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5. Ryanodine receptor leak triggers fiber Ca²⁺ redistribution to preserve force and elevate basal metabolism in skeletal muscle

Author

Lamboley, CR, Pearce, L, Seng, C, Meizoso-Huesca, A, Singh, DP, Frankish, BP, Kaura, V, Lo, HP, Ferguson, C, Allen, PD, Hopkins, PM, Parton, RG, Murphy, RM, van der Poel, C, Barclay, CJ, and Launikonis, BS

Subjects
musculoskeletal system, tissues
Abstract

Muscle contraction depends on tightly regulated Ca2+ release. Aberrant Ca2+ leak through ryanodine receptor 1 (RyR1) on the sarcoplasmic reticulum (SR) membrane can lead to heatstroke and malignant hyperthermia (MH) susceptibility, as well as severe myopathy. However, the mechanism by which Ca2+ leak drives these pathologies is unknown. Here, we investigate the effects of four mouse genotypes with increasingly severe RyR1 leak in skeletal muscle fibers. We find that RyR1 Ca2+ leak initiates a cascade of events that cause precise redistribution of Ca2+ among the SR, cytoplasm, and mitochondria through altering the Ca2+ permeability of the transverse tubular system membrane. This redistribution of Ca2+ allows mice with moderate RyR1 leak to maintain normal function; however, severe RyR1 leak with RYR1 mutations reduces the capacity to generate force. Our results reveal the mechanism underlying force preservation, increased ATP metabolism, and susceptibility to MH in individuals with gain-of-function RYR1 mutations.

Published
2021

7. HCV and blood transfusion

Author

Reesink, H. W., van der Poel, C. L., Cuypers, H. T. M., Lelie, P. N., De Bac, C., editor, Taliani, G., editor, and Gerlich, W. H., editor

Published
1992
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9. Effects of elevated physiological temperatures on sarcoplasmic reticulum function in mechanically skinned muscle fibers of the rat

Author

van der Poel, C. and Stephenson, D.G.

Subjects
Sarcoplasmic reticulum -- Research, Muscle cells -- Research, Muscles -- Research, Calcium ions -- Research, Superoxide -- Research, Cell research, Biological sciences
Abstract

Properties of the sarcoplasmic reticulum (SR) with respect to [Ca.sup.2+] loading and release were measured in mechanically skinned fiber preparations from isolated extensor digitorum longus (EDL) muscles of the rat that were either kept at room temperature (23[degrees]C) or exposed to temperatures in the upper physiological range for mammalian skeletal muscle (30 min at 40 or 43[degrees]C). The ability of the SR to accumulate [Ca.sup.2+] was significantly reduced by a factor of 1.9-2.1 after the temperature treatments due to a marked increase in SR [Ca.sup.2+] leak, which persisted for at least 3 h after treatment. Results with blockers of [Ca.sup.2+] release channels (ruthenium red) and SR [Ca.sup.2+] pumps [2,5-di(tert-butyl)- 1,4-hydroquinone] indicate that the increased [Ca.sup.2+] leak was not through the SR [Ca.sup.2+] release channel or the SR [Ca.sup.2+] pump, although it is possible that the leak pathway was via oligomerized [Ca.sup.2+] pump molecules. No significant change in the maximum SR [Ca.sup.2+]-ATPase activity was observed after the temperature treatment, although there was a tendency for a decrease in the SR [Ca.sup.2+]-ATPase. The observed changes in SR properties were fully prevented by the snperoxide ([O.sub.2.sup.*-]) scavenger Tiron (20 mM), indicating that the production of [O.sub.2.sup.*-] at elevated temperatures is responsible for the increase in SR [Ca.sup.2+] leak. Results show that physiologically relevant elevated temperatures 1) induce lasting changes in SR properties with respect to [Ca.sup.2+] handling that contribute to a marked increase in the SR [Ca.sup.2+] leak and, consequently, to the reduction in the average coupling ratio between [Ca.sup.2+] transport and SR [Ca.sup.2+]-ATPase and muscle performance, and 2) that these changes are mediated by temperature-induced [O.sub.2.sup.*-] production. skeletal muscle; calcium ion leak; superoxide; skinned fibers doi:10.1152/ajpcell.00052.2006

Published
2007

28. Authorʼs reply

Author

van der Poel, C. L., Seifried, E., and Schaasberg, W.

