Science.gov

Sample records for aaa subgrupo cavendish

  1. Effect of microgravity simulation using 3D clinostat on cavendish banana (Musa acuminata AAA Group) ripening process

    NASA Astrophysics Data System (ADS)

    Dwivany, Fenny Martha; Esyanti, Rizkita R.; Prapaisie, Adeline; Puspa Kirana, Listya; Latief, Chunaeni; Ginaldi, Ari

    2016-11-01

    The objective of the research was to determine the effect of microgravity simulation by 3D clinostat on Cavendish banana (Musa acuminata AAA group) ripening process. In this study, physical, physiological changes as well as genes expression were analysed. The result showed that in microgravity simulation condition ripening process in banana was delayed and the MaACOl, MaACSl and MaACS5 gene expression were affected.

  2. Random amplified polymorphic DNA (RAPD) detection of dwarf off-types in micropropagated Cavendish (Musa spp. AAA) bananas.

    PubMed

    Damasco, O P; Graham, G C; Henry, R J; Adkins, S W; Smiths, M K; Godwin, I D

    1996-11-01

    A RAPD marker specific to the dwarf off-type (hereafter known as dwarf) from micropropagation of Cavendish banana (Musa spp. AAA) cultivars New Guinea Cavendish and Williams was identified following an analysis of 57 normal (true-to-type) and 59 dwarf plants generated from several different micropropagation events. Sixty-six random decamer primers were used in the initial screen, of which 19 (28.8%) revealed polymorphisms between normal and dwarf plants. Primer OPJ-04 (5'-CCGAACACGG-3') was found to amplify an approx. 1.5 kb band which was consistently present in all normal but absent in all dwarf plants of both cultivars. Reliable detection of dwarf plants was achieved using this marker, providing the only available means ofin vitro detection of dwarfs. The use of this marker could facilitate early detection and elimination of dwarfs from batches of micropropagated bananas, and may be a useful tool in determining what factors in the tissue culture process lead to this off type production.Other micropropagation-induced RAPD polymorphisms were observed but were not associated with the dwarf trait.

  3. Activation of salicylic acid metabolism and signal transduction can enhance resistance to Fusarium wilt in banana (Musa acuminata L. AAA group, cv. Cavendish).

    PubMed

    Wang, Zhuo; Jia, Caihong; Li, Jingyang; Huang, Suzhen; Xu, Biyu; Jin, Zhiqiang

    2015-01-01

    Fusarium wilt caused by the fungus Fusarium oxysporum f. sp. cubens (Foc) is the most serious disease that attacks banana plants. Salicylic acid (SA) can play a key role in plant-microbe interactions. Our study is the first to examine the role of SA in conferring resistance to Foc TR4 in banana (Musa acuminata L. AAA group, cv. Cavendish), which is the greatest commercial importance cultivar in Musa. We used quantitative real-time reverse polymerase chain reaction (qRT-PCR) to analyze the expression profiles of 45 genes related to SA biosynthesis and downstream signaling pathways in a susceptible banana cultivar (cv. Cavendish) and a resistant banana cultivar (cv. Nongke No. 1) inoculated with Foc TR4. The expression of genes involved in SA biosynthesis and downstream signaling pathways was suppressed in a susceptible cultivar and activated in a resistant cultivar. The SA levels in each treatment arm were measured using high-performance liquid chromatography. SA levels were decreased in the susceptible cultivar and increased in the resistant cultivar. Finally, we examined the contribution of exogenous SA to Foc TR4 resistance in susceptible banana plants. The expression of genes involved in SA biosynthesis and signal transduction pathways as well as SA levels were significantly increased. The results suggest that one reason for banana susceptibility to Foc TR4 is that expression of genes involved in SA biosynthesis and SA levels are suppressed and that the induced resistance observed in banana against Foc TR4 might be a case of salicylic acid-dependent systemic acquired resistance.

  4. Comparative biochemical analysis after steam pretreatment of lignocellulosic agricultural waste biomass from Williams Cavendish banana plant (Triploid Musa AAA group).

    PubMed

    Kamdem, Irénée; Jacquet, Nicolas; Tiappi, Florian Mathias; Hiligsmann, Serge; Vanderghem, Caroline; Richel, Aurore; Jacques, Philippe; Thonart, Philippe

    2015-11-01

    The accessibility of fermentable substrates to enzymes is a limiting factor for the efficient bioconversion of agricultural wastes in the context of sustainable development. This paper presents the results of a biochemical analysis performed on six combined morphological parts of Williams Cavendish Lignocellulosic Biomass (WCLB) after steam cracking (SC) and steam explosion (SE) pretreatments. Solid (S) and liquid (L) fractions (Fs) obtained from SC pretreatment performed at 180°C (SLFSC180) and 210°C (SLFSC210) generated, after diluted acid hydrolysis, the highest proportions of neutral sugar (NS) contents, specifically 52.82 ± 3.51 and 49.78 ± 1.39%w/w WCLB dry matter (DM), respectively. The highest proportions of glucose were found in SFSC210 (53.56 ± 1.33%w/w DM) and SFSC180 (44.47 ± 0.00%w/w DM), while the lowest was found in unpretreated WCLB (22.70 ± 0.71%w/w DM). Total NS content assessed in each LF immediately after SC and SE pretreatments was less than 2%w/w of the LF DM, thus revealing minor acid autohydrolysis consequently leading to minor NS production during the steam pretreatment. WCLB subjected to SC at 210 °C (SC210) generated up to 2.7-fold bioaccessible glucan and xylan. SC and SE pretreatments showed potential for the deconstruction of WCLB (delignification, depolymerization, decrystallization and deacetylation), enhancing its enzymatic hydrolysis. The concentrations of enzymatic inhibitors, such as 2-furfuraldehyde and 5-(hydroxymethyl)furfural from LFSC210, were the highest (41 and 21 µg ml(-1), respectively). This study shows that steam pretreatments in general and SC210 in particular are required for efficient bioconversion of WCLB. Yet, biotransformation through biochemical processes (e.g., anaerobic digestion) must be performed to assess the efficiency of these pretreatments. © The Author(s) 2015.

  5. Molecular cloning and expression of five glutathione S-transferase (GST) genes from Banana (Musa acuminata L. AAA group, cv. Cavendish).

    PubMed

    Wang, Zhuo; Huang, Suzhen; Jia, Caihong; Liu, Juhua; Zhang, Jianbin; Xu, Biyu; Jin, Zhiqiang

    2013-09-01

    Three tau class MaGSTs responded to abiotic stress, MaGSTF1 and MaGSTL1 responded to signaling molecules, they may play an important role in the growth of banana plantlet. Glutathione S-transferases (GST) are multifunctional detoxification enzymes that participate in a variety of cellular processes, including stress responses. In this study, we report the molecular characteristics of five GST genes (MaGSTU1, MaGSTU2, MaGSTU3, MaGSTF1 and MaGSTL1) cloned from banana (Musa acuminate L. AAA group, cv. Cavendish) using a RACE-PCR-based strategy. The predicted molecular masses of these GSTs range from 23.4 to 27.7 kDa and their pIs are acidic. At the amino acid level, they share high sequence similarity with GSTs in the banana DH-Pahang (AA group) genome. Phylogenetic analysis showed that the deduced amino acid sequences of MaGSTs also have high similarity to GSTs of other plant species. Expression analysis by semi-quantitative RT-PCR revealed that these genes are differentially expressed in various tissues. In addition, their expression is regulated by various stress conditions, including exposure to signaling molecules, cold, salinity, drought and Fusarium oxysporum f specialis(f. Sp) cubense Tropical Race 4 (Foc TR4) infection. The expression of the tau class MaGSTs (MaGSTU1, MaGSTU2 and MaGSTU3) mainly responded to cold, salinity and drought while MaGSTF1 and MaGSTL1 expressions were upregulated by signaling molecules. Our findings suggest that MaGSTs play a key role in both development and abiotic stress responses.

  6. Comparative biochemical analysis during the anaerobic digestion of lignocellulosic biomass from six morphological parts of Williams Cavendish banana (Triploid Musa AAA group) plants.

    PubMed

    Kamdem, Irénée; Hiligsmann, Serge; Vanderghem, Caroline; Bilik, Igor; Paquot, Michel; Thonart, Philippe

    2013-12-01

    We studied banana lignocellulosic biomass (BALICEBIOM) that is abandoned after fruit harvesting, and assessed its biochemical methane potential, because of its potential as an energy source. We monitored biogas production from six morphological parts (MPs) of the "Williams Cavendish" banana cultivar using a modified operating procedure (KOP) using KOH. Volatile fatty acid (VFA) production was measured using high performance liquid chromatography. The bulbs, leaf sheaths, petioles-midribs, leaf blades, rachis stems, and floral stalks gave total biogas production of 256, 205, 198, 126, 253, and 221 ml g⁻¹ dry matter, respectively, and total biomethane production of 150, 141, 127, 98, 162, and 144 ml g⁻¹, respectively. The biogas production rates and yields depended on the biochemical composition of the BALICEBIOM and the ability of anaerobic microbes to access fermentable substrates. There were no significant differences between the biogas analysis results produced using KOP and gas chromatography. Acetate was the major VFA in all the MP sample culture media. The bioconversion yields for each MP were below 50 %, showing that these substrates were not fully biodegraded after 188 days. The estimated electricity that could be produced from biogas combustion after fermenting all of the BALICEBIOM produced annually by the Cameroon Development Corporation-Del Monte plantations for 188 days is approximately 10.5 × 10⁶ kW h (which would be worth 0.80-1.58 million euros in the current market). This bioenergy could serve the requirements of about 42,000 people in the region, although CH₄ productivity could be improved.

  7. Cavendish Balance Automation

    NASA Technical Reports Server (NTRS)

    Thompson, Bryan

    2000-01-01

    This is the final report for a project carried out to modify a manual commercial Cavendish Balance for automated use in cryostat. The scope of this project was to modify an off-the-shelf manually operated Cavendish Balance to allow for automated operation for periods of hours or days in cryostat. The purpose of this modification was to allow the balance to be used in the study of effects of superconducting materials on the local gravitational field strength to determine if the strength of gravitational fields can be reduced. A Cavendish Balance was chosen because it is a fairly simple piece of equipment for measuring gravity, one the least accurately known and least understood physical constants. The principle activities that occurred under this purchase order were: (1) All the components necessary to hold and automate the Cavendish Balance in a cryostat were designed. Engineering drawings were made of custom parts to be fabricated, other off-the-shelf parts were procured; (2) Software was written in LabView to control the automation process via a stepper motor controller and stepper motor, and to collect data from the balance during testing; (3)Software was written to take the data collected from the Cavendish Balance and reduce it to give a value for the gravitational constant; (4) The components of the system were assembled and fitted to a cryostat. Also the LabView hardware including the control computer, stepper motor driver, data collection boards, and necessary cabling were assembled; and (5) The system was operated for a number of periods, data collected, and reduced to give an average value for the gravitational constant.

  8. Effect of physiological harvest stages on the composition of bioactive compounds in Cavendish bananas*

    PubMed Central

    Bruno Bonnet, Christelle; Hubert, Olivier; Mbeguie-A-Mbeguie, Didier; Pallet, Dominique; Hiol, Abel; Reynes, Max; Poucheret, Patrick

    2013-01-01

    The combined influence of maturation, ripening, and climate on the profile of bioactive compounds was studied in banana (Musa acuminata, AAA, Cavendish, cv. Grande Naine). Their bioactive compounds were determined by the Folin-Ciocalteu assay and high-performance thin layer chromatographic (HPTLC) method. The polyphenol content of bananas harvested after 400 degree days remained unchanged during ripening, while bananas harvested after 600 and 900 degree days exhibited a significant polyphenol increase. Although dopamine was the polyphenol with the highest concentration in banana peels during the green developmental stage and ripening, its kinetics differed from the total polyphenol profile. Our results showed that this matrix of choice (maturation, ripening, and climate) may allow selection of the banana (M. acuminata, AAA, Cavendish, cv. Grande Naine) status that will produce optimal concentrations of identified compounds with human health relevance. PMID:23549844

  9. Effect of physiological harvest stages on the composition of bioactive compounds in Cavendish bananas.

    PubMed

    Bruno Bonnet, Christelle; Hubert, Olivier; Mbeguie-A-Mbeguie, Didier; Pallet, Dominique; Hiol, Abel; Reynes, Max; Poucheret, Patrick

    2013-04-01

    The combined influence of maturation, ripening, and climate on the profile of bioactive compounds was studied in banana (Musa acuminata, AAA, Cavendish, cv. Grande Naine). Their bioactive compounds were determined by the Folin-Ciocalteu assay and high-performance thin layer chromatographic (HPTLC) method. The polyphenol content of bananas harvested after 400 degree days remained unchanged during ripening, while bananas harvested after 600 and 900 degree days exhibited a significant polyphenol increase. Although dopamine was the polyphenol with the highest concentration in banana peels during the green developmental stage and ripening, its kinetics differed from the total polyphenol profile. Our results showed that this matrix of choice (maturation, ripening, and climate) may allow selection of the banana (M. acuminata, AAA, Cavendish, cv. Grande Naine) status that will produce optimal concentrations of identified compounds with human health relevance.

  10. Margaret Cavendish and the Royal Society.

    PubMed

    Wilkins, Emma

    2014-09-20

    It is often claimed that Margaret Cavendish was an anti-experimentalist who was deeply hostile to the activities of the early Royal Society--particularly in relation to Robert Hooke's experiments with microscopes. Some scholars have argued that her views were odd or even childish, while others have claimed that they were shaped by her gender-based status as a scientific 'outsider'. In this paper I examine Cavendish's views in contemporary context, arguing that her relationship with the Royal Society was more nuanced than previous accounts have suggested. This contextualized approach reveals two points: first, that Cavendish's views were not isolated or odd when compared with those of her contemporaries, and second, that the early Royal Society was less intellectually homogeneous than is sometimes thought. I also show that, although hostile to some aspects of experimentalism, Cavendish nevertheless shared many of the Royal Society's ambitions for natural philosophy, especially in relation to its usefulness and the importance of plain language as a means to disseminate new ideas.

  11. Margaret Cavendish and the Royal Society

    PubMed Central

    Wilkins, Emma

    2014-01-01

    It is often claimed that Margaret Cavendish was an anti-experimentalist who was deeply hostile to the activities of the early Royal Society—particularly in relation to Robert Hooke's experiments with microscopes. Some scholars have argued that her views were odd or even childish, while others have claimed that they were shaped by her gender-based status as a scientific ‘outsider’. In this paper I examine Cavendish's views in contemporary context, arguing that her relationship with the Royal Society was more nuanced than previous accounts have suggested. This contextualized approach reveals two points: first, that Cavendish's views were not isolated or odd when compared with those of her contemporaries, and second, that the early Royal Society was less intellectually homogeneous than is sometimes thought. I also show that, although hostile to some aspects of experimentalism, Cavendish nevertheless shared many of the Royal Society's ambitions for natural philosophy, especially in relation to its usefulness and the importance of plain language as a means to disseminate new ideas. PMID:25254278

  12. Margaret Cavendish's materialist critique of van Helmontian chymistry.

    PubMed

    Clucas, Stephen

    2011-03-01

    A striking omission in the scholarship on the reception of the chymical philosophy of Jan Baptista van Helmont in England in the seventeenth century is the work of the mid-seventeenth-century natural philosopher Margaret Cavendish, Duchess of Newcastle. In her Philosophical Letters (1664), Cavendish offers an extended critique of Van Helmont's work (whose Ortus Medicince had recently been translated into English by John Sadler). In this paper, I compare Cavendish's criticisms with those of Robert Boyle in his Sceptical Chymist (1661). Both Boyle and Cavendish attacked Van Helmont for the obscurity of his chymical vocabulary and concepts, and attacked his seminalism. Although their critiques had much in common, they diverged in their attitudes to Van Helmont's experiments. As an opponent of the experimental philosophy, Cavendish had little interest in the quality of Van Helmont's experimental claims, whereas Boyle was critical of their unreplicability. I also try to show that the two writers had very different polemical agendas, with Boyle defending his vision of chymistry based on a corpuscularian natural philosophy, and Cavendish being as much concerned with establishing her religious orthodoxy as with defending the truth claims of her own materialist vitalism. For Cavendish, Van Helmont was an example of the dangers of mingling theology and natural philosophy.

  13. AAA Foundation for Traffic Safety

    MedlinePlus

    ... of Top Deadly Mistakes Made by Teen Drivers -- AAA AAA: Road debris causes avoidable crashes, deaths Save the ... and 500 deaths! Foundation News Stay Tuned New AAA Foundation for Traffic Safety website coming Fall 2017 ...

  14. Improved tolerance toward fungal diseases in transgenic Cavendish banana (Musa spp. AAA group) cv. Grand Nain.

    PubMed

    Vishnevetsky, Jane; White, Thomas L; Palmateer, Aaron J; Flaishman, Moshe; Cohen, Yuval; Elad, Yigal; Velcheva, Margarita; Hanania, Uri; Sahar, Nachman; Dgani, Oded; Perl, Avihai

    2011-02-01

    The most devastating disease currently threatening to destroy the banana industry worldwide is undoubtedly Sigatoka Leaf spot disease caused by Mycosphaerella fijiensis. In this study, we developed a transformation system for banana and expressed the endochitinase gene ThEn-42 from Trichoderma harzianum together with the grape stilbene synthase (StSy) gene in transgenic banana plants under the control of the 35S promoter and the inducible PR-10 promoter, respectively. The superoxide dismutase gene Cu,Zn-SOD from tomato, under control of the ubiquitin promoter, was added to this cassette to improve scavenging of free radicals generated during fungal attack. A 4-year field trial demonstrated several transgenic banana lines with improved tolerance to Sigatoka. As the genes conferring Sigatoka tolerance may have a wide range of anti-fungal activities we also inoculated the regenerated banana plants with Botrytis cinerea. The best transgenic lines exhibiting Sigatoka tolerance were also found to have tolerance to B. cinerea in laboratory assays.

  15. AAAS: Politics. . . and Science

    ERIC Educational Resources Information Center

    Science News, 1978

    1978-01-01

    Reviews topics discussed during the American Association for the Advancement of Science (AAAS) meeting held in Washington, D.C. Topics included: the equal rights amendment, laetrile, nuclear radiation hazards, sociobiology, and various science topics. (SL)

  16. The Scientific Papers of the Honourable Henry Cavendish, F. R. S. 2 Volume Set

    NASA Astrophysics Data System (ADS)

    Cavendish, Henry; Clerk Maxwell, James; Thorpe, Edward, , Sir; Larmor, Joseph, , Sir

    2011-02-01

    Volume 1: Preface Sir Joseph Larmor; Introduction; First published paper on electricity, 1771; Preliminary propositions; Appendix; Thoughts concerning electricity; Account of the experiments; Second published paper on electricity, 1776; Experiments in 1771; Experiments in 1772; Experiments in 1773; Measurers; Experiments with the artificial torpedo; Resistance to electricity; Results of comparisons of charges; Results on resistance; Notes by the editor, 1879 James Clerk Maxwell; Life of Cavendish Thomas Young; Index to Cavendish Manuscripts. Volume 2: Introduction; Reprint of papers communicated by Cavendish to the Royal Society and published in the Philosophical Transactions; Unpublished papers from the original manuscripts in the possession of the Duke of Devonshire, K. G., LL. D., F. R. S.; Cavendish's mathematical and dynamical manuscripts Sir Joseph Larmor; Cavendish as a geologist Sir Archibald Geikie; Cavendish's astronomical manuscripts Sir Frank W. Dyson; Cavendish's magnetic work Charles Chree; Index.

  17. Multifunctional Mitochondrial AAA Proteases

    PubMed Central

    Glynn, Steven E.

    2017-01-01

    Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle. PMID:28589125

  18. Multifunctional Mitochondrial AAA Proteases.

    PubMed

    Glynn, Steven E

    2017-01-01

    Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

  19. Early Attempts to Detect the Neutrino at the Cavendish Laboratory

    NASA Astrophysics Data System (ADS)

    Navarro, Jaume

    2006-03-01

    In the 1920s and early 1930s the Cavendish Laboratory in Cambridge was preeminent in experimental research on radioactivity and nuclear physics, with theoretical physics playing a subsidiary role in guiding, but not determining the course of experimental research. Soon after Wolfgang Pauli (1900 1958) proposed his neutrino hypothesis in 1930 to preserve conservation of energy and momentum in beta decay, experiments the first of their kind were carried out in the Cavendish Laboratory to detect Pauli’s elusive particle, but they were abandoned in 1936. I trace these early attempts and suggest reasons for their abandonment, which may contribute to an understanding of the complex way in which theoretical entities are accepted by physicists.

  20. [Margaret Cavendish vs Robert Hooke: An impossible duel].

    PubMed

    Aït-Touati, Frédérique

    2016-12-01

    In 1665, Robert Hooke published his major work in microscopy, Micrographia, a defense of experimental philosophy. The following year, Margaret Cavendish, Duchess of Newcastle, published at her own expense a treatise and a novel that undermined the basis of this new science. The dispute broke out at the initiative of the Duchess, in the context of a vast controversy about the legitimacy and the efficiency of optical instruments in natural philosophy. All the figures of the dual are used, except one: the counterattack. Cavendish, indeed, was alone on the battlefield. Is it possible to call a dual a battle with only one combatant? This particular case of dispute that stops owing to the shortage of combatants is the subject of this article.

  1. Transgenic Cavendish bananas with resistance to Fusarium wilt tropical race 4.

    PubMed

    Dale, James; James, Anthony; Paul, Jean-Yves; Khanna, Harjeet; Smith, Mark; Peraza-Echeverria, Santy; Garcia-Bastidas, Fernando; Kema, Gert; Waterhouse, Peter; Mengersen, Kerrie; Harding, Robert

    2017-11-14

    Banana (Musa spp.) is a staple food for more than 400 million people. Over 40% of world production and virtually all the export trade is based on Cavendish banana. However, Cavendish banana is under threat from a virulent fungus, Fusarium oxysporum f. sp. cubense tropical race 4 (TR4) for which no acceptable resistant replacement has been identified. Here we report the identification of transgenic Cavendish with resistance to TR4. In our 3-year field trial, two lines of transgenic Cavendish, one transformed with RGA2, a gene isolated from a TR4-resistant diploid banana, and the other with a nematode-derived gene, Ced9, remain disease free. Transgene expression in the RGA2 lines is strongly correlated with resistance. Endogenous RGA2 homologs are also present in Cavendish but are expressed tenfold lower than that in our most resistant transgenic line. The expression of these homologs can potentially be elevated through gene editing, to provide non-transgenic resistance.

  2. NASA Airborne Astronomy Ambassadors (AAA)

    NASA Astrophysics Data System (ADS)

    Backman, D. E.; Harman, P. K.; Clark, C.

    2016-12-01

    NASA's Airborne Astronomy Ambassadors (AAA) is a three-part professional development (PD) program for high school physics and astronomy teachers. The AAA experience consists of: (1) blended-learning professional development composed of webinars, asynchronous content learning, and a series of hands-on workshops (2) a STEM immersion experience at NASA Armstrong Flight Research Center's B703 science research aircraft facility in Palmdale, California, and (3) ongoing participation in the AAA community of practice (CoP) connecting participants with astrophysics and planetary science Subject Matter Experts (SMEs). The SETI Institute (SI) is partnering with school districts in Santa Clara and Los Angeles Counties during the AAA program's "incubation" period, calendar years 2016 through 2018. AAAs will be selected by the school districts based on criteria developed during spring 2016 focus group meetings led by the program's external evaluator, WestEd.. Teachers with 3+ years teaching experience who are assigned to teach at least 2 sections in any combination of the high school courses Physics (non-AP), Physics of the Universe (California integrated model), Astronomy, or Earth & Space Sciences are eligible. Partner districts will select at least 48 eligible applicants with SI oversight. WestEd will randomly assign selected AAAs to group A or group B. Group A will complete PD in January - June of 2017 and then participate in SOFIA science flights during fall 2017 (SOFIA Cycle 5). Group B will act as a control during the 2017-18 school year. Group B will then complete PD in January - June of 2018 and participate in SOFIA science flights in fall 2018 (Cycle 6). Under the current plan, opportunities for additional districts to seek AAA partnerships with SI will be offered in 2018 or 2019. A nominal two-week AAA curriculum component will be developed by SI for classroom delivery that will be aligned with selected California Draft Science Framework Disciplinary Core Ideas

  3. Suppression of Type-II Diabetes with Dyslipidemia and Nephropathy by Peels of Musa cavendish Fruit.

    PubMed

    Navghare, Vijay; Dhawale, Shashikant

    2016-10-01

    Musa cavendish, peels has local and traditional use to promote wound healing, hyperglycemia, ulceration etc. The present work investigated the lipid lowering; nephroprotective and glucose lowering properties of ethanolic extract of peels of Musa cavendish (EMC) in alloxan-induced diabetic rats. The EMC 250, 500 and 1000 mg/kg/day and the vehicle were administered orally to alloxan-induced diabetic rats (n = 6) for 3 weeks. Changes in plasma glucose, lipid profile along with kidney function before and after treatment with EMC were recorded. The ethanolic extract of peels of Musa cavendish reduced blood glucose, serum triglyceride, cholesterol, LDL cholesterol and creatinine levels and improvement in body weight, liver glycogen, serum HDL cholesterol, serum albumin and total protein level when compared with untreated rats. Musa cavendish has lipid lowering, nephroprotective and antidiabetic property by regulating glucose uptake in the liver and muscles by restoring the intracellular energy balance.

  4. Speculative Truth - Henry Cavendish, Natural Philosophy, and the Rise of Modern Theoretical Science

    NASA Astrophysics Data System (ADS)

    McCormmach, Russell

    2004-03-01

    With a never-before published paper by Lord Henry Cavendish, as well as a biography on him, this book offers a fascinating discourse on the rise of scientific attitudes and ways of knowing. A pioneering British physicist in the late 18th and early 19th centuries, Cavendish was widely considered to be the first full-time scientist in the modern sense. Through the lens of this unique thinker and writer, this book is about the birth of modern science.

  5. Henry Cavendish (1731-1810): hydrogen, carbon dioxide, water, and weighing the world.

    PubMed

    West, John B

    2014-07-01

    Henry Cavendish (1731-1810) was an outstanding chemist and physicist. Although he was not a major figure in the history of respiratory physiology he made important discoveries concerning hydrogen, carbon dioxide, atmospheric air, and water. Hydrogen had been prepared earlier by Boyle but its properties had not been recognized; Cavendish described these in detail, including the density of the gas. Carbon dioxide had also previously been studied by Black, but Cavendish clarified its properties and measured its density. He was the first person to accurately analyze atmospheric air and reported an oxygen concentration very close to the currently accepted value. When he removed all the oxygen and nitrogen from an air sample, he found that there was a residual portion of about 0.8% that he could not characterize. Later this was shown to be argon. He produced large amounts of water by burning hydrogen in oxygen and recognized that these were its only constituents. Cavendish also worked on electricity and heat. However, his main contribution outside chemistry was an audacious experiment to measure the density of the earth, which he referred to as "weighing the world." This involved determining the gravitational attraction between lead spheres in a specially constructed building. Although this was a simple experiment in principle, there were numerous complexities that he overcame with meticulous attention to experimental details. His result was very close to the modern accepted value. The Cavendish Experiment, as it is called, assures his place in the history of science. Copyright © 2014 the American Physiological Society.

  6. Cavendish's crocodile and dark horse: the lives of Rutherford and Aston in parallel.

    PubMed

    Downard, Kevin M

    2007-01-01

    Ernest Rutherford and Francis Aston were born a world apart but both would become two of the most influential physicists of their time. Their separate training, under the direction of J.J. Thomson at the Cavendish Laboratory, shaped their future and allowed both men to develop and apply their considerable skills in experimental physics. It also catalyzed their careers and ultimately led to each receiving a Nobel Prize. Although they had very different characters, Rutherford and Aston became close colleagues and confidants who spent considerable time together within the confines of the Cavendish Laboratory, at Trinity College, and elsewhere in Cambridge. They also traveled the world in company, usually as part of a group or British delegation of scientists attending conferences and meetings overseas. This article parallels the lives of the two men. It describes how they came to work at the Cavendish, their scientific accomplishments and accolades, and their activities and interactions away from the laboratory.

  7. Abraham Pais Prize for History of Physics Talk: Henry Cavendish, John Michell, Weighing the Stars

    NASA Astrophysics Data System (ADS)

    McCormmach, Russell

    2010-03-01

    This talk is about an interaction between two 18th-century natural philosophers (physical scientists), Henry Cavendish and John Michell, and its most important outcome, the experiment of weighing the world (their name for it) using a torsion balance (our name for it). Michell was the most inventive of the 18th century English natural philosophers, and Cavendish was the first of his countrymen to possess abilities at all comparable with Newton's. By their interests and skills, they were drawn to one another. Both were universal natural philosophers, equally adept at building scientific instruments, performing experiments, constructing theory, and using mathematics; both had a penchant for exacting, quantitative work. Both also had fitful habits of publication, which did not begin to reveal the range of their work, to the mystification of later scientists and historians. Late in life, Cavendish and Michell turned their attention to the force that Newton had examined most completely, a singular triumph of his natural philosophy, the force of universal gravitation. Over the course of the 18th century, abundant evidence of attraction had been gathered from the motions of the earth, moon, planets, and comets, phenomena which span the intermediate range of masses, sizes, and distances. But in three domains of experience, involving the extreme upper and lower limits of masses and dimensions, the universality of gravitation remained an article of faith. These were the gravity of the ``fixed'' stars, the mutual attraction of terrestrial bodies, and the gravitation of light and other special substances. Michell took on himself the task of deducing observable consequences from each of these prospective instances of universal gravitation. Cavendish encouraged Michell, and he followed up the resulting observational and experimental questions. The experiment of weighing the world was the last experiment Mitchell planned and the last experiment Cavendish published. The capstone of

  8. AAA-ATPases in Protein Degradation

    PubMed Central

    Yedidi, Ravikiran S.; Wendler, Petra; Enenkel, Cordula

    2017-01-01

    Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea. PMID:28676851

  9. AAA-ATPases in Protein Degradation.

    PubMed

    Yedidi, Ravikiran S; Wendler, Petra; Enenkel, Cordula

    2017-01-01

    Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea.

  10. The Cavendish Experiment as a Tool for Historical Understanding of Science

    ERIC Educational Resources Information Center

    Ducheyne, Steffen

    2012-01-01

    Following an ever growing literature which takes serious the relevance of case-studies in the history of science for science education and understanding of science, I provide a detailed historical reconstruction of the Cavendish Experiment, which remains as close as possible to the original. In this paper, I call attention to three educational…

  11. "[N]ot subject to our sense” : Margaret Cavendish's fusion of Renaissance science, magic and fairy lore.

    PubMed

    Walters, Lisa

    2010-01-01

    This article explores Margaret Cavendish's depictions of alchemy, witchcraft and fairy lore in her scientific treatise Philosophical Letters and in fictional texts from Natures Pictures and Poems and Fancies. Though Cavendish was a dedicated materialist, she appropriates theories of magic from early modern science and folklore into her materialist epistemology. As Cavendish draws upon a fusion of early modern conceptions of magic, she creates a radical theory of matter which not only challenges patriarchy and binary oppositions, but also explores the plurality and mystery that can exist within an infinitely complex material world.

  12. Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA patients.

    PubMed

    van de Luijtgaarden, Koen M; Rouwet, Ellen V; Hoeks, Sanne E; Stolker, Robert J; Verhagen, Hence Jm; Majoor-Krakauer, Danielle

    2017-04-01

    Sex affects the presentation, treatment, and outcomes of abdominal aortic aneurysm (AAA). Although AAAs are less prevalent in women, at least in the general population, women with an AAA have a poorer prognosis in comparison to men. Sex differences in the genetic predisposition for aneurysm disease remain to be established. In this study we investigated the familial risk of AAA for women compared to men. All living AAA patients included in a 2004-2012 prospective database were invited to the multidisciplinary vascular/genetics outpatient clinic between 2009 and 2012 for assessment of family history using detailed questionnaires. AAA risk for male and female relatives was calculated separately and stratified by sex of the AAA patients. Families of 568 AAA patients were investigated and 22.5% of the patients had at least one affected relative. Female relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the estimated sex-specific population risk. Relatives of female AAA patients had a higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022), corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and male relatives, respectively. The risk for aortic aneurysm in relatives of AAA patients is higher than expected from population risk. The excess risk is highest for the female relatives of AAA patients and for the relatives of female AAA patients. These findings endorse targeted AAA family screening for female and male relatives of all AAA patients.

  13. Genetic analysis of abdominal aortic aneurysms (AAA)

    SciTech Connect

    St. Jean, P.L.; Hart, B.K.; Zhang, X.C.

    1994-09-01

    The association between AAA and gender, smoking (SM), hypertension (HTN) and inguinal herniation (IH) was examined in 141 AAA probands and 139 of their 1st degree relatives with aortic exam (36 affected, 103 unaffected). There was no significant difference between age at diagnosis of affecteds and age at exam of unaffecteds. Of 181 males, 142 had AAA; of 99 females, 35 had AAA. Using log-linear modeling AAA was significantly associated at the 5% level with gender, SM and HTN but not IH. The association of AAA with SM and HTN held when males and females were analyzed separately. HTN wasmore » -1.5 times more common in both affected males and females, while SM was 1.5 and 2 times more common in affected males and females, respectively. Tests of association and linkage analyses were performed with relevant candidate genes: 3 COL3A1 polymorphisms (C/T, ALA/THR, AvaII), 2 ELN polymorphisms (SER/GLY, (CA)n), FBN1(TAAA)n, 2 APOB polymorphisms (Xbal,Ins/Del), CLB4B (CA)n, PI and markers D1S243 (CA)n, HPR (CA)n and MFD23(CA)n. The loci were genotyped in > 100 AAA probands and > 95 normal controls. No statistically significant evidence of association at the 5% level was obtained for any of the loci using chi-square test of association. 28 families with 2 or more affecteds were analyzed using the affected pedigree member method (APM) and lod-score analyses. There was no evidence for linkage with any loci using APM. Lod-score analysis under an autosomal recessive model resulted in excluding linkage (lod score < -2) of all loci to AAA at {theta}=0.0. Under an autosomal dominant model, linkage was excluded at {theta}=0.0 to ELN, APOB, CLG4B, D1S243, HPR and MFD23. The various genes previously proposed in AAA pathogenesis are neither associated nor casually related in our study population.« less

  14. Pathophysiology of AAA: heredity vs environment.

    PubMed

    Björck, Martin; Wanhainen, Anders

    2013-01-01

    Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Updates on AAA screening and surveillance

    PubMed

    Theivendran, Mayo; Chuen, Jason

    2018-05-01

    Screening and diagnostic surveillance of latent conditions have a profound impact on public healthcare expenditure and clinical outcomes. Abdominal aortic aneurysm (AAA) remains one of the hallmark pathologies in vascular surgery and an area of intense research interest. This article is the second of two that will outline current areas of controversy and research in AAA disease in order to support a more detailed understanding of issues in managing patients with this condition, and inform the development of Australasian clinical guidelines and health policy. Screening and surveillance of AAA should be evidence-based and follow clinical guidelines; however, advances in treatment technology and epidemiological data have influenced results. Goals of care and cost‑effectiveness should play central parts in screening and surveillance strategies.

  16. LMIP/AAA: Local Authentication, Authorization and Accounting (AAA) Protocol for Mobile IP

    NASA Astrophysics Data System (ADS)

    Chenait, Manel

    Mobile IP represents a simple and scalable global mobility solution. However, it inhibits various vulnerabilities to malicious attacks and, therefore, requires the integration of appropriate security services. In this paper, we discuss two authentication schemes suggested for Mobile IP: standard authentication and Mobile IP/AAA authentication. In order to provide Mobile IP roaming services including identity verication, we propose an improvement to Mobile/AAA authentication scheme by applying a local politic key management in each domain, hence we reduce hando latency by avoiding the involvement of AAA infrastructure during mobile node roaming.

  17. Physiological, molecular and ultrastructural analyses during ripening and over-ripening of banana (Musa spp., AAA group, Cavendish sub-group) fruit suggest characteristics of programmed cell death.

    PubMed

    Ramírez-Sánchez, Maricruz; Huber, Donald J; Vallejos, C Eduardo; Kelley, Karen

    2018-01-01

    Programmed cell death (PCD) is a part of plant development that has been studied for petal senescence and vegetative tissue but has not been thoroughly investigated for fleshy fruits. The purpose of this research was to examine ripening and over-ripening in banana fruit to determine if there were processes in common to previously described PCD. Loss of cellular integrity (over 40%) and development of senescence related dark spot (SRDS) occurred after day 8 in banana peel. Nuclease and protease activity in the peel increased during ripening starting from day 2, and decreased during over-ripening. The highest activity was for proteases and nucleases with apparent molecular weights of 86 kDa and 27 kDa, respectively. Images of SRDS showed shrinkage of the upper layers of cells, visually suggesting cell death. Decrease of electron dense areas was evident in TEM micrographs of nuclei. This study shows for the first time that ripening and over-ripening of banana peel share physiological and molecular processes previously described in plant PCD. SRDS could represent a morphotype of PCD that characterizes a structural and biochemical failure in the upper layers of the peel, thereafter spreading to lower and adjacent layers of cells. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  18. Comparison of tissue deterioration of ripening banana fruit (Musa spp., AAA group, Cavendish subgroup) under chilling and non-chilling temperatures.

    PubMed

    Ramírez-Sánchez, Maricruz; Huber, Donald J; Vallejos, Carlos E

    2018-03-08

    In fleshy fruits, induced programmed cell death (PCD) has been observed in heat-treated tomato, and in ethylene-treated and low-temperature exposure in immature cucumber. No other fleshy fruit has been evaluated for chilling-injury-induced PCD, especially mature fruit with full ripening capacity. The purpose of this research was to identify and evaluate the presence of PCD processes during the development of low-temperature-induced physiopathy of banana fruit. Exposure of fruit to 5 °C for 4 days induced degradative processes similar to those occurring during ripening and overripening of non-chilled fruit. Nuclease from banana peel showed activity in both DNA substrates and RNA substrates. No exclusive low-temperature-induced proteases and nucleases were observed. DNA of chilled peel showed earlier signs of degradation and higher levels of DNA tailing during overripening. This study shows that exposure to low temperatures did not induce a pattern of degradative processes that differed from that occurring during ripening and overripening of non-chilled fruit. DNA showed earlier signs of degradation and higher levels of DNA tailing. Nuclease activity analysis showed bifunctionality in both chilled and non-chilled tissue and no chilling-exclusive protease and nuclease. Fleshy fruit might use their available resources on degradative processes and adjust them depending on environmental conditions. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  19. Inflorescence proliferation for somatic embryogenesis induction and suspension-derived plant regeneration from banana (Musa AAA, cv. 'Dwarf Cavendish') male flowers.

    PubMed

    Pérez-Hernández, Juan Bernardo; Rosell-García, Purificación

    2008-06-01

    Availability of explants with adequate embryogenic competence is one of the most important limitations for the development of regenerable cell suspensions in banana. To increase the number and ease of accessibility to potentially embryogenic explants, a novel methodology is described by which young male flower clusters isolated from adult plants are induced to form new flower buds and proliferate in vitro. Different concentrations of the plant growth regulator thidiazuron (TDZ) induced inflorescence proliferation, which could be maintained over time as a continuous source of young flower buds. Intensity of proliferation was evaluated during successive subcultures. At the third cycle of proliferation, the highest multiplication rate (2.89) was obtained on the medium containing 5 microM TDZ. Newly generated floral tissues were assessed for embryogenic competence, resulting in an average embryogenic frequency of 12.5%. The observed embryogenic capacity, together with the recurrent availability of immature flowers, allowed for the direct initiation of cell suspensions from bulked explant cultures. Regular observation and regeneration tests during the development of suspended cell cultures confirmed their embryogenic condition. Produced embryos successfully matured and germinated to regenerate hundreds of somatic in vitro plants.

  20. AAA-DDD triple hydrogen bond complexes.

    PubMed

    Blight, Barry A; Camara-Campos, Amaya; Djurdjevic, Smilja; Kaller, Martin; Leigh, David A; McMillan, Fiona M; McNab, Hamish; Slawin, Alexandra M Z

    2009-10-07

    Experiment and theory both suggest that the AAA-DDD pattern of hydrogen bond acceptors (A) and donors (D) is the arrangement of three contiguous hydrogen bonding centers that results in the strongest association between two species. Murray and Zimmerman prepared the first example of such a system (complex 3*2) and determined the lower limit of its association constant (K(a)) in CDCl(3) to be 10(5) M(-1) by (1)H NMR spectroscopy (Murray, T. J. and Zimmerman, S. C. J. Am. Chem. Soc. 1992, 114, 4010-4011). The first cationic AAA-DDD pair (3*4(+)) was described by Bell and Anslyn (Bell, D. A. and Anslyn, E. A. Tetrahedron 1995, 51, 7161-7172), with a K(a) > 5 x 10(5) M(-1) in CH(2)Cl(2) as determined by UV-vis spectroscopy. We were recently able to quantify the strength of a neutral AAA-DDD arrangement using a more chemically stable AAA-DDD system, 6*2, which has an association constant of 2 x 10(7) M(-1) in CH(2)Cl(2) (Djurdjevic, S., Leigh, D. A., McNab, H., Parsons, S., Teobaldi, G. and Zerbetto, F. J. Am. Chem. Soc. 2007, 129, 476-477). Here we report on further AA(A) and DDD partners, together with the first precise measurement of the association constant of a cationic AAA-DDD species. Complex 6*10(+)[B(3,5-(CF(3))(2)C(6)H(3))(4)(-)] has a K(a) = 3 x 10(10) M(-1) at RT in CH(2)Cl(2), by far the most strongly bound triple hydrogen bonded system measured to date. The X-ray crystal structure of 6*10(+) with a BPh(4)(-) counteranion shows a planar array of three short (NH...N distances 1.95-2.15 A), parallel (but staggered rather than strictly linear; N-H...N angles 165.4-168.8 degrees), primary hydrogen bonds. These are apparently reinforced, as theory predicts, by close electrostatic interactions (NH-*-N distances 2.78-3.29 A) between each proton and the acceptor atoms of the adjacent primary hydrogen bonds.

  1. No actual measurement … was required: Maxwell and Cavendish's null method for the inverse square law of electrostatics.

    PubMed

    Falconer, Isobel

    In 1877 James Clerk Maxwell and his student Donald MacAlister refined Henry Cavendish's 1773 null experiment demonstrating the absence of electricity inside a charged conductor. This null result was a mathematical prediction of the inverse square law of electrostatics, and both Cavendish and Maxwell took the experiment as verifying the law. However, Maxwell had already expressed absolute conviction in the law, based on results of Michael Faraday's. So, what was the value to him of repeating Cavendish's experiment? After assessing whether the law was as secure as he claimed, this paper explores its central importance to the electrical programme that Maxwell was pursuing. It traces the historical and conceptual re-orderings through which Maxwell established the law by constructing a tradition of null tests and asserting the superior accuracy of the method. Maxwell drew on his developing 'doctrine of method' to identify Cavendish's experiment as a member of a wider class of null methods. By doing so, he appealed to the null practices of telegraph engineers, diverted attention from the flawed logic of the method, and sought to localise issues around the mapping of numbers onto instrumental indications, on the grounds that 'no actual measurement … was required'. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Microbiological and physicochemical factors affecting Aspergillus section Flavi incidence in Cavendish banana (Musa cavendishii) chips production in Southern Philippines.

    PubMed

    Sales, A C; Azanza, P V; Yoshizawa, T

    2005-01-01

    Microbiological and physicochemical factors affecting the incidence of Aspergillus section Flavi in dried Cavendish banana (Musa cavendishii) chips production in Southern Philippines were examined. The average counts of Aspergillus section Flavi (AFC) in fresh and dried Cavendish bananas from 10 production batches of the Philippine Agro-Industrial Development Cooperative in Davao del Norte, Southern Philippines were 1.2 x 10(2) and 1.6 x 10(2) cfu/g, respectively. Isolates from both samples were identified to be Aspergillus flavus based on spore type and conidial structure of isolates. An increasing trend in the AFC of Cavendish bananas was observed during dried banana chips processing. Variability in the AFC between production batches was attributed to differences in aerobic and fungal populations and physicochemical characteristics of the fruits, peel damage of the raw materials, concentration of AFC in the air and food-contact surfaces of the production area, and temperature and relative humidity (RH) conditions of the environment during production and storage. Physicochemical characteristics of Cavendish bananas from the receipt of raw materials up to the first day of drying were within the reported range of values allowing growth and toxin production by aflatoxigenic fungi. Air-borne AFC varied depending on the section of the production area examined. The close proximity of the waste disposal area from the production operation to the preparation, drying and storage areas suggests that cross-contamination, probably air-borne or insect-borne was a likely occurrence. The hands of workers were also identified as AFC sources. Results of this study highlight the need for the development of strategies to control aflatoxigenic fungi and aflatoxin contamination in Philippine dried Cavendish bananas.

  3. The Weekend Effect in AAA Repair.

    PubMed

    O'Donnell, Thomas F X; Li, Chun; Swerdlow, Nicholas J; Liang, Patric; Pothof, Alexander B; Patel, Virendra I; Giles, Kristina A; Malas, Mahmoud B; Schermerhorn, Marc L

    2018-04-18

    Conflicting reports exist regarding whether patients undergoing surgery on the weekend or later in the week experience worse outcomes. We identified patients undergoing abdominal aortic aneurysm (AAA) repair in the Vascular Quality Initiative between 2009 and 2017 [n = 38,498; 30,537 endovascular aneurysm repair (EVAR) and 7961 open repair]. We utilized mixed effects logistic regression to compare adjusted rates of perioperative mortality based on the day of repair. Tuesday was the most common day for elective repair (22%), Friday for symptomatic repairs (20%), and ruptured aneurysms were evenly distributed. Patients with ruptured aneurysms experienced similar adjusted mortality whether they underwent repair during the week or on weekends. Transfers of ruptured AAA were more common over the weekend. However, patients transferred on the weekend experienced higher adjusted mortality than those transferred during the week (28% vs 21%, P = 0.02), despite the fact that during the week, transferred patients actually experienced lower adjusted mortality than patients treated at the index hospital (21% vs 31%, P < 0.01). Among symptomatic patients, adjusted mortality was higher for those undergoing repair over the weekend than those whose surgeries were delayed until a weekday (7.9% vs 3.1%, P = 0.02). Adjusted mortality in elective cases did not vary across the days of the week. Results were consistent between open and EVAR patients. We found no evidence of a weekend effect for ruptured or symptomatic AAA repair. However, patients with ruptured AAA transferred on the weekend experienced higher mortality than those transferred during the week, suggesting a need for improvement in weekend transfer processes.

  4. AAA+ Machines of Protein Destruction in Mycobacteria.

    PubMed

    Alhuwaider, Adnan Ali H; Dougan, David A

    2017-01-01

    The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or proteostasis) is vital for cell survival during normal and stressful conditions. The two key aspects of protein homeostasis are, (i) the correct folding and assembly of proteins (coupled with their delivery to the correct cellular location) and (ii) the timely removal of unwanted or damaged proteins from the cell, which are performed by molecular chaperones and proteases, respectively. A major class of proteins that contribute to both of these tasks are the AAA+ (ATPases associated with a variety of cellular activities) protein superfamily. Although much is known about the structure of these machines and how they function in the model Gram-negative bacterium Escherichia coli , we are only just beginning to discover the molecular details of these machines and how they function in mycobacteria. Here we review the different AAA+ machines, that contribute to proteostasis in mycobacteria. Primarily we will focus on the recent advances in the structure and function of AAA+ proteases, the substrates they recognize and the cellular pathways they control. Finally, we will discuss the recent developments related to these machines as novel drug targets.

  5. Epigenesis and the rationality of nature in William Harvey and Margaret Cavendish.

    PubMed

    Goldberg, Benjamin

    2017-06-01

    The generation of animals was a difficult phenomenon to explain in the seventeenth century, having long been a problem in natural philosophy, theology, and medicine. In this paper, I explore how generation, understood as epigenesis, was directly related to an idea of rational nature. I examine epigenesis-the idea that the embryo was constructed part-by-part, over time-in the work of two seemingly dissimilar English philosophers: William Harvey, an eclectic Aristotelian, and Margaret Cavendish, a radical materialist. I chart the ways that they understood and explained epigenesis, given their differences in philosophy and ontology. I argue for the importance of ideas of harmony and order in structuring their accounts of generation as a rational process. I link their experiences during the English Civil war to how they see nature as a possible source for the rationality and concord sorely missing in human affairs.

  6. Advanced, Analytic, Automated (AAA) Measurement of Engagement during Learning

    ERIC Educational Resources Information Center

    D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

    2017-01-01

    It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in…

  7. NASA Airborne Astronomy Ambassadors (AAA) Professional Development and NASA Connections

    NASA Astrophysics Data System (ADS)

    Backman, D. E.; Clark, C.; Harman, P. K.

    2017-12-01

    NASA's Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content learning, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong's B703 science research aircraft facility in Palmdale, California, and (3) ongoing opportunities for connection with NASA astrophysics and planetary science Subject Matter Experts (SMEs). AAA implementation in 2016-18 involves partnerships between the SETI Institute and seven school districts in northern and southern California. AAAs in the current cohort were selected by the school districts based on criteria developed by AAA program staff working with WestEd evaluation consultants. The selected teachers were then randomly assigned by WestEd to a Group A or B to support controlled testing of student learning. Group A completed their PD during January - August 2017, then participated in NASA SOFIA science flights during fall 2017. Group B will act as a control during the 2017-18 school year, then will complete their professional development and SOFIA flights during 2018. A two-week AAA electromagnetic spectrum and multi-wavelength astronomy curriculum aligned with the Science Framework for California Public Schools and Next Generation Science Standards was developed by program staff for classroom delivery. The curriculum (as well as the AAA's pre-flight PD) capitalizes on NASA content by using "science snapshot" case studies regarding astronomy research conducted by SOFIA. AAAs also interact with NASA SMEs during flight weeks and will translate that interaction into classroom content. The AAA program will make controlled measurements of student gains in standards-based learning plus changes in student attitudes towards STEM, and observe & record the AAAs' implementation of curricular changes. Funded by NASA: NNX16AC51

  8. AAAS Communicating Science Program: Reflections on Evaluation

    NASA Astrophysics Data System (ADS)

    Braha, J.

    2015-12-01

    The AAAS Center for Public Engagement (Center) with science builds capacity for scientists to engage public audiences by fostering collaboration among natural or physical scientists, communication researchers, and public engagement practitioners. The recently launched Leshner Leadership Institute empowers cohorts of mid-career scientists to lead public engagement by supporting their networks of scientists, researchers, and practitioners. The Center works closely with social scientists whose research addresses science communication and public engagement with science to ensure that the Communicating Science training program builds on empirical evidence to inform best practices. Researchers ( Besley, Dudo, & Storkdieck 2015) have helped Center staff and an external evaluator develop pan instrument that measures progress towards goals that are suggested by the researcher, including internal efficacy (increasing scientists' communication skills and confidence in their ability to engage with the public) and external efficacy (scientists' confidence in engagement methods). Evaluation results from one year of the Communicating Science program suggest that the model of training yields positive results that support scientists in the area that should lead to greater engagement. This talk will explore the model for training, which provides a context for strategic communication, as well as the practical factors, such as time, access to public engagement practitioners, and technical skill, that seems to contribute to increased willingness to engage with public audiences. The evaluation program results suggest willingness by training participants to engage directly or to take preliminary steps towards engagement. In the evaluation results, 38% of trained scientists reported time as a barrier to engagement; 35% reported concern that engagement would distract from their work as a barrier. AAAS works to improve practitioner-researcher-scientist networks to overcome such barriers.

  9. Protein quality control in organelles - AAA/FtsH story.

    PubMed

    Janska, Hanna; Kwasniak, Malgorzata; Szczepanowska, Joanna

    2013-02-01

    This review focuses on organellar AAA/FtsH proteases, whose proteolytic and chaperone-like activity is a crucial component of the protein quality control systems of mitochondrial and chloroplast membranes. We compare the AAA/FtsH proteases from yeast, mammals and plants. The nature of the complexes formed by AAA/FtsH proteases and the current view on their involvement in degradation of non-native organellar proteins or assembly of membrane complexes are discussed. Additional functions of AAA proteases not directly connected with protein quality control found in yeast and mammals but not yet in plants are also described shortly. Following an overview of the molecular functions of the AAA/FtsH proteases we discuss physiological consequences of their inactivation in yeast, mammals and plants. The molecular basis of phenotypes associated with inactivation of the AAA/FtsH proteases is not fully understood yet, with the notable exception of those observed in m-AAA protease-deficient yeast cells, which are caused by impaired maturation of mitochondrial ribosomal protein. Finally, examples of cytosolic events affecting protein quality control in mitochondria and chloroplasts are given. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Fundamental Characteristics of AAA+ Protein Family Structure and Function

    PubMed Central

    2016-01-01

    Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins. PMID:27703410

  11. Fundamental Characteristics of AAA+ Protein Family Structure and Function.

    PubMed

    Miller, Justin M; Enemark, Eric J

    2016-01-01

    Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

  12. Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning.

    PubMed

    D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

    2017-01-01

    It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research.

  13. Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning

    PubMed Central

    D’Mello, Sidney; Dieterle, Ed; Duckworth, Angela

    2017-01-01

    It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research. PMID:29038607

  14. Transcriptome profiling of resistant and susceptible Cavendish banana roots following inoculation with Fusarium oxysporum f. sp. cubense tropical race 4

    PubMed Central

    2012-01-01

    Background Fusarium wilt, caused by the fungal pathogen Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), is considered the most lethal disease of Cavendish bananas in the world. The disease can be managed in the field by planting resistant Cavendish plants generated by somaclonal variation. However, little information is available on the genetic basis of plant resistance to Foc TR4. To a better understand the defense response of resistant banana plants to the Fusarium wilt pathogen, the transcriptome profiles in roots of resistant and susceptible Cavendish banana challenged with Foc TR4 were compared. Results RNA-seq analysis generated more than 103 million 90-bp clean pair end (PE) reads, which were assembled into 88,161 unigenes (mean size = 554 bp). Based on sequence similarity searches, 61,706 (69.99%) genes were identified, among which 21,273 and 50,410 unigenes were assigned to gene ontology (GO) categories and clusters of orthologous groups (COG), respectively. Searches in the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG) mapped 33,243 (37.71%) unigenes to 119 KEGG pathways. A total of 5,008 genes were assigned to plant-pathogen interactions, including disease defense and signal transduction. Digital gene expression (DGE) analysis revealed large differences in the transcriptome profiles of the Foc TR4-resistant somaclonal variant and its susceptible wild-type. Expression patterns of genes involved in pathogen-associated molecular pattern (PAMP) recognition, activation of effector-triggered immunity (ETI), ion influx, and biosynthesis of hormones as well as pathogenesis-related (PR) genes, transcription factors, signaling/regulatory genes, cell wall modification genes and genes with other functions were analyzed and compared. The results indicated that basal defense mechanisms are involved in the recognition of PAMPs, and that high levels of defense-related transcripts may contribute to Foc TR4 resistance in banana

  15. A methodology for developing anisotropic AAA phantoms via additive manufacturing.

    PubMed

    Ruiz de Galarreta, Sergio; Antón, Raúl; Cazón, Aitor; Finol, Ender A

    2017-05-24

    An Abdominal Aortic Aneurysm (AAA) is a permanent focal dilatation of the abdominal aorta at least 1.5 times its normal diameter. The criterion of maximum diameter is still used in clinical practice, although numerical studies have demonstrated the importance of biomechanical factors for rupture risk assessment. AAA phantoms could be used for experimental validation of the numerical studies and for pre-intervention testing of endovascular grafts. We have applied multi-material 3D printing technology to manufacture idealized AAA phantoms with anisotropic mechanical behavior. Different composites were fabricated and the phantom specimens were characterized by biaxial tensile tests while using a constitutive model to fit the experimental data. One composite was chosen to manufacture the phantom based on having the same mechanical properties as those reported in the literature for human AAA tissue; the strain energy and anisotropic index were compared to make this choice. The materials for the matrix and fibers of the selected composite are, respectively, the digital materials FLX9940 and FLX9960 developed by Stratasys. The fiber proportion for the composite is equal to 0.15. The differences between the composite behavior and the AAA tissue are small, with a small difference in the strain energy (0.4%) and a maximum difference of 12.4% in the peak Green strain ratio. This work represents a step forward in the application of 3D printing technology for the manufacturing of AAA phantoms with anisotropic mechanical behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Structural Elements Regulating AAA+ Protein Quality Control Machines.

    PubMed

    Chang, Chiung-Wen; Lee, Sukyeong; Tsai, Francis T F

    2017-01-01

    Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines.

  17. Assessing heterogeneity in oligomeric AAA+ machines.

    PubMed

    Sysoeva, Tatyana A

    2017-03-01

    ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.

  18. AAA (2010) CAPD clinical practice guidelines: need for an update.

    PubMed

    DeBonis, David A

    2017-09-01

    Review and critique of the clinical value of the AAA CAPD guidance document in light of criteria for credible and useful guidance documents, as discussed by Field and Lohr. A qualitative review of the of the AAA CAPD guidelines using a framework by Field and Lohr to assess their relative value in supporting the assessment and management of CAPD referrals. Relevant literature available through electronic search tools and published texts were used along with the AAA CAPD guidance document and the chapter by Field and Lohr. The AAA document does not meet many of the key requirements discussed by Field and Lohr. It does not reflect the current literature, fails to help clinicians understand for whom auditory processing testing and intervention would be most useful, includes contradictory suggestions which reduce clarity and appears to avoid conclusions that might cast the CAPD construct in a negative light. It also does not include input from diverse affected groups. All of these reduce the document's credibility. The AAA CAPD guidance document will need to be updated and re-conceptualised in order to provide meaningful guidance for clinicians.

  19. Bears in Eden, or, this is not the garden you're looking for: Margaret Cavendish, Robert Hooke and the limits of natural philosophy.

    PubMed

    Lawson, Ian

    2015-12-01

    This paper investigates Margaret Cavendish's characterization of experimental philosophers as hybrids of bears and men in her 1666 story The Description of a New World, Called the Blazing World. By associating experimental philosophers, in particular Robert Hooke and his microscope, with animals familiar to her readers from the sport of bear-baiting, Cavendish constructed an identity for the fellows of the Royal Society of London quite unlike that which they imagined for themselves. Recent scholarship has illustrated well how Cavendish's opposition to experimental philosophy is linked to her different natural-philosophical, political and anthropological ideas. My contribution to this literature is to examine the meanings both of bears in early modern England and of microscopes in experimental rhetoric, in order to illustrate the connection that Cavendish implies between the two. She parodied Hooke's idea that his microscope extended his limited human senses, and mocked his aim that by so doing he could produce useful knowledge. The bear-men reflect inhuman ambition and provide a caution against ignoring both the order of English society and the place of humans in nature.

  20. Role of AAA(+)-proteins in peroxisome biogenesis and function.

    PubMed

    Grimm, Immanuel; Erdmann, Ralf; Girzalsky, Wolfgang

    2016-05-01

    Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.

  1. m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration

    PubMed Central

    Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

    2018-01-01

    The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders. PMID:29451229

  2. Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines.

    PubMed

    Monroe, Nicole; Hill, Christopher P

    2016-05-08

    Meiotic clade AAA ATPases (ATPases associated with diverse cellular activities), which were initially grouped on the basis of phylogenetic classification of their AAA ATPase cassette, include four relatively well characterized family members, Vps4, spastin, katanin and fidgetin. These enzymes all function to disassemble specific polymeric protein structures, with Vps4 disassembling the ESCRT-III polymers that are central to the many membrane-remodeling activities of the ESCRT (endosomal sorting complexes required for transport) pathway and spastin, katanin p60 and fidgetin affecting multiple aspects of cellular dynamics by severing microtubules. They share a common domain architecture that features an N-terminal MIT (microtubule interacting and trafficking) domain followed by a single AAA ATPase cassette. Meiotic clade AAA ATPases function as hexamers that can cycle between the active assembly and inactive monomers/dimers in a regulated process, and they appear to disassemble their polymeric substrates by translocating subunits through the central pore of their hexameric ring. Recent studies with Vps4 have shown that nucleotide-induced asymmetry is a requirement for substrate binding to the pore loops and that recruitment to the protein lattice via MIT domains also relieves autoinhibition and primes the AAA ATPase cassettes for substrate binding. The most striking, unifying feature of meiotic clade AAA ATPases may be their MIT domain, which is a module that is found in a wide variety of proteins that localize to ESCRT-III polymers. Spastin also displays an adjacent microtubule binding sequence, and the presence of both ESCRT-III and microtubule binding elements may underlie the recent findings that the ESCRT-III disassembly function of Vps4 and the microtubule-severing function of spastin, as well as potentially katanin and fidgetin, are highly coordinated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.

