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Sample records for aleksandrov jaanus purga

  1. Jalapinoside, a macrocyclic bisdesmoside from the resin glycosides of Ipomea purga, as a modulator of multidrug resistance in human cancer cells.

    PubMed

    Bautista, Elihú; Fragoso-Serrano, Mabel; Pereda-Miranda, Rogelio

    2015-01-23

    The first macrocyclic bisdesmoside resin glycoside, jalapinoside (4), was purified by preparative-scale recycling HPLC from the MeOH-soluble extracts of Ipomoea purga roots, the officinal jalap. Purgic acid C (3), a new glycosidic acid of ipurolic acid, was identified as 3-O-β-d-quinovopyranoside, 11-O-β-d-quinovopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→3)-O-[β-d-fucopyranosyl-(1→4)]-O-α-l-rhamnopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→2)-O-β-d-quinovopyranoside (3S,11S)-dihydroxytetradecanoic acid. The acylating residues of this core were acetic, (+)-(2S)-methylbutanoic, and dodecanoic acids. The site of lactonization was defined as C-3 of the second saccharide moiety. Reversal of multidrug resistance by this noncytotoxic compound was evaluated in vinblastine-resistant human breast carcinoma cells. PMID:25536852

  2. Literacy Update. Volume 19, Number 1

    ERIC Educational Resources Information Center

    Gallagher, Jan, Ed.

    2009-01-01

    This newsletter, published five times a year, features articles on issues of concern to adult, family, and youth literacy practitioners, as well as recommended resources, announcements, and teaching strategies. This issue includes: (1) Literacy Zones Fight Poverty and Close Education Gaps (Robert Purga); (2) Staying at the Table: Building a…

  3. About some erroneous hypotheses in the kinetics of chain processes

    NASA Astrophysics Data System (ADS)

    Rubtsov, N. M.

    2009-08-01

    Works by Aleksandrov et al. concerned with some chain combustion problems contain statements that contradict the experimental data and modern concepts of the science of combustion based on the classic works by Semenov and Hinshelwood. Some of these statements are analyzed.

  4. Distinct proteins encoded by alternative transcripts of the PURG gene, located contrapodal to WRN on chromosome 8, determined by differential termination/polyadenylation.

    PubMed

    Liu, Hong; Johnson, Edward M

    2002-06-01

    A gene encoding a new member of the Pur protein family, Purgamma, has been detected upstream of, and contrapodal to, the gene encoding the Werner syndrome helicase, Wrn, at human chromosome band 8p11-12. Both the PURG and WRN genes initiate transcription at multiple sites, the major clusters of which are approximately 90 bp apart. A segment containing this region strongly promotes transcription of a reporter gene in both directions. Both promoters are TATA-less and CAAT-less and both are positively regulated by Sp1 elements. While promoter elements for the two genes are interleaved, in the contrapodal direction, certain elements critical for each gene are distinct. Sequencing of cDNAs for Purgamma mRNA reveals that two alternative coding sequences are generated from a single gene, resulting in different Purgamma C-termini. PURG-A mRNA consists of a single intronless transcript of approximately 3 kb. PURG-B mRNA results from transcription through the PURG-A polyadenylation site and splicing out of an intron of >30 kb. In this unique example of a switch, splicing of a single intron either occurs or does not occur depending upon differential termination/polyadenylation. PURG-B is the primary PURG transcript detected in testis, but it is undetectable in all members of a normal adult tissue cDNA panel. PURG-A levels are low or undetectable in the normal tissue panel, but they are greatly elevated in all members of a tumor tissue panel. PURG-B is detected in several tumor panel members. PMID:12034829

  5. Numerical modeling of SHS reaction wave propagating speed using various thermal conductivity values for titanium and carbon mixture

    SciTech Connect

    Cui, T.; Azad, G.S.; Huque, Z.

    1996-12-01

    A numerical model was developed to predict the propagation speed of a Self-Propagating High-Temperature Synthesis (SHS) reaction wave along a vertical cylindrical reactant compact made from a mixture of titanium and carbon powders. Various thermal conductivity values are used corresponding to the supply mole ratio of titanium and carbon powder mixture and initial sample density. These values are obtained experimentally in the laboratory. Results are also obtained for variation of particle sizes in the mixture. The reaction kinetics employed are Aleksandrov (1987) kinetic model and Kanury (1989). The prediction results are compared with Huque`s (1993) earlier work.

