Search

Your search keyword '"Bica, L"' showing total 29 results
Start Over Author "Bica, L"
29 results on '"Bica, L"'

1. The O/OREOS mission—Astrobiology in low Earth orbit

Author

Ehrenfreund, P., Ricco, A.J., Squires, D., Kitts, C., Agasid, E., Bramall, N., Bryson, K., Chittenden, J., Conley, C., Cook, A., Mancinelli, R., Mattioda, A., Nicholson, W., Quinn, R., Santos, O., Tahu, G., Voytek, M., Beasley, C., Bica, L., Diaz-Aguado, M., Friedericks, C., Henschke, M., Landis, D., Luzzi, E., Ly, D., Mai, N., Minelli, G., McIntyre, M., Neumann, M., Parra, M., Piccini, M., Rasay, R., Ricks, R., Schooley, A., Stackpole, E., Timucin, L., Yost, B., and Young, A.

Published
2014
Full Text
View/download PDF

2. The O/OREOS Mission - Astrobiology in Low Earth Orbit

Author

Ehrenfreund, P, Ricco, A.J, Squires, D, Kitts, C, Agasid, E, Bramall, N, Bryson, K, Chittenden, J, Conley, C, Cook, A, Mancinelli, R, Mattioda, A, Nicholson, W, Quinn, R, Santos, O, Tahu, G, Voytek, M, Beasley, C, Bica, L, Diaz-Aguado, M, Friedericks, C, Henschke, M, Hines, J.W, Landis, D, Luzzi, E, Ly, D, Mai, N, Minelli, G, McIntyre, M, Neumann, M, Parra, M, Piccini, M, Rasay, R, Ricks, R, Schooley, A, Stackpole, E, Timucin, L, Yost, B, and Young, A

Subjects
Life Sciences (General), Space Processing
Abstract

The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small- Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72°), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cu.cm) modules: (i) a control bus, (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment, and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for micro-organisms at 3 times during the 6-month mission. We will report on the spacecraft characteristics, payload capabilities and first operational phase of the O/OREOS mission. The science and technology rationale of O/OREOS supports NASA’s scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities.

Published
2011

3. Contemporary Presentation and Management of Valvular Heart Disease The EURObservational Research Programme Valvular Heart Disease II Survey