Published
2003

35. A Concomitant Muscle Injury Does Not Worsen Traumatic Brain Injury Outcomes in Mice

Author

Sun, M, Brady, RD, van der Poel, C, Apted, D, Semple, BD, Church, JE, O'Brien, TJ, McDonald, SJ, Shultz, SR, Sun, M, Brady, RD, van der Poel, C, Apted, D, Semple, BD, Church, JE, O'Brien, TJ, McDonald, SJ, and Shultz, SR

Abstract

Traumatic brain injury (TBI) often involves multitrauma in which concurrent extracranial injury occurs. We previously demonstrated that a long bone fracture exacerbates neuroinflammation and functional outcomes in mice given a TBI. Whether other forms of concomitant peripheral trauma that are common in the TBI setting, such as skeletal muscle injury, have similar effects is unknown. As such, here we developed a novel mouse multitrauma model by combining a closed-skull TBI with a cardiotoxin (CTX)-induced muscle injury to investigate whether muscle injury affects TBI outcomes. Adult male mice were assigned to four groups: sham-TBI + sham-muscle injury (SHAM); sham-TBI + CTX-muscle injury (CTX); TBI + sham-muscle injury (TBI); TBI + CTX-muscle injury (MULTI). Some mice were euthanized at 24 h post-injury to assess neuroinflammation and cerebral edema. The remaining mice underwent behavioral testing after a 30-day recovery period, and were euthanized at 35 days post-injury for post-mortem analysis. At 24 h post-injury, both TBI and MULTI mice had elevated edema, increased expression of GFAP (i.e., a marker for reactive astrocytes), and increased mRNA levels of inflammatory chemokines. There was also an effect of injury on cytokine levels at 35 days post-injury. However, the TBI and MULTI mice did not significantly differ on any of the measures assessed. These initial findings suggest that a concomitant muscle injury does not significantly affect preclinical TBI outcomes. Future studies should investigate the combination of different injury models, additional outcomes, and other post-injury time points.

Published
2018

36. Sexual transmission of hepatitis C virus.

Author

Bresters, D, Mauser-Bunschoten, E P, Reesink, H W, Roosendaal, G, van der Poel, C L, Chamuleau, R A F M, Jansen, P L M, Weegink, C J, Cuypers, H T M, Lelie, P N, and van den Berg, H M.