  6. Elastic properties of minerals

    SciTech Connect

    Aleksandrov, K.S.; Prodaivoda, G.T.

    1993-09-01

    Investigations of the elastic properties of the main rock-forming minerals were begun by T.V. Ryzhova and K.S. Aleksandrov over 30 years ago on the initiative of B.P. Belikov. At the time, information on the elasticity of single crystals in general, and especially of minerals, was very scanty. In the surveys of that time there was information on the elasticity of 20 or 30 minerals. These, as a rule, did not include the main rock-forming minerals; silicates were represented only by garnets, quartz, topaz, tourmaline, zircon, beryl, and staurolite, which are often found in nature in the form of large and fairly high-quality crystals. Then and even much later it was still necessary to prove a supposition which now seems obvious: The elastic properties of rocks, and hence the velocities of elastic (seismic) waves in the earth`s crust, are primarily determined by the elastic characteristics of the minerals composing these rocks. Proof of this assertion, with rare exceptions of mono-mineralic rocks (marble, quartzite, etc.) cannot be obtained without information on the elasticities of a sufficiently large number of minerals, primarily framework, layer, and chain silicates which constitute the basis of most rocks. This also served as the starting point and main problem of the undertakings of Aleksandrov, Ryzhova, and Belikov - systematic investigations of the elastic properties of minerals and then of various rocks. 108 refs., 7 tabs.

  7. 120th anniversary of the birth of Sergei Ivanovich Vavilov (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 30 March 2011)

    NASA Astrophysics Data System (ADS)

    2011-12-01

    A scientific session of the Physical Sciences Division of the Russian Academy of Sciences (RAS) dedicated to the 120th anniversary of the birth of Sergei Ivanovich Vavilov was held in the Conference Hall of the P N Lebedev Physical Institute, RAS, on 30 March 2011. The following reports were put on the session's agenda posted on the web site www.gpad.ac.ru of the Physical Sciences Division, RAS: (1) Masalov A V (P N Lebedev Physical Institute, RAS, Moscow) "S I Vavilov and nonlinear optics"; (2) Basiev T T (Laser Materials and Technology Research Center, A M Prokhorov General Physics Institute, RAS, Moscow) "Luminescent nanophotonics and high-power lasers"; (3) Vitukhnovsky A G (P N Lebedev Physical Institute, RAS, Moscow) "Advances in luminescent light sources and displays"; (4) Aleksandrov E B (Ioffe Physical Technical Institute, RAS, St. Petersburg) "Sergei Ivanovich Vavilov and the special theory of relativity"; (5) Bolotovsky B M (P N Lebedev Physical Institute, RAS, Moscow) "Vavilov-Cherenkov effect"; (6) Vizgin V P (S I Vavilov Institute of the History of Natural Scienses and Technology, RAS, Moscow) "Sergei Ivanovich Vavilov as a historian of science"; (7) Ginzburg A S (Knowledge Society) "Academician S I Vavilov — a devotee of the enlightenment and the first president of the Knowledge Society of the USSR". The papers written on the basis of reports 1-4 and 6 are given below. The main contents of report 5 is reflected in the paper "Vavilov-Cherenkov radiation: its discovery and application" [Usp. Fiz. Nauk 179 1161 (2009); Phys. Usp. 52 1099 (2009)] published earlier by B M Bolotovsky. • S I Vavilov and nonlinear optics, A V Masalov, Z A Chizhikova Physics-Uspekhi, 2011, Volume 54, Number 12, Pages 1257-1262 • Luminescent nanophotonics, fluoride laser ceramics, and crystals, T T Basiev, I T Basieva, M E Doroshenko Physics-Uspekhi, 2011, Volume 54, Number 12, Pages 1262-1268 • Advances in light sources and displays, A G Vitukhnovsky Physics

  8. International Program and Local Organizing Committees

    NASA Astrophysics Data System (ADS)