    PubMed

    Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

    2018-03-01

    The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders.

  4. Readily functionalized AAA-DDD triply hydrogen-bonded motifs.

    PubMed

    Tong, Feng; Linares-Mendez, Iamnica J; Han, Yi-Fei; Wisner, James A; Wang, Hong-Bo

    2018-04-25

    Herein we present a new, readily functionalized AAA-DDD hydrogen bond array. A novel AAA monomeric unit (3a-b) was obtained from a two-step synthetic procedure starting with 2-aminonicotinaldehyde via microwave radiation (overall yield of 52-66%). 1H NMR and fluorescence spectroscopy confirmed the complexation event with a calculated association constant of 1.57 × 107 M-1. Likewise, the usefulness of this triple hydrogen bond motif in supramolecular polymerization was demonstrated through viscosity measurements in a crosslinked supramolecular alternating copolymer.

  5. Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis

    PubMed Central

    Elsholz, Alexander K. W.; Birk, Marlene S.; Charpentier, Emmanuelle; Turgay, Kürşad

    2017-01-01

    Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis. We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics. PMID:28748186

  6. The Airborne Astronomy Ambassadors (AAA) Program and NASA Astrophysics Connections

    NASA Astrophysics Data System (ADS)

    Backman, Dana Edward; Clark, Coral; Harman, Pamela

    2018-01-01

    The NASA Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content delivery, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong’s B703 science research aircraft facility in Palmdale, California, including interactions with NASA astrophysics & planetary science Subject Matter Experts (SMEs) during science flights on SOFIA, and (3) continuing post-flight opportunities for teacher & student connections with SMEs.

  7. Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis.

    PubMed

    Elsholz, Alexander K W; Birk, Marlene S; Charpentier, Emmanuelle; Turgay, Kürşad

    2017-01-01

    Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis . We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics.

  8. Molecularly Defined Nanostructures Based on a Novel AAA-DDD Triple Hydrogen-Bonding Motif.

    PubMed

    Papmeyer, Marcus; Vuilleumier, Clément A; Pavan, Giovanni M; Zhurov, Konstantin O; Severin, Kay

    2016-01-26

    A facile and flexible method for the synthesis of a new AAA-DDD triple hydrogen-bonding motif is described. Polytopic supramolecular building blocks with precisely oriented AAA and DDD groups are thus accessible in few steps. These building blocks were used for the assembly of large macrocycles featuring four AAA-DDD interactions and a macrobicyclic complex with a total of six AAA-DDD interactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. The Adult Asperger Assessment (AAA): A Diagnostic Method

    ERIC Educational Resources Information Center

    Baron-Cohen, Simon; Wheelwright, Sally; Robinson, Janine; Woodbury-Smith, Marc

    2005-01-01

    At the present time there are a large number of adults who have "suspected" Asperger syndrome (AS). In this paper we describe a new instrument, the Adult Asperger Assessment (AAA), developed in our clinic for adults with AS. The need for a new instrument relevant to the diagnosis of AS in adulthood arises because existing instruments are designed…

  10. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  11. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  12. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  13. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAX (CONTINUED) INCOME TAXES Small Business Corporations and Their Shareholders § 1.1368-2 Accumulated... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  14. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  15. AAAS: Automated Affirmative Action System. General Description, Phase 1.

    ERIC Educational Resources Information Center

    Institute for Services to Education, Inc., Washington, DC. TACTICS Management Information Systems Directorate.

    This document describes phase 1 of the Automated Affirmative Action System (AAAS) of the Tuskegee Institute, which was designed to organize an inventory of any patterns of job classification and assignment identifiable by sex or minority group; any job classification or organizational unit where women and minorities are not employed or are…

  16. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model.

    PubMed

    Kloster, Brian O; Lund, Lars; Lindholt, Jes S

    2016-05-01

    The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms.

  17. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

    PubMed Central

    Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

    2014-01-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

  18. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

    PubMed

    Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

    2014-06-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair.

    PubMed

    Bhat, Javaid Y; Thieulin-Pardo, Gabriel; Hartl, F Ulrich; Hayer-Hartl, Manajit

    2017-01-01

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO 2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO 2 molecule and binding of a Mg 2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are "misfire" products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins.

  20. Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair

    PubMed Central

    Bhat, Javaid Y.; Thieulin-Pardo, Gabriel; Hartl, F. Ulrich; Hayer-Hartl, Manajit

    2017-01-01

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO2 molecule and binding of a Mg2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are “misfire” products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins. PMID:28443288

  1. Structure and evolution of N-domains in AAA metalloproteases.

    PubMed

    Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D; Habeck, Michael; Martin, Jörg; Lupas, Andrei N; Alva, Vikram

    2015-02-27

    Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn(2+)-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichia coli FtsH-N, exhibiting an unusual α+β fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors. Copyright © 2015. Published by Elsevier Ltd.

  2. Characterization of the Modular Design of the Autolysin/Adhesin Aaa from Staphylococcus Aureus

    PubMed Central

    Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

    2012-01-01

    Background Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Methodology/Principal Findings Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. Conclusions/Significance We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus

  3. Prior Radiological Investigations in 65-Year-Old Men Screened for AAA.

    PubMed

    Meecham, Lewis; Summerour, Virginia; Hobbs, Simon; Newman, Jeremy; Wall, Michael L

    2018-05-01

    The National Health Service abdominal aortic aneurysm screening programme (NAAASP) is now fully operational. Those who have previously been formally investigated for abdominal aortic aneurysm (AAA) are excluded; however, many patients undergo radiological investigation of the abdomen for other reasons. Such practices may find incidental AAA which may be eroding the performance of the NAAASP. We investigated the rates of preinvestigation before invitation to screening in our local AAA screening programme. Electronic patient records were retrospectively reviewed for all patients called between March 2013 and February 2016 in 1 local AAA screening programme. Their records were interrogated to identify any abdominal imaging within 5 years of their invitation to screening. Two thousand six hundred thirty-eight men were invited for screening; of these, 563 (21.3%) had been "prescreened". Median time between prescreening and screening was 19 months (0-60 months). Ultrasound abdomen was the most prevalent at 248 (44.0%). Two thousand two hundred forty-three (85.0%) men attended screening, and 6 (0.27%) were excluded for known AAA. Prevalence of AAA was 1.8% (n = 41). Of these, 15 (36.6%) had prior investigation with 6 (40.0%) having AAA diagnosed. Therefore, 9 (22.0%) had potential missed AAA on "prescreening" (mean diameter 35 mm [30-45], mean time lapse between investigation and screening 21.1 months [1-49]). Incidence of missed aneurysm in the "prescreened" cohort was 1.6% (9/563). Large numbers of men invited for AAA screening have undergone preinvestigation of their abdominal aorta, with 60% of the present AAA being missed. Reliance on incidental detection of AAA would leave many patients undiagnosed in the community-at risk of future rupture. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Characterization of the modular design of the autolysin/adhesin Aaa from Staphylococcus aureus.

    PubMed

    Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

    2012-01-01

    Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for

  5. Biosynthesis of silver nanoparticles from Cavendish banana peel extract and its antibacterial and free radical scavenging assay: a novel biological approach

    NASA Astrophysics Data System (ADS)

    Kokila, T.; Ramesh, P. S.; Geetha, D.

    2015-12-01

    Biosynthesis of metallic silver nanoparticles has now become an alternative to physical and chemical approaches. In the present study, silver nanoparticles (AgNPs) were synthesized from Cavendish banana peel extract (CBPE) and characterized by UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, Atomic force microscopy (AFM), Field emission scanning electronic microscope (FESEM), Dynamic light scattering (DLS) and zeta potential (ZP). The AgNPs formation was confirmed by UV-visible spectroscopy through color conversion due to surface plasma resonance band at 430 nm. The effect of pH on nanoparticle synthesis was determined by adjusting the various pH of the reaction mixtures. The crystalline nature of nanoparticles was confirmed from the XRD pattern, and the grain size was found to be around 34 nm. To identify the compounds responsible for the bioreduction of Ag+ ion and the stabilization of AgNPs produced, the functional group present in Cavendish banana peel extract was investigated using FTIR. AFM has proved to be very helpful in determining morphological features and the diameter of AgNPs in the range of 23-30 nm was confirmed by FESEM. DLS studies revealed that the average size of AgNPs was found to be around 297 nm. Zeta potential value for AgNPs obtained was -11 mV indicating the moderate stability of synthesized nanoparticles. The antibacterial activity of the nanoparticles was studied against Gram-positive and Gram-negative bacteria. Biosynthesized AgNPs showed a strong DPPH radical and ABTS scavengers compared to the aqueous peel extract of Cavendish banana.

  6. Mechanism of Enzyme Repair by the AAA+ Chaperone Rubisco Activase.

    PubMed

    Bhat, Javaid Y; Miličić, Goran; Thieulin-Pardo, Gabriel; Bracher, Andreas; Maxwell, Andrew; Ciniawsky, Susanne; Mueller-Cajar, Oliver; Engen, John R; Hartl, F Ulrich; Wendler, Petra; Hayer-Hartl, Manajit

    2017-09-07

    How AAA+ chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA+ protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Multibands tunneling in AAA-stacked trilayer graphene

    NASA Astrophysics Data System (ADS)

    Redouani, Ilham; Jellal, Ahmed; Bahaoui, Abdelhadi; Bahlouli, Hocine

    2018-04-01

    We study the electronic transport through np and npn junctions for AAA-stacked trilayer graphene. Two kinds of gates are considered where the first is a single gate and the second is a double gate. After obtaining the solutions for the energy spectrum, we use the transfer matrix method to determine the three transmission probabilities for each individual cone τ = 0 , ± 1 . We show that the quasiparticles in AAA-stacked trilayer graphene are not only chiral but also labeled by an additional cone index τ. The obtained bands are composed of three Dirac cones that depend on the chirality indexes. We show that there is perfect transmission for normal or near normal incidence, which is a manifestation of the Klein tunneling effect. We analyze also the corresponding total conductance, which is defined as the sum of the conductance channels in each individual cone. Our results are numerically discussed and compared with those obtained for ABA- and ABC-stacked trilayer graphene.

  8. Analysis of a Typical Chinese High School Biology Textbook Using the AAAS Textbook Standards

    ERIC Educational Resources Information Center

    Liang, Ye; Cobern, William W.

    2013-01-01

    The purpose of this study was to evaluate a typical Chinese high school biology textbook using the textbook standards of the American Association for the Advancement of Science (AAAS). The data were composed of three chapters selected from the textbook. Each chapter was analyzed and rated using the AAAS textbook standards. Pearson correlations…

  9. APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

    PubMed

    Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

    2013-11-01

    To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

  10. Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

    PubMed

    Htun, Nay Min; Peter, Karlheinz

    2014-10-01

    Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Combination of endovascular graft exclusion and drug therapy in AAA with hypertension or hyperglycemia.

    PubMed

    Wang, Dile; Qu, Bihui; He, Tao

    2017-08-01

    The objective of the present study was to evaluate the efficacy of combination of endovascular graft exclusion and drugs for hypertension/hyperglycemia for the treatment of abdominal aortic aneurysm (AAA). We analyzed 156 patients with AAA. Eighty-four patients were hypertensive and 72 were hyperglycemic. After endovascular graft exclusion, hypertensive patients were divided into four groups and treated with cyclopenthiazide, reserpine, propranolol, and placebo respectively. Hyperglycemic patients were divided into three groups and treated with metformin, insulin, and placebo respectively. Body temperature and peripheral blood leukocytes were measured at day 1, 2, 7, and 14 after endovascular graft exclusion. Size of AAAs, blood pressure, and blood sugar were measured again after 1 year. In hypertensive patients, the size of AAAs reduced after endovascular graft exclusion, while the combined treatments with cyclopenthiazide, reserpine, or propranolol helped to reduce blood pressure (blood pressure decrease <10 mmHg (18/21), <10 mmHg (12/21), <10 mmHg (8/21), and <10 mmHg (10/21) in the control group, cyclopenthiazide group, reserpine group, and propranolol group, respectively. AAA size decreased in the control group (P<0.001) and in the other three groups (P<0.0001). Similar results were obtained in hyperglycemic patients. The size of AAAs reduced after endovascular graft exclusion. Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar >7.8 mmol/L (22/24), AAA size (P<0.001); metformin, blood sugar >7.8 mmol/L (14/24), AAA size (P<0.0001); insulin, blood sugar >7.8 mmol/L (11/24), AAA size (P<0.0001). Combination of endovascular graft exclusion with medicine is more effective than the former treatment alone for AAA therapy.

  12. Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration.

    PubMed

    Qi, Y; Liu, H; Daniels, M P; Zhang, G; Xu, H

    2016-02-01

    Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L(del)). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L(del) flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L(del) flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency.

  13. Assessment of the accuracy of AortaScan for detection of abdominal aortic aneurysm (AAA).

    PubMed

    Abbas, A; Smith, A; Cecelja, M; Waltham, M

    2012-02-01

    AortaScan AMI 9700 is a portable 3D ultrasound device that automatically measures the maximum diameter of the abdominal aorta without the need for a trained sonographer. It is designed to rapidly diagnose or exclude an AAA and may have particular use in screening programs. Our objective was to determine its accuracy to detect AAA. Subjects from our AAA screening and surveillance programs were examined. The aorta was scanned using the AortaScan and computed tomography (CT). Ninety-one subjects underwent imaging (44 AAA on conventional ultrasound surveillance and 47 controls). The largest measurement obtained by AortaScan was compared against the CT-aortic measurement. The mean aortic diameter was 2.8 cm. The CT scan confirmed the diagnosis of AAA in 43 subjects. There was one false positive measurement on conventional ultrasound. AortaScan missed the diagnosis of AAA in eight subjects. There were thirteen false positive measurements. The sensitivity, specificity, positive and negative predictive values were 81%, 72%, 72% and 81% respectively. A device to detect AAA without the need for a trained operator would have potential in a community-based screening programme. The AortaScan, however, lacks adequate sensitivity and significant technical improvement is necessary before it could be considered a replacement for trained screening personnel. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  14. Mitochondrial AAA proteases--towards a molecular understanding of membrane-bound proteolytic machines.

    PubMed

    Gerdes, Florian; Tatsuta, Takashi; Langer, Thomas

    2012-01-01

    Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Multi-Centre Study on Cardiovascular Risk Management on Patients Undergoing AAA Surveillance.

    PubMed

    Saratzis, A; Dattani, N; Brown, A; Shalhoub, J; Bosanquet, D; Sidloff, D; Stather, P

    2017-07-01

    The risk of cardiovascular events and death in patients with abdominal aortic aneurysms (AAA) is high. Screening has been introduced to reduce AAA related mortality; however, after AAA diagnosis, cardiovascular modification may be as important to patient outcomes as surveillance. The aim of this study was to assess cardiovascular risk reduction in patients with small AAA. Institutional approval was granted for The Vascular and Endovascular Research Network (VERN) to retrospectively collect data pertaining to cardiovascular risk reduction from four tertiary vascular units in England. Patients with small AAA (January 2013-December 2015) were included. Demographic details, postcode, current medications, and smoking status were recorded using a bespoke electronic database and analysed. In a secondary analysis VERN contacted all AAA screening units in England and Wales to assess their current protocols relating to CV protection. In total, 1053 patients were included (mean age 74 ± 9 years, all men). Of these, 745 patients (70.8%) had been prescribed an antiplatelet agent and 787 (74.7%) a statin. Overall, only 666 patients (63.2%) were prescribed both a statin and antiplatelet. Two hundred and sixty eight patients (32.1%) were current smokers and the proportion of patients who continued to smoke decreased with age. Overall, only 401 patients (48.1%) were prescribed a statin, antiplatelet, and had stopped smoking. In the secondary analysis 38 AAA screening units (84% national coverage) replied. Thirty-one units (82%) suggest changes to the patient's prescription; however, none monitor compliance with these recommendations or assess whether the general practitioner has been made aware of the AAA diagnosis or prescription advice. Many patients with small AAA are not prescribed an antiplatelet/statin, and still smoke cigarettes, and therefore remain at high risk of cardiovascular morbidity and mortality. National guidance to ensure this high risk group of patients is

  16. Midterm outcomes of the Zenith Renu AAA Ancillary Graft.

    PubMed

    Jim, Jeffrey; Rubin, Brian G; Geraghty, Patrick J; Money, Samuel R; Sanchez, Luis A

    2011-08-01

    The Zenith Renu abdominal aortic aneurysm (AAA) Ancillary Graft (Cook Medical Inc, Bloomington, Ind) provides active proximal fixation for treatment of pre-existing endografts with failed or failing proximal fixation or seal. The purpose of this study was to evaluate the midterm outcomes of treatment with this device. From September 2005 to November 2006, a prospective, nonrandomized, multicenter, postmarket registry was utilized to collect physician experiences from 151 cases (89 converters and 62 main body extensions) at 95 institutions. Preoperative indications and procedural and postimplantation outcomes were collected and analyzed. Technical success and clinical success were determined as defined by the Society of Vascular Surgery reporting standards. Patients were predominantly male (87%) with a mean age of 77 years. The interval between the original endograft implantation to Renu treatment was 43.4 ± 18.7 months. The indications for treatment were endoleak (n = 111), migration (n = 136), or both (n = 94). Technical success was 98.0% with two cases of intraoperative conversion and one case of persistent type IA endoleak. The median follow-up for the cohort was 45.0 months (range, 0-56 months; interquartile range, 25.0 months). Overall, 32 cases had treatment failures that included at least one of the following: death (n = 5), type I/III endoleak (n = 18), graft infection (n = 1), thrombosis (n = 1), aneurysm enlargement >5 mm (n = 9), rupture (n = 4), conversion (n = 9, with 7 after 30 days), and migration (n = 1). Overall, the clinical success for the entire cohort during the follow-up period was 78.8% (119/151). The postmarket registry data confirm that the Zenith Renu AAA Ancillary Graft can be used to treat endovascular repairs that failed due to proximal attachment failures. The salvage treatment with the Renu device had high technical success rate and resulted in clinical success in a majority of patients (78.8%). While failed endovascular repairs can

  17. Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease.

    PubMed

    Lee, Sukyeong; Augustin, Steffen; Tatsuta, Takashi; Gerdes, Florian; Langer, Thomas; Tsai, Francis T F

    2011-02-11

    FtsH-related AAA proteases are conserved membrane-anchored, ATP-dependent molecular machines, which mediate the processing and turnover of soluble and membrane-embedded proteins in eubacteria, mitochondria, and chloroplasts. Homo- and hetero-oligomeric proteolytic complexes exist, which are composed of homologous subunits harboring an ATPase domain of the AAA family and an H41 metallopeptidase domain. Mutations in subunits of mitochondrial m-AAA proteases have been associated with different neurodegenerative disorders in human, raising questions on the functional differences between homo- and hetero-oligomeric AAA proteases. Here, we have analyzed the hetero-oligomeric yeast m-AAA protease composed of homologous Yta10 and Yta12 subunits. We combined genetic and structural approaches to define the molecular determinants for oligomer assembly and to assess functional similarities between Yta10 and Yta12. We demonstrate that replacement of only two amino acid residues within the metallopeptidase domain of Yta12 allows its assembly into homo-oligomeric complexes. To provide a molecular explanation, we determined the 12 Å resolution structure of the intact yeast m-AAA protease with its transmembrane domains by electron cryomicroscopy (cryo-EM) and atomic structure fitting. The full-length m-AAA protease has a bipartite structure and is a hexamer in solution. We found that residues in Yta12, which facilitate homo-oligomerization when mutated, are located at the interface between neighboring protomers in the hexamer ring. Notably, the transmembrane and intermembrane space domains are separated from the main body, creating a passage on the matrix side, which is wide enough to accommodate unfolded but not folded polypeptides. These results suggest a mechanism regarding how proteins are recognized and degraded by m-AAA proteases.

  18. Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

    PubMed

    Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

    2017-01-01

    There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights

  19. The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders

    PubMed Central

    Law, Kelsey B.; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O.; Moser, Ann; Brumell, John H.; Braverman, Nancy

    2017-01-01

    ABSTRACT Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs. PMID:28521612

  20. The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders.

    PubMed

    Law, Kelsey B; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O; Moser, Ann; Brumell, John H; Braverman, Nancy; Kim, Peter K

    2017-05-04

    Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs.

  1. Abdominal aorta aneurysm (AAA): Is there a role for prevention and therapy using antioxidants?

    PubMed

    Pincemail, Joël; Defraigne, Jean-Olivier; Courtois, Audrey; Albert, Adelin; Cheramy-Bien, Jean-Paul; Sakalihasan, Natzi

    2017-09-18

    Abdominal aortic aneurysm (AAA) is a degenerative disease that cause mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seems to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. Reducing oxidative stress by antioxidants has been shown to be a potential strategy for limiting AAA development. Human studies confirmed that oxidative stress and endothelial dysfunction are well associated with AAA development. Unfortunately, there is currently no evidence showing that strategies using low molecular weight antioxidants (vitamins C and E, β-carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function but also their capacity to stimulate enzymatic antioxidants trough activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. Clinical studies are therefore urgently necessary to confirm such a suggestion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.

    PubMed

    König, Tim; Tröder, Simon E; Bakka, Kavya; Korwitz, Anne; Richter-Dennerlein, Ricarda; Lampe, Philipp A; Patron, Maria; Mühlmeister, Mareike; Guerrero-Castillo, Sergio; Brandt, Ulrich; Decker, Thorsten; Lauria, Ines; Paggio, Angela; Rizzuto, Rosario; Rugarli, Elena I; De Stefani, Diego; Langer, Thomas

    2016-10-06

    Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca 2+ uniporter MCU. While MAIP1 assists biogenesis of the MCU subunit EMRE, the m-AAA protease degrades non-assembled EMRE and ensures efficient assembly of gatekeeper subunits with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria and facilitates mitochondrial Ca 2+ overload, mitochondrial permeability transition pore opening, and neuronal death. Together, our results explain neuronal loss in m-AAA protease deficiency by deregulated mitochondrial Ca 2+ homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue.

    PubMed

    O'Leary, Siobhan A; Mulvihill, John J; Barrett, Hilary E; Kavanagh, Eamon G; Walsh, Michael T; McGloughlin, Tim M; Doyle, Barry J

    2015-02-01

    Varying degrees of calcification are present in most abdominal aortic aneurysms (AAAs). However, their impact on AAA failure properties and AAA rupture risk is unclear. The aim of this work is evaluate and compare the failure properties of partially calcified and predominantly fibrous AAA tissue and investigate the potential reasons for failure. Uniaxial mechanical testing was performed on AAA samples harvested from 31 patients undergoing open surgical repair. Individual tensile samples were divided into two groups: fibrous (n=31) and partially calcified (n=38). The presence of calcification was confirmed by fourier transform infrared spectroscopy (FTIR). A total of 69 mechanical tests were performed and the failure stretch (λf), failure stress (σf) and failure tension (Tf) were recorded for each test. Following mechanical testing, the failure sites of a subset of both tissue types were examined using scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) to investigate the potential reasons for failure. It has been shown that the failure properties of partially calcified tissue are significantly reduced compared to fibrous tissue and SEM and EDS results suggest that the junction between a calcification deposit and the fibrous matrix is highly susceptible to failure. This study implicates the presence of calcification as a key player in AAA rupture risk and provides further motivation for the development of non-invasive methods of measuring calcification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. An AAA-DDD triply hydrogen-bonded complex easily accessible for supramolecular polymers.

    PubMed

    Han, Yi-Fei; Chen, Wen-Qiang; Wang, Hong-Bo; Yuan, Ying-Xue; Wu, Na-Na; Song, Xiang-Zhi; Yang, Lan

    2014-12-15

    For a complementary hydrogen-bonded complex, when every hydrogen-bond acceptor is on one side and every hydrogen-bond donor is on the other, all secondary interactions are attractive and the complex is highly stable. AAA-DDD (A=acceptor, D=donor) is considered to be the most stable among triply hydrogen-bonded sequences. The easily synthesized and further derivatized AAA-DDD system is very desirable for hydrogen-bonded functional materials. In this case, AAA and DDD, starting from 4-methoxybenzaldehyde, were synthesized with the Hantzsch pyridine synthesis and Friedländer annulation reaction. The association constant determined by fluorescence titration in chloroform at room temperature is 2.09×10(7)  M(-1) . The AAA and DDD components are not coplanar, but form a V shape in the solid state. Supramolecular polymers based on AAA-DDD triply hydrogen bonded have also been developed. This work may make AAA-DDD triply hydrogen-bonded sequences easily accessible for stimuli-responsive materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.

    PubMed

    Wang, Shuaiyu; Jacquemyn, Julie; Murru, Sara; Martinelli, Paola; Barth, Esther; Langer, Thomas; Niessen, Carien M; Rugarli, Elena I

    2016-12-01

    The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.

  6. The AAA+ ATPase p97, a cellular multitool

    PubMed Central

    Stach, Lasse

    2017-01-01

    The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy. PMID:28819009

  7. Engineering Silicone Rubbers for In vitro Studies: Creating AAA Models and ILT Analogues with Physiological Properties

    PubMed Central

    Corbett, T.J.; Doyle, B.J.; Callanan, A.; Walsh, M.T.; McGloughlin, T.M

    2010-01-01

    Background In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogues are used to mimic the AAA in vivo. While the models used may be physiological, their properties are frequently either not reported or investigated. Method of Approach This study is concerned with the testing and characterisation of previously used vessel analogue materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection moulding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (β) and compliance) the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared to published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure – diameter change behaviour of the models could be predicted numerically. ILT analogues were also manufactured and characterised. Ideal models were manufactured with ILT analogue internal to the aneurysm region and the effect of the ILT analogue on the model compliance and stiffness was investigated. Results The wall materials had similar properties to aortic tissue at physiological pressures (Einit 2.22MPa and 1.57MPa (aortic tissue: 1.8MPa)). ILT analogues had similar Young’s modulus to the medial layer of ILT (0.24 and 0.33MPa (ILT: 0.28MPa)). All models had aneurysm sac compliance in the physiological range (2.62 – 8.01×10-4/mmHg (AAA in vivo: 1.8 – 9.4×10-4/mmHg)). The necks of our AAA models had similar stiffness to healthy aortas (20.44 – 29.83 (healthy aortas in vivo: 17.5±5.5)). Good agreement was seen between the diameter changes due to pressurisation in the experimental and FEA wall models with a maximum error of 7.3% at 120mmHg. It was also determined that the inclusion of ILT analogue

  8. m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

    PubMed

    Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

    2018-04-09

    The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

  9. Identifying patients with AAA with the highest risk following endovascular repair.

    PubMed

    Cadili, Ali; Turnbull, Robert; Hervas-Malo, Marilou; Ghosh, Sunita; Chyczij, Harold

    2012-08-01

    It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. Patients with AAA greater than 85 years of age are at a greater risk of mortality

  10. Regionalization of Emergent Vascular Surgery for Patients With Ruptured AAA Improves Outcomes.

    PubMed

    Warner, Courtney J; Roddy, Sean P; Chang, Benjamin B; Kreienberg, Paul B; Sternbach, Yaron; Taggert, John B; Ozsvath, Kathleen J; Stain, Steven C; Darling, R Clement

    2016-09-01

    Safe and efficient endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (r-AAA) requires advanced infrastructure and surgical expertise not available at all US hospitals. The objective was to assess the impact of regionalizing r-AAA care to centers equipped for both open surgical repair (r-OSR) and EVAR (r-EVAR) by vascular surgeons. A retrospective review of all patients with r-AAA undergoing open or endovascular repair in a 12-hospital region. Patient demographics, transfer status, type of repair, and intraoperative variables were recorded. Outcomes included perioperative morbidity and mortality. Four hundred fifty-one patients with r-AAA were treated from 2002 to 2015. Three hundred twenty-one patients (71%) presented initially to community hospitals (CHs) and 130 (29%) presented to the tertiary medical center (MC). Of the 321 patients presenting to CH, 133 (41%) were treated locally (131 OSR; 2 EVAR) and 188 (59%) were transferred to the MC. In total, 318 patients were treated at the MC (122 OSR; 196 EVAR). At the MC, r-EVAR was associated with a lower mortality rate than r-OSR (20% vs 37%, P = 0.001). Transfer did not influence r-EVAR mortality (20% in r-EVAR presenting to MC vs 20% in r-EVAR transferred, P > 0.2). Overall, r-AAA mortality at the MC was 20% lower than CH (27% vs 46%, P < 0.001). Regionalization of r-AAA repair to centers equipped for both r-EVAR and r-OSR decreased mortality by approximately 20%. Transfer did not impact the mortality of r-EVAR at the tertiary center. Care of r-AAA in the US should be centralized to centers equipped with available technology and vascular surgeons.

  11. On the Impact of Intraluminal Thrombus Mechanical Behavior in AAA Passive Mechanics.

    PubMed

    Riveros, Fabián; Martufi, Giampaolo; Gasser, T Christian; Rodriguez-Matas, Jose F

    2015-09-01

    Intraluminal thrombus (ILT) is a pseudo-tissue that develops from coagulated blood, and is found in most abdominal aortic aneurysms (AAAs) of clinically relevant size. A number of studies have suggested that ILT mechanical characteristics may be related to AAA risk of rupture, even though there is still great controversy in this regard. ILT is isotropic and inhomogeneous and may appear as a soft (single-layered) or stiff (multilayered fibrotic) tissue. This paper aims to investigate how ILT constitution and topology influence the magnitude and location of peak wall stress (PWS). In total 21 patient-specific AAAs (diameter 4.2-5.4 cm) were reconstructed from computer tomography images and biomechanically analyzed using state-of-the-art modeling assumptions. Results indicated that PWS correlated stronger with ILT volume (ρ = 0.44, p = 0.05) and minimum thickness of ILT layer (ρ = 0.73, p = 0.001) than with maximum AAA diameter (ρ = 0.05, p = 0.82). On average PWS was 20% (SD 12%) higher for FE models that used soft instead of stiff ILT models (p < 0.001). PWS location strongly correlated with sites of minimum ILT thickness in the section of maximum AAA diameter and was independent from ILT stiffness. In addition, ILT heterogeneity, i.e., the spatial composition of soft and stiff thrombus tissue, can considerably influence stress in the AAA wall. The present study is limited to identification of influential biomechanical factors, and how its findings translate to an AAA rupture risk assessment remains to be explored by clinical studies.

  12. The Diverse AAA+ Machines that Repair Inhibited Rubisco Active Sites

    PubMed Central

    Mueller-Cajar, Oliver

    2017-01-01

    Gaseous carbon dioxide enters the biosphere almost exclusively via the active site of the enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). This highly conserved catalyst has an almost universal propensity to non-productively interact with its substrate ribulose 1,5-bisphosphate, leading to the formation of dead-end inhibited complexes. In diverse autotrophic organisms this tendency has been counteracted by the recruitment of dedicated AAA+ (ATPases associated with various cellular activities) proteins that all use the energy of ATP hydrolysis to remodel inhibited Rubisco active sites leading to release of the inhibitor. Three evolutionarily distinct classes of these Rubisco activases (Rcas) have been discovered so far. Green and red-type Rca are mostly found in photosynthetic eukaryotes of the green and red plastid lineage respectively, whereas CbbQO is associated with chemoautotrophic bacteria. Ongoing mechanistic studies are elucidating how the various motors are utilizing both similar and contrasting strategies to ultimately perform their common function of cracking the inhibited Rubisco active site. The best studied mechanism utilized by red-type Rca appears to involve transient threading of the Rubisco large subunit C-terminal peptide, reminiscent of the action performed by Clp proteases. As well as providing a fascinating example of convergent molecular evolution, Rca proteins can be considered promising crop-improvement targets. Approaches aiming to replace Rubisco in plants with improved enzymes will need to ensure the presence of a compatible Rca protein. The thermolability of the Rca protein found in crop plants provides an opportunity to fortify photosynthesis against high temperature stress. Photosynthesis also appears to be limited by Rca when light conditions are fluctuating. Synthetic biology strategies aiming to enhance the autotrophic CO2 fixation machinery will need to take into consideration the requirement for Rubisco activases

  13. Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

    PubMed

    An, Young Jun; Na, Jung-Hyun; Kim, Myung-Il; Cha, Sun-Shin

    2015-10-01

    Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.

  14. Persistent type II endoleak after EVAR: the predictive value of the AAA thrombus volume.

    PubMed

    Gallitto, Enrico; Gargiulo, Mauro; Mascoli, Chiara; Freyrie, Antonio; DE Matteis, Massimo; Serra, Carla; Bianchini Massoni, Claudio; Faggioli, Gianluca; Stella, Andrea

    2018-02-01

    Persistent type II endoleaks (ELIIp, ≥6 months) after an endovascular aneurysm repair (EVAR) can be associated with adverse outcomes. The aims of this study are the evaluation of the incidence of ELIIp, their preoperative morphological predictive features (PMF) and the post-EVAR abdominal aortic aneurysm (AAA) evolution in the presence of ELIIp. Patients underwent EVAR between 2008 and 2010 were prospectively collected. Cases with ELIIp (group A: AG) were identified. A control group without ELIIp (group B: BG), homogeneous for clinical characteristics, follow-up timing and methods (CTA and/or CEUS at 6.12 months and yearly thereafter) was retrospectively selected. The PMF evaluated by computed-tomography-angiography (CTA) were: AAA-diameter, number and diameter of AAA efferent patent vessels (EPV), AAA-total volume (TV), AAA-thrombus volume (THV) and TV/THV rate (%VR). Volumes were calculated by the dedicated vessels analysis software. AG and BG were compared. The primary endpoint was to evaluate the incidence of ELIIp. Secondary endpoints were to analyze the relation between PMF and ELIIp and to assess the post-EVAR AAA-evolution in the presence of ELIIp. Between 2008 and 2010, 200 patients underwent EVAR to treat AAA electively. An ELIIp was detected in 35cases (17.5%) (AG). Twenty-seven patients (13.5%) were included in BG. An overall of 62 patients (GA+GB) were analyzed. The mean pre-operative AAA diameter and EPV were 58±11.6 mm and 5.5±1.8 mm, respectively. The mean TV and THV were 187±111.5 cc and 82±75 cc, respectively. The median %VR was 42.3%. ELIIp was correlated to EPV≥6 (χ2, p=.015) and %VR <40% (logistic regression, P=0.032). The mean follow-up was 22±9 months. Seven (20%) ELIIp spontaneously sealed and 6 (17%) required reinterventions (2 conversions to OR). There were not PMF associated to ELIIp evolution and AAA growth post-EVAR. ELIIp is a not rare complication and it could require re-interventions. Our data suggest that VEP≥6 or %VT<40

  15. Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

    PubMed

    Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

    2018-01-15

    Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

    PubMed

    Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

    2011-07-01

    ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

  17. Hepatorenal revascularization enables EVAR repair on a patient with AAA and an ectopic right renal artery.

    PubMed

    Lazaris, A M; Moulakakis, K; Mantas, G; Poulou, K; Alexiou, E; Vasdekis, S; Geroulakos, G

    2018-06-07

    The last thirty years the endovascular repair (EVAR) has become the standard method of treatment of abdominal aortic aneurysms (AAA). Nevertheless, the method has limitations based mainly on the anatomic characteristics of the specific aneurysm. In these cases a combination of endovascular and open techniques can be used. We describe a case of a patient with an infrarenal AAA and an ectopic right renal artery emerging from within the aneurysm sac. The patient was treated with a combination of endovascular and open techniques. In particular, he underwent a hepatorenal revascularization followed by a standard EVAR procedure, with a successful final outcome. For the treatment of AAA disease, the combination of open and endovascular procedures can overcome difficulties where a standard EVAR cannot be an option. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. The AAA protein spastin possesses two levels of basal ATPase activity.

    PubMed

    Fan, Xiangyu; Lin, Zhijie; Fan, Guanghui; Lu, Jing; Hou, Yongfei; Habai, Gulijiazi; Sun, Linyue; Yu, Pengpeng; Shen, Yuequan; Wen, Maorong; Wang, Chunguang

    2018-05-01

    The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected. © 2018 Federation of European Biochemical Societies.

  19. Role of mitochondrial processing peptidase and AAA proteases in processing of the yeast acetohydroxyacid synthase precursor.

    PubMed

    Dasari, Suvarna; Kölling, Ralf

    2016-07-01

    We studied presequence processing of the mitochondrial-matrix targeted acetohydroxyacid synthase (Ilv2). C-terminal 3HA-tagging altered the cleavage pattern from a single step to sequential two-step cleavage, giving rise to two Ilv2-3HA forms (A and B). Both cleavage events were dependent on the mitochondrial processing peptidase (MPP). We present evidence for the involvement of three AAA ATPases, m- and i-AAA proteases, and Mcx1, in Ilv2-3HA processing. Both, precursor to A-form and A-form to B-form cleavage were strongly affected in a ∆yme1 mutant. These defects could be suppressed by overexpression of MPP, suggesting that MPP activity is limiting in the ∆yme1 mutant. Our data suggest that for some substrates AAA ATPases could play an active role in the translocation of matrix-targeted proteins.

  20. Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

    PubMed

    Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

    2017-07-24

    This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (p<0.05). AAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

  1. Dosimetric comparison of Acuros XB, AAA, and XVMC in stereotactic body radiotherapy for lung cancer.

    PubMed

    Tsuruta, Yusuke; Nakata, Manabu; Nakamura, Mitsuhiro; Matsuo, Yukinori; Higashimura, Kyoji; Monzen, Hajime; Mizowaki, Takashi; Hiraoka, Masahiro

    2014-08-01

    To compare the dosimetric performance of Acuros XB (AXB), anisotropic analytical algorithm (AAA), and x-ray voxel Monte Carlo (XVMC) in heterogeneous phantoms and lung stereotactic body radiotherapy (SBRT) plans. Water- and lung-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. The radiation treatment machine Novalis (BrainLab AG, Feldkirchen, Germany) with an x-ray beam energy of 6 MV was used to calculate the doses in the composite phantom at a source-to-surface distance of 100 cm with a gantry angle of 0°. Subsequently, the clinical lung SBRT plans for the 26 consecutive patients were transferred from the iPlan (ver. 4.1; BrainLab AG) to the Eclipse treatment planning systems (ver. 11.0.3; Varian Medical Systems, Palo Alto, CA). The doses were then recalculated with AXB and AAA while maintaining the XVMC-calculated monitor units and beam arrangement. Then the dose-volumetric data obtained using the three different radiation dose calculation algorithms were compared. The results from AXB and XVMC agreed with measurements within ± 3.0% for the lung-equivalent phantom with a 6 × 6 cm(2) field size, whereas AAA values were higher than measurements in the heterogeneous zone and near the boundary, with the greatest difference being 4.1%. AXB and XVMC agreed well with measurements in terms of the profile shape at the boundary of the heterogeneous zone. For the lung SBRT plans, AXB yielded lower values than XVMC in terms of the maximum doses of ITV and PTV; however, the differences were within ± 3.0%. In addition to the dose-volumetric data, the dose distribution analysis showed that AXB yielded dose distribution calculations that were closer to those with XVMC than did AAA. Means ± standard deviation of the computation time was 221.6 ± 53.1 s (range, 124-358 s), 66.1 ± 16.0 s (range, 42-94 s), and 6.7 ± 1.1 s (range, 5-9 s) for XVMC, AXB, and AAA, respectively. In the phantom evaluations, AXB and XVMC agreed better with

  2. Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

    PubMed

    Dunne, Jonathan A; Bailey, Marc A; Griffin, Kathryn J; Sohrabi, Soroush; Coughlin, Patrick A; Scott, D Julian A

    2014-01-01

    In the era of Abdominal Aortic Aneurysm (AAA) screening, pharmacotherapies to attenuate AAA growth are sought. HMG Co-A reductase inhibitors (statins) have pleiotropic actions independent of their lipid lowering effects and have been suggested as potential treatment for small AAAs. We systematically review the clinical evidence for this effect. Medline, EMBASE and the Cochrane Central Register of Controlled Trials (1950-2011) were searched for studies reporting data on the role of statin therapy on AAA growth rate. No language restrictions were placed on the search. References of retrieved articles and pertinent journals were hand searched. Included studies were reviewed by 2 independent observers. The search retrieved 164 papers, 100 were irrelevant based on their title, 47 were reviews and 1 was a letter. 8 studies were excluded based on review of their abstract leaving 8 for inclusion in the study. Eight observational clinical studies with a total of 4,466 patients were reviewed. Four studies demonstrated reduced AAA expansion in statin users while 4 studies failed to demonstrate this effect. The method of determining AAA growth rates varied significantly between the studies and the ability of many studies to control for misclassification bias was poor. The claim that statins attenuate AAA growth remains questionable. Further prospective studies with stringent identification and verification of statin usage and a standardised method of estimating AAA growth rates are required. Statin type and dose also merit consideration.

  3. Selective Intra-procedural AAA sac Embolization During EVAR Reduces the Rate of Type II Endoleak.

    PubMed

    Mascoli, C; Freyrie, A; Gargiulo, M; Gallitto, E; Pini, R; Faggioli, G; Serra, C; De Molo, C; Stella, A

    2016-05-01

    The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp. Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p < .001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p = .001, and 5/25 vs. 32/44, respectively, p < .001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p < .001). No differences in median AAA sac

  4. Stan Bull, Long-Time NREL Leader, Named AAAS Fellow | News | NREL

    Science.gov Websites

    , Named AAAS Fellow January 11, 2011 Stanley R. Bull, former associate director for Science and Technology emeritus researcher. He was cited for "distinguished leadership in creating new programs, development partner with existing energy companies, including the fossil-fuel industry, and to "provide our

  5. Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes.

    PubMed

    Saffert, Paul; Enenkel, Cordula; Wendler, Petra

    2017-01-01

    Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria. Tremendous efforts have been undertaken to understand the conformational dynamics of protein remodeling type II AAA+ complexes. A uniform mode of action has not been derived from these works. This review focuses on p97/VCP and the Pex1/6 complex, which both structurally remodel ubiquitinated substrate proteins. P97/VCP plays a role in many processes, including ER- associated protein degradation, and the Pex1/Pex6 complex dislocates and recycles the transport receptor Pex5 from the peroxisomal membrane during peroxisomal protein import. We give an introduction into existing knowledge about the biochemical and cellular activities of the complexes before discussing structural information. We particularly emphasize recent electron microscopy structures of the two AAA+ complexes and summarize their structural differences.

  6. Effects of doping and bias voltage on the screening in AAA-stacked trilayer graphene

    NASA Astrophysics Data System (ADS)

    Mohammadi, Yawar; Moradian, Rostam; Shirzadi Tabar, Farzad

    2014-09-01

    We calculate the static polarization of AAA-stacked trilayer graphene (TLG) and study its screening properties within the random phase approximation (RPA) in all undoped, doped and biased regimes. We find that the static polarization of undoped AAA-stacked TLG is a combination of the doped and undoped single-layer graphene static polarization. This leads to an enhancement of the dielectric background constant along a Thomas-Fermi screening with the Thomas-Fermi wave vector which is independent of carrier concentrations and a 1/r3 power law decay for the long-distance behavior of the screened Coulomb potential. We show that effects of a bias voltage can be taken into account by a renormalization of the interlayer hopping energy to a new bias-voltage-dependent value, indicating screening properties of AAA-stacked TLG can be tuned electrically. We also find that screening properties of doped AAA-stacked TLG, when μ exceeds √{2}γ, are similar to that of doped SLG only depending on doping. While for μ<√{2}γ, its screening properties are combination of SLG and AA-stacked bilayer graphene screening properties and they are determined by doping and the interlayer hopping energy.

  7. Improved Resident Adherence to AAA Screening Guidelines via an Electronic Reminder.

    PubMed

    Sypert, David; Van Dyke, Kenneth; Dhillon, Namrata; Elliott, John O; Jordan, Kim

    The 2014 United States Preventive Services Task Force systematic review found abdominal aortic aneurysm (AAA) screening decreased related mortality by close to half. Despite the simplicity of screening, research suggests poor adherence to the recommended AAA screening guidelines. Using the quality improvement plan-study-do-act cycle, we retrospectively established poor adherence to AAA screening and poor documentation of smoking history in our resident clinic. An electronic reminder was prospectively implemented into our electronic medical record (EMR) with the goal of improving screening rates. After 1 year, a retrospective chart review was conducted. Comparisons of the pre- and post-electronic reminder intervention data were made using chi-square tests and odds ratios (OR). The purposeful AAA screening rate improved 27.8% during the intervention, 40.3% (95% confidence interval [CI]: 28.6-52.0%) versus 12.5% (95% CI: 3.1-21.9%), p = .002, suggesting patients were more likely to be screened as a result of the electronic reminder, OR = 4.73 (95% CI: 1.77-12.65). This improvement translates to a large effect size, Cohen's d = 0.86 (95% CI: 0.31-1.40). Electronic reminders are a simple EMR addition that can provide evidence-based education while improving adherence rates with preventive health screening measures.

  8. Structure of Lmaj006129AAA, a hypothetical protein from Leishmania major

    SciTech Connect

    Arakaki, Tracy; Le Trong, Isolde; Structural Genomics of Pathogenic Protozoa

    2006-03-01

    The crystal structure of a conserved hypothetical protein from L. major, Pfam sequence family PF04543, structural genomics target ID Lmaj006129AAA, has been determined at a resolution of 1.6 Å. The gene product of structural genomics target Lmaj006129 from Leishmania major codes for a 164-residue protein of unknown function. When SeMet expression of the full-length gene product failed, several truncation variants were created with the aid of Ginzu, a domain-prediction method. 11 truncations were selected for expression, purification and crystallization based upon secondary-structure elements and disorder. The structure of one of these variants, Lmaj006129AAH, was solved by multiple-wavelength anomalous diffraction (MAD)more » using ELVES, an automatic protein crystal structure-determination system. This model was then successfully used as a molecular-replacement probe for the parent full-length target, Lmaj006129AAA. The final structure of Lmaj006129AAA was refined to an R value of 0.185 (R{sub free} = 0.229) at 1.60 Å resolution. Structure and sequence comparisons based on Lmaj006129AAA suggest that proteins belonging to Pfam sequence families PF04543 and PF01878 may share a common ligand-binding motif.« less

  9. Fan filter cleaning on the CHeCS AAA in the US Lab

    NASA Image and Video Library

    2009-05-05

    ISS019-E-013710 (5 May 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, cleans a fan filter on the Crew Health Care System Avionics Air Assembly (CHeCS AAA) in the Destiny laboratory of the International Space Station.

  10. National dosimetric audit network finds discrepancies in AAA lung inhomogeneity corrections.

    PubMed

    Dunn, Leon; Lehmann, Joerg; Lye, Jessica; Kenny, John; Kron, Tomas; Alves, Andrew; Cole, Andrew; Zifodya, Jackson; Williams, Ivan

    2015-07-01

    This work presents the Australian Clinical Dosimetry Service's (ACDS) findings of an investigation of systematic discrepancies between treatment planning system (TPS) calculated and measured audit doses. Specifically, a comparison between the Anisotropic Analytic Algorithm (AAA) and other common dose-calculation algorithms in regions downstream (≥2cm) from low-density material in anthropomorphic and slab phantom geometries is presented. Two measurement setups involving rectilinear slab-phantoms (ACDS Level II audit) and anthropomorphic geometries (ACDS Level III audit) were used in conjunction with ion chamber (planar 2D array and Farmer-type) measurements. Measured doses were compared to calculated doses for a variety of cases, with and without the presence of inhomogeneities and beam-modifiers in 71 audits. Results demonstrate a systematic AAA underdose with an average discrepancy of 2.9 ± 1.2% when the AAA algorithm is implemented in regions distal from lung-tissue interfaces, when lateral beams are used with anthropomorphic phantoms. This systemic discrepancy was found for all Level III audits of facilities using the AAA algorithm. This discrepancy is not seen when identical measurements are compared for other common dose-calculation algorithms (average discrepancy -0.4 ± 1.7%), including the Acuros XB algorithm also available with the Eclipse TPS. For slab phantom geometries (Level II audits), with similar measurement points downstream from inhomogeneities this discrepancy is also not seen. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  11. SOFIA Technology: The NASA Airborne Astronomy Ambassador (AAA) Experience and Online Resources

    NASA Astrophysics Data System (ADS)

    Clark, C.; Harman, P. K.; Backman, D. E.

    2016-12-01

    SOFIA, an 80/20 partnership of NASA and the German Aerospace Center (DLR), consists of a modified Boeing 747SP carrying a reflecting telescope with an effective diameter of 2.5 meters. SOFIA is the largest airborne observatory in the world, capable of observations impossible for even the largest and highest ground-based telescopes. The SOFIA Program Office is at NASA ARC, Moffett Field, CA; the aircraft is based in Palmdale, CA. During its planned 20-year lifetime, SOFIA will foster development of new scientific instrumentation and inspire the education of young scientists and engineers. Astrophysicists are awarded time on SOFIA to study many kinds of astronomical objects and phenomena. Among the most interesting are: Star birth, evolution, and death Formation of new planetary systems Chemistry of complex molecules in space Planet and exoplanet atmospheres Galactic gas & dust "ecosystems" Environments around supermassive black holes SOFIA currently has eight instruments, five US-made and three German. The instruments — cameras, spectrometers, and a photometer,— operate at near-, mid- and far-infrared wavelengths, each spectral range being best suited to studying particular celestial phenomena. NASA's Airborne Astronomy Ambassadors' (AAAs) experience includes a STEM immersion component. AAAs are onboard during two overnight SOFIA flights that provide insight into the acquisition of scientific data as well as the interfaces between the telescope, instrument, & aircraft. AAAs monitor system performance and view observation targets from their dedicated workstation during flights. Future opportunities for school district partnerships leading to selection of future AAA cohorts will be offered in 2018-19. AAAs may access public archive data via the SOFIA Data Cycle System (DCS) https://dcs.sofia.usra.edu/. Additional SOFIA science and other resources are available at: www.sofia.usra.edu, including lessons that use photovoltaic circuits, and other technology for the

  12. Asymmetric processing of a substrate protein in sequential allosteric cycles of AAA+ nanomachines

    NASA Astrophysics Data System (ADS)

    Kravats, Andrea N.; Tonddast-Navaei, Sam; Bucher, Ryan J.; Stan, George

    2013-09-01

    Essential protein quality control includes mechanisms of substrate protein (SP) unfolding and translocation performed by powerful ring-shaped AAA+ (ATPases associated with various cellular activities) nanomachines. These SP remodeling actions are effected by mechanical forces imparted by AAA+ loops that protrude into the central channel. Sequential intra-ring allosteric motions, which underlie repetitive SP-loop interactions, have been proposed to comprise clockwise (CW), counterclockwise (CCW), or random (R) conformational transitions of individual AAA+ subunits. To probe the effect of these allosteric mechanisms on unfoldase and translocase functions, we perform Langevin dynamics simulations of a coarse-grained model of an all-alpha SP processed by the single-ring ClpY ATPase or by the double-ring p97 ATPase. We find that, in all three allosteric mechanisms, the SP undergoes conformational transitions along a common set of pathways, which reveals that the active work provided by the ClpY machine involves single loop-SP interactions. Nevertheless, the rates and yields of SP unfolding and translocation are controlled by mechanism-dependent loop-SP binding events, as illustrated by faster timescales of SP processing in CW allostery compared with CCW and R allostery. The distinct efficacy of allosteric mechanisms is due to the asymmetric collaboration of adjacent subunits, which involves CW-biased structural motions of AAA+ loops and results in CW-compatible torque applied onto the SP. Additional simulations of mutant ClpY rings, which render a subset of subunits catalytically-defective or reduce their SP binding affinity, reveal that subunit-based conformational transitions play the major role in SP remodeling. Based on these results we predict that the minimally functional AAA+ ring includes three active subunits, only two of which are adjacent.

  13. Molecular insights into the m-AAA protease-mediated dislocation of transmembrane helices in the mitochondrial inner membrane.

    PubMed

    Lee, Seoeun; Lee, Hunsang; Yoo, Suji; Kim, Hyun

    2017-12-08

    Protein complexes involved in respiration, ATP synthesis, and protein import reside in the mitochondrial inner membrane; thus, proper regulation of these proteins is essential for cell viability. The m -AAA protease, a conserved hetero-hexameric AAA (ATPase associated with diverse cellular activities) protease, composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates the dislocation of membrane-embedded substrates, including foreign transmembrane (TM) segments, but the molecular mechanism involved in these processes remains elusive. This study investigated the role of the TM domains in the m -AAA protease by systematic replacement of one TM domain at a time in yeast. Our data indicated that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs membrane dislocation for all tested substrates, suggesting different roles of the TM domains in each m -AAA protease subunit. Furthermore, m -AAA protease-mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate. This finding suggested that the m -AAA protease cannot dislocate large hydrophilic domains across the membrane, indicating that the membrane dislocation probably occurs in a lipid environment. In summary, this study highlights previously underappreciated biological roles of TM domains of the m -AAA proteases in mediating the recognition and dislocation of membrane-embedded substrates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.

    PubMed

    Prattes, Michael; Loibl, Mathias; Zisser, Gertrude; Luschnig, Daniel; Kappel, Lisa; Rössler, Ingrid; Grassegger, Manuela; Hromic, Altijana; Krieger, Elmar; Gruber, Karl; Pertschy, Brigitte; Bergler, Helmut

    2017-03-17

    AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research. Here, we present the characterization of a novel mutant variant of the eukaryotic AAA-ATPase Drg1 that shows dysregulation of ATPase activity and altered interaction with Rlp24, its substrate in ribosome biogenesis. This defective regulation is the consequence of amino acid exchanges at the interface between the regulatory N-domain and the adjacent D1 AAA-domain. The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). Our results therefore suggest well conserved mechanisms of regulation between structurally, but not functionally related members of the AAA-family.

  15. SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

    SciTech Connect

    Lamichhane, N; Studenski, M

    2016-06-15

    Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobendmore » block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.« less

  16. Prevalence of abdominal aortic aneurysm (AAA) in a population undergoing computed tomography colonography in Canterbury, New Zealand.

    PubMed

    Khashram, M; Jones, G T; Roake, J A

    2015-08-01

    There is compelling level 1 evidence in support of screening men for abdominal aortic aneurysm (AAA) to reduce AAA mortality. However, New Zealand (NZ) lacks data on AAA prevalence, and national screening has not been implemented. The aim of this study was to determine the prevalence of AAA in a population undergoing a computed tomography colonography (CTC) for gastrointestinal symptoms. This was an observational study; all consecutive CTCs performed in three regions of the South Island of NZ over a 4 year period were reviewed. Data on abdominal and thoracic aorta diameters ≥30 mm, and iliac and femoral aneurysms ≥20 mm were recorded. Previous aortic surgical grafts or endovascular stents were also documented. Demographics, survival, and AAA related outcomes were collected and used for analysis. Included were 4,893 scans on 4,644 patients (1,933 men [41.6%], 2,711 women [58.4%]) with a median age of 69.3 years (range 17.0-97.0 years). There were 309 scans on 289 patients (75.4% men) who had either an aneurysm or a previous aortic graft with a median age of 79.6 years (range 57.0-96.0 years). Of these, 223 had a native AAA ≥30 mm. The prevalence of AAA rose with age from 1.3% in men aged 55-64 years, to 9.1% in 65-74 year olds, 16.8% in 75-84 year olds, and 22.0% in ≥85 year olds. The corresponding figures in women were 0.4%, 2%, 3.9%, and 6.2%, respectively. In this observational study, the prevalence of AAA was high and warrants further evaluation. The results acquired help to define a population that may benefit from a national AAA screening programme. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  17. Clinical implementation of AXB from AAA for breast: Plan quality and subvolume analysis.

    PubMed

    Guebert, Alexandra; Conroy, Leigh; Weppler, Sarah; Alghamdi, Majed; Conway, Jessica; Harper, Lindsay; Phan, Tien; Olivotto, Ivo A; Smith, Wendy L; Quirk, Sarah

    2018-05-01

    Two dose calculation algorithms are available in Varian Eclipse software: Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB). Many Varian Eclipse-based centers have access to AXB; however, a thorough understanding of how it will affect plan characteristics and, subsequently, clinical practice is necessary prior to implementation. We characterized the difference in breast plan quality between AXB and AAA for dissemination to clinicians during implementation. Locoregional irradiation plans were created with AAA for 30 breast cancer patients with a prescription dose of 50 Gy to the breast and 45 Gy to the regional node, in 25 fractions. The internal mammary chain (IMC CTV ) nodes were covered by 80% of the breast dose. AXB, both dose-to-water and dose-to-medium reporting, was used to recalculate plans while maintaining constant monitor units. Target coverage and organ-at-risk doses were compared between the two algorithms using dose-volume parameters. An analysis to assess location-specific changes was performed by dividing the breast into nine subvolumes in the superior-inferior and left-right directions. There were minimal differences found between the AXB and AAA calculated plans. The median difference between AXB and AAA for breast CTV V 95% , was <2.5%. For IMC CTV , the median differences V 95% , and V 80% were <5% and 0%, respectively; indicating IMC CTV coverage only decreased when marginally covered. Mean superficial dose increased by a median of 3.2 Gy. In the subvolume analysis, the medial subvolumes were "hotter" when recalculated with AXB and the lateral subvolumes "cooler" with AXB; however, all differences were within 2 Gy. We observed minimal difference in magnitude and spatial distribution of dose when comparing the two algorithms. The largest observable differences occurred in superficial dose regions. Therefore, clinical implementation of AXB from AAA for breast radiotherapy is not expected to result in changes in clinical

  18. Substituent effects in double-helical hydrogen-bonded AAA-DDD complexes.

    PubMed

    Wang, Hong-Bo; Mudraboyina, Bhanu P; Wisner, James A

    2012-01-27

    Two series of DDD and AAA hydrogen-bond arrays were synthesized that form triply-hydrogen-bonded double-helical complexes when combined in CDCl(3) solution. Derivatization of the DDD arrays with electron-withdrawing groups increases the complex association constants by up to a factor of 30 in those arrays examined. Derivatization of the AAA arrays with electron donating substituents reveals a similar magnitude effect on the complex stabilities. The effect of substitution on both types of arrays are modeled quite satisfactorily (R(2) > 0.96 in all cases) as free energy relationships with respect to the sums of their Hammett substituent constants. In all, the complex stabilities can be manipulated over more than three orders of magnitude (>20 kJ mol(-1)) using this type of modification. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. SFM-FDTD analysis of triangular-lattice AAA structure: Parametric study of the TEM mode

    NASA Astrophysics Data System (ADS)

    Hamidi, M.; Chemrouk, C.; Belkhir, A.; Kebci, Z.; Ndao, A.; Lamrous, O.; Baida, F. I.

    2014-05-01

    This theoretical work reports a parametric study of enhanced transmission through annular aperture array (AAA) structure arranged in a triangular lattice. The effect of the incidence angle in addition to the inner and outer radii values on the evolution of the transmission spectra is carried out. To this end, a 3D Finite-Difference Time-Domain code based on the Split Field Method (SFM) is used to calculate the spectral response of the structure for any angle of incidence. In order to work through an orthogonal unit cell which presents the advantage to reduce time and space of computation, special periodic boundary conditions are implemented. This study provides a new modeling of AAA structures useful for producing tunable ultra-compact devices.

  20. Structural Basis of ATP Hydrolysis and Intersubunit Signaling in the AAA+ ATPase p97.

    PubMed

    Hänzelmann, Petra; Schindelin, Hermann

    2016-01-05

    p97 belongs to the superfamily of AAA+ ATPases and is characterized by a tandem AAA module, an N-terminal domain involved in substrate and cofactor interactions, and a functionally important unstructured C-terminal tail. The ATPase activity is controlled by an intradomain communication within the same protomer and an interdomain communication between neighboring protomers. Here, we present for the first time crystal structures in which the physiologically relevant p97 hexamer constitutes the content of the asymmetric unit, namely in the apo state without nucleotide in either the D1 or D2 module and in the pre-activated state with ATPγS bound to both modules. The structures provide new mechanistic insights into the interdomain communication mediated by conformational changes of the C terminus as well as an intersubunit signaling network, which couples the nucleotide state to the conformation of the central putative substrate binding pore. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine

    PubMed Central

    Iosefson, Ohad; Nager, Andrew R.; Baker, Tania A.; Sauer, Robert T.

