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1. Nuclear astrophysics with radioactive ions at FAIR

Author

R Reifarth, S Altstadt, K Göbel, T Heftrich, M Heil, A Koloczek, C Langer, R Plag, M Pohl, K Sonnabend, M Weigand, T Adachi, F Aksouh, J Al-Khalili, M AlGarawi, S AlGhamdi, G Alkhazov, N Alkhomashi, H Alvarez-Pol, R Alvarez-Rodriguez, V Andreev, B Andrei, L Atar, T Aumann, V Avdeichikov, C Bacri, S Bagchi, C Barbieri, S Beceiro, C Beck, C Beinrucker, G Belier, D Bemmerer, M Bendel, J Benlliure, G Benzoni, R Berjillos, D Bertini, C Bertulani, S Bishop, N Blasi, T Bloch, Y Blumenfeld, A Bonaccorso, K Boretzky, A Botvina, A Boudard, P Boutachkov, I Boztosun, A Bracco, S Brambilla, J Briz Monago, M Caamano, C Caesar, F Camera, E Casarejos, W Catford, J Cederkall, B Cederwall, M Chartier, A Chatillon, M Cherciu, L Chulkov, P Coleman-Smith, D Cortina-Gil, F Crespi, R Crespo, J Cresswell, M Csatlós, F Déchery, B Davids, T Davinson, V Derya, P Detistov, P Diaz Fernandez, D DiJulio, S Dmitry, D Doré, J Dueñas, E Dupont, P Egelhof, I Egorova, Z Elekes, J Enders, J Endres, S Ershov, O Ershova, B Fernandez-Dominguez, A Fetisov, E Fiori, A Fomichev, M Fonseca, L Fraile, M Freer, J Friese, M G. Borge, D Galaviz Redondo, S Gannon, U Garg, I Gasparic, L Gasques, B Gastineau, H Geissel, R Gernhäuser, T Ghosh, M Gilbert, J Glorius, P Golubev, A Gorshkov, A Gourishetty, L Grigorenko, J Gulyas, M Haiduc, F Hammache, M Harakeh, M Hass, M Heine, A Hennig, A Henriques, R Herzberg, M Holl, A Ignatov, A Ignatyuk, S Ilieva, M Ivanov, N Iwasa, B Jakobsson, H Johansson, B Jonson, P Joshi, A Junghans, B Jurado, G Körner, N Kalantar, R Kanungo, A Kelic-Heil, K Kezzar, E Khan, A Khanzadeev, O Kiselev, M Kogimtzis, D Körper, S Kräckmann, T Kröll, R Krücken, A Krasznahorkay, J Kratz, D Kresan, T Krings, A Krumbholz, S Krupko, R Kulessa, S Kumar, N Kurz, E Kuzmin, M Labiche, K Langanke, I Lazarus, T Le Bleis, C Lederer, A Lemasson, R Lemmon, V Liberati, Y Litvinov, B Löher, J Lopez Herraiz, G Münzenberg, J Machado, E Maev, K Mahata, D Mancusi, J Marganiec, M Martinez Perez, V Marusov, D Mengoni, B Million, V Morcelle, O Moreno, A Movsesyan, E Nacher, M Najafi, T Nakamura, F Naqvi, E Nikolski, T Nilsson, C Nociforo, P Nolan, B Novatsky, G Nyman, A Ornelas, R Palit, S Pandit, V Panin, C Paradela, V Parkar, S Paschalis, P Pawłowski, A Perea, J Pereira, C Petrache, M Petri, S Pickstone, N Pietralla, S Pietri, Y Pivovarov, P Potlog, A Prokofiev, G Rastrepina, T Rauscher, G Ribeiro, M Ricciardi, A Richter, C Rigollet, K Riisager, A Rios, C Ritter, T Rodriguez Frutos, J Rodriguez Vignote, M Röder, C Romig, D Rossi, P Roussel-Chomaz, P Rout, S Roy, P Söderström, M Saha Sarkar, S Sakuta, M Salsac, J Sampson, J Sanchez, del Rio Saez, J Sanchez Rosado, S Sanjari, P Sarriguren, A Sauerwein, D Savran, C Scheidenberger, H Scheit, S Schmidt, C Schmitt, L Schnorrenberger, P Schrock, R Schwengner, D Seddon, B Sherrill, A Shrivastava, S Sidorchuk, J Silva, H Simon, E Simpson, P Singh, D Slobodan, D Sohler, M Spieker, D Stach, E Stan, M Stanoiu, S Stepantsov, P Stevenson, F Strieder, L Stuhl, T Suda, K Sümmerer, B Streicher, J Taieb, M Takechi, I Tanihata, J Taylor, O Tengblad, G Ter-Akopian, S Terashima, P Teubig, R Thies, M Thoennessen, T Thomas, J Thornhill, G Thungstrom, J Timar, Y Togano, U Tomohiro, T Tornyi, J Tostevin, C Townsley, W Trautmann, T Trivedi, S Typel, E Uberseder, J Udias, T Uesaka, L Uvarov, Z Vajta, P Velho, V Vikhrov, M Volknandt, V Volkov, P von Neumann-Cosel, M von Schmid, A Wagner, F Wamers, H Weick, D Wells, L Westerberg, O Wieland, M Wiescher, C Wimmer, K Wimmer, J S Winfield, M Winkel, P Woods, R Wyss, D Yakorev, M Yavor, J Zamora Cardona, I Zartova, T Zerguerras, M Zgura, A Zhdanov, M Zhukov, M Zieblinski, A Zilges, K Zuber, Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Grand Accélérateur National d'Ions Lourds (GANIL), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Helmholtz International Center for FAIR, German Research Foundation, Helmholtz Association, SCOAP, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
History, Astrophysics and Astronomy, FOS: Physical sciences, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], nucl-ex, 01 natural sciences, Education, Nuclear physics, Subatomär fysik, Nucleosynthesis, 0103 physical sciences, Subatomic Physics, Nuclear astrophysics, Fysik, Neutron, Nuclear Physics - Experiment, ddc:530, Nuclear Experiment (nucl-ex), 010306 general physics, Nuclear Experiment, 010303 astronomy & astrophysics, Instrumentation and Methods for Astrophysics (astro-ph.IM), Physics, Radionuclide, Isotope, rp-process, Computer Science Applications, FAIR nuclear astrophysics radioactive ion beams, Valley of stability, r-process nucleosynthesis, weak-interaction rates, s-process, stars, supernovae, light, Physical Sciences, Facility for Antiproton and Ion Research, Física nuclear, Astrophysics - Instrumentation and Methods for Astrophysics, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], astro-ph.IM
Abstract