Author

Iung, B., Delgado, V., Rosenhek, R., Price, S., Prendergast, B., Wendler, O., Bonis, M. de, Tribouilloy, C., Evangelista, A., Bogachev-Prokophiev, A., Apor, A., Ince, H., Laroche, C., Popescu, B.A., Pierard, L., Haude, M., Hindricks, G., Ruschitzka, F., Windecker, S., Bax, J.J., Maggioni, A., Vahanian, A., Mekhaldi, S., Lemaitre, K., Authier, S., Druais, H., Goda, A., Mascherbauer, J., Samadov, F., Pasquet, A., Linhartova, K., Ihlemann, N., Abdelhamid, M., Saraste, A., Kostovska, E.S., Bajraktari, G., Mirrakhimov, E., Erglis, A., Mizariene, V., Cassar, D., Tomkiewicz-Pajak, L., Ribeiras, R., Popescu, B., Beleslin, B., Simkova, I., Dogan, S.M., Rahman-Haley, S., Shirka, E., Dado, E., Zera, E., Bica, L., Heger, M., Muslumova, F., Jahangirov, T., Ahmedov, T., Husseynov, S., Cosyns, B., Camp, G. van, Sindelarova, S., Branny, M., Parenicova, I., Vondrackova, D.J., Homza, M., Ostransky, J., Hasan-Ali, H., Abdelhady, Y., Hassan, M., Soliman, H., Mostafa, A.E., Moaaz, M., Kazamel, G., Sadek, Y., Eltobgi, S., Kamal, D., Kylmala, M., Turpeinen, A., Monin, J.L., Jobic, Y., Attias, D., Magne, J., Marechaux, S., Donal, E., Biere, L., Bernard, A., Daudin, M., Khounlaboud, M., Habib, G., Bardet, H., Audonnet, M., Thuny, F., Plurien, F., Berenfeld, A., Gervais, R., Sorbets, E., Charbonnier, A., Bauer, F., Menager-Gangloff, C., Gjerakorska-Radovikj, M., Jordanova, S., Caglayan, E., Hambrecht, R., Akin, I., Maier, L., Nickenig, G., Scholtz, W., Schulze, P.C., Heintzen, M., Er, F., Sigusch, H., Spargias, K., Kamperidis, V., Sachpekidis, V., Bellos, V., Kanakakis, I., Papafaklis, M., Makris, A., Poulimenos, L., Katsaros, A., Lampropoulos, K., Bartha, E., Zsary, A., Jebelovszki, E., Cziraki, A., Borsanyi, T., Lupkovics, G., Jarai, Z., Ibrahimi, P., Arapova, R., Laahunova, E., Sime, I., Rancane, G., Radauskaite, G., Raugaliene, R., Xuereb, R.G., Djaberi, R., Komar, M., Szymanski, P., Zaborska, B., Mizia-Stec, K., Regulski, M., Bogacki, P., Sedziwy, E., Komor, K., Myszor, J., Joao, I., Martins, R., Cabral, S., Gago, P., Cardoso, G., Almeida, I., Antunes, N., Carvalho, S., Galrinho, A., Freitas, A., Grigorica, L., Mitre, A., Ionac, A., Tint, D., Popescu, A., Petris, A.O., Onut, R., Pop, C., Usurelu, C., Beyer, R., Militaru, C., Eminovici, G., Arsenescu-Georgescu, C., Irtyuga, O., Semenova, E., Boldyrev, S., Kozmin, D., Gross, Y., Zotov, A., Kuznetsov, D., Nemchenko, E., Kulumbegov, O., Jakubov, R., Stefanov, S., Schneider, Y., Tsechanovich, V., Gamzaev, A., Fomenko, M., Mayorova, O., Skripkina, E., Safina, V., Slastin, Y., Koroleva, T., Polyaeva, L., Tarasenko, I., Alekseeva, S., Magamet, V., Medvedev, I., Khilova, L., Verevetinov, A., Stojsic-Milosavljevic, A., Nikolic, N.M., Ostric, D.K., Ruzicic, D., Pavlovic, S., Milosavljevic, J., Jovovic, L., Margoczy, R., Valocik, G., Studencan, M., Iglesias, F.C., Mendez, I., Gomez, A.G., Sanchez Fernandez, P.L., Valenzuela, G.M., Cladellas, M., Villegas, D.V., Moral, S., Gallego, I.M., Paya, R., Caballero, L., Paton, R.R., Esteban, E., Iglesia-Carreno, C., Alberca, M.T., Valle, A., Molina-Mora, M.J., Castro, N., Sayar, N., Demirtas, A.O., Yesilay, A., Demir, S., Bozkurt, A., Kanar, B., Gudul, N.E., Yildirim, T., Taylan, G., Mert, K.U., Yilmaztepe, M.A., Mert, G.O., Cosansu, K., Sayin, M.R., Karabag, T., EORP VHD II Investigators, Instituto Universitario de Investigacion de Nanocienca de Aragon, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Instituto de Física de Cantabria (IFCA), Universidad de Cantabria [Santander]-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Leibniz Institute for Astrophysics Potsdam (AIP), St. Josef Hospital, Ruhr-University Bochum, Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM), Leiden University Medical Center (LUMC), Universiteit Leiden, Medizinische Universität Wien = Medical University of Vienna, Department of Imaging Royal Brompton Hospital, Royal Brompton Hospital, Guy's and St Thomas' Hospital [London], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Vall d'Hebron University Hospital [Barcelona], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Liège (CHU-Liège), Lukaskrankenhaus, Universität Leipzig, University Heart Centre Freiburg - Bad Krozingen, Research Center [Associazione Nazionale Medici Cardiologi Ospedalieri] (ANMCO Research Center), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Uppsala University, SAFRAN Group, Laboratory of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel (VUB), Université de Lille, Sciences et Technologies, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), CHU Pontchaillou [Rennes], Laboratoire de Protection et Remodelage du Myocarde (PMRM), Université d'Angers (UA)-Université d'Angers (UA), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU de Saint-Brieuc, Hôpital Lapeyronie [Montpellier] (CHU), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Latvia (LU), Dipartimento di Scienza dei Materiali = Department of Materials Science [Milano-Bicocca], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), MDM Laboratory, IMM-CNR, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Réseaux épuration et qualité des eaux (UR REBX), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), King Abdullah University of Science and Technology (KAUST), INSTITUTO NACIONAL DE INVESTIGACAO AGRARIA E VETERINARIA VILA DO CONDE PRT, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Université de Médecine Carol Davila, Emergency Institute for Cardiovascular Diseases 'Prof. Dr. C.C. Iliescu' [Bucharest, Romania], Département Intelligence Ambiante et Systèmes Interactifs (DIASI), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Department of photonics engineering, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Clinical sciences, Cardio-vascular diseases, Cardiology, Universität Leipzig [Leipzig], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Technical University of Denmark [Lyngby] (DTU), Université d'Angers (UA), Iung, Bernard, Delgado, Victoria, Rosenhek, Raphael, Price, Susanna, Prendergast, Bernard, Wendler, Olaf, De Bonis, Michele, Tribouilloy, Christophe, Evangelista, Arturo, Bogachev-Prokophiev, Alexander, Apor, Astrid, Ince, Hüseyin, Laroche, Cécile, Popescu, Bogdan A, Piérard, Luc, Haude, Michael, Hindricks, Gerhard, Ruschitzka, Frank, Windecker, Stephan, Bax, Jeroen J, Maggioni, Aldo, and Vahanian, Alec

Subjects
Male, Time Factors, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, heart valve diseases, valvular surgery, Cardiologists, 0302 clinical medicine, Time-to-Treatment/trends, Referral and Consultation/trends, Heart Valve Diseases/diagnosis, Medicine, echocardiography, 03.02. Klinikai orvostan, 030212 general & internal medicine, Prospective Studies, Practice Patterns, Physicians', 610 Medicine & health, Referral and Consultation, valvular heart disease, Middle Aged, Europe, Practice Guidelines as Topic, cardiovascular system, Healthcare Disparities/trends, transcatheter aortic valve replacement, Female, Guideline Adherence, Presentation (obstetrics), Cardiology and Cardiovascular Medicine, guideline, Cardiologists/trends, medicine.medical_specialty, transcatheter intervention, Clinical Decision-Making, Time-to-Treatment, Europe/epidemiology, 03 medical and health sciences, Physiology (medical), Guideline Adherence/trends, Humans, Healthcare Disparities, Intensive care medicine, Aged, business.industry, medicine.disease, Practice Patterns, Physicians'/trends, Health Care Surveys, business, aged, 80 and over, guidelines as topic
Abstract