    2014-01-01

    Hexameric AAA+ unfoldases of ATP-dependent proteases and protein-remodeling machines use conserved loops that line the axial pore to apply force to substrates during the mechanical processes of protein unfolding and translocation. Whether loops from multiple subunits act independently or coordinately in these processes is a critical aspect of mechanism but is currently unknown for any AAA+ machine. By studying covalently linked hexamers of the E. coli ClpX unfoldase bearing different numbers and configurations of wild-type and mutant pore loops, we show that loops function synergistically, with the number of wild-type loops required for efficient degradation depending upon the stability of the protein substrate. Our results support a mechanism in which a power stroke initiated in one subunit of the ClpX hexamer results in the concurrent movement of all six pore loops, which coordinately grip and apply force to the substrate. PMID:25599533

  2. SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA Algorithms.

    PubMed

    Yuan, Y; Duan, J; Popple, R; Brezovich, I

    2012-06-01

    To evaluate the accuracy of dose calculation for intensity modulated radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic Algorithm (AAA) computation algorithms. IMRT plans of twelve patients with different treatment sites, including head/neck, lung and pelvis, were investigated. For each patient, dose calculation with PB and AAA algorithms using dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite-beam ion chamber and film measurements in patient specific QA. Discrepancies between the calculation and the measurement were evaluated by percentage error for ion chamber dose and γ〉l failure rate in gamma analysis (3%/3mm) for film dosimetry. For 9 patients, ion chamber dose calculated with AAA-algorithms is closer to ion chamber measurement than that calculated with PB algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are within 3% of the measurements. For head/neck patients and other patients with large treatment volumes, γ〉l failure rate is significantly reduced (within 5%) with AAA-based treatment planning compared to generally more than 10% with PB-based treatment planning (grid size=2.5 mm). For lung and brain cancer patients with medium and small treatment volumes, γ〉l failure rates are typically within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For both PB and AAA-based treatment planning, improvements of dose calculation accuracy with finer dose grids were observed in film dosimetry of 11 patients and in ion chamber measurements for 3 patients. AAA-based treatment planning provides more accurate dose calculation for head/neck patients and other patients with large treatment volumes. Compared with film dosimetry, a γ〉l failure rate within 5% can be achieved for AAA-based treatment planning. © 2012 American Association of Physicists in Medicine.

  3. The two faces of hydrogen-bond strength on triple AAA-DDD arrays.

    PubMed

    Lopez, Alfredo Henrique Duarte; Caramori, Giovanni Finoto; Coimbra, Daniel Fernando; Parreira, Renato Luis Tame; da Silva, Éder Henrique

    2013-12-02

    Systems that are connected through multiple hydrogen bonds are the cornerstone of molecular recognition processes in biology, and they are increasingly being employed in supramolecular chemistry, specifically in molecular self-assembly processes. For this reason, the effects of different substituents (NO2, CN, F, Cl, Br, OCH3 and NH2) on the electronic structure, and consequently on the magnitude of hydrogen bonds in triple AAA-DDD arrays (A=acceptor, D=donor) were evaluated in the light of topological [electron localization function (ELF) and quantum theory of atoms in molecules (QTAIM)], energetic [Su-Li energy-decomposition analysis (EDA) and natural bond orbital analysis (NBO)], and geometrical analysis. The results based on local H-bond descriptors (geometries, QTAIM, ELF, and NBO) indicate that substitutions with electron-withdrawing groups on the AAA module tend to strengthen, whereas electron-donating substituents tend to weaken the covalent character of the AAA-DDD intermolecular H-bonds, and also indicate that the magnitude of the effect is dependent on the position of substitution. In contrast, Su-Li EDA results show an opposite behavior when compared to local H-bond descriptors, indicating that electron-donating substituents tend to increase the magnitude of H-bonds in AAA-DDD arrays, and thus suggesting that the use of local H-bond descriptors describes the nature of H bonds only partially, not providing enough insight about the strength of such H bonds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Antibacterial and cytotoxic activity of isoprenylated coumarin mammea A/AA isolated from Mammea africana.

    PubMed

    Canning, Corene; Sun, Shi; Ji, Xiangming; Gupta, Smiti; Zhou, Kequan

    2013-05-02

    The stem bark of Mammea africana is widely distributed in tropical Africa and commonly used in traditional medicine. This study aims to identify the active compound in Mammea africana and to evaluate its antimicrobial and antiproliferative activity. Methanol extract from the bark of the Mammea africana was separated by liquid-liquid extraction, followed by open column chromatography. A principal antimicrobial compound was purified by high performance liquid chromatography (HPLC) and its structure was elucidated by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The antibacterial activity of the purified compound was determined using the broth microdilution method against 7 common pathogenic bacteria. The compound was also evaluated for cytotoxicity by cell proliferation assay (MTS) using the mouse embryonic fibroblast cell line NIH 3T3 and the non-small cell lung cancer cell line A549. The purified active compound was determined to be mammea A/AA and was found to be highly active against Campylobacter jejuni (MIC=0.5 μg/ml), Streptococcus pneumoniae (MIC=0.25 μg/ml), and Clostridium difficile (MIC=0.25 μg/ml). The compound exhibited significant antiproliferative activities against both NIH 3T3 and A549 cell lines. Mammea A/AA isolated from Mammea africana exerts specific inhibitory activity against Campylobacter jejuni, Streptococcus pneumoniae, and Campylobacter difficile. Mammea A/AA was also found to exhibit significant cytotoxicity against both cancer and normal cell lines. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Structural Insights into the Allosteric Operation of the Lon AAA+ Protease.

    PubMed

    Lin, Chien-Chu; Su, Shih-Chieh; Su, Ming-Yuan; Liang, Pi-Hui; Feng, Chia-Cheng; Wu, Shih-Hsiung; Chang, Chung-I

    2016-05-03

    The Lon AAA+ protease (LonA) is an evolutionarily conserved protease that couples the ATPase cycle into motion to drive substrate translocation and degradation. A hallmark feature shared by AAA+ proteases is the stimulation of ATPase activity by substrates. Here we report the structure of LonA bound to three ADPs, revealing the first AAA+ protease assembly where the six protomers are arranged alternately in nucleotide-free and bound states. Nucleotide binding induces large coordinated movements of conserved pore loops from two pairs of three non-adjacent protomers and shuttling of the proteolytic groove between the ATPase site and a previously unknown Arg paddle. Structural and biochemical evidence supports the roles of the substrate-bound proteolytic groove in allosteric stimulation of ATPase activity and the conserved Arg paddle in driving substrate degradation. Altogether, this work provides a molecular framework for understanding how ATP-dependent chemomechanical movements drive allosteric processes for substrate degradation in a major protein-destruction machine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Identification of a Degradation Signal Sequence within Substrates of the Mitochondrial i-AAA Protease.

    PubMed

    Rampello, Anthony J; Glynn, Steven E

    2017-03-24

    The i-AAA protease is a component of the mitochondrial quality control machinery that regulates respiration, mitochondrial dynamics, and protein import. The protease is required to select specific substrates for degradation from among the diverse complement of proteins present in mitochondria, yet the rules that govern this selection are unclear. Here, we reconstruct the yeast i-AAA protease, Yme1p, to examine the in vitro degradation of two intermembrane space chaperone subunits, Tim9 and Tim10. Yme1p degrades Tim10 more rapidly than Tim9 despite high sequence and structural similarity, and loss of Tim10 is accelerated by the disruption of conserved disulfide bonds within the substrate. An unstructured N-terminal region of Tim10 is necessary and sufficient to target the substrate to the protease through recognition of a short phenylalanine-rich motif, and the presence of similar motifs in other small Tim proteins predicts robust degradation by the protease. Together, these results identify the first specific degron sequence within a native i-AAA protease substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

    PubMed

    Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

    2018-01-29

    Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

  8. Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

    PubMed

    Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

    2015-08-01

    Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

  9. Endothelial MMP-9 drives the inflammatory response in abdominal aortic aneurysm (AAA).

    PubMed

    Ramella, Martina; Boccafoschi, Francesca; Bellofatto, Kevin; Md, Antonia Follenzi; Fusaro, Luca; Boldorini, Renzo; Casella, Francesco; Porta, Carla; Settembrini, Piergiorgio; Cannas, Mario

    2017-01-01

    Progression of abdominal aortic aneurysm (AAA) is typified by chronic inflammation and extracellular matrix (ECM) degradation of the aortic wall. Vascular inflammation involves complex interactions among inflammatory cells, endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and ECM. Although vascular endothelium and medial neoangiogenesis play a key role in AAA, the molecular mechanisms underlying their involvement are only partially understood. In AAA biopsies, we found increased MMP-9, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which correlated with massive medial neo-angiogenesis (C4d positive staining). In this study, we developed an in vitro model in order to characterize the role of endothelial matrix metalloproteinase-9 (e-MMP-9) as a potential trigger of medial disruption and in the inflammatory response bridging between ECs and vSMC. Lentiviral-mediated silencing of e-MMP-9 through RNA interference inhibited TNF-alpha-mediated activation of NF-κB in EA.hy926 human endothelial cells. In addition, EA.hy926 cells void of MMP-9 failed to migrate in a 3D matrix. Moreover, silenced EA.hy926 affected vSMC behavior in terms of matrix remodeling. In fact, also MMP-9 in vSMC resulted inhibited when endothelial MMP-9 was suppressed.

  10. Assessment of resistomycin, as an anticancer compound isolated and characterized from Streptomyces aurantiacus AAA5.

    PubMed

    Vijayabharathi, Rajendran; Bruheim, Per; Andreassen, Trygve; Raja, Duraisamy Senthil; Devi, Palanisamy Bruntha; Sathyabama, Sathyaseelan; Priyadarisini, Venkatesan Brindha

    2011-12-01

    A new actinomycete strain, isolated from humus soils in the Western Ghats, was found to be an efficient pigment producer. The strain, designated AAA5, was identified as a putative Streptomyces aurantiacus strain based on cultural properties, morphology, carbon source utilization, and analysis of the 16S rRNA gene. The strain produced a reddish-brown pigmented compound during the secondary metabolites phase. A yellow compound was derived from the extracted pigment and was identified as the quinone-related antibiotic resistomycin based on ultraviolet-visible spectrophotometry, fourier transform infrared spectroscopy, liquid chromatography and mass spectroscopy, and nuclear magnetic resonance analyses. The AAA5 strain was found to produce large quantities of resistomycin (52.5 mg/L). It showed potent cytotoxic activity against cell lines viz. HepG2 (hepatic carcinoma) and HeLa (cervical carcinoma) in vitro, with growth inhibition (GI(50)) of 0.006 and 0.005 μg/ml, respectively. The strain also exhibited broad antimicrobial activities against both Gram-positive and Gram-negative bacteria. Therefore, AAA5 may have great potential as an industrial resistomycin-producing strain.

  11. A pull-back algorithm to determine the unloaded vascular geometry in anisotropic hyperelastic AAA passive mechanics.

    PubMed

    Riveros, Fabián; Chandra, Santanu; Finol, Ender A; Gasser, T Christian; Rodriguez, Jose F

    2013-04-01

    Biomechanical studies on abdominal aortic aneurysms (AAA) seek to provide for better decision criteria to undergo surgical intervention for AAA repair. More accurate results can be obtained by using appropriate material models for the tissues along with accurate geometric models and more realistic boundary conditions for the lesion. However, patient-specific AAA models are generated from gated medical images in which the artery is under pressure. Therefore, identification of the AAA zero pressure geometry would allow for a more realistic estimate of the aneurysmal wall mechanics. This study proposes a novel iterative algorithm to find the zero pressure geometry of patient-specific AAA models. The methodology allows considering the anisotropic hyperelastic behavior of the aortic wall, its thickness and accounts for the presence of the intraluminal thrombus. Results on 12 patient-specific AAA geometric models indicate that the procedure is computational tractable and efficient, and preserves the global volume of the model. In addition, a comparison of the peak wall stress computed with the zero pressure and CT-based geometries during systole indicates that computations using CT-based geometric models underestimate the peak wall stress by 59 ± 64 and 47 ± 64 kPa for the isotropic and anisotropic material models of the arterial wall, respectively.

  12. Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein*

    PubMed Central

    Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

    2013-01-01

    The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function. PMID:23979136

  13. Structural insights into the unusually strong ATPase activity of the AAA domain of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.

    PubMed

    Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

    2013-10-11

    The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function.

  14. SU-F-T-609: Impact of Dosimetric Variation for Prescription Dose Using Analytical Anisotropic Algorithm (AAA) in Lung SBRT

    SciTech Connect

    Kawai, D; Takahashi, R; Kamima, T

    Purpose: Actual irradiated prescription dose to patients cannot be verified. Thus, independent dose verification and second treatment planning system are used as the secondary check. AAA dose calculation engine has contributed to lung SBRT. We conducted a multi-institutional study to assess variation of prescription dose for lung SBRT when using AAA in reference to using Acuros XB and Clarkson algorithm. Methods: Six institutes in Japan participated in this study. All SBRT treatments were planed using AAA in Eclipse and Adaptive Convolve (AC) in Pinnacle3. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU,more » Triangle Product, Ishikawa, Japan), which implemented a Clarkson-based dose calculation algorithm using CT image dataset. A retrospective analysis for lung SBRT plans (73 patients) was performed to compute the confidence limit (CL, Average±2SD) in dose between the AAA and the SMU. In one of the institutes, a additional analysis was conducted to evaluate the variations between the AAA and the Acuros XB (AXB). Results: The CL for SMU shows larger systematic and random errors of 8.7±9.9 % for AAA than the errors of 5.7±4.2 % for AC. The variations of AAA correlated with the mean CT values in the voxels of PTV (a correlation coefficient : −0.7) . The comparison of AXB vs. AAA shows smaller systematic and random errors of −0.7±1.7%. The correlation between dose variations for AXB and the mean CT values in PTV was weak (0.4). However, there were several plans with more than 2% deviation of AAPM TG114 (Maximum: −3.3 %). Conclusion: In comparison for AC, prescription dose calculated by AAA may be more variable in lung SBRT patient. Even AXB comparison shows unexpected variation. Care should be taken for the use of AAA in lung SBRT. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

  15. Adsorption Study on Moringa Oleifera Seeds and Musa Cavendish as Natural Water Purification Agents for Removal of Lead, Nickel and Cadmium from Drinking Water

    NASA Astrophysics Data System (ADS)

    Aziz, N. A. A.; Jayasuriya, N.; Fan, L.

    2016-07-01

    The effectiveness of plant based materials Moringa oleifera (Moringa) seeds and Musa cavendish (banana peel) for removing heavy metals namely lead (Pb), nickel (Ni) and cadmium (Cd) from contaminated groundwater was studied. Tests were carried out with individual and combined biomass at neutral pH condition on synthetic groundwater samples. The optimum biomass doses were determined as 200 mg/L for single biomass and 400 mg/L (in the ratio of 200 mg/L: 200 mg/L) for combined biomasses and used for adsorption isotherm studies with contact time of 30 minutes. Results showed that combined biomasses was able to met the Pb, Ni and Cd WHO standards from higher Pb, Ni and Cd initial concentrations which were up to 40 µg/L, 50 µg/L 9 µg/L, respectively compared to individual biomass of Moringa seed and banana peel. Moringa seeds exhibited the highest removal of Pb (81%) while the combined biomasses was most effective in removing Ni (74%) and Cd (97%) over wider their initial concentration ranges. The experimental data were linearized with Langmuir and Freundlich adsorption isotherm models. Freundlich model described the Pb adsorption better than the Langmuir model for all the tested biomasses. However, the Langmuir model fit better with the experimental data of Ni adsorption by Moringa seeds. Both models showed negligible differences in the coefficient of determination (R2) when applied for Ni and Cd adsorption on banana peel and combined biomasses, suggesting that there were multiple layers on the biomass interacting with the metals. Chemisorption is suggested to be involved in Pb adsorption for all tested biomasses as the value of nF calculated was lower than one. This type of adsorption could explain the phenomenon of different behavior of Pb removal and the higher Pb adsorption capacity (represented by KF values) compared to Ni and Cd. The study demonstrates that Moringa seeds, banana peel and their combination have the potential to be used as a natural alternative

  16. Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA) in comparison to Ulex europaeus agglutinin I (UEA-I).

    PubMed

    Baldus, S E; Thiele, J; Park, Y O; Hanisch, F G; Bara, J; Fischer, R

    1996-08-01

    Using immunochemical and immunohistochemical methods, the binding site of Anguilla anguilla agglutinin (AAA) was characterized and compared with the related fucose-specific lectin from Ulex europaeus (UEA-I). In solid-phase enzyme-linked immunoassays, the two lectins recognized Fuc alpha 1-2Gal beta-HSA. AAA additionally cross-reacted with neoglycolipids bearing lacto-N-fucopentaose (LNFP) I [H type 1] and II [Le(a)] and lactodifucotetraose (LDFT) as glycan moieties. UEA-I, on the other hand, bound to a LDFT-derived neoglycolipid but not to the other neoglycolipids tested. Binding of AAA to gastric mucin was competitively neutralized by Le(a)-specific monoclonal antibodies. UEA-I binding, on the other hand, was reduced after co-incubation with H type 2- and Le(y)-specific monoclonal antibodies. According to our results, AAA reacts with fucosylated type 1 chain antigens, whereas UEA-I binds only to the alpha 1-2-fucosylated LDFT-derived neoglycolipid. In immunohistochemical studies, the reactivity of AAA and UEA-I in normal pyloric mucosa from individuals with known Lewis and secretor status was analysed. AAA showed a broad reaction in the superficial pyloric mucosa from secretors and non-secretors, but AAA reactivity was more pronounced in Le(a+b-) individuals. On the other hand, UEA-I stained the superficial pyloric mucosa only from secretor individuals. A staining of deep mucous glands by the lectins was found in all specimens. Both reacted with most human carcinomas of different origin. Slight differences in their binding pattern were observed and may be explained by the different fine-specificities of the lectins.

  17. Family Members of Patients with Abdominal Aortic Aneurysms are at Increased Risk for Aneurysms: Analysis of 618 Probands and their Families from the Liège AAA Family Study

    PubMed Central

    Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T.; Tromp, Gerard; Kuivaniemi, Helena

    2014-01-01

    Background The objectives were to answer the following questions using a well-characterized population in Liège, Belgium: 1) what percentage of abdominal aortic aneurysm (AAA) patients have a positive family history for AAA, 2) what is the prevalence of AAAs among relatives of AAA patients; and 3) do familial and sporadic AAA cases differ in clinical characteristics. Methods and Results Unrelated AAA patients diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. In the initial interview 62 (10%) of the 618 AAA patients reported a positive family history for AAA. We divided the 618 patients into two study groups: Group I: 296 AAA patients (268; 91% males) were followed up with computerized tomography combined with positron emission tomography, and Group II: 322 AAA patients (295; 92% males) whose families were invited to ultrasonography screening. Ultrasonography screening identified 24 new AAAs among 186 relatives (≥ 50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonography screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P<0.0001). Conclusions The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis and provide rationale for targeted screening of relatives of AAA patients. PMID:24365082

  18. Family members of patients with abdominal aortic aneurysms are at increased risk for aneurysms: analysis of 618 probands and their families from the Liège AAA Family Study.

    PubMed

    Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T; Tromp, Gerard; Kuivaniemi, Helena

    2014-05-01

    The objectives were to answer the following questions with the help of a well-characterized population in Liège, Belgium: 1) what percentage of patients with abdominal aortic aneurysm (AAA) have a positive family history for AAA? 2) what is the prevalence of AAAs among relatives of patients with AAA? and 3) do familial and sporadic AAA cases differ in clinical characteristics? Patients with unrelated AAA diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. We divided the 618 patients into 2 study groups: group I, 296 patients with AAA (268; 91% men) were followed up with computerized tomography combined with positron emission tomography; and group II, 322 patients with AAA (295; 92% men) whose families were invited to ultrasonographic screening. In the initial interview, 62 (10%) of the 618 patients with AAA reported a positive family history for AAA. Ultrasonographic screening identified 24 new AAAs among 186 relatives (≥50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonographic screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P < 0.0001). The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis, and provide rationale for targeted screening of relatives of patients with AAA. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. NASA Astrophysics E/PO Impact: NASA SOFIA AAA Program Evaluation Results

    NASA Astrophysics Data System (ADS)

    Harman, Pamela; Backman, Dana E.; Clark, Coral; Inverness Research Sofia Aaa Evaluation Team, Wested Sofia Aaa Evaluation Team

    2015-01-01

    SOFIA is an airborne observatory, studying the universe at infrared wavelengths, capable of making observations that are impossible for even the largest and highest ground-based telescopes. SOFIA also inspires the development of new scientific instrumentation and fosters the education of young scientists and engineers.SOFIA is an 80% - 20% partnership of NASA and the German Aerospace Center (DLR), consisting of an extensively modified Boeing 747SP aircraft carrying a reflecting telescope with an effective diameter of 2.5 meters (100 inches). The SOFIA aircraft is based at NASA Armstrong Flight Research Center, Building 703, in Palmdale, California. The Science Program and Outreach Offices are located at NASA Ames Research center. SOFIA is a program in NASA's Science Mission Directorate, Astrophysics Division.Data will be collected to study many different kinds of astronomical objects and phenomena, including star cycles, solar system formation, identification of complex molecules in space, our solar system, galactic dust, nebulae and ecosystems.Airborne Astronomy Ambassador (AAA) Program:The SOFIA Education and Communications program exploits the unique attributes of airborne astronomy to contribute to national goals for the reform of science, technology, engineering, and math (STEM) education, and to elevate public scientific and technical literacy.The AAA effort is a professional development program aspiring to improve teaching, inspire students, and inform the community. To date, 55 educators from 21 states; Cycles 0, 1 and 2; have completed their astronomy professional development and their SOFIA science flight experience. Evaluation has confirmed the program's positive impact on the teacher participants, on their students, and in their communities. The inspirational experience has positively impacted their practice and career trajectory. AAAs have incorporated content knowledge and specific components of their experience into their curricula, and have given

  20. Morphological State as a Predictor for Reintervention and Mortality After EVAR for AAA

    SciTech Connect

    Ohrlander, Tomas; Dencker, Magnus; Acosta, Stefan, E-mail: stefan.acosta@telia.com

    2012-10-15

    Purpose: This study was designed to assess aorto-iliac morphological characteristics in relation to reintervention and all-cause long-term mortality in patients undergoing standard EVAR for infrarenal AAA. Methods: Patients treated with EVAR (Zenith{sup Registered-Sign} Stentgrafts, Cook) between May 1998 and February 2006 were prospectively enrolled in a computerized database where comorbidities and preoperative aneurysm morphology were entered. Reinterventions and mortality were checked until December 1, 2010. Median follow-up time was 68 months. Results: A total of 304 patients were included, of which 86% were men. Median age was 74 years. The reintervention rate was 23.4% (71/304). A greater diameter of themore » common iliac artery (p = 0.037; hazard ratio (HR) 1.037 [1.002-1.073]) was an independent factor for an increased number of reinterventions. The 30-day mortality rate was 3.0% (9/304). Aneurysm-related deaths due to AAA occurred in 4.9% (15/304). Five patients died due to a concomitant ruptured thoracic aortic aneurysm. The mortality until end of follow-up was 54.3% (165/304). The proportion of deaths caused by vascular diseases was 61.6%. The severity of angulation of the iliac arteries (p = 0.014; HR 1.018 [95% confidence interval (CI) 1.004-1.033]) and anemia (p = 0.044; HR 2.79 [95% CI 1.029-7.556]) remained as independent factors associated with all-cause long-term mortality. The crude reintervention-free survival rate at 1, 3, and 5 years was 84.5%, 64.8%, and 51.6%, respectively. Conclusions: The initial aorto-iliac morphological state in patients scheduled for standard EVAR for AAA seems to be strongly related to the need for reinterventions and long-term mortality.« less

  1. Peak AAA fatty acid homolog contaminants present in the dietary supplement l-Tryptophan associated with the onset of eosinophilia-myalgia syndrome.

    PubMed

    Klarskov, Klaus; Gagnon, Hugo; Racine, Mathieu; Boudreault, Pierre-Luc; Normandin, Chad; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

    2018-05-22

    The eosinophilia-myalgia syndrome (EMS) outbreak that occurred in the USA and elsewhere in 1989 was caused by the ingestion of Showa Denko K.K. (SD) L-tryptophan (L-Trp). "Six compounds" detected in the L-Trp were reported as case-associated contaminants. Recently the final and most statistically significant contaminant, "Peak AAA" was structurally characterized. The "compound" was actually shown to be two structural isomers resulting from condensation reactions of L-Trp with fatty acids derived from the bacterial cell membrane. They were identified as the indole C-2 anteiso (AAA 1 -343) and linear (AAA 2 -343) aliphatic chain isomers. Based on those findings, we utilized a combination of on-line HPLC-electrospray ionization mass spectrometry (LC-MS), as well as both precursor and product ion tandem mass spectrometry (MS/MS) to facilitate identification of a homologous family of condensation products related to AAA 1 -343 and AAA 2 -343. We structurally characterized eight new AAA 1 -XXX/AAA 2 -XXX contaminants, where XXX represents the integer molecular ions of all the related homologs, differing by aliphatic chain length and isomer configuration. The contaminants were derived from the following fatty acids of the bacterial cell membrane, 5-methylheptanoic acid (anteiso-C8:0) for AAA 1 -315; n-octanoic acid (n-C8:0) for AAA 2 -315; 6-methyloctanoic acid (anteiso-C9:0) for AAA 1 -329; n-nonanoic acid (n-C9:0) for AAA 2 -329; 10-methyldodecanoic acid (anteiso-C13:0) for AAA 1 -385; n-tridecanoic acid (n-C13:0) for AAA 2 -385; 11-methyltridecanoic acid (anteiso-C14:0) for AAA 1 -399; and n-tetradecanoic acid (n-C14:0) for AAA 2 -399. The concentration levels for these contaminants were estimated to be 0.1-7.9 μg / 500 mg of an individual SD L-Trp tablet or capsule The structural similarity of these homologs to case-related contaminants of Spanish Toxic Oil Syndrome (TOS) is discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

    PubMed

    Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

    2017-11-15

    Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  3. Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

    NASA Astrophysics Data System (ADS)

    Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

    2014-03-01

    Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell.

  4. Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

    PubMed Central

    Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

    2014-01-01

    Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. PMID:24658080

  5. Science | AAAS

    Science.gov Websites

    be caused by haywire immune system eating brain connections CRISPR Stopping CRISPR's genome-editing scissors from snipping out of control CRISPR patent hearing produces no clear winner, only 'soft signals ' Did a Swedish researcher eat the first CRISPR meal ever served? Top articles in Careers dollars in a

  6. 367-AAA

    NASA Image and Video Library

    1969-11-18

    Apollo 12 Public Affairs Officer (PAO) Mission Commentary, November 17-18, 1969. This is 3.25 hours of audio covering communications occurring between 82 hours, 41 minutes into the mission, through 86 hours, 38 minutes which was on November 17, 1969, 21:03 CST until November 18, 1969, 1:00 CST. Communication is quite sparse on the recording, with large sections of silence or miscellaneous noise. Transcript of audio is available at http://www.jsc.nasa.gov/history/mission_trans/AS12_PAO.PDF, on pages 239-259 of the 979-page document.

  7. The Abdominal Aortic Aneurysm Statistically Corrected Operative Risk Evaluation (AAA SCORE) for predicting mortality after open and endovascular interventions.

    PubMed

    Ambler, Graeme K; Gohel, Manjit S; Mitchell, David C; Loftus, Ian M; Boyle, Jonathan R

    2015-01-01

    Accurate adjustment of surgical outcome data for risk is vital in an era of surgeon-level reporting. Current risk prediction models for abdominal aortic aneurysm (AAA) repair are suboptimal. We aimed to develop a reliable risk model for in-hospital mortality after intervention for AAA, using rigorous contemporary statistical techniques to handle missing data. Using data collected during a 15-month period in the United Kingdom National Vascular Database, we applied multiple imputation methodology together with stepwise model selection to generate preoperative and perioperative models of in-hospital mortality after AAA repair, using two thirds of the available data. Model performance was then assessed on the remaining third of the data by receiver operating characteristic curve analysis and compared with existing risk prediction models. Model calibration was assessed by Hosmer-Lemeshow analysis. A total of 8088 AAA repair operations were recorded in the National Vascular Database during the study period, of which 5870 (72.6%) were elective procedures. Both preoperative and perioperative models showed excellent discrimination, with areas under the receiver operating characteristic curve of .89 and .92, respectively. This was significantly better than any of the existing models (area under the receiver operating characteristic curve for best comparator model, .84 and .88; P < .001 and P = .001, respectively). Discrimination remained excellent when only elective procedures were considered. There was no evidence of miscalibration by Hosmer-Lemeshow analysis. We have developed accurate models to assess risk of in-hospital mortality after AAA repair. These models were carefully developed with rigorous statistical methodology and significantly outperform existing methods for both elective cases and overall AAA mortality. These models will be invaluable for both preoperative patient counseling and accurate risk adjustment of published outcome data. Copyright © 2015 Society

  8. Structure determination of disease associated peak AAA from l-Tryptophan implicated in the eosinophilia-myalgia syndrome.

    PubMed

    Klarskov, Klaus; Gagnon, Hugo; Boudreault, Pierre-Luc; Normandin, Chad; Plancq, Baptiste; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

    2018-01-05

    The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA and elsewhere was caused by the ingestion of l-Tryptophan (L-Trp) solely manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present in the SD L-Trp were reported to be case-associated contaminants. However, "one" of these compounds, Peak AAA has remained structurally uncharacterized, despite the fact that it was described as "the only statistically significant (p=0.0014) contaminant". Here, we employ on-line microcapillary-high performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS), and tandem mass spectrometry (MS/MS) to determine that Peak AAA is in fact two structurally related isomers. Peak AAA 1 and Peak AAA 2 differed in LC retention times, and were determined by accurate mass-LC-MS to both have a protonated molecular ion (MH +) of mass 343.239Da (Da), corresponding to a molecular formula of C 21 H 30 N 2 O 2, and possessing eight degrees of unsaturation (DoU) for the non-protonated molecule. By comparing the LC-MS and LC-MS-MS retention times and spectra with authentic synthetic standards, Peak AAA 1 was identified as the intermolecular condensation product of L-Trp with anteiso 7-methylnonanoic acid, to afford (S)-2-amino-3-(2-((S,E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Peak AAA 2 was determined to be a condensation product of L-Trp with decanoic acid, which produced (S)-2-amino-3-(2-((E)-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine.

    PubMed

    Liu, Jing; Mei, Ziqing; Li, Ningning; Qi, Yutao; Xu, Yanji; Shi, Yigong; Wang, Feng; Lei, Jianlin; Gao, Ning

    2013-06-14

    The MecA-ClpC complex is a bacterial type II AAA(+) molecular machine responsible for regulated unfolding of substrates, such as transcription factors ComK and ComS, and targeting them to ClpP for degradation. The six subunits of the MecA-ClpC complex form a closed barrel-like structure, featured with three stacked rings and a hollow passage, where substrates are threaded and translocated through successive pores. Although the general concepts of how polypeptides are unfolded and translocated by internal pore loops of AAA(+) proteins have long been conceived, the detailed mechanistic model remains elusive. With cryoelectron microscopy, we captured four different structures of the MecA-ClpC complexes. These complexes differ in the nucleotide binding states of the two AAA(+) rings and therefore might presumably reflect distinctive, representative snapshots from a dynamic unfolding cycle of this hexameric complex. Structural analysis reveals that nucleotide binding and hydrolysis modulate the hexameric complex in a number of ways, including the opening of the N-terminal ring, the axial and radial positions of pore loops, the compactness of the C-terminal ring, as well as the relative rotation between the two nucleotide-binding domain rings. More importantly, our structural and biochemical data indicate there is an active allosteric communication between the two AAA(+) rings and suggest that concerted actions of the two AAA(+) rings are required for the efficiency of the substrate unfolding and translocation. These findings provide important mechanistic insights into the dynamic cycle of the MecA-ClpC unfoldase and especially lay a foundation toward the complete understanding of the structural dynamics of the general type II AAA(+) hexamers.

  10. OGLE16aaa - a signature of a hungry supermassive black hole

    NASA Astrophysics Data System (ADS)

    Wyrzykowski, Łukasz; Zieliński, M.; Kostrzewa-Rutkowska, Z.; Hamanowicz, A.; Jonker, P. G.; Arcavi, I.; Guillochon, J.; Brown, P. J.; Kozłowski, S.; Udalski, A.; Szymański, M. K.; Soszyński, I.; Poleski, R.; Pietrukowicz, P.; Skowron, J.; Mróz, P.; Ulaczyk, K.; Pawlak, M.; Rybicki, K. A.; Greiner, J.; Krühler, T.; Bolmer, J.; Smartt, S. J.; Maguire, K.; Smith, K.

    2017-02-01

    We present the discovery and first three months of follow-up observations of a currently on-going unusual transient detected by the Optical Gravitational Lensing Experiment (OGLE-IV) survey, located in the centre of a galaxy at redshift z = 0.1655. The long rise to absolute magnitude of -20.5 mag, slow decline, very broad He and H spectral features make OGLE16aaa similar to other optical/UV tidal disruption events (TDEs). Weak narrow emission lines in the spectrum and archival photometric observations suggest the host galaxy is a weak-line active galactic nucleus, which has been accreting at higher rate in the past. OGLE16aaa, along with SDSS J0748, seems to form a sub-class of TDEs by weakly or recently active supermassive black holes (SMBHs). This class might bridge the TDEs by quiescent SMBHs and flares observed as `changing-look quasars', if we interpret the latter as TDEs. If this picture is true, the previously applied requirement for identifying a flare as a TDE that it had to come from an inactive nucleus, could be leading to observational bias in TDE selection, thus affecting TDE-rate estimations.

  11. Structural basis of protein translocation by the Vps4-Vta1 AAA ATPase

    PubMed Central

    Monroe, Nicole; Han, Han; Shen, Peter S; Sundquist, Wesley I; Hill, Christopher P

    2017-01-01

    Many important cellular membrane fission reactions are driven by ESCRT pathways, which culminate in disassembly of ESCRT-III polymers by the AAA ATPase Vps4. We report a 4.3 Å resolution cryo-EM structure of the active Vps4 hexamer with its cofactor Vta1, ADP·BeFx, and an ESCRT-III substrate peptide. Four Vps4 subunits form a helix whose interfaces are consistent with ATP binding, is stabilized by Vta1, and binds the substrate peptide. The fifth subunit approximately continues this helix but appears to be dissociating. The final Vps4 subunit completes a notched-washer configuration as if transitioning between the ends of the helix. We propose that ATP binding propagates growth at one end of the helix while hydrolysis promotes disassembly at the other end, so that Vps4 ‘walks’ along ESCRT-III until it encounters the ordered N-terminal domain to destabilize the ESCRT-III lattice. This model may be generally applicable to other protein-translocating AAA ATPases. DOI: http://dx.doi.org/10.7554/eLife.24487.001 PMID:28379137

  12. Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs.

    PubMed

    Machado-Pinilla, Rosario; Liger, Dominique; Leulliot, Nicolas; Meier, U Thomas

    2012-10-01

    The AAA+ ATPases pontin and reptin function in a staggering array of cellular processes including chromatin remodeling, transcriptional regulation, DNA damage repair, and assembly of macromolecular complexes, such as RNA polymerase II and small nucleolar (sno) RNPs. However, the molecular mechanism for all of these AAA+ ATPase associated activities is unknown. Here we document that, during the biogenesis of H/ACA RNPs (including telomerase), the assembly factor SHQ1 holds the pseudouridine synthase NAP57/dyskerin in a viselike grip, and that pontin and reptin (as components of the R2TP complex) are required to pry NAP57 from SHQ1. Significantly, the NAP57 domain captured by SHQ1 harbors most mutations underlying X-linked dyskeratosis congenita (X-DC) implicating the interface between the two proteins as a target of this bone marrow failure syndrome. Homing in on the essential first steps of H/ACA RNP biogenesis, our findings provide the first insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes.

  13. Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs

    PubMed Central

    Machado-Pinilla, Rosario; Liger, Dominique; Leulliot, Nicolas; Meier, U. Thomas

    2012-01-01

    The AAA+ ATPases pontin and reptin function in a staggering array of cellular processes including chromatin remodeling, transcriptional regulation, DNA damage repair, and assembly of macromolecular complexes, such as RNA polymerase II and small nucleolar (sno) RNPs. However, the molecular mechanism for all of these AAA+ ATPase associated activities is unknown. Here we document that, during the biogenesis of H/ACA RNPs (including telomerase), the assembly factor SHQ1 holds the pseudouridine synthase NAP57/dyskerin in a viselike grip, and that pontin and reptin (as components of the R2TP complex) are required to pry NAP57 from SHQ1. Significantly, the NAP57 domain captured by SHQ1 harbors most mutations underlying X-linked dyskeratosis congenita (X-DC) implicating the interface between the two proteins as a target of this bone marrow failure syndrome. Homing in on the essential first steps of H/ACA RNP biogenesis, our findings provide the first insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes. PMID:22923768

  14. Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

    PubMed Central

    Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

    2015-01-01

    Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

  15. TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

    DOE PAGES

    Ye, Qiaozhen; Rosenberg, Scott C.; Moeller, Arne; ...

    2015-04-28

    The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from amore » signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.« less

  16. Crystal Structure and Biochemical Characterization of a Mycobacterium smegmatis AAA-Type Nucleoside Triphosphatase Phosphohydrolase (Msm0858).

    PubMed

    Unciuleac, Mihaela-Carmen; Smith, Paul C; Shuman, Stewart

    2016-05-15

    AAA proteins (ATPases associated with various cellular activities) use the energy of ATP hydrolysis to drive conformational changes in diverse macromolecular targets. Here, we report the biochemical characterization and 2.5-Å crystal structure of a Mycobacterium smegmatis AAA protein Msm0858, the ortholog of Mycobacterium tuberculosis Rv0435c. Msm0858 is a magnesium-dependent ATPase and is active with all nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) as substrates. The Msm0858 structure comprises (i) an N-terminal domain (amino acids [aa] 17 to 201) composed of two β-barrel modules and (ii) two AAA domains, D1 (aa 212 to 473) and D2 (aa 476 to 744), each of which has ADP in the active site. Msm0858-ADP is a monomer in solution and in crystallized form. Msm0858 domains are structurally homologous to the corresponding modules of mammalian p97. However, the position of the N-domain modules relative to the AAA domains in the Msm0858-ADP tertiary structure is different and would impede the formation of a p97-like hexameric quaternary structure. Mutational analysis of the A-box and B-box motifs indicated that the D1 and D2 AAA domains are both capable of ATP hydrolysis. Simultaneous mutations of the D1 and D2 active-site motifs were required to abolish ATPase activity. ATPase activity was effaced by mutation of the putative D2 arginine finger, suggesting that Msm0858 might oligomerize during the ATPase reaction cycle. A truncated variant Msm0858 (aa 212 to 745) that lacks the N domain was characterized as a catalytically active homodimer. Recent studies have underscored the importance of AAA proteins (ATPases associated with various cellular activities) in the physiology of mycobacteria. This study reports the ATPase activity and crystal structure of a previously uncharacterized mycobacterial AAA protein, Msm0858. Msm0858 consists of an N-terminal β-barrel domain and two AAA domains, each with ADP bound in the active site. Msm0858 is a

  17. Introducing AAA-MS, a rapid and sensitive method for amino acid analysis using isotope dilution and high-resolution mass spectrometry.

    PubMed

    Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Dupierris, Véronique; Couté, Yohann; Bruley, Christophe; Garin, Jérôme; Dupuis, Alain; Jaquinod, Michel; Brun, Virginie

    2012-07-06

    Accurate quantification of pure peptides and proteins is essential for biotechnology, clinical chemistry, proteomics, and systems biology. The reference method to quantify peptides and proteins is amino acid analysis (AAA). This consists of an acidic hydrolysis followed by chromatographic separation and spectrophotometric detection of amino acids. Although widely used, this method displays some limitations, in particular the need for large amounts of starting material. Driven by the need to quantify isotope-dilution standards used for absolute quantitative proteomics, particularly stable isotope-labeled (SIL) peptides and PSAQ proteins, we developed a new AAA assay (AAA-MS). This method requires neither derivatization nor chromatographic separation of amino acids. It is based on rapid microwave-assisted acidic hydrolysis followed by high-resolution mass spectrometry analysis of amino acids. Quantification is performed by comparing MS signals from labeled amino acids (SIL peptide- and PSAQ-derived) with those of unlabeled amino acids originating from co-hydrolyzed NIST standard reference materials. For both SIL peptides and PSAQ standards, AAA-MS quantification results were consistent with classical AAA measurements. Compared to AAA assay, AAA-MS was much faster and was 100-fold more sensitive for peptide and protein quantification. Finally, thanks to the development of a labeled protein standard, we also extended AAA-MS analysis to the quantification of unlabeled proteins.

  18. A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPases.

    PubMed

    Pöhler, Robert; Krahn, Jan H; van den Boom, Johannes; Dobrynin, Grzegorz; Kaschani, Farnusch; Eggenweiler, Hans-Michael; Zenke, Frank T; Kaiser, Markus; Meyer, Hemmo

    2018-02-05

    AAA ATPases have pivotal functions in diverse cellular processes essential for survival and proliferation. Revealing strategies for chemical inhibition of this class of enzymes is therefore of great interest for the development of novel chemotherapies or chemical tools. Here, we characterize the compound MSC1094308 as a reversible, allosteric inhibitor of the type II AAA ATPase human ubiquitin-directed unfoldase (VCP)/p97 and the type I AAA ATPase VPS4B. Subsequent proteomic, genetic and biochemical studies indicate that MSC1094308 binds to a previously characterized drugable hotspot of p97, thereby inhibiting the D2 ATPase activity. Our results furthermore indicate that a similar allosteric site exists in VPS4B, suggesting conserved allosteric circuits and drugable sites in both type I and II AAA ATPases. Our results may thus guide future chemical tool and drug discovery efforts for the biomedically relevant AAA ATPases. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Student-Athlete Perceptions of a Summer Pre-Enrollment Experience at an NCAA Division I-AAA Institution

    ERIC Educational Resources Information Center

    Dalgety, Michael Franklin

    2012-01-01

    The purpose of this exploratory qualitative study was to examine student-athlete perceptions of the role of summer pre-enrollment in their adjustment and transition to college. The study focused on student-athletes who received athletically-related financial aid at a National Collegiate Athletic Association (NCAA) Division I-AAA institution. The…

  20. Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48.

    PubMed

    Esaki, Masatoshi; Islam, Md Tanvir; Tani, Naoki; Ogura, Teru

    2017-07-14

    Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism.

  1. McArthur removes AAA clamps and ducts inside the CHeCS Rack during Expedition 12

    NASA Image and Video Library

    2005-12-09

    ISS012-E-10817 (9 December 2005) --- Astronaut William S. (Bill) McArthur Jr., Expedition 12 commander and NASA space station science officer, opens the back panel of the Crew Health Care System (CHeCS) rack and removes the Avionics Air Assembly (AAA) air ducts during in-flight maintenance (IFM) in the Destiny laboratory of the International Space Station.

  2. SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells.

    PubMed

    Toghill, Bradley J; Saratzis, Athanasios; Freeman, Peter J; Sylvius, Nicolas; Bown, Matthew J

    2018-01-01

    Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter ( P  < 0.0001, R 2  = 0.3175).We then determined CpG methylation status of regulatory regions in genes located at AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R , 2 CpGs were hyper-methylated ( P  = 0.0145); in ERG , 13 CpGs were hyper-methylated ( P  = 0.0005); in SERPINB9 , 6 CpGs were hypo-methylated ( P  = 0.0037) and 1 CpG was hyper-methylated ( P  = 0.0098); and in SMYD2 , 4 CpGs were hypo-methylated ( P  = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression ( P  = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that

  3. [Incidence and risk factors of ischemic colitis after AAA repair in our cohort of patients from 2005 through 2009].

    PubMed

    Biros, E; Staffa, R

    2011-12-01

    Using retrospective analysis, we sought to investigate the incidence, risk factors and therapeutic outcomes of ischemic colitis in patients after surgical and endovascular repair of abdominal aortic aneurysms (AAA). The complete inpatient and outpatient medical records of all patients undergoing surgical or endovascular AAA repair in our Department from January 2005 to December 2009 were retrospectively reviewed. We selected all patients who had developed an acute or chronic form of postoperative large or small bowel ischemia. We carried out data analysis and focused on determining the incidence and risk factors of this complication and the outcomes of its treatment. Two hundred and seven AAA repairs were performed in the 2nd Department of Surgery of St. Anne's University Hospital in Brno and the Faculty of Medicine of Masaryk University in Brno during the studied period. This number includes endovascular AAA repairs (13 patients; 6.3%) as well as one robot-assisted operation, and also the whole clinical spectrum of AAA manifestations, from non-symptomatic forms to ruptured aneurysm forms. The rest of the patients underwent open operation. Bowel ischemia developed in a total of 11 patients (5.3 %), who all underwent open AAA repair. Six of these patients presented with non-ruptured AAA and the remaining 5 with ruptured AAA. In 3 patients, bowel ischemia was diagnosed with a delay of several months from the original revascularization operation in the clinical form of postischemic stricture of the large bowel (2 patients) or postischemic colitis (1 patient). 8 patients were diagnosed with acute ischemic colitis affecting an isolated segment of the small bowel in one patient, extended segments of the large bowel (descending colon + sigmoid colon + rectum) in 2 patients, and typically the descending and sigmoid colon in 5 patients. None of the three patients with late manifestation of ischemic colitis died. Of the 8 patients with acute presentation, resection of the

  4. Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2

    PubMed Central

    Izumi, Natsuko; Yamashita, Akio; Ohno, Shigeo

    2012-01-01

    Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (AAA+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative “PIKK regulatory chaperone complex” including other PIKK regulators, Hsp90 and the Tel2 complex. PMID:22540023

  5. Morphological Differences in the Aorto-iliac Segment in AAA Patients of Caucasian and Asian Origin.

    PubMed

    Banzic, I; Lu, Q; Zhang, L; Stepak, H; Davidovic, L; Oszkinis, G; Mladenovic, A; Markovic, M; Rancic, Z; Jing, Z; Brankovic, M

    2016-06-01

    The objective was to quantify aorto-iliac morphology differences between AAA patients of Caucasian and Asian origin. Additionally, the impact of patient demographic characteristics was assessed, which could influence the morphological differences. This international multicentre study included two tertiary referral institutions from Europe and one from China. CT scans with 3D reconstruction of 296 patients with infrarenal AAA >5 cm were analysed. Eighteen measurements were recorded from each CT scan and compared between Caucasian and Asian patients. Caucasian patients had longer common iliac arteries (right: 65.0 vs. 33.1 mm, p < .001 left: 65.0 vs. 35.2 mm, p < .001), longer aneurysm neck (33.0 vs. 28.4 mm, p < .001), greater aneurysm to aortic axis angle (153.0° vs. 142.2°, p < .001), and longer combined aorto-iliac length (195.7 vs. 189.2 mm, p < .001). However, Asian patients had a longer infrarenal abdominal aorta (152.0 vs. 130.0 mm, p < .001), longer AAA (126.2 vs. 93.0 mm), and greater linear distance from renal artery to aorto-iliac bifurcation (143.6 vs. 116.0 mm, p < .001). Caucasian patients had a larger inner common iliac artery diameter (right: 16.0 vs. 14.9 mm, p < .001, left: 16.0 vs. 15.2 mm, p < .001), larger inner exernal iliac artery diameter (right: 9.0 vs. 7.5 mm, p < .001 left: 9.0 vs. 7.7 mm, p < .001), and larger inner common femoral artery diameter (right: 10.0 vs. 5.9 mm, p < .001 left: 10.0 vs. 6.1 mm, p < .001). No difference was observed in AAA transverse diameter (62.0 vs. 63.1 mm, p = .492). The results showed that aorto-iliac anatomy in Caucasians differs significantly from Asians, particularly in the length of the common iliac arteries and infrarenal abdominal aorta, and in the transverse diameter of the common, external iliac, and common femoral arteries. Therefore, the exact criteria for stent graft design are dependent on the racial origin of the patient. Copyright © 2015 European

  6. Characterisation of pectins extracted from banana peels (Musa AAA) under different conditions using an experimental design.

    PubMed

    Happi Emaga, Thomas; Ronkart, Sébastien N; Robert, Christelle; Wathelet, Bernard; Paquot, Michel

    2008-05-15

    An experimental design was used to study the influence of pH (1.5 and 2.0), temperature (80 and 90°C) and time (1 and 4h) on extraction of pectin from banana peels (Musa AAA). Yield of extracted pectins, their composition (neutral sugars, galacturonic acid, and degree of esterification) and some macromolecular characteristics (average molecular weight, intrinsic viscosity) were determined. It was found that extraction pH was the most important parameter influencing yield and pectin chemical composition. Lower pH values negatively affected the galacturonic acid content of pectin, but increased the pectin yield. The values of degree of methylation decreased significantly with increasing temperature and time of extraction. The average molecular weight ranged widely from 87 to 248kDa and was mainly influenced by pH and extraction time. Copyright © 2007 Elsevier Ltd. All rights reserved.

  7. Conformational changes in the AAA ATPase p97–p47 adaptor complex

    PubMed Central

    Beuron, Fabienne; Dreveny, Ingrid; Yuan, Xuemei; Pye, Valerie E; Mckeown, Ciaran; Briggs, Louise C; Cliff, Matthew J; Kaneko, Yayoi; Wallis, Russell; Isaacson, Rivka L; Ladbury, John E; Matthews, Steve J; Kondo, Hisao; Zhang, Xiaodong; Freemont, Paul S

    2006-01-01

    The AAA+ATPase p97/VCP, helped by adaptor proteins, exerts its essential role in cellular events such as endoplasmic reticulum-associated protein degradation or the reassembly of Golgi, ER and the nuclear envelope after mitosis. Here, we report the three-dimensional cryo-electron microscopy structures at ∼20 Å resolution in two nucleotide states of the endogenous hexameric p97 in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins involved in membrane fusion. Depending on the nucleotide state, we observe the p47 trimer to be in two distinct arrangements on top of the p97 hexamer. By combining the EM data with NMR and other biophysical measurements, we propose a model of ATP-dependent p97(N) domain motions that lead to a rearrangement of p47 domains, which could result in the disassembly of target protein complexes. PMID:16601695

  8. Inter-ring rotations of AAA ATPase p97 revealed by electron cryomicroscopy

    PubMed Central

    Yeung, Heidi O.; Förster, Andreas; Bebeacua, Cecilia; Niwa, Hajime; Ewens, Caroline; McKeown, Ciarán; Zhang, Xiaodong; Freemont, Paul S.

    2014-01-01

    The type II AAA+ protein p97 is involved in numerous cellular activities, including endoplasmic reticulum-associated degradation, transcription activation, membrane fusion and cell-cycle control. These activities are at least in part regulated by the ubiquitin system, in which p97 is thought to target ubiquitylated protein substrates within macromolecular complexes and assist in their extraction or disassembly. Although ATPase activity is essential for p97 function, little is known about how ATP binding or hydrolysis is coupled with p97 conformational changes and substrate remodelling. Here, we have used single-particle electron cryomicroscopy (cryo-EM) to study the effect of nucleotides on p97 conformation. We have identified conformational heterogeneity within the cryo-EM datasets from which we have resolved two major p97 conformations. A comparison of conformations reveals inter-ring rotations upon nucleotide binding and hydrolysis that may be linked to the remodelling of target protein complexes. PMID:24598262

  9. Beneficial effect of statins on total mortality in abdominal aortic aneurysm (AAA) repair.

    PubMed

    Mathisen, Sven Ross; Abdelnoor, Michael

    2017-10-01

    In this single center, retrospective cohort study we wished to compare early and total mortality for all patients treated for abdominal aortic aneurysms (AAA) with open surgery who were taking statins compared to those who were not. A cohort of 640 patients with AAA was treated with open surgery between 1999 and 2012. Patients were consecutively recruited from a source population of 390,000; 21.3% were female, and the median age was 73 years. The median follow-up was 3.93 years, with an interquartile range of 1.79-6.58 years. The total follow-up was 2855 patient-years. An explanatory strategy was used. The propensity score (PS) was implemented to control for selection bias and confounders. The crude effect of statin use showed a 78% reduction of the 30-day mortality. A stratified analysis using the Mantel-Haenszel method on quintiles of the PS gave an adjusted effect of the odds ratio equal to 0.43 (95% CI: 0.18-0.96), indicating a 57% reduction of the 30-day mortality for statin users. The adjusted rate ratio was 0.62 (95% CI: 0.45-0.83), indicating a reduction of long-term mortality of 38% for statin users compared to non-users for a median follow-up of 3.93 years. This retrospective cohort study showed a significant beneficial effect of statin use on early and long-term survival for patients treated with open surgery. To be conclusive, our results need to be replicated by a randomized clinical trial.

  10. Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters

    PubMed Central

    2013-01-01

    Purpose Retrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA. Methods The 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms. Results In the prostate plans, the AAA predicted lower NTCP value (NTCPAAA) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCPAAA, that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCPPBC’s ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCPAAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCPPBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCPAAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCPAAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0

  11. Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters.

    PubMed

    Bufacchi, Antonella; Nardiello, Barbara; Capparella, Roberto; Begnozzi, Luisa

    2013-07-04

    Retrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA. The 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms. In the prostate plans, the AAA predicted lower NTCP value (NTCPAAA) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCPAAA, that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCPPBC's ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCPAAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCPPBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCPAAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCPAAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0.3%), while the mean NTCPPBC

  12. Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome.

    PubMed

    Gavali, H; Mani, K; Tegler, G; Kawati, R; Covaciu, L; Wanhainen, A

    2017-08-01

    The aim of the study was to investigate the frequency and outcome of prolonged intensive care unit (ICU) length of stay (LOS) after abdominal aortic aneurysm (AAA) repair in the endovascular era. All patients operated on for AAA between 1999 and 2013 at Uppsala University hospital were identified. Data were retrieved from the Swedish Vascular registry, the Swedish Intensive Care registry, the National Population registry, and case records. Prolonged ICU LOS was defined as ≥ 48 h during the primary hospital stay. Patients surviving ≥ 48 h after AAA surgery were included in the analysis. A total of 725 patients were identified, of whom 707 (97.5%) survived ≥ 48 h; 563 (79.6%) underwent intact AAA repair and 144 (20.4%) ruptured AAA repair. A total of 548 patients (77.5%) required < 48 h of intensive care, 115 (16.3%) 2-6 days and 44 (6.2%) ≥ 7 days. The rate of prolonged ICU LOS declined considerably over time, from 41.4% of all AAA repairs in 1999 to 7.3% in 2013 (p < .001) whereas the use of endovascular aortic repair (EVAR) increased from 6.9% in 1999 to 78.0% in 2013 (p < .001). The 30 day survival rate was 98.2% for those with < 48 h ICU stay versus 93.0% for 2-6 days versus 81.8% for ≥ 7 days (p < .001); the corresponding 90 day survival was 97.1% versus 86.1% versus 63.6% (p < .001) respectively. For patients surviving 90 days after repair, there was no difference in long-term survival between the groups. During the period of progressively increasing use of EVAR, a simultaneous significant reduction in frequency of prolonged ICU LOS occurred. Although prolonged ICU LOS was associated with a high short-term mortality, long-term outcome among those surviving the initial 90 days was less affected. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  13. SU-E-T-122: Anisotropic Analytical Algorithm (AAA) Vs. Acuros XB (AXB) in Stereotactic Treatment Planning

    SciTech Connect

    Mynampati, D; Scripes, P Godoy; Kuo, H

    2015-06-15

    Purpose: To evaluate dosimetric differences between superposition beam model (AAA) and determinant photon transport solver (AXB) in lung SBRT and Cranial SRS dose computations. Methods: Ten Cranial SRS and ten Lung SBRT plans using Varian, AAA -11.0 were re-planned using Acuros -XB-11.0 with fixed MU. 6MV photon Beam model with HD120-MLC used for dose calculations. Four non-coplanar conformal arcs used to deliver 21Gy or 18Gy to SRS targets (0.4 to 6.2cc). 54Gy (3Fractions) or 50Gy (5Fractions) was planned for SBRT targets (7.3 to 13.9cc) using two VAMT non-coplanar arcs. Plan comparison parameters were dose to 1% PTV volume (D1), dosemore » to 99% PTV volume( D99), Target mean (Dmean), Conformity index (ratio of prescription isodose volume to PTV), Homogeneity Index [ (D2%-D98%)/Dmean] and R50 (ratio of 50% of prescription isodose volume to PTV). OAR parameters were Brain volume receiving 12Gy dose (V12Gy) and maximum dose (D0.03) to Brainstem for SRS. For lung SBRT, maximum dose to Heart and Cord, Mean lung dose (MLD) and volume of lung receiving 20Gy (V20Gy) were computed. PTV parameters compared by percentage difference between AXB and AAA parameters. OAR parameters and HI compared by absolute difference between two calculations. For analysis, paired t-test performed over the parameters. Results: Compared to AAA, AXB SRS plans have on average 3.2% lower D99, 6.5% lower CI and 3cc less Brain-V12. However, AXB SBRT plans have higher D1, R50 and Dmean by 3.15%, 1.63% and 2.5%. For SRS and SBRT, AXB plans have average HI 2 % and 4.4% higher than AAA plans. In both techniques, all other parameters vary within 1% or 1Gy. In both sets only two parameters have P>0.05. Conclusion: Even though t-test results signify difference between AXB and AAA plans, dose differences in dose estimations by both algorithms are clinically insignificant.« less

  14. Materials Related Forensic Analysis and Special Testing : Drying Shrinkage Evaluation of Bridge Decks with Class AAA and Class W/WD Type K Cement

    DOT National Transportation Integrated Search

    2001-07-01

    This work pertains to preparation of concrete drying shrinkage data for proposed concrete mixtures during normal concrete : trial batch verification. Selected concrete mixtures will include PennDOT Classes AAA and AA and will also include the use of ...

  15. AAAS Mass Media Science and Engineering Fellowship Program: Building Communication Skills in Young Scientists

    NASA Astrophysics Data System (ADS)

    Pasco, S.

    2006-12-01

    The AAAS Mass Media Science &Engineering Fellowship program has succeeded in training scientists to become more effective communicators for more than 30 years. The program places advanced science, engineering and mathematics students at media sites to work as science reporters for ten weeks each summer. AAAS places between 15 to 20 students a year at newspapers, magazines and radio stations. Our goal is to create better science communicators who understand their role in fostering the public's understanding of science. Fellows leave the program with a greater awareness of how to communicate complex issues by making the connection as to why people should be interested in certain developments, and more specifically, how they will impact their communities. 2004 AGU Fellow Rei Ueyama put her lessons learned to good use during her Fellowship at the Sacramento Bee. "In a regional paper like The Bee, a (story) also had to have a local touch. I needed to show why people in Sacramento (or California) should bother to read the story. One example is the story I wrote about seeding the ocean with iron particles to fight global warming. Since ocean fertilization is a global issue, I had to clearly specify the reason why The Bee and not The New York Times was running the story. The local angle I chose was to point out that the core group of scientists involved in this study was from Monterey Bay, Calif." Many alumni tell us the program has been an integral force in shaping the course of their career. Similarly, sites often report that having a scientist on staff is an invaluable resource that allows them to cover additional science stories as well as report some technical stories in more depth. The American Geophysical Union has sponsored a Mass Media Fellow since 1997. Sponsorship allows affiliate program partners to establish connections with young professionals in their field. They are then also able to take advantage of the communication skills resident in their alumni base

  16. Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

    PubMed

    Park, Brian; Dargon, Phong; Binette, Christopher; Babic, Bruna; Thomas, Tina; Divinagracia, Thomas; Dahn, Michael S; Menzoian, James O

    2011-10-01

    Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

  17. Analysis of the cooperative ATPase cycle of the AAA+ chaperone ClpB from Thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.

    PubMed

    Yamasaki, Takashi; Oohata, Yukiko; Nakamura, Toshiki; Watanabe, Yo-hei

    2015-04-10

    The ClpB/Hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with DnaK/Hsp70 and its cofactors. The ClpB/Hsp104 protomer has two AAA+ modules, AAA-1 and AAA-2, and forms a homohexamer. In the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic AAA+ modules. By ATP binding and its hydrolysis at these AAA+ modules, ClpB/Hsp104 exerts the mechanical power required for protein disaggregation. Although ATPase cycle of this chaperone has been studied by several groups, an integrated understanding of this cycle has not been obtained because of the complexity of the mechanism and differences between species. To improve our understanding of the ATPase cycle, we prepared many ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately and measured their nucleotide binding, ATP hydrolysis, and disaggregation abilities. The results indicated that the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring was sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. We also found that cooperative ATP hydrolysis in at least one ring was needed for the disaggregation activity of ClpB. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. AAA and AXB algorithms for the treatment of nasopharyngeal carcinoma using IMRT and RapidArc techniques.

