of PP2A bound to PP2A phosphatase activator (PTPA) and ATPγS reveals that PTPA makes broad contacts with the structural elements surrounding the PP2A active site and the adenine moiety of ATP. PTPA-binding stabilizes the protein fold of apo-PP2A required for activation, and orients ATP phosphoryl groups to bind directly to the PP2A active site. This allows ATP to modulate the metal-binding preferences of the PP2A active site and utilize the PP2A active site for ATP hydrolysis. In vitro, ATP selectively and drastically enhances binding of endogenous catalytic metal ions, which requires ATP hydrolysis and is crucial for acquisition of pSer/Thr-specific phosphatase activity. Furthermore, both PP2A- and ATP-binding are required for PTPA function in cell proliferation and survival. Our results suggest novel mechanisms of PTPA in PP2A activation with structural economy and a unique ATP-binding pocket that could potentially serve as a specific therapeutic target.

  3. An Aptamer-Based Nanobiosensor for Real-Time Measurements of ATP Dynamics

    DEFF Research Database (Denmark)

    Özalp, Cengiz; Nielsen, Lise Junker; Olsen, Lars Folke

    2010-01-01

    A nanosensor based on a new DNA aptamer can show changes in intracellular concentration of ATP of 0.5 to 8 mM and thereby the kinetics of ATP-consuming reactions in real-time. The biosensor was protected against nuclease attack by being buried in a polyacrylamide nanoparticle. This strategy can...

  4. Small amounts of functional ATP7A protein permit mild phenotype

    DEFF Research Database (Denmark)

    Møller, Lisbeth Birk

    2015-01-01

    in the ATP7A gene. We have conducted several studies in the hope of uncovering the relationship between genotype and phenotype. We have examined the X-inactivation pattern in affected females, the effect of exon-deletions and-duplications, and splice-site mutations on the composition and amount of ATP7A...... individuals exhibited preferential inactivation of the X-chromosome with the mutated ATP7A gene. The observed mild phenotype in some patients with mutations that effect the composition of the ATP7A transcript, seems to be explained by the presence of a small amount of normal ATP7A transcript. The location...... of missense mutations on structural models of the ATP7A protein suggests that affected conserved residues generally lead to a severe phenotype. The ATP7A protein traffics within the cells. At low copper levels, ATP7A locates to the Trans-Golgi Network (TGN) to load cuproenzymes with copper, whereas at higher...

  5. Energetic and metabolic consequences of aerobic and an-aerobic ATP-production.

    NARCIS (Netherlands)

    Schreurs, V.V.A.M.; Aarts, M.J.; IJssennagger, N.; Hermans, J.; Hendriks, W.H.

    2007-01-01

    ATP, the currency of cellular energy metabolism, can be produced during aerobic and an-aerobic oxidation of metabolic substrates. The aerobic oxidation yields CO2 + H2O as metabolic end products while ATP is produced by oxidative phosphorylation in the mitochondria. Carbohydrate, protein and fat

  6. Optimization of ATP synthase function in mitochondria and chloroplasts via the adenylate kinase equilibrium

    Directory of Open Access Journals (Sweden)

    Abir U Igamberdiev

    2015-01-01

    Full Text Available The bulk of ATP synthesis in plants is performed by ATP synthase, the main bioenergetics engine of cells, operating both in mitochondria and in chloroplasts. The reaction mechanism of ATP synthase has been studied in detail for over half a century; however, its optimal performance depends also on the steady delivery of ATP synthase substrates and the removal of its products. For mitochondrial ATP synthase, we analyze here the provision of stable conditions for (i the supply of ADP and Mg2+, supported by adenylate kinase (AK equilibrium in the intermembrane space, (ii the supply of phosphate via membrane transporter in symport with H+, and (iii the conditions of outflow of ATP by adenylate transporter carrying out the exchange of free adenylates. We also show that, in chloroplasts, AK equilibrates adenylates and governs Mg2+ contents in the stroma, optimizing ATP synthase and Calvin cycle operation, and affecting the import of inorganic phosphate in exchange with triose phosphates. It is argued that chemiosmosis is not the sole component of ATP synthase performance, which also depends on AK-mediated equilibrium of adenylates and Mg2+, adenylate transport and phosphate release and supply.