R. Reifarth et al: ; 12 págs.; 9 figs.; Open Access funded by Creative Commons Atribution Licence 3.0 ; Nuclear Physics in Astrophysics VI (NPA6), The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process ow and r-process -decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will oer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes., This project was supported by the HGF Young Investigators Project VH-NG-327, EMMI, H4F, HGS-HIRe, JINA, NAVI, DFG and ATHENA.

Published
2016
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2. La antibioterapia en monodosis: una opción de mejora en las neumonías adquiridas en la comunidad

Author

Eva Coma, José M. Guardiola, M. Antonia Baraldes, Salvador Benito, Guillermo J. Vázquez, Mercè Gurguí, José Antonio Arroyo, and Francisco R. Alvarez Rodriguez

Subjects
business.industry, Health Policy, Medicine, General Medicine, business, Humanities, Resource utilization
Abstract

Resumen Introduccion El tratamiento de las neumonias adquiridas en la comunidad (NAC) con antibioticos en monoterapia y monodosis (MM) ha demostrado la misma efectividad clinica que las pautas clasicas de antibioterapia fraccionada, a la vez que disminuye la estancia hospitalaria. Esto hace que la MM constituya una opcion de mejora. Objetivo: Comprobar si las caracteristicas del tratamiento de las NAC con MM eran exportables a un hospital diferente de aquellos en los que se habian descrito inicialmente. Material y metodo Estudio de intervencion para la mejora de la calidad, en el periodo de enero a mayo de 1999. Tipo de muestreo: consecutivo. Datos recogidos: edad, sexo, puntuacion APACHE II e indice de Charlson para comorbilidades, tiempo de estancia, mortalidad a 30 dias, reingresos en los 10 dias siguientes del alta hospitalaria, tiempos de enfermeria en preparar y suministrar el tratamiento. En la etapa I se compararon las pautas de MM con levofloxacino o ceftriaxona frente a la pauta clasica de cefotaxima cada 6 h acompanada de un macrolido cada 12 h. En la etapa II se compararon entre si las pautas de MM: levofloxacino frente a ceftriaxona. Durante todo el estudio se aplicaron guias de practica clinica comunes a todos los pacientes con NAC. En la etapa III, segun los resultados obtenidos y a las evidencias bibliograficas, el grupo de expertos selecciono la pauta definitiva. Resultados En la etapa I el tiempo medio ± desviacion estandar (DE) de estancia de las NAC tratadas con MM fue de 151 ± 80,6 h frente a 204 ± 110,4 horas en el tratamiento clasico, siendo la diferencia estadisticamente significativa y clinicamente relevante. No se detectaron diferencias en la mortalidad y reingresos; el tiempo de enfermeria fue de 4 min/paciente/dia en la MM frente a 16 minutos en el tratamiento clasico. En la segunda etapa no se detectaron diferencias entre los dos tipos de MM empleadas, si bien no se alcanzo el tamano adecuado de la muestra. El grupo de expertos selecciono la MM con levofloxacino por permitir un tratamiento secuencial sin cambio de farmaco y porque su biodisponibilidad oral proxima al cien por cien permite iniciar el tratamiento oral rapidamente. Comentario Nuestros resultados ponen de manifiesto que la MM supone una opcion de mejora en nuestro hospital, dado que al disminuir los tiempos de estancia por paciente junto con un ahorro en el tiempo de enfermeria mejora la utilizacion de las camas sin incrementar los riesgos para el paciente.