Background: Valvular heart disease (VHD) is an important cause of mortality and morbidity and has been subject to important changes in management. The VHD II survey was designed by the EURObservational Research Programme of the European Society of Cardiology to analyze actual management of VHD and to compare practice with guidelines. Methods: Patients with severe native VHD or previous valvular intervention were enrolled prospectively across 28 countries over a 3-month period in 2017. Indications for intervention were considered concordant if the intervention was performed or scheduled in symptomatic patients, corresponding to Class I recommendations specified in the 2012 European Society of Cardiology and in the 2014 American Heart Association/American College of Cardiology VHD guidelines. Results: A total of 7247 patients (4483 hospitalized, 2764 outpatients) were included in 222 centers. Median age was 71 years (interquartile range, 62–80 years); 1917 patients (26.5%) were ≥80 years; and 3416 were female (47.1%). Severe native VHD was present in 5219 patients (72.0%): aortic stenosis in 2152 (41.2% of native VHD), aortic regurgitation in 279 (5.3%), mitral stenosis in 234 (4.5%), mitral regurgitation in 1114 (21.3%; primary in 746 and secondary in 368), multiple left-sided VHD in 1297 (24.9%), and right-sided VHD in 143 (2.7%). Two thousand twenty-eight patients (28.0%) had undergone previous valvular intervention. Intervention was performed in 37.0% and scheduled in 26.8% of patients with native VHD. The decision for intervention was concordant with Class I recommendations in symptomatic patients with severe single left-sided native VHD in 79.4% (95% CI, 77.1–81.6) for aortic stenosis, 77.6% (95% CI, 69.9–84.0) for aortic regurgitation, 68.5% (95% CI, 60.8–75.4) for mitral stenosis, and 71.0% (95% CI, 66.4–75.3) for primary mitral regurgitation. Valvular interventions were performed in 2150 patients during the survey; of them, 47.8% of patients with single left-sided native VHD were in New York Heart Association class III or IV. Transcatheter procedures were performed in 38.7% of patients with aortic stenosis and 16.7% of those with mitral regurgitation. Conclusions: Despite good concordance between Class I recommendations and practice in patients with aortic VHD, the suboptimal number in mitral VHD and late referral for valvular interventions suggest the need to improve further guideline implementation.

Published
2019
Full Text
View/download PDF

4. Deregulation of subcellular biometal homeostasis through loss of the metal transporter, Zip7, in a childhood neurodegenerative disorder

Author

Grubman, A, Lidgerwood, GE, Duncan, C, Bica, L, Tan, J-L, Parker, SJ, Caragounis, A, Meyerowitz, J, Volitakis, I, Moujalled, D, Liddell, JR, Hickey, JL, Horne, M, Longmuir, S, Koistinaho, J, Donnelly, PS, Crouch, PJ, Tammen, I, White, AR, Kanninen, KM, Grubman, A, Lidgerwood, GE, Duncan, C, Bica, L, Tan, J-L, Parker, SJ, Caragounis, A, Meyerowitz, J, Volitakis, I, Moujalled, D, Liddell, JR, Hickey, JL, Horne, M, Longmuir, S, Koistinaho, J, Donnelly, PS, Crouch, PJ, Tammen, I, White, AR, and Kanninen, KM

Abstract

BACKGROUND: Aberrant biometal metabolism is a key feature of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Metal modulating compounds are promising therapeutics for neurodegeneration, but their mechanism of action remains poorly understood. Neuronal ceroid lipofuscinoses (NCLs), caused by mutations in CLN genes, are fatal childhood neurodegenerative lysosomal storage diseases without a cure. We previously showed biometal accumulation in ovine and murine models of the CLN6 variant NCL, but the mechanism is unknown. This study extended the concept that alteration of biometal functions is involved in pathology in these disorders, and investigated molecular mechanisms underlying impaired biometal trafficking in CLN6 disease. RESULTS: We observed significant region-specific biometal accumulation and deregulation of metal trafficking pathways prior to disease onset in CLN6 affected sheep. Substantial progressive loss of the ER/Golgi-resident Zn transporter, Zip7, which colocalized with the disease-associated protein, CLN6, may contribute to the subcellular deregulation of biometal homeostasis in NCLs. Importantly, the metal-complex, ZnII(atsm), induced Zip7 upregulation, promoted Zn redistribution and restored Zn-dependent functions in primary mouse Cln6 deficient neurons and astrocytes. CONCLUSIONS: This study demonstrates the central role of the metal transporter, Zip7, in the aberrant biometal metabolism of CLN6 variants of NCL and further highlights the key contribution of deregulated biometal trafficking to the pathology of neurodegenerative diseases. Importantly, our results suggest that ZnII(atsm) may be a candidate for therapeutic trials for NCLs.

Published
2014

5. Neuroprotective Copper Bis(thiosemicarbazonato) Complexes Promote Neurite Elongation

Author

Ginsberg, SD, Bica, L, Liddell, JR, Donnelly, PS, Duncan, C, Caragounis, A, Volitakis, I, Paterson, BM, Cappai, R, Grubman, A, Camakaris, J, Crouch, PJ, White, AR, Ginsberg, SD, Bica, L, Liddell, JR, Donnelly, PS, Duncan, C, Caragounis, A, Volitakis, I, Paterson, BM, Cappai, R, Grubman, A, Camakaris, J, Crouch, PJ, and White, AR

Abstract

Abnormal biometal homeostasis is a central feature of many neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and motor neuron disease. Recent studies have shown that metal complexing compounds behaving as ionophores such as clioquinol and PBT2 have robust therapeutic activity in animal models of neurodegenerative disease; however, the mechanism of neuroprotective action remains unclear. These neuroprotective or neurogenerative processes may be related to the delivery or redistribution of biometals, such as copper and zinc, by metal ionophores. To investigate this further, we examined the effect of the bis(thiosemicarbazonato)-copper complex, Cu(II)(gtsm) on neuritogenesis and neurite elongation (neurogenerative outcomes) in PC12 neuronal-related cultures. We found that Cu(II)(gtsm) induced robust neurite elongation in PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous effects were observed with an alternative copper bis(thiosemicarbazonato) complex, Cu(II)(atsm), but at a higher concentration. Induction of neurite elongation by Cu(II)(gtsm) was restricted to neurites within the length range of 75-99 µm with a 2.3-fold increase in numbers of neurites in this length range with 50 nM Cu(II)(gtsm) treatment. The mechanism of neurogenerative action was investigated and revealed that Cu(II)(gtsm) inhibited cellular phosphatase activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase inhibitor) resulted in analogous elongation of neurites compared to 50 nM Cu(II)(gtsm), suggesting a potential link between Cu(II)(gtsm)-mediated phosphatase inhibition and neurogenerative outcomes.