  7. Effect of visible laser light on ATP level of anaemic red blood cell.

    Science.gov (United States)

    Suardi, Nursakinah; Sodipo, Bashiru Kayode; Mustafa, Mohd Zulkifli; Ali, Zalila

    2016-09-01

    In this work we present influence of visible laser light on ATP level and viability of anaemic red blood cell (RBC). The visible laser lights used in this work are 460nm and 532nm. The responses of ATP level in anaemic and normal RBC before and after laser irradiation at different exposure time (30, 40, 50 and 60s) were observed. Three aliquots were prepared from the ethylenediaminetetraacetic acid (EDTA) blood sample. One served as a control (untreated) and another two were irradiated with 460nm and 560nm lasers. Packed RBC was prepared to study ATP level in the RBC using CellTiter-GloLuminescent cell Viability Assay kit. The assay generates a glow type signal produced by luciferase reaction, which is proportional to the amount of ATP present in RBCs. Paired t-test were done to analyse ATP level before and after laser irradiation. The results revealed laser irradiation improve level of ATP in anaemic RBC. Effect of laser light on anaemic RBCs were significant over different exposure time for both 460nm (p=0.000) and 532nm (p=0.003). The result of ATP level is further used as marker for RBC viability. The influence of ATP level and viability were studied. Optical densities obtained from the data were used to determine cell viability of the samples. Results showed that laser irradiation increased viability of anaemic RBC compared to normal RBC. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Structural, biochemical and genetic characterization of dissimilatory ATP sulfurylase from Allochromatium vinosum.

    Directory of Open Access Journals (Sweden)

    Kristian Parey

    Full Text Available ATP sulfurylase (ATPS catalyzes a key reaction in the global sulfur cycle by reversibly converting inorganic sulfate (SO4 (2- with ATP to adenosine 5'-phosphosulfate (APS and pyrophosphate (PPi. In this work we report on the sat encoded dissimilatory ATP sulfurylase from the sulfur-oxidizing purple sulfur bacterium Allochromatium vinosum. In this organism, the sat gene is located in one operon and co-transcribed with the aprMBA genes for membrane-bound APS reductase. Like APS reductase, Sat is dispensible for growth on reduced sulfur compounds due to the presence of an alternate, so far unidentified sulfite-oxidizing pathway in A. vinosum. Sulfate assimilation also proceeds independently of Sat by a separate pathway involving a cysDN-encoded assimilatory ATP sulfurylase. We produced the purple bacterial sat-encoded ATP sulfurylase as a recombinant protein in E. coli, determined crucial kinetic parameters and obtained a crystal structure in an open state with a ligand-free active site. By comparison with several known structures of the ATPS-APS complex in the closed state a scenario about substrate-induced conformational changes was worked out. Despite different kinetic properties ATPS involved in sulfur-oxidizing and sulfate-reducing processes are not distinguishable on a structural level presumably due to the interference between functional and evolutionary processes.

  9. ATP Changes the Fluorescence Lifetime of Cyan Fluorescent protein via an Interaction with His148

    NARCIS (Netherlands)

    Borst, J.W.; Willemse, M.; Slijkhuis, R.; Krogt, G.; Laptenok, S.; Jalink, K.; Wieringa, B.; Fransen, J.A.M.

    2010-01-01

    Recently, we described that ATP induces changes in YFP/CFP fluorescence intensities of Fluorescence Resonance Energy Transfer (FRET) sensors based on CFP-YFP. To get insight into this phenomenon, we employed fluorescence lifetime spectroscopy to analyze the influence of ATP on these fluorescent

  10. ATP changes the fluorescence lifetime of cyan fluorescent protein via an interaction with His148.

    NARCIS (Netherlands)

    Borst, J.W.; Willemse, M.P.; Slijkhuis, R.; Krogt, G. van der; Laptenok, S.P.; Jalink, K.; Wieringa, B.; Fransen, J.A.M.

    2010-01-01

    Recently, we described that ATP induces changes in YFP/CFP fluorescence intensities of Fluorescence Resonance Energy Transfer (FRET) sensors based on CFP-YFP. To get insight into this phenomenon, we employed fluorescence lifetime spectroscopy to analyze the influence of ATP on these fluorescent

  11. Cation Transport Coupled to ATP Hydrolysis by the (Na, K)-ATPase: An Integrated, Animated Model

    Science.gov (United States)

    Leone, Francisco A.; Furriel, Rosa P. M.; McNamara, John C.; Horisberger, Jean D.; Borin, Ivana A.