Published
2002
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3. The electronion scattering experiment ELISe at the International Facility for Antiproton and Ion Research (FAIR) - A conceptual design study

Author

E. Garrido, Igor Meshkov, E. Khan, Pedro Sarriguren, B. Franzke, A. Chatillon, Marielle Chartier, M. Aiche, D. Doré, B. Jurado, Dirk Rudolph, I.A. Koop, S. N. Ershov, M. Fujiwara, Mikhail V. Zhukov, Roy Crawford Lemmon, R. Johnson, S. A. Krupko, D. N. Kadrev, S. Karataglidis, Yurii M. Shatunov, G. Belier, Thomas Nilsson, Oliver Kester, C. Schmitt, C. Fernandez Ramirez, E. Moya de Guerra, Norbert Pietralla, S. Czajkowski, F. Nolden, M. K. Gaidarov, Thomas Rauscher, G. P. A. Berg, E. Berthoumieux, Harald Merkel, D. Ridikas, I. Seleznev, Achim Richter, Andreas Zilges, F. Farget, A. Kelic-Heil, J. A. Caballero, L. V. Chulkov, Tatuya Adachi, V. Lisin, Helmut Weick, H. Lenske, Håkan T Johansson, Kai Hencken, Anton Nikolaev Antonov, K.-H. Schmidt, B. Krusche, A.A. Korsheninnikov, A. M. Rodin, Björn Jonson, Y. Litvinov, A.V. Otboev, P. Beller, Nasser Kalantar-Nayestanaki, U. Müller, Ch. Scheidenberger, L. V. Grigorenko, A. Dolinskii, N. Kurz, D. G. Jenkins, Laurent Tassan-Got, Pavel Golubev, N. V. Rudnev, Thomas Aumann, Andreas Martin Heinz, Seigo Kato, J. Taieb, A.N. Skrinsky, R. Alvarez Rodriguez, W. N. Catford, M. J. G. Borge, A. A. Ogloblin, J. Jourdan, A. V. Gorshkov, G. Münzenberg, Elena Litvinova, A. Letourneau, Takeshi Suda, A. Artukh, B. V. Danilin, G. Schrieder, A.N. Vorontsov, G. M. Ter-Akopian, P.V. Logatchov, D.I. Shvartz, S. Hamieh, K. Boretzky, Sergei Kamerdzhiev, A. N. Mushkarenkov, C. J. Barton, Peter Egelhof, Jim Al-Khalili, H. Emling, Paul Stevenson, Carlos A. Bertulani, Arnd R. Junghans, D. M. Cullen, E. Dupont, Dirk Trautmann, Joachim Enders, M. Steck, J. Udias-Moinelo, L.M. Fraile Prieto, M. O. Distler, Vasilii V. Parkhomchuk, Mohsen Harakeh, Göran Hugo Nyman, M. V. Ivanov, Vladimir Avdeichikov, Stefano Panebianco, Y. Sereda, J.E. Amaro Soriano, S.V. Shiyankov, D. Kiselev, A. S. Fomichev, E. Syresin, Hans Geissel, V. Volkov, L. Audouin, E. A. Kuzmin, Y. Teterev, S. Klygin, A. Polonski, A. A. Turinge, S. I. Sidorchuk, T. Granier, H. J. Wörtche, V. G. Nedorezov, P.Y. Shatunov, J. R. Vignote, J. Lopez Herraiz, A.M. Lallena Rojo, D.N. Shatilov, Haik Simon, Y. Grishkin, G. Barreau, S. V. Stepantsov, M. S. Golovkov, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Grand Accélérateur National d'Ions Lourds (GANIL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), KVI - Center for Advanced Radiation Technology, Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)