Published
2014

6. Diacetylbis(N(4)-methylthiosemicarbazonato) Copper(II) (CuII(atsm)) Protects against Peroxynitrite-induced Nitrosative Damage and Prolongs Survival in Amyotrophic Lateral Sclerosis Mouse Model

Author

Soon, CPW, Donnelly, PS, Turner, BJ, Hung, LW, Crouch, PJ, Sherratt, NA, Tan, J-L, Lim, NK-H, Lam, L, Bica, L, Lim, S, Hickey, JL, Morizzi, J, Powell, A, Finkelstein, DI, Culvenor, JG, Masters, CL, Duce, J, White, AR, Barnham, KJ, Li, Q-X, Soon, CPW, Donnelly, PS, Turner, BJ, Hung, LW, Crouch, PJ, Sherratt, NA, Tan, J-L, Lim, NK-H, Lam, L, Bica, L, Lim, S, Hickey, JL, Morizzi, J, Powell, A, Finkelstein, DI, Culvenor, JG, Masters, CL, Duce, J, White, AR, Barnham, KJ, and Li, Q-X

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which is an orally bioavailable, blood-brain barrier-permeable complex. In vitro the compound inhibits the action of peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) and subsequent nitration of cellular proteins. Oral treatment of transgenic SOD1G93A mice with CuII(atsm) at presymptomatic and symptomatic ages was performed. The mice were examined for improvement in lifespan and motor function, as well as histological and biochemical changes to key disease markers. Systemic treatment of SOD1G93A mice significantly delayed onset of paralysis and prolonged lifespan, even when administered to symptomatic animals. Consistent with the properties of this compound, treated mice had reduced protein nitration and carbonylation, as well as increased antioxidant activity in spinal cord. Treatment also significantly preserved motor neurons and attenuated astrocyte and microglial activation in mice. Furthermore, CuII(atsm) prevented the accumulation of abnormally phosphorylated and fragmented TAR DNA-binding protein-43 (TDP-43) in spinal cord, a protein pivotal to the development of ALS. CuII(atsm) therefore represents a potential new class of neuroprotective agents targeting multiple major disease pathways of motor neurons with therapeutic potential for ALS.

Published
2011

7. AUTONOMOUS MICROSYSTEMS FOR ASTROBIOLOGY: DEVELOPMENT OF, AND SPACEFLIGHT RESULTS FROM, THE O/OREOS NANOSATELLITE

Author

Ricco, A.J., primary, Ehrenfreund, P., additional, Squires, D., additional, Piccini, M., additional, Beasley, C., additional, Bramall, N., additional, Minelli, G., additional, Agasid, E., additional, Bryson, K., additional, Cook, A., additional, Diaz-Aguado, M., additional, Bica, L., additional, Chittenden, J., additional, Friedericks, C., additional, Henschke, M., additional, Hines, J.W., additional, Kitts, C., additional, Landis, D., additional, Luzzi, E., additional, Ly, D., additional, Mai, N., additional, Mancinelli, R., additional, Mattioda, A., additional, McIntyre, M., additional, Neumann, M., additional, Nicholson, W., additional, Parra, M., additional, Quinn, R., additional, Rasay, R., additional, Ricks, R., additional, Santos, O., additional, Schooley, A., additional, Stackpole, E., additional, Timucin, L., additional, Yost, B., additional, and Young, A., additional