    2010-01-01

    An Adobe[R] animation is presented for use in undergraduate Biochemistry courses, illustrating the mechanism of Na[superscript +] and K[superscript +] translocation coupled to ATP hydrolysis by the (Na, K)-ATPase, a P[subscript 2c]-type ATPase, or ATP-powered ion pump that actively translocates cations across plasma membranes. The enzyme is also…

  12. Protein Phosphorylation and Prevention of Cytochrome Oxidase Inhibition by ATP: Coupled Mechanisms of Energy Metabolism Regulation

    National Research Council Canada - National Science Library

    Acin-Perez, Rebeca; Gatti, Domenico L; Bai, Yidong; Manfredi, Giovanni

    2011-01-01

    ... cytochrome oxidase (COX), the terminal enzyme of the electron transfer chain (ETC), as one of its targets ( Acin-Perez et al., 2009a, 2009b ). COX translocates protons across the inner mitochondrial membrane, contributing to the proton electrochemical gradient used by the ATP synthase to generate ATP. In living cells, COX is a pacemaker ...

  13. MRP transporters as membrane machinery in the bradykinin-inducible export of ATP.

    Science.gov (United States)

    Zhao, Yumei; Migita, Keisuke; Sun, Jing; Katsuragi, Takeshi

    2010-04-01

    Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18alpha-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl(-) channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3(+) and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 muM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2(+)-activated Cl(-) channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2(+)-activated Cl(-) channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl(-) channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.

  14. Characterization of the Saccharomyces cerevisiae ATP-Interactome using the iTRAQ-SPROX Technique

    Science.gov (United States)

    Geer, M. Ariel; Fitzgerald, Michael C.

    2016-02-01

    The stability of proteins from rates of oxidation (SPROX) technique was used in combination with an isobaric mass tagging strategy to identify adenosine triphosphate (ATP) interacting proteins in the Saccharomyces cerevisiae proteome. The SPROX methodology utilized in this work enabled 373 proteins in a yeast cell lysate to be assayed for ATP interactions (both direct and indirect) using the non-hydrolyzable ATP analog, adenylyl imidodiphosphate (AMP-PNP). A total of 28 proteins were identified with AMP-PNP-induced thermodynamic stability changes. These protein hits included 14 proteins that were previously annotated as ATP-binding proteins in the Saccharomyces Genome Database (SGD). The 14 non-annotated ATP-binding proteins included nine proteins that were previously found to be ATP-sensitive in an earlier SPROX study using a stable isotope labeling with amino acids in cell culture (SILAC)-based approach. A bioinformatics analysis of the protein hits identified here and in the earlier SILAC-SPROX experiments revealed that many of the previously annotated ATP-binding protein hits were kinases, ligases, and chaperones. In contrast, many of the newly discovered ATP-sensitive proteins were not from these protein classes, but rather were hydrolases, oxidoreductases, and nucleic acid-binding proteins.

  15. The Contribution of Red Blood Cell Dynamics to Intrinsic Viscosity and Functional ATP Release

    Science.gov (United States)

    Forsyth, Alison; Abkarian, Manouk; Wan, Jiandi; Stone, Howard

    2010-11-01

    In shear flow, red blood cells (RBCs) exhibit a variety of behaviors such as rouleaux formation, tumbling, swinging, and tank-treading. The physiological consequences of these dynamic behaviors are not understood. In vivo, ATP is known to signal vasodilation; however, to our knowledge, no one has deciphered the relevance of RBC microrheology to the functional release of ATP. Previously, we correlated RBC deformation and ATP release in microfluidic constrictions (Wan et al., 2008). In this work, a cone-plate rheometer is used to shear a low hematocrit solution of RBCs at varying viscosity ratios (λ) between the inner cytoplasmic hemoglobin and the outer medium, to determine the intrinsic viscosity of the suspension. Further, using a luciferin-luciferase enzymatic reaction, we report the relative ATP release at varying shear rates. Results indicate that for λ = 1.6, 3.8 and 11.1, ATP release is constant up to 500 s-1, which suggests that the tumbling-tanktreading transition does not alter ATP release in pure shear. For lower viscosity ratios, λ = 1.6 and 3.8, at 500 s-1 a change in slope occurs in the intrinsic viscosity data and is marked by an increase in ATP release. Based on microfluidic observations, this simultaneous change in viscosity and ATP release occurs within the tank-treading regime.

  16. Proposal Improvements That Work

    Science.gov (United States)

    Dunn, F.