Subjects
Nuclear and High Energy Physics, electronscattering, FORM-FACTORS, [PHYS.PHYS.PHYS-ACC-PH]Physics [physics]/Physics [physics]/Accelerator Physics [physics.acc-ph], Electron, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], DATA-ACQUISITION SYSTEM, NUCLEAR-STRUCTURE, 01 natural sciences, BINDING-ENERGIES, CHARGE-DENSITY DISTRIBUTIONS, Ion, CROSS-SECTIONS, Nuclear physics, Nuclei far off stability, Conceptual design, eA collider, 0103 physical sciences, CENTRAL DEPRESSION, Electron scattering, 010306 general physics, Instrumentation, Physics, 010308 nuclear & particles physics, Scattering, 29.27.-a, 25.30.Bf,25.30.Dh,21.10.Ft,29.20.Dh,29.30.-h, RELATIVISTIC HEAVY-IONS, EXOTIC NUCLEI, Facility for Antiproton and Ion Research, GIANT-RESONANCES, Storage ring
Abstract

The electronion scattering experiment ELISe is part of the installations envisaged at the new experimental storage ring at the International Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany. It offers an unique opportunity to use electrons as probe in investigations of the structure of exotic nuclei. The conceptual design and the scientific challenges of ELISe are presented. © 2011 Elsevier B.V. All rights reserved., The authors acknowledge financial support from the EC via the INTAS pro- gramme, grants No. 03-54-6545 and 05-1000008-8272. This work was partially supported by the Hessian LOEWE initiative Helmholtz International Center for FAIR

Published
2011
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5. Unusual Nasal Insufficiency in an Infant: What's Behind the Nostril?

Author

Alzate Amaya F, Invencio da Costa LF, Martinez Moran A, and Alvarez Rodriguez R

Subjects
Diagnosis, Differential, Epistaxis diagnosis, Humans, Infant, Magnetic Resonance Imaging, Male, Neoplasms, Muscle Tissue complications, Neoplasms, Muscle Tissue surgery, Paranasal Sinus Neoplasms complications, Paranasal Sinus Neoplasms surgery, Tomography, X-Ray Computed, Endoscopy methods, Epistaxis etiology, Nasal Cavity pathology, Neoplasms, Muscle Tissue diagnosis, Paranasal Sinus Neoplasms diagnosis, Paranasal Sinuses diagnostic imaging
Abstract

Objectives: Inflammatory myofibroblastic tumor (IMT) is a rare benign lesion, especially in the pediatric age. There are several cases described in pulmonary, digestive and renal localizations, but involvement in head and neck area is infrequent., Methods: Case report and review of the literature., Results: A 1 year and 11 months old child, during 2 months had clinical signs of nasal respiratory insufficiency and epistaxis subsequently developing a purulent rhinorrhea and a sleep apnea. His pediatrician previously requested a sinus and cavum X-ray with the finding of an image compatible with an intranasal mass. Endoscopic resection was performed of the mass with further immunohistochemical analysis showing the result of a lesion compatible with IMT., Conclusions: Even though there are very few cases in scientific literature of a tumor with these characteristics in infants, IMT must be present as a differential diagnosis of intranasal masses. The role of the pathologist is essential to reach the definitive diagnosis and the performance of an early surgical treatment decreases aesthetic consequences in this pathology.

Published
2019
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6. Congenital Malformations of the Central Nervous System in Rural Western Honduras: A 6-Year Report on Trends.