Published
2012
Full Text
View/download PDF

9. Cohort profile. the ESC-EORP chronic ischemic cardiovascular disease long-term (CICD LT) registry

Author

Komajda, Michel, Cosentino, Francesco, Ferrari, Roberto, Laroche, Cécile, Maggioni, Aldo, Steg, Philippe Gabriel, Tavazzi, Luigi, Kerneis, Mathieu, Valgimigli, Marco, Gale, Chris, P, Chris, P Gale, Branko, Beleslin, Andrzej, Budaj, Ovidiu, Chioncel, Nikolaos, Dagres, Nicolas, Danchin, Jonathan, Emberson, David, Erlinge, Michael, Glikson, Alastair, Gray, Meral, Kayikcioglu, Aldo, P Maggioni, Vivien Klaudia Nagy, Aleksandr, Nedoshivin, Anna-Sonia, Petronio, Jolien, Roos-Hesselink, Lars, Wallentin, Uwe, Zeymer, Michel, Komajda, Francesco, Cosentino, Roberto, Ferrari, Gabriel, Steg, Luigi, Tavazzi, Marco, Valgimigli, Gani, Bajraktari, Pedro, Braga, Vakhtang, Chumburidze, Ana Djordjevic Dikic, Adel El Etriby, Fedele, Francesco, Jean Louis Georges, Artan, Goda, Mathieu, Kerneis, Robert, Klempfner, Peep, Laanmets, Abdallah, Mahdhaoui, Iveta, Mintale, Erkin, Mirrakhimov, Zoran, Olivari, Arman, Postadjian, Harald, Rittger, Luis, Rodriguez-Padial, David, Rott, Carlos, Serrano, Evgeny, Shlyakhto, Rimvydas, Slapikas, Maksym, Sokolov, Volha, Sujayeva, Konstantinos, Tsioufis, Dragos, Vinereanu, Parounak, Zelveian, Tase, M, Koci, J, Kuka, S, Nelaj, E, Goda, A, Simoni, L, Beka, V, Dragoti, J, Karanxha, J, Refatllari, I, Shehu, B, Bileri, A, Luzati, M, Shuperka, E, Gace, A, Shirka, E, Knuti, G, Dado, E, Dibra, L, Gjana, A, Kristo, A, Bica, L, Kabili, S, Pjeci, R, Siqeca, M, Hazarapetyan, L, Drambyan, M, Asatrya, K, Nersesyan, S, Ter-Margaryan, A, Zelveian, P, Gharibyan, H, Hakobyan, Z, Sujayeva, V, Koshlataya, O, Rozumovitch, A, Bychkovskaya, E, Lavrenova, T, Tkacheva, L, Dmitrieva, I, Serrano, C, A Cuoco, M, Favarato, D, Garzillo, C, Goes, M, Lima, E, Pitta, F, Rached, F, Segre, C, Ayres, S, Torres, M, S Hussein, M, Ragy, H, Essam, S, Fadala, H, Hassan, A, Zaghloul, S, Zarif, B, A-E, Elbakery, Nabil, M, W Mohammed Mounir, Radwan, F, Elmenyawy, E, Nafee, W, Sabri, M, A Magdy Moustafa, Helal, A, E Mohamed Abdelrahim, A M, A Elseaidy, Yousef, A, Albert, F, Dasoveanu, M, Demicheli, T, Dutoiu, T, Gorka, H, Laure, C, Range, G, Thuaire, C, Lattuca, B, Cayla, G, Delelo, E, Jouve, B, Khachab, H, Rahal, Y, Lacrimini, M, Chayeb, S, Baron, N, Chavelas, C, Cherif, G, Nay, L, Nistor, M, Vienet-Legue, A, J-B, Azowa, Noichri, Y, Kerneis, M, E Van Belle, Cosenza, A, Delhaye, C, Vincent, F, Gaul, A, Pin, G, Valy, Y, Trouillet, C, Laurencon, V, Couppie, P, J-M, Daessle, F De Poli, Goioran, F, Delarche, N, Livarek, B, L Georges, J, M Ben Aziza, Blicq, E, Charbonnel, C, Convers, R, Gibault-Genty, G, Schiele, F, L Perruche, M, Cador, R, B Lesage, J, J Aroulanda, M, Belle, L, Madiot, H, Chumburidze, V, Kikalishvili, T, Kharchilava, N, Todua, T, Melia, A, Gogoberidze, D, Katsiashvili, T, Lominadze, Z, Chubinidze, T, Brachmann, J, Schnupp, S, Linss, A, Truthan, K, M-A, Ohlow, Rosenthal, A, Ungethüm, K, Rieber, J, Deichstetter, M, Hitzke, E, Rump, S, Tonch, R, Achenbach, S, Gerlach, A, Schlundt, C, Fechner, S, Ücker, C, D Garlichs, C, Petersen, I, Thieme, M, Greiner, R, Kessler, A, Rädlein, M, Edelmann, S, Hofrichter, J, Kirchner-Rückert, V, Klug, A, Papsdorf, E, Waibl, P, Rittger, H, Karg, M, Kuhls, B, Kuhls, S, Eichinger, G, Pohle, K, Paleczny, S, Tsioufis, K, Galanakos, S, Georgiopoulos, G, Panagiotis, T, Peskesis, G, Pylarinou, V, Kanakakis, I, Stamatelopoulos, K, Tourikis, P, Tsoumani, Z, Alexopoulos, D, Bei, I, Davlouros, P, Xanthopoulou, I, Trikas, A, Grigoriou, K, Thomopoulos, T, Foussas, S, Vassaki, M, Athanasiou, K, Dimopoulos, A, Papakonstantinou, N, Patsourakos, N, Ionia, N, Patsilinakos, S, Kintis, K, Tziakas, D, Chalikias, G, Kikas, P, Lantzouraki, A, Karvounis, H, Didagelos, M, Ziakas, A, Sarrafzadegan, N, Khosravi, A, Kermani-Alghoraishi, M, Cinque, A, Fedele, F, Mancone, M, Manzo, D, L De Luca, Figliozzi, S, Tarantini, G, Fraccaro, C, Sinagra, G, Perkan, A, Priolo, L, Ramani, F, Ferrari, R, Campo, G, Biscaglia, S, Cortesi, S, Gallo, F, Pecoraro, A, Spitaleri, G, Tebaldi, M, Tumscitz, C, Lodolini, V, Mosele, E, Indolfi, C, Ambrosio, G, S De Rosa, Canino, G, Critelli, C, Calzolari, D, Zaina, C, F