    PubMed

    Kamaleldin, Maha; Elsherbini, Nader A; Elshemey, Wael M

    2017-09-27

    The aim of this study is to evaluate the impact of anisotropic analytical algorithm (AAA) and 2 reporting systems (AXB-D m and AXB-D w ) of Acuros XB algorithm (AXB) on clinical plans of nasopharyngeal patients using intensity-modulated radiotherapy (IMRT) and RapidArc (RA) techniques. Six plans of different algorithm-technique combinations are performed for 10 patients to calculate dose-volume histogram (DVH) physical parameters for planning target volumes (PTVs) and organs at risk (OARs). The number of monitor units (MUs) and calculation time are also determined. Good coverage is reported for all algorithm-technique combination plans without exceeding the tolerance for OARs. Regardless of the algorithm, RA plans persistently reported higher D 2% values for PTV-70. All IMRT plans reported higher number of MUs (especially with AXB) than did RA plans. AAA-IMRT produced the minimum calculation time of all plans. Major differences between the investigated algorithm-technique combinations are reported only for the number of MUs and calculation time parameters. In terms of these 2 parameters, it is recommended to employ AXB in calculating RA plans and AAA in calculating IMRT plans to achieve minimum calculation times at reduced number of MUs. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  19. Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

    PubMed

    Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

    2017-11-22

    Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

  20. Agreement between activity-monitoring devices during home rehabilitation: a substudy of the AAA STOP trial.

    PubMed

    Myers, Jonathan; Dupain, Mandi; Vu, Andrew; Jaffe, Alyssa; Smith, Kimberly; Fonda, Holly; Dalman, Ronald

    2014-01-01

    As part of a home-based rehabilitation program, 24 older adult patients (71 ± 3 years) with abdominal aortic aneurysm (AAA) disease underwent 3 days (12 awake hr/day) of activity monitoring using an accelerometer (ACC), a pedometer, and a heart rate (HR) monitor, and recorded hourly activity logs. Subjects then underwent an interview to complete a 3-day activity recall questionnaire (3-DR). Mean energy expenditure (EE) in kcals/ day for HR, ACC, and 3-DR were 1,687 ± 458, 2,068 ± 529, and 1,974 ± 491, respectively. Differences in EE were not significant between 3-DR and ACC, but HR differed from both ACC (p < .001) and 3-DR (p < .01). ACC and 3-DR had the highest agreement, with a coefficient of variation of 7.9% and r = .86. Thus, ACC provided a reasonably accurate reflection of EE based the criterion measure, an activity recall questionnaire. ACC can be effectively used to monitor EE to achieve an appropriate training stimulus during home-based cardiac rehabilitation.

  1. Structure of a AAA+ unfoldase in the process of unfolding substrate

    PubMed Central

    Ripstein, Zev A; Huang, Rui; Augustyniak, Rafal; Kay, Lewis E; Rubinstein, John L

    2017-01-01

    AAA+ unfoldases are thought to unfold substrate through the central pore of their hexameric structures, but how this process occurs is not known. VAT, the Thermoplasma acidophilum homologue of eukaryotic CDC48/p97, works in conjunction with the proteasome to degrade misfolded or damaged proteins. We show that in the presence of ATP, VAT with its regulatory N-terminal domains removed unfolds other VAT complexes as substrate. We captured images of this transient process by electron cryomicroscopy (cryo-EM) to reveal the structure of the substrate-bound intermediate. Substrate binding breaks the six-fold symmetry of the complex, allowing five of the six VAT subunits to constrict into a tight helix that grips an ~80 Å stretch of unfolded protein. The structure suggests a processive hand-over-hand unfolding mechanism, where each VAT subunit releases the substrate in turn before re-engaging further along the target protein, thereby unfolding it. DOI: http://dx.doi.org/10.7554/eLife.25754.001 PMID:28390173

  2. The Rice AAA-ATPase OsFIGNL1 Is Essential for Male Meiosis

    PubMed Central

    Zhang, Peipei; Zhang, Yingxin; Sun, Lianping; Sinumporn, Sittipun; Yang, Zhengfu; Sun, Bin; Xuan, Dandan; Li, Zihe; Yu, Ping; Wu, Weixun; Wang, Kejian; Cao, Liyong; Cheng, Shihua

    2017-01-01

    Meiosis is crucial in reproduction of plants and ensuring genetic diversity. Although several genes involved in homologous recombination and DNA repair have been reported, their functions in rice (Oryza sativa) male meiosis remain poorly understood. Here, we isolated and characterized the rice OsFIGNL1 (OsFidgetin-like 1) gene, encoding a conserved AAA-ATPase, and explored its function and importance in male meiosis and pollen formation. The rice Osfignl1 mutant exhibited normal vegetative growth, but failed to produce seeds and displayed pollen abortion phenotype. Phenotypic comparisons between the wild-type and Osfignl1 mutant demonstrated that OsFIGNL1 is required for anther development, and that the recessive mutation of this gene causes male sterility in rice. Complementation and CRISPR/Cas9 experiments demonstrated that wild-type OsFIGNL1 is responsible for the male sterility phenotype. Subcellular localization showed that OsFIGNL1-green fluorescent protein was exclusively localized in the nucleus of rice protoplasts. Male meiosis in the Osfignl1 mutant exhibited abnormal chromosome behavior, including chromosome bridges and multivalent chromosomes at diakinesis, lagging chromosomes, and chromosome fragments during meiosis. Yeast two-hybrid assays demonstrated OsFIGNL1 could interact with RAD51A1, RAD51A2, DMC1A, DMC1B, and these physical interactions were further confirmed by BiFC assay. Taken together, our results suggest that OsFIGNL1 plays an important role in regulation of male meiosis and anther development. PMID:29021797

  3. The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding

    SciTech Connect

    Ye, Qiaozhen; Kim, Dong Hyun; Dereli, Ihsan

    Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD2 and the meiotic HORMADs, assemble into signaling complexes by binding short peptides termed “closure motifs”. The AAA+ ATPase TRIP13 regulates both MAD2 and meiotic HORMADs by disassembling these HORMA domain–closure motif complexes, but its mechanisms of substrate recognition and remodeling are unknown. Here, we combine X-ray crystallography and crosslinking mass spectrometry to outline how TRIP13 recognizes MAD2 with the help of the adapter protein p31comet. We show that p31comet binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 “poremore » loops”, which then unfold MAD2 in the presence of ATP. N-terminal truncation of MAD2 renders it refractory to TRIP13 action in vitro, and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function. Similar truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain–closure motif complexes by TRIP13.« less

  4. Patient and Aneurysm Characteristics Predicting Prolonged Length of Stay After Elective Open AAA Repair in the Endovascular Era.

    PubMed

    Casillas-Berumen, Sergio; Rojas-Miguez, Florencia A; Farber, Alik; Komshian, Sevan; Kalish, Jeffrey A; Rybin, Denis; Doros, Gheorghe; Siracuse, Jeffrey J

    2018-01-01

    Open aortic aneurysm repair (AAA) repair can be resource intensive and associated with a prolonged length of stay (LOS). We sought to examine patient and aneurysm predictors of prolonged LOS to better identify those at risk in the preoperative setting. Patient data were obtained from the targeted AAA American College of Surgery National Surgical Quality Improvement Program database from 2012 to 2014 of patients undergoing open AAA repair. Multivariable logistic regression was used to determine predictors of prolonged postoperative LOS defined as greater than 10 days (75th percentile). There were 1172 open AAA repairs identified. The majority (54%) of patients were older than 70 years and male (74%). Surgical approach was transperitoneal (70.9%) and retroperitoneal (29.1%). Aneurysms were 51.4% infrarenal, 33% juxtarenal, 5.7% pararenal, 7.4% suprarenal, and 2.5% type IV thoracoabdominal. Mean and median LOS were 9.1 ± 7.4 and 7 (0-72) days, respectively. Independently associated with extended LOS factors were visceral revascularization (odds ratio [OR]: 5.32, 95% confidence interval [CI]: 2.77-10.22, P < .001), type IV thoracoabdominal extent (OR: 3.09, 95% CI: 1.01-9.46, P = .048), suprarenal extent (OR: 1.89, 95% CI: 1.07-3.34, P = .029) and juxtarenal (OR: 1.43, 95% CI: 1.01-2.02, P = .004), non-Caucasian race (OR: 2.80, 95% CI: 1.77-4.41, P < .001), chronic obstructive pulmonary disease (OR: 1.76, 95% CI: 1.20-2.59, P = .004), not-from-home admission (OR: 1.91, 95% CI: 1.13-3.24), and age greater than 70 (OR: 1.49, 95% CI: 1.08-2.05, P = .014). We identified patient and aneurysm characteristics independently associated with protracted LOS following open AAA repair. Prospective identification of high-risk patients may allow physicians and hospitals to engage in multidisciplinary collaborations preoperatively to try to improve LOS in this resource-intensive population.

  5. Prevalence of previously undiagnosed abdominal aortic aneurysms in the area of Como: the ComoCuore "looking for AAA" ultrasonography screening.

    PubMed

    Corrado, Giovanni; Durante, Alessandro; Genchi, Vincenzo; Trabattoni, Loris; Beretta, Sandro; Rovelli, Enza; Foglia-Manzillo, Giovanni; Ferrari, Giovanni

    2016-08-01

    The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p < 0.0001). Independent predictors of AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p < 0.0001), male gender (OR 8.23, 1.79-37.91; p = 0.007), and both current (OR 4.98, 1.57-15.79; p = 0.007) and previous smoking (OR 2.76, 1.12-8.94; p = 0.03). Our study confirms the feasibility of one time US screening for AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy.

  6. Design of experiments in medical physics: Application to the AAA beam model validation.

    PubMed

    Dufreneix, S; Legrand, C; Di Bartolo, C; Bremaud, M; Mesgouez, J; Tiplica, T; Autret, D

    2017-09-01

    The purpose of this study is to evaluate the usefulness of the design of experiments in the analysis of multiparametric problems related to the quality assurance in radiotherapy. The main motivation is to use this statistical method to optimize the quality assurance processes in the validation of beam models. Considering the Varian Eclipse system, eight parameters with several levels were selected: energy, MLC, depth, X, Y 1 and Y 2 jaw dimensions, wedge and wedge jaw. A Taguchi table was used to define 72 validation tests. Measurements were conducted in water using a CC04 on a TrueBeam STx, a TrueBeam Tx, a Trilogy and a 2300IX accelerator matched by the vendor. Dose was computed using the AAA algorithm. The same raw data was used for all accelerators during the beam modelling. The mean difference between computed and measured doses was 0.1±0.5% for all beams and all accelerators with a maximum difference of 2.4% (under the 3% tolerance level). For all beams, the measured doses were within 0.6% for all accelerators. The energy was found to be an influencing parameter but the deviations observed were smaller than 1% and not considered clinically significant. Designs of experiment can help define the optimal measurement set to validate a beam model. The proposed method can be used to identify the prognostic factors of dose accuracy. The beam models were validated for the 4 accelerators which were found dosimetrically equivalent even though the accelerator characteristics differ. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  7. Phenotype–genotype spectrum of AAA syndrome from Western India and systematic review of literature

    PubMed Central

    Patt, Hiren; Koehler, Katrin; Lodha, Sailesh; Yerawar, Chaitanya; Huebner, Angela; Thakkar, Kunal; Arya, Sneha; Nair, Sandhya; Goroshi, Manjunath; Ganesh, Hosahithlu; Sarathi, Vijaya; Lila, Anurag; Bandgar, Tushar; Shah, Nalini

    2017-01-01

    Objective To study genotype–phenotype spectrum of triple A syndrome (TAS). Methods Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8) and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications). Results Median age at presentation was 4.75 years (range: 4–10) and 5 years (range: 1–42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8 (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group. Conclusion Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research. PMID:29180348

  8. Differential proteome analysis during early somatic embryogenesis in Musa spp. AAA cv. Grand Naine.

    PubMed

    Kumaravel, Marimuthu; Uma, Subbaraya; Backiyarani, Suthanthiram; Saraswathi, Marimuthu Somasundaram; Vaganan, Muthu Mayil; Muthusamy, Muthusamy; Sajith, Kallu Purayil

    2017-01-01

    Endogenous hormone secretion proteins along with stress and defense proteins play predominant role in banana embryogenesis. This study reveals the underlying molecular mechanism during transition from vegetative to embryogenic state. Banana (Musa spp.) is well known globally as a food fruit crop for millions. The requirement of quality planting material of banana is enormous. Although mass multiplication through tissue culture is in vogue, high-throughput techniques like somatic embryogenesis (SE) as a mass multiplication tool needs to be improved. Apart from clonal propagation, SE has extensive applications in genetic improvement and mutation. SE in banana is completely genome-dependent and most of the commercial cultivars exhibit recalcitrance. Thus, understanding the molecular basis of embryogenesis in Musa will help to develop strategies for mass production of quality planting material. In this study, differentially expressed proteins between embryogenic calli (EC) and non-embryogenic calli (NEC) with respect to the explant, immature male flower buds (IMFB), of cv. Grand Naine (AAA) were determined using two-dimensional gel electrophoresis (2DE). The 2DE results were validated through qRT-PCR. In total, 65 proteins were identified: 42 were highly expressed and 23 were less expressed in EC compared to NEC and IMFB. qRT-PCR analysis of five candidate proteins, upregulated in EC, were well correlated with expression at transcript level. Further analysis of proteins showed that embryogenesis in banana is associated with the control of oxidative stress. The regulation of ROS scavenging system and protection of protein structure occurred in the presence of heat shock proteins. Alongside, high accumulation of stress-related cationic peroxidase and plant growth hormone-related proteins like indole-3-pyruvate monooxygenase and adenylate isopentenyltransferase in EC revealed the association with the induction of SE.

  9. Evaluation of the dose calculation accuracy for small fields defined by jaw or MLC for AAA and Acuros XB algorithms.

    PubMed

    Fogliata, Antonella; Lobefalo, Francesca; Reggiori, Giacomo; Stravato, Antonella; Tomatis, Stefano; Scorsetti, Marta; Cozzi, Luca

    2016-10-01

    Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis. Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 ; MLC-defined: 0.5 × 0.5 cm 2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 . MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed. Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm 2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm 2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the

  10. m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal Growth Conditions Despite Their Importance for Mitochondrial Translation.

    PubMed

    Kolodziejczak, Marta; Skibior-Blaszczyk, Renata; Janska, Hanna

    2018-05-01

    For optimal mitochondrial activity, the mitochondrial proteome must be properly maintained or altered in response to developmental and environmental stimuli. Based on studies of yeast and humans, one of the key players in this control are m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes. This study focuses on the importance of m-AAA proteases in plant mitochondria, providing their first experimentally proven physiological substrate. We found that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial translation and functionality of OXPHOS (oxidative phosphorylation) complexes are impaired. However, in contrast to their mammalian or yeast counterparts, plant m-AAA complexes are not critical for the survival of Arabidopsis under optimal conditions; ftsh3/10 plants are only slightly smaller in size at the early developmental stage compared with plants containing m-AAA complexes. Our data suggest that a lack of significant visible morphological alterations under optimal growth conditions involves mechanisms which rely on existing functional redundancy and induced functional compensation in Arabidopsis mitochondria.

  11. A dosimetric evaluation of the Eclipse AAA algorithm and Millennium 120 MLC for cranial intensity-modulated radiosurgery

    SciTech Connect

    Calvo Ortega, Juan Francisco, E-mail: jfcdrr@yahoo.es; Moragues, Sandra; Pozo, Miquel

    2014-07-01

    The aim of this study is to assess the accuracy of a convolution-based algorithm (anisotropic analytical algorithm [AAA]) implemented in the Eclipse planning system for intensity-modulated radiosurgery (IMRS) planning of small cranial targets by using a 5-mm leaf-width multileaf collimator (MLC). Overall, 24 patient-based IMRS plans for cranial lesions of variable size (0.3 to 15.1 cc) were planned (Eclipse, AAA, version 10.0.28) using fixed field-based IMRS produced by a Varian linear accelerator equipped with a 120 MLC (5-mm width on central leaves). Plan accuracy was evaluated according to phantom-based measurements performed with radiochromic film (EBT2, ISP, Wayne, NJ). Film 2Dmore » dose distributions were performed with the FilmQA Pro software (version 2011, Ashland, OH) by using the triple-channel dosimetry method. Comparison between computed and measured 2D dose distributions was performed using the gamma method (3%/1 mm). Performance of the MLC was checked by inspection of the DynaLog files created by the linear accelerator during the delivery of each dynamic field. The absolute difference between the calculated and measured isocenter doses for all the IMRS plans was 2.5% ± 2.1%. The gamma evaluation method resulted in high average passing rates of 98.9% ± 1.4% (red channel) and 98.9% ± 1.5% (blue and green channels). DynaLog file analysis revealed a maximum root mean square error of 0.46 mm. According to our results, we conclude that the Eclipse/AAA algorithm provides accurate cranial IMRS dose distributions that may be accurately delivered by a Varian linac equipped with a Millennium 120 MLC.« less

  12. Nanomechanical and thermophoretic analyses of the nucleotide-dependent interactions between the AAA + subunits of magnesium chelatase

    DOE PAGES

    Adams, Nathan B. P.; Vasilev, Cvetelin; Brindley, Amanda A.; ...

    2016-04-30

    In chlorophyll biosynthesis, the magnesium chelatase enzyme complex catalyzes the insertion of a Mg 2+ ion into protoporphyrin IX. Prior to this event, two of the three subunits, the AAA + proteins ChlI and ChlD, form a ChlID–MgATP complex. We used microscale thermophoresis to directly determine dissociation constants for the I-D subunits from Synechocystis, and to show that the formation of a ChlID–MgADP complex, mediated by the arginine finger and the sensor II domain on ChlD, is necessary for the assembly of the catalytically active ChlHID–MgATP complex. The N-terminal AAA + domain of ChlD is essential for complex formation, butmore » some stability is preserved in the absence of the C-terminal integrin domain of ChlD, particularly if the intervening polyproline linker region is retained. Single molecule force spectroscopy (SMFS) was used to determine the factors that stabilize formation of the ChlID–MgADP complex at the single molecule level; ChlD was attached to an atomic force microscope (AFM) probe in two different orientations, and the ChlI subunits were tethered to a silica surface; the probability of subunits interacting more than doubled in the presence of MgADP, and we show that the N-terminal AAA + domain of ChlD mediates this process, in agreement with the microscale thermophoresis data. Analysis of the unbinding data revealed a most probable interaction force of around 109 pN for formation of single ChlID–MgADP complexes. Finally, these experiments provide a quantitative basis for understanding the assembly and function of the Mg chelatase complex.« less

  13. Morphology-related limitations of EVAR applicability in the treatment of AAA in West-Central Poland.

    PubMed

    Dzieciuchowicz, Łukasz; Tomczak, Jolanta; Strauss, Ewa; Oszkinis, Grzegorz

    2018-05-14

    To analyze the current applicability of endovascular aneurysm repair (EVAR) in patients with an infrarenal abdominal aortic aneurysm (AAAs) with indication for elective treatment in West-Central Poland. Computed tomography angiograms of 100 consecutive patients with infrarenal AAA deemed to require treatment were analyzed with an OsiriX DICOM viewer in 3D-MPR mode. Proximal neck diameter, length, angulation, shape, the presence of thrombus and calcification, distal neck diameter, and morphology of the iliac arteries were determined. Three sets of morphological criteria were established. The optimal criteria consisted of a non-conical proximal neck without moderate or severe calcification or thrombus, with a diameter of 18-28 mm, length of ≥15 mm, and β angulation of <60%; a distal neck with a diameter of ≥20 mm; a landing zone in the common iliac arteries with a length of ≥ 10 mm and diameter of ≤ 20 mm; and external iliac arteries with diameters of ≥7 mm. The suboptimal criteria included proximal neck diameters of 18-32 mm, neck lengths ≥10 mm, infrarenal neck angulations of up to 75˚, and common iliac artery diameters of up to 25 mm. Finally, the extended suboptimal criteria included proximal neck diameters of 16-34 mm and infrarenal neck angulations ≤90˚, without limits in the maximal diameter of the common iliac arteries. The median maximum aneurysm diameter was 61 mm. The optimal, suboptimal, and extended suboptimal criteria were met by 23%, 32%, and 53% of patients, respectively. The most common deviations were wide, conical, and angulated proximal necks and aneurysmal iliac arteries. The majority of patients with AAA deemed to be candidates for elective repair do not meet the most favorable criteria for EVAR. Availability of better endovascular solutions for conical, angulated, and wide necks and aneurysmal iliac arteries would likely expand EVAR applicability. Open repair remains a valid option. Copyright © 2018 Elsevier Inc. All rights

  14. The INNOVATION Trial: four-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System for endovascular repair.

    PubMed

    Pratesi, Giovanni; Pratesi, Carlo; Chiesa, Roberto; Coppi, Gioacchino; Scheinert, Dierk; Brunkwall, Jan S; van der Meulen, Stefaan; Torsello, Giovanni

    2017-10-01

    This paper reports the 4-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System (Cordis Corp., Milpitas, CA, USA), an ultra-low-profile device for the treatment of abdominal aortic aneurysms. The INNOVATION Trial is the prospective, first-in-human, multicenter trial to evaluate the safety and effectiveness of the INCRAFT® System. Patients underwent annual clinical and computed tomography angiography examination as part of the study protocol. The INCRAFT® AAA Stent-Graft System is a customizable tri-modular design, with an ultra-low profile (14-Fr) delivery system. Patient were treated under approved protocol, the prescribed clinical and imaging follow-up at annually through 5 years. Results analyzed and adjudicated by a clinical events committee, independent core laboratory, and a data safety and monitoring board. This manuscript reports results through 4 years of follow-up. A total of 60 patients were enrolled in the trial, all of whom were successfully treated. Follow-up rates at 1 and 4 years were 93% (56/60) and 85% (51/60), respectively. All-cause mortality at 4 years was 17.6% and no death was AAA-, device-, or procedure-related. The secondary reintervention rate at 1 year was 4.6%, primarily the result of stent thrombosis. In total, 10 patients required 13 post-procedure interventions within 4-years of follow-up (2 to repair a type I endoleak, 4 to repair a type II endoleak, 1 for stent thrombosis, 1 for renal stenosis, 1 for aneurysm enlargement, 2 for limb migration and 2 for prosthesis stenosis or occlusion). There were 4 cases (10%) of aneurysm enlargement reported at the 4 year follow-up. At 4 years, 38 out of 39 patients were free from type I and III endoleaks. There were no proximal type I or type III endoleaks at 4-year follow-up. Core laboratory evaluation of the postoperative imaging studies indicated absence of endograft migration while a single fracture was demonstrated without any clinical sequelae. The INCRAFT® AAA Stent

  15. Developmental Localization and Methylesterification of Pectin Epitopes during Somatic Embryogenesis of Banana (Musa spp. AAA)

    PubMed Central

    Xu, Chunxiang; Zhao, Lu; Pan, Xiao; Šamaj, Jozef

    2011-01-01

    Background The plant cell walls play an important role in somatic embryogenesis and plant development. Pectins are major chemical components of primary cell walls while homogalacturonan (HG) is the most abundant pectin polysaccharide. Developmental regulation of HG methyl-esterification degree is important for cell adhesion, division and expansion, and in general for proper organ and plant development. Methodology/Principal Findings Developmental localization of pectic homogalacturonan (HG) epitopes and the (1→4)-β-D-galactan epitope of rhamnogalacturonan I (RG-I) and degree of pectin methyl-esterification (DM) were studied during somatic embryogenesis of banana (Musa spp. AAA). Histological analysis documented all major developmental stages including embryogenic cells (ECs), pre-globular, globular, pear-shaped and cotyledonary somatic embryos. Histochemical staining of extracellularly secreted pectins with ruthenium red showed the most intense staining at the surface of pre-globular, globular and pear-shaped somatic embryos. Biochemical analysis revealed developmental regulation of galacturonic acid content and DM in diverse embryogenic stages. Immunodots and immunolabeling on tissue sections revealed developmental regulation of highly methyl-esterified HG epitopes recognized by JIM7 and LM20 antibodies during somatic embryogenesis. Cell walls of pre-globular/globular and late-stage embryos contained both low methyl-esterified HG epitopes as well as partially and highly methyl-esterified ones. Extracellular matrix which covered surface of early developing embryos contained pectin epitopes recognized by 2F4, LM18, JIM5, JIM7 and LM5 antibodies. De-esterification of cell wall pectins by NaOH caused a decrease or an elimination of immunolabeling in the case of highly methyl-esterified HG epitopes. However, immunolabeling of some low methyl-esterified epitopes appeared stronger after this base treatment. Conclusions/Significance These data suggest that both low

  16. Preferences of AAA/AAG codon recognition by modified nucleosides, τm5s2U34 and t6A37 present in tRNALys.

    PubMed

    Sonawane, Kailas D; Kamble, Asmita S; Fandilolu, Prayagraj M

    2017-12-27

    Deficiency of 5-taurinomethyl-2-thiouridine, τm 5 s 2 U at the 34th 'wobble' position in tRNA Lys causes MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a neuromuscular disease. This modified nucleoside of mt tRNA Lys , recognizes AAA/AAG codons during protein biosynthesis process. Its preference to identify cognate codons has not been studied at the atomic level. Hence, multiple MD simulations of various molecular models of anticodon stem loop (ASL) of mt tRNA Lys in presence and absence of τm 5 s 2 U 34 and N 6 -threonylcarbamoyl adenosine (t 6 A 37 ) along with AAA and AAG codons have been accomplished. Additional four MD simulations of multiple ASL mt tRNA Lys models in the context of ribosomal A-site residues have also been performed to investigate the role of A-site in recognition of AAA/AAG codons. MD simulation results show that, ASL models in presence of τm 5 s 2 U 34 and t 6 A 37 with codons AAA/AAG are more stable than the ASL lacking these modified bases. MD trajectories suggest that τm 5 s 2 U recognizes the codons initially by 'wobble' hydrogen bonding interactions, and then tRNA Lys might leave the explicit codon by a novel 'single' hydrogen bonding interaction in order to run the protein biosynthesis process smoothly. We propose this model as the 'Foot-Step Model' for codon recognition, in which the single hydrogen bond plays a crucial role. MD simulation results suggest that, tRNA Lys with τm 5 s 2 U and t 6 A recognizes AAA codon more preferably than AAG. Thus, these results reveal the consequences of τm 5 s 2 U and t 6 A in recognition of AAA/AAG codons in mitochondrial disease, MERRF.

  17. The I domain of the AAA+ HslUV protease coordinates substrate binding, ATP hydrolysis, and protein degradation

    PubMed Central

    Sundar, Shankar; Baker, Tania A; Sauer, Robert T

    2012-01-01

    In the AAA+ HslUV protease, substrates are bound and unfolded by a ring hexamer of HslU, before translocation through an axial pore and into the HslV degradation chamber. Here, we show that the N-terminal residues of an Arc substrate initially bind in the HslU axial pore, with key contacts mediated by a pore loop that is highly conserved in all AAA+ unfoldases. Disordered loops from the six intermediate domains of the HslU hexamer project into a funnel-shaped cavity above the pore and are positioned to contact protein substrates. Mutations in these I-domain loops increase KM and decrease Vmax for degradation, increase the mobility of bound substrates, and prevent substrate stimulation of ATP hydrolysis. HslU-ΔI has negligible ATPase activity. Thus, the I domain plays an active role in coordinating substrate binding, ATP hydrolysis, and protein degradation by the HslUV proteolytic machine. PMID:22102327

  18. Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study

    PubMed Central

    Huang, Rui; Ripstein, Zev A.; Augustyniak, Rafal; Lazniewski, Michal; Ginalski, Krzysztof; Kay, Lewis E.; Rubinstein, John L.

    2016-01-01

    The AAA+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous AAA+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl-transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded. PMID:27402735

  19. Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study.

    PubMed

    Huang, Rui; Ripstein, Zev A; Augustyniak, Rafal; Lazniewski, Michal; Ginalski, Krzysztof; Kay, Lewis E; Rubinstein, John L

    2016-07-19

    The AAA+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous AAA+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl-transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded.

  20. HTTP as a Data Access Protocol: Trials with XrootD in CMS’s AAA Project

    NASA Astrophysics Data System (ADS)

    Balcas, J.; Bockelman, B. P.; Kcira, D.; Newman, H.; Vlimant, J.; Hendricks, T. W.; CMS Collaboration

    2017-10-01

    The main goal of the project to demonstrate the ability of using HTTP data federations in a manner analogous to the existing AAA infrastructure of the CMS experiment. An initial testbed at Caltech has been built and changes in the CMS software (CMSSW) are being implemented in order to improve HTTP support. The testbed consists of a set of machines at the Caltech Tier2 that improve the support infrastructure for data federations at CMS. As a first step, we are building systems that produce and ingest network data transfers up to 80 Gbps. In collaboration with AAA, HTTP support is enabled at the US redirector and the Caltech testbed. A plugin for CMSSW is being developed for HTTP access based on the DaviX software. It will replace the present fork/exec or curl for HTTP access. In addition, extensions to the XRootD HTTP implementation are being developed to add functionality to it, such as client-based monitoring identifiers. In the future, patches will be developed to better integrate HTTP-over-XRootD with the Open Science Grid (OSG) distribution. First results of the transfer tests using HTTP are presented in this paper together with details about the initial setup.

  1. An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome.

    PubMed

    Worden, Evan J; Dong, Ken C; Martin, Andreas

    2017-09-07

    Poly-ubiquitin chains direct protein substrates to the 26S proteasome, where they are removed by the deubiquitinase Rpn11 during ATP-dependent substrate degradation. Rapid deubiquitination is required for efficient degradation but must be restricted to committed substrates that are engaged with the ATPase motor to prevent premature ubiquitin chain removal and substrate escape. Here we reveal the ubiquitin-bound structure of Rpn11 from S. cerevisiae and the mechanisms for mechanochemical coupling of substrate degradation and deubiquitination. Ubiquitin binding induces a conformational switch of Rpn11's Insert-1 loop from an inactive closed state to an active β hairpin. This switch is rate-limiting for deubiquitination and strongly accelerated by mechanical substrate translocation into the AAA+ motor. Deubiquitination by Rpn11 and ubiquitin unfolding by the ATPases are in direct competition. The AAA+ motor-driven acceleration of Rpn11 is therefore important to ensure that poly-ubiquitin chains are removed only from committed substrates and fast enough to prevent their co-degradation. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors

    PubMed Central

    Matias, Pedro M.; Baek, Sung Hee; Bandeiras, Tiago M.; Dutta, Anindya; Houry, Walid A.; Llorca, Oscar; Rosenbaum, Jean

    2015-01-01

    Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10–12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models. PMID:25988184

  3. The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors.

    PubMed

    Matias, Pedro M; Baek, Sung Hee; Bandeiras, Tiago M; Dutta, Anindya; Houry, Walid A; Llorca, Oscar; Rosenbaum, Jean

    2015-01-01

    Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10-12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models.

  4. Cotranslocational processing of the protein substrate calmodulin by an AAA+ unfoldase occurs via unfolding and refolding intermediates.

    PubMed

    Augustyniak, Rafal; Kay, Lewis E

    2018-05-22

    Protein remodeling by AAA+ enzymes is central for maintaining proteostasis in a living cell. However, a detailed structural description of how this is accomplished at the level of the substrate molecules that are acted upon is lacking. Here, we combine chemical cross-linking and methyl transverse relaxation-optimized NMR spectroscopy to study, at atomic resolution, the stepwise unfolding and subsequent refolding of the two-domain substrate calmodulin by the VAT AAA+ unfoldase from Thermoplasma acidophilum By engineering intermolecular disulphide bridges between the substrate and VAT we trap the substrate at different stages of translocation, allowing structural studies throughout the translocation process. Our results show that VAT initiates substrate translocation by pulling on intrinsically unstructured N or C termini of substrate molecules without showing specificity for a particular amino acid sequence. Although the B1 domain of protein G is shown to unfold cooperatively, translocation of calmodulin leads to the formation of intermediates, and these differ on an individual domain level in a manner that depends on whether pulling is from the N or C terminus. The approach presented generates an atomic resolution picture of substrate unfolding and subsequent refolding by unfoldases that can be quite different from results obtained via in vitro denaturation experiments.

  5. From AAA to Acuros XB-clinical implications of selecting either Acuros XB dose-to-water or dose-to-medium.

    PubMed

    Zifodya, Jackson M; Challens, Cameron H C; Hsieh, Wen-Long

    2016-06-01

    When implementing Acuros XB (AXB) as a substitute for anisotropic analytic algorithm (AAA) in the Eclipse Treatment Planning System, one is faced with a dilemma of reporting either dose to medium, AXB-Dm or dose to water, AXB-Dw. To assist with decision making on selecting either AXB-Dm or AXB-Dw for dose reporting, a retrospective study of treated patients for head & neck (H&N), prostate, breast and lung is presented. Ten patients, previously treated using AAA plans, were selected for each site and re-planned with AXB-Dm and AXB-Dw. Re-planning was done with fixed monitor units (MU) as well as non-fixed MUs. Dose volume histograms (DVH) of targets and organs at risk (OAR), were analyzed in conjunction with ICRU-83 recommended dose reporting metrics. Additionally, comparisons of plan homogeneity indices (HI) and MUs were done to further highlight the differences between the algorithms. Results showed that, on average AAA overestimated dose to the target volume and OARs by less than 2.0 %. Comparisons between AXB-Dw and AXB-Dm, for all sites, also showed overall dose differences to be small (<1.5 %). However, in non-water biological media, dose differences between AXB-Dw and AXB-Dm, as large as 4.6 % were observed. AXB-Dw also tended to have unexpectedly high 3D maximum dose values (>135 % of prescription dose) for target volumes with high density materials. Homogeneity indices showed that AAA planning and optimization templates would need to be adjusted only for the H&N and Lung sites. MU comparison showed insignificant differences between AXB-Dw relative to AAA and between AXB-Dw relative to AXB-Dm. However AXB-Dm MUs relative to AAA, showed an average difference of about 1.3 % signifying an underdosage by AAA. In conclusion, when dose is reported as AXB-Dw, the effect that high density structures in the PTV has on the dose distribution should be carefully considered. As the results show overall small dose differences between the algorithms, when

  6. SU-E-T-516: Dosimetric Validation of AcurosXB Algorithm in Comparison with AAA & CCC Algorithms for VMAT Technique.

    PubMed

    Kathirvel, M; Subramanian, V Sai; Arun, G; Thirumalaiswamy, S; Ramalingam, K; Kumar, S Ashok; Jagadeesh, K

    2012-06-01

    To dosimetrically validate AcurosXB algorithm for Volumetric Modulated Arc Therapy (VMAT) in comparison with standard clinical Anisotropic Analytic Algorithm(AAA) and Collapsed Cone Convolution(CCC) dose calculation algorithms. AcurosXB dose calculation algorithm is available with Varian Eclipse treatment planning system (V10). It uses grid-based Boltzmann equation solver to predict dose precisely in lesser time. This study was made to realize algorithms ability to predict dose accurately as its delivery for which five clinical cases each of Brain, Head&Neck, Thoracic, Pelvic and SBRT were taken. Verification plans were created on multicube phantom with iMatrixx-2D detector array and then dose prediction was done with AcurosXB, AAA & CCC (COMPASS System) algorithm and the same were delivered onto CLINAC-iX treatment machine. Delivered dose was captured in iMatrixx plane for all 25 plans. Measured dose was taken as reference to quantify the agreement between AcurosXB calculation algorithm against previously validated AAA and CCC algorithm. Gamma evaluation was performed with clinical criteria distance-to-agreement 3&2mm and dose difference 3&2% in omnipro-I'MRT software. Plans were evaluated in terms of correlation coefficient, quantitative area gamma and average gamma. Study shows good agreement between mean correlation 0.9979±0.0012, 0.9984±0.0009 & 0.9979±0.0011 for AAA, CCC & Acuros respectively. Mean area gamma for criteria 3mm/3% was found to be 98.80±1.04, 98.14±2.31, 98.08±2.01 and 2mm/2% was found to be 93.94±3.83, 87.17±10.54 & 92.36±5.46 for AAA, CCC & Acuros respectively. Mean average gamma for 3mm/3% was 0.26±0.07, 0.42±0.08, 0.28±0.09 and 2mm/2% was found to be 0.39±0.10, 0.64±0.11, 0.42±0.13 for AAA, CCC & Acuros respectively. This study demonstrated that the AcurosXB algorithm had a good agreement with the AAA & CCC in terms of dose prediction. In conclusion AcurosXB algorithm provides a valid, accurate and speedy alternative to AAA

  7. Postural stabilizing effect of alfacalcidol and active absorbable algal calcium (AAA Ca) compared with calcium carbonate assessed by computerized posturography.

    PubMed

    Fujita, Takuo; Nakamura, Shoji; Ohue, Mutsumi; Fujii, Yoshio; Miyauchi, Akimitsu; Takagi, Yasuyuki; Tsugeno, Hirofumi

    2007-01-01

    Sway and postural instability have drawn attention as a risk factor for osteoporotic fracture, in addition to low bone mineral density (BMD) and poor bone quality. In view of the fracture-reducing effect of alfacalcidol and active absorbable algal calcium (AAA Ca) not readily explained by rather mild increases of BMD, attempts were made to evaluate postural stabilizing effect of alfacalcidol, AAA Ca, and calcium carbonate (CaCO(3)) by computerized posturography. Track of the gravity center was analyzed to calculate parameters related to tract length, track range, and track density to express the degree of sway before and after supplementation in 126 subjects ranging in age between 20 and 81 years randomly divided into four groups. Supplementation with AAA Ca containing 900 mg elemental Ca (group A), no calcium (group B), CaCO(3) also containing 900 mg elemental Ca (group C), or alfacalcidol (group D) continued daily for 12 months. For each parameter, the ratio closed eye value/open eye value (Romberg ratio) was calculated to detect aggravation of sway by eye closure. Age, parameters of Ca and P, and proportions of subjects with fracture and those with low BMD showed no marked deviation among the groups. With eyes open, significant decreases of a track range parameter (REC) from group B was noted in groups A (P = 0.0397) and D (P = 0.0296), but not in group C according to multiple comparison by Scheffe, indicating superior postural stabilizing effect of A and D over C. In the first 2 months, a significant fall was already evident in REC from group B in group D (P = 0.0120) with eyes open. Paired comparison of sway parameters before and after supplementation revealed a significant increase of track density parameter (LNGA), indicating sway control efficiency and a significant decrease of REC in groups A and D compared to group B with eyes open. With eyes closed, only group A showed a significant improvement from group B (P = 0.0456; Fig. 1), with a significant

  8. 42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458aaa-8...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... section 509 of the Act [25 U.S.C. 458aaa-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...

  9. 42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458aaa-8...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... section 509 of the Act [25 U.S.C. 458aaa-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...

  10. 42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458aaa-8...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... section 509 of the Act [25 U.S.C. 458aaa-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...

  11. 42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458aaa-8...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... section 509 of the Act [25 U.S.C. 458aaa-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...

  12. 42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458aaa-8...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... section 509 of the Act [25 U.S.C. 458aaa-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...

  13. Comparison of Acuros (AXB) and Anisotropic Analytical Algorithm (AAA) for dose calculation in treatment of oesophageal cancer: effects on modelling tumour control probability.

    PubMed

    Padmanaban, Sriram; Warren, Samantha; Walsh, Anthony; Partridge, Mike; Hawkins, Maria A

    2014-12-23

    To investigate systematic changes in dose arising when treatment plans optimised using the Anisotropic Analytical Algorithm (AAA) are recalculated using Acuros XB (AXB) in patients treated with definitive chemoradiotherapy (dCRT) for locally advanced oesophageal cancers. We have compared treatment plans created using AAA with those recalculated using AXB. Although the Anisotropic Analytical Algorithm (AAA) is currently more widely used in clinical routine, Acuros XB (AXB) has been shown to more accurately calculate the dose distribution, particularly in heterogeneous regions. Studies to predict clinical outcome should be based on modelling the dose delivered to the patient as accurately as possible. CT datasets from ten patients were selected for this retrospective study. VMAT (Volumetric modulated arc therapy) plans with 2 arcs, collimator rotation ± 5-10° and dose prescription 50 Gy / 25 fractions were created using Varian Eclipse (v10.0). The initial dose calculation was performed with AAA, and AXB plans were created by re-calculating the dose distribution using the same number of monitor units (MU) and multileaf collimator (MLC) files as the original plan. The difference in calculated dose to organs at risk (OAR) was compared using dose-volume histogram (DVH) statistics and p values were calculated using the Wilcoxon signed rank test. The potential clinical effect of dosimetric differences in the gross tumour volume (GTV) was evaluated using three different TCP models from the literature. PTV Median dose was apparently 0.9 Gy lower (range: 0.5 Gy - 1.3 Gy; p < 0.05) for VMAT AAA plans re-calculated with AXB and GTV mean dose was reduced by on average 1.0 Gy (0.3 Gy -1.5 Gy; p < 0.05). An apparent difference in TCP of between 1.2% and 3.1% was found depending on the choice of TCP model. OAR mean dose was lower in the AXB recalculated plan than the AAA plan (on average, dose reduction: lung 1.7%, heart 2.4%). Similar trends were seen for CRT plans

  14. Prime Contract Awards Over $25,000 by Major System, Contractor and State Part 1 (AAA-NAVY-AVG NAVY)

    DTIC Science & Technology

    1990-01-01

    Q-COC’) -4 M’i (a -4 c"a(aeo - ( D 0 AC 1 -ao f-.r qva 0(%Ioa.4 ()t a. c~cv(vc4 z *Za in -0f (4Jl w -44- m - .41 C,4 Ui 0 C4 IC4 P- -a l~~II I II cLE E...AO-A236 155iiiilulll l I l 1990 ANNUAL Prime Contract Awards Over $25,000 by Major System, Contractor and State Part 1 (AAA-NAVY-AVG NAVY) WHS...Special . 1 -9 __28284 pages I1 ~ . - e21 M(%I% cm -40W -4 I4 m V .. 4 mt WC)a r a- 4-r w~l w zl- qt qt V .4- 01-4 41-4 . 40 o r Lu V) c I OL 9 C U c

  15. Interaction studies of resistomycin from Streptomyces aurantiacus AAA5 with calf thymus DNA and bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Vijayabharathi, R.; Sathyadevi, P.; Krishnamoorthy, P.; Senthilraja, D.; Brunthadevi, P.; Sathyabama, S.; Priyadarisini, V. Brindha

    2012-04-01

    Resistomycin, a secondary metabolite produced by Streptomyces aurantiacus AAA5. The binding interaction of resistomycin with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) was investigated by spectrophotometry, spectrofluorimetry, circular dichroism (CD) and synchronous fluorescence techniques under physiological conditions in vitro. Absorption spectral studies along with the fluorescence competition with ethidium bromide measurements and circular dichroism clearly suggest that the resistomycin bind with CT DNA relatively strong via groove binding. BSA interaction results revealed that the drug was found to quench the fluorescence intensity of the protein through a static quenching mechanism. The number of binding sites 'n' and apparent binding constant 'K' calculated according to the Scatchard equation exhibit a good binding property to bovine serum albumin protein. In addition, the results observed from synchronous fluorescence measurements clearly demonstrate the occurrence of conformational changes of BSA upon addition of the test compound.

  16. High-intensity interval exercise training before abdominal aortic aneurysm repair (HIT-AAA): protocol for a randomised controlled feasibility trial.

    PubMed

    Tew, Garry A; Weston, Matthew; Kothmann, Elke; Batterham, Alan M; Gray, Joanne; Kerr, Karen; Martin, Denis; Nawaz, Shah; Yates, David; Danjoux, Gerard

    2014-01-10

    In patients with large abdominal aortic aneurysm (AAA), open surgical or endovascular aneurysm repair procedures are often used to minimise the risk of aneurysm-related rupture and death; however, aneurysm repair itself carries a high risk. Low cardiopulmonary fitness is associated with an increased risk of early post-operative complications and death following elective AAA repair. Therefore, fitness should be enhanced before aneurysm repair. High-intensity interval exercise training (HIT) is a potent, time-efficient strategy for enhancing cardiopulmonary fitness. Here, we describe a feasibility study for a definitive trial of a pre-operative HIT intervention to improve post-operative outcomes in patients undergoing elective AAA repair. A minimum of 50 patients awaiting elective repair of a 5.5-7.0 cm infrarenal AAA will be allocated by minimisation to HIT or usual care control in a 1:1 ratio. The patients allocated to HIT will complete three hospital-based exercise sessions per week, for 4 weeks. Each session will include 2 or 4 min of high-intensity stationary cycling followed by the same duration of easy cycling or passive recovery, repeated until a total of 16 min of high-intensity exercise is accumulated. Outcomes to be assessed before randomisation and 24-48 h before aneurysm repair include cardiopulmonary fitness, maximum AAA diameter and health-related quality of life. In the post-operative period, we will record destination (ward or critical care unit), organ-specific morbidity, mortality and the durations of critical care and hospital stay. Twelve weeks after the discharge, participants will be interviewed to reassess quality of life and determine post-discharge healthcare utilisation. The costs associated with the exercise intervention and healthcare utilisation will be calculated. Ethics approval was secured through Sunderland Research Ethics Committee. The findings of the trial will be disseminated through peer-reviewed journals, and national and

  17. In vitro propagation and assessment of the genetic fidelity of Musa acuminata (AAA) cv. Vaibalhla derived from immature male flowers.

    PubMed

    Hrahsel, Lalremsiami; Basu, Adreeja; Sahoo, Lingaraj; Thangjam, Robert

    2014-02-01

    An efficient in vitro propagation method has been developed for the first time for Musa acuminata (AAA) cv. Vaibalhla, an economically important banana cultivar of Mizoram, India. Immature male flowers were used as explants. Murashige and Skoog's (MS) medium supplemented with plant growth regulators (PGRs) were used for the regeneration process. Out of different PGR combinations, MS medium supplemented with 2 mg L(-1) 6-benzylaminopurine (BAP) + 0.5 mg L(-1) α-naphthalene acetic acid (NAA) was optimal for production of white bud-like structures (WBLS). On this medium, explants produced the highest number of buds per explant (4.30). The highest percentage (77.77) and number (3.51) of shoot formation from each explants was observed in MS medium supplemented with 2 mg L(-1) kinetin + 0.5 mg L(-1) NAA. While MS medium supplemented with a combination of 2 mg L(-1) BAP + 0.5 mg L(-1) NAA showed the maximum shoot length (14.44 cm). Rooting efficiency of the shoots was highest in the MS basal medium without any PGRs. The plantlets were hardened successfully in the greenhouse with 96% survival rate. Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers were employed to assess the genetic stability of in vitro regenerated plantlets of M. acuminata (AAA) cv. Vaibalhla. Eight RAPD and 8 ISSR primers were successfully used for the analysis from the 40 RAPD and 30 ISSR primers screened initially. The amplified products were monomorphic across all the regenerated plants and were similar to the mother plant. The present standardised protocol will find application in mass production, conservation and genetic transformation studies of this commercially important banana.

  18. Structural Characterization of a Newly Identified Component of α-Carboxysomes: The AAA+ Domain Protein CsoCbbQ

    DOE PAGES

    Sutter, Markus; Roberts, Evan W.; Gonzalez, Raul C.; ...

    2015-11-05

    Carboxysomes are bacterial microcompartments that enhance carbon fixation by concentrating ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and its substrate CO 2 within a proteinaceous shell. They are found in all cyanobacteria, some purple photoautotrophs and many chemoautotrophic bacteria. Carboxysomes consist of a protein shell that encapsulates several hundred molecules of RuBisCO, and contain carbonic anhydrase and other accessory proteins. Genes coding for carboxysome shell components and the encapsulated proteins are typically found together in an operon. The α-carboxysome operon is embedded in a cluster of additional, conserved genes that are presumably related to its function. In many chemoautotrophs, products of the expanded carboxysomemore » locus include CbbO and CbbQ, a member of the AAA+ domain superfamily. We bioinformatically identified subtypes of CbbQ proteins and show that their genes frequently co-occur with both Form IA and Form II RuBisCO. The α-carboxysome-associated ortholog, CsoCbbQ, from Halothiobacillus neapolitanus forms a hexamer in solution and hydrolyzes ATP. The crystal structure shows that CsoCbbQ is a hexamer of the typical AAA+ domain; the additional C-terminal domain, diagnostic of the CbbQ subfamily, structurally fills the inter-monomer gaps, resulting in a distinctly hexagonal shape. Finally, we show that CsoCbbQ interacts with CsoCbbO and is a component of the carboxysome shell, the first example of ATPase activity associated with a bacterial microcompartment.« less

  19. The Whipple Museum and Cavendish Laboratory, Cambridge

    NASA Astrophysics Data System (ADS)

    Pippard, Brian

    The Whipple Museum is part of the History and Philosophy of Science Department in the University of Cambridge. It is on your right as soon as you enter Free School Lane from Pembroke Street, and is normally open between 1:30 and 4:30 P.M. on weekdays. The main room, a hall with hammer-beam roof, is a relic of Stephen Perse’s school (1624) now flourishing elsewhere in the city. It houses a large collection of mathematical, physical and astronomical instruments — abaci, Napier’s bones, slide rules; sextants and other surveying instruments; telescopes, compasses and pocket sundials (especially of ivory from Nuremberg 1500-1700); and a Grand Orrery by George Adams (1750). The gallery of a second room is used for special exhibitions, often of items from the well-stocked store. Some specialist catalogues have been compiled and are on sale.

  20. Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

    PubMed

    Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

    2018-04-12

    Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright

  1. SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

    SciTech Connect

    Yaparpalvi, R; Mynampati, D; Kuo, H

    Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performedmore » using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose

  2. Substrate delivery by the AAA+ ClpX and ClpC1 unfoldases activates the mycobacterial ClpP1P2 peptidase

    PubMed Central

    Schmitz, Karl R.; Sauer, Robert T.

    2014-01-01

    Summary Mycobacterial Clp-family proteases function via collaboration of the heteromeric ClpP1P2 peptidase with a AAA+ partner, ClpX or ClpC1. These enzymes are essential for M. tuberculosis viability and are validated antibacterial drug targets, but the requirements for assembly and regulation of functional proteolytic complexes are poorly understood. Here, we report the reconstitution of protein degradation by mycobacterial Clp proteases in vitro and describe novel features of these enzymes that distinguish them from orthologs in other bacteria. Both ClpX and ClpC1 catalyze ATP-dependent unfolding and degradation of native protein substrates in conjunction with ClpP1P2, but neither mediates protein degradation with just ClpP1 or ClpP2. ClpP1P2 alone has negligible peptidase activity, but is strongly stimulated by translocation of protein substrates into ClpP1P2 by either AAA+ partner. Interestingly, our results support a model in which both binding of a AAA+ partner and protein-substrate delivery are required to stabilize active ClpP1P2. Our model has implications for therapeutically targeting ClpP1P2 in dormant M. tuberculosis, and our reconstituted systems should facilitate identification of novel Clp protease inhibitors and activators. PMID:24976069

  3. Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

    PubMed Central

    Zhuang, Lei; Zhang, Jun; Xiang, Xin

    2007-01-01

    Cytoplasmic dynein performs multiple cellular tasks but its regulation remains unclear. The dynein heavy chain has a N-terminal stem that binds to other subunits and a C-terminal motor unit that contains six AAA (ATPase associated with cellular activities) domains and a microtubule-binding site located between AAA4 and AAA5. In Aspergillus nidulans, NUDF (a LIS1 homolog) functions in the dynein pathway, and two nudF6 partial suppressors were mapped to the nudA dynein heavy chain locus. Here we identified these two mutations. The nudAL1098F mutation resides in the stem region, and nudAR3086C is in the end of AAA4. These mutations partially suppress the phenotype of nudF deletion but do not suppress the phenotype exhibited by mutants of dynein intermediate chain and Arp1. Surprisingly, the stronger ΔnudF suppressor, nudAR3086C, causes an obvious decrease in the basal level of dynein's ATPase activity and an increase in dynein's distribution along microtubules. Thus, suppression of the ΔnudF phenotype may result from mechanisms other than simply the enhancement of dynein's ATPase activity. The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo. PMID:17237507

  4. The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane

    PubMed Central

    Weir, Nicholas R; Kamber, Roarke A; Martenson, James S

    2017-01-01

    Msp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-inducible gene expression to dissect Msp1 function. We found that a small fraction of peroxisomal Pex15, exaggerated by overexpression, is turned over by Msp1. Kinetic measurements guided by theoretical modeling revealed that Pex15 molecules at mitochondria display age-independent Msp1 sensitivity. By contrast, Pex15 molecules at peroxisomes are rapidly converted from an initial Msp1-sensitive to an Msp1-resistant state. Lastly, we show that Pex15 interacts with the peroxisomal membrane protein Pex3, which shields Pex15 from Msp1-dependent turnover. In sum, our work argues that Msp1 selects its substrates on the basis of their solitary membrane existence. PMID:28906250

  5. Ultrastructural changes and the distribution of arabinogalactan proteins during somatic embryogenesis of banana (Musa spp. AAA cv. 'Yueyoukang 1').

    PubMed

    Pan, Xiao; Yang, Xiao; Lin, Guimei; Zou, Ru; Chen, Houbin; Samaj, Jozef; Xu, Chunxiang

    2011-08-01

    A better understanding of somatic embryogenesis in banana (Musa spp.) may provide a practical way to improve regeneration of banana plants. In this study, we applied scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to visualize the ultrastructural changes during somatic embryogenesis of banana (Musa AAA cv. 'Yueyoukang 1'). We also used histological and immunohistochemical techniques with 16 monoclonal antibodies to study the spatial distribution and cellular/subcellular localization of different arabinogalactan protein (AGP) components of the cell wall during somatic embryogenesis. Histological study with periodic acid-Schiff staining documented diverse embryogenic stages from embryogenic cells (ECs) to the late embryos. SEM revealed a mesh-like structure on the surface of proembryos which represented an early structural marker of somatic embryogenesis. TEM showed that ECs were rich in juvenile mitochondria, endoplasmic reticulum and Golgi stacks. Cells in proembryos and early globular embryos resembled ECs, but they were more vacuolated, showed more regular nuclei and slightly more developed organelles. Immunocytochemical study revealed that the signal of most AGP epitopes was stronger in starch-rich cells when compared with typical ECs. The main AGP component in the extracellular matrix surface network of banana proembryos was the MAC204 epitope. Later, AGP immunolabelling patterns varied with the developmental stages of the embryos. These results about developmental regulation of AGP epitopes along with developmental changes in the ultrastructure of cells are providing new insights into the somatic embryogenesis of banana. Copyright © Physiologia Plantarum 2011.

  6. In-situ monitoring of blood glucose level for dialysis machine by AAA-battery-size ATR Fourier spectroscopy

    NASA Astrophysics Data System (ADS)

    Hosono, Satsuki; Sato, Shun; Ishida, Akane; Suzuki, Yo; Inohara, Daichi; Nogo, Kosuke; Abeygunawardhana, Pradeep K.; Suzuki, Satoru; Nishiyama, Akira; Wada, Kenji; Ishimaru, Ichiro

    2015-07-01

    For blood glucose level measurement of dialysis machines, we proposed AAA-battery-size ATR (Attenuated total reflection) Fourier spectroscopy in middle infrared light region. The proposed one-shot Fourier spectroscopic imaging is a near-common path and spatial phase-shift interferometer with high time resolution. Because numerous number of spectral data that is 60 (= camera frame rare e.g. 60[Hz]) multiplied by pixel number could be obtained in 1[sec.], statistical-averaging improvement realize high-accurate spectral measurement. We evaluated the quantitative accuracy of our proposed method for measuring glucose concentration in near-infrared light region with liquid cells. We confirmed that absorbance at 1600[nm] had high correlations with glucose concentrations (correlation coefficient: 0.92). But to measure whole-blood, complex light phenomenon caused from red blood cells, that is scattering and multiple reflection or so, deteriorate spectral data. Thus, we also proposed the ultrasound-assisted spectroscopic imaging that traps particles at standing-wave node. Thus, if ATR prism is oscillated mechanically, anti-node area is generated around evanescent light field on prism surface. By elimination complex light phenomenon of red blood cells, glucose concentration in whole-blood will be quantify with high accuracy. In this report, we successfully trapped red blood cells in normal saline solution with ultrasonic standing wave (frequency: 2[MHz]).

  7. Structural insights into the Escherichia coli lysine decarboxylases and molecular determinants of interaction with the AAA+ ATPase RavA

    PubMed Central

    Kandiah, Eaazhisai; Carriel, Diego; Perard, Julien; Malet, Hélène; Bacia, Maria; Liu, Kaiyin; Chan, Sze W. S.; Houry, Walid A.; Ollagnier de Choudens, Sandrine; Elsen, Sylvie; Gutsche, Irina

    2016-01-01

    The inducible lysine decarboxylase LdcI is an important enterobacterial acid stress response enzyme whereas LdcC is its close paralogue thought to play mainly a metabolic role. A unique macromolecular cage formed by two decamers of the Escherichia coli LdcI and five hexamers of the AAA+ ATPase RavA was shown to counteract acid stress under starvation. Previously, we proposed a pseudoatomic model of the LdcI-RavA cage based on its cryo-electron microscopy map and crystal structures of an inactive LdcI decamer and a RavA monomer. We now present cryo-electron microscopy 3D reconstructions of the E. coli LdcI and LdcC, and an improved map of the LdcI bound to the LARA domain of RavA, at pH optimal for their enzymatic activity. Comparison with each other and with available structures uncovers differences between LdcI and LdcC explaining why only the acid stress response enzyme is capable of binding RavA. We identify interdomain movements associated with the pH-dependent enzyme activation and with the RavA binding. Multiple sequence alignment coupled to a phylogenetic analysis reveals that certain enterobacteria exert evolutionary pressure on the lysine decarboxylase towards the cage-like assembly with RavA, implying that this complex may have an important function under particular stress conditions. PMID:27080013

  8. The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects

    PubMed Central

    Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A.

    2016-01-01

    Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. PMID:27257060

  9. The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects.

    PubMed

    Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A

    2016-09-19

    Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Experimental verification of the Acuros XB and AAA dose calculation adjacent to heterogeneous media for IMRT and RapidArc of nasopharygeal carcinoma.

    PubMed

    Kan, Monica W K; Leung, Lucullus H T; So, Ronald W K; Yu, Peter K N

    2013-03-01

    To compare the doses calculated by the Acuros XB (AXB) algorithm and analytical anisotropic algorithm (AAA) with experimentally measured data adjacent to and within heterogeneous medium using intensity modulated radiation therapy (IMRT) and RapidArc(®) (RA) volumetric arc therapy plans for nasopharygeal carcinoma (NPC). Two-dimensional dose distribution immediately adjacent to both air and bone inserts of a rectangular tissue equivalent phantom irradiated using IMRT and RA plans for NPC cases were measured with GafChromic(®) EBT3 films. Doses near and within the nasopharygeal (NP) region of an anthropomorphic phantom containing heterogeneous medium were also measured with thermoluminescent dosimeters (TLD) and EBT3 films. The measured data were then compared with the data calculated by AAA and AXB. For AXB, dose calculations were performed using both dose-to-medium (AXB_Dm) and dose-to-water (AXB_Dw) options. Furthermore, target dose differences between AAA and AXB were analyzed for the corresponding real patients. The comparison of real patient plans was performed by stratifying the targets into components of different densities, including tissue, bone, and air. For the verification of planar dose distribution adjacent to air and bone using the rectangular phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 98.7%, 99.5%, and 97.7% on the axial plane for AAA, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans, while they were 97.6%, 98.2%, and 97.7%, respectively, on the coronal plane. For the verification of planar dose distribution within the NP region of the anthropomorphic phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 95.1%, 91.3%, and 99.0% for AAA, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans. Within the NP region where air and bone were present, the film measurements represented the dose close to unit density water

  11. The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes.

    PubMed

    Mérai, Zsuzsanna; Chumak, Nina; García-Aguilar, Marcelina; Hsieh, Tzung-Fu; Nishimura, Toshiro; Schoft, Vera K; Bindics, János; Slusarz, Lucyna; Arnoux, Stéphanie; Opravil, Susanne; Mechtler, Karl; Zilberman, Daniel; Fischer, Robert L; Tamaru, Hisashi

    2014-11-11

    Centromeres mediate chromosome segregation and are defined by the centromere-specific histone H3 variant (CenH3)/centromere protein A (CENP-A). Removal of CenH3 from centromeres is a general property of terminally differentiated cells, and the persistence of CenH3 increases the risk of diseases such as cancer. However, active mechanisms of centromere disassembly are unknown. Nondividing Arabidopsis pollen vegetative cells, which transport engulfed sperm by extended tip growth, undergo loss of CenH3; centromeric heterochromatin decondensation; and bulk activation of silent rRNA genes, accompanied by their translocation into the nucleolus. Here, we show that these processes are blocked by mutations in the evolutionarily conserved AAA-ATPase molecular chaperone, CDC48A, homologous to yeast Cdc48 and human p97 proteins, both of which are implicated in ubiquitin/small ubiquitin-like modifier (SUMO)-targeted protein degradation. We demonstrate that CDC48A physically associates with its heterodimeric cofactor UFD1-NPL4, known to bind ubiquitin and SUMO, as well as with SUMO1-modified CenH3 and mutations in NPL4 phenocopy cdc48a mutations. In WT vegetative cell nuclei, genetically unlinked ribosomal DNA (rDNA) loci are uniquely clustered together within the nucleolus and all major rRNA gene variants, including those rDNA variants silenced in leaves, are transcribed. In cdc48a mutant vegetative cell nuclei, however, these rDNA loci frequently colocalized with condensed centromeric heterochromatin at the external periphery of the nucleolus. Our results indicate that the CDC48A(NPL4) complex actively removes sumoylated CenH3 from centromeres and disrupts centromeric heterochromatin to release bulk rRNA genes into the nucleolus for ribosome production, which fuels single nucleus-driven pollen tube growth and is essential for plant reproduction.