Published
1993

37. Measurement of charm production in antineutrino charged-current interactions

Author

Onengüt, G, Van Dantzig, R, De Jong, M, Konijn, J, Melzer, O, Oldeman, R G C, Pesen, E, Van der Poel, C A F J, Visschers, J L, Güler, M, Köse, U, Serin-Zeyrek, M, Kama, S, Sever, R, Tolun, P, Zeyrek, M T, Catanesi, M G, De Serio, M, Ieva, M, Muciaccia, M T, Radicioni, E, Simone, S, Bülte, A, Winter, Klaus, Van de Vyver, B, Vilain, P, Wilquet, G, Saitta, B, Di Capua, E, Ogawa, S, Shibuya, H, Artamonov, A V, Brunner, J, Chizhov, M, Cussans, D G, Doucet, M, Fabre, Jean-Paul, Hristova, I R, Kawamura, T, Kolev, D, Litmaath, M, Meinhard, H, Panman, J, Papadopoulos, I M, Ricciardi, S, Rozanov, A, Saltzberg, D, Tsenov, R V, Uiterwijk, J W E, Zucchelli, P, Goldberg, J, Chikawa, M, Arik, E, Song, J S, Yoon, C S, Kodama, K, Ushida, N, Aoki, S, Hara, T, Delbar, T, Favart, D, Grégoire, G, Kalinin, S, Makhlyoueva, I V, Gorbunov, P, Khovanskii, V D, Shamanov, V V, Tsukerman, I, Bruski, N, Frekers, D, Rondeshagen, D, Wolff, T, Hoshino, K, Kawada, J, Komatsu, M, Miyanishi, M, Nakamura, M, Nakano, T, Narita, K, Niu, K, Niwa, K, Nonaka, N, Sato, O, Toshito, T, Buontempo, S, Cocco, A G, D'Ambrosio, N, De Lellis, G, De Rosa, G, Di Capua, F, Ereditato, A, Fiorillo, G, Marotta, A, Messina, M, Migliozzi, P, Pistillo, C, Santorelli, R, Scotto-Lavina, L, Strolin, P, Tioukov, V, Nakamura, K, Okusawa, T, Dore, U, FLoverre, P, Ludovici, L, Maslennikov, A L, Righini, P, Rosa, G, Santacesaria, R, Satta, A, Spada, F R, Barbuto, E, Bozza, C, Grella, G, Romano, G, Sirignano, C, Sorrentino, S, Sato, Y, Tezuka, I, Other Research IHEF (IoP, FNWI), UCL - SC/PHYS - Département de physique, Çukurova Üniversitesi, Önengüt, G., van Dantzig, R., de Jong, M., Melzer, O., Oldeman, R. G. C., Pesen, E., Visschers, J. L., Güler, M., Köse, U., Serin Zeyrek, M., Sever, R., Tolun, P., Zeyrek, M. T., Catanesi, M. G., De Serio, M., Ieva, M., Muciaccia, M. T., Radicioni, E., Simone, S., Bülte, A., Winter, K., Van de Vyver, B., Vilain, P., Wilquet, G., Saitta, B., Di Capua, E., Ogawa, S., Shibuya, H., Artamonov, A., Chizhov, M., Doucet, M., Hristova, I. R., Kayis Topaksu, A., Kawamura, T., Kolev, D., Meinhard, H., Panman, J., Papadopoulos, I. M., Ricciardi, S., Rozanov, A., Tsenov, R., Uiterwijk, J. W. E., Zucchelli, P., Goldberg, J., Chikawa, M., Arik, E., Song, J. S., Yoon, C. S., Kodama, K., Ushida, N., Aoki, S., Hara, T., Delbar, T., Favart, D., Grégoire, G., Kalinin, S., Makhlioueva, I., Gorbunov, P., Khovansky, V., Shamanov, V., Tsukerman, I., Bruski, N., Frekers, D., Hoshino, K., Kawada, J., Komatsu, M., Miyanishi, M., Nakamura, M., Nakano, T., Narita, K., Niu, K., Niwa, K., Nonaka, N., Sato, O., Toshito, T., Buontempo, S., Cocco, A. G., D'Ambrosio, N., De Lellis, G., De Rosa, G., DI CAPUA, Francesco, Ereditato, A., Fiorillo, Giuliana, Marotta, A., Messina, M., Migliozzi, P., Pistillo, C., Scotto Lavina, L., Strolin, P., Tioukov, V., Nakamura, K., Okusawa, T., Dore, U., Loverre, P. F., Ludovici, L., Righini, P., Rosa, G., Santacesaria, R., Satta, A., Spada, F. R., Barbuto, E., Bozza, C., Grella, G., Romano, G., Sirignano, C., Sorrentino, S., Sato, Y., Tezuka, I., G., Onengut, R. v., Dantzig, M. d., Jong, O., Melzer, R. G., C., E., Pesen, J. L., Visscher, M., Guler, U., Kose, M., Serin Zeyrek, R., Sever, P., Tolun, M. T., Zeyrek, M. G., Catanesi, M. D., Serio, M., Ieva, M. T., Muciaccia, E., Radicioni, S., Simone, A., Bulte, K., Winter, B. V., De, P., Vilain, G., Wilquet, B., Saitta, E. D., Capua, S., Ogawa, H., Shibuya, A., Artamonov, M., Chizhov, M., Doucet, I. R., Hristova, A., Kayis Topaksu, T., Kawamura, D., Kolev, H., Meinhard, J., Panman, I. M., Papadopoulo, S., Ricciardi, A., Rozanov, R., Tsenov, J. W., E., P., Zucchelli, J., Goldberg, M., Chikawa, J. S., Song, C. S., Yoon, K., Kodama, N., Ushida, S., Aoki, T., Hara, T., Delbar, D., Favart, G., Gregoire, S., Kalinin, I., Makhlioueva, P., Gorbunov, V., Khovansky, V., Shamanov, I., Tsukerman, N., Bruski, D., Freker, K., Hoshino, J., Kawada, M., Komatsu, M., Miyanishi, M., Nakamura, T., Nakano, K., Narita, K., Niu, K., Niwa, N., Nonaka, O., Sato, T., Toshito, S., Buontempo, A. G., Cocco, N., D'Ambrosio, DE LELLIS, Giovanni, DE ROSA, Gianfranca, A., Ereditato, A., Marotta, M., Messina, P., Migliozzi, C., Pistillo, L. S., Lavina, P., Strolin, V., Tioukov, K., Nakamura, T., Okusawa, U., Dore, P. F., Loverre, L., Ludovici, P., Righini, G., Rosa, R., Santacesaria, A., Satta, F. R., Spada, E., Barbuto, C., Bozza, G., Grella, G., Romano, C., Sirignano, S., Sorrentino, Y., Sato, and I., Tezuka