Grisolia, E, Ammendolea, C, Russo, P, Gulizia, M, Bonmassari, R, Battaia, E, Moretti, M, Bajraktari, G, Ibrahimi, P, Ibërhysaj, F, Tishukaj, A, Berisha, G, Percuku, L, Mirrakhimov, E, Kerimkulova, A, Bektasheva, E, Neronova, K, Kaneps, P, Libins, A, Sorokins, N, Stirna, V, Rancane, G, Putne, S, Ivanova, L, Mintale, I, Roze, R, Kalnins, A, Strelnieks, A, Vasiljevs, D, Slapikas, R, Babarskiene, R, Viezelis, M, Brazaitis, G, Orda, P, Petrauskaite, J, Kovaite, E, A Rimkiene, M, Skiauteryte, M, Janion, M, Raszka, D, Szwed, H, Dąbrowski, R, Korczyńska, A, Mączyńska, J, Jaroch, J, Ołpińska, B, Sołtowska, A, Wysokiński, A, Kania, A, Sałacki, A, Zapolski, T, Krzesinski, P, Skrobowski, A, Buczek, K, Golebiewska, K, Kolaszyńska-Tutka, K, Piotrowicz, K, Stanczyk, A, Sobolewski, P, Przybylski, A, Harpula, P, Kurianowicz, R, Wojcik, M, Czarnecka, D, Jankowski, P, Drożdż, T, Pęksa, J, Mendes, M, Brito, J, Freitas, P, V Gama Ribeiro, Braga, P, G Ribeiro, V, Melica, B, G Pires de Morais, Rodrigues, A, Santos, L, Almeida, C, L Pop-Moldovan, A, Darabantiu, D, Lala, R, Mercea, S, Sirbovan, I, Pop, D, Zdrenghea, D, Caloian, B, Comșa, H, Fringu, F, Gurzau, D, Iliesiu, A, Ciobanu, A, Nicolae, C, Parvu, I, Vinereanu, D, A Udroiu, C, G Cotoban, A, Pop, C, Dicu, D, Kozma, G, Matei, C, Mercea, D, Tarusi, M, Burca, M, Bengus, C, Ochean, V, Petrescu, L, Alina-Ramona, N, Crisan, S, Dan, R, Matei, O, Buzas, R, Ciobotaru, G, O Petris, A, I Costache, I, Mitu, O, Tudorancea, I, R Parepa, I, Cojocaru, L, Ionescu, M, Mazilu, L, Rusali, A, I Suceveanu, A, C-J, Sinescu, Axente, L, Dimitriu, I, Samoila, N, Mot, S, Cocoi, M, Iuga, H, Dorobantu, M, Calmac, L, Bataila, V, Cosmin, M, Dragoescu, B, Marinescu, M, Tase, A, Usurelu, C, Dondoi, R, C Tudorica, C, A-M, Vintilă, Ciomag, R, Gurghean, A, Ianula, R, Isacoff, D, Savulescu-Fiedler, I, Spataru, D, V Spătaru, D, Horumbă, M, Mihalcea, R, C-I, Balogh, Bakcsi, F, O-B, Szakacs, Iancu, A, Doroltan, P, Dregoesc, I, Marc, M, Niculina, S, Chernova, A, Kuskaeva, A, Novikova, D, Kirillova, I, Markelova, E, Udachkina, E, Khaisheva, L, Razumovskiy, I, Zakovryashina, I, Chumakova, G, Gritzenko, O, Lomteva, E, Shtyrova, T, Vasileva, L, Gosteva, E, Malukov, D, Pyshnograeva, L, Nedbaykin, A, Iusova, I, Gadgiev, R, Grechova, L, Kazakovtseva, M, Maksimchuk-Kolobova, N, Semenova, Y, Rusina, A, Govorin, A, Mukha, N, Radaeva, E, Vasilenko, P, Zhanataeva, L, Kosmachova, E, Tatarintseva, Z, Tripolskaya, N, Borovkova, N, Tokareva, A, Semenova, A, Spiropulos, N, Ginter, Y, Kovalenko, F, Brodskaia, T, A Nevzorova, V, Golovkin, N, Golofeevskii, S, Shcheglova, E, Aleinik, O, Glushchenko, N, Podbolotova, A, Petrova, M, Harkov, E, Lobanova, A, Tsybulskaya, N, Iakushin, S, Kuzmin, D, Pereverzeva, K, Shevchenko, I, Elistratova, O, Fetisova, E, Galyavich, A, Galeeva, Z, Chepisova, M, Eseva, S, Panov, A, Lokhovinina, N, Boytsov, S, Drapkina, O, Shepel, R, Vasilyev, D, Yavelov, I, Kochergina, A, Sedykh, D, Tavlueva, E, Duplyakov, D, Antimonova, M, Kocharova, K, Libis, R, Lopina, E, Osipova, L, Bukatov, V, Kletkina, A, Plaksin, K, Suyazova, S, Nedogoda, S, Chumachek, E, Ledyaeva, A, Totushev, M, Asadulaeva, G, Tarlovskaya, E, Kozlova, N, V Mazalov, K, Valiculova, F, Merezhanova, A, Efremova, E, Menzorov, M, Shutov, A, Garganeeva, A, Aleksandrenko, V, Kuzheleva, E, Tukish, O, Ryabov, V, Belokopytova, N, Lipnyagova, D, Simakin, N, Ivanov, K, Levashov, S, Karaulovskaya, N, Stepanovic, J, Beleslin, B, Djordjevic-Dikic, A, Giga, V, Boskovic, N, Nedeljkovic, I, Dzelebdzic, S, Arsic, S, Jovanovic, S, Katic, J, Milak, J, Pletikosic, I, Rastovic, M, Vukelic, M, Lazar, Z, J Lukic Petrov, Stankov, S, Djokic, D, Kulic, N, Stojiljkovic, G, Stojkovic, G, Stojsic-Milosavljevic, A, Ilic, A, D Ilic, M, Petrovic, D, A Martínez Cámara, L Rodriguez Padial, P Sánchez-Aguilera Sánchez-Paulete, M Iniesta Manjavacas, A, J Irazusta, F, Merás, P, Rial, V, Cejudo, L, J Fernandez Anguita, M, V Martinez Mateo, Gonzalez-Juanatey, C, S de Dios, Martí, D, C Suarez, R, D Garcia Fuertes, D, Pavlovic, D, Mazuelos, F, J Suárez de Lezo, Marin, F, M Rivera Caravaca, J, A Veliz Martínez, Zhurba, S, Mikitchuk, V, Sokolov, M, and Levchuk, N