    2012-12-01

    International Program Committee Dionisio Bermejo (Spain) Roman Ciurylo (Poland) Elisabeth Dalimier (France) Alexander Devdariani (Russia) Milan S Dimitrijevic (Serbia) Robert Gamache (USA) Marco A Gigosos (Spain) Motoshi Goto (Japan) Magnus Gustafsson (Sweden) Jean-Michel Hartmann (France) Carlos Iglesias (USA) John Kielkopf (USA) John C Lewis (Canada) Valery Lisitsa (Russia) Eugene Oks (USA) Christian G Parigger (USA) Gillian Peach (UK) Adriana Predoi-Cross (Canada) Roland Stamm (Germany) Local Organizing Committee Nikolay G Skvortsov (Chair, St Petersburg State University) Evgenii B Aleksandrov (Ioffe Physico-Technical Institute, St Petersburg) Vadim A Alekseev (Scientific Secretary, St Petersburg State University) Sergey F Boureiko (St.Petersburg State University) Yury N Gnedin (Pulkovo Observatory, St Petersburg) Alexander Z Devdariani (Deputy Chair, St Petersburg State University) Alexander P Kouzov (Deputy Chair, St Petersburg State University) Nikolay A Timofeev (St Petersburg State University)

  9. Evidence of a halo formation mechanism in the Spallation Neutron Source linac

    NASA Astrophysics Data System (ADS)

    Jeon, Dong-O.

    2013-04-01

    A new halo formation mechanism and its mitigation scheme [D. Jeon, J. Stovall, A. Aleksandrov, J. Wei, J. Staples, R. Keller, L. Young, H. Takeda, and S. Nath, Phys. Rev. ST Accel. Beams 5, 094201 (2002)PRABFM1098-440210.1103/PhysRevSTAB.5.094201] are verified experimentally through a series of emittance measurements performed during the drift tube linac tank 1 commissioning of the Spallation Neutron Source. This is a rare experiment evidence of a halo formation mechanism. As the simulation predicts, the emittance measurements clearly show a visible halo reduction as well as a significant rms emittance reduction when the proposed round beam optics is employed. The emittance measurement results are consistent with multiparticle simulations and also consistent with wire scanner results. These measurements serve as a valuable code benchmarking for a beam under an intense space charge effect.

  10. Paleosols in depressions of the central Russian upland in the Early Valdai time

    NASA Astrophysics Data System (ADS)

    Pushkina, P. R.; Sycheva, S. A.

    2014-05-01

    The genesis, evolution, and paleoecology of soils of the Early Valdai interstadials were investigated in the Aleksandrov quarry (Kursk oblast), a key section of the Late Pleistocene deposits in the periglacial area of the East European Plain. The soils developed in the uppermost parts of the buried hollows (investigated in 2009) were compared with the soils developed in the lower parts of the same hollows (investigated in 1988). The data obtained suggest that the soils in the upper parts of the hollows were developed under wetter and, at the same time, more percolative water regime than the soils in the lower parts of the hollows. These soils were formed in a semihumid climate under the forest-steppe vegetation. Forest groves existed in the upper parts of the erosional network amidst herbaceous meadow steppes. In general, the soil cover pattern of the Early Valdai interstadials corresponded to the modern soil cover pattern within the analogous landscapes.

  11. Mg2+ -dependent ATP occlusion at the first nucleotide-binding domain (NBD1) of CFTR does not require the second (NBD2).

    PubMed

    Aleksandrov, Luba; Aleksandrov, Andrei; Riordan, John R

    2008-11-15

    ATP binding to the first and second NBDs (nucleotide-binding domains) of CFTR (cystic fibrosis transmembrane conductance regulator) are bivalent-cation-independent and -dependent steps respectively [Aleksandrov, Aleksandrov, Chang and Riordan (2002) J. Biol. Chem. 277, 15419-15425]. Subsequent to the initial binding, Mg(2+) drives rapid hydrolysis at the second site, while promoting non-exchangeable trapping of the nucleotide at the first site. This occlusion at the first site of functional wild-type CFTR is somewhat similar to that which occurs when the catalytic glutamate residues in both of the hydrolytic sites of P-glycoprotein are mutated, which has been proposed to be the result of dimerization of the two NBDs and represents a transient intermediate formed during ATP hydrolysis [Tombline and Senior (2005) J. Bioenerg. Biomembr. 37, 497-500]. To test the possible relevance of this interpretation to CFTR, we have now characterized the process by which NBD1 occludes [(32)P]N(3)ATP (8-azido-ATP) and [(32)P]N(3)ADP (8-azido-ADP). Only N(3)ATP, but not N(3)ADP, can be bound initially at NBD1 in the absence of Mg(2+). Despite the lack of a requirement for Mg(2+) for ATP binding, retention of the NTP at 37 degrees C was dependent on the cation. However, at reduced temperature (4 degrees C), N(3)ATP remains locked in the binding pocket with virtually no reduction over a 1 h period, even in the absence of Mg(2+). Occlusion occurred identically in a DeltaNBD2 construct, but not in purified recombinant NBD1, indicating that the process is dependent on the influence of regions of CFTR in addition to NBD1, but not NBD2. PMID:18605986

  12. The First Nucleotide Binding Domain of Cystic Fibrosis Transmembrane Conductance Regulator Is a Site of Stable Nucleotide Interaction, whereas the Second Is a Site of Rapid Turnover.