    1998-01-01

    Rocketdyne Propulsion and Power, an operating location of Boeing in Canoga Park, California is under contract with NASA's Marshall Space Flight Center (MSFC) in Huntsville, Alabama for design, development, production, and mission support of Space Shuttle Main Engines (SSMEs). The contract was restructured in 1996 to emphasize a mission contracting environment under which Rocketdyne supports the Space Transportation System launch manifest of seven flights a year without the need for a detailed list of contract deliverables such as nozzles, turbopumps, and combustion devices. This contract structure is in line with the overall Space Shuttle program goals established by the NASA to fly safely, meet the flight manifest, and reduce cost. Rocketdyne's Contracts, Pricing, and Estimating team has worked for the past several years with representatives from MSFC, the local Defense Contract Management Command, and the DCAA to improve the quality of cost proposals to MSFC for contract changes on the SSME. The contract changes on the program result primarily from engineering change proposals for product enhancements to improve safety, maintainability, or operability in the space environment. This continuous improvement team effort has been successful in improving proposal quality, reducing cycle time, and reducing cost. Some of the principal lessons learned are highlighted here to show how proposal improvements can be implemented to enhance customer satisfaction and ensure cost proposals can be evaluated easily by external customers.

  17. Draft Supplement to the Environmental Statement Fiscal Year 1975 Proposed Program : Facility Location Evaluation for Sappho Service, Study Area 75-13.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1974-03-08

    The proposed plan for meeting electrical requirements consists of the construction of a new substation near the town of Sappho located in Clallam County, Washington. Land requirements for the new substation would be approximately 3.6 acres and, depending upon the actual site location chosen, an access road ranging from 100 to 800 feet in length would also be required. As a result of the construction of the proposed facility, from 1.6 to 6 acres of timberland would be permanently removed from production. Disturbance of game in the immediate vicinity of the route would occur during construction, as would some soil erosion primarily during and immediately after construction, siltation in nearby streams, disturbance of nearby residents from noise and dust during construction, and some degradation of AM reception immediately adjacent to the right-of-way. 2 figs.

  18. Draft Supplement to the Environmental Statement Fiscal Year 1976 Proposed Program : Facility Location Evaluation for Pleasant Prairie Service (Bigelow Substation) Study Area 75-8.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1974-10-22

    The proposed plan of service consists of the construction of a new substation near Millwood, Washington. Land requirements for the new substation would be approximately 3 to 5 acres of land depending on the final site location chosen, and approximately 100 to 500 feet of access road would also be needed. The above requirements would remove 3 to 5 acres of land from agricultural production. Disturbance to wildlife during construction would occur and habitat associated with the above agricultural land would be eliminated. Grading requirements for the substation site and access road would result in slight erosion and sedimentation for alternate site 1 and high levels of erosion for alternate site 2. The proposed facility would be visible from a local road and several residences. Noise and other disturbances to residents will occur during construction.

  19. Towards the development of an automated ATP measuring platform to monitor microbial quality of drinking water

    DEFF Research Database (Denmark)

    Tatari, Karolina; Hansen, C. B.; Rasmussen, A.

    This work aimed to develop an automated and nearly on-line method to monitor ATP levels in drinking water as an indicator of microbial contamination. The system consists of a microfluidic cartridge installed in a light tight box, where the sample is mixed with the reagents and the emitted light...... is detected by a photomultiplier. Temperature in the assay box is controlled and set to 25°C. Calibration of the system using ATP standard solutions was successful, both for free and for total ATP. Chemical release of ATP by reagent addition however resulted in the formation of particles that ultimately...... clogged the microfluidic channels. An alternative thermal lysis step was implemented, by adding a flow-though heating/cooling step to the system. Thermal lysis showed efficient release of ATP from an E. coli dilution, but the releasing efficiency varied according to the type of water. Overall...

  20. Hydrogen peroxide lowers ATP levels in platelets without altering adenyalte energy charge and platelet function.

    Science.gov (United States)

    Holmsen, H; Robkin, L

    1977-03-10

    H2O2 irreversibly reduced metabolic platelet ATP levels with a corresponding accumulation of hypoxanthine. This process was enhanced by sodium azide or potassium cyanide and by increasing H2O2 concentrations. The adenylate energy charge was unaltered when less than two thirds of the metabolic ATP had disappeared but decreased markedly when more ATP disappeared. Platelet shape change, primary aggregation, dense granule and alpha-granule secretion were unaffected by H2O2-induced lowering of ATP provided that the adenylate energy charge did not fall by more than 5%; at greater adenylate energy charge reduction, platelet functions were inhibited. These results indicate that cell functions depend more on adenyalte energy charge than on the ATP level and expands the applicability of this view from bacterial systems to a mammalian cell, the human platelet.