Subjects
chronic coronary disease, clinical outcomes, demographics, medications, registry

11. Conversazione con Bolivar

Author

COSTANZO, Cristina, Bica, L, and Costanzo, C

Subjects
Settore L-ART/03 - Storia Dell'Arte Contemporanea, Movimento MADI Inernazionale
Abstract

Il contributo in catalogo consistente nell'intervista all'artista Bolivar, uno dei testimoni più accreditati del Movimento Madi Internazionale, fornisce un inedito approfondimento scientifico sulla storia e sulla critica che ha caratterizzato il Movimento Internazionale Madi dal 1946 ad oggi.

Published
2012

12. Botticelli di A Venturi. N.6 della Collana di studi'Scrigni D'Arte', a cura di Laura Bica

Author

BICA, Laura and BICA, L

Subjects
Botticelli, Arte, Settore L-ART/02 - Storia Dell'Arte Moderna
Abstract

La personalità artistica di Sandro Botticelli viene qui messa in evidenza grazie alla rilettura critica del saggio di Adolfo Venturi, esaminato nelle sue componenti storiche e filosofico-scientifiche insieme. Il profilo dell’artista ed “eccellentissimo pittore”,come lo definisce Vasari, si delinea in tutta la sua originale creatività a partire dalla produzione giovanile fino alle ultime opere certe attribuite. Il volume è corredato da ampio repertorio iconografico che facilita e completa il percoso di lettura e di acquisizione storico-scientifica.

Published
2012

15. Laura Bica (a cura di), Lionello Venturi. La critica e l'arte di Leonardo Da Vinci, n. 5 della collana 'Scrigni d'Arte', a cura di Laura Bica

Author

BICA, Laura and BICA, L

Subjects
Critica, Arte, Leonardo Da Vinci, Settore L-ART/02 - Storia Dell'Arte Moderna
Abstract

La personalità artistica di Leonardo Da Vinci viene anallizzata attraverso la lettura critico-filologica del saggio di Lionello Venturi, storico e critico d'arte fra i più noti in Italia per avere per primo proposto un nuovo metodo di indagine artistica, ben lontano dall'interpretazione vasariana. Il saggio è corredato da repertorio iconografico.

Published
2010

17. A. Venturi, Antonello da Messina

Author

BICA, Laura and BICA L

Abstract

N. 2 della Collana "Scrigni d'Arte" a cura di Laura Bica. Nella Collana "Scrigni d'arte" vengono selezionati veri e propri gioielli di rilevante interesse scientifico e culturale, riletti e rieditati con una introduzione critico-filologica e scientifica insieme. La personalità dell'artista viene così rivisitata ed alla luce delle nuove acquisizioni e delle moderne interpretazioni si avanzano originali proposte di lettura, che costituiscono nel loro insieme il contenuto prezioso della collana stessa. Con brevi ma incisivi tratti viene qui delineata la figura di Antonello da Messina, grande personalità artistica della Storia dell'Arte in Sicilia e in Europa. Il breve saggio di Adolfo Venturi, qui sinteticamente analizzato, segna una svolta nella interpretazione critica del pittore sia per la puntualità delle osservazioni storico artistiche sia per la peculiarità della scrittura, cronologicamente datata ma letterariamente avvincente.

Published
2006

18. Storia dell'Arte nell'Europa del Mediterraneo. Sicilia

Author

BICA, Laura and BICA L

Abstract

Nel complesso quadro artistico europeo si pone in evidenza la presenza dell'arte italiana, quale originale protagonista di eventi e fatti condizionanti lo svolgersi e l'evolversi della storia. Attraverso l'analisi di singole personalità della pittura, da Giotto a Morandi, da Botticelli a De Chirico, da Raffaello a Balla, viene delineato il carattere unitario, ma stilisticamente diversificato, delle varie espressioni artistiche in Italia. Ne risulta il taglio innovativo del volume, che si presenta in una originale veste grafica e si avvale di un ampio repertorio iconografico.

Published
2006

20. A rare and challenging case of intrapericardial hydatidosis.

Author

Caushi F, Hysa E, Skenduli I, Lisha L, Hatibi A, Bica L, Bala S, and Rulli F

Subjects
Male, Humans, Young Adult, Adult, Pericardium pathology, Pulmonary Infarction complications, Echinococcosis diagnosis, Echinococcosis surgery, Echinococcosis pathology, Mediastinal Cyst surgery, Pleural Effusion
Abstract

Background: Hydatid cysts are most frequently located in the liver and lungs and very rarely can be found in the pericardium. Diagnosis and treatment are quite challenging, as the disease can present itself in many forms depending to the location and the complications that it might cause., Case Presentation: A 22-year-old man presented to our hospital with ongoing dry cough for more than 1 month prior to admission. Other symptoms included chest pain, fatigue, low grade fever, and night sweats, which have worsened in the past 2 weeks. Physical examination revealed normal respiratory and heart function. Chest X-ray demonstrated mediastinal enlargement and left pleural effusion. Contrast-enhanced computed tomography images showed a walled cystic mass lesion measuring up to 56 × 50 mm in close proximity to the upper left atrium, ascending aorta and pulmonary artery, potentially localized in the pericardium, with a 10 mm endoatrial filling defect, findings were compatible with hydatid cyst, left pleural effusion and peripheral pulmonary upper left lobe consolidation. Cardiac involvement was excluded on magnetic resonance imaging and trans-esophageal ultrasound. The patient underwent fine needle aspiration of the affected lung and thoracocentesis. No malignancy was found, meanwhile the biopsy confirmed the presence of pulmonary infarction. In view of the imaging findings were highly suspicious of a hydatid cyst, we performed a test of antibody titers that was negative. The patient underwent left anterolateral thoracotomy, and after the opening of the pericardium, a cystic mass of 5 cm in diameter was found next to the left atrium and in close proximity with the left pulmonary veins. The content of the cyst was completely removed after the surgical area was isolated with gauze impregnated with hypertonic solution (NaCl 10%). The mass resulted to be an echinococcal cyst with multiple daughter cysts within it that did not penetrate/involve (perforate) the cardiac wall., Conclusion: Pericardial echinococcosis is a very rare pathology in which a high expertise multidisciplinary approach is required. The compression mass effect caused by the cyst can lead to complications, such as in our case where the pulmonary vein was compressed, leading to pulmonary infarction. The value of radiology studies and transoesophageal ultrasound are very important in the diagnosis. Surgery in these cases is always recommended, but preferred surgical approach is questionable. In cases such as ours, we recommend anterolateral thoracotomy., (© 2023. The Author(s).)