Subjects
Physics, NEUTRINO INTERACTIONS, CHORUS EXPERIMENT, Nuclear and High Energy Physics, Particle physics, Muon, Large Hadron Collider, Physics::Instrumentation and Detectors, High Energy Physics::Phenomenology, Charge (physics), BEAMS, EVENTS, Nuclear physics, OPPOSITE-SIGN DIMUONS, High Energy Physics::Experiment, Production (computer science), Charm (quantum number), Neutrino, Nuclear Experiment, Particle Physics - Experiment, Charged current, Beam (structure)
Abstract

During the years 1994-1997, the emulsion target of the CHORUS detector was exposed to the wide-band neutrino beam of the CERN SPS collecting about 10 6 neutrino interactions. A measurement of ?¯µ-induced charm production is performed by using the presence of a 5% ?¯µ component in the ?µ beam. The measurement takes advantage of the capability to observe the decay topology in the emulsion. The analysis is based on a sample of charged-current interactions with at least one identified muon. About 100000 were located in the emulsion target and fully reconstructed. By requiring a positive muon charge as determined by the CHORUS muon spectrometer, 32?¯µ-induced charm events were observed with an estimated background of 3.2 events. At an average antineutrino energy in the neutrino beam of 18 GeV, the charm production rate induced by antineutrinos is measured to be ?(?¯µN›µ+c¯X)/?(?¯µN›µ+X) =(5.0-0.9+1.4(stat)±0.7(syst))%. The ratio between neutral and charged charm production rates in this process is (2.6-1.0+1.7(stat)±0.8(syst)). The charm production rate as a function of the antineutrino energy is found to be in good agreement with previous results derived from di-lepton data. © 2004 Elsevier B.V. All rights reserved. Bundesministerium für Bildung und Forschung Promotion and Mutual Aid Corporation for Private Schools of Japan Grant Foundation: KRF-2003-005-C00014 Israel Science Foundation: 328/94 CERN Brussels Instituut voor Milieubeheer Instituto Nazionale di Fisica Nucleare Foundation for Fundamental Research on Matter Korean Foundation for Cancer Research We gratefully acknowledge the help and support of the neutrino-beam staff and of the numerous technical collaborators who contributed to the detector construction, operation, emulsion pouring, development, and scanning. The experiment was made possible by grants from the Institut Interuniversitaire des Sciences Nucléaires and the Interuniversitair Instituut voor Kernwetenschappen (Belgium); the Israel Science Foundation (Grant 328/94) and the Technion Vice President Fund for the Promotion of Research (Israel); CERN (Geneva, Switzerland); the German Bundesministerium für Bildung und Forschung (Germany); the Institute of Theoretical and Experimental Physics (Moscow, Russia); the Istituto Nazionale di Fisica Nucleare (Italy); the Promotion and Mutual Aid Corporation for Private Schools of Japan and Japan Society for the Promotion of Science (Japan); Korea Research Foundation Grant (KRF-2003-005-C00014) (Republic of Korea); the Foundation for Fundamental Research on Matter FOM and the National Scientific Research Organization NWO (The Netherlands); and the Scientific, and Technical Research Council of Turkey (Turkey). We gratefully acknowledge their support.

Published
2004

38. Promotion de la paix en Bosnie-Herzégovine : l'idée 'démocratique' à l'épreuve des processus de mise en œuvre

Author

Chetail, V, Van der Poel, C, Ramel, S, Chetail, V ( V ), Van der Poel, C ( C ), Ramel, S ( S ), Ramel, Sylvie, Chetail, V, Van der Poel, C, Ramel, S, Chetail, V ( V ), Van der Poel, C ( C ), Ramel, S ( S ), and Ramel, Sylvie

Abstract

Les processus de pacification et de démocratisation aujourd'hui en cours en Bosnie-Herzégovine révèlent un écart parfois important entre l'énonciation de certaines politiques et leurs mises en oeuvre. L'objectif de cet article est à la fois de mettre en évidence des questionnements révélateurs de cet écart et de les examiner à travers trois éléments principaux : les valeurs implicites soustendant les programmes d'aide internationale, la notion de "culture globale", et la question de la représentativité des minorités. À terme, la reconnaissance et la prise en compte de cet écart devraient permettre d'élaborer de nouveaux cadres d'analyse et paradigmes explicatifs. Une re-négociation théorique qui devrait également faciliter la définition de nouveaux rapports dialectiques entre fournisseurs d'aide et bénéficiaires.