    PubMed

    Aleksandrov, Luba; Aleksandrov, Andrei A; Chang, Xiu-Bao; Riordan, John R

    2002-05-01

    As in other adenine nucleotide binding cassette (ABC) proteins the nucleotide binding domains of the cystic fibrosis transmembrane conductance regulator (CFTR) bind and hydrolyze ATP and in some manner regulate CFTR ion channel gating. Unlike some other ABC proteins, however, there are preliminary indications that the two domains of CFTR are nonequivalent in their nucleotide interactions (Szabo, K., Szakacs, G., Hegeds, T., and Sarkadi, B. (1999) J. Biol. Chem. 274, 12209-12212; Aleksandrov, L., Mengos, A., Chang, X., Aleksandrov, A., and Riordan, J. R. (2001) J. Biol. Chem. 276, 12918-12923). We have now characterized the interactions of the 8-azido-photoactive analogues of ATP, ADP, and 5'-adenyl-beta,gamma-imidodiphosphate (AMP-PNP) with the two domains of functional membrane-bound CFTR. The results show that the two domains appear to act independently in the binding and hydrolysis of 8-azido-ATP. At NBD1 binding does not require a divalent cation. This binding is followed by minimal Mg(2+)-dependent hydrolysis and retention of the hydrolysis product, 8-azido-ADP, but not as a vanadate stabilized post-hydrolysis transition state complex. In contrast, at NBD2, MgN(3)ATP is hydrolyzed as rapidly as it is bound and the nucleoside diphosphate hydrolysis product dissociates immediately. Confirming this characterization of NBD1 as a site of more stable nucleotide interaction and NBD2 as a site of fast turnover, the non-hydrolyzable N(3)AMP-PNP bound preferentially to NBD1. This demonstration of NBD2 as the rapid nucleotide turnover site is consistent with the strong effect on channel gating kinetics of inactivation of this domain by mutagenesis. PMID:11861646

  13. CONFERENCES AND SYMPOSIA: Seventy years of the Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Waves Propagation (IZMIRAN) (Scientific session of the Physical Sciences Division of the Russian Academy of Sciences, 25 November 2009)

    NASA Astrophysics Data System (ADS)

    2010-08-01

    A scientific session of the Physical Sciences Division of the Russian Academy of Sciences dedicated to the 70th anniversary of the Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation of the Russian Academy of Sciences (IZMIRAN) (Troitsk, Moscow region) was held in the conference hall of IZMIRAN on 25 November 2009. The following reports were put on the session agenda posted on the web site www.gpad.ac.ru of the Physical Sciences Division, RAS: (1) Gurevich A V (Lebedev Physical Institute RAS, Moscow) "The role of cosmic rays and runaway electron breakdown in atmospheric lightning discharges"; (2) Aleksandrov E B (Ioffe Physical Technical Institute, RAS, St. Petersburg) "Advances in quantum magnetometry for geomagnetic research"; (3) Dorman L I (IZMIRAN, Troitsk, Moscow region, CR & SWC, Israel) "Cosmic ray variations and space weather"; (4) Mareev E A (Institute of Applied Physics, RAS, Nizhnii Novgorod) "Global electric circuit research: achievements and prospects"; (5) Tereshchenko E D, Safargaleev V V (Polar Geophysical Institute, Kola Research Center, RAS, Murmansk) "Geophysical research in Spitsbergen Archipelago: status and prospects"; (6) Gulyaev Yu V, Armand N A, Efimov A I, Matyugov S S, Pavelyev A G, Savich N A, Samoznaev L N, Smirnov V V, Yakovlev O I (Kotel'nikov Institute of Radio Engineering and Electronics RAS, Fryazino Branch, Fryazino, Moscow region) "Results of solar wind and planetary ionosphere research using radiophysical methods"; (7) Kunitsyn V E (Lomonosov Moscow State University, Moscow) "Satellite radio probing and the radio tomography of the ionosphere"; (8) Kuznetsov V D (IZMIRAN, Troitsk, Moscow region) "Space Research at the Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation, Russian Academy of Sciences." Papers based on reports 2-8 are published below. The main contents of report 1 are reproduced in A V Gurevich's review, "Nonlinear effects in the ionosphere" [Phys. Usp. 50

  14. Multiple Membrane-Cytoplasmic Domain Contacts in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mediate Regulation of Channel Gating*S⃞

    PubMed Central

    He, Lihua; Aleksandrov, Andrei A.; Serohijos, Adrian W. R.; Hegedüs, Tamás; Aleksandrov, Luba A.; Cui, Liying; Dokholyan, Nikolay V.; Riordan, John R.