  12. The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes

    PubMed Central

    Mérai, Zsuzsanna; Chumak, Nina; García-Aguilar, Marcelina; Hsieh, Tzung-Fu; Nishimura, Toshiro; Schoft, Vera K.; Bindics, János; Ślusarz, Lucyna; Arnoux, Stéphanie; Opravil, Susanne; Mechtler, Karl; Zilberman, Daniel; Fischer, Robert L.; Tamaru, Hisashi

    2014-01-01

    Centromeres mediate chromosome segregation and are defined by the centromere-specific histone H3 variant (CenH3)/centromere protein A (CENP-A). Removal of CenH3 from centromeres is a general property of terminally differentiated cells, and the persistence of CenH3 increases the risk of diseases such as cancer. However, active mechanisms of centromere disassembly are unknown. Nondividing Arabidopsis pollen vegetative cells, which transport engulfed sperm by extended tip growth, undergo loss of CenH3; centromeric heterochromatin decondensation; and bulk activation of silent rRNA genes, accompanied by their translocation into the nucleolus. Here, we show that these processes are blocked by mutations in the evolutionarily conserved AAA-ATPase molecular chaperone, CDC48A, homologous to yeast Cdc48 and human p97 proteins, both of which are implicated in ubiquitin/small ubiquitin-like modifier (SUMO)-targeted protein degradation. We demonstrate that CDC48A physically associates with its heterodimeric cofactor UFD1-NPL4, known to bind ubiquitin and SUMO, as well as with SUMO1-modified CenH3 and mutations in NPL4 phenocopy cdc48a mutations. In WT vegetative cell nuclei, genetically unlinked ribosomal DNA (rDNA) loci are uniquely clustered together within the nucleolus and all major rRNA gene variants, including those rDNA variants silenced in leaves, are transcribed. In cdc48a mutant vegetative cell nuclei, however, these rDNA loci frequently colocalized with condensed centromeric heterochromatin at the external periphery of the nucleolus. Our results indicate that the CDC48ANPL4 complex actively removes sumoylated CenH3 from centromeres and disrupts centromeric heterochromatin to release bulk rRNA genes into the nucleolus for ribosome production, which fuels single nucleus-driven pollen tube growth and is essential for plant reproduction. PMID:25344531

  13. PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

    PubMed

    Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

    2015-11-01

    Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

  14. DnaA protein DNA-binding domain binds to Hda protein to promote inter-AAA+ domain interaction involved in regulatory inactivation of DnaA.

    PubMed

    Keyamura, Kenji; Katayama, Tsutomu

    2011-08-19

    Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis.

  15. DnaA Protein DNA-binding Domain Binds to Hda Protein to Promote Inter-AAA+ Domain Interaction Involved in Regulatory Inactivation of DnaA*

    PubMed Central

    Keyamura, Kenji; Katayama, Tsutomu

    2011-01-01

    Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis. PMID:21708944

  16. AAA+ ATPases Reptin and Pontin as potential diagnostic and prognostic biomarkers in salivary gland cancer - a short report.

    PubMed

    Mikesch, Jan-Henrik; Hartmann, Wolfgang; Angenendt, Linus; Huber, Otmar; Schliemann, Christoph; Arteaga, Maria Francisca; Wardelmann, Eva; Rudack, Claudia; Berdel, Wolfgang E; Stenner, Markus; Grünewald, Inga

    2018-06-05

    Salivary gland cancer (SGC) is a rare and heterogeneous disease with significant differences in recurrence and metastasis characteristics. As yet, little is known about the mechanisms underlying the initiation and/or progression of these diverse tumors. In recent years, the AAA+ ATPase family members Pontin (RuvBL1, Tip49a) and Reptin (RuvBL2, Tip49b) have been implicated in various processes, including transcription regulation, chromatin remodeling and DNA damage repair, that are frequently deregulated in cancer. The aim of this study was to assess the clinical and functional significance of Reptin and Pontin expression in SGC. Immunohistochemical staining of Pontin, Reptin, β-catenin, Cyclin D1, TP53 and MIB-1 was performed on a collection of 94 SGC tumor samples comprising 13 different histological subtypes using tissue microarrays. We found that Reptin and Pontin were expressed in the majority of SGC samples across all histological subtypes. Patients with a high Reptin expression showed a significantly inferior 5-year overall survival rate compared to patients with a low Reptin expression (47.7% versus 78.3%; p = 0.033), whereas no such difference was observed for Pontin. A high Reptin expression strongly correlated with a high expression of the proliferation marker MIB-1 (p = 0.003), the cell cycle regulator Cyclin D1 (p = 0.006), accumulation of TP53 as a surrogate p53 mutation marker (p = 0.042) and cytoplasmic β-catenin expression (p = 0.002). Increased Pontin expression was found to significantly correlate with both cytoplasmic and nuclear β-catenin expression (p = 0.037 and p = 0.018, respectively), which is indicative for its oncogenic function. Our results suggest a role of Reptin and Pontin in SGC tumor progression and/or patient survival. Therefore, SGC patients exhibiting a high Reptin expression may benefit from more aggressive therapeutic regimens. Future studies should clarify whether such patients may be considered

  17. Abdominal Aortic Aneurysm (AAA)

    MedlinePlus

    ... plaque buildup causes the walls of the abdominal aorta to become weak and bulge outward like a ... treated? What is an abdominal aortic aneurysm? The aorta, the largest artery in the body, is a ...

  18. AAAS Science Film Catalog.

    ERIC Educational Resources Information Center

    Seltz-Petrash, Ann, Ed.; Wolff, Kathryn, Ed.

    Currently available American 16mm films in the areas of pure science, applied science and technology, and science and society are identified and listed. Included are films that are available from commercial, government, university, and industry producers. The first section of the catalog lists in Dewey Decimal order films intended for junior high…

  19. 366-AAA_audio

    NASA Image and Video Library

    1969-11-17

    Apollo 12 Public Affairs Officer (PAO) Mission Commentary, November 17, 1969. This is an hour of audio covering communications occurring between 64 hours, 38 minutes into the mission, through 79 hours, 2 minutes which was on November 17, 1969, from 0300-17:09 CST. Transcript of attached audio is available at http://www.jsc.nasa.gov/history/mission_trans/AS12_PAO.PDF, on pages 207-224 of the 979-page document.

  20. The Multivesicular Bodies (MVBs)-Localized AAA ATPase LRD6-6 Inhibits Immunity and Cell Death Likely through Regulating MVBs-Mediated Vesicular Trafficking in Rice

    PubMed Central

    Liang, Sihui; Liang, Ruihong; Zhou, Xiaogang; Chen, Zhixiong; Zhao, Wen; Wang, Jing; Li, Weitao; He, Min; Yuan, Can; Miyamoto, Koji; Ma, Bingtian; Wang, Jichun; Qin, Peng; Chen, Weilan; Wang, Yuping; Wang, Wenming; Wu, Xianjun; Yamane, Hisakazu; Zhu, Lihuang; Li, Shigui; Chen, Xuewei

    2016-01-01

    Previous studies have shown that multivesicular bodies (MVBs)/endosomes-mediated vesicular trafficking may play key roles in plant immunity and cell death. However, the molecular regulation is poorly understood in rice. Here we report the identification and characterization of a MVBs-localized AAA ATPase LRD6-6 in rice. Disruption of LRD6-6 leads to enhanced immunity and cell death in rice. The ATPase activity and homo-dimerization of LRD6-6 is essential for its regulation on plant immunity and cell death. An ATPase inactive mutation (LRD6-6E315Q) leads to dominant-negative inhibition in plants. The LRD6-6 protein co-localizes with the MVBs marker protein RabF1/ARA6 and interacts with ESCRT-III components OsSNF7 and OsVPS2. Further analysis reveals that LRD6-6 is required for MVBs-mediated vesicular trafficking and inhibits the biosynthesis of antimicrobial compounds. Collectively, our study shows that the AAA ATPase LRD6-6 inhibits plant immunity and cell death most likely through modulating MVBs-mediated vesicular trafficking in rice. PMID:27618555

  1. Comparison of build-up region doses in oblique tangential 6 MV photon beams calculated by AAA and CCC algorithms in breast Rando phantom

    NASA Astrophysics Data System (ADS)

    Masunun, P.; Tangboonduangjit, P.; Dumrongkijudom, N.

    2016-03-01

    The purpose of this study is to compare the build-up region doses on breast Rando phantom surface with the bolus covered, the doses in breast Rando phantom and also the doses in a lung that is the heterogeneous region by two algorithms. The AAA in Eclipse TPS and the collapsed cone convolution algorithm in Pinnacle treatment planning system were used to plan in tangential field technique with 6 MV photon beam at 200 cGy total doses in Breast Rando phantom with bolus covered (5 mm and 10 mm). TLDs were calibrated with Cobalt-60 and used to measure the doses in irradiation process. The results in treatment planning show that the doses in build-up region and the doses in breast phantom were closely matched in both algorithms which are less than 2% differences. However, overestimate of doses in a lung (L2) were found in AAA with 13.78% and 6.06% differences at 5 mm and 10 mm bolus thickness, respectively when compared with CCC algorithm. The TLD measurements show the underestimate in buildup region and in breast phantom but the doses in a lung (L2) were overestimated when compared with the doses in the two plannings at both thicknesses of the bolus.

  2. Comparison of doses and NTCP to risk organs with enhanced inspiration gating and free breathing for left-sided breast cancer radiotherapy using the AAA algorithm.

    PubMed

    Edvardsson, Anneli; Nilsson, Martin P; Amptoulach, Sousana; Ceberg, Sofie

    2015-04-10

    The purpose of this study was to investigate the potential dose reduction to the heart, left anterior descending (LAD) coronary artery and the ipsilateral lung for patients treated with tangential and locoregional radiotherapy for left-sided breast cancer with enhanced inspiration gating (EIG) compared to free breathing (FB) using the AAA algorithm. The radiobiological implication of such dose sparing was also investigated. Thirty-two patients, who received tangential or locoregional adjuvant radiotherapy with EIG for left-sided breast cancer, were retrospectively enrolled in this study. Each patient was CT-scanned during FB and EIG. Similar treatment plans, with comparable target coverage, were created in the two CT-sets using the AAA algorithm. Further, the probability of radiation induced cardiac mortality and pneumonitis were calculated using NTCP models. For tangential treatment, the median V25Gy for the heart and LAD was decreased for EIG from 2.2% to 0.2% and 40.2% to 0.1% (p < 0.001), respectively, whereas there was no significant difference in V20Gy for the ipsilateral lung (p = 0.109). For locoregional treatment, the median V25Gy for the heart and LAD was decreased for EIG from 3.3% to 0.2% and 51.4% to 5.1% (p < 0.001), respectively, and the median ipsilateral lung V20Gy decreased from 27.0% for FB to 21.5% (p = 0.020) for EIG. The median excess cardiac mortality probability decreased from 0.49% for FB to 0.02% for EIG (p < 0.001) for tangential treatment and from 0.75% to 0.02% (p < 0.001) for locoregional treatment. There was no significant difference in risk of radiation pneumonitis for tangential treatment (p = 0.179) whereas it decreased for locoregional treatment from 6.82% for FB to 3.17% for EIG (p = 0.004). In this study the AAA algorithm was used for dose calculation to the heart, LAD and left lung when comparing the EIG and FB techniques for tangential and locoregional radiotherapy of breast cancer patients. The results support the dose and

  3. Levels of H-ras codon 61 CAA to AAA mutation: response to 4-ABP-treatment and Pms2-deficiency.

    PubMed

    Parsons, Barbara L; Delongchamp, Robert R; Beland, Frederick A; Heflich, Robert H

    2006-01-01

    DNA mismatch repair (MMR) deficiencies result in increased frequencies of spontaneous mutation and tumor formation. In the present study, we tested the hypothesis that a chemically-induced mutational response would be greater in a mouse with an MMR-deficiency than in the MMR-proficient mouse models commonly used to assay for chemical carcinogenicity. To accomplish this, the induction of H-ras codon 61 CAA-->AAA mutation was examined in Pms2 knockout mice (Pms2-/-, C57BL/6 background) and sibling wild-type mice (Pms2+/+). Groups of five or six neonatal male mice were treated with 0.3 micromol 4-aminobiphenyl (4-ABP) or the vehicle control, dimethylsulfoxide. Eight months after treatment, liver DNAs were isolated and analysed for levels of H-ras codon 61 CAA-->AAA mutation using allele-specific competitive blocker-PCR. In Pms2-proficient and Pms2-deficient mice, 4-ABP treatment caused an increase in mutant fraction (MF) from 1.65x10(-5) to 2.91x10(-5) and from 3.40x10(-5) to 4.70x10(-5), respectively. Pooling data from 4-ABP-treated and control mice, the approximately 2-fold increase in MF observed in Pms2-deficient as compared with Pms2-proficient mice was statistically significant (P=0.0207) and consistent with what has been reported previously in terms of induction of G:C-->T:A mutation in a Pms2-deficient background. Pooling data from both genotypes, the increase in H-ras MF in 4-ABP-treated mice, as compared with control mice, did not reach the 95% confidence level of statistical significance (P=0.0606). The 4-ABP treatment caused a 1.76-fold and 1.38-fold increase in average H-ras MF in Pms2-proficient and Pms2-deficient mice, respectively. Furthermore, the levels of induced mutation in Pms2-proficient and Pms2-deficient mice were nearly identical (1.26x10(-5) and 1.30x10(-5), respectively). We conclude that Pms2-deficiency does not result in an amplification of the H-ras codon 61 CAA-->AAA mutational response induced by 4-ABP.

  4. 9-AAA inhibits growth and induces apoptosis in human melanoma A375 and rat prostate adenocarcinoma AT-2 and Mat-LyLu cell lines but does not affect the growth and viability of normal fibroblasts.

    PubMed

    Korohoda, Włodzimierz; Hapek, Anna; Pietrzak, Monika; Ryszawy, Damian; Madeja, Zbigniew

    2016-11-01

    The present study found that, similarly to 5-fluorouracil, low concentrations (1-10 µM) of 9-aminoacridine (9-AAA) inhibited the growth of the two rat prostate cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line. However, at the same concentrations, 9-AAA had no effect on the growth and apoptosis of normal human skin fibroblasts (HSFs). The differences between the cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in malignancy, were found to be relatively small compared with the differences between normal HSFs and the cancer cell lines. Visible effects on the cell growth and survival of tumor cell lines were observed after 24-48 h of treatment with 9-AAA, and increased over time. The inhibition of cancer cell growth was found to be due to the gradually increasing number of cells dying by apoptosis, which was observed using two methods, direct counting and FlowSight analysis. Simultaneously, cell motile activity decreased to the same degree in cancer and normal cells within the first 8 h of incubation in the presence of 9-AAA. The results presented in the current study suggest that short-lasting tests for potential anticancer substances can be insufficient; which may result in cell type-dependent differences in the responses of cells to tested compounds that act with a delay being overlooked. The observed differences in responses between normal human fibroblasts and cancer cells to 9-AAA show the requirement for additional studies to be performed simultaneously on differently reacting cancer and normal cells, to determine the molecular mechanisms responsible for these differences.

  5. Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

    PubMed Central

    Martinelli, Paola; Cherukuri, Praveen F.; Teer, Jamie K.; Hansen, Nancy F.; Cruz, Pedro; Mullikin for the NISC Comparative Sequencing Program, James C.; Blakesley, Robert W.; Golas, Gretchen; Kwan, Justin; Sandler, Anthony; Fuentes Fajardo, Karin; Markello, Thomas; Tifft, Cynthia; Blackstone, Craig; Rugarli, Elena I.; Langer, Thomas; Gahl, William A.; Toro, Camilo

    2011-01-01

    We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias. PMID:22022284

  6. TU-C-BRE-05: Clinical Implications of AAA Commissioning Errors and Ability of Common Commissioning ' Credentialing Procedures to Detect Them

    SciTech Connect

    McVicker, A; Oldham, M; Yin, F

    2014-06-15

    Purpose: To test the ability of the TG-119 commissioning process and RPC credentialing to detect errors in the commissioning process for a commercial Treatment Planning System (TPS). Methods: We introduced commissioning errors into the commissioning process for the Anisotropic Analytical Algorithm (AAA) within the Eclipse TPS. We included errors in Dosimetric Leaf Gap (DLG), electron contamination, flattening filter material, and beam profile measurement with an inappropriately large farmer chamber (simulated using sliding window smoothing of profiles). We then evaluated the clinical impact of these errors on clinical intensity modulated radiation therapy (IMRT) plans (head and neck, low and intermediate riskmore » prostate, mesothelioma, and scalp) by looking at PTV D99, and mean and max OAR dose. Finally, for errors with substantial clinical impact we determined sensitivity of the RPC IMRT film analysis at the midpoint between PTV and OAR using a 4mm distance to agreement metric, and of a 7% TLD dose comparison. We also determined sensitivity of the 3 dose planes of the TG-119 C-shape IMRT phantom using gamma criteria of 3% 3mm. Results: The largest clinical impact came from large changes in the DLG with a change of 1mm resulting in up to a 5% change in the primary PTV D99. This resulted in a discrepancy in the RPC TLDs in the PTVs and OARs of 7.1% and 13.6% respectively, which would have resulted in detection. While use of incorrect flattening filter caused only subtle errors (<1%) in clinical plans, the effect was most pronounced for the RPC TLDs in the OARs (>6%). Conclusion: The AAA commissioning process within the Eclipse TPS is surprisingly robust to user error. When errors do occur, the RPC and TG-119 commissioning credentialing criteria are effective at detecting them; however OAR TLDs are the most sensitive despite the RPC currently excluding them from analysis.« less

  7. Unique ATPase site architecture triggers cis-mediated synchronized ATP binding in heptameric AAA+-ATPase domain of flagellar regulatory protein FlrC.

    PubMed

    Dey, Sanjay; Biswas, Maitree; Sen, Udayaditya; Dasgupta, Jhimli

    2015-04-03

    Bacterial enhancer-binding proteins (bEBPs) oligomerize through AAA(+) domains and use ATP hydrolysis-driven energy to isomerize the RNA polymerase-σ(54) complex during transcriptional initiation. Here, we describe the first structure of the central AAA(+) domain of the flagellar regulatory protein FlrC (FlrC(C)), a bEBP that controls flagellar synthesis in Vibrio cholerae. Our results showed that FlrC(C) forms heptamer both in nucleotide (Nt)-free and -bound states without ATP-dependent subunit remodeling. Unlike the bEBPs such as NtrC1 or PspF, a novel cis-mediated "all or none" ATP binding occurs in the heptameric FlrC(C), because constriction at the ATPase site, caused by loop L3 and helix α7, restricts the proximity of the trans-protomer required for Nt binding. A unique "closed to open" movement of Walker A, assisted by trans-acting "Glu switch" Glu-286, facilitates ATP binding and hydrolysis. Fluorescence quenching and ATPase assays on FlrC(C) and mutants revealed that although Arg-349 of sensor II, positioned by trans-acting Glu-286 and Tyr-290, acts as a key residue to bind and hydrolyze ATP, Arg-319 of α7 anchors ribose and controls the rate of ATP hydrolysis by retarding the expulsion of ADP. Heptameric state of FlrC(C) is restored in solution even with the transition state mimicking ADP·AlF3. Structural results and pulldown assays indicated that L3 renders an in-built geometry to L1 and L2 causing σ(54)-FlrC(C) interaction independent of Nt binding. Collectively, our results underscore a novel mechanism of ATP binding and σ(54) interaction that strives to understand the transcriptional mechanism of the bEBPs, which probably interact directly with the RNA polymerase-σ(54) complex without DNA looping. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. ACB-PCR measurement of spontaneous and furan-induced H-ras codon 61 CAA to CTA and CAA to AAA mutation in B6C3F1 mouse liver.

    PubMed

    Banda, Malathi; Recio, Leslie; Parsons, Barbara L

    2013-10-01

    Furan is a rodent liver carcinogen, but the mode of action for furan hepatocarcinogenicity is unclear. H-ras codon 61 mutations have been detected in spontaneous liver tumors of B6C3F1 mice, and the fraction of liver tumors carrying H-ras codon 61 CAA to AAA mutation increased in furan-treated mice. Allele-specific competitive blocker PCR (ACB-PCR) has been used previously to quantify early, carcinogen-induced increases in tumor-associated mutations. The present pilot study investigated whether furan drives clonal expansion of pre-existing H-ras mutant cells in B6C3F1 mouse liver. H-ras codon 61 CAA to CTA and CAA to AAA mutations were measured in DNA isolated from liver tissue of female mice treated with 0, 1, 2, 4, or 8 mg furan/kg body weight, five days per week for three weeks, using five mice per treatment group. Spontaneous levels of mutation were low, with two of five control mice having an H-ras codon 61 CTA or AAA mutant fraction (MF) greater than 10(-5) . Several furan-treated mice had H-ras codon 61 AAA or CTA MFs greater than those measured in control mice and lower bound estimates of induced MF were calculated. However, no statistically-significant differences were observed between treatment groups. Therefore, while sustained exposure to furan is carcinogenic, at the early stage of carcinogenesis examined in this study (three weeks), there was not a significant expansion of H-ras mutant cells. Copyright © 2013 Wiley Periodicals, Inc.

  9. Expression in Whole Blood Samples of miRNA-191 and miRNA-455-3p in Patients with AAA and Their Relationship to Clinical Outcomes after Endovascular Repair.

    PubMed

    Tenorio, Emanuel Junio Ramos; Braga, Andre Felipe Farias; Tirapelli, Daniela Pretti Da Cunha; Ribeiro, Mauricio Serra; Piccinato, Carlos Eli; Joviliano, Edwaldo Edner

    2018-03-05

    The purpose of this study was to quantify and evaluate the expression response of miRNA-191 and miRNA-455-3p endovascular repair of abdominal aortic aneurysm (AAA) based in whole blood samples. This report describes a prospective study of a single center of 30 patients with AAA who underwent endovascular repair. Blood samples were collected preoperatively and 6 months postoperatively. The differential expression of the miRNAs was performed by the real-time polymerase chain reaction method, after extraction of the RNA from the blood samples at the 2 moments. In addition, bioinformatic tools were used to determine pathophysiological pathways related to AAA. The miR-191 and miR-455-3p were overexpressed preoperatively. After 6 months postoperatively, miR-191 (median 0.98, IQR 0.5-2.1, P < 0.0001) and miR-455-3p (median 1.4, IQR 0.6-3.1, P = 0.0003) presented a significant reduction in their expressions. There was no correlation between the diameter of the aneurysm and the expression of the miRNAs studied. In addition, analysis of the influence of the various types of devices used for the endovascular treatment of AAA showed no significant differences in the expression of miR-191 and miR-455-3p. Exclusion of the aneurysmal sac after endovascular treatment induces a decrease in the expression of the studied miRNAs in whole blood samples, which suggests a possible use of them as biomarkers of therapeutic success. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. A Fragment-Based Ligand Screen Against Part of a Large Protein Machine: The ND1 Domains of the AAA+ ATPase p97/VCP.

    PubMed

    Chimenti, Michael S; Bulfer, Stacie L; Neitz, R Jeffrey; Renslo, Adam R; Jacobson, Matthew P; James, Thomas L; Arkin, Michelle R; Kelly, Mark J S

    2015-07-01

    The ubiquitous AAA+ ATPase p97 functions as a dynamic molecular machine driving several cellular processes. It is essential in regulating protein homeostasis, and it represents a potential drug target for cancer, particularly when there is a greater reliance on the endoplasmic reticulum-associated protein degradation pathway and ubiquitin-proteasome pathway to degrade an overabundance of secreted proteins. Here, we report a case study for using fragment-based ligand design approaches against this large and dynamic hexamer, which has multiple potential binding sites for small molecules. A screen of a fragment library was conducted by surface plasmon resonance (SPR) and followed up by nuclear magnetic resonance (NMR), two complementary biophysical techniques. Virtual screening was also carried out to examine possible binding sites for the experimental hits and evaluate the potential utility of fragment docking for this target. Out of this effort, 13 fragments were discovered that showed reversible binding with affinities between 140 µM and 1 mM, binding stoichiometries of 1:1 or 2:1, and good ligand efficiencies. Structural data for fragment-protein interactions were obtained with residue-specific [U-(2)H] (13)CH3-methyl-labeling NMR strategies, and these data were compared to poses from docking. The combination of virtual screening, SPR, and NMR enabled us to find and validate a number of interesting fragment hits and allowed us to gain an understanding of the structural nature of fragment binding. © 2015 Society for Laboratory Automation and Screening.

  11. Peroxisomal monoubiquitinated PEX5 interacts with the AAA ATPases PEX1 and PEX6 and is unfolded during its dislocation into the cytosol.

    PubMed

    Pedrosa, Ana G; Francisco, Tânia; Bicho, Diana; Dias, Ana F; Barros-Barbosa, Aurora; Hagmann, Vera; Dodt, Gabriele; Rodrigues, Tony A; Azevedo, Jorge E

    2018-06-08

    PEX1 and PEX6 are two members of the ATPases Associated with diverse cellular Activities (AAA) family and the core components of the receptor export module (REM) of the peroxisomal matrix protein import machinery. Their role is to extract monoubiquitinated PEX5, the peroxisomal protein shuttling receptor, from the peroxisomal membrane docking/translocation module (DTM), so that a new cycle of protein transportation can start. Recent data have shown that PEX1 and PEX6 form a heterohexameric complex which unfolds substrates by processive threading. However, whether the natural substrate of the PEX1.PEX6 complex is monoubiquitinated PEX5 (Ub-PEX5) itself or some Ub-PEX5-interacting component(s) of the DTM remains unknown. In this work, we used an established cell-free in vitro system coupled with photoaffinity crosslinking and protein PEGylation assays to address this problem. We provide evidence suggesting that DTM-embedded Ub-PEX5 interacts directly with both PEX1 and PEX6 through its ubiquitin moiety and that the PEX5 polypeptide chain is globally unfolded during the ATP-dependent extraction event. These findings strongly suggest that DTM-embedded Ub-PEX5 is a bona fide substrate of the PEX1.PEX6 complex. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  12. In response to an open invitation for comments on AAAS project 2061's Benchmark books on science. Part 1: documentation of serious errors in cell biology.

    PubMed

    Ling, Gilbert

    2006-01-01

    Project 2061 was founded by the American Association for the Advancement of Science (AAAS) to improve secondary school science education. An in-depth study of ten 9 to 12th grade biology textbooks led to the verdict that none conveyed "Big Ideas" that would give coherence and meaning to the profusion of lavishly illustrated isolated details. However, neither the Project report itself nor the Benchmark books put out earlier by the Project carries what deserves the designation of "Big Ideas." Worse, in the two earliest-published Benchmark books, the basic unit of all life forms--the living cell--is described as a soup enclosed by a cell membrane, that determines what can enter or leave the cell. This is astonishing since extensive experimental evidence has unequivocally disproved this idea 60 years ago. A "new" version of the membrane theory brought in to replace the discredited (sieve) version is the pump model--currently taught as established truth in all high-school and college biology textbooks--was also unequivocally disproved 40 years ago. This comment is written partly in response to Bechmark's gracious open invitation for ideas to improve the books and through them, to improve US secondary school science education.

  13. Engagement of Arginine Finger to ATP Triggers Large Conformational Changes in NtrC1 AAA+ ATPase for Remodeling Bacterial RNA Polymerase

    SciTech Connect

    Chen, Baoyu; Sysoeva, Tatyana A.; Chowdhury, Saikat

    The NtrC-like AAA+ ATPases control virulence and other important bacterial activities through delivering mechanical work to {sigma}54-RNA polymerase to activate transcription from {sigma}54-dependent genes. We report the first crystal structure for such an ATPase, NtrC1 of Aquifex aeolicus, in which the catalytic arginine engages the {gamma}-phosphate of ATP. Comparing the new structure with those previously known for apo and ADP-bound states supports a rigid-body displacement model that is consistent with large-scale conformational changes observed by low-resolution methods. First, the arginine finger induces rigid-body roll, extending surface loops above the plane of the ATPase ring to bind {sigma}54. Second, ATP hydrolysismore » permits Pi release and retraction of the arginine with a reversed roll, remodeling {sigma}54-RNAP. This model provides a fresh perspective on how ATPase subunits interact within the ring-ensemble to promote transcription, directing attention to structural changes on the arginine-finger side of an ATP-bound interface.« less

  14. TIMP‑3 suppresses the proliferation and migration of SMCs from the aortic neck of atherosclerotic AAA in rabbits, via decreased MMP‑2 and MMP‑9 activity, and reduced TNF‑α expression.

    PubMed

    Zhai, Huan; Qi, Xun; Li, Zixuan; Zhang, Wei; Li, Chenguang; Ji, Lu; Xu, Ke; Zhong, Hongshan

    2018-06-26

    The present study investigated the role of tissue inhibitor of matrix metalloproteinase‑3 (TIMP‑3) in regulating the proliferation, migration, apoptosis and activity of matrix metalloproteinase (MMP)‑2 and ‑9, during the development of an atherosclerotic abdominal artery aneurysm (AAA). Experiments were conducted using rabbit AAA neck (NA) smooth muscle cells (SMCs), to investigate the potential for TIMP‑3 to be used as a novel stent coating in preventing aortic dilation adjacent to the AAA. The atherosclerotic AAA model was induced in New Zealand white rabbits via a 6‑week high‑cholesterol diet, followed by incubation of the targeted aortic region with elastase. SMCs were isolated from the aorta adjacent to the aneurysm 30 days after AAA model induction, and stimulated with 3, 10, 30 or 100 ng/ml TIMP‑3. Cell proliferation was investigated using Cell Counting Kit‑8 reagent, migration was examined using a Boyden chamber assay and apoptotic rate was analyzed using the Annexin V‑fluorescein isothiocyanate Apoptosis Detection kit. Gelatin zymography and ELISA were used to measure the activity of MMP‑2 and MMP‑9, and the expression of tumor necrosis factor‑α (TNF‑α), respectively. Analysis of cell proliferation indicated that 10, 30 and 100 ng/ml TIMP‑3 reduced cell viability. Cell migration was decreased by 10, 30 and 100 ng/ml TIMP‑3. MMP‑2 activity was inhibited by 10, 30 and 100 ng/ml TIMP‑3, and MMP‑9 activity was suppressed by 30 and 100 ng/ml TIMP‑3. The protein levels of secreted TNF‑α were reduced by 10, 30 and 100 ng/ml TIMP‑3. The present study demonstrated the ability of 30 and 100 ng/ml TIMP‑3 to attenuate migration and proliferation, and to inhibit the activity of MMP‑2, MMP‑9 and TNF‑α secretion of NA SMCs. In conclusion, TIMP‑3 may be considered a potential therapeutic drug for use in a novel drug‑eluting stent, to attenuate the progressive dilation of the aortic NA.

  15. Upregulation of MicroRNA-15a Contributes to Pathogenesis of Abdominal Aortic Aneurysm (AAA) by Modulating the Expression of Cyclin-Dependent Kinase Inhibitor 2B (CDKN2B).

    PubMed

    Gao, Peng; Si, Jiyuan; Yang, Bin; Yu, Jixiang

    2017-02-18

    BACKGROUND The objective of the present study was to identify the association between miR-15a-5p and CDKN2B, and their roles in regulating the development of abdominal aortic aneurysm (AAA). MATERIAL AND METHODS We searched the miRNA database online (www.mirdb.org) and used a luciferase reporter assay system to study the regulatory relationship between miR-15a-5p and CDKN2B. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CDKN2B among different patient groups (participants with abdominal aortic aneurysm (AAA) and normal controls) or cells treated with scramble control, miR-15a-5p mimics, CDKN2B siRNA, and miR-15a-5p inhibitors. RESULTS We found that CDKN2B was a virtual target of miR-15a-5p with potential binding sites in the 3'UTR of CDKN2B (77-83 bp). We also showed that miR-15a-5p could bind to the CDKN2B 3'UTR, resulting in a significant decrease in luciferase activity compared with the scramble control. Furthermore, we found that the cells isolated from AAA participants showed an over-expression of miR-15a-5p compared to the normal controls, while the CDKN2B mRNA and protein expression level of the AAA group were much lower than the normal control group. Additionally, the expression of CDKN2B mRNA and the protein of the cells transfected with miR-15a-5p mimics and CDKN2B siRNA was downregulated, while the cells showed upregulated expression subsequent to transfection with miR-15a-5p inhibitors compared to the scramble control. CONCLUSIONS The data revealed a negative regulatory role of miR-15a-5p in the apoptosis of smooth muscle cells via targeting CDKN2B, and showed that miR-15a-5p could be a novel therapeutic target of AAA.

  16. Identification and expression analysis of four 14-3-3 genes during fruit ripening in banana (Musa acuminata L. AAA group, cv. Brazilian).

    PubMed

    Li, Mei-Ying; Xu, Bi-Yu; Liu, Ju-Hua; Yang, Xiao-Liang; Zhang, Jian-Bin; Jia, Cai-Hong; Ren, Li-Cheng; Jin, Zhi-Qiang

    2012-02-01

    To investigate the regulation of 14-3-3 proteins in banana (Musa acuminata L. AAA group, cv. Brazilian) fruit postharvest ripening, four cDNAs encoding 14-3-3 proteins were isolated from banana and designated as Ma-14-3-3a, Ma-14-3-3c, Ma-14-3-3e, and Ma-14-3-3i, respectively. Amino acid sequence alignment showed that the four 14-3-3 proteins shared a highly conserved core structure and variable C-terminal as well as N-terminal regions with 14-3-3 proteins from other plant species. Phylogenetic analysis revealed that the four 14-3-3 genes belong to the non-ε groups. They were differentially and specifically expressed in various tissues. Real-time RT-PCR analysis indicated that these four genes function differentially during banana fruit postharvest ripening. Three genes, Ma-14-3-3a, Ma-14-3-3c, and Ma-14-3-3e, were significantly induced by exogenous ethylene treatment. However, gene function differed in naturally ripened fruits. Ethylene could induce Ma-14-3-3c expression during postharvest ripening, but expression patterns of Ma-14-3-3a and Ma-14-3-3e suggest that these two genes appear to be involved in regulating ethylene biosynthesis during fruit ripening. No obvious relationship emerged between Ma-14-3-3i expression in naturally ripened and 1-MCP (1-methylcyclopropene)-treated fruit groups during fruit ripening. These results indicate that the 14-3-3 proteins might be involved in various regulatory processes of banana fruit ripening. Further studies will mainly focus on revealing the detailed biological mechanisms of these four 14-3-3 genes in regulating banana fruit postharvest ripening.

  17. The AAA-ATPase NVL2 is a component of pre-ribosomal particles that interacts with the DExD/H-box RNA helicase DOB1

    SciTech Connect

    Nagahama, Masami; Yamazoe, Takeshi; Hara, Yoshimitsu

    2006-08-04

    Nuclear VCP/p97-like protein 2 (NVL2) is a member of the chaperone-like AAA-ATPase family with two conserved ATP-binding modules. Our previous studies have shown that NVL2 is localized to the nucleolus by interacting with ribosomal protein L5 and may participate in ribosome synthesis, a process involving various non-ribosomal factors including chaperones and RNA helicases. Here, we show that NVL2 is associated with pre-ribosomal particles in the nucleus. Moreover, we used yeast two-hybrid and co-immunoprecipitation assays to identify an NVL2-interacting protein that could yield insights into NVL2 function in ribosome biogenesis. We found that NVL2 interacts with DOB1, a DExD/H-box RNA helicase,more » whose yeast homologue functions in a late stage of the 60S subunit synthesis. DOB1 can interact with a second ATP-binding module mutant of NVL2, which shows a dominant negative effect on ribosome synthesis. In contrast, it cannot interact with a first ATP-binding module mutant, which does not show the dominant negative effect. When the dominant negative mutant of NVL2 was overexpressed in cells, DOB1 appeared to remain associated with nuclear pre-ribosomal particles. Such accumulation was not observed upon overexpression of wild-type NVL2 or a nondominant-negative mutant. Taken together, our results suggest that NVL2 might regulate the association/dissociation reaction of DOB1 with pre-ribosomal particles by acting as a molecular chaperone.« less

  18. Interaction between the AAA ATPase p97/VCP and a concealed UBX domain in the copper transporter ATP7A is associated with motor neuron degeneration.

    PubMed

    Yi, Ling; Kaler, Stephen G

    2018-05-18

    The copper-transporting ATPase ATP7A contains eight transmembrane domains and is required for normal human copper homeostasis. Mutations in the ATP7A gene may lead to infantile-onset cerebral degeneration (Menkes disease); occipital horn syndrome (OHS), a related but much milder illness; or an adult-onset isolated distal motor neuropathy. The ATP7A missense mutation T994I is located in the sixth transmembrane domain of ATP7A, represents one of the variants associated with the latter phenotype, and is associated with an abnormal interaction with p97/valosin-containing protein (VCP), a hexameric AAA ATPase (ATPase associated with diverse cellular activities) with multiple biological functions. In this study, we further characterized this interaction and discovered a concealed UBX domain in the third lumenal loop of ATP7A, between its fifth and sixth transmembrane domains. We show that the T994I substitution results in conformational exposure of the UBX domain, which then binds the N-terminal domain of p97/VCP. We also show that this abnormal interaction occurs at or near the cell plasma membrane. The UBX domain has a conserved hydrophobic FP (Phe-Pro) motif, and substitution with di-alanine abrogated the interaction and restored the proper intracellular localization of ATP7A in the trans -Golgi network. Using protein MS, we identified potential coordinating components of the ATP7A T994I -p97 complex, including NSFL1 cofactor (NSF1C or p47) that may be relevant to the pathophysiology and clinical effects associated with ATP7A T994I Our study represents the first report of p97/VCP binding to a UBX domain that is not normally exposed, resulting in an aberrant protein-protein interaction leading to motor neuron degeneration.

  19. Novel essential residues of Hda for interaction with DnaA in the regulatory inactivation of DnaA: unique roles for Hda AAA Box VI and VII motifs.

    PubMed

    Nakamura, Kenta; Katayama, Tsutomu

    2010-04-01

    Escherichia coli ATP-DnaA initiates chromosomal replication. For preventing extra-initiations, a complex of ADP-Hda and the DNA-loaded replicase clamp promotes DnaA-ATP hydrolysis, yielding inactive ADP-DnaA. However, the Hda-DnaA interaction mode remains unclear except that the Hda Box VII Arg finger (Arg-153) and DnaA sensor II Arg-334 within each AAA(+) domain are crucial for the DnaA-ATP hydrolysis. Here, we demonstrate that direct and functional interaction of ADP-Hda with DnaA requires the Hda residues Ser-152, Phe-118 and Asn-122 as well as Hda Arg-153 and DnaA Arg-334. Structural analyses suggest intermolecular interactions between Hda Ser-152 and DnaA Arg-334 and between Hda Phe-118 and the DnaA Walker B motif region, in addition to an intramolecular interaction between Hda Asn-122 and Arg-153. These interactions likely sustain a specific association of ADP-Hda and DnaA, promoting DnaA-ATP hydrolysis. Consistently, ATP-DnaA and ADP-DnaA interact with the ADP-Hda-DNA-clamp complex with similar affinities. Hda Phe-118 and Asn-122 are contained in the Box VI region, and their hydrophobic and electrostatic features are basically conserved in the corresponding residues of other AAA(+) proteins, suggesting a conserved role for Box VI. These findings indicate novel interaction mechanisms for Hda-DnaA as well as a potentially fundamental mechanism in AAA(+) protein interactions.

  20. SU-F-P-39: End-To-End Validation of a 6 MV High Dose Rate Photon Beam, Configured for Eclipse AAA Algorithm Using Golden Beam Data, for SBRT Treatments Using RapidArc

    SciTech Connect

    Ferreyra, M; Salinas Aranda, F; Dodat, D

    Purpose: To use end-to-end testing to validate a 6 MV high dose rate photon beam, configured for Eclipse AAA algorithm using Golden Beam Data (GBD), for SBRT treatments using RapidArc. Methods: Beam data was configured for Varian Eclipse AAA algorithm using the GBD provided by the vendor. Transverse and diagonals dose profiles, PDDs and output factors down to a field size of 2×2 cm2 were measured on a Varian Trilogy Linac and compared with GBD library using 2% 2mm 1D gamma analysis. The MLC transmission factor and dosimetric leaf gap were determined to characterize the MLC in Eclipse. Mechanical andmore » dosimetric tests were performed combining different gantry rotation speeds, dose rates and leaf speeds to evaluate the delivery system performance according to VMAT accuracy requirements. An end-to-end test was implemented planning several SBRT RapidArc treatments on a CIRS 002LFC IMRT Thorax Phantom. The CT scanner calibration curve was acquired and loaded in Eclipse. PTW 31013 ionization chamber was used with Keithley 35617EBS electrometer for absolute point dose measurements in water and lung equivalent inserts. TPS calculated planar dose distributions were compared to those measured using EPID and MapCheck, as an independent verification method. Results were evaluated with gamma criteria of 2% dose difference and 2mm DTA for 95% of points. Results: GBD set vs. measured data passed 2% 2mm 1D gamma analysis even for small fields. Machine performance tests show results are independent of machine delivery configuration, as expected. Absolute point dosimetry comparison resulted within 4% for the worst case scenario in lung. Over 97% of the points evaluated in dose distributions passed gamma index analysis. Conclusion: Eclipse AAA algorithm configuration of the 6 MV high dose rate photon beam using GBD proved efficient. End-to-end test dose calculation results indicate it can be used clinically for SBRT using RapidArc.« less

  1. NOUS41 KWBC 061721 AAA

    Science.gov Websites

    . UPCOMING CHANGES...THE CHANGES LISTED BELOW WILL BE INCORPORATED INTO THE MODEL ON THE EFFECTIVE CHANGE /WPS/. IF YOU HAVE ANY QUESTIONS CONCERNING THESE CHANGES...PLEASE CONTACT: GEOFF DIMEGO NCEP

  2. The major-effect quantitative trait locus CsARN6.1 encodes an AAA ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation.

    PubMed

    Xu, Xuewen; Ji, Jing; Xu, Qiang; Qi, Xiaohua; Weng, Yiqun; Chen, Xuehao

    2018-03-01

    In plants, the formation of hypocotyl-derived adventitious roots (ARs) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole-genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL, ARN6.1, that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that CsARN6.1 is the most possible candidate for ARN6.1 which encodes an AAA ATPase. The increased formation of ARs under waterlogging in Zaoer-N could be attributed to a non-synonymous SNP in the coiled-coil domain region of this gene. CsARN6.1 increases the number of ARs via its ATPase activity. Ectopic expression of CsARN6.1 in Arabidopsis resulted in better rooting ability and lateral root development in transgenic plants. Transgenic cucumber expressing the CsARN6.1 Asp allele from Zaoer-N exhibited a significant increase in number of ARs compared with the wild type expressing the allele from Pepino under waterlogging conditions. Taken together, these data support that the AAA ATPase gene CsARN6.1 has an important role in increasing cucumber AR formation and waterlogging tolerance. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  3. SU-E-T-196: Comparative Analysis of Surface Dose Measurements Using MOSFET Detector and Dose Predicted by Eclipse - AAA with Varying Dose Calculation Grid Size

    SciTech Connect

    Badkul, R; Nejaiman, S; Pokhrel, D

    2015-06-15

    Purpose: Skin dose can be the limiting factor and fairly common reason to interrupt the treatment, especially for treating head-and-neck with Intensity-modulated-radiation-therapy(IMRT) or Volumetrically-modulated - arc-therapy (VMAT) and breast with tangentially-directed-beams. Aim of this study was to investigate accuracy of near-surface dose predicted by Eclipse treatment-planning-system (TPS) using Anisotropic-Analytic Algorithm (AAA)with varying calculation grid-size and comparing with metal-oxide-semiconductor-field-effect-transistors(MOSFETs)measurements for a range of clinical-conditions (open-field,dynamic-wedge, physical-wedge, IMRT,VMAT). Methods: QUASAR™-Body-Phantom was used in this study with oval curved-surfaces to mimic breast, chest wall and head-and-neck sites.A CT-scan was obtained with five radio-opaque markers(ROM) placed on the surface of phantom to mimic themore » range of incident angles for measurements and dose prediction using 2mm slice thickness.At each ROM, small structure(1mmx2mm) were contoured to obtain mean-doses from TPS.Calculations were performed for open-field,dynamic-wedge,physical-wedge,IMRT and VMAT using Varian-21EX,6&15MV photons using twogrid-sizes:2.5mm and 1mm.Calibration checks were performed to ensure that MOSFETs response were within ±5%.Surface-doses were measured at five locations and compared with TPS calculations. Results: For 6MV: 2.5mm grid-size,mean calculated doses(MCD)were higher by 10%(±7.6),10%(±7.6),20%(±8.5),40%(±7.5),30%(±6.9) and for 1mm grid-size MCD were higher by 0%(±5.7),0%(±4.2),0%(±5.5),1.2%(±5.0),1.1% (±7.8) for open-field,dynamic-wedge,physical-wedge,IMRT,VMAT respectively.For 15MV: 2.5mm grid-size,MCD were higher by 30%(±14.6),30%(±14.6),30%(±14.0),40%(±11.0),30%(±3.5)and for 1mm grid-size MCD were higher by 10% (±10.6), 10%(±9.8),10%(±8.0),30%(±7.8),10%(±3.8) for open-field, dynamic-wedge, physical-wedge, IMRT, VMAT respectively.For 6MV, 86% and 56% of all measured

  4. The BiP Molecular Chaperone Plays Multiple Roles during the Biogenesis of TorsinA, an AAA+ ATPase Associated with the Neurological Disease Early-onset Torsion Dystonia*

    PubMed Central

    Zacchi, Lucía F.; Wu, Hui-Chuan; Bell, Samantha L.; Millen, Linda; Paton, Adrienne W.; Paton, James C.; Thomas, Philip J.; Zolkiewski, Michal; Brodsky, Jeffrey L.

    2014-01-01

    Early-onset torsion dystonia (EOTD) is a neurological disorder characterized by involuntary and sustained muscle contractions that can lead to paralysis and abnormal posture. EOTD is associated with the deletion of a glutamate (ΔE) in torsinA, an endoplasmic reticulum (ER) resident AAA+ ATPase. To date, the effect of ΔE on torsinA and the reason that this mutation results in EOTD are unclear. Moreover, there are no specific therapeutic options to treat EOTD. To define the underlying biochemical defects associated with torsinAΔE and to uncover factors that might be targeted to offset defects associated with torsinAΔE, we developed a yeast torsinA expression system and tested the roles of ER chaperones in mediating the folding and stability of torsinA and torsinAΔE. We discovered that the ER lumenal Hsp70, BiP, an associated Hsp40, Scj1, and a nucleotide exchange factor, Lhs1, stabilize torsinA and torsinAΔE. BiP also maintained torsinA and torsinAΔE solubility. Mutations predicted to compromise specific torsinA functional motifs showed a synthetic interaction with the ΔE mutation and destabilized torsinAΔE, suggesting that the ΔE mutation predisposes torsinA to defects in the presence of secondary insults. In this case, BiP was required for torsinAΔE degradation, consistent with data that specific chaperones exhibit either pro-degradative or pro-folding activities. Finally, using two independent approaches, we established that BiP stabilizes torsinA and torsinAΔE in mammalian cells. Together, these data define BiP as the first identified torsinA chaperone, and treatments that modulate BiP might improve symptoms associated with EOTD. PMID:24627482

  5. AAAS Presidential Lecture: Voices from the Pipeline

    NASA Astrophysics Data System (ADS)

    Widnall, Sheila E.

    1988-09-01

    The number of white males of college age, who have been the dominant participants in the fields of science and engineering, is predicted to drop significantly in the future. Rapid increases in the participation of women offer some hope of filling anticipated vacancies in the ranks of scientifically trained personnel, although this rapid growth has reached a plateau in many fields. Most studies show that women enter graduate school at about the same rate as men; the dropoff in women's participation occurs sometime before the attainment of the Ph.D. Recent surveys of graduate students indicate that men and women respond differently to the pressures of graduate school and often have a different image of themselves and of their advisers' perceptions of them as graduate students. Some clues from these results may show how the environment can be made more supportive for all students, and for women and minority students in particular.

  6. NREL Scientist Named AAAS Fellow | News | NREL

    Science.gov Websites

    competition, which includes solar and lithium ion battery car races for middle-school students. Ginley holds a thin films, hybrid organic-inorganic solar cells, fuel cells, and lithium batteries. Many scientists

  7. Reinterventions after open and endovascular AAA repair.

    PubMed

    Malina, M

    2015-04-01

    Reinterventions seem to occur more frequently after endovascular aneurysm repair than after open surgical repair and are encountered in about 20% versus 10% of the cases, respectively. However, reinterventions following endovascular repair are predominantly endoluminal and early reinterventions are more frequent after open repair. The indications for reintervention after EVAR have changed over time. The incidence and type of reintervention depends on the complexity of the primary procedure, irrespective of whether it was open or endovascular. The use of a device outside instructions for use is associated with a higher complication rate but it may nevertheless be fully justified. Advanced stent-grafts such as fenestrated and branched devices require secondary procedures more often than a standard stent-graft. Similarly, more complex open repair, e.g. a bifurcated bypass, reimplantation of visceral arteries or a redo procedure, is also associated with more reinterventions than a simple tube graft. This manuscript presents some of the most common complications of open and endovascular aortic aneurysm repair and the reinterventions they require. Many of the complications are similar with both open and endovascular techniques. Limb thrombosis, infections and endoleaks are the most frequent indications for reintervention.

  8. Sequential Actions of the AAA-ATPase Valosin-containing Protein (VCP)/p97 and the Proteasome 19 S Regulatory Particle in Sterol-accelerated, Endoplasmic Reticulum (ER)-associated Degradation of 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase*

    PubMed Central

    Morris, Lindsey L.; Hartman, Isamu Z.; Jun, Dong-Jae; Seemann, Joachim; DeBose-Boyd, Russell A.

    2014-01-01

    Accelerated endoplasmic reticulum (ER)-associated degradation (ERAD) of the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase results from its sterol-induced binding to ER membrane proteins called Insig-1 and Insig-2. This binding allows for subsequent ubiquitination of reductase by Insig-associated ubiquitin ligases. Once ubiquitinated, reductase becomes dislocated from ER membranes into the cytosol for degradation by 26 S proteasomes through poorly defined reactions mediated by the AAA-ATPase valosin-containing protein (VCP)/p97 and augmented by the nonsterol isoprenoid geranylgeraniol. Here, we report that the oxysterol 25-hydroxycholesterol and geranylgeraniol combine to trigger extraction of reductase across ER membranes prior to its cytosolic release. This conclusion was drawn from studies utilizing a novel assay that measures membrane extraction of reductase by determining susceptibility of a lumenal epitope in the enzyme to in vitro protease digestion. Susceptibility of the lumenal epitope to protease digestion and thus membrane extraction of reductase were tightly regulated by 25-hydroxycholesterol and geranylgeraniol. The reaction was inhibited by RNA interference-mediated knockdown of either Insigs or VCP/p97. In contrast, reductase continued to become membrane-extracted, but not cytosolically dislocated, in cells deficient for AAA-ATPases of the proteasome 19 S regulatory particle. These findings establish sequential roles for VCP/p97 and the 19 S regulatory particle in the sterol-accelerated ERAD of reductase that may be applicable to the ERAD of other substrates. PMID:24860107

  9. EIN3-like gene expression during fruit ripening of Cavendish banana (Musa acuminata cv. Grande naine).

    PubMed

    Mbéguié-A-Mbéguié, Didier; Hubert, Olivier; Fils-Lycaon, Bernard; Chillet, Marc; Baurens, Franc-Christophe

    2008-06-01

    Ethylene signal transduction initiates with ethylene binding at receptor proteins and terminates in a transcription cascade involving the EIN3/EIL transcription factors. Here, we have isolated four cDNAs homologs of the Arabidopsis EIN3/EIN3-like gene, MA-EILs (Musa acuminata ethylene insensitive 3-like) from banana fruit. Sequence comparison with other banana EIL gene already registered in the database led us to conclude that, at this day, at least five different genes namely MA-EIL1, MA-EIL2/AB266318, MA-EIL3/AB266319, MA-EIL4/AB266320 and AB266321 exist in banana. Phylogenetic analyses included all banana EIL genes within a same cluster consisting of rice OsEILs, a monocotyledonous plant as banana. However, MA-EIL1, MA-EIL2/AB266318, MA-EIL4/AB266320 and AB266321 on one side, and MA-EIL3/AB266319 on the other side, belong to two distant subclusters. MA-EIL mRNAs were detected in all examined banana tissues but at lower level in peel than in pulp. According to tissues, MA-EIL genes were differentially regulated by ripening and ethylene in mature green fruit and wounding in old and young leaves. MA-EIL2/AB266318 was the unique ripening- and ethylene-induced gene; MA-EIL1, MA-EIL4/Ab266320 and AB266321 genes were downregulated, while MA-EIL3/AB266319 presented an unusual pattern of expression. Interestingly, a marked change was observed mainly in MA-EIL1 and MA-EIL3/Ab266319 mRNA accumulation concomitantly with changes in ethylene responsiveness of fruit. Upon wounding, the main effect was observed in MA-EIL4/AB266320 and AB266321 mRNA levels, which presented a markedly increase in both young and old leaves, respectively. Data presented in this study suggest the importance of a transcriptionally step control in the regulation of EIL genes during banana fruit ripening.

  10. Cavendish Experiment in Physics Textbooks: Why Do Authors Continue to Repeat a Denounced Error?

    ERIC Educational Resources Information Center

    Slisko, Josip; Hadzibegovic, Zalkida

    2011-01-01

    Since long time ago, many authors advocated for more presence of physics history in physics teaching and learning in order to give students a better vision of the "nature of science", in other words, to let them learn not only established physics knowledge but also the ways of how physicists managed to get that knowledge. Generally,…

  11. Malate synthase gene expression during fruit ripening of Cavendish banana (Musa acuminata cv. Williams).

    PubMed

    Pua, Eng-Chong; Chandramouli, Sumana; Han, Ping; Liu, Pei

    2003-01-01

    Malate synthase (MS) is a key enzyme responsible for malic acid synthesis in the glyoxylate cycle, which functions to convert stored lipids to carbohydrates, by catalysing the glyoxylate condensation reaction with acetyl-CoA in the peroxisome. In this study, the cloning of an MS cDNA, designated MaMS-1, from the banana fruit is reported. MaMS-1 was 1801 bp in length encoding a single polypeptide of 556 amino acid residues. Sequence analysis revealed that MaMS-1 possessed the conserved catalytic domain and a putative peroxisomal targeting signal SK(I/L) at the carboxyl terminal. MaMS-1 also shared an extensive sequence homology (79-81.3%) with other plant MS homologues. Southern analysis indicated that MS might be present as multiple members in the banana genome. In Northern analysis, MaMS-1 was expressed specifically in ripening fruit tissue and transcripts were not detected in other organs such as roots, pseudostem, leaves, ovary, male flower, and in fruit at different stages of development. However, the transcript abundance in fruit was affected by stage of ripening, during which transcript was barely detectable at the early stage of ripening (FG and TY), but the level increased markedly in MG and in other fruits at advanced ripening stages. Furthermore, MaMS-1 expression in FG fruit could be stimulated by treatment with 1 microl l(-1) exogenous ethylene, but the stimulatory effect was abolished by the application of an ethylene inhibitor, norbornadiene. Results of this study clearly show that MS expression in banana fruit is temporally regulated during ripening and is ethylene-inducible.

  12. A novel amperometric biosensor based on banana peel (Musa cavendish) tissue homogenate for determination of phenolic compounds.

    PubMed

    Ozcan, Hakki Mevlut; Sagiroglu, Ayten

    2010-08-01

    In this study the biosensor was constructed by immobilizing tissue homogenate of banana peel onto a glassy carbon electrode surface. Effects of immobilization materials amounts, effects of pH, buffer concentration and temperature on biosensor response were studied. In addition, the detection ranges of 13 phenolic compounds were obtained with the help of the calibration graphs. Storage stability, repeatability of the biosensor, inhibitory effect and sample applications were also investigated. A typical calibration curve for the sensor revealed a linear range of 10-80 microM catechol. In reproducibility studies, variation coefficient and standard deviation were calculated as 2.69%, 1.44 x 10(-3) microM, respectively.

  13. Expression of a ripening-related cytochrome P450 cDNA in Cavendish banana (Musa acuminata cv. Williams).

    PubMed

    Pua, Eng-Chong; Lee, Yi-Chuan

    2003-02-13

    As part of a study to understand the molecular basis of fruit ripening, this study reports the isolation and characterization of a banana cytochrome P450 (P450) cDNA, designated as MAP450-1, which was associated with fruit ripening of banana. MAP450-1 encoded a single polypeptide of 507 amino acid residues that shared an overall identity of 27-45% with that of several plant P450s, among which MAP450-1 was most related phylogenetically to the avocado P450 CYP71A1. The polypeptide that possessed residue domains conserved in all P450s was classified as CYP71N1. Expression of CYP71N1 varied greatly between banana organs. Transcripts were detected only in peel and pulp of the ripening fruit and not in unripe fruit tissues at all developmental stages or other organs (root, leaf, ovary and flower). During ripening, transcripts were barely detectable in pre-climacteric and climacteric fruits but, as ripening progressed, they began to accumulate and reached a maximum in post-climacteric fruits. CYP71N1 expression in pre-climacteric fruit could be upregulated by exogenous application of ethylene (1-5 ppm) and treatment of overripe fruit with exogenous sucrose (50-300 mM) but not glucose downregulated the expression. These results indicate that P450s may not play a role in fruit development and its expression is associated with ripening, which may be regulated, in part, by ethylene and/or sucrose, at the transcript level.

  14. AAA Roadmap for Navigating Religion in Physical Education

    ERIC Educational Resources Information Center

    Kahan, David

    2011-01-01

    The majority of Americans identify with a religious faith, and the connection between religious beliefs/behaviors and health behaviors make it important to understand teachers' role and influence in this regard. The purpose of this article is to inform readers regarding (1) religious demographics in the United States; (2) the relationship between…

  15. Update on the status of infrarenal AAA devices.

    PubMed

    Hart, Theodore; Milner, Ross

    2018-06-01

    There are a variety of endografts currently available for endovascular repair of abdominal aortic aneurysms. Aneurysms of increasing anatomic complexity are being repaired with devices that are either newly approved or redesigned relative to the initial published experience with infrarenal endovascular aortic aneurysm repair (EVAR). This article describes the contemporary devices approved for infrarenal EVAR in the United States and includes an up-to-date compilation of the data addressing outcomes specific to each device.

  16. China takes microgravity work to new heights | Science | AAAS

    Science.gov Websites

    China takes microgravity work to new heights By Dennis Normile Apr. 5, 2016 , 2:00 PM China's space :10.1126/science.aaf9876 Dennis Normile More from News illustration of GOES-17 Cooling failure threatens

  17. Nuclear Forensics: Report of the AAAS/APS Working Group

    NASA Astrophysics Data System (ADS)

    Tannenbaum, Benn

    2008-04-01

    This report was produced by a Working Group of the American Physical Society's Program on Public Affairs in conjunction with the American Association for the Advancement of Science Center for Science, Technology and Security Policy. The primary purpose of this report is to provide the Congress, U.S. government agencies and other institutions involved in nuclear forensics with a clear unclassified statement of the state of the art of nuclear forensics; an assessment of its potential for preventing and identifying unattributed nuclear attacks; and identification of the policies, resources and human talent to fulfill that potential. In the course of its work, the Working Group observed that nuclear forensics was an essential part of the overall nuclear attribution process, which aims at identifying the origin of unidentified nuclear weapon material and, in the event, an unidentified nuclear explosion. A credible nuclear attribution capability and in particular nuclear forensics capability could deter essential participants in the chain of actors needed to smuggle nuclear weapon material or carry out a nuclear terrorist act and could also encourage states to better secure such materials and weapons. The Working Group also noted that nuclear forensics result would take some time to obtain and that neither internal coordination, nor international arrangements, nor the state of qualified personnel and needed equipment were currently enough to minimize the time needed to reach reliable results in an emergency such as would be caused by a nuclear detonation or the intercept of a weapon-size quantity of material. The Working Group assesses international cooperation to be crucial for forensics to work, since the material would likely come from inadequately documented foreign sources. In addition, international participation, if properly managed, could enhance the credibility of the deterrent effect of attribution. Finally the Working Group notes that the U.S. forensics capability involved a number of agencies and other groups that would have to cooperate rapidly in an emergency and that suitable exercises to ensure such cooperation were needed.