Published
2006

44. Implementation of donor screening for infectious agents transmitted by blood by nucleic acid technology: update to 2003

Author

Coste, J., Reesink, H. W., Engelfriet, C. P., Laperche, S., Brown, S., Busch, M. P., Cuijpers, H. T., Elgin, R., Ekermo, B., Epstein, J. S., Flesland, O., Heier, H. E., Henn, G., Hernandez, J. M., Hewlett, I. K., Hyland, C., Keller, A. J., Krusius, T., Levicnik-Stezina, S., Levy, G., Lin, C. K., Margaritis, A. R., Muylle, L., Niederhauser, C., Neiderhauser, C., Pastila, S., Pillonel, J., Pineau, J., van der Poel, C. L., Politis, C., Roth, W. K., Sauleda, S., Seed, C. R., Sondag-Thull, D., Stramer, S. L., Strong, M., Vamvakas, E. C., Velati, C., Vesga, M. A., Zanetti, A., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Other departments

Published
2005

45. Measurement of fragmentation properties of charmed particle production in charged-current neutrino interactions

Author

Onengüt, G, Van Dantzig, R, De Jong, M, Konijn, J, Melzer, O, Oldeman, R G C, Pesen, E, Van der Poel, C A F J, Visschers, J L, Güler, M, Köse, U, Serin-Zeyrek, M, Kama, S, Sever, R, Tolun, P, Zeyrek, M T, Catanesi, M G, De Serio, M, Ieva, M, Muciaccia, M T, Radicioni, E, Simone, S, Bülte, A, Winter, Klaus, Van de Vyver, B, Vilain, P, Wilquet, G, Saitta, B, Di Capua, E, Ogawa, S, Shibuya, H, Artamonov, A V, Brunner, J, Chizhov, M, Cussans, D G, Doucet, M, Fabre, Jean-Paul, Hristova, I R, Kawamura, T, Kolev, D, Litmaath, M, Meinhard, H, Panman, J, Papadopoulos, I M, Ricciardi, S, Rozanov, A, Saltzberg, D, Tsenov, R V, Uiterwijk, J W E, Zucchelli, P, Goldberg, J, Chikawa, M, Arik, E, Song, J S, Yoon, C S, Kodama, K, Ushida, N, Aoki, S, Hara, T, Delbar, T, Favart, D, Grégoire, G, Kalinin, S, Makhlyoueva, I V, Gorbunov, P, Khovanskii, V D, Shamanov, V V, Tsukerman, I, Bruski, N, Frekers, D, Rondeshagen, D, Wolff, T, Hoshino, K, Kawada, J, Komatsu, M, Miyanishi, M, Nakamura, M, Nakano, T, Narita, K, Niu, K, Niwa, K, Nonaka, N, Sato, O, Toshito, T, Buontempo, S, Cocco, A G, D'Ambrosio, N, De Lellis, G, De Rosa, G, Di Capua, F, Ereditato, A, Fiorillo, G, Marotta, A, Messina, M, Migliozzi, P, Pistillo, C, Santorelli, R, Scotto-Lavina, L, Strolin, P, Tioukov, V, Nakamura, K, Okusawa, T, Dore, U, FLoverre, P, Ludovici, L, Maslennikov, A L, Righini, P, Rosa, G, Santacesaria, R, Satta, A, Spada, F R, Barbuto, E, Bozza, C, Grella, G, Romano, G, Sirignano, C, Sorrentino, S, Sato, Y, Tezuka, I, Other Research IHEF (IoP, FNWI), UCL - SC/PHYS - Département de physique, and Çukurova Üniversitesi

Subjects
Physics, Nuclear and High Energy Physics, Particle physics, Muon, Large Hadron Collider, media_common.quotation_subject, Asymmetry, Nuclear physics, Transverse plane, symbols.namesake, symbols, Feynman diagram, Nuclear emulsion, High Energy Physics::Experiment, Astrophysics::Earth and Planetary Astrophysics, Neutrino, Nuclear Experiment, Charged current, Particle Physics - Experiment, media_common
Abstract