    2008-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique ATP-binding cassette (ABC) ion channel mutated in patients with cystic fibrosis. The most common mutation, deletion of phenylalanine 508 (ΔF508) and many other disease-associated mutations occur in the nucleotide binding domains (NBD) and the cytoplasmic loops (CL) of the membrane-spanning domains (MSD). A recently constructed computational model of the CFTR three-dimensional structure, supported by experimental data (Serohijos, A. W., Hegedus, T., Aleksandrov, A. A., He, L., Cui, L., Dokholyan, N. V., and Riordan, J. R. (2008) Proc. Natl. Acad. Sci. U. S. A. 105, 3256–3261) revealed that several of these mutations including ΔF508 disrupted interfaces between these domains. Here we have used cysteine cross-linking experiments to verify all NBD/CL interfaces predicted by the structural model and observed that their cross-linking has a variety of different effects on channel gating. The interdomain contacts comprise aromatic clusters important for stabilization of the interfaces and also involve the Q-loops and X-loops that are in close proximity to the ATP binding sites. Cross-linking of all domain-swapping contacts between NBDs and MSD cytoplasmic loops in opposite halves of the protein rapidly and reversibly arrest single channel gating while those in the same halves have lesser impact. These results reinforce the idea that mediation of regulatory signals between cytoplasmic- and membrane-integrated domains of the CFTR channel apparently relies on an array of precise but highly dynamic interdomain structural joints. PMID:18658148

  15. Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein

    PubMed Central

    He, Lihua; Kota, Pradeep; Aleksandrov, Andrei A.; Cui, Liying; Jensen, Tim; Dokholyan, Nikolay V.; Riordan, John R.

    2013-01-01

    Most cystic fibrosis is caused by the deletion of a single amino acid (F508) from CFTR and the resulting misfolding and destabilization of the protein. Compounds identified by high-throughput screening to improve ΔF508 CFTR maturation have already entered clinical trials, and it is important to understand their mechanisms of action to further improve their efficacy. Here, we showed that several of these compounds, including the investigational drug VX-809, caused a much greater increase (5- to 10-fold) in maturation at 27 than at 37°C (<2-fold), and the mature product remained short-lived (T1/2∼4.5 h) and thermally unstable, even though its overall conformational state was similar to wild type, as judged by resistance to proteolysis and interdomain cross-linking. Consistent with its inability to restore thermodynamic stability, VX-809 stimulated maturation 2–5-fold beyond that caused by several different stabilizing modifications of NBD1 and the NBD1/CL4 interface. The compound also promoted maturation of several disease-associated processing mutants on the CL4 side of this interface. Although these effects may reflect an interaction of VX-809 with this interface, an interpretation supported by computational docking, it also rescued maturation of mutants in other cytoplasmic loops, either by allosteric effects or via additional sites of action. In addition to revealing the capabilities and some of the limitations of this important investigational drug, these findings clearly demonstrate that ΔF508 CFTR can be completely assembled and evade cellular quality control systems, while remaining thermodynamically unstable. He, L., Kota, P., Aleksandrov, A. A., Cui, L., Jensen, T., Dokholyan, N. V., Riordan, J. R. Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein. PMID:23104983

  16. Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein.

    PubMed

    He, Lihua; Kota, Pradeep; Aleksandrov, Andrei A; Cui, Liying; Jensen, Tim; Dokholyan, Nikolay V; Riordan, John R