Author

Estevez-Ordonez D, Dewan MC, Feldman MJ, Montalvan-Sanchez EE, Montalvan-Sanchez DM, Rodriguez-Murillo AA, Urrutia-Argueta SA, Cherry CB, Morgan DR, Alvarez-Rodriguez R, and Bonfield CM

Subjects
Anencephaly epidemiology, Child, Child, Preschool, Cost of Illness, Female, Honduras epidemiology, Humans, Infant, Infant, Newborn, Male, Neural Tube Defects epidemiology, Prevalence, Retrospective Studies, Rural Health, Spinal Dysraphism epidemiology, Nervous System Malformations epidemiology
Abstract

Background: Central nervous system (CNS) malformations, including neural tube defects (NTDs), are the second most common type of birth defects worldwide and are major causes of childhood disability and mortality. We report the first analysis of birth prevalence in Western Honduras of CNS malformations including NTDs over 6 consecutive years., Methods: Data from all patients with congenital CNS malformations and total live births for the period 2010-2015 were obtained through institution and regional registries from all 3 public referral hospitals in Western Honduras, representing 67 municipalities. Cases were identified using the International Classification of Diseases, Tenth Revision CNS malformation codes. Birth prevalence was calculated as cases per 10,000 live births., Results: From 123,903 live births, 275 cases of CNS malformations were identified (54% females, 58% NTDs). Six-year birth prevalence of CNS malformations was 13.9-31.1. Spina bifida variants and anencephaly represented 80% and 19% of reported NTDs, respectively. Total 6-year prevalence of NTDs in Western Honduras was 7.0-17.4 over years studied. In 6 municipalities, average prevalence was >30 (maximum 49.0)., Conclusion: This is the first study reporting disease burden of CNS malformations in Western Honduras. The nationwide birth prevalence of NTDs in rural Honduras may have decreased since the implementation of prenatal health policies in 2005. However, we identified regions with unexpectedly elevated prevalence, indicating high regional prevalence that could be targeted for improved preventive efforts, ultimately decreasing the burden of these conditions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Published
2017
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7. Metastatic renal cell carcinoma presenting as shoulder monoarthritis: diagnosis based on synovial fluid cytology and immunocytochemistry.

Author

Placed IG, Alvarez-Rodriguez R, Pombo-Otero J, Vázquez-Bartolomé P, Hermida-Romero T, and Pombo-Felipe F

Subjects
Aged, Diagnosis, Differential, Humans, Male, Pain etiology, Pain pathology, Arthritis diagnosis, Bone Neoplasms secondary, Carcinoma, Renal Cell secondary, Kidney Neoplasms pathology, Shoulder pathology, Synovial Fluid cytology
Published
2010
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8. Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base.

Author

Barzi M, Berenguer J, Menendez A, Alvarez-Rodriguez R, and Pons S

Subjects
A Kinase Anchor Proteins metabolism, Animals, Cell Proliferation, Cells, Cultured, Cerebral Cortex cytology, Cerebral Cortex growth & development, Cilia, Enzyme Activation, Mice, Protein Binding, Protein Transport, Signal Transduction, Stem Cells cytology, Cerebral Cortex metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Hedgehog Proteins metabolism, Protein Subunits metabolism, Stem Cells metabolism
Abstract

Cerebellar granular neuronal precursors (CGNPs) proliferate in response to the mitogenic activity of Sonic hedgehog (Shh), and this proliferation is negatively regulated by activation of cAMP-dependent protein kinase (PKA). In the basal state, the PKA catalytic subunits (C-PKA) are inactive because of their association with the regulatory subunits (R-PKA). As the level of cAMP increases, it binds to R-PKA, displacing and thereby activating the C-PKA. Here we report that, in the presence of Shh, inactive C-PKA accumulates at the cilium base of proliferative CGNPs whereas removal of Shh triggers the activation of PKA at this particular location. Furthermore, we demonstrate that the anchoring of the PKA holoenzyme to the cilium base is mediated by the specific binding of the type II PKA regulatory subunit (RII-PKA) to the A-kinase anchoring proteins (AKAPs). Disruption of the interaction between RII-PKA and AKAPs inhibits Shh activity and, therefore, blocks proliferation of CGNP cultures. Collectively, these results demonstrate that the pool of PKA localized to the cilium base of CGNP plays an essential role in the integration of Shh signal transduction.

Published
2010
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