  18. NREL Scientist Brian Gregg Named AAAS Fellow | News | NREL

    Science.gov Websites

    discovered an entirely new photovoltaic effect. Even when sandwiched between two identical electrodes (i.e ., with zero bandbending) a PV effect is observed in these devices. Such an observation was unprecedented and challenged common assumptions about how solar cells work. This research set off a lifelong passion

  19. Careers Other Than Academia EPA/AAAS Graduate Fellowship Expo

    EPA Science Inventory

    NCER invited Emilie to speak to the EPA STAR graduate fellows about her transition from graduate school into a postdoctoral position with the EPA. Discussion of what led Emilie to seek a position with the EPA, how she conducted her job search, and what qualities she thinks gradu...

  20. Scavenge/remove an AAA (Avionics Air Assembly) filter

    NASA Image and Video Library

    2009-08-25

    ISS020-E-033979 (25 Aug. 2009) --- NASA astronaut Michael Barratt, Expedition 20 flight engineer, works with the Crew Health Care System (CHeCS) rack in the Kibo laboratory of the International Space Station.

  1. Scientific Society AAAS Honors NREL's Tumas as Fellow | News | NREL

    Science.gov Websites

    materials chemistry, for pioneering work in green chemistry and energy, and for enlightened scientific management." Tumas, who earned his doctorate in organic chemistry from Stanford University and holds a founding board member of the Green Chemistry Institute, which is now part of the American Chemical Society

  2. NREL Scientist Maria Ghirardi Named AAAS Fellow | News | NREL

    Science.gov Websites

    extreme sensitivity of the hydrogenase enzyme to oxygen, one of the byproducts of photosynthesis. Ghirardi pathways in photosynthesis, and in deconvoluting the metabolic partners of a crucial redox enzyme

  3. Two Argonne scientists named 2012 AAAS fellows | Argonne National

    Science.gov Websites

    "contributions to understanding structural dynamics of molecular excited states with special . "I'm really interested in how molecules respond to light and how light could influence molecular is being honored for her "contributions to understanding structural dynamics of molecular

  4. Changes in resistant starch from two banana cultivars during postharvest storage.

    PubMed

    Wang, Juan; Tang, Xue Juan; Chen, Ping Sheng; Huang, Hui Hua

    2014-08-01

    Banana resistant starch samples were extracted and isolated from two banana cultivars (Musa AAA group, Cavendish subgroup and Musa ABB group, Pisang Awak subgroup) at seven ripening stages during postharvest storage. The structures of the resistant starch samples were analysed by light microscopy, polarising microscopy, scanning electron microscopy, X-ray diffraction, and infrared spectroscopy. Physicochemical properties (e.g., water-holding capacity, solubility, swelling power, transparency, starch-iodine absorption spectrum, and Brabender microviscoamylograph profile) were determined. The results revealed significant differences in microstructure and physicochemical characteristics among the banana resistant starch samples during different ripening stages. The results of this study provide valuable information for the potential applications of banana resistant starches. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Effect of banana pulp and peel flour on physicochemical properties and in vitro starch digestibility of yellow alkaline noodles.

    PubMed

    Ramli, Saifullah; Alkarkhi, Abbas F M; Shin Yong, Yeoh; Min-Tze, Liong; Easa, Azhar Mat

    2009-01-01

    The present study describes the utilization of banana--Cavendish (Musa acuminata L., cv cavendshii) and Dream (Musa acuminata colla. AAA, cv 'Berangan')--pulp and peel flours as functional ingredients in yellow alkaline noodles. Noodles were prepared by partial substitution of wheat flour with ripe banana pulp or peel flours. In most cases, the starch hydrolysis index, predicted glycaemic index (pGI) and physicochemical properties of cooked noodles were affected by banana flour addition. In general, the pGI values of cooked noodles were in the order; banana peel noodles < banana pulp noodles < control noodles. Since the peel flour was higher in total dietary fibre but lower in resistant starch contents than the pulp flour, the low pGI of banana peel noodles was mainly due to its high dietary fibre content. In conclusion, banana pulp and peel flour could be useful for controlling starch hydrolysis of yellow noodles, even though some physicochemical properties of the noodles were altered.

  6. Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease.

    PubMed

    Sriramoju, Manoj Kumar; Chen, Yen; Lee, Yun-Tzai Cloud; Hsu, Shang-Te Danny

    2018-05-04

    More than one thousand knotted protein structures have been identified so far, but the functional roles of these knots remain elusive. It has been postulated that backbone entanglement may provide additional mechanostability. Here, we employed a bacterial proteasome, ClpXP, to mechanically unfold 5 2 -knotted human ubiquitin C-terminal hydrolase (UCH) paralogs from their C-termini, followed by processive translocation into the proteolytic chamber for degradation. Our results revealed unprecedentedly slow kinetics of ClpXP-mediated proteolysis for the proteasome-associated UCHL5: ten thousand times slower than that of a green fluorescence protein (GFP), which has a comparable size to the UCH domain but much higher chemical and thermal stabilities. The ClpXP-dependent mechanostability positively correlates with the intrinsic unfolding rates of the substrates, spanning over several orders of magnitude for the UCHs. The broad range of mechanostability within the same protein family may be associated with the functional requirements for their differential malleabilities.

  7. AAAS Symposium: Community-driven Citizen Science for Health and the Environment

    EPA Pesticide Factsheets

    Panelists will reflect various viewpoints, from funders, to researchers, to members of impacted communities. They will address policy considerations and contributions, broadening participation of underrepresented groups, project design, and outcomes.

  8. Supramolecular Polymers Based on Non-Coplanar AAA-DDD Hydrogen-Bonded Complexes.

    PubMed

    Mendez, Iamnica J Linares; Wang, Hong-Bo; Yuan, Ying-Xue; Wisner, James A

    2018-03-01

    Non-coplanar triple-hydrogen-bond arrays are connected as telechelic groups to alkyl chains and their properties as AA/BB type supramolecular polymers are examined. Viscosity studies at three temperatures are used to study the ring-chain equilibrium and determine the critical concentrations where polymer chains are formed. It is observed that neither the temperature range studied nor the alkyl chain length of one component significantly affect the polymerization properties in this system. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Atmospheric Sciences. Test Edition. AAAS Study Guides on Contemporary Problems, No. 6.

    ERIC Educational Resources Information Center

    Schaefer, Vincent J.; Mohnen, Volker A.

    This is one of several study guides on contemporary problems produced by the American Association for the Advancement of Science with support of the National Science Foundation. This study guide includes the following sections: (1) Solar Radiation and Its Interaction with the Earth's Atmosphere System; (2) The Water Cycle; (3) Fundamentals of Air…

  10. 1995 AAAS annual meeting and science innovation exposition: Unity in diversity

    SciTech Connect

    Strauss, M.S.; Heasley, C.

    1995-12-31

    Abstracts are presented from the 161st National Meeting of the American Association for the advancement of Science. Topics include environmental technologies, genetics, physical science research, information management, nuclear weapon issues, and education. Individual topics have been processed separately for the United States Department of Energy databases.

  11. Former NCI Researcher, George Vande Woude, Receives AAAS Fellowship Award | Poster

    Cancer.gov

    Editor’s Note: This article was adapted from a press release and biographical information from the Van Andel Research Institute’s website: http://www.vai.org/en/NewsRoom/press-release-01-28-14.aspx.

  12. Science as Intellectual Property: Who Controls Research? AAAS Series on Issues in Science and Technology.

    ERIC Educational Resources Information Center

    Nelkin, Dorothy

    The controversial question of who controls research stands at the center of a growing number of legal and administrative disputes which raise critical issues of professional sovereignty, scientific secrecy, and proprietary rights. Although the idea of knowledge as property is not new, the scale and changing nature and structure of contemporary…

  13. Use of Banana (Musa acuminata Colla AAA) Peel Extract as an Antioxidant Source in Orange Juices.

    PubMed

    Ortiz, Lucía; Dorta, Eva; Gloria Lobo, M; González-Mendoza, L Antonio; Díaz, Carlos; González, Mónica

    2017-03-01

    Using banana peel extract as an antioxidant in freshly squeezed orange juices and juices from concentrate was evaluated. Free radical scavenging capacity increased by adding banana peel extracts to both types of orange juice. In addition, remarkable increases in antioxidant capacity using 2,2'-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical were observed when equal or greater than 5 mg of banana peel extract per ml of freshly squeezed juice was added. No clear effects were observed in the capacity to inhibit lipid peroxidation. Adding 5 mg banana peel extract per ml of orange juice did not substantially modify the physicochemical and sensory characteristics of either type of juice. However, undesirable changes in the sensory characteristics (in-mouth sensations and colour) were detected when equal or greater than 10 mg banana peel extract per ml of orange juice was added. These results confirm that banana peel is a promising natural additive that increases the capacity to scavenge free radicals of orange juice with acceptable sensory and physicochemical characteristics for the consumer.

  14. In Search of a Cure for Proteostasis-Addicted Cancer: A AAA Target Revealed.

    PubMed

    Xia, Di; Ye, Yihong

    2015-11-09

    Tumorigenesis is often associated with an unbalanced protein homeostasis (proteostasis) network, which sensitizes cancer cells to drugs targeting protein quality control (PQC) regulators. In this issue of Cancer Cell, Anderson and colleagues investigated the anti-cancer activity of a new class of inhibitor against a multi-functional ATPase essential for proteostasis maintenance. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Consensus models to predict endocrine disruption for all human-exposure chemicals (AAAS Annual Meeting)

    EPA Science Inventory

    Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been te...

  16. A gunner model for an AAA tracking task with interrupted observations

    NASA Technical Reports Server (NTRS)

    Yu, C. F.; Wei, K. C.; Vikmanis, M.

    1982-01-01

    The problem of modeling a trained human operator's tracking performance in an anti-aircraft system under various display blanking conditions is discussed. The input to the gunner is the observable tracking error subjected to repeated interruptions (blanking). A simple and effective gunner model was developed. The effect of blanking on the gunner's tracking performance is approached via modeling the observer and controller gains.

  17. Application of optimal control principles to describe the supervisory control behavior of AAA crew members

    NASA Technical Reports Server (NTRS)

    Hale, C.; Valentino, G. J.

    1982-01-01

    Supervisory decision making and control behavior within a C(3) oriented, ground based weapon system is being studied. The program involves empirical investigation of the sequence of control strategies used during engagement of aircraft targets. An engagement is conceptually divided into several stages which include initial information processing activity, tracking, and ongoing adaptive control decisions. Following a brief description of model parameters, two experiments which served as initial investigation into the accuracy of assumptions regarding the importance of situation assessment in procedure selection are outlined. Preliminary analysis of the results upheld the validity of the assumptions regarding strategic information processing and cue-criterion relationship learning. These results indicate that this model structure should be useful in studies of supervisory decision behavior.

  18. A Study Guide on Holography (Draft). Test Edition. AAAS Study Guides on Contemporary Problems.

    ERIC Educational Resources Information Center

    Jeong, Tung H.

    This is one of several study guides on contemporary problems produced by the American Association for the Advancement of Science with support of the National Science Foundation. The primary purpose of this guide is to provide a student with sufficient practical and technical information to begin independently practicing holography, with occasional…

  19. AAA gunnermodel based on observer theory. [predicting a gunner's tracking response

    NASA Technical Reports Server (NTRS)

    Kou, R. S.; Glass, B. C.; Day, C. N.; Vikmanis, M. M.

    1978-01-01

    The Luenberger observer theory is used to develop a predictive model of a gunner's tracking response in antiaircraft artillery systems. This model is composed of an observer, a feedback controller and a remnant element. An important feature of the model is that the structure is simple, hence a computer simulation requires only a short execution time. A parameter identification program based on the least squares curve fitting method and the Gauss Newton gradient algorithm is developed to determine the parameter values of the gunner model. Thus, a systematic procedure exists for identifying model parameters for a given antiaircraft tracking task. Model predictions of tracking errors are compared with human tracking data obtained from manned simulation experiments. Model predictions are in excellent agreement with the empirical data for several flyby and maneuvering target trajectories.

  20. Ethical Issues and the Life Sciences. Test Edition. AAAS Study Guides on Contemporary Problems.

    ERIC Educational Resources Information Center

    Kieffer, George H.

    This is one of several study guides on contemporary problems produced by the American Association for the Advancement of Science with support of the National Science Foundation. This study guide on Ethical Issues and the Life Sciences includes the following sections: (1) Introduction; (2) The Search for an Ethic; (3) Biomedical Issues including…

  1. Tobacco arabinogalactan protein NtEPc can promote banana (Musa AAA) somatic embryogenesis.

    PubMed

    Shu, H; Xu, L; Li, Z; Li, J; Jin, Z; Chang, S

    2014-12-01

    Banana is an important tropical fruit worldwide. Parthenocarpy and female sterility made it impossible to improve banana varieties through common hybridization. Genetic transformation for banana improvement is imperative. But the low rate that banana embryogenic callus was induced made the transformation cannot be performed in many laboratories. Finding ways to promote banana somatic embryogenesis is critical for banana genetic transformation. After tobacco arabinogalactan protein gene NtEPc was transformed into Escherichia coli (DE3), the recombinant protein was purified and filter-sterilized. A series of the sterilized protein was added into tissue culture medium. It was found that the number of banana immature male flowers developing embryogenic calli increased significantly in the presence of NtEPc protein compared with the effect of the control medium. Among the treatments, explants cultured on medium containing 10 mg/l of NtEPc protein had the highest chance to develop embryogenic calli. The percentage of lines that developed embryogenic calli on this medium was about 12.5 %. These demonstrated that NtEPc protein can be used to promote banana embryogenesis. This is the first paper that reported that foreign arabinogalactan protein (AGP) could be used to improve banana somatic embryogenesis.

  2. Cadaveric verification of the Eclipse AAA algorithm for spine SBRT treatments with titanium hardware.

    PubMed

    Grams, Michael P; Fong de Los Santos, Luis E; Antolak, John A; Brinkmann, Debra H; Clarke, Michelle J; Park, Sean S; Olivier, Kenneth R; Whitaker, Thomas J

    2016-01-01

    To assess the accuracy of the Eclipse Analytical Anisotropic Algorithm when calculating dose for spine stereotactic body radiation therapy treatments involving surgically implanted titanium hardware. A human spine was removed from a cadaver, cut sagittally along the midline, and then separated into thoracic and lumbar sections. The thoracic section was implanted with titanium stabilization hardware; the lumbar section was not implanted. Spine sections were secured in a water phantom and simulated for treatment planning using both standard and extended computed tomography (CT) scales. Target volumes were created on both spine sections. Dose calculations were performed using (1) the standard CT scale with relative electron density (RED) override of image artifacts and hardware, (2) the extended CT scale with RED override of image artifacts only, and (3) the standard CT scale with no RED overrides for hardware or artifacts. Plans were delivered with volumetric modulated arc therapy using a 6-MV beam with and without a flattening filter. A total of 3 measurements for each plan were made with Gafchromic film placed between the spine sections and compared with Eclipse dose calculations using gamma analysis with a 2%/2 mm passing criteria. A single measurement in a homogeneous phantom was made for each plan before actual delivery. Gamma passing rates for measurements in the homogeneous phantom were 99.6% or greater. Passing rates for measurements made in the lumbar spine section without hardware were 99.3% or greater; measurements made in the thoracic spine containing titanium were 98.6 to 99.5%. Eclipse Analytical Anisotropic Algorithm can adequately model the effects of titanium implants for spine stereotactic body radiation therapy treatments using volumetric modulated arc therapy. Calculations with standard or extended CT scales give similarly accurate results. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  3. Reduced-Order Observer Model for Antiaircraft Artillery (AAA) Tracker Response

    DTIC Science & Technology

    1979-08-01

    a22 -ka1 2) z + (a22 - ka1 2) ky + (a21 - kall ) y + (b2 - kb) uc (10) Next, the actual output of this model is expressed as the sum of the output u...a22x2 + b2u + f2eT = (a2 2 - kal2) z + (a2 2 - ka12) ky + (a21 - kall ) y + (b2 - kb l ) uc u=u +vC [Ti Y2] [y] By introducing new variables: X3 = x2...x3 [(a22- ka2)k + (a2- kall ) - (b2- kb) (YI + kY2) Y + [a22 - ka12 - (b2 - kbl) Y2] X3 + (b2 -kbl) y2 e + (2 - kbI) v + (f2 - kfl) 0 T e = (a22- ka12

  4. Pineapple juice and its fractions in enzymatic browning inhibition of banana [Musa (AAA group) Gros Michel].

    PubMed

    Chaisakdanugull, Chitsuda; Theerakulkait, Chockchai; Wrolstad, Ronald E

    2007-05-16

    The effectiveness of pineapple juice in enzymatic browning inhibition was evaluated on the cut surface of banana slices. After storage of banana slices at 15 degrees C for 3 days, pineapple juice showed browning inhibition to a similar extent as 8 mM ascorbic acid but less than 4 mM sodium metabisulfite. Fractionation of pineapple juice by a solid-phase C18 cartridge revealed that the directly eluted fraction (DE fraction) inhibited banana polyphenol oxidase (PPO) about 100% when compared to the control. The DE fraction also showed more inhibitory effect than 8 mM ascorbic acid in enzymatic browning inhibition of banana puree during storage at 5 degrees C for 24 h. Further identification of the DE fraction by fractionation with ion exchange chromatography and confirmation using model systems indicated that malic acid and citric acid play an important role in the enzymatic browning inhibition of banana PPO.

  5. ARCHIE, FLAK, AAA, AND SAM A Short Operational History of Ground-Based Air Defense

    DTIC Science & Technology

    1988-12-01

    81 44 Nike Ajax...83 45 Nike Hercules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 46 Hawk...German Artillery of World War II (London: Arms and Armour , 1975), 162, 167 ; R. A. Devereux, "German Experience with Antiaircraft Artillery Guns in WWII

  6. An Instructors Guide to Water Pollution. Test Edition. AAAS Study Guides on Contemporary Problems, No. 5.

    ERIC Educational Resources Information Center

    Kidd, David E.

    This is one of several study guides on contemporary problems produced by the American Association for the Advancement of Science with support of the National Science Foundation. This study guide on water pollution includes the following units: (1) Overview of World Pollution; (2) History, Definition, Criteria; (3) Ecosystem Theory; (4) Biological…

  7. Alacrima as a Harbinger of Adrenal Insufficiency in a Child with Allgrove (AAA) Syndrome

    PubMed Central

    Brown, Brande; Agdere, Levon; Muntean, Cornelia; David, Karen

    2016-01-01

    Patient: Female, 6 Final Diagnosis: Allgrove syndrome Symptoms: Achalasia • adrenal insufficiency • alacrima Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology Objective: Rare disease Background: Allgrove syndrome, or triple “A” syndrome (3A syndrome), is a rare autosomal recessive syndrome with variable phenotype, and an estimated prevalence of 1 per 1,000,000 individuals. Patients usually display the triad of achalasia, alacrima, and adrenocorticotropin (ACTH) insensitive adrenal insufficiency, though the presentation is inconsistent. Case Report: Here, the authors report a case of Allgrove syndrome in a pediatric patient with delayed diagnosis in order to raise awareness of this potentially fatal disease as a differential diagnosis of alacrima. Conclusions: The prevalence of Allgrove syndrome may be much higher as a result of underdiagnosis and missed diagnosis due to the variable presentation and sudden unexplained childhood death from adrenal crisis. The authors review the characteristic symptoms of Allgrove syndrome in relation to the case study in order to avoid missed or delayed diagnosis, potentially decreasing morbidity, and mortality in those affected by this disease. PMID:27698338

  8. CCC for AAA: Tapping Creativity, Collaboration & Cooperation for Quality in Teacher Education

    ERIC Educational Resources Information Center

    Praveen, C.

    2006-01-01

    Information and Communication Technology in education is changing the way we teach, learn and conduct research. Today we have WIRE, WEB and WINDOWS leading to CONNECTIVITY, NETWORKING and APPLICATIONS. Not surprisingly the National Council of Teacher Education, (NCTE) India, decided to make ICT Literacy a compulsory part of the Pre-service course…

  9. A NASTRAN Vibration Model of the AH-1G Helicopter Airframe. Volume 1

    DTIC Science & Technology

    1974-06-01

    Bulkhead .012 ZZ 1863343 Bulkhead .012 AAA 1863345 Bulkhead .012 j EBB 1863546 Bulkhead .012 j ccc 1863746 Bulkhead .012 \\ ODD 1863748...123 12) 123 RULE AAA AAA AAA AAA BBB EBB AAA AAA AAA AAA BBB BBB OMIT D.O.F. 456 456 123 123 123 123 123 123 123 123 RULE...load in the member Increases. The program determines the section properties, unsytnmetrical bending stresses, element loads and shear flows for a

  10. Rhizobacteria in mycorrhizosphere improved plant health and yield of banana by offering proper nourishment and protection against diseases.

    PubMed

    Phirke, Niteen V; Kothari, Raman M; Chincholkar, Sudhir B

    2008-12-01

    The corporate R&D banana orchards of Musa paradisiaca (dwarf Cavendish AAA, var. shrimanti) on a medium black alluvial soil with low nutrients harboured diversified species of vesicular-arbuscular mycorrhizal (VAM) fungi. These fungi infected the roots severely (69.2%), showed elevated (69.8 g(-1) soil) spore density, increased soil bacterial density (245 x 10(8) cfu g(-1)), produced siderophores (58.2%) and reduced nematode population (2.3 g(-1)) in the mycorrhizosphere of plants for integrated plant nutrition management (IPNM) system as compared to traditional treatment of applying chemical fertilisers alone and other test treatments. The interactions of plant roots with native VAM and local and applied rhizobacteria in the matrix of soil conditioner enabled proper nourishment and protection of crop in IPNM treatment as compared to traditional way. Hence, exploitation of plant growth promoting rhizobacteria through judiciously designed IPNM system revealed the (a) relatively increased banana productivity (21.6%, 76 MT ha(-1)), (b) least occurrence of fusarial wilt and negligible evidence of Sigatoka, (c) saving of 50% chemical fertilisers and (d) permitted control over soil fertility in producer's favour over traditional cultivation practices. These findings are discussed in detail.

  11. Comparative study of the banana pulp browning process of 'Giant Dwarf' and FHIA-23 during fruit ripening based on image analysis and the polyphenol oxidase and peroxidase biochemical properties.

    PubMed

    Escalante-Minakata, Pilar; Ibarra-Junquera, Vrani; Ornelas-Paz, José de Jesús; García-Ibáñez, Victoria; Virgen-Ortíz, José J; González-Potes, Apolinar; Pérez-Martínez, Jaime D; Orozco-Santos, Mario

    2018-01-01

    This work presents a novel method to associate the polyphenol oxidase (PPO) and the peroxidase (POD) activities with the ripening-mediated color changes in banana peel and pulp by computational image analysis. The method was used to follow up the de-greening of peel and browning of homogenized pulp from 'Giant Dwarf' (GD: Musa AAA, subgroup Cavendish) and FHIA-23 (tetraploid hybrid, AAAA) banana cultivars. In both cultivars, the color changes of peel during the ripening process clearly showed four stages, which were used to group the fruit into ripening stages. The PPO and POD were extracted from pulp of fruit at these ripening stages, precipitated, and partially purified by gel filtration chromatography. Moreover, the pulp browning was digitally monitored after homogenization for a span time of up to 120 min. The browning level was higher for GD than FHIA-23 tissues. This fact correlated with an 11.7-fold higher PPO activity in the GD cultivar, as compared with that of FHIA-23. POD activity was 8.1 times higher for GD as compared that that of FHIA-23.

  12. Differential feedback regulation of ethylene biosynthesis in pulp and peel tissues of banana fruit.

    PubMed

    Inaba, Akitsugu; Liu, Xuejun; Yokotani, Naoki; Yamane, Miki; Lu, Wang-Jin; Nakano, Ryohei; Kubo, Yasutaka

    2007-01-01

    The feedback regulation of ethylene biosynthesis in banana [Musa sp. (AAA group, Cavendish subgroup) cv. Grand Nain] fruit was investigated in an attempt to clarify the opposite effect of 1-methylcyclopropene (1-MCP), an ethylene action inhibitor, before and after the onset of ripening. 1-MCP pre-treatment completely prevented the ripening-induced effect of propylene in pre-climacteric banana fruit, whereas treatment after the onset of ripening stimulated ethylene production. In pre-climacteric fruit, higher concentrations of propylene suppressed ethylene production more strongly, despite their earlier ethylene-inducing effect. Exposure of the fruit ripened by propylene to 1-MCP increased ethylene production concomitantly with an increase in 1-aminocyclopropane-1-carboxylate (ACC) synthase activity and ACC content, and prevented a transient decrease in MA-ACS1 transcripts in the pulp tissues. In contrast, in the peel of ripening fruit, 1-MCP prevented the increase in ethylene production and subsequently the ripening process by reduction of the increase in MA-ACS1 and MA-ACO1 transcripts and of ACC synthase and ACC oxidase activities. These results suggest that ethylene biosynthesis in ripening banana fruit may be controlled negatively in the pulp tissue and positively in the peel tissue. This differential regulation by ethylene in pulp and peel tissues was also observed for MA-PL, MA-Exp, and MA-MADS genes.

  13. Role of sucrose phosphate synthase in sucrose biosynthesis in ripening bananas and its relationship to the respiratory climacteric.

    PubMed

    Hubbard, N L; Pharr, D M; Huber, S C

    1990-09-01

    During ripening of bananas (Musa spp. [AAA group, Cavendish subgroup]), there is a massive conversion of starch to sucrose. Also during ripening there is a rise in respiration known as the respiratory climacteric. In this study changes in carbohydrate content, activities of starch and sucrose metabolizing enzymes, and respiration were measured to assess their potential interrelationships. Sucrose phosphate synthase activity increased dramatically during the first 4 days after initiation of ripening by ethylene treatment. Starch concentration decreased and sucrose concentration increased during this time period. Developmental changes in sucrose phosphate synthase activity were measured with limiting substrate (plus Pi) and saturating substrate concentrations. Activities were not parallel under the two assay conditions, providing tentative evidence that kinetically different forms of the enzyme may exist at different stages of ripening. Sucrose accumulation rate was most highly correlated with sucrose phosphate synthase activity assayed with limiting substrate concentrations (plus Pi). The cumulative amount of CO(2) respired during ripening was positively correlated with sugar accumulation (R(2) = 0.97). From this linear regression it was calculated that a constant 0.605 millimoles of CO(2) was evolved per mole of sucrose formed throughout ripening. Using this quantity, the percentage of the total respiratory ATP produced which was required for the conversion of starch to sucrose was calculated assuming different models for carbon export from the amyloplast. The results suggest that sucrose biosynthesis during ripening constitutes a significant sink for respiratory ATP.

  14. Role of Sucrose Phosphate Synthase in Sucrose Biosynthesis in Ripening Bananas and Its Relationship to the Respiratory Climacteric 1

    PubMed Central

    Hubbard, Natalie L.; Pharr, D. Mason; Huber, Steven C.

    1990-01-01

    During ripening of bananas (Musa spp. [AAA group, Cavendish subgroup]), there is a massive conversion of starch to sucrose. Also during ripening there is a rise in respiration known as the respiratory climacteric. In this study changes in carbohydrate content, activities of starch and sucrose metabolizing enzymes, and respiration were measured to assess their potential interrelationships. Sucrose phosphate synthase activity increased dramatically during the first 4 days after initiation of ripening by ethylene treatment. Starch concentration decreased and sucrose concentration increased during this time period. Developmental changes in sucrose phosphate synthase activity were measured with limiting substrate (plus Pi) and saturating substrate concentrations. Activities were not parallel under the two assay conditions, providing tentative evidence that kinetically different forms of the enzyme may exist at different stages of ripening. Sucrose accumulation rate was most highly correlated with sucrose phosphate synthase activity assayed with limiting substrate concentrations (plus Pi). The cumulative amount of CO2 respired during ripening was positively correlated with sugar accumulation (R2 = 0.97). From this linear regression it was calculated that a constant 0.605 millimoles of CO2 was evolved per mole of sucrose formed throughout ripening. Using this quantity, the percentage of the total respiratory ATP produced which was required for the conversion of starch to sucrose was calculated assuming different models for carbon export from the amyloplast. The results suggest that sucrose biosynthesis during ripening constitutes a significant sink for respiratory ATP. PMID:16667688

  15. Characterization of Ethylene Biosynthesis Associated with Ripening in Banana Fruit1

    PubMed Central

    Liu, Xuejun; Shiomi, Shinjiro; Nakatsuka, Akira; Kubo, Yasutaka; Nakamura, Reinosuke; Inaba, Akitsugu

    1999-01-01

    We investigated the characteristics of ethylene biosynthesis associated with ripening in banana (Musa sp. [AAA group, Cavendish subgroup] cv Grand Nain) fruit. MA-ACS1 encoding 1-aminocyclopropane-1-carboxylic acid (ACC) synthase in banana fruit was the gene related to the ripening process and was inducible by exogenous ethylene. At the onset of the climacteric period in naturally ripened fruit, ethylene production increased greatly, with a sharp peak concomitant with an increase in the accumulation of MA-ACS1 mRNA, and then decreased rapidly. At the onset of ripening, the in vivo ACC oxidase activity was enhanced greatly, followed by an immediate and rapid decrease. Expression of the MA-ACO1 gene encoding banana ACC oxidase was detectable at the preclimacteric stage, increased when ripening commenced, and then remained high throughout the later ripening stage despite of a rapid reduction in the ACC oxidase activity. This discrepancy between enzyme activity and gene expression of ACC oxidase could be, at least in part, due to reduced contents of ascorbate and iron, cofactors for the enzyme, during ripening. Addition of these cofactors to the incubation medium greatly stimulated the in vivo ACC oxidase activity during late ripening stages. The results suggest that ethylene production in banana fruit is regulated by transcription of MA-ACS1 until climacteric rise and by reduction of ACC oxidase activity possibly through limited in situ availability of its cofactors once ripening has commenced, which in turn characterizes the sharp peak of ethylene production. PMID:10594112

  16. Development of a new paper based nano-biosensor using the co-catalytic effect of tyrosinase from banana peel tissue (Musa Cavendish) and functionalized silica nanoparticles for voltammetric determination of l-tyrosine.

    PubMed

    Rahimi-Mohseni, Mohadeseh; Raoof, Jahan Bakhsh; Ojani, Reza; Aghajanzadeh, Tahereh A; Bagheri Hashkavayi, Ayemeh

    2018-07-01

    In this paper, a new and facile method for the electrochemical determination of l-tyrosine was designed. First, 3-mercaptopropyl trimethoxysilane-functionalized silica nanoparticles were added to a paper disc. Then, the banana peel tissue and the mediator potassium hexacyanoferrate were dropped onto the paper, respectively. The modified paper disc was placed on the top of the graphite screen printed electrode and electrochemical characterization of this biosensor was studied by cyclic voltammetry and electrochemical impedance spectroscopy methods. The effective parameters like pH, banana peel tissue percentage, and the amount of mediator loading were optimized. l-tyrosine measurements were done by differential pulse voltammetry with a little sample (3 μL) for analysis. The biosensor showed a linear response for l-tyrosine in the wide concentration range of 0.05-600 μM and a low detection limit about 0.02 μM because of the co-catalytic effect of enzyme and nanoparticles. The stability of the biosensor and its selectivity were evaluated. This biosensor was applied for the voltammetric determination of l-tyrosine in the blood plasma sample. The results of the practical application study were comparable with the standard method (HPLC). In conclusion, a simple, inexpensive, rapid, sensitive and selective technique was successfully applied to the l-tyrosine analysis of the little samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Improving observational study estimates of treatment effects using joint modeling of selection effects and outcomes: the case of AAA repair.

    PubMed

    O'Malley, A James; Cotterill, Philip; Schermerhorn, Marc L; Landon, Bruce E

    2011-12-01

    When 2 treatment approaches are available, there are likely to be unmeasured confounders that influence choice of procedure, which complicates estimation of the causal effect of treatment on outcomes using observational data. To estimate the effect of endovascular (endo) versus open surgical (open) repair, including possible modification by institutional volume, on survival after treatment for abdominal aortic aneurysm, accounting for observed and unobserved confounding variables. Observational study of data from the Medicare program using a joint model of treatment selection and survival given treatment to estimate the effects of type of surgery and institutional volume on survival. We studied 61,414 eligible repairs of intact abdominal aortic aneurysms during 2001 to 2004. The outcome, perioperative death, is defined as in-hospital death or death within 30 days of operation. The key predictors are use of endo, transformed endo and open volume, and endo-volume interactions. There is strong evidence of nonrandom selection of treatment with potential confounding variables including institutional volume and procedure date, variables not typically adjusted for in clinical trials. The best fitting model included heterogeneous transformations of endo volume for endo cases and open volume for open cases as predictors. Consistent with our hypothesis, accounting for unmeasured selection reduced the mortality benefit of endo. The effect of endo versus open surgery varies nonlinearly with endo and open volume. Accounting for institutional experience and unmeasured selection enables better decision-making by physicians making treatment referrals, investigators evaluating treatments, and policy makers.

  18. Immunoreactivity of the AAA+ chaperone ClpB from Leptospira interrogans with sera from Leptospira-infected animals.

    PubMed

    Krajewska, Joanna; Arent, Zbigniew; Więckowski, Daniel; Zolkiewski, Michal; Kędzierska-Mieszkowska, Sabina

    2016-07-16

    Leptospira interrogans is a spirochaete responsible for leptospirosis in mammals. The molecular mechanisms of the Leptospira virulence remain mostly unknown. Recently, it has been demonstrated that L. interrogans ClpB (ClpBLi) is essential for bacterial survival under stressful conditions and also during infection. The aim of this study was to provide further insight into the role of ClpB in L. interrogans and answer the question whether ClpBLi as a potential virulence factor may be a target of the humoral immune response during leptospiral infections in mammals. ClpBLi consists of 860 amino acid residues with a predicted molecular mass of 96.3 kDa and shows multi-domain organization similar to that of the well-characterized ClpB from Escherichia coli. The amino acid sequence identity between ClpBLi and E. coli ClpB is 52 %. The coding sequence of the clpB Li gene was cloned and expressed in E. coli BL21(DE3) strain. Immunoreactivity of the recombinant ClpBLi protein was assessed with the sera collected from Leptospira-infected animals and uninfected healthy controls. Western blotting and ELISA analysis demonstrated that ClpBLi activates the host immune system, as evidenced by an increased level of antibodies against ClpBLi in the sera from infected animals, as compared to the control group. Additionally, ClpBLi was found in kidney tissues of Leptospira-infected hamsters. ClpBLi is both synthesized and immunogenic during the infectious process, further supporting its involvement in the pathogenicity of Leptospira. In addition, the immunological properties of ClpBLi point to its potential value as a diagnostic antigen for the detection of leptospirosis.

  19. A general method of aquitard control of flow for arbitrary orientation of wells in Aquitard- Aquifer-Aquitard System (AAA)

    NASA Astrophysics Data System (ADS)

    Zhan, H.; Sun, D.

    2006-12-01

    Aquitards are low permeable sedimentary layers that often serve as interfaces through which recharge, contaminants, and nutrients from the vadose zone enter aquifers. Aquitards are capable of storing water, yet lack of ability to transmit water. Hydrologists have recognized the importance of aquitards on subsurface flow and transport for many decades. However, for various reasons, studies of aquitards have received much less attention than that of the aquifers for many years. In this study, we have investigated the effects of aquitard on drawdown caused by arbitrary orientation of well pumping in an aquitard-aquifer-aquitard system. Pumping well could be partial penetrating vertical well, horizontal well or slanted well at arbitrary angles to horizontal plane. We have derived the solutions for six cases with various combinations of water table, aquitard, aquifer, aquitard, and bedrocks. Previous study treated the leakage from aquitard-aquifer mass flux as a volumetric source/sink term in the governing equation of flow in the aquifer. In this study, new semi-analytical solutions are acquired for the aquitard-aquifer-aquitard system via rigorous mass conservation laws. Flows in aquitard and aquifer are treated as separate systems which are linked through the continuity of flux and head at the aquitard-aquifer boundary. This general solution is applicable to both water table aquifer and leaky-confined aquifer. Examples illustrate the effect of aquitard properties at different well configurations. The results will be used to generate type curves for various situations. The results of this paper are useful for parameter identification and water resource management. Keywords: Aquitard-Aquifer-Aquitard; Pumping Well, Slanted Well, Horizontal well, Type curves.

  20. Origin of Man: Problems in the Interpretation of New Evidence. Test Edition. AAAS Study Guides on Contemporary Problems.

    ERIC Educational Resources Information Center

    Almquist, Alan J.; Cronin, John E.

    This is one of several study guides on contemporary problems produced by the American Association for the Advancement of Science with support of the National Science Foundation. This guide focuses on the origin of man. Part I, The Biochemical Evidence for Human Evolution, contains four sections: (1) Introduction; (2) Macromolecular Data; (3)…

  1. Academic Achievement Academy (AAA), 2011-12. Eye on Evaluation. D&A Report No. 13.03

    ERIC Educational Resources Information Center

    Rhea, Anisa

    2013-01-01

    Extending the school day through programs that will supplement core courses, such as offering intensive, after-school tutoring or small-group study sessions in reading and mathematics, is one method districts use to boost school performance and narrow educational achievement gaps between students of different racial and economic backgrounds (Redd…

  2. Wound-induced pectin methylesterases enhance banana (Musa spp. AAA) susceptibility to Fusarium oxysporum f. sp. cubense.

    PubMed

    Ma, Li; Jiang, Shuang; Lin, Guimei; Cai, Jianghua; Ye, Xiaoxi; Chen, Houbin; Li, Minhui; Li, Huaping; Takác, Tomás; Samaj, Jozef; Xu, Chunxiang

    2013-05-01

    Recent studies suggest that plant pectin methylesterases (PMEs) are directly involved in plant defence besides their roles in plant development. However, the molecular mechanisms of PME action on pectins are not well understood. In order to understand how PMEs modify pectins during banana (Musa spp.)-Fusarium interaction, the expression and enzyme activities of PMEs in two banana cultivars, highly resistant or susceptible to Fusarium, were compared with each other. Furthermore, the spatial distribution of PMEs and their effect on pectin methylesterification of 10 individual homogalacturonan (HG) epitopes with different degrees of methylesterification (DMs) were also examined. The results showed that, before pathogen treatment, the resistant cultivar displayed higher PME activity than the susceptible cultivar, corresponding well to the lower level of pectin DM. A significant increase in PME expression and activity and a decrease in pectin DM were observed in the susceptible cultivar but not in the resistant cultivar when plants were wounded, which was necessary for successful infection. With the increase of PME in the wounded susceptible cultivar, the JIM5 antigen (low methyestrified HGs) increased. Forty-eight hours after pathogen infection, the PME activity and expression in the susceptible cultivar were higher than those in the resistant cultivar, while the DM was lower. In conclusion, the resistant and the susceptible cultivars differ significantly in their response to wounding. Increased PMEs and thereafter decreased DMs acompanied by increased low methylesterified HGs in the root vascular cylinder appear to play a key role in determination of banana susceptibility to Fusarium.

  3. Transcripts and MicroRNAs Responding to Salt Stress in Musa acuminata Colla (AAA Group) cv. Berangan Roots.

    PubMed

    Lee, Wan Sin; Gudimella, Ranganath; Wong, Gwo Rong; Tammi, Martti Tapani; Khalid, Norzulaani; Harikrishna, Jennifer Ann

    2015-01-01

    Physiological responses to stress are controlled by expression of a large number of genes, many of which are regulated by microRNAs. Since most banana cultivars are salt-sensitive, improved understanding of genetic regulation of salt induced stress responses in banana can support future crop management and improvement in the face of increasing soil salinity related to irrigation and climate change. In this study we focused on determining miRNA and their targets that respond to NaCl exposure and used transcriptome sequencing of RNA and small RNA from control and NaCl-treated banana roots to assemble a cultivar-specific reference transcriptome and identify orthologous and Musa-specific miRNA responding to salinity. We observed that, banana roots responded to salinity stress with changes in expression for a large number of genes (9.5% of 31,390 expressed unigenes) and reduction in levels of many miRNA, including several novel miRNA and banana-specific miRNA-target pairs. Banana roots expressed a unique set of orthologous and Musa-specific miRNAs of which 59 respond to salt stress in a dose-dependent manner. Gene expression patterns of miRNA compared with those of their predicted mRNA targets indicated that a majority of the differentially expressed miRNAs were down-regulated in response to increased salinity, allowing increased expression of targets involved in diverse biological processes including stress signaling, stress defence, transport, cellular homeostasis, metabolism and other stress-related functions. This study may contribute to the understanding of gene regulation and abiotic stress response of roots and the high-throughput sequencing data sets generated may serve as important resources related to salt tolerance traits for functional genomic studies and genetic improvement in banana.

  4. Developmental localization and the role of hydroxyproline rich glycoproteins during somatic embryogenesis of banana (Musa spp. AAA)

    PubMed Central

    2011-01-01

    Background Hydroxyproline rich glycoproteins (HRGPs) are implicated to have a role in many aspects of plant growth and development but there is limited knowledge about their localization and function during somatic embryogenesis of higher plants. In this study, the localization and function of hydroxyproline rich glycoproteins in embryogenic cells (ECs) and somatic embryos of banana were investigated by using immunobloting and immunocytochemistry with monoclonal JIM11 and JIM20 antibodies as well as by treatment with 3,4-dehydro-L-proline (3,4-DHP, an inhibitor of extensin biosynthesis), and by immunomodulation with the JIM11 antibody. Results Immunofluorescence labelling of JIM11 and JIM20 hydroxyproline rich glycoprotein epitopes was relatively weak in non-embryogenic cells (NECs), mainly on the edge of small cell aggregates. On the other hand, hydroxyproline rich glycoprotein epitopes were found to be enriched in early embryogenic cells as well as in various developmental stages of somatic embryos. Embryogenic cells (ECs), proembryos and globular embryos showed strong labelling of hydroxyproline rich glycoprotein epitopes, especially in their cell walls and outer surface layer, so-called extracellular matrix (ECM). This hydroxyproline rich glycoprotein signal at embryo surfaces decreased and/or fully disappeared during later developmental stages (e.g. pear-shaped and cotyledonary stages) of embryos. In these later developmental embryogenic stages, however, new prominent hydroxyproline rich glycoprotein labelling appeared in tri-cellular junctions among parenchymatic cells inside these embryos. Overall immunofluorescence labelling of late stage embryos with JIM20 antibody was weaker than that of JIM11. Western blot analysis supported the above immunolocalization data. The treatment with 3,4-DHP inhibited the development of embryogenic cells and decreased the rate of embryo germination. Embryo-like structures, which developed after 3,4-DHP treatment showed aberrant non-compact epidermis with discontinuous ECM at the outer surface as well as much less immunolabelling with the JIM11 antibody. This treatment also decreased the plant regeneration capacity in embryogenic banana cultures. Finally, immunomodulation of surface hydroxyproline rich glycoproteins by co-culture of embryos with the JIM11 antibody resulted in a much lower germination capacity of these embryos. Conclusions These results suggest that hydroxyproline rich glycoproteins play an important developmental role, especially in the process of regeneration and germination of embryos during plant regeneration via somatic embryogenesis. Proper content and localization of hydroxyproline rich glycoproteins seem to be essential for the formation and regeneration of banana somatic embryos. PMID:21349190

  5. The Hetero-Hexameric Nature of a Chloroplast AAA+ FtsH Protease Contributes to Its Thermodynamic Stability

    PubMed Central

    Ziv, Tamar; Adam, Zach; Prag, Gali

    2012-01-01

    FtsH is an evolutionary conserved membrane-bound metalloprotease complex. While in most prokaryotes FtsH is encoded by a single gene, multiple FtsH genes are found in eukaryotes. Genetic and biochemical data suggest that the Arabidopsis chloroplast FtsH is a hetero-hexamer. This raises the question why photosynthetic organisms require a heteromeric complex, whereas in most bacteria a homomeric one is sufficient. To gain structural information of the possible complexes, the Arabidopsis FtsH2 (type B) and FtsH5 (type A) were modeled. An in silico study with mixed models of FtsH2/5 suggests that heteromeric hexamer structure with ratio of 4∶2 is more likely to exists. Specifically, calculation of the buried surface area at the interfaces between neighboring subunits revealed that a hetero-complex should be thermodynamically more stable than a homo-hexamer, due to the presence of additional hydrophobic and hydrophilic interactions. To biochemically assess this model, we generated Arabidopsis transgenic plants, expressing epitope-tagged FtsH2 and immuno-purified the protein. Mass-spectrometry analysis showed that FtsH2 is associated with FtsH1, FtsH5 and FtsH8. Interestingly, we found that ‘type B’ subunits (FtsH2 and FtsH8) were 2–3 fold more abundant than ‘type A’ (FtsH1 and FtsH5). The biochemical data corroborate the in silico model and suggest that the thylakoid FtsH hexamer is composed of two ‘type A’ and four ‘type B’ subunits. PMID:22558304

  6. Transcripts and MicroRNAs Responding to Salt Stress in Musa acuminata Colla (AAA Group) cv. Berangan Roots

    PubMed Central

    Lee, Wan Sin; Gudimella, Ranganath; Wong, Gwo Rong; Tammi, Martti Tapani; Khalid, Norzulaani; Harikrishna, Jennifer Ann

    2015-01-01

    Physiological responses to stress are controlled by expression of a large number of genes, many of which are regulated by microRNAs. Since most banana cultivars are salt-sensitive, improved understanding of genetic regulation of salt induced stress responses in banana can support future crop management and improvement in the face of increasing soil salinity related to irrigation and climate change. In this study we focused on determining miRNA and their targets that respond to NaCl exposure and used transcriptome sequencing of RNA and small RNA from control and NaCl-treated banana roots to assemble a cultivar-specific reference transcriptome and identify orthologous and Musa-specific miRNA responding to salinity. We observed that, banana roots responded to salinity stress with changes in expression for a large number of genes (9.5% of 31,390 expressed unigenes) and reduction in levels of many miRNA, including several novel miRNA and banana-specific miRNA-target pairs. Banana roots expressed a unique set of orthologous and Musa-specific miRNAs of which 59 respond to salt stress in a dose-dependent manner. Gene expression patterns of miRNA compared with those of their predicted mRNA targets indicated that a majority of the differentially expressed miRNAs were down-regulated in response to increased salinity, allowing increased expression of targets involved in diverse biological processes including stress signaling, stress defence, transport, cellular homeostasis, metabolism and other stress-related functions. This study may contribute to the understanding of gene regulation and abiotic stress response of roots and the high-throughput sequencing data sets generated may serve as important resources related to salt tolerance traits for functional genomic studies and genetic improvement in banana. PMID:25993649

  7. Wound-induced pectin methylesterases enhance banana (Musa spp. AAA) susceptibility to Fusarium oxysporum f. sp. cubense

    PubMed Central

    Ma, Li; Jiang, Shuang; Lin, Guimei; Cai, Jianghua; Ye, Xiaoxi; Chen, Houbin; Li, Minhui; Li, Huaping; Takáč, Tomáš; Šamaj, Jozef; Xu, Chunxiang

    2013-01-01

    Recent studies suggest that plant pectin methylesterases (PMEs) are directly involved in plant defence besides their roles in plant development. However, the molecular mechanisms of PME action on pectins are not well understood. In order to understand how PMEs modify pectins during banana (Musa spp.)–Fusarium interaction, the expression and enzyme activities of PMEs in two banana cultivars, highly resistant or susceptible to Fusarium, were compared with each other. Furthermore, the spatial distribution of PMEs and their effect on pectin methylesterification of 10 individual homogalacturonan (HG) epitopes with different degrees of methylesterification (DMs) were also examined. The results showed that, before pathogen treatment, the resistant cultivar displayed higher PME activity than the susceptible cultivar, corresponding well to the lower level of pectin DM. A significant increase in PME expression and activity and a decrease in pectin DM were observed in the susceptible cultivar but not in the resistant cultivar when plants were wounded, which was necessary for successful infection. With the increase of PME in the wounded susceptible cultivar, the JIM5 antigen (low methyestrified HGs) increased. Forty-eight hours after pathogen infection, the PME activity and expression in the susceptible cultivar were higher than those in the resistant cultivar, while the DM was lower. In conclusion, the resistant and the susceptible cultivars differ significantly in their response to wounding. Increased PMEs and thereafter decreased DMs acompanied by increased low methylesterified HGs in the root vascular cylinder appear to play a key role in determination of banana susceptibility to Fusarium. PMID:23580752

  8. Revolution rather than rotation of AAA+ hexameric phi29 nanomotor for viral dsDNA packaging without coiling☆

    PubMed Central

    Schwartz, Chad; De Donatis, Gian Marco; Zhang, Hui; Fang, Huaming; Guo, Peixuan

    2013-01-01

    It has long been believed that the DNA-packaging motor of dsDNA viruses utilizes a rotation mechanism. Here we report a revolution rather than rotation mechanism for the bacteriophage phi29 DNA packaging motor. The phi29 motor contains six copies of the ATPase (Schwartz et al., this issue); ATP binding to one ATPase subunit stimulates the ATPase to adopt a conformation with a high affinity for dsDNA. ATP hydrolysis induces a new conformation with a lower affinity, thus transferring the dsDNA to an adjacent subunit by a power stroke. DNA revolves unidirectionally along the hexameric channel wall of the ATPase, but neither the dsDNA nor the ATPase itself rotates along its own axis. One ATP is hydrolyzed in each transitional step, and six ATPs are consumed for one helical turn of 360°. Transition of the same dsDNA chain along the channel wall, but at a location 60° different from the last contact, urges dsDNA to move forward 1.75 base pairs each step (10.5 bp per turn/6ATP=1.75 bp per ATP). Each connector subunit tilts with a left-handed orientation at a 30° angle in relation to its vertical axis that runs anti-parallel to the right-handed dsDNA helix, facilitating the one-way traffic of dsDNA. The connector channel has been shown to cause four steps of transition due to four positively charged lysine rings that make direct contact with the negatively charged DNA phosphate backbone. Translocation of dsDNA into the procapsid by revolution avoids the difficulties during rotation that are associated with DNA supercoiling. Since the revolution mechanism can apply to any stoichiometry, this motor mechanism might reconcile the stoichiometry discrepancy in many phage systems where the ATPase has been found as a tetramer, hexamer, or nonamer. PMID:23763768

  9. Prime Contract Awards Over $25,000 by Major System, Contractor and State. Part 1. (AAA-BSG)

    DTIC Science & Technology

    1989-01-01

    estimated to average I hour per response. including the time for reviewng instructions searching existing data sources,gathering and maintaining the data ...JeffersonDavis highway. Suite 1204, Arlington, VA 22202,4302, and to the Office of Management and Budget. Paperwork Reduction Prolect (0704.018I), Washington, DC...IN W) MNMP l )C)C) ciMP l l1-I z cJ~ ICC cl IN C) 0(Du’)-. It) Nr.~- (DM In- - 141 I 4~~ t 06 0. E E I I CLcIcII T . I I UcI . u ) c ct)a 4)C ) wa

  10. Randomised clinical trial: efficacy, safety and dosage of adjunctive allopurinol in azathioprine/mercaptopurine nonresponders (AAA Study).

    PubMed

    Friedman, A B; Brown, S J; Bampton, P; Barclay, M L; Chung, A; Macrae, F A; McKenzie, J; Reynolds, J; Gibson, P R; Hanauer, S B; Sparrow, M P

    2018-04-01

    Thiopurine hypermethylation towards 6-methylmercaptopurine (6MMP) instead of 6-thioguanine nucleotides (6TGN) is associated with inefficacy in patients with IBD. Allopurinol reverses such hypermethylation. To prospectively determine efficacy of allopurinol-thiopurine combination and to compare 2 doses of allopurinol. In a multicentre, double-blind trial, patients with clinically active or steroid-dependent IBD and thiopurine shunting were randomised to 50 or 100 mg/d allopurinol and 25% of their screening thiopurine dose, which was subsequently optimised, aiming for 6TGN of 260-500 pmol/8x10 8 RBCs. The primary endpoint was steroid-free clinical remission at 24 weeks. Of 73 patients, 39 (53% [95% CI 42-65]) achieved steroid-free remission, (54% with 50 mg/d and 53% with 100 mg/d). 81% were able to discontinue steroids. Therapeutic 6TGN levels were achieved in both groups. Final thiopurine doses were lower with 100 mg/d allopurinol (P < 0.005). 6MMP: 6TGN ratio decreased from mean 64 to 4 (P < 0.001), being higher with 50 mg/d (6 ± 1.83) than for 100 mg/d ([1 ± 0.16], P = 0.003). Three patients on 50 mg/d failed to sustain low ratios at 24 weeks. Toxicity was minimal; three patients on 50 mg/d allopurinol developed transient leukopenia. Alanine aminotransferase concentrations decreased (P < 0.001) similarly in both arms. Faecal calprotectin levels at study end were lower in patients who achieved the primary endpoint (median 171 [85-541] vs 821[110-5892] ug/g, P = 0.03). Low-dose allopurinol-thiopurine combination safely reverses shunting and optimises 6TGN with associated improvement in disease activity. 100 mg/d allopurinol is preferable due to greater metabolite profile stability and lower thiopurine dose without additional toxicity. © 2018 John Wiley & Sons Ltd.

  11. Optimatization of transient transformation methods to study gene expression in Musa acuminata (AAA group) cultivar Ambon Lumut

    NASA Astrophysics Data System (ADS)

    Prayuni, Kinasih; Dwivany, Fenny M.

    2015-09-01

    Banana is classified as a climateric fruit, whose ripening is regulated by ethylene. Ethylene is synthesized from ACC (1-aminocyclopropane-1-carboxylic acid) by ACC oxidase enzyme which is encoded by ACO gene. Controling an important gene expression in ethylene biosynthesis pathway has became a target to delay the ripening process. Therefore in the previous study we have designed a MaACO-RNAi construct to control MaACO gene expression. In this research, we study the effectiveness of different transient transformation methods to deliver the construct. Direct injection, with or no vaccum infiltration methods were used to deliver MaACO-RNAi construct. All of the methods succesfully deliver the construct into banana fruits based on RT-PCR result.

  12. Evaluation of optimal control type models for the human gunner in an Anti-Aircraft Artillery (AAA) system

    NASA Technical Reports Server (NTRS)

    Phatak, A. V.; Kessler, K. M.

    1975-01-01

    The selection of the structure of optimal control type models for the human gunner in an anti aircraft artillery system is considered. Several structures within the LQG framework may be formulated. Two basic types are considered: (1) kth derivative controllers; and (2) proportional integral derivative (P-I-D) controllers. It is shown that a suitable criterion for model structure determination can be based on the ensemble statistics of the tracking error. In the case when the ensemble tracking steady state error is zero, it is suggested that a P-I-D controller formulation be used in preference to the kth derivative controller.

  13. McArthur rotates the CHeCS rack back into position after cleaning the AAA fan

    NASA Image and Video Library

    2005-12-01

    ISS012-E-09931 (1 December 2005) --- Astronaut William S. (Bill) McArthur Jr., Expedition 12 commander and NASA space station science officer, rotates the Crew Health Care System (CHeCS) rack back into position after cleaning the Avionics Air Assembly fan in the Destiny laboratory of the International Space Station.

  14. Human Origins: Problems in the Interpretation of New Evidence. Third Edition. AAAS Study Guides on Contemporary Problems.

    ERIC Educational Resources Information Center

    Almquist, Alan J.; Cronin, John E.

    This Chautauqua-type short course in human evolution is divided into two parts: The Biochemical Evidence for Human Evolution, and the Fossil Evidence for Human Evolution. The first part covers the comparison of macromolecular differences between species. This includes comparison of DNA base-ratios and amino acid substitution in enzymes and other…

  15. Proceedings of an AAAS Symposium on January 8, 1980: How Much does the Defense Department Advance Science?

    DTIC Science & Technology

    1980-09-24

    DEFENSE OF FREEDOM 18 Edward Teller DANGERS OF USING SCIENCE FOR THE ARMS BUSINESS IN A CORPORATE STATE 21 George Wald DISCUSSION . 25...many other questions. Does the Don’s basic-research program oversupport research which is oriented to the solution of applied problems? Has DOD...long-range goal of being technologically superior in the world. We would be very short-sighted if our program was directed only to the solution of

  16. Description of human AAA by cytokine and immune cell aberrations compared to risk-factor matched controls.

    PubMed

    Wang, S Keisin; Green, Linden A; Gutwein, Ashley R; Drucker, Natalie A; Motaganahalli, Raghu L; Gupta, Alok K; Fajardo, Andres; Murphy, Michael P

    2018-04-28

    The pathogenesis driving the formation of abdominal aortic aneurysms continues to be poorly understood. Therefore, we systemically define the cytokine and circulating immune cell environment observed in human abdominal aortic aneurysm compared with risk-factor matched controls. From 2015 to 2017, a total of 274 patients donated blood to the Indiana University Center for Aortic Disease. Absolute concentrations of circulating cytokines were determined, using enzyme-linked immunosorbent assays while the expression of circulating immune cell phenotypes were assayed via flow cytometric analysis. Human abdominal aortic aneurysm is characterized by a significant depletion of the antigen-specific, CD4 + Tr1 regulatory lymphocyte that corresponds to an upregulation of the antigen-specific, inflammatory Th17 cell. We found no differences in the incidence of Treg, B10, and myeloid-derived suppressor regulatory cells. Similarly, no disparities were noted in the following inflammatory cytokines: IL-1β, C-reactive protein, tumor necrosis factor α, interferon γ, and IL-23. However, significant upregulation of the inflammatory cytokines osteopontin, IL-6, and IL-17 were noted. Additionally, no changes were observed in the regulatory cytokines IL-2, IL-4, IL-13, TNF-stimulated gene 6 protein, and prostaglandin E2, but we did observe a significant decrease in the essential regulatory cytokine IL-10. In this investigation, we systematically characterize the abdominal aortic aneurysm-immune environment and present preliminary evidence that faulty immune regulation may also contribute to aneurysm formation and growth. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. The Role of the N-Domain in the ATPase Activity of the Mammalian AAA ATPase p97/VCP*

    PubMed Central

    Niwa, Hajime; Ewens, Caroline A.; Tsang, Chun; Yeung, Heidi O.; Zhang, Xiaodong; Freemont, Paul S.

    2012-01-01

    p97/valosin-containing protein (VCP) is a type II ATPase associated with various cellular activities that forms a homohexamer with each protomer containing an N-terminal domain (N-domain); two ATPase domains, D1 and D2; and a disordered C-terminal region. Little is known about the role of the N-domain or the C-terminal region in the p97 ATPase cycle. In the p97-associated human disease inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, the majority of missense mutations are located at the N-domain D1 interface. Structure-based predictions suggest that such mutations affect the interaction of the N-domain with D1. Here we have tested ten major inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia-linked mutants for ATPase activity and found that all have increased activity over the wild type, with one mutant, p97A232E, having three times higher activity. Further mutagenesis of p97A232E shows that the increase in ATPase activity is mediated through D2 and requires both the N-domain and a flexible ND1 linker. A disulfide mutation that locks the N-domain to D1 in a coplanar position reversibly abrogates ATPase activity. A cryo-EM reconstruction of p97A232E suggests that the N-domains are flexible. Removal of the C-terminal region also reduces ATPase activity. Taken together, our data suggest that the conformation of the N-domain in relation to the D1-D2 hexamer is directly linked to ATP hydrolysis and that the C-terminal region is required for hexamer stability. This leads us to propose a model where the N-domain adopts either of two conformations: a flexible conformation compatible with ATP hydrolysis or a coplanar conformation that is inactive. PMID:22270372

  18. Molecular cloning and characterisation of banana fruit polyphenol oxidase.

    PubMed

    Gooding, P S; Bird, C; Robinson, S P

    2001-09-01

    Polyphenol oxidase (PPO; EC 1.10.3.2) is the enzyme thought to be responsible for browning in banana [Musa cavendishii (AAA group, Cavendish subgroup) cv. Williams] fruit. Banana flesh was high in PPO activity throughout growth and ripening. Peel showed high levels of activity early in development but activity declined until ripening started and then remained constant. PPO activity in fruit was not substantially induced after wounding or treatment with 5-methyl jasmonate. Banana flowers and unexpanded leaf roll had high PPO activities with lower activities observed in mature leaves, roots and stem. Four different PPO cDNA clones were amplified from banana fruit (BPO1, BPO11, BPO34 and BPO35). Full-length cDNA and genomic clones were isolated for the most abundant sequence (BPO1) and the genomic clone was found to contain an 85-bp intron. Introns have not been previously found in PPO genes. Northern analysis revealed the presence of BPO1 mRNA in banana flesh early in development but little BPO1 mRNA was detected at the same stage in banana peel. BPO11 transcript was only detected in very young flesh and there was no detectable expression of BPO34 or BPO35 in developing fruit samples. PPO transcripts were also low throughout ripening in both flesh and peel. BPO1 transcripts were readily detected in flowers, stem, roots and leaf roll samples but were not detected in mature leaves. BPO11 showed a similar pattern of expression to BPO1 in these tissues but transcript levels were much lower. BPO34 and BPO35 mRNAs were only detected at a low level in flowers and roots and BPO34 transcript was detected in mature leaves, the only clone to do so. The results suggest that browning of banana fruit during ripening results from release of pre-existing PPO enzyme, which is synthesised very early in fruit development.