    2013-02-01

    Most cystic fibrosis is caused by the deletion of a single amino acid (F508) from CFTR and the resulting misfolding and destabilization of the protein. Compounds identified by high-throughput screening to improve ΔF508 CFTR maturation have already entered clinical trials, and it is important to understand their mechanisms of action to further improve their efficacy. Here, we showed that several of these compounds, including the investigational drug VX-809, caused a much greater increase (5- to 10-fold) in maturation at 27 than at 37°C (<2-fold), and the mature product remained short-lived (T(1/2)∼4.5 h) and thermally unstable, even though its overall conformational state was similar to wild type, as judged by resistance to proteolysis and interdomain cross-linking. Consistent with its inability to restore thermodynamic stability, VX-809 stimulated maturation 2-5-fold beyond that caused by several different stabilizing modifications of NBD1 and the NBD1/CL4 interface. The compound also promoted maturation of several disease-associated processing mutants on the CL4 side of this interface. Although these effects may reflect an interaction of VX-809 with this interface, an interpretation supported by computational docking, it also rescued maturation of mutants in other cytoplasmic loops, either by allosteric effects or via additional sites of action. In addition to revealing the capabilities and some of the limitations of this important investigational drug, these findings clearly demonstrate that ΔF508 CFTR can be completely assembled and evade cellular quality control systems, while remaining thermodynamically unstable. He, L., Kota, P., Aleksandrov, A. A., Cui, L., Jensen, T., Dokholyan, N. V., Riordan, J. R. Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein. PMID:23104983

  17. Multiple membrane-cytoplasmic domain contacts in the cystic fibrosis transmembrane conductance regulator (CFTR) mediate regulation of channel gating.

    PubMed

    He, Lihua; Aleksandrov, Andrei A; Serohijos, Adrian W R; Hegedus, Tamás; Aleksandrov, Luba A; Cui, Liying; Dokholyan, Nikolay V; Riordan, John R

    2008-09-26

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique ATP-binding cassette (ABC) ion channel mutated in patients with cystic fibrosis. The most common mutation, deletion of phenylalanine 508 (DeltaF508) and many other disease-associated mutations occur in the nucleotide binding domains (NBD) and the cytoplasmic loops (CL) of the membrane-spanning domains (MSD). A recently constructed computational model of the CFTR three-dimensional structure, supported by experimental data (Serohijos, A. W., Hegedus, T., Aleksandrov, A. A., He, L., Cui, L., Dokholyan, N. V., and Riordan, J. R. (2008) Proc. Natl. Acad. Sci. U. S. A. 105, 3256-3261) revealed that several of these mutations including DeltaF508 disrupted interfaces between these domains. Here we have used cysteine cross-linking experiments to verify all NBD/CL interfaces predicted by the structural model and observed that their cross-linking has a variety of different effects on channel gating. The interdomain contacts comprise aromatic clusters important for stabilization of the interfaces and also involve the Q-loops and X-loops that are in close proximity to the ATP binding sites. Cross-linking of all domain-swapping contacts between NBDs and MSD cytoplasmic loops in opposite halves of the protein rapidly and reversibly arrest single channel gating while those in the same halves have lesser impact. These results reinforce the idea that mediation of regulatory signals between cytoplasmic- and membrane-integrated domains of the CFTR channel apparently relies on an array of precise but highly dynamic interdomain structural joints. PMID:18658148

  18. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration

    PubMed Central

    Clunes, Lucy A.; Davies, Catrin M.; Coakley, Raymond D.; Aleksandrov, Andrei A.; Henderson, Ashley G.; Zeman, Kirby L.; Worthington, Erin N.; Gentzsch, Martina; Kreda, Silvia M.; Cholon, Deborah; Bennett, William D.; Riordan, John R.; Boucher, Richard C.; Tarran, Robert

    2012-01-01

    Cigarette smoke (CS) exposure induces mucus obstruction and the development of chronic bronchitis (CB). While many of these responses are determined genetically, little is known about the effects CS can exert on pulmonary epithelia at the protein level. We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB. In vivo and in vitro studies demonstrated that CS rapidly decreased CFTR activity, leading to airway surface liquid (ASL) volume depletion (i.e., dehydration). Further studies revealed that CS induced internalization of CFTR. Surprisingly, CS-internalized CFTR did not colocalize with lysosomal proteins. Instead, the bulk of CFTR shifted to a detergent-resistant fraction within the cell and colocalized with the intermediate filament vimentin, suggesting that CS induced CFTR movement into an aggresome-like, perinuclear compartment. To test whether airway dehydration could be reversed, we used hypertonic saline (HS) as an osmolyte to rehydrate ASL. HS restored ASL height in CS-exposed, dehydrated airway cultures. Similarly, inhaled HS restored mucus transport and increased clearance in patients with CB. Thus, we propose that CS exposure rapidly impairs CFTR function by internalizing CFTR, leading to ASL dehydration, which promotes mucus stasis and a failure of mucus clearance, leaving smokers at risk for developing CB. Furthermore, our data suggest that strategies to rehydrate airway surfaces may provide a novel form of therapy for patients with CB.—Clunes, L. A., Davies, C. M., Coakley, R. D., Aleksandrov, A. A., Henderson, A. G., Zeman, K. L., Worthington, E. N., Gentzsch, M., Kreda, S. M., Cholon, D., Bennett, W. D., Riordan, J. R., Boucher, R. C., Tarran, R. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. PMID:21990373