During the years 1994-1997, the emulsion target of the CHORUS detector was exposed to the wide-band neutrino beam of the CERN SPS. In total about 100 000 charged-current neutrino interactions were located in the nuclear emulsion target and fully reconstructed. From this sample of events which was based on the data acquired by new automatic scanning systems, 1048 D0 events were selected by a pattern recognition program. They were confirmed as neutral-particle decays through visual inspection. Fragmentation properties of deep-inelastic charm production were measured using these events. Distributions of the D0 momentum, Feynman x (xF), z and tan?out, the transverse angle out of the leptonic plane defined by the muon and the neutrino, are presented. The mean value of z was measured to be =0.63±0.03(stat)±0.01(syst). From fits to the z distribution, values for the Peterson parameter ?P=0.108±0.017(stat) ±0.013(syst) and the Collins-Spiller parameter ?CS=0.21-0.04+0. 05(stat)±0.04(syst) are found. For the average value of xF we find =0.38±0.04(stat)±0.03(syst) and for the forward-backward asymmetry A=0.79±0.14(stat)±0.05(syst). The distribution of tan?out was measured with an average value =0.030±0.002. © 2004 Elsevier B.V. All rights reserved. Promotion and Mutual Aid Corporation for Private Schools of Japan CERN Grant Foundation: KRF-2003-005-C00014 Israel Science Foundation: 328/94 Bundesministerium für Bildung und Forschung Instituto Nazionale di Fisica Nucleare Foundation for Fundamental Research on Matter Korean Foundation for Cancer Research We gratefully acknowledge the help and support of the neutrino beam staff and of the numerous technical collaborators who contributed to the detector construction, operation, emulsion pouring, development, and scanning. The experiment was made possible by grants from the Institut Interuniversitaire des Sciences Nucléaires and the Interuniversitair Instituut voor Kernwetenschappen (Belgium), the Israel Science Foundation (grant 328/94) and the Technion Vice President Fund for the Promotion of Research (Israel), CERN (Geneva, Switzerland), the German Bundesministerium für Bildung und Forschung (Germany), the Institute of Theoretical and Experimental Physics (Moscow, Russia), the Istituto Nazionale di Fisica Nucleare (Italy), the Promotion and Mutual Aid Corporation for Private Schools of Japan and Japan Society for the Promotion of Science (Japan), the Korea Research Foundation Grant (KRF-2003-005-C00014) (Republic of Korea), the Foundation for Fundamental Research on Matter FOM and the National Scientific Research Organization NWO (The Netherlands), and the Scientific and Technical Research Council of Turkey (Turkey). We gratefully acknowledge their support.

Published
2004

46. Phase-change optical recording in TeSeSb alloys.

Author

van der Poel, C. J., Gravesteijn, D. J., Rippens, W. G. V. M., Stockx, H. T. L. P., and van Uijen, C. M. J.

Subjects
*ALLOYS, *TELLURIUM, *SELENIUM, *ANTIMONY, *OPTICAL storage systems
Abstract

Presents a study which examined the characteristics of reversible phase-change optical data storage in tellurium selenium antimony alloys. Information on the pregrooved substrates used in the optical recording experiments; Utilization of a normalized carrier-to-noise ratio; Discussion of alloy composition.

Published
1986
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47. Visible Y-junction diode laser with mixed coupling.

Author

van der Poel, C. J., Opschoor, J., Valster, A., Drenten, R. R., and Andre, J. P.

Subjects
*DIODES, *LASERS, *LASER beams
Abstract

Presents a study which examined a phase-locked, visible Y-junction diode laser with mixed coupling. Details of the experiments; Theoretical analysis; Discussion of the results in a framework of the model based on the beam propagation method.

Published
1990
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48. Measurement of the Z/A dependence of neutrino charged-current total cross-sections