  19. Characterization of an AGAMOUS-like MADS Box Protein, a Probable Constituent of Flowering and Fruit Ripening Regulatory System in Banana

    PubMed Central

    Roy Choudhury, Swarup; Roy, Sujit; Nag, Anish; Singh, Sanjay Kumar; Sengupta, Dibyendu N.

    2012-01-01

    The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ∼95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development. PMID:22984496

  20. Characterization of an AGAMOUS-like MADS box protein, a probable constituent of flowering and fruit ripening regulatory system in banana.

    PubMed

    Roy Choudhury, Swarup; Roy, Sujit; Nag, Anish; Singh, Sanjay Kumar; Sengupta, Dibyendu N

    2012-01-01

    The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ~95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development.

  1. Characterization of differential ripening pattern in association with ethylene biosynthesis in the fruits of five naturally occurring banana cultivars and detection of a GCC-box-specific DNA-binding protein.

    PubMed

    Choudhury, Swarup Roy; Roy, Sujit; Saha, Progya Paramita; Singh, Sanjay Kumar; Sengupta, Dibyendu N

    2008-07-01

    MA-ACS1 and MA-ACO1 are the two major ripening genes in banana and play crucial role in the regulation of ethylene production during ripening. Here, we report a comparative ripening pattern in five different naturally occurring banana cultivars namely Cavendish (AAA), Rasthali (AAB), Kanthali (AB), Poovan (AAB) and Monthan (ABB), which have distinct genome composition. We found a distinct variation in the climacteric ethylene production and in-vivo ACC oxidase activity level during the ripening stages in the five cultivars. We identified the cDNAs for MA-ACS1 and MA-ACO1 from the five cultivars and studied the transcript accumulation patterns of the two genes, which correlated well with the differential timing in the expression of these two genes during ripening. The GCC-box is one of the ethylene-responsive elements (EREs) found in the promoters of many ethylene-inducible genes. We have identified a GCC-box motif (putative ERE) in the promoters of MA-ACS1 and MA-ACO1 in banana cultivars. DNA-protein interaction studies revealed the presence of a GCC-box-specific DNA-binding activity in the fruit nuclear extract and such DNA-binding activity was enhanced following ethylene treatment. South-Western blotting revealed a 25-kDa nuclear protein that binds specifically to GCC-box DNA in the climacteric banana fruit. Together, these results indicate the probable involvement of the GCC-box motif as the cis-acting ERE in the regulation of MA-ACS1 and MA-ACO1 during ripening in banana fruits via binding of specific ERE-binding protein.

  2. Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm

    PubMed Central

    Uchida, Haruhito A.; Kakio, Yuki; Umebayashi, Ryoko; Okuyama, Yuka; Fujii, Yasuhiro; Ozawa, Susumu; Yoshida, Masashi; Oshima, Yu; Sano, Shunji; Wada, Jun

    2016-01-01

    Background and Aims Chronic kidney disease (CKD) and diabetes mellitus (DM) are considered as risk factors for cardiovascular diseases. The purpose of this study was to clarify the relationship of CKD and DM with the presence of abdominal aortic aneurysm (AAA). Methods We enrolled 261 patients with AAA (AAA+) and age-and-sex matched 261 patients without AAA (AAA-) at two hospitals between 2008 and 2014, and examined the association between the risk factors and the presence of AAA. Furthermore, in order to investigate the prevalence of AAA in each group, we enrolled 1126 patients with CKD and 400 patients with DM. Results The presence of CKD in patients with AAA+ was significantly higher than that in patients with AAA- (AAA+; 65%, AAA-; 52%, P = 0.004). The presence of DM in patients with AAA+ was significantly lower than that in patients with AAA- (AAA+; 17%, AAA-; 35%, P < 0.001). A multivariate logistic regression analysis demonstrated that hypertension, ischemic heart disease and CKD were independent determinants, whereas, DM was a negatively independent determinant, for the presence of AAA. The prevalence of AAA in patients with CKD 65 years old and above was 5.1%, whereas, that in patients with DM 65 years old and above was only 0.6%. Conclusion CKD is a positively associated with the presence of AAA. In contrast, DM is a negatively associated with the presence of AAA in Japanese population. PMID:27764090

  3. Dietary intervention with green dwarf banana flour (Musa sp AAA) prevents intestinal inflammation in a trinitrobenzenesulfonic acid model of rat colitis.

    PubMed

    Scarminio, Viviane; Fruet, Andrea C; Witaicenis, Aline; Rall, Vera L M; Di Stasi, Luiz C

    2012-03-01

    Dietary products are among the therapeutic approaches used to modify intestinal microflora and to promote protective effects during the intestinal inflammatory process. Because the banana plant is rich in resistant starch, which is used by colonic microbiota for the anaerobic production of the short-chain fatty acids that serve as a major fuel source for colonocytes: first, green dwarf banana flour produces protective effects on the intestinal inflammation acting as a prebiotic and, second, combination of this dietary supplementation with prednisolone presents synergistic effects. For this, we used the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Our results revealed that the protective effect produced by a combination of 10% green dwarf banana flour with prednisolone was more pronounced than those promoted by a single administration of prednisolone or a diet containing 10% or 20% banana flour. This beneficial effect was associated with an improvement in the colonic oxidative status because the banana flour diet prevented the glutathione depletion and inhibited myeloperoxidase activity and lipid peroxidation. In addition, the intestinal anti-inflammatory activity was associated with an inhibition of alkaline phosphatase activity, a reduction in macroscopic and microscopic scores, and an extension of the lesions. In conclusion, the dietary use of the green dwarf banana flour constitutes an important dietary supplement and complementary medicine product to prevention and treatment of human inflammatory bowel disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Contributions to the history of psychology: XC. Evolutionary biology and heritable traits (with reference to oriental-white-black differences): the 1989 AAAS paper.

    PubMed

    Rushton, J P

    1992-12-01

    Genetic distance estimates calculated from DNA sequencing indicate that in years since emergence from the ancestral hominid line, Mongoloids = 41,000, Caucasoids = 110,000, and Negroids = 200,000. Data also show that this succession is matched by numerous other differences such that Mongoloids > Caucasoids > Negroids in brain size and intelligence (cranial capacity = 1448, 1408, 1334 cm3; brain weight = 1351, 1336, 1286 gm.; millions of excess neurons = 8900, 8650, 8550; IQ = 107, 100, 85); maturational delay (age to walk alone, age of first intercourse, age of death); sexual restraint (ovulation rate, intercourse frequencies, sexually transmitted diseases including AIDS); quiescent temperament (aggressiveness, anxiety, sociability); and social organization (law abidingness, marital stability, mental health). This pattern is ordered by a theory of r/K reproductive strategies in which Mongoloids are posited to be more K-selected than Caucasoids and especially more than Negroids. (K-selected reproductive strategies emphasize parental care and are to be contrasted with r-selected strategies which emphasize fecundity, the bioenergetic trade-off between which is postulated to underlie cross-species differences in brain size, speed of maturation, reproductive effort, and longevity.) It is suggested that this pattern came about because the ice ages exerted greater selection pressures on the later emerging populations to produce larger brains, longer lives, and more K-like behavior. One theoretical possibility is that evolution is progressive and that some populations are more "advanced" than others. Predictions are made concerning economic projections and the spread of AIDS.

  5. The AAA Risk Factors Scale: A New Model to Screen for the Risk of Asthma, Allergic Rhinitis and Atopic Dermatitis in Children.

    PubMed

    Hallit, Souheil; Raherison, Chantal; Malaeb, Diana; Hallit, Rabih; Kheir, Nelly; Salameh, Pascale

    2018-06-07

    To create an allergic disease risk factors scale score that would screen for the risk assessment of asthma, allergic rhinitis and atopic dermatitis in children from 3-17 years. This case-control study, conducted between December 2015 and April 2016, enrolled 1274 children. The allergic disease risk factors scale was created by combining environmental, exposure to toxics during pregnancy and breastfeeding and parental history of allergic diseases. Playing on carpets, male gender, child's respiratory problems or history of eczema before the age of 2 years, and humidity significantly increased the odds of allergies in the child. Maternal waterpipe smoking, maternal history of rhinitis, history of asthma in the mother or the father, along with the maternal drug intake or alcohol consumption during pregnancy significantly increased the odds of allergies in the child. There was a significant increase in allergy diseases per category of the allergic disease risk factors scale (p < 0.001 for trend). Scores ≤ 2.60 best represented control individuals, while scores > 5.31 best represented children with allergic diseases. Allergic diseases seem to be linked to several risk factors in our population of school children. Many environmental factors might be incriminated in these allergic diseases. ©2018The Author(s). Published by S. Karger AG, Basel.

  6. Gerald L. Epstein, PhD: director, center for science, technology, and security policy, American Association for the Advancement of Science (AAAS). Interview by Madeline Drexler.

    PubMed

    Epstein, Gerald L

    2009-12-01

    Over his entire career, Gerald Epstein has toiled at the nexus of science, technology, and security. From 2003 to 2009, he was Senior Fellow for Science and Security at the Center for Strategic and International Studies Homeland Security Program, where he worked on reducing biological weapons threats, improving national preparedness, and easing potential tensions between the scientific research and national security communities. Epstein came to CSIS from the Institute for Defense Analyses. From 1996 to 2001, he served in the White House Office of Science and Technology Policy. And from 1983 to 1989, and again from 1991 until its demise in 1995, Epstein worked at the Congressional Office of Technology Assessment, where he directed a study on the proliferation of weapons of mass destruction, alongside research on other global security topics. A recognized expert in biological risk reduction, Epstein was actually trained as a physicist, having received SB degrees in physics and electrical engineering from MIT, and a PhD in physics from the University of California at Berkeley. How, then, did he come to study the evolving threat from bioterrorism? "What compelled me about bioterrorism was that it was a stellar example of a topic that would lead to a train wreck between the scientific community and the security community unless they figured out how to work together," he said. "The distance between a laboratory and a very large consequence event is a lot shorter in biology than in any other field. I got into bioterrorism to help make sure that the security community doesn't get so scared of the science that it shuts it down, and that the science community isn't so oblivious of security concerns that it pays no attention to them." Epstein spoke on November 6, 2009, with contributing writer Madeline Drexler, author of Emerging Epidemics: The Menace of New Infections (Penguin, 2009), an updated version of an earlier volume. Drexler holds a visiting appointment at the Harvard School of Public Health and is a senior fellow at Brandeis University's Schuster Institute for Investigative Journalism.

  7. Proposal of AAA-battery-size one-shot ATR Fourier spectroscopic imager for on-site analysis: Simultaneous measurement of multi-components with high accuracy

    NASA Astrophysics Data System (ADS)

    Hosono, Satsuki; Qi, Wei; Sato, Shun; Suzuki, Yo; Fujiwara, Masaru; Hiramatsu, Hiroyuki; Suzuki, Satoru; Abeygunawardhana, P. K. W.; Wada, Kenji; Nishiyama, Akira; Ishimaru, Ichiro

    2015-03-01

    For simultaneous measurement of multi-components on-site like factories, the ultra-compact (diameter: 9[mm], length: 45[mm], weight: 200[g]) one-shot ATR (Attenuated Total Reflection) Fourier spectroscopic imager was proposed. Because the proposed one-shot Fourier spectroscopic imaging is based on spatial-phase-shift interferometer, interferograms could be obtained with simple optical configurations. We introduced the transmission-type relativeinclined phase-shifter, that was constructed with a cuboid prism and a wedge prism, onto the optical Fourier transform plane of infinity corrected optical systems. And also, small light-sources and cameras in the mid-infrared light region, whose size are several millimeter on a side, are essential components for the ultra-compact spectroscopic configuration. We selected the Graphite light source (light source area: 1.7×1.7[mm], maker: Hawkeye technologies) whose radiation factor was high. Fortunately, in these days we could apply the cost-effective 2-dimensional light receiving device for smartphone (e.g. product name: LEPTON, maker: FLIR, price: around 400USD). In the case of alcoholic drinks factory, conventionally workers measure glucose and ethanol concentrations by bringing liquid solution back to laboratories every day. The high portable spectroscopy will make it possible to measure multi-components simultaneously on manufacturing scene. But we found experimentally that absorption spectrum of glucose and water and ethanol were overlapped each other in near infrared light region. But for mid-infrared light region, we could distinguish specific absorption peaks of glucose (@10.5[μm]) and ethanol (@11.5[μm]) independently from water absorption. We obtained standard curve between absorption (@9.6[μm]) and ethanol concentration with high correlation coefficient 0.98 successfully by ATR imaging-type 2-dimensional Fourier spectroscopy (wavelength resolution: 0.057[μm]) with the graphite light source (maker: Hawkeye technologies, type: IR-75).

  8. Enhanced yield of phenolic extracts from banana peels (Musa acuminata Colla AAA) and cinnamon barks (Cinnamomum varum) and their antioxidative potentials in fish oil.

    PubMed

    Anal, Anil Kumar; Jaisanti, Sirorat; Noomhorm, Athapol

    2014-10-01

    The bioactive compounds of banana peels and cinnamon barks were extracted by vacuum microwave and ultrasonic-assisted extraction methods at pre-determined temperatures and times. These methods enhance the yield extracts in shorter time. The highest yields of both extracts were obtained from the conditions which employed the highest temperature and the longest time. The extracts' yield from cinnamon bark method was higher by ultrasonic than vacuum microwave method, while vacuum microwave method gave higher extraction yield from banana peel than ultrasonic method. The phenolic contents of cinnamon bark and banana peel extracts were 467 and 35 mg gallic acid equivalent/g extract, respectively. The flavonoid content found in banana peel and cinnamon bark extracts were 196 and 428 mg/g quercetin equivalent, respectively. In addition, it was found that cinnamon bark gave higher 2,2-Diphenyl-1-1 picryhydrazyl (DPPH) radical scavenging activity and total antioxidant activity (TAA). The antioxidant activity of the extracts was analyzed by measuring the peroxide and p-anisidine values after oxidation of fish oils, stored for a month (30 days) at 25 °C and showed lesser peroxide and p-anisidine values in the fish oils containing the sample extracts in comparison to the fish oil without containing any extract. The banana peel and cinnamon extracts had shown the ability as antioxidants to prevent the oxidation of fish oil and might be considered as rich sources of natural antioxidant.

  9. The Influence of Preoperative Aneurysmal Thrombus Quantity and Distribution on the Development of Type II Endoleaks with Aneurysm Sac Enlargement After EVAR of AAA

    SciTech Connect

    Müller-Wille, R., E-mail: rene.mueller-wille@ukr.de; Güntner, O., E-mail: oliverguentner@yahoo.de; Zeman, F., E-mail: florian.zeman@ukr.de

    PurposeTo determine the influence of preoperative aneurysmal thrombus quantity and distribution on the development of type II endoleak with aneurysm sac enlargement after endovascular aneurysm repair (EVAR).Materials and MethodsWe retrospectively analyzed the pre- and postoperatively performed CT scans of 118 patients who had follow-up imaging for at least 1 year after EVAR available. We assessed preoperative thrombus perimeter (T{sub Peri}), diameter (T{sub Dia}), cross-sectional area (T{sub CSA}), and volume (T{sub Vol}). The preoperative thrombus distribution was classified into no thrombus, semilunar-shaped (anterior, right side, left side, posterior) thrombus, and circumferential type thrombus. The number of preoperative patent aortic side branches (ASB)more » was identified. Endpoint was type II endoleak with aneurysm volume (A{sub Vol}) increase of ≥5 % during follow-up.ResultsDuring follow-up (2 years, range 1–9 years), 17 patients with type II endoleak had significant A{sub Vol} increase. Less preoperative T{sub Peri}, T{sub Dia}, T{sub CSA}, and T{sub Vol} were associated with A{sub Vol} increase. A circumferential thrombus distribution significantly protected against aneurysm enlargement (p = 0.028). The variables with the strongest significance for A{sub Vol} increase were preoperative T{sub Vol}/A{sub Vol} ratio (OR 0.95; p = 0.037) and number of patent ASB (OR 3.52; p < 0.001).ConclusionA low preoperative T{sub Vol}/A{sub Vol} ratio and a high number of patent ASB were associated with aneurysm sac enlargement after EVAR.« less

  10. Potential of UVC germicidal irradiation in suppressing crown rot disease, retaining postharvest quality and antioxidant capacity of Musa AAA "Berangan" during fruit ripening.

    PubMed

    S Mohamed, Nuratika Tamimi; Ding, Phebe; Kadir, Jugah; M Ghazali, Hasanah

    2017-09-01

    Crown rot caused by fungal pathogen is the most prevalent postharvest disease in banana fruit that results significant economic losses during transportation, storage, and ripening period. Antifungal effects of ultraviolet C (UVC) irradiation at doses varied from 0.01 to 0.30 kJ m -2 were investigated in controlling postharvest crown rot disease, maintenance of fruit quality, and the effects on antioxidant capacity of Berangan banana fruit during ripening days at 25 ± 2°C and 85% RH. Fruits irradiated with 0.30 kJ m -2 exhibited the highest (i.e., 62.51%) reduction in disease severity. However, the application of UVC at all doses caused significant browning damages on fruit peel except the dose of 0.01 kJ m -2 . This dose synergistically reduced 46.25% development of postharvest crown and did not give adverse effects on respiration rate, ethylene production, weight loss, firmness, color changes, soluble solids concentration, titratable acidity, and pH in banana as compared to the other treatments and control. Meanwhile, the dose also enhanced a significant higher level of total phenolic content, FRAP, and DPPH values than in control fruits indicating the beneficial impact of UVC in fruit nutritional quality. The results of scanning electron micrographs confirmed that UVC irradiation retarded the losses of wall compartments, thereby maintained the cell wall integrity in the crown tissue of banana fruit. The results suggest that using 0.01 kJ m -2 UVC irradiation dose as postharvest physical treatment, the crown rot disease has potential to be controlled effectively together with maintaining quality and antioxidant of banana fruit.

  11. Selection of assessment methods for evaluating banana weevil Cosmopolites sordidus (Coleoptera: Curculionidae) damage on highland cooking banana (Musa spp., genome group AAA-EA).

    PubMed

    Gold, C S; Ragama, P E; Coe, R; Rukazambuga, N D T M

    2005-04-01

    Cosmopolites sordidus (Germar) is an important pest on bananas and plantains. Population build-up is slow and damage becomes increasingly important in successive crop cycles (ratoons). Yield loss results from plant loss, mat disappearance and reduced bunch size. Damage assessment requires destructive sampling and is most often done on corms of recently harvested plants. A wide range of damage assessment methods exist and there are no agreed protocols. It is critical to know what types of damage best reflect C. sordidus pest status through their relationships with yield loss. Multiple damage assessment parameters (i.e. for the corm periphery, cortex and central cylinder) were employed in two yield loss trials and a cultivar-screening trial in Uganda. Damage to the central cylinder had a greater effect on plant size and yield loss than damage to the cortex or corm periphery. In some cases, a combined assessment of damage to the central cylinder and cortex showed a better relationship with yield loss than an assessment of the central cylinder alone. Correlation, logistic and linear regression analyses showed weak to modest correlations between damage to the corm periphery and damage to the central cylinder. Thus, damage to the corm periphery is not a strong predictor of the more important damage to the central cylinder. Therefore, C. sordidus damage assessment should target the central cylinder and cortex.

  12. Effects of pretreatments of banana (Musa AAA,Omini) on the composition, rheological properties, and baking quality of its flour and composite blends with wheat flour.

    PubMed

    Bakare, Adegoke H; Ogunbowale, Olukemi D; Adegunwa, Mojisola O; Olusanya, Joseph O

    2017-03-01

    Effects of chemical and heat pretreatments on the protein, gluten, and alpha-amylase activity, pasting (Peak [ P ], Final [ F ] setback [ S ] viscosity, pasting temperature [ PT ] and time [ T ]) and alveogram (Energy [ E ], maximum inflation [ MI ], P / L , and elasticity index [ EI ]) properties of flour from the pretreated bananas and its composite with wheat flour (WF) were examined. The baking (water absorption [WA] and specific volume [SV]) and sensory properties of bread produced from the flour were also examined. Protein, gluten, and alpha-amylase activity ranged from 4.75 ± 0.07%, 30.25 ± 0.05%, and 4.00 ± 0.05 min to 13.75 ± 0.06%, 35.64 ± 0.06%, and 39.61 ± 1.18 min with WF:PTBF/95:05, WF:CTBF/00:100, WF:BBF/80:20, WF:100 and WF:CTBF/00:100, WF:PTBF/95:05, WF:100, WF:PTBF/00:100 having lowest and highest values, respectively. P , F , S viscosities, PT and T ranged from 186.17 ± 0.71, 217.08 ± 1.41, 38.92 ± 5.42 RVU, 84.70 ± 0.28°C, 5.04 ± 0.05 min to 461.0 ± 5.07, 348.5 ± 8.84, 88.83 ± 0.24 RVU, 87.20 ± 0.00°C, 6.24 ± 0.05 min, respectively. E , MI , P / L , and EI ranged from 141.50 ± 0.71 × 10 -4 J, 15.35 ± 0.07, 0.59 ± 0.83 and 35.85 ± 0.07 to 325.00 ± 1.4 × 10 -4 J, 22.55 ± 0.07, 2.75 ± 0.07, and 70.50 ± 0.71, respectively. WA and SV were 48.12 ± 0.07 to 52.60 ± 0.14 and 2.850 ± 0.07 to 5.635 ± 0.18 with the WF having significantly ( P  < 0.05) higher values than other blends and the most acceptable in terms of appearance and taste.

  13. Isolation and Identification of Putative Protein Substrates of the AAA+ Molecular Chaperone ClpB from the Pathogenic Spirochaete Leptospira interrogans.

    PubMed

    Krajewska, Joanna; Arent, Zbigniew; Zolkiewski, Michal; Kędzierska-Mieszkowska, Sabina

    2018-04-18

    Bacterial ClpB is an ATP-dependent Hsp100 chaperone that reactivates aggregated proteins in cooperation with the DnaK chaperone system and promotes survival of bacteria under stress conditions. A large number of publications also indicate that ClpB supports the virulence of bacteria, including a pathogenic spirochaete Leptospira interrogans responsible for leptospirosis in both animals and humans. However, the exact role of ClpB in bacterial pathogenicity remains poorly characterized. It can be assumed that ClpB, due to its role as the molecular chaperone, mediates refolding of essential bacterial proteins, including the known virulence factors, which may become prone to aggregation under infection-induced stresses. In this study, we identified putative substrates of ClpB from L. interrogans (ClpB Li ). For this purpose, we used a proteomic approach combining the ClpB-Trap affinity pull-down assays, Liquid chromatography-tandem mass spectrometry (LC-MS-MS/MS), and bioinformatics analyses. Most of the identified proteins were enzymes predominantly associated with major metabolic pathways like the tricarboxylic acid (TCA) cycle, glycolysis–gluconeogenesis and amino acid and fatty acid metabolism. Based on our proteomic study, we suggest that ClpB can support the virulence of L. interrogans by protecting the conformational integrity and catalytic activity of multiple metabolic enzymes, thus maintaining energy homeostasis in pathogen cells.

  14. The Crystal Structure of the Ubiquitin-like Domain of Ribosome Assembly Factor Ytm1 and Characterization of Its Interaction with the AAA-ATPase Midasin*

    PubMed Central

    Romes, Erin M.; Sobhany, Mack; Stanley, Robin E.

    2016-01-01

    The synthesis of eukaryotic ribosomes is a complex, energetically demanding process requiring the aid of numerous non-ribosomal factors, such as the PeBoW complex. The mammalian PeBoW complex, composed of Pes1, Bop1, and WDR12, is essential for the processing of the 32S preribosomal RNA. Previous work in Saccharomyces cerevisiae has shown that release of the homologous proteins in this complex (Nop7, Erb1, and Ytm1, respectively) from preribosomal particles requires Rea1 (midasin or MDN1 in humans), a large dynein-like protein. Midasin contains a C-terminal metal ion-dependent adhesion site (MIDAS) domain that interacts with the N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 as well as the UBL domain of Rsa4/Nle1 in a later step in the ribosome maturation pathway. Here we present the crystal structure of the UBL domain of the WDR12 homologue from S. cerevisiae at 1.7 Å resolution and demonstrate that human midasin binds to WDR12 as well as Nle1 through their respective UBL domains. Midasin contains a well conserved extension region upstream of the MIDAS domain required for binding WDR12 and Nle1, and the interaction is dependent upon metal ion coordination because removal of the metal or mutation of residues that coordinate the metal ion diminishes the interaction. Mammalian WDR12 displays prominent nucleolar localization that is dependent upon active ribosomal RNA transcription. Based upon these results, we propose that release of the PeBoW complex and subsequent release of Nle1 by midasin is a well conserved step in the ribosome maturation pathway in both yeast and mammalian cells. PMID:26601951

  15. The Antiaircraft Journal. Volume 95, Number 2, March-April 1952

    DTIC Science & Technology

    1952-04-01

    Command, Yoko- hama. Breuning, E. G., Far East Command, Yoko- hama Cacchiotti, Ralph R., 31st AAA Brig., Ft Lewis, Wash. Colbert , Edward F., 197th AAA Gp...Wilbur B., 47th AAA Brig., Cp Stew- art, Ga. Frick, Edwin J., 336th AAA Gun Bn, Cp Ed- wards. Mass. Gildon, Milo E., USA Alaska, Fort Richard- son

  16. Distinguishing Grenvillian basement from pre-Taconian cover rocks in the Northern Appalachians

    USGS Publications Warehouse

    Karabinos, P.; Aleinikoff, J.N.; Fanning, C.M.

    1999-01-01

    Distinguishing Grenvillian basement rocks from pre-Taconian cover sequences in the Appalachians is a first-order problem essential for accurate structural interpretations. The Cavendish Formation in southeastern Vermont presents a classic example of this problem. Doll and others (1961) showed the Cavendish Formation as younger than the Middle Proterozoic Mount Holly Complex but older than the lithologically similar Cambrian Tyson and Hoosac Formations. More recently, the name Cavendish Formation has been informally abandoned, and its metasedimentary units have been mapped as the Tyson and Hoosac Formations of Late Proterozoic to Cambrian age. In a radical departure from these interpretations, Ratcliffe and others (1997) reassigned metasedimentary rocks of the Cavendish Formation to the Mount Holly Complex based on an inferred intrusive relationship between them and a 1.42 Ga tonalite. This new age assignment, if correct, requires a completely new structural interpretation of the region. SHRIMP and Pb evaporation ages of detrital zircons extracted from a quartzite layer from Cavendish Gorge near the proposed intrusive contact with the tonalite constrain the time of deposition of the Cavendish Formation. Grain shapes of the zircons vary from euhedral to nearly spherical. Virtually all the grains have pitted surfaces and show at least some rounding of edges and terminations; grains exhibit oscillatory zoning typical of zircons that crystallized from a magma. Single-grain Pb evaporation analyses of ten zircons and SHRIMP analyses of 15 zircons all yield ages less than 1.42 Ga. Seven of the grains are consistent with derivation from the Bull Hill Gneiss that postdates the Grenville orogenic cycle and predates deposition of the Cavendish Formation. Thus, the metasedimentary units of the Cavendish Formation should not be assigned to the Mount Holly Complex.

  17. Isolation and heterologous expression of a polygalacturonase produced by Fusarium oxysporum f. sp. cubense race 1 and 4.

    PubMed

    Dong, Zhangyong; Wang, Zhenzhong

    2015-04-03

    Fusarium wilt (Panama disease) caused by Fusarium oxysporum f. sp. cubense (FOC) represents a significant threat to banana (Musa spp.) production. Musa AAB is susceptible to Race 1 (FOC1) and Race 4 (FOC4), while Cavendish Musa AAA is found to be resistant to FOC1 but still susceptible to Race 4. A polygalacturonase (PGC3) was purified from the supernatant of Fusarium oxysporum f. sp. cubense race 4 (FOC4), which is the pathogen of Fusarium wilt. PGC3 had an apparent molecular weight of 45 kDa according to SDS-PAGE. The enzyme hydrolyzed polygalacturonic acid in an exo-manner, as demonstrated by analysis of degradation products. The Km and Vmax values of PGC3 from FOC4 were determined to be 0.70 mg·mL-1 and 101.01 Units·mg·protein-1·min-1, respectively. Two pgc3 genes encoding PGC3 from FOC4 and FOC1, both genes of 1368 bp in length encode 456 amino-acid residues with a predicted signal peptide sequence of 21 amino acids. There are 16 nucleotide sites difference between FOC4-pgc3 and FOC1-pgc3, only leading to four amino acid residues difference. In order to obtain adequate amounts of protein required for functional studies, two genes were cloned into the expression vector pPICZaA and then expressed in Pichia pastoris strains of SMD1168. The recombinant PGC3, r-FOC1-PGC3 and r-FOC4-PGC3, were expressed and purified as active proteins. The optimal PGC3 activity was observed at 50 °C and pH 4.5. Both recombinant PGC3 retained >40% activity at pH 3-7 and >50% activity in 10-50 °C. Both recombinant PGC3 proteins could induce a response but with different levels of tissue maceration and necrosis in banana plants. In sum, our results indicate that PGC3 is an exo-PG and can be produced with full function in P. pastoris.

  18. Mycosphaerella fijiensis, the black leaf streak pathogen of banana: progress towards understanding pathogen biology and detection, disease development, and the challenges of control.

    PubMed

    Churchill, Alice C L

    2011-05-01

    Banana (Musa spp.) is grown throughout the tropical and subtropical regions of the world. The fruits are a key staple food in many developing countries and a source of income for subsistence farmers. Bananas are also a major, multibillion-dollar export commodity for consumption primarily in developed countries, where few banana cultivars are grown. The fungal pathogen Mycosphaerella fijiensis causes black leaf streak disease (BLSD; aka black Sigatoka leaf spot) on the majority of edible banana cultivars grown worldwide. The fact that most of these cultivars are sterile and unsuitable for the breeding of resistant lines necessitates the extensive use of fungicides as the primary means of disease control. BLSD is a significant threat to the food security of resource-poor populations who cannot afford fungicides, and increases the environmental and health hazards where large-acreage monocultures of banana (Cavendish subgroup, AAA genome) are grown for export. Mycosphaerella fijiensis M. Morelet is a sexual, heterothallic fungus having Pseudocercospora fijiensis (M. Morelet) Deighton as the anamorph stage. It is a haploid, hemibiotrophic ascomycete within the class Dothideomycetes, order Capnodiales and family Mycosphaerellaceae. Its taxonomic placement is based on DNA phylogeny, morphological analyses and cultural characteristics. Mycosphaerella fijiensis is a leaf pathogen that causes reddish-brown streaks running parallel to the leaf veins, which aggregate to form larger, dark-brown to black compound streaks. These streaks eventually form fusiform or elliptical lesions that coalesce, form a water-soaked border with a yellow halo and, eventually, merge to cause extensive leaf necrosis. The disease does not kill the plants immediately, but weakens them by decreasing the photosynthetic capacity of leaves, causing a reduction in the quantity and quality of fruit, and inducing the premature ripening of fruit harvested from infected plants. Although Musa spp. are the

  19. Staff members' perceptions of an animal-assisted activity.

    PubMed

    Bibbo, Jessica

    2013-07-01

    To examine the perceptions of staff members toward the implementation of an animal-assisted activity (AAA) in an outpatient regional cancer center. Quasi-experimental, post-test design. An adult outpatient regional cancer center in northern California. 34 facility staff members. Self-report questionnaire following four weeks of AAA visitation. Visits took place three times a week for a total of 12 visits. Perceptions of the AAA. Previous perceptions toward AAA influenced the perceptions of the visitation's efficacy. Direct and indirect interaction with the visiting AAA teams was positively associated with perceptions of the AAA. A disagreement occurred that the AAA had caused extra stress or work for staff. Enjoyment of interacting with the dog handler was not significantly different from interacting with the dog; however, it was more positively correlated to acceptance of the AAA. The study provided evidence that the AAA was generally accepted by staff members. Individual staff members' perceptions of dogs and AAAs can influence their receptivity to AAA interventions. Interaction with AAA teams should be voluntary and available for patients and staff members. AAA may be introduced into facilities without creating the perception of extra stress or work for staff members. Providing staff the opportunity to interact with visiting AAA teams may be beneficial for the success of such programs. The human handler in AAA teams may play a vital role in the staff acceptance of such programs.

  20. Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm

    PubMed Central

    Sasaki, Takeshi; Sano, Masaki; Yamamoto, Naoto; Saito, Takaaki; Inuzuka, Kazunori; Hayasaka, Takahiro; Goto-Inoue, Naoko; Sugiura, Yuki; Sato, Kohji; Kugo, Hirona; Moriyama, Tatsuya; Konno, Hiroyuki; Setou, Mitsutoshi; Unno, Naoki

    2015-01-01

    The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA. PMID:26308526

  1. Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm.

    PubMed

    Sawada, Hisashi; Hao, Hiroyuki; Naito, Yoshiro; Oboshi, Makiko; Hirotani, Shinichi; Mitsuno, Masataka; Miyamoto, Yuji; Hirota, Seiichi; Masuyama, Tohru

    2015-06-01

    Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive. Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression. © 2015 American Heart Association, Inc.

  2. Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm.

    PubMed

    Crawford, Jeffrey D; Chivukula, Venkat Keshav; Haller, Stephen; Vatankhah, Nasibeh; Bohannan, Colin J; Moneta, Gregory L; Rugonyi, Sandra; Azarbal, Amir F

    2016-12-01

    Current threshold recommendations for elective abdominal aortic aneurysm (AAA) repair are based solely on maximal AAA diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than AAA diameter of AAA rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict AAA rupture risk. Patients treated at our institution from 2001 to 2014 for ruptured AAA (rAAA) were retrospectively identified and grouped into patients with small rAAA (maximum diameter <6 cm) or large rAAA (>6 cm). Patients with large (>6 cm) non-rAAA were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. We identified 61 patients with rAAA, of which 15 ruptured with AAA diameter <60 mm (small rAAA group). Patients with small rAAAs were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-rAAA group. Patients with small rAAAs were also more likely to have AOO compared with non-rAAAs >60 mm (27% vs 8%; P = .047). Among all patients with rAAAs, those with AOO ruptured at smaller mean AAA diameters than in patients without AOO (62.1 ± 11.8 mm vs 72.5 ± 16.4 mm; P = .024). PWS calculations of a representative small rAAA and a large non-rAAA showed a substantial increase in PWS with AOO. We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at

  3. Long-term outcomes after repair of symptomatic abdominal aortic aneurysms.

    PubMed

    Chandra, Venita; Trang, Karen; Virgin-Downey, Whitt; Dalman, Ronald L; Mell, Matthew W

    2018-04-25

    Previous studies have reported increased perioperative mortality of nonruptured symptomatic abdominal aortic aneurysms (Sx-AAA) compared with asymptomatic elective AAA (E-AAA) repairs, but no long-term-outcomes have been reported. We sought to compare long-term outcomes of Sx-AAA and E-AAA after repair at a single academic institution. Patients receiving AAA repair for Sx-AAA and E-AAA from 1995 through 2015 were included. Ruptured AAA and suprarenal or thoracoabdominal AAA were excluded. Demographics, comorbidities, and operative approach were collected. Long-term mortality was the primary outcome, determined by chart review or link to Social Security Death Index. Additionally, long-term mortality and reinterventions were compared after groups were matched with nearest neighbor propensity to reduce bias. AAA repair was performed for 1054 E-AAA (383 open repair [36%], 671 endovascular aneurysm repair [EVAR] [64%]), and 139 symptomatic aneurysms (60 open repair [43%], 79 EVAR [57%]). Age (73 years vs 74 years; P = .13) and aneurysm diameter were similar between Sx-AAA and E-AAA (6.0 cm vs 5.8 cm; P = .5). The proportion of women was higher for Sx-AAA (26% vs 16%; P = .003), as was the proportion of non-Caucasians (40% vs 29%; P = .009). After propensity matching, there were no differences between groups for patient characteristics, AAA diameter, treatment modality, or comorbidities, including hypertension, coronary artery disease, congestive heart failure, diabetes, hyperlipidemia, lung disease, diabetes, renal disease, and smoking history. Women were treated for Sx-AAA at significantly smaller aortic diameters; however, compared with men (5.1 cm vs 6.3 cm; P < .001). Perioperative mortality was 5.0% for Sx-AAA and 2.3% for E-AAA (P = .055). By life-table analysis, Sx-AAA had lower 5-year (62% vs 71%) and 10-year (39% vs 51%) survivals (P = .01) compared with E-AAA for the entire cohort. Similar trends were observed for 5-year and 10-year mortality

  4. Effect of a High-sucrose Diet on Abdominal Aortic Aneurysm Development in a Hypoperfusion-induced Animal Model.

    PubMed

    Miyamoto, Chie; Kugo, Hirona; Hashimoto, Keisuke; Sawaragi, Ayaka; Zaima, Nobuhiro; Moriyama, Tatsuya

    2018-05-01

    Abdominal aortic aneurysm (AAA) is a vascular disease that results in rupture of the abdominal aorta. The risk factors for the development of AAA include smoking, male sex, hypertension, and age. AAA has a high mortality rate, but therapy for AAA is restricted to surgery in cases of large aneurysms. Clarifying the effect of dietary food on the development of AAA would be helpful for patients with AAAs. However, the relationship between dietary habits and the development of AAA is largely unknown. In our previous study, we demonstrated that adipocytes in vascular wall can induce the rupture of AAA. Therefore, we focused on the diet-induced abnormal triglyceride metabolism, which has the potential to drive AAA development. In this study, we have evaluated the effects of a high-sucrose diet on the development of AAA in a vascular hypoperfusion-induced animal model. A high sucrose diet induced high serum TG level and fatty liver. However, the AAA rupture risk and the AAA diameter were not significantly different between the control and high-sucrose groups. The intergroup differences in the elastin degradation score and collagen-positive area were insignificant. Moreover, matrix metalloproteinases, macrophages, and monocyte chemoattractant protein-1-positive areas did not differ significantly between groups. These results suggest that a high-sucrose diet does not affect the appearance of vascular adipocyte and AAA development under the vascular hypoperfusion condition.

  5. Functional Characterization of Ice Plant SKD1, an AAA-Type ATPase Associated with the Endoplasmic Reticulum-Golgi Network, and Its Role in Adaptation to Salt Stress1[W

    PubMed Central

    Jou, Yingtzy; Chiang, Chih-Pin; Jauh, Guang-Yuh; Yen, Hungchen Emilie

    2006-01-01

    A salt-induced gene mcSKD1 (suppressor of K+ transport growth defect) able to facilitate K+ uptake has previously been identified from the halophyte ice plant (Mesembryanthemum crystallinum). The sequence of mcSKD1 is homologous to vacuolar protein sorting 4, an ATPase associated with a variety of cellular activities-type ATPase that participates in the sorting of vacuolar proteins into multivesicular bodies in yeast (Saccharomyces cerevisiae). Recombinant mcSKD1 exhibited ATP hydrolytic activities in vitro with a half-maximal rate at an ATP concentration of 1.25 mm. Point mutations on active site residues abolished its ATPase activity. ADP is both a product and a strong inhibitor of the reaction. ADP-binding form of mcSDK1 greatly reduced its catalytic activity. The mcSKD1 protein accumulated ubiquitously in both vegetative and reproductive parts of plants. Highest accumulation was observed in cells actively engaging in the secretory processes, such as bladder cells of leaf epidermis. Membrane fractionation and double-labeling immunofluorescence showed the predominant localization of mcSKD1 in the endoplasmic reticulum-Golgi network. Immunoelectron microscopy identified the formation of mcSKD1 proteins into small aggregates in the cytosol and associated with membrane continuum within the endomembrane compartments. These results indicated that this ATPase participates in the endoplasmic reticulum-Golgi mediated protein sorting machinery for both housekeeping function and compartmentalization of excess Na+ under high salinity. PMID:16581876

  6. Department of Defense Prime Contract Awards Over $25,000 by Weapon System, Contractor and Work Performed. Fiscal Year 1993. (AAA Navy A-1 Skyraider-SMR Navy Harbor IGE YTB)

    DTIC Science & Technology

    1994-03-01

    ui ac < 10 Z BPP - ft ~ F.UB O 00)-m BGBBN Cr (0jW-4 () 0 NO 000-4 C4 r)NB 4 V V ~C% O : 0 B . C)O:M-4 WO GONO=O -4 NC’)c)(0-V B N M0.-4 MMMOCr-MM~ M...0 L. CW 0 ) - L-a L.C a4*.4 CUOI Q, O. C I.-4 Co. E 4on _1 ’ 4 L. 1.C C- E.4 -041-- E.4 U U. 0 C I I 0 4 W; C C. X - ..41- 5. in C &I.U 5L. L Sbl W4

  7. The major-effect quantitative trait locus CsARN6.1 encodes an AAA ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation

    USDA-ARS?s Scientific Manuscript database

    In plants, the formation of hypocotyl-derived adventitious roots (AR) is an important morphological acclimation to waterlogging stress, but its genetic basis is largely unknown. In the present study, with combined use of bulked segregant analysis-based high throughput next-gen whole genome sequencin...

  8. Science Education in Global Perspective: Lessons from Five Countries. Selected Papers Presented at the Annual Meeting of the American Association for the Advancement of Science (Washington, D.C., January 3-8, 1982). AAAS Selected Symposium 100.

    ERIC Educational Resources Information Center

    Klein, Margrete Siebert, Ed.; Rutherford, F. James, Ed.

    Designed to provide an international cross-section of data on science and mathematics education, this document describes the educational systems of countries that developed innovative approaches to science education. The science-centered systems of Japan, People's Republic of China, East Germany, West Germany, and the Soviet Union are featured in…

  9. Compound heterozygosity for Hb S [beta6(A3)GluVal, GAG-->GTG] and a new thalassemic mutation [beta132(H10)Lys-->term, AAA-->TAA] detected in a family from West Africa.

    PubMed

    Frischknecht, Hannes; Troxler, Heinz; Greiner, Jeanette; Hengartner, Heinz; Dutly, Fabrizio

    2008-01-01

    We describe a Hb S/beta-thalassemia (beta-thal) mutation involving an AT transition at codon 132 of the beta-globin gene. The mutation, in the heterozygous state, unlike several other mutations in exon 3, shows no signs of dominant thalassemia but those of a typical beta(0) carrier. Compound heterozygosity with Hb S [beta6(A3)GluVal, GAGGTG] showed a severe clinical picture.

  10. 75 FR 67973 - Ocean Transportation Intermediary License Applicants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... Office of Transportation Intermediaries, Federal Maritime Commission, Washington, DC 20573. AAA Cargo, Inc. dba AAA Cargo Express Inc. (OFF), 14536 Roscoe Blvd., Suite 99 & 101, Panorama City, CA 91402...

  11. 75 FR 49380 - Application of Section 108(i) to Partnerships and S Corporations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... recognized. Moreover, an S corporation's accumulated adjustments account (AAA) is not adjusted to account for... basis adjustments and adjustments to AAA for deferred OID deductions that apply to the issuing entity. H...

  12. 78 FR 70039 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; NSPS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-22

    ... Heaters (40 CFR Part 60, Subpart AAA) (Renewal)'' (EPA ICR No. 1176.11, OMB Control No. 2060-0161 to the.... Respondent's obligation to respond: Mandatory (40 CFR part 60, subpart AAA) Estimated number of respondents...

  13. Home Health Care

    MedlinePlus

    ... neighbors, and your local Area Agency on Aging (AAA) to learn more about the home health care ... and assistance provider or Area Agency on Aging (AAA). For help connecting to these agencies, contact the ...

  14. 75 FR 34939 - Approval and Promulgation of Air Quality Implementation Plans; Ohio; Final Approval and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ...)(5), (OO), (OO)(1), (OO)(2), (OO)(3), (OO)(4), (PP)(2), (UU)(3), (AAA), (DDD), and Appendix A. EPA is... Compounds from Stationary Sources, Paragraph (AAA), as adopted by Ohio on October 25, 2002, effective on...

  15. 77 FR 25148 - Request for Information Regarding Scope, Methods, and Data Sources for Conducting Study of Pre...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... Association (``AAA'') announced that it would not administer any consumer finance debt collection arbitrations filed by companies. The AAA's policy is still in effect according to a ``Notice on Consumer Debt...

  16. Respite Care

    MedlinePlus

    ... local church group or area agency on aging (AAA) will even run a formal “Friendly Visitor Program” ... of the cost of respite care. Your local AAA will have more information on whether financial assistance ...

  17. Live Well

    MedlinePlus

    ... talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content ... talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content ...

  18. Abdominal aortic aneurysm repair - open

    MedlinePlus

    AAA - open; Repair - aortic aneurysm - open ... Open surgery to repair an AAA is sometimes done as an emergency procedure when there is bleeding inside your body from the aneurysm. You may have an ...

  19. HIV/AIDS Basics

    MedlinePlus

    ... talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content ... talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content ...

  20. Screening for Abdominal Aortic Aneurysm

    MedlinePlus

    ... signs or symptoms of an abdominal aortic aneurysm (AAA). The final recommendation statement summarizes what the Task ... the potential benefits and harms of screening for AAA: (1) Men ages 65 to 75 who smoke ...

  1. 78 FR 34608 - Proposed Establishment of Class D Airspace; Bryant AAF, Anchorage, AK

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-10

    ... Association (AOPA), Alaska Airmen's Association (AAA), and the Alaskan Aviation Safety Foundation (AASF). One... D airspace. The AAA requested additional time to review the proposal and that the entire composition...

  2. 29 CFR 2520.103-6 - Definition of reportable transaction for Annual Return/Report.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... plan assets. (2) During the plan year, AAA plan purchases a commercial lot from ZZZ corporation at a cost equal to 2 percent of the current value of the plan assets. Two months later, AAA plan loans ZZZ...

  3. 42 CFR 440.340 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... individual who is a member of the American Academy of Actuaries (AAA). (2) Using generally accepted actuarial principles and methodologies of the AAA. (3) Using a standardized set of utilization and price factors. (4...

  4. 2016 Traffic Safety Culture Index

    MedlinePlus

    ... for Traffic Safety. For media inquiries, contact: Tamra Johnson 202-942-2079 TRJohnson@national.aaa.com Authors ... for Traffic Safety. For media inquiries, contact: Tamra Johnson 202-942-2079 TRJohnson@national.aaa.com Authors ...

  5. Spatial Analysis of Hospital Incidence and in Hospital Mortality of Abdominal Aortic Aneurysms in Germany: Secondary Data Analysis of Nationwide Hospital Episode (DRG) Data.

    PubMed

    Kuehnl, Andreas; Salvermoser, Michael; Erk, Alexander; Trenner, Matthias; Schmid, Volker; Eckstein, Hans-Henning

    2018-06-01

    This study aimed to analyze the spatial distribution and regional variation of the hospital incidence and in hospital mortality of abdominal aortic aneurysms (AAA) in Germany. German DRG statistics (2011-2014) were analysed. Patients with ruptured AAA (rAAA, I71.3, treated or not) and patients with non-ruptured AAA (nrAAA, I71.4, treated by open or endovascular aneurysm repair) were included. Age, sex, and risk standardisation was done using standard statistical procedures. Regional variation was quantified using systematic component of variation. To analyse spatial auto-correlation and spatial pattern, global Moran's I and Getis-Ord Gi* were calculated. A total of 50,702 cases were included. Raw hospital incidence of AAA was 15.7 per 100,000 inhabitants (nrAAA 13.1; all rAAA 2.7; treated rAAA 1.6). The standardised hospital incidence of AAA ranged from 6.3 to 30.3 per 100,000. Systematic component of variation proportion was 96% in nrAAA and 55% in treated rAAA. Incidence rates of all AAA were significantly clustered with above average values in the northwestern parts of Germany and below average values in the south and eastern regions. Standardised mortality of nrAAA ranged from 1.7% to 4.3%, with that of treated rAAA ranging from 28% to 52%. Regional variation and spatial distribution of standardised mortality was not different from random. There was significant regional variation and clustering of the hospital incidence of AAA in Germany, with higher rates in the northwest and lower rates in the southeast. There was no significant variation in standardised (age/sex/risk) mortality between counties. Copyright © 2018. Published by Elsevier B.V.

  6. [Identifying barriers to screening for abdominal aortic aneurysm in general practice: Qualitative study of 14 general practitioners in Paris].

    PubMed

    Niclot, J; Stansal, A; Saint-Lary, O; Lazareth, I; Priollet, P

    2018-05-01

    Abdominal aortic aneurysm (AAA) is a silent pathology with often fatal consequences in case of rupture. AAA screening, recommended in France and many other countries, has shown its effectiveness in reducing specific mortality. However, AAA screening rate remains insufficient. To identify barriers to AAA screening in general practice. Qualitative study carried out during 2016 among general practitioners based in Paris. Fourteen physicians were included. Most of the barriers were related to the physician: unawareness about AAA and screening recommendations, considering AAA as a secondary question not discussed with the patient, abdominal aorta not included in cardiovascular assessment, no search for a familial history of AAA, AAA considered a question for the specialist, lack of time, lack of training, numerous screenings to propose, oversight. Some barriers are related to the patient: unawareness of the pathology and family history of AAA, refusal, questioning the pertinence of the doctor's comments, failure to respect the care pathway. Others are related to AAA: source of anxiety, low prevalence, rarity of complications. The remaining barriers are related to screening: cost-benefit and risk-benefit ratios, sonographer unavailability, constraint for the patient, overmedicalization. Information and training of general practitioners about AAA must be strengthened in order to optimize AAA screening and reduce specific mortality. Copyright © 2018. Published by Elsevier Masson SAS.

  7. 78 FR 39973 - Application of Section 108(i) to Partnerships and S Corporations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-03

    ... (AAA), as defined in section 1368(e)(1), of an S corporation partner that has a deferred amount with... amount in the taxable year of the reacquisition. The AAA of an S corporation partner is not decreased by its share of any deferred OID deduction in the taxable year in which the deferred OID accrues. The AAA...

  8. Abdominal Aortic Aneurysm: Evolving Controversies and Uncertainties.

    PubMed

    Carino, Davide; Sarac, Timur P; Ziganshin, Bulat A; Elefteriades, John A

    2018-06-01

    Abdominal aortic aneurysm (AAA) is defined as a permanent dilatation of the abdominal aorta that exceeds 3 cm. Most AAAs arise in the portion of abdominal aorta distal to the renal arteries and are defined as infrarenal. Most AAAs are totally asymptomatic until catastrophic rupture. The strongest predictor of AAA rupture is the diameter. Surgery is indicated to prevent rupture when the risk of rupture exceeds the risk of surgery. In this review, we aim to analyze this disease comprehensively, starting from an epidemiological perspective, exploring etiology and pathophysiology, and concluding with surgical controversies. We will pursue these goals by addressing eight specific questions regarding AAA: (1) Is the incidence of AAA increasing? (2) Are ultrasound screening programs for AAA effective? (3) What causes AAA: Genes versus environment? (4) Animal models: Are they really relevant? (5) What pathophysiology leads to AAA? (6) Indications for AAA surgery: Are surgeons over-eager to operate? (7) Elective AAA repair: Open or endovascular? (8) Emergency AAA repair: Open or endovascular?

  9. A Quantitative Methodology for Determining the Critical Benchmarks for Project 2061 Strand Maps

    ERIC Educational Resources Information Center

    Kuhn, G.

    2008-01-01

    The American Association for the Advancement of Science (AAAS) was tasked with identifying the key science concepts for science literacy in K-12 students in America (AAAS, 1990, 1993). The AAAS Atlas of Science Literacy (2001) has organized roughly half of these science concepts or benchmarks into fifty flow charts. Each flow chart or strand map…

  10. 77 FR 13608 - Proposed Data Collections Submitted for Public Comment and Recommendations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ... Against AIDS (AAA) in 2009, a 5-year, multifaceted communication campaign consisting of several campaigns targeting various high-risk populations. The overall goals of AAA are to increase HIV/AIDS awareness and reduce HIV incidence in the United States. Each AAA campaign uses mass media and direct-to-consumer...

  11. Matricellular protein CCN3 mitigates abdominal aortic aneurysm

    PubMed Central

    Zhang, Chao; van der Voort, Dustin; Shi, Hong; Qing, Yulan; Hiraoka, Shuichi; Takemoto, Minoru; Yokote, Koutaro; Moxon, Joseph V.; Norman, Paul; Rittié, Laure; Atkins, G. Brandon; Gerson, Stanton L.; Shi, Guo-Ping; Golledge, Jonathan; Dong, Nianguo; Perbal, Bernard; Prosdocimo, Domenick A.

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent AAA models, including angiotensin II–induced AAA and elastase perfusion–stimulated AAA. CCN3 levels were also reduced in human AAA biopsies compared with those in controls. In murine models of induced AAA, germline deletion of Ccn3 resulted in severe phenotypes characterized by elastin fragmentation, vessel dilation, vascular inflammation, dissection, heightened ROS generation, and smooth muscle cell loss. Conversely, overexpression of CCN3 mitigated both elastase- and angiotensin II–induced AAA formation in mice. BM transplantation experiments suggested that the AAA phenotype of CCN3-deficient mice is intrinsic to the vasculature, as AAA was not exacerbated in WT animals that received CCN3-deficient BM and WT BM did not reduce AAA severity in CCN3-deficient mice. Genetic and pharmacological approaches implicated the ERK1/2 pathway as a critical regulator of CCN3-dependent AAA development. Together, these results demonstrate that CCN3 is a nodal regulator in AAA biology and identify CCN3 as a potential therapeutic target for vascular disease. PMID:26974158

  12. 40 CFR 78.3 - Petition for administrative review and request for evidentiary hearing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for administrative review of a decision of the Administrator that is made under subparts AAA through... Administrator that is made under subparts AAA through III of part 97 and that is appealable under § 78.1(a): (i... of this chapter, subparts AAA through III of part 96 of this chapter, subparts AAAA through IIII of...

  13. 40 CFR 78.1 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., subparts AAA through III of part 96 of this chapter or State regulations approved under § 51.124(o)(1) or... HHHH of part 60 of this chapter, subparts AA through II of part 96 of this chapter, subparts AAA... chapter. (8) Under subparts AAA through III of part 96 of this chapter, (i) The decision on the deduction...

  14. 40 CFR 280.104 - Local government bond rating test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... million or more, excluding refunded obligations, with a Moody's rating of Aaa, Aa, A, or Baa, or a Standard & Poor's rating of AAA, AA, A, or BBB. Where a local government has multiple outstanding issues... bonds of $1 million or more, excluding refunded issues and by also having a Moody's rating of Aaa, A, A...

  15. Aryl acylamidase activity exhibited by butyrylcholinesterase is higher in chick than in horse, but much lower than in fetal calf serum.

    PubMed

    Weitnauer, E; Robitzki, A; Layer, P G

    1998-10-02

    Several side activities have been attributed to butyrylcholinesterase (BChE), including aryl acylamidase (AAA) activity, which is an amidase-like activity with unknown physiological function splitting the artificial substrate o-nitroacetanilide. For avians, extensive developmental data have pointed to neurogenetic functions of BChE, however, a possible AAA activity of BChE has not been studied. In this study, we first compare the relative levels of AAA exhibited by BChE in whole sera from chick, fetal calves (FCS) and horse. Remarkably, FCS exhibits a 400-fold higher ratio of AAA/BChE than horse and 80-fold higher than chick serum. We then show that an immunoisolated preparation of BChE from chicken serum presents significant activity for AAA. Both in sera and with the purified enzyme, the AAA activity is fully inhibited by anticholinesterase drugs, showing that AAA activity is exclusively conveyed by the BChE molecule. Noticeably, AAA inhibition even occurs at lower drug concentrations than that of BChE activity itself. Moreover, AAA is sensitive to serotonin. These data indicate that (1) AAA is a general feature of serum BChE of vertebrates including avians, (2) AAA is effectively inhibited by cholinergic and serotonergic agents, and (3) AAA may have a developmental role, since it is much pronounced in a serum from fetal animals. Functionally, deamination of neuropeptides, a link between cholinergic and serotonergic neurotransmitter systems, and roles in lipoprotein metabolism could be relevant.

  16. Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

    PubMed Central

    Wu, Xiaoyu; Cakmak, Sinan; Wortmann, Markus; Hakimi, Maani; Zhang, Jian; Böckler, Dittmar; Dihlmann, Susanne

    2016-01-01

    Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sex-matched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared with matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 versus 0.01 pg/mL) and IL-1β plasma levels (mean = 12.07 versus 0.04 pg/mL) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients. PMID:27474483

  17. CXCL8 hyper-signaling in the aortic abdominal aneurysm.

    PubMed

    Kokje, Vivianne B C; Gäbel, Gabor; Dalman, Ron L; Koole, Dave; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

    2018-08-01

    There are indications for elevated CXCL8 levels in abdominal aortic aneurysm disease (AAA). CXCL8 is concurrently involved in neutrophil-mediated inflammation and angiogenesis, two prominent and distinctive characteristics of AAA. As such we considered an evaluation of a role for CXCL8 in AAA progression relevant. ELISA's, real time PCR and array analysis were used to explore CXCL8 signaling in AAA wall samples. A role for CXCL8 in AAA disease was tested through the oral CXCR1/2 antagonist DF2156A in the elastase model of AAA disease. There is an extreme disparity in aortic wall CXCL8 content between AAA and aortic atherosclerotic disease (median [IQR] aortic wall CXCL8 content: 425 [141-1261] (AAA) vs. 23 [2.8-89] (atherosclerotic aorta) µg/g protein (P < 1 · 10 -14 )), and abundant expression of the CXCR1 and 2 receptors in AAA. Array analysis followed by pathway analysis showed that CXCL8 hyper-expression in AAA is followed increased by IL-8 signaling (Z-score for AAA vs. atherosclerotic control: 2.97, p < 0.0001). Interference with CXCL8 signaling through DF2156A fully abrogated AAA formation and prevented matrix degradation in the murine elastase model of AAA disease (p < 0.001). CXCL8-signaling is a prominent and distinctive feature of AAA, interference with the pathway constitutes a promising target for medical stabilization of AAA. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Designation as “Unfit for Open Repair” Is Associated With Poor Outcomes After Endovascular Aortic Aneurysm Repair

    PubMed Central

    De Martino, Randall R.; Brooke, Benjamin S.; Robinson, William; Schanzer, Andres; Indes, Jeffrey E.; Wallaert, Jessica B.; Nolan, Brian W.; Cronenwett, Jack L.; Goodney, Philip P.

    2014-01-01

    Background Endovascular aortic aneurysm repair (EVAR) is often offered to patients with abdominal aortic aneurysms (AAAs) considered preoperatively to be unfit for open AAA repair (oAAA). This study describes the short- and long-term outcomes of patients undergoing EVAR with AAAs <6.5 cm who are considered unfit for oAAA. Methods and Results We analyzed elective EVARs for AAAs <6.5 cm diameter in the Vascular Study Group of New England (2003–2011). Patients were designated as fit or unfit for oAAA by the treating surgeon. End points included in-hospital major adverse events and long-term mortality. We identified patient characteristics associated with being unfit for open repair and predictors of survival using multivariable analyses. Of 1653 EVARs, 309 (18.7%) patients were deemed unfit for oAAA. These patients were more likely to have advanced age, cardiac disease, chronic obstructive pulmonary disease, and larger aneurysms at the time of repair (54 versus 56 mm, P=0.001). Patients unfit for oAAA had higher rates of cardiac (7.8% versus 3.1%, P<0.01) and pulmonary (3.6 versus 1.6, P<0.01) complications and worse survival rates at 5 years (61% versus 80%; log rank P<0.01) compared with those deemed fit for oAAA. Finally, patients designated as unfit for oAAA had worse survival, even adjusting for patient characteristics and aneurysm size (hazard ratio, 1.6; 95% confidence interval, 1.2–2.2; P<0.01). Conclusions In patients with AAAs <6.5 cm, designation by the operating surgeon as unfit for oAAA provides insight into both short- and long-term efficacy of EVAR. Patients unable to tolerate oAAA may not benefit from EVAR unless their risk of AAA rupture is very high. PMID:24046399

  19. Sex differences in abdominal aortic aneurysms.

    PubMed

    Boese, Austin C; Chang, Lin; Yin, Ke-Jie; Chen, Y Eugene; Lee, Jean-Pyo; Hamblin, Milton H

    2018-06-01

    Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.