  19. PREFACE: 2nd Russia-Japan-USA Symposium on the Fundamental and Applied Problems of Terahertz Devices and Technologies (RJUS TeraTech - 2013)

    NASA Astrophysics Data System (ADS)

    Karasik, Valeriy; Ryzhii, Viktor; Yurchenko, Stanislav

    2014-03-01

    The 2nd Russia-Japan-USA Symposium 'The Fundamental & Applied Problems of Terahertz Devices & Technologies' (RJUS TeraTech - 2013) Bauman Moscow State Technical University Moscow, Russia, 3-6 June, 2013 The 2nd Russia-Japan-USA Symposium 'The Fundamental & Applied Problems of Terahertz Devices & Technologies' (RJUS TeraTech - 2013) was held in Bauman Moscow State Technical University on 3-6 June 2013 and was devoted to modern problems of terahertz optical technologies. RJUS TeraTech 2013 was organized by Bauman Moscow State Technical University in cooperation with Tohoku University (Sendai, Japan) and University of Buffalo (The State University of New York, USA). The Symposium was supported by Bauman Moscow State Technical University (Moscow, Russia) and Russian Foundation for Basic Research (grant number 13-08-06100-g). RJUS TeraTech - 2013 became a foundation for sharing and discussing modern and promising achievements in fundamental and applied problems of terahertz optical technologies, devices based on grapheme and grapheme strictures, condensed matter of different nature. Among participants of RJUS TeraTech - 2013, there were more than 100 researchers and students from different countries. This volume contains proceedings of the 2nd Russia-Japan-USA Symposium 'The Fundamental & Applied Problems of Terahertz Devices & Technologies'. Valeriy Karasik, Viktor Ryzhii and Stanislav Yurchenko Bauman Moscow State Technical University Symposium chair Anatoliy A Aleksandrov, Rector of BMSTU Symposium co-chair Valeriy E Karasik, Head of the Research and Educational Center 'PHOTONICS AND INFRARED TECHNOLOGY' (Russia) Invited Speakers Taiichi Otsuji, Research Institute of Electrical Communication, Tohoku University, Sendai, Japan Akira Satou, Research Institute of Electrical Communication, Tohoku University, Sendai, Japan Michael Shur, Electrical, Computer and System Engineering and Physics, Applied Physics, and Astronomy, Rensselaer Polytechnic Institute, NY, USA Natasha

  20. From the first nuclear power plant to fourth-generation nuclear power installations [on the 60th anniversary of the World's First nuclear power plant

    NASA Astrophysics Data System (ADS)

    Rachkov, V. I.; Kalyakin, S. G.; Kukharchuk, O. F.; Orlov, Yu. I.; Sorokin, A. P.

    2014-05-01

    Successful commissioning in the 1954 of the World's First nuclear power plant constructed at the Institute for Physics and Power Engineering (IPPE) in Obninsk signaled a turn from military programs to peaceful utilization of atomic energy. Up to the decommissioning of this plant, the AM reactor served as one of the main reactor bases on which neutron-physical investigations and investigations in solid state physics were carried out, fuel rods and electricity generating channels were tested, and isotope products were bred. The plant served as a center for training Soviet and foreign specialists on nuclear power plants, the personnel of the Lenin nuclear-powered icebreaker, and others. The IPPE development history is linked with the names of I.V. Kurchatov, A.I. Leipunskii, D.I. Blokhintsev, A.P. Aleksandrov, and E.P. Slavskii. More than 120 projects of various nuclear power installations were developed under the scientific leadership of the IPPE for submarine, terrestrial, and space applications, including two water-cooled power units at the Beloyarsk NPP in Ural, the Bilibino nuclear cogeneration station in Chukotka, crawler-mounted transportable TES-3 power station, the BN-350 reactor in Kazakhstan, and the BN-600 power unit at the Beloyarsk NPP. Owing to efforts taken on implementing the program for developing fast-neutron reactors, Russia occupied leading positions around the world in this field. All this time, IPPE specialists worked on elaborating the principles of energy supertechnologies of the 21st century. New large experimental installations have been put in operation, including the nuclear-laser setup B, the EGP-15 accelerator, the large physical setup BFS, the high-pressure setup SVD-2; scientific, engineering, and technological schools have been established in the field of high- and intermediate-energy nuclear physics, electrostatic accelerators of multicharge ions, plasma processes in thermionic converters and nuclear-pumped lasers, physics of compact