Author

Kayis Topaksu, A., Oneng¨ut C¸ ukurova University, G., Adana, van Dantzig, Turkey R., de Jong, M., Konijn, J., Melzer, O., Oldeman1, R. G. C., Pesen, E., van der Poel, C. A. F. J., Spada2, F. R., Visschers NIKHEF, J. L., Amsterdam, G¨uler3, The Netherlands M., Serin Zeyrek, M., Kama, S., Sever, R., Tolun, P., Zeyrek METU, M. T., Ankara, Armenise, Turkey N., Catanesi, M. G., De Serio, M., Ieva, M., Muciaccia, M. T., Radicioni, E., Simone Universit`a di Bari, S., Infn, Bari, B¨ulte, Italy A., Winter Humboldt Universit¨at, K., Berlin, El Aidi, Germany4 R., Van de Vyver5, B., 6, Vilain7, P., Wilquet7 Inter University Institute for High Energies Brussels, G., Saitta Universit`a di Cagliari, Belgium B., Infn, Cagliari, Di Capua Universit`a di Ferrara, Italy E., Infn, Ferrara, Ogawa, Italy S., Shibuya Toho University, H., Funabashi, Artamonov8, Japan A., Brunner9, J., Chizhov10, M., Cussans11, D., Doucet12, M., Fabre, J. P., Hristova10, I. R., Kawamura, T., Kolev10, D., Litmaath13, M., Meinhard, H., Panman, J., Papadopoulos, I. M., Ricciardi14, S., Rozanov9, A., Saltzberg15, D., Tsenov10, R., Uiterwijk, J. W. E., Zucchelli16 CERN, P., Geneva, Goldberg Technion, Switzerland J., Haifa, Chikawa Kinki University, Israel M., Higashiosaka, Arik Bogazici University, Japan E., Istanbul, Song, Turkey J. S., Yoon Gyeongsang National University, C. S., Jinju, Kodama, Korea K., Ushida Aichi University of Education, N., Kariya, Aoki, Japan S., Hara Kobe University, T., Kobe, Delbar, Japan T., Favart, D., Gr´egoire, G., Kalinin, S., Makhlyoueva Universit´e Catholique de Louvain, I., Louvain la Neuve, Gorbunov6, Belgium P., Khovansky, V., Shamanov, V., Tsukerman Institute for Theoretical, I., Experimental, Physics, Moscow, Bruski, Russian Federation N., Frekers, D., Rondeshagen, D., Wolff Westf¨alische Wilhelms Universit¨at, T., M¨unster, Hoshino, Germany4 160 The CHORUS Collaboration: Measurement of the Z/A dependence of neutrino charged current total cross sections K., Kawada, J., Komatsu, M., Miyanishi, M., Nakamura, M., Nakano, T., Narita, K., Niu, K., Niwa, K., Nonaka, N., Sato, O., Toshito Nagoya University, T., Nagoya, Buontempo, Japan S., Cocco, A. G., D’Ambrosio, N., De Lellis, G., De Rosa, G., Di Capua, F., Ereditato, A., Fiorillo, G., Marotta, A., Messina, M., Migliozzi, P., Pistillo, C., Santorelli, R., Scotto Lavina, L., Strolin, P., Tioukov Universit`a 'Federico II', V., Infn, Naples, Nakamura, Italy K., Okusawa Osaka City University, T., Osaka, Dore, Japan U., Loverre, P. F., Ludovici, L., Maslennikov17, A., Righini, P., Rosa, G., Santacesaria, R., Satta Universit`a La Sapienza, A., Infn, Rome, Barbuto, Italy E., Bozza, C., Grella, G., Romano, G., Sirignano, Chiara, and Sorrentino, S.

Published
2003

49. Deletion of Skeletal Muscle SOCS3 Prevents Insulin Resistance in Obesity

Author

Jorgensen, SB, O'Neill, HM, Sylow, L, Honeyman, J, Hewitt, KA, Palanivel, R, Fullerton, MD, Oberg, L, Balendran, A, Galic, S, van der Poel, C, Trounce, IA, Lynch, GS, Schertzer, JD, Steinberg, GR, Jorgensen, SB, O'Neill, HM, Sylow, L, Honeyman, J, Hewitt, KA, Palanivel, R, Fullerton, MD, Oberg, L, Balendran, A, Galic, S, van der Poel, C, Trounce, IA, Lynch, GS, Schertzer, JD, and Steinberg, GR

Abstract

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance.

Published
2013

50. Hsp72 preserves muscle function and slows progression of severe muscular dystrophy

Author

Gehrig, SM, van der Poel, C, Sayer, TA, Schertzer, JD, Henstridge, DC, Church, JE, Lamon, S, Russell, AP, Davies, KE, Febbraio, MA, Lynch, GS, Gehrig, SM, van der Poel, C, Sayer, TA, Schertzer, JD, Henstridge, DC, Church, JE, Lamon, S, Russell, AP, Davies, KE, Febbraio, MA, and Lynch, GS

Abstract

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies.

Published
2012

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