  20. The Antiaircraft Journal. Volume 94, Number 6, November-December 1951

    DTIC Science & Technology

    1951-12-01

    authorized by the Visiting Forces Act. Getting their heads together, the Yanks and Tommies have discovered each other to be pretty regular fellows...Francis A., to 3Sth AAA Brig, Ft Meade, Md. McDaniel, Otto L., to Hq Fourth Army, Ft Sam Houston, Tex. Pape, Robin B., to SOth AAA Gp, Ft Totten , NY...to 71 Sth AAA Gun Bn, Ft Totten , NJ. Kee, Pat M., to 209th AAA Gp, Indiantown Gap, Pa. Kennaman, Jack R., to SOlst AAA Gun Bn, North Richland, Wash

  1. Update on Abdominal Aortic Aneurysm Research: From Clinical to Genetic Studies

    PubMed Central

    Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Hinterseher, Irene; Smelser, Diane T.; Tromp, Gerard

    2014-01-01

    An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person's risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks. PMID:24834361

  2. Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease

    PubMed Central

    Moran, Corey S.; Schreurs, Charlotte; Lindeman, Jan H. N.; Walker, Philip J.; Nataatmadja, Maria; West, Malcolm; Holdt, Lesca M.; Hinterseher, Irene; Pilarsky, Christian; Golledge, Jonathan

    2015-01-01

    Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human AAA and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small AAAs (≤ 55mm), 29 patients with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large AAAs, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large AAAs. Examples of validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the AAA and AOD transcriptomes were very different suggesting that AAA and AOD have distinct pathogenic mechanisms. PMID:25944698

  3. Time trends in hospital admissions and mortality due to abdominal aortic aneurysms in France, 2002-2013.

    PubMed

    Robert, M; Juillière, Y; Gabet, A; Kownator, S; Olié, V

    2017-05-01

    Abdominal aortic aneurysms (AAA) are serious disease with a high fatality rate but recent epidemiologic data showed a decrease of AAA mortality. Our objective was to estimate, in France, the hospitalization, inhospital mortality and mortality rates due to AAA and to analyze their trends over time. Hospitalization data were extracted from the hospital discharge summaries in the national database between 2002 and 2013. The analysis covered all patients hospitalized for AAA as a principal diagnosis. During the same period, all death certificates mentioning AAA as an initial cause of death were included in the study. Crude and standardized rates were calculated according to age and sex. Poisson regression was used to analyze the average annual percent change. In 2013, there were 8853 patients hospitalized for AAA in France (7986 unruptured and 867 ruptured). Between 2002 and 2013, the rate of patients hospitalized for unruptured AAA decreased slightly in men (-5.0%) but increased in women (+5.2%). By contrast, the rate of patients hospitalized for ruptured AAA has decreased by >20% in men and women. The proportion of endovascular treatment of unruptured AAA rose from <10% in 2005 to 35% in women and 40% in men in 2013. In 2013, 939 deaths from AAA were recorded. Mortality for this disease declined significantly from 2002 to 2013 in men and women. The unfavorable epidemiological trends in women and important evolution of the management of AAA call for an epidemiological surveillance of this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Abdominal aortic aneurysms: pre- and post-procedural imaging.

    PubMed

    Hallett, Richard L; Ullery, Brant W; Fleischmann, Dominik

    2018-05-01

    Abdominal aortic aneurysm (AAA) is a relatively common, potentially life-threatening disorder. Rupture of AAA is potentially catastrophic with high mortality. Intervention for AAA is indicated when the aneurysm reaches 5.0-5.5 cm or more, when symptomatic, or when increasing in size > 10 mm/year. AAA can be accurately assessed by cross-sectional imaging including computed tomography angiography and magnetic resonance angiography. Current options for intervention in AAA patients include open surgery and endovascular aneurysm repair (EVAR), with EVAR becoming more prevalent over time. Cross-sectional imaging plays a crucial role in AAA surveillance, pre-procedural assessment, and post-EVAR management. This paper will discuss the current role of imaging in the assessment of AAA patients prior to intervention, in evaluation of procedural complications, and in long-term follow-up of EVAR patients.

  5. The accuracy of combined physical examination and ultrasonography for the detection of abdominal aorta aneurysm.

    PubMed

    Cârstea, Doina; Streba, Letiţia Adela Maria; Glodeanu, Adina; Cârstea, A P; Vancu, Mihaela; Ninulescu, Ana-Maria

    2008-01-01

    Atherosclerosis is the most frequent cause in the appearance of an abdominal aorta aneurysm (AAA) and plays an important role in his development. Most AAA does not cause any symptoms, especially when talking about elderly patients, however, many of those aneurysms can be detected during physical examination. Their detection is very important because the natural evolution and the major reason in treating AAA is their tendency to rupture. We present the case of an adult man with a complex clinical pathology, but not related to the AAA. The diagnosis of the AAA has been suspicion through palpation, and the abdominal ultrasound exam confirmed it. This case is particular interesting, as the AAA requires surgical intervention, while patient's health status was poor. An essential issue is establishing the importance of the AAA screening, when there are no symptoms present. For now, there are not satisfactory studies to be used as a guide.

  6. From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

    PubMed

    Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J

    2014-07-03

    Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

  7. Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study: The ARIC Study (Atherosclerosis Risk in Communities).

    PubMed

    Tang, Weihong; Yao, Lu; Roetker, Nicholas S; Alonso, Alvaro; Lutsey, Pamela L; Steenson, Carol C; Lederle, Frank A; Hunter, David W; Bengtson, Lindsay G S; Guan, Weihua; Missov, Emil; Folsom, Aaron R

    2016-12-01

    Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs. In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA. © 2016 American Heart Association, Inc.

  8. Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine.

    PubMed

    Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

    2015-09-01

    Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA-spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA-spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients.

  9. Stories of Discovery Stimulate the Physics Major--A Polemic, with Examples.

    ERIC Educational Resources Information Center

    Leitner, Alfred

    1980-01-01

    Provides historical examples of intuitive discovery applicable to the teaching of physics for majors. Cites details for the discovery of Coulomb's law, emphasizing the roles of Joseph Priestley and Henry Cavendish. Also discusses the career of Ivar Giaever, a Nobel Prize winner of 1973 in solid state physics. (CS)

  10. Residual effects of low oxygen storage of mature green fruit on ripening processes and ester biosynthesis during ripening in bananas

    USDA-ARS?s Scientific Manuscript database

    Mature green banana (Musa sapientum L. cv. Cavendish) fruit were stored in 0.5%, 2 %, or 21% O2 for 7 days at 20 °C before ripening was initiated by ethylene. Residual effects of low O2 storage in mature green fruit on ripening and ester biosynthesis in fruit were investigated during ripening period...

  11. First report of alternaria leaf spot of banana caused by Alternaria alternata in the United States

    USDA-ARS?s Scientific Manuscript database

    Research efforts were initiated in 2003 to identify and introduce banana (Musa spp.) cultivars suitable for production in Georgia. In spring and summer 2012, seven of the cultivars (Veinte Cohol, Novaria, Cacambou, Chinese Cavendish, Raja Puri, Blue Torres Island, and African Red) grown in the field...

  12. Improving Counterterrorism Efforts by Removing Misconceptions about Islam in the Western World

    DTIC Science & Technology

    2010-12-01

    on November 6, 2010). 152 Edward Elgar, Terrorism, Protest, and Power, ed. Martin Warner and Roger Crisp (Aldershot Hants, England, Gower...257 Petra Weyland, “Islam-Islamism-Islamist Terrorism? A Proposal to come to Terms with the Nexus of...Relating to Terrorism. London: Cavendish Publishing, 1995. Elgar, Edward. Terrorism, Protest, and Power. Edited by Martin Warner and Roger Crisp

  13. Abdus Salam and his International Influences

    Science.gov Websites

    College, Cambridge where he distinguished himself with a double First in mathematics and physics in 1949 as well as the Smith's Prize for the most outstanding pre-doctoral contribution to physics in 1950 . By the time he received his doctorate in Theoretical Physics at the Cavendish Laboratory in 1951, his

  14. Spall Strength of Tungsten Carbide

    DTIC Science & Technology

    2004-09-01

    1 PCS GROUP CAVENDISH LABORATORY W G PROUD MADINGLEY RD CAMBRIDGE UNITED KINGDOM 1 CENTRE D ETUDES DE GRAMAT J Y TRANCHET...46500 GRAMAT FRANCE 1 MINISTERE DE LA DEFENSE DR G BRAULT DGA DSP STTC 4 RUE DE LA PORTE DISSY 75015 PARIS FRANCE 1 SPART

  15. A Genetic Linkage Map of Mycosphaerella Fijiensis, using SSR and DArT Markers

    USDA-ARS?s Scientific Manuscript database

    Mycosphaerella fijiensis is the causal agent of black leaf streak or Black Sigatoka disease in bananas. This pathogen threatens global banana production as the main export Cavendish cultivars are highly susceptible. Previously a genetic linkage map was generated predominantly using anonymous AFLP ma...

  16. An Historical Note on the Conservation of Mass

    ERIC Educational Resources Information Center

    Whitaker, Robert D.

    1975-01-01

    Discusses the fact that although most historians of science attribute the formulation of the law of conservation of matter in chemical reactions to Antoine Lavoisier at the end of the eighteenth century, several earlier researchers had already assumed this law in their work. These researchers include Joseph Black, Henry Cavendish, M. V. Lomonosov,…

  17. Early Cold-Induced Peroxidases and Aquaporins Are Associated With High Cold Tolerance in Dajiao (Musa spp. ‘Dajiao’)

    PubMed Central

    He, Wei-Di; Gao, Jie; Dou, Tong-Xin; Shao, Xiu-Hong; Bi, Fang-Cheng; Sheng, Ou; Deng, Gui-Ming; Li, Chun-Yu; Hu, Chun-Hua; Liu, Ji-Hong; Zhang, Sheng; Yang, Qiao-Song; Yi, Gan-Jun

    2018-01-01

    Banana is an important tropical fruit with high economic value. One of the main cultivars (‘Cavendish’) is susceptible to low temperatures, while another closely related specie (‘Dajiao’) has considerably higher cold tolerance. We previously reported that some membrane proteins appear to be involved in the cold tolerance of Dajiao bananas via an antioxidation mechanism. To investigate the early cold stress response of Dajiao, here we applied comparative membrane proteomics analysis for both cold-sensitive Cavendish and cold-tolerant Dajiao bananas subjected to cold stress at 10°C for 0, 3, and 6 h. A total of 2,333 and 1,834 proteins were identified in Cavendish and Dajiao, respectively. Subsequent bioinformatics analyses showed that 692 Cavendish proteins and 524 Dajiao proteins were predicted to be membrane proteins, of which 82 and 137 differentially abundant membrane proteins (DAMPs) were found in Cavendish and Dajiao, respectively. Interestingly, the number of DAMPs with increased abundance following 3 h of cold treatment in Dajiao (80) was seven times more than that in Cavendish (11). Gene ontology molecular function analysis of DAMPs for Cavendish and Dajiao indicated that they belong to eight categories including hydrolase activity, binding, transporter activity, antioxidant activity, etc., but the number in Dajiao is twice that in Cavendish. Strikingly, we found peroxidases (PODs) and aquaporins among the protein groups whose abundance was significantly increased after 3 h of cold treatment in Dajiao. Some of the PODs and aquaporins were verified by reverse-transcription PCR, multiple reaction monitoring, and green fluorescent protein-based subcellular localization analysis, demonstrating that the global membrane proteomics data are reliable. By combining the physiological and biochemical data, we found that membrane-bound Peroxidase 52 and Peroxidase P7, and aquaporins (MaPIP1;1, MaPIP1;2, MaPIP2;4, MaPIP2;6, MaTIP1;3) are mainly involved in

  18. High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.

    PubMed

    Rajesh, Ramanna V; Layer, Paul G; Boopathy, Rathanam

    2009-01-01

    Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (AAA) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of AAA activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes. Remarkably cobra venom showed the highest AAA activity and also high AAA/AChE ratio. Both serotonergenic and cholinergic inhibitors inhibited the cobra venom AAA activity in a concentration dependent manner, which also underlines the association of AAA with AChE of cobra venom. The study becomes interesting because of i) the cobra venom AChE exists in monomeric globular forms; ii) in Alzheimer's disease too the most abundant forms of cholinesterases are monomeric globular forms, thought to be involved in the pathogenesis of Alzheimer's disease; iii) the effect of Alzheimer's disease drugs on the AAA activity of cobra venom, indicated that AAA activity of cobra venom was more sensitive than AChE and iv) Huperzine and Tacrine showed more pronounced effect on AAA. Thus, this study elucidates the high AAA associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources were found to have lower activity.

  19. Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate

    PubMed Central

    Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E

    2012-01-01

    Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA. PMID:23173106

  20. Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate.

    PubMed

    Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E

    2012-01-01

    Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA.

  1. Epidemiology and outcome of aortic aneurysms in Hong Kong.

    PubMed

    Cheng, Stephen W K; Ting, Albert C W; Tsang, Simon H Y

    2003-02-01

    The objective of this study was to determine epidemiology and mortality statistics for abdominal aortic aneurysms (AAAs) in Hong Kong. Data from three sources were obtained and analyzed: (1) Hong Kong Hospital Authority discharge statistics for 1999 and 2000; (2) a survey on aortic aneurysms in public hospitals conducted by the Working Group of Vascular Surgery; and (3) the Department of Surgery, University of Hong Kong Medical Center aortic aneurysm database. The disease pattern, distribution, and operative mortality were determined. The annual incidence of AAA in Hong Kong is 13.7 per 100,000 population and 105 per 100,000 for those aged 65 and above. About 10% of the AAAs that presented were ruptured. The mean age of the AAA patients was 74 years, with 84% of them over age 65. The operative repair rate for AAAs was low, being only 8% for intact aneurysms and 54% for ruptured ones. Overall, 45% of all aneurysm repairs were performed for a ruptured AAA. There is diverse practice between major vascular centers and smaller regional hospitals. The territory-wide operative mortality rates for intact and ruptured aneurysms were 10% (range 4-24%) and 70% (range 38--100%), respectively. There was no gender bias in the rupture and operative rates. The overall mortality was 17% for intact AAAs and 78% for ruptured AAAs. The average length of hospital stay was 19 days for elective AAA surgery and 13 days for ruptured AAAs. The number of operations in high-volume centers is increasing with a concomitant decrease in operative mortality. There are no definitive data to indicate that the incidence of AAAs is rising, but a trend toward an increasing number of operations in referral centers is noted. The low repair rates for intact AAAs and the high proportion of repairs for ruptured aneurysms suggest that AAAs are undertreated in Hong Kong.

  2. Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms.

    PubMed

    Skibba, Afshin A; Evans, James R; Hopkins, Steven P; Yoon, H Richard; Katras, Tony; Kalbfleisch, John H; Rush, Daniel S

    2015-12-01

    Abdominal aortic aneurysms (AAAs) may rupture at smaller diameters in women than in men, and women may be at higher risk and have poorer outcomes in elective and emergent interventions because of age and comorbidities. Practice guidelines recommending elective AAA repair at >5.5 cm are gender neutral and may not adequately reflect increased risks in women or the potential advantages of elective lower risk endovascular procedures. Patients with a diagnosis of AAA discharged from a single referral hospital during a 14-year period were identified for retrospective analysis. A total of 2121 patients with AAAs were studied, 499 women (23.5%) and 1622 men (76.5%). Women were older and had a greater incidence of hypertension, smoking, chronic obstructive pulmonary disease, dyslipidemia, and renal insufficiency. Intact AAAs in 467 women had a mean diameter of 4.4 ± 1.3 cm compared with 1538 men at 5.0 ± 1.4 cm (P < .01). The ruptured AAAs in 32 women (6.4%) had a mean diameter of 6.1 ± 1.5 cm compared with 84 men (5.2%) at 7.7 ± 1.9 cm (P < .01). Women had a twofold increased frequency of AAA rupture than men at all size intervals (P < .01). The frequency of ruptured AAAs <5.5 cm among 10 of 32 women with ruptured AAAs was 31.3%; among 7 of 84 men with ruptured AAAs, it was 8.3% (P < .01). The frequency of ruptured AAAs <5.5 cm in all 383 women with AAAs <5.5 cm was 2.6%; in 1042 men, it was 0.6% (P < .01). Of the 1211 AAA repairs, 574 (47.4%) were open aneurysm repair (OAR) and 637 (52.6%) were endovascular aneurysm repair (EVAR). Mortality after elective OAR in 475 patients of both sexes was 5.1%; for EVAR in 676 patients, mortality was 1.6% (P < .01). No differences in mortality with respect to OAR or EVAR were found between the female and male cohorts in either intact or ruptured AAAs. Women with AAAs are older and have a higher frequency of cardiovascular risk factors than men. Women rupture AAAs with a greater frequency than men at all size intervals and have a

  3. Variations in Abdominal Aortic Aneurysm Care: A Report From the International Consortium of Vascular Registries

    PubMed Central

    Sedrakyan, Art; Mao, Jialin; Venermo, Maarit; Faizer, Rumi; Debus, Sebastian; Behrendt, Christian-Alexander; Scali, Salvatore; Altreuther, Martin; Schermerhorn, Marc; Beiles, Barry; Szeberin, Zoltan; Eldrup, Nikolaj; Danielsson, Gudmundur; Thomson, Ian; Wigger, Pius; Björck, Martin; Cronenwett, Jack L.; Mani, Kevin

    2016-01-01

    Background: This project by the ICVR (International Consortium of Vascular Registries), a collaboration of 11 vascular surgical quality registries, was designed to evaluate international variation in the contemporary management of abdominal aortic aneurysm (AAA) with relation to recommended treatment guidelines from the Society for Vascular Surgery and the European Society for Vascular Surgery. Methods: Registry data for open and endovascular AAA repair (EVAR) during 2010 to 2013 were collected from 11 countries. Variations in patient selection and treatment were compared across countries and across centers within countries. Results: Among 51 153 patients, 86% were treated for intact AAA (iAAA) and 14% for ruptured AAA. Women constituted 18% of the entire cohort (range, 12% in Switzerland–21% in the United States; P<0.01). Intact AAAs were repaired at diameters smaller than recommended by guidelines in 31% of men (<5.5 cm; range, 6% in Iceland–41% in Germany; P<0.01) and 12% of women with iAAA (<5 cm; range, 0% in Iceland–16% in the United States; P<0.01). Overall, use of EVAR for iAAA varied from 28% in Hungary to 79% in the United States (P<0.01) and for ruptured AAA from 5% in Denmark to 52% in the United States (P<0.01). In addition to the between-country variations, significant variations were present between centers in each country in terms of EVAR use and rate of small AAA repair. Countries that more frequently treated small AAAs tended to use EVAR more frequently (trend: correlation coefficient, 0.51; P=0.14). Octogenarians made up 23% of all patients, ranging from 12% in Hungary to 29% in Australia (P<0.01). In countries with a fee-for-service reimbursement system (Australia, Germany, Switzerland, and the United States), the proportions of small AAA (33%) and octogenarians undergoing iAAA repair (25%) were higher compared with countries with a population-based reimbursement model (small AAA repair, 16%; octogenarians, 18%; P<0.01). In general

  4. Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

    DTIC Science & Technology

    2016-07-01

    5’-aat tat ttt ata tgg aat gag caa gta tgt ttt atc ata att gac cag ttc att tca agg acc ttc aaa aat ata cct acg aat tcg agc tcg ttt aaa c-3’), or...oTsc13 (5’-tta aga gtt cag att tgc ttt atg tgg tta ttc tgc tga agg tcc taa ttt att gac gtt gaa aaa taa agg cca cat agc gga tcc ccg ggt taa tta a-3...and oTsc14 (5’-ata aaa aaa att aat taa tga tgg caa ggc aca atc gta atc aat ctt tta att tag gac ttt tta tat gcc ctt atg gcg aat tcg agc tcg ttt aaa c

  5. Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

    PubMed

    Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

    2009-08-01

    To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

  6. Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation

    PubMed Central

    Annambhotla, Suman; Bourgeois, Sebastian; Wang, Xinwen; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

    2010-01-01

    Abdominal Aortic Aneurysm (AAA) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of AAA formation remains poorly understood. Currently, the treatment for AAA remains primarily surgical with the lone innovation of endovascular therapy. With advance in the human genome, understanding precisely which molecules and genes mediate AAA development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of AAA formation including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA. PMID:18259804

  7. Low prevalence of abdominal aortic aneurysm in the Seychelles population aged 50 to 65 years.

    PubMed

    Yerly, Patrick; Madeleine, George; Riesen, Walter; Bovet, Pascal

    2013-03-01

    The prevalence of abdominal aortic aneurysm (AAA) and its risk factors are well known in Western countries but few data are available from low- and middle- income countries. We are not aware of systematically collected population- based data on AAA in the African region. We evaluated the prevalence of AAA in a population- based cardiovascular survey conducted in the Republic of Seychelles in 2004 (Indian Ocean, African region). Among the 353 participants aged 50 to 64 years and screened with ultrasound, the prevalence of AAA was 0.3% (95% CI: 0- 0.9) and the prevalence of ectatic dilatations of the abdominal aorta was 1.5% (95% CI: 0.2- 2.8). The prevalence of AAA in the general population seemed lower in Seychelles than in Western countries, despite a high prevalence in Seychelles of risk factors of AAA, such as smoking (in men), high blood pressure and hypercholesterolaemia.

  8. US Army And The Emergence Of Unmanned Threats

    DTIC Science & Technology

    2016-05-26

    43 iv Acronyms A2/AD Anti-Access/Area Denial AAA Anti-aircraft Artillery ADP Army...possessed sufficient resources and motivation to challenge local air superiority at the bridgehead. 66 Allied anti-aircraft artillery ( AAA ) raced to...Remagen. 482nd AAA , organic to Ninth Armored Division advanced through the division column to emplace at the bridge. With the vulnerability of the

  9. Genetic Variations in SLCO Transporter Genes Contributing to Racial Disparity in Aggressiveness of Prostate Cancer

    DTIC Science & Technology

    2016-10-01

    Contract Specialist U.S. Army Medical Research Acquisition Activity, MCMR- AAA -E, 820 Chandler Street, Fort Detrick, MD 21702-5014 Phone: (301) 619-4018...Funding Agency’s Procuring Contracting/Grants Officer: Ayi Ayayi, Contract Specialist U.S. Army Medical Research Acquisition Activity, MCMR- AAA -E, 820...Ayayi, Contract Specialist, U.S. Army Medical Research Acquisition Activity, MCMR- AAA -E, 820 Chandler Street, Fort Detrick, MD 21702-5014 Phone

  10. Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine

    PubMed Central

    Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

    2015-01-01

    Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA–spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA–spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients. PMID:26158885

  11. Transformation of the People’s Army of Vietnam, 1954-1975

    DTIC Science & Technology

    2016-05-26

    career. My family, both at home and the Army, are the reason I come to work. vi Acronyms AAA Anti-Aircraft Artillery ARVN Army of the...transformation in response to the United States war effort was the modernization of their Anti-Aircraft Artillery ( AAA ). On 2 March 1965, the United States...the AAA into a capable force, the north sought external support. The DRV turned to the USSR to procure equipment to combat the air threat from the

  12. 26 CFR 1.1368-3 - Examples.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... date. On March 1, 2001, S makes a distribution of $38 to A. The balance in Corporation S's AAA is $100... stock and debt to $0. Under § 1.1368-2(a)(3), S's AAA as of December 31, 1997, has a deficit of $150 as... distributes $110 to B. The balance in the AAA (negative $150 from 1997) is increased by $220 for S's income...

  13. Previously Identified Deficiencies Not Corrected in the General Fund Enterprise Business System Program

    DTIC Science & Technology

    2011-06-15

    Army AAA Report No. A-2009-0226- FFM , “Examination of Federal Financial Management Improvement Act Compliance - Test Validation General Fund Enterprise...Business System Release 1.2,” September 30, 2009 AAA Report No. A-2009-0231- FFM , “General Fund Enterprise Business System - Federal Financial...Management Improvement Act Compliance Examination of Release 1.3 Functionality,” September 30, 2009 AAA Report No. A-2009-0232- FFM , “General Fund

  14. Army Needs to Improve Controls and Audit Trails for the General Fund Enterprise Business System Acquire-to-Retire Business Process

    DTIC Science & Technology

    2013-09-13

    Event 1.4.4,” August 7, 2012 AAA Attestation Report A-2010-0187- FFM , “General Fund Enterprise Business System - Federal Financial Management...Improvement Act Compliance. Examination of Requirements Through Test Event 1.4.0,” September 14, 2010 AAA Audit Report A-2009-0232- FFM , “General Fund...September 30, 2009 AAA Audit Report A-2009-0231- FFM , “General Fund Enterprise Business System - Federal Financial Management Improvement Act

  15. Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms.

    PubMed

    Khosla, S; Morris, D R; Moxon, J V; Walker, P J; Gasser, T C; Golledge, J

    2014-10-01

    Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. Nine studies assessing 348 individuals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0·95, 95 per cent confidence interval 0·71 to 1·18; P < 0·001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0·68, 0·39 to 0·96; P < 0·001). Minimal heterogeneity between studies was noted (I(2)  = 0 per cent). This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  16. --No Title--

    Science.gov Websites

    ;background-color:#ddd;border-bottom:3px solid #aaa;padding:8px;margin-top:12px;height:auto;overflow:hidden }#how_use_car{clear:both;background-color:#ddd;border-bottom:3px solid #aaa;padding:8px;margin-top:20px ;height:auto;overflow:hidden}#results{clear:both;background-color:#ddd;border-bottom:3px solid #aaa;padding:8px

  17. A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals.

    PubMed

    Parthasarathy, Anutthaman; Cross, Penelope J; Dobson, Renwick C J; Adams, Lily E; Savka, Michael A; Hudson, André O

    2018-01-01

    Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The AAA and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the AAA by microbes and plants, and the branching out of AAA metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of AAA must obtain these primary metabolites from their diet. Therefore, the metabolism of AAA by the host animal and the resident microflora are important for the health of all animals. In addition, the AAA metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful AAA-derived compounds produced by gut bacteria are discussed. Apart from the AAA biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with AAA catabolism in plants, AAA degradation via the monoamine and kynurenine pathways in animals, and AAA catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key AAA-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type

  18. Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

    PubMed Central

    Burillo, Elena; Jorge, Inmaculada; Martínez-López, Diego; Camafeita, Emilio; Blanco-Colio, Luis Miguel; Trevisan-Herraz, Marco; Ezkurdia, Iakes; Egido, Jesús; Michel, Jean-Baptiste; Meilhac, Olivier; Vázquez, Jesús; Martin-Ventura, Jose Luis

    2016-01-01

    High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA. PMID:27934969

  19. Abdominal aortic aneurysm with periaortic malignant lymphoma differentiated from aneurysmal rupture by clinical presentation and magnetic resonance imaging.

    PubMed

    Kamata, Sokichi; Itou, Yoshito; Idoguchi, Koji; Imakita, Masami; Funatsu, Toshihiro; Yagihara, Toshikatsu

    2018-06-01

    Abdominal aortic aneurysm (AAA) associated with periaortic malignant lymphoma is difficult to differentiate from aneurysmal rupture because of similarities in their clinical presentation and appearance on computed tomography images. We here report a case of AAA associated with periaortic malignant lymphoma diagnosed preoperatively with an absence of typical symptoms, showing that AAA in periaortic malignant lymphoma can present without any clinical correlates. Magnetic resonance imaging was used to confirm the diagnosis. The patient was treated by endovascular repair, which may be safer and more effective than open surgery for AAA associated with malignant lymphoma because of the tight adhesion between the aneurysm and the lymphoid tissue.

  20. A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals

    PubMed Central

    Parthasarathy, Anutthaman; Cross, Penelope J.; Dobson, Renwick C. J.; Adams, Lily E.; Savka, Michael A.; Hudson, André O.

    2018-01-01

    Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The AAA and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the AAA by microbes and plants, and the branching out of AAA metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of AAA must obtain these primary metabolites from their diet. Therefore, the metabolism of AAA by the host animal and the resident microflora are important for the health of all animals. In addition, the AAA metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful AAA-derived compounds produced by gut bacteria are discussed. Apart from the AAA biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with AAA catabolism in plants, AAA degradation via the monoamine and kynurenine pathways in animals, and AAA catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key AAA-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type

  1. Enhancing human-animal relationships through veterinary medical instruction in animal-assisted therapy and animal-assisted activities.

    PubMed

    Schaffer, Caroline Brunsman

    2008-01-01

    Instruction in animal-assisted therapy (AAT) and animal-assisted activities (AAAs) teaches veterinary medical students to confidently and assertively maximize the benefits and minimize the risks of this union of animals and people. Instruction in AAT/AAA also addresses requirements by the American Veterinary Medical Association Council on Education that accredited schools/colleges of veterinary medicine include in their standard curriculum the topics of the human-animal bond, behavior, and the contributions of the veterinarian to the overall public and professional health care teams. Entry-level veterinarians should be prepared to: (1) assure that animals who provide AAT/AAA are healthy enough to visit nursing homes, hospitals, or other institutions; (2) promote behavior testing that selects animals who will feel safe, comfortable, and connected; (3) advise facilities regarding infection control and ways to provide a safe environment where the animals, their handlers, and the people being visited will not be injured or become ill; and (4) advocate for their patients and show compassion for their clients when animals are determined to be inappropriate participants in AAT/AAA programs. This article presents AAT/AAA terminology, ways in which veterinarians can advocate for AAT/AAA, the advantages of being involved in AAT/AAA, a model AAT/AAA practicum from Tuskegee University's School of Veterinary Medicine (TUSVM), and examples of co-curricular activities in AAT/AAA by TUSVM's student volunteers.

  2. Jaundice as a Rare Indication for Aortic Aneurysm Repair.

    PubMed

    Rieß, Henrik C; Tsilimparis, Nikolaos; Behrendt, Christian A; Wipper, Sabine; Debus, Eike S; Larena-Avellaneda, Axel

    2015-10-01

    Compression of adjacent anatomic structures by an abdominal aortic aneurysm (AAA) can result in a variety of symptoms. We describe the case of an 88-year-old Caucasian woman with jaundice, elevated laboratory parameters for extrahepatic and intrahepatic cholestasis, and concomitant juxtarenal AAA compressing the liver hilum. Following exclusion of other common causes for cholestasis, the patient was considered to have a symptomatic AAA. Open abdominal aortic surgery revealed a contained rupture and was repaired. Obstructive jaundice secondary to a compromising AAA is a rare condition and to the best of our knowledge has not been reported to date. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Lipoprotein(a) Levels in Patients With Abdominal Aortic Aneurysm.

    PubMed

    Kotani, Kazuhiko; Sahebkar, Amirhossein; Serban, Maria-Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P; Mariscalco, Giovanni; Jones, Steven R; Martin, Seth; Blaha, Michael J; Toth, Peter P; Rizzo, Manfredi; Kostner, Karam; Rysz, Jacek; Banach, Maciej

    2017-02-01

    Circulating markers relevant to the development of abdominal aortic aneurysm (AAA) are currently required. Lipoprotein(a), Lp(a), is considered a candidate marker associated with the presence of AAA. The present meta-analysis aimed to evaluate the association between circulating Lp(a) levels and the presence of AAA. The PubMed-based search was conducted up to April 30, 2015, to identify the studies focusing on Lp(a) levels in patients with AAA and controls. Quantitative data synthesis was performed using a random effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Overall, 9 studies were identified. After a combined analysis, patients with AAA were found to have a significantly higher level of Lp(a) compared to the controls (SMD: 0.87, 95% CI: 0.41-1.33, P < .001). This result remained robust in the sensitivity analysis, and its significance was not influenced after omitting each of the included studies from the meta-analysis. The present meta-analysis confirmed a higher level of circulating Lp(a) in patients with AAA compared to controls. High Lp(a) levels can be associated with the presence of AAA, and Lp(a) may be a marker in screening for AAA. Further studies are needed to establish the clinical utility of measuring Lp(a) in the prevention and management of AAA.

  4. Science, Society, and Social Networking

    NASA Astrophysics Data System (ADS)

    White, K. S.; Lohwater, T.

    2009-12-01

    The increased use of social networking is changing the way that scientific societies interact with their members and others. The American Association for the Advancement of Science (AAAS) uses a variety of online networks to engage its members and the broader scientific community. AAAS members and non-members can interact with AAAS staff and each other on AAAS sites on Facebook, YouTube, and Twitter, as well as blogs and forums on the AAAS website (www.aaas.org). These tools allow scientists to more readily become engaged in policy by providing information on current science policy topics as well as methods of involvement. For example, members and the public can comment on policy-relevant stories from Science magazine’s ScienceInsider blog, download a weekly policy podcast, receive a weekly email update of policy issues affecting the scientific community, or watch a congressional hearing from their computer. AAAS resource websites and outreach programs, including Communicating Science (www.aaas.org/communicatingscience), Working with Congress (www.aaas.org/spp/cstc/) and Science Careers (http://sciencecareers.sciencemag.org) also provide tools for scientists to become more personally engaged in communicating their findings and involved in the policy process.

  5. Association of statin prescription with small abdominal aortic aneurysm progression

    PubMed Central

    Ferguson, Craig D.; Clancy, Paula; Bourke, Bernard; Walker, Philip J.; Dear, Anthony; Buckenham, Tim; Norman, Paul; Golledge, Jonathan

    2009-01-01

    Background Statins have been suggested to reduce expansion of abdominal aortic aneurysms (AAA) independent of lipid lowering effects. Methods We assessed the association of statin treatment and serum low density lipoprotein (LDL) concentrations with small AAA expansion. 652 patients undergoing surveillance of small AAAs were entered into the study from five vascular centers. In a subset fasting lipids (n=451) and other biomarkers (n=216) were measured. AAA diameter was followed by ultrasound surveillance for a median of 5 years. Results 349 (54%) of the patients were prescribed statins. Adjusting for other risk factors statin prescription was not associated with AAA growth (odds ratio, OR, 1.23, 95% confidence interval, CI, 0.86–1.76). Above median AAA growth was positively associated with initial diameter (OR 1.78 per 4.35mm larger initial aortic diameter, 95% CI 1.49–2.14) and negatively associated with diabetes (OR 0.37, 95% CI 0.22–0.62). Above median serum LDL concentration was not associated with AAA growth. Patients receiving statins had lower serum C-reactive protein concentrations but similar matrix metalloproteinase-9 and interleukin-6 concentrations to those not prescribed these medications. Conclusions We found no association between statin prescription or LDL concentration with AAA expansion. The results do not support the findings of smaller studies and suggest that statins may have no benefit in reducing AAA progression. PMID:20152231

  6. Association between osteopontin and human abdominal aortic aneurysm.

    PubMed

    Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

    2007-03-01

    In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

  7. Comparison of Conscious Sedation and Asleep-Awake-Asleep Techniques for Awake Craniotomy.

    PubMed

    Dilmen, Ozlem Korkmaz; Akcil, Eren Fatma; Oguz, Abdulvahap; Vehid, Hayriye; Tunali, Yusuf

    2017-01-01

    Since awake craniotomy (AC) has become a standard of care for supratentorial tumour resection, especially in the motor and language cortex, determining the most appropriate anaesthetic protocol is very important. The aim of this retrospective study is to compare the effectiveness of conscious sedation (CS) to "awake-asleep-awake" (AAA) techniques for supratentorial tumour resection. Forty-two patients undergoing CS and 22 patients undergoing AAA were included in the study. The primary endpoint was to compare the CS and AAA techniques with respect to intraoperative pain and agitation in patients undergoing supratentorial tumour resection. The secondary endpoint was comparison of the other intraoperative complications. This study results show that the incidence of intraoperative agitation and seizure were lower in the AAA group than in the CS group. Intraoperative blood pressures were significantly higher in the CS group than in the AAA group during the pinning and incision, but the level of blood pressures did not need antihypertensive treatment. Otherwise, blood pressures were significantly higher in the AAA group than in the CS group during the neurological examination and the severity of hypertension needed statistically significant more antihypertensive treatment in the AAA group. As a result of hypertension, the amount of intraoperative bleeding was higher in the AAA group than in the CS group. In conclusion, the AAA technique may provide better results with respect to agitation and seizure, but intraoperative hypertension needed a vigilant follow-up especially in the wake-up period. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Variation in Death Rate After Abdominal Aortic Aneurysmectomy in the United States

    PubMed Central

    Dimick, Justin B.; Stanley, James C.; Axelrod, David A.; Kazmers, Andris; Henke, Peter K.; Jacobs, Lloyd A.; Wakefield, Thomas W.; Greenfield, Lazar J.; Upchurch, Gilbert R.

    2002-01-01

    Objective To determine whether high-volume hospitals (HVHs) have lower in-hospital death rates after abdominal aortic aneurysm (AAA) repair compared with low-volume hospitals (LVHs). Summary Background Data Select statewide studies have shown that HVHs have superior outcomes compared with LVHs for AAA repair, but they may not be representative of the true volume–outcome relationship for the entire United States. Methods Patients undergoing repair of intact or ruptured AAAs in the Nationwide Inpatient Sample (NIS) for 1996 and 1997 were included (n = 13,887) for study. The NIS represents a 20% stratified random sample representative of all U.S. hospitals. Unadjusted and case mix-adjusted analyses were performed. Results The overall death rate was 3.8% for intact AAA repair and 47% for ruptured AAA repair. For repair of intact AAAs, HVHs had a lower death rate than LVHs. The death rate after repair of ruptured AAA was also slightly lower at HVHs. In a multivariate analysis adjusting for case mix, having surgery at an LVH was associated with a 56% increased risk of in-hospital death. Other independent risk factors for in-hospital death included female gender, age older than 65 years, aneurysm rupture, urgent or emergent admission, and comorbid disease. Conclusions This study from a representative national database documents that HVHs have a significantly lower death rate than LVHs for repair of both intact and ruptured AAA. These data support the regionalization of patients to HVHs for AAA repair. PMID:11923615

  9. Intervisceral artery origins in patients with abdominal aortic aneurysmal disease; evidence for systemic vascular remodelling.

    PubMed

    Bailey, Damian M; Evans, Tom G; Thomas, Kate Gower; White, Richard D; Twine, Chistopher P; Lewis, Michael H; Williams, Ian M

    2016-08-01

    What is the central question of this study? To what extent focal abdominal aortic aneurysmal (AAA) disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between distances of the intervisceral artery origins and AAA location/size in patients with disease compared with healthy patients. What is the main finding and its importance? Intervisceral artery distances were shown to be consistently greater in AAA patients, highlighting the systemic nature of AAA disease that extends proximally to the abdominal aorta and its branches. The anatomical description of the natural variation in visceral artery origins has implications for the design of stent grafts and planning complex open aortic surgery. The initial histopathology of abdominal aortic aneurysmal (AAA) disease is atherosclerotic, later diverting towards a distinctive dilating rather than occlusive aortic phenotype. To what extent focal AAA disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between the intervisceral artery origins and AAA location/size in patients with AAA disease (AAA+) relative to those without (AAA-). Preoperative contrast-enhanced computerized tomograms were reviewed in 90 consecutive AAA+ patients scheduled for open repair who underwent an infrarenal (n = 45), suprarenal (n = 26) or supracoeliac clamp (n = 19). These were compared with 39 age-matched AAA- control patients. Craniocaudal measurements were recorded from the distal origin of the coeliac artery to the superior mesenteric artery and from the origin of the superior mesenteric artery to both renal artery origins. Serial blood samples were obtained for estimation of the glomerular filtration rate before and after surgery. Intervisceral artery origins were shown to be consistently greater in AAA+ patients (P < 0.05 versus AAA-), although

  10. Understanding the molecular mechanism of aryl acylamidase activity of acetylcholinesterase - An in silico study.

    PubMed

    Chinnadurai, Raj Kumar; Saravanaraman, Ponne; Boopathy, Rathanam

    2015-08-15

    Acetylcholinesterase (AChE) exhibits two different activities, namely esterase and aryl acylamidase (AAA). Unlike esterase, AAA activity of AChE is inhibited by the active site inhibitors while remaining unaffected by the peripheral anionic site inhibitors. This differential inhibitory pattern of active and peripheral anionic site inhibitors on the AAA activity remains unanswered. To answer this, we investigated the mechanism of binding and trafficking of AAA substrates using in silico tools. Molecular docking of serotonin and AAA substrates (o-nitroacetanilide, and o-nitrotrifluoroacetanilide,) onto AChE shows that these compounds bind at the side door of AChE. Thus, we conceived that the AAA substrates prefer the side door to reach the active site for their catalysis. Further, steered molecular dynamics simulations show that the force required for binding and trafficking of the AAA substrate through the side door is comparatively lesser than their dissociation (900kJ/mol/nm). Among the two substrates, o-nitrotrifluoroacetanilide required lesser force (380kJ/mol/nm) than o-nitroacetanilide the (550kJ/mol/nm) for its binding, thus validating o-nitrotrifluoroacetanilide as a better substrate. With these observations, we resolve that the AAA activity of AChE is mediated through its side door. Therefore, binding of PAS inhibitors at the main door of AChE remain ineffective against AAA activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Development and Characterization of Novel Bioluminecent Systems

    DTIC Science & Technology

    2013-07-01

    Ppy I108R. The following primers and their respective reverse compliments were used: Y447E, 5´- CT TTA ATT AAA TAC AAA GGA GAG CAG GTG GCC CCC GCT G...3´ [EcoRV] and I108R, 5´- GGA GTT GCA GTG GCG CCC GCG AAC GAC CGT TAT AAT GAA CGT-3´ [KasI] (bold represents the mutated codons, underlined...primers and their respective reverse compliments: Y447C, 5´- G AAG TCT TTA ATA AAA TAC AAA GGA TGT CAG GTG GCC CCC GCT G -3´ [PacI] and I108C, 5´- GGA

  12. American Academy of Audiology

    MedlinePlus

    ... AAA Foundation Volunteer Opportunities Professional Advancement eAudiology Continuing Education ABA Certification Meetings & Events Employee Resources Research Academia Practice Management Reimbursement Coding Compliance ...

  13. Epidemiology and contemporary management of abdominal aortic aneurysms.

    PubMed

    Ullery, Brant W; Hallett, Richard L; Fleischmann, Dominik

    2018-05-01

    Abdominal aortic aneurysm (AAA) is most commonly defined as a maximal diameter of the abdominal aorta in excess of 3 cm in either anterior-posterior or transverse planes or, alternatively, as a focal dilation ≥ 1.5 times the diameter of the normal adjacent arterial segment. Risk factors for the development of AAA include age > 60, tobacco use, male gender, Caucasian race, and family history of AAA. Aneurysm growth and rupture risk appear to be associated with persistent tobacco use, female gender, and chronic pulmonary disease. The majority of AAAs are asymptomatic and detected incidentally on various imaging studies, including abdominal ultrasound, and computed tomographic angiography. Symptoms associated with AAA may include abdominal or back pain, thromboembolization, atheroembolization, aortic rupture, or development of an arteriovenous or aortoenteric fistula. The Screening Abdominal Aortic Aneurysms Efficiently (SAAAVE) Act provides coverage for a one-time screening abdominal ultrasound at age 65 for men who have smoked at least 100 cigarettes and women who have family history of AAA disease. Medical management is recommended for asymptomatic patients with AAAs < 5 cm in diameter and focuses on modifiable risk factors, including smoking cessation and blood pressure control. Primary indications for intervention in patients with AAA include development of symptoms, rupture, rapid aneurysm growth (> 5 mm/6 months), or presence of a fusiform aneurysm with maximum diameter of 5.5 cm or greater. Intervention for AAA includes conventional open surgical repair and endovascular aortic stent graft repair.

  14. Genetic analysis on HLA loci in Japanese patients with abdominal aortic aneurysm.

    PubMed

    Sugimoto, T; Sada, M; Miyamoto, T; Yao, H

    2003-08-01

    autoimmunity has been proposed as one of the pathogenesis of abdominal aortic aneurysm (AAA). There is also a likelihood that when aorto-iliac occlusive disease (AIOD) coexists with AAA, some other occlusive atherosclerotic diseases, such as ischemic heart disease and cerebrovascular disease, may develop, leading to a very poor long-term prognosis. Previous studies using serological HLA typing showed that HLA-DR15 was a risk factor for AAA. In this study, we performed HLA-DNA typing by PCR to clarify the relationship between AAA and HLA genotypes in Japanese patients with AAA. In addition, we analyzed whether HLA genotypes are involved in the pathogenesis of AIOD. we examined 78 HLA genotypes of class I (HLA-A and -B) and class II (HLA-DR) and found that 60.4 and 30.4% of 49 AAA patients had HLA-A2 and HLA-B61, respectively. These frequencies were significantly higher than those in control individuals (HLA-A2, p < 0.05; HLA-B61, p < 0.005). We also found that 55.6% of nine AAA patients with AIOD had both HLA-B52 and HLA-DR B1*1502. In contrast, only 10.0% each of 40 AAA patients without AIOD showed HLA-B53 or HLA-DR B1*1502. this study showed that HLA A-2 and HLA B-61, but not HLA DR-15, were important genetic risk factors for the development of AAA among the Japanese population. We also found high frequencies of HLA-B52 and HLA-DR B1*1502 in the AAA patients with AIOD than in those without, although this must be confirmed using a larger number of AAA patients with AIOD.

  15. Inhibition of plasmin-mediated TAFI activation may affect development but not progression of abdominal aortic aneurysms

    PubMed Central

    Bridge, Katherine; Revill, Charlotte; Macrae, Fraser; Bailey, Marc; Yuldasheva, Nadira; Wheatcroft, Stephen; Butlin, Roger; Foster, Richard; Scott, D. Julian; Gils, Ann; Ariёns, Robert

    2017-01-01

    Objective Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (AAA) disease. The role of TAFI inhibition on AAA formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on AAA development and progression. Methods Using the Angiotensin II model of AAA, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. Results Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with AAA rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of AAA from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once AAA were already established had no effect on the progression of AAA in this model. Conclusions The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of AAA, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent AAA progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of AAA development, but not in its progression. PMID:28472123

  16. Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm

    PubMed Central

    Sun, Jingyuan; Deng, Hongping; Zhou, Zhen

    2018-01-01

    Abdominal aortic aneurysm (AAA) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for AAA. However, so far, it is unclear whether such drugs have any beneficial effect on AAA prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that AAA is highly associated with endothelial dysfunction in the aged population. Additionally, animal models of endothelial dysfunction and endothelial nitric oxide synthase (eNOS) uncoupling had a very high rate of AAA formation, indicating there is crucial involvement of the endothelium and a possible pharmacological solution targeting the endothelium in AAA treatment. Endothelial cells have been found to trigger vascular wall remodeling by releasing proteases, or recruiting macrophages along with other neutrophils, into the medial layer. Moreover, inflammation and oxidative stress of the arterial wall were induced by endothelial dysfunction. Interestingly, there is a paradoxical differential correlation between diabetes and aneurysm formation in retinal capillaries and the aorta. Deciphering the significance of such a difference may explain current unsuccessful AAA medications and offer a solution to this treatment challenge. It is now believed that AAA and atherosclerosis are two separate but related diseases, based on their different clinical patterns which have further complicated the puzzle. Therefore, a thorough investigation of the interaction between endothelium and medial/adventitial layer may provide us a better understanding and new perspective on AAA formation, especially after taking into account the importance of endothelium in the development of AAA. Moreover, a novel medication strategy replacing the currently used, but suboptimal treatments for AAA, could be

  17. TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

    PubMed

    Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

    2017-11-01

    Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

  18. Two C-C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm.

    PubMed

    Jones, Gregory T; Phillips, L Victoria; Williams, Michael J A; van Rij, Andre M; Kabir, Tasnuva D

    2016-04-28

    Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (AAA). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA. Tissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T-cell expressed and secreted (RANTES), eotaxin, and macrophage inflammatory protein 1 beta (MIP-1b), had increased expression in AAA, particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor (bFGF) had reduced expression in all layers of the AAA wall. Examination of the circulating plasma profiles of AAA (n=442) and AAA-free controls (n=970) suggested a (risk factor adjusted) AAA-association with eotaxin, RANTES, and high sensitivity C-reactive protein (hsCRP). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with AAA (odds ratio, 4.8; 95% CI, 3.5-6.7; P<0.0001), independent of age, sex, history of ischemic heart disease, and smoking. Contrary to reports suggesting a distinct T helper 2-associated inflammatory profile in AAA, this current study suggests a more-generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES. In combination with hsCRP, these markers may have potential utility as AAA biomarkers. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  19. Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression.

    PubMed

    Iida, Yasunori; Xu, Baohui; Xuan, Haojun; Glover, Keith J; Tanaka, Hiroki; Hu, Xiaolei; Fujimura, Naoki; Wang, Wei; Schultz, Joshua R; Turner, Court R; Dalman, Ronald L

    2013-04-01

    Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence AAA progression in murine models. AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase infusion also stabilized or reduced enlargement of existing AAAs. Finally, MKEY treatment was effective in limiting AAA formation after angiotensin II infusion in apolipoprotein E-deficient mice. MKEY suppresses AAA formation and progression in 2 complementary experimental models. Peptide inhibition of CXCL4-CCL5 interactions may represent a viable translational strategy to limit progression of human AAA disease.

  20. Impact of isotropic constitutive descriptions on the predicted peak wall stress in abdominal aortic aneurysms.

    PubMed

    Man, V; Polzer, S; Gasser, T C; Novotny, T; Bursa, J

    2018-03-01

    Biomechanics-based assessment of Abdominal Aortic Aneurysm (AAA) rupture risk has gained considerable scientific and clinical momentum. However, computation of peak wall stress (PWS) using state-of-the-art finite element models is time demanding. This study investigates which features of the constitutive description of AAA wall are decisive for achieving acceptable stress predictions in it. Influence of five different isotropic constitutive descriptions of AAA wall is tested; models reflect realistic non-linear, artificially stiff non-linear, or artificially stiff pseudo-linear constitutive descriptions of AAA wall. Influence of the AAA wall model is tested on idealized (n=4) and patient-specific (n=16) AAA geometries. Wall stress computations consider a (hypothetical) load-free configuration and include residual stresses homogenizing the stresses across the wall. Wall stress differences amongst the different descriptions were statistically analyzed. When the qualitatively similar non-linear response of the AAA wall with low initial stiffness and subsequent strain stiffening was taken into consideration, wall stress (and PWS) predictions did not change significantly. Keeping this non-linear feature when using an artificially stiff wall can save up to 30% of the computational time, without significant change in PWS. In contrast, a stiff pseudo-linear elastic model may underestimate the PWS and is not reliable for AAA wall stress computations. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

  1. Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

    PubMed Central

    Yang, Le; Shen, Lin; Gao, Peixian; Li, Gang; He, Yuxiang; Wang, Maohua; Zhou, Hua; Yuan, Hai; Jin, Xing; Wu, Xuejun

    2017-01-01

    Background and aims Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). Methods AAA was induced in ApoE−/− mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. Results Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. Conclusions Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA. PMID:29190959

  2. The African American Acculturation Scale II: Cross-Validation and Short Form.

    ERIC Educational Resources Information Center

    Landrine, Hope; Klonoff, Elizabeth A.

    1995-01-01

    Studied African American culture, using a new, shortened, 33-item African American Acculturation Scale (AAAS-33) to assess the scale's validity and reliability. Comparisons between the original form and AAAS-33 reveal high correlations, however, the longer form may be sensitive to some beliefs, practices, and attitudes not assessed by the short…

  3. African American Acculturation and Black Racial Identity: A Preliminary Investigation.

    ERIC Educational Resources Information Center

    Pope-Davis, Donald B.; Liu, William M.; Ledesma-Jones, Shannon; Nevitt, Jonathan

    2000-01-01

    Examines the relationship between acculturation and racial identity among African Americans. One hundred eighty-seven African American students completed the Black Racial Identity Attitude Scale and the African American Acculturation Scale (AAAS). Acculturation was associated with three of the five AAAS subscales: Dissonance, Immersion, and…

  4. Vision and Change in Biology Undergraduate Education: Vision and Change from the Funding Front

    ERIC Educational Resources Information Center

    Holm, Bethany; Carter, Virginia Celeste; Woodin, Terry

    2011-01-01

    The purpose of this short article is to (a) briefly summarize the findings of two important recent resources concerning the future of biology in the 21st century; one, Vision and Change, A Call to Action [AAAS, 2009. AAAS, Washington, DC], concerned with undergraduate education in biology, the other, A New Biology for the 21st Century [National…

  5. Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm

    PubMed Central

    Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan

    2018-01-01

    Abdominal aortic aneurysm (AAA) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of AAA, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for AAAs. However, these treatments are not appropriate for the majority of AAAs, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of AAA. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as AAA. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of AAA. Mechanisms of action underlying the effects of CHMs on AAA are also discussed. PMID:29732374

  6. The Antiaircraft Journal. Volume 92, Number 3, May-June 1949

    DTIC Science & Technology

    1949-06-01

    Ft. Sill, Okla. Daley, Edward J., to 4051st STU Det Arty Sch, Ft. Sill, Okla. Dalton, Joseph R., to Marianas- Bonins Comd, Guam. Darden, Harry 1., to...AAA and GM Br, Ft. Bliss, Tex. Edwards, Dave W., to 4052d ASU AAA and GM Cen, Ft. Bliss, Tex. Eiler, Donald 1., to US Army Caribbean, Quarry Heights

  7. You...Alcohol and Driving.

    ERIC Educational Resources Information Center

    American Automobile Association, Falls Church, VA. Traffic Engineering and Safety Dept.

    This pamphlet is an example of cooperation between the private sector (AAA) and the National Highway Traffic Safety Administration. AAA has adapted materials prepared by the National Public Service Research Institute under an NHTSA contract and developed a 54-page student manual. The manual takes a complete and objective look at drinking and…

  8. An Interpretation of the "Science--A Process Approach" Objectives in Terms of Existing Psychological Theory and Experimentation.

    ERIC Educational Resources Information Center

    Cole, Henry P.

    This paper examines the sequence and hierarchy of objectives in the American Association for the Advancement of Science (AAAS) "Science--A Process Approach" curriculum. The work of Piaget, Bruner forms a framework from which the learning objectives and tasks in the AAAS science curriculum are examined. The points of correspondence…

  9. Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men.

    PubMed

    Wang, Lu; Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O; Matsumoto, Chisa; Manson, JoAnn E; Gaziano, J Michael; Sesso, Howard D

    2017-01-01

    Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m 2 , the multivariable hazard ratio (HR [95% CI]) of newly diagnosed AAA was 1.30 [1.06-1.59] for BMI 25-<30 kg/m 2 and 1.69 [1.24-2.30] for BMI ≥ 30 kg/m 2 . The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57-1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up.

  10. 10 CFR Appendix C to Part 30 - Criteria Relating to Use of Financial Tests and Self Guarantees for Providing Reasonable...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... thereof. (3) A current rating for its most recent bond issuance of AAA, AA, or A as issued by Standard and Poors (S&P), or Aaa, Aa, or A as issued by Moodys. B. To pass the financial test, a company must meet...

  11. 10 CFR Appendix A to Part 30 - Criteria Relating to Use of Financial Tests and Parent Company Guarantees for Providing...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... company must have: (i) A current rating for its most recent bond issuance of AAA, AA, A, or BBB as issued by Standard and Poor's or Aaa, Aa, A, or Baa as issued by Moody's; and (ii) Tangible net worth each...

  12. Histopathological analysis of cellular localization of cathepsins in abdominal aortic aneurysm wall.

    PubMed

    Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Zimmermann, Alexander; Ockert, Stefan; Eckstein, Hans-Henning; Pelisek, Jaroslav

    2012-08-01

    An important feature of abdominal aortic aneurysm (AAA) is the destruction of vessel wall, especially elastin and collagen. Besides matrix metalloproteinases, cathepsins are the most potent elastolytic enzymes. The expression of cathepsins with known elastolytic and collagenolytic activities in the individual cells within AAA has not yet been determined. The vessel wall of 32 AAA patients and 10 organ donors was analysed by immunohistochemistry for expression of cathepsins B, D, K, L and S, and cystatin C in all cells localized within AAA. Luminal endothelial cells (ECs) of AAA were positive for cathepsin D and partially for cathepsins B, K and S. Endothelial cells of the neovessels and smooth muscle cells in the media were positive for all cathepsins tested, especially for cathepsin B. In the inflammatory infiltrate all cathepsins were expressed in the following pattern: B > D = S > K = L. Macrophages showed the highest staining intensity for all cathepsins. Furthermore, weak overall expression of cystatin C was observed in all the cells localized in the AAA with the exception of the ECs. There is markedly increased expression of the various cathepsins within the AAA wall compared to healthy aorta. Our data are broadly consistent with a role for cathepsins in AAA; and demonstrate expression of cathepsins D, B and S in phagocytic cells in the inflammatory infiltrate; and also may reveal a role for cathepsin B in lymphocytes. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

  13. Simultaneous repair of abdominal aortic aneurysm and resection of unexpected, associated abdominal malignancies.

    PubMed

    Illuminati, Giulio; Calio', Francesco G; D'Urso, Antonio; Lorusso, Riccardo; Ceccanei, Gianluca; Vietri, Francesco

    2004-12-15

    The management of unexpected intra-abdominal malignancy, discovered at laparotomy for elective treatment of an abdominal aortic aneurysm (AAA), is controversial. It is still unclear whether both conditions should be treated simultaneously or a staged approach is to be preferred. To contribute in improving treatment guidelines, we retrospectively reviewed the records of patients undergoing laparotomy for elective AAA repair. From January 1994 to March 2003, 253 patients underwent elective, trans-peritoneal repair of an AAA. In four patients (1.6%), an associated, unexpected neoplasm was detected at abdominal exploration, consisting of one renal, one gastric, one ileal carcinoid, and one ascending colon tumor. All of them were treated at the same operation, after aortic repair and careful isolation of the prosthetic graft. The whole series' operative mortality was 3.6%. None of the patients simultaneously treated for AAA and tumor resection died in the postoperative period. No graft-related infections were observed. Simultaneous treatment of AAA and tumor did not prolong significantly the mean length of stay in the hospital, compared to standard treatment of AAA alone. Except for malignancies of organs requiring major surgical resections, simultaneous AAA repair and resection of an associated, unexpected abdominal neoplasm can be safely performed, in most of the patients, sparing the need for a second procedure. Endovascular grafting of the AAA can be a valuable tool in simplifying simultaneous treatment, or in staging the procedures with a very short delay.

  14. On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm.

    PubMed

    Pincemail, J; Defraigne, J O; Cheramy-Bien, J P; Dardenne, N; Donneau, A F; Albert, A; Labropoulos, N; Sakalihasan, N

    2012-01-01

    Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients. Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤ 50 or > 50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.

  15. Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis

    PubMed Central

    Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Wang, Junpeng; Shao, Yang; Liu, Bing; Xin, Shijie

    2014-01-01

    Objectives Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review. Methods We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects. Results 7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63–8.82). Conclusion This meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA. PMID:24465733

  16. Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm.

    PubMed

    Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan

    2018-01-01

    Abdominal aortic aneurysm (AAA) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of AAA, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for AAAs. However, these treatments are not appropriate for the majority of AAAs, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of AAA. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as AAA. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of AAA. Mechanisms of action underlying the effects of CHMs on AAA are also discussed.

  17. Airpower as a Tool of Foreign Policy, Two Case Studies of Airpower’s Use: The Philippines in 1941 and Berlin in 1948

    DTIC Science & Technology

    1993-05-01

    Vallance , RAF, ed., Air Power Doctrine (United Kingdom: Crown Copyright, 1990). Group Captain Vallance provides a comprehensive discussion of The...Spring 1964): 1-7. Current, Richard N. �How Stimson Meant to �Manuever� the Japanese.� The Mississippi Valley Historical Review, 11 (June 1953...War II, the Pacific War. New York: Marshall Cavendish, 1992. Collier, Richard . The Road to Pearl Harbor: 1941. New York: Atheneum, 1981

  18. On the Possibility to Construct Gravitational Eye

    NASA Astrophysics Data System (ADS)

    Chen, Ying-Tian

    2007-05-01

    The possibility of modifying a conventional Cavendish torsion pendulum into a half-armed pendulum oscillator to measure the horizontal gravitational acceleration is discussed. A new kind of gravitational detector, gravieye, as we named, can be made by a proper combination of such oscillators to ``see'' remote objects and to be used, e.g. to detect the movement of huge mass at a long distance.

  19. The discovery of the structure of DNA

    NASA Astrophysics Data System (ADS)

    Squires, G. L.

    2003-04-01

    On 25 April 1953, Nature published a letter by Francis Crick and James Watson, at the Cavendish Laboratory, Cambridge, proposing a structure for DNA. This letter marked the beginning of a revolution in biology. Besides Crick and Watson, two other scientists, Rosalind Franklin and Maurice Wilkins, played key roles in the discovery. After sketching the early careers of the four scientists, the present article gives an account of the physics and chemistry involved in the discovery, and the events leading up to it.

  20. Adventitial adipogenic degeneration is an unidentified contributor to aortic wall weakening in the abdominal aortic aneurysm.

    PubMed

    Doderer, Stefan A; Gäbel, Gabor; Kokje, Vivianne B C; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

    2018-06-01

    The processes driving human abdominal aortic aneurysm (AAA) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in AAA progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and AAAs; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in AAA-related wall debilitation. A better understanding of the pathophysiologic processes driving AAA growth can contribute to pharmaceutical treatments in the future. Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture. Histologic evaluation of AAAs, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (AAA), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of AAAs (P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in AAA tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of AAA adventitial mesenchymal cells (P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured AAA (P < .0003) supports an association between the extent of fatty degeneration and rupture. This