  1. Spin noise spectroscopy from acoustic to GHz frequencies

    NASA Astrophysics Data System (ADS)

    Hübner, Jens

    2010-03-01

    Performing perturbation free measurements on semiconductor quantum systems has long been banished to textbooks on quantum mechanics. The emergent technique of spin noise spectroscopy is challenging this restriction. Empowered only by the ever present intrinsic spin fluctuation dynamics in thermal equilibrium, spin noise spectroscopy is capable to directly deduce several physical properties of carriers spins in semiconductors from these fluctuations. Originating from spin noise measurements on alkali metal vapors in quantum optics [1] the method has become a powerful technique to unravel the intrinsic spin dynamics in semiconductors [2]. In this talk I will present the recent progress of spin noise spectroscopy and how it is used to monitor the spin dynamic in semiconductor quantum wells at thermal equilibrium and as a consequence thereof directly detect the spatial dynamics of the carriers being marked with their own spin on a microscopic scale [3]. Further I will present measurements of how the non-perturbative nature of spin noise spectroscopy gives valuable insight into the delicate dependence of the spin relaxation time of electrons on doping density and temperature in semiconductors n-doped in the vicinity of the metal-insulator transition where hyperfine and intra-band depolarization compete [4]. Also the measurement bandwidth can be extended to GHz frequencies by ultrafast optical probing [5] yielding in conjunction with depth resolved spin noise measurements insights into the origin of inhomogeneous spin dephasing effects at high magnetic fields [5]. Additionally I will present how spin noise spectroscopy can be employed to spatially depth resolve doping profiles with optical resolution [6] and give a summary on easy to implement techniques of spin noise spectroscopy at acoustic frequencies in alkali metal vapors. [4pt] [1] E. Aleksandrov and V. Zapassky, Zh. Eksp. Teor. Fiz. 81, 132 (1981); S. A. Crooker, D. G. Rickel, A. V. Balatsky, and D. L. Smith

  2. Restoration of domain folding and interdomain assembly by second-site suppressors of the ΔF508 mutation in CFTR

    PubMed Central

    He, Lihua; Aleksandrov, Luba A.; Cui, Liying; Jensen, Timothy J.; Nesbitt, Kenneth L.; Riordan, John R.

    2010-01-01

    Deletion of PHE508 (ΔF508) from the first nucleotide-binding domain (NBD1) of CFTR, which causes most cystic fibrosis, disrupts the folding and assembly of the protein. Although the folding pathways and yield of isolated NBD1 are altered, its global structure is not, and details of the changes in the rest of the protein remain unclear. To gain further insight into how the whole mutant protein is altered, we have determined the influence of known second-site suppressor mutations in NBD1 on the conformation of this domain and key interfaces between domains. We found that the suppressors restored maturation of only those processing mutations located in NBD1, but not in other domains, including those in the C-terminal cytoplasmic loop of the second membrane-spanning domain, which forms an interface with the NBD1 surface. Nevertheless, the suppressors promoted the formation of this interface and others in the absence of F508. The suppressors restored maturation in a ΔF508 construct from which NBD2 was absent but to a lesser extent than in the full-length, indicating that ΔF508 disrupts interactions involving NBD2, as well as other domains. Rescue of ΔF508-CFTR by suppressors required the biosynthesis of the entire full-length protein in continuity, as it did not occur when N- and C-terminal “halves” were coexpressed. Simultaneous with these interdomain perturbations, ΔF508 resulted in suppressor reversed alterations in accessibility of residues both in the F508-containing NBD1 surface loop and in the Q loop within the domain core. Thus, in the context of the full-length protein, ΔF508 mutation causes detectable changes in NBD1 conformation, as well as interdomain interactions.—He, L., Aleksandrov, L. A., Cui, L., Jensen, T. J., Nesbitt, K. L., Riordan, J. R. Restoration of domain folding and interdomain assembly by second-site suppressors of the ΔF508 mutation in CFTR. PMID:20233947