Published
2023
Full Text
View/download PDF

21. Neuroprotective copper bis(thiosemicarbazonato) complexes promote neurite elongation.

Author

Bica L, Liddell JR, Donnelly PS, Duncan C, Caragounis A, Volitakis I, Paterson BM, Cappai R, Grubman A, Camakaris J, Crouch PJ, and White AR

Subjects
Animals, Calcineurin metabolism, Calcineurin Inhibitors, Coordination Complexes chemical synthesis, Copper metabolism, Enzyme Inhibitors pharmacology, Neurites enzymology, Neurites ultrastructure, Neuroprotective Agents chemical synthesis, PC12 Cells, Rats, Tacrolimus pharmacology, Zinc metabolism, Coordination Complexes pharmacology, Copper chemistry, Neurites drug effects, Neuroprotective Agents pharmacology, Thiosemicarbazones chemistry
Abstract

Abnormal biometal homeostasis is a central feature of many neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and motor neuron disease. Recent studies have shown that metal complexing compounds behaving as ionophores such as clioquinol and PBT2 have robust therapeutic activity in animal models of neurodegenerative disease; however, the mechanism of neuroprotective action remains unclear. These neuroprotective or neurogenerative processes may be related to the delivery or redistribution of biometals, such as copper and zinc, by metal ionophores. To investigate this further, we examined the effect of the bis(thiosemicarbazonato)-copper complex, Cu(II)(gtsm) on neuritogenesis and neurite elongation (neurogenerative outcomes) in PC12 neuronal-related cultures. We found that Cu(II)(gtsm) induced robust neurite elongation in PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous effects were observed with an alternative copper bis(thiosemicarbazonato) complex, Cu(II)(atsm), but at a higher concentration. Induction of neurite elongation by Cu(II)(gtsm) was restricted to neurites within the length range of 75-99 µm with a 2.3-fold increase in numbers of neurites in this length range with 50 nM Cu(II)(gtsm) treatment. The mechanism of neurogenerative action was investigated and revealed that Cu(II)(gtsm) inhibited cellular phosphatase activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase inhibitor) resulted in analogous elongation of neurites compared to 50 nM Cu(II)(gtsm), suggesting a potential link between Cu(II)(gtsm)-mediated phosphatase inhibition and neurogenerative outcomes.

Published
2014
Full Text
View/download PDF

22. Deregulation of subcellular biometal homeostasis through loss of the metal transporter, Zip7, in a childhood neurodegenerative disorder.

Author

Grubman A, Lidgerwood GE, Duncan C, Bica L, Tan JL, Parker SJ, Caragounis A, Meyerowitz J, Volitakis I, Moujalled D, Liddell JR, Hickey JL, Horne M, Longmuir S, Koistinaho J, Donnelly PS, Crouch PJ, Tammen I, White AR, and Kanninen KM

Subjects
Age Factors, Alkaline Phosphatase metabolism, Animals, Astrocytes enzymology, Cation Transport Proteins genetics, Cells, Cultured, Dipeptides pharmacology, Disease Models, Animal, Embryo, Mammalian, Homeostasis genetics, Humans, Membrane Proteins genetics, Mice, Mice, Transgenic, Mutation genetics, Neurodegenerative Diseases genetics, Sheep, Tropomyosin pharmacology, Up-Regulation drug effects, Zinc pharmacology, Biological Transport genetics, Cation Transport Proteins deficiency, Metals metabolism, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Up-Regulation genetics
Abstract

Background: Aberrant biometal metabolism is a key feature of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Metal modulating compounds are promising therapeutics for neurodegeneration, but their mechanism of action remains poorly understood. Neuronal ceroid lipofuscinoses (NCLs), caused by mutations in CLN genes, are fatal childhood neurodegenerative lysosomal storage diseases without a cure. We previously showed biometal accumulation in ovine and murine models of the CLN6 variant NCL, but the mechanism is unknown. This study extended the concept that alteration of biometal functions is involved in pathology in these disorders, and investigated molecular mechanisms underlying impaired biometal trafficking in CLN6 disease., Results: We observed significant region-specific biometal accumulation and deregulation of metal trafficking pathways prior to disease onset in CLN6 affected sheep. Substantial progressive loss of the ER/Golgi-resident Zn transporter, Zip7, which colocalized with the disease-associated protein, CLN6, may contribute to the subcellular deregulation of biometal homeostasis in NCLs. Importantly, the metal-complex, ZnII(atsm), induced Zip7 upregulation, promoted Zn redistribution and restored Zn-dependent functions in primary mouse Cln6 deficient neurons and astrocytes., Conclusions: This study demonstrates the central role of the metal transporter, Zip7, in the aberrant biometal metabolism of CLN6 variants of NCL and further highlights the key contribution of deregulated biometal trafficking to the pathology of neurodegenerative diseases. Importantly, our results suggest that ZnII(atsm) may be a candidate for therapeutic trials for NCLs.

Published
2014
Full Text
View/download PDF

23. Copper modulates the large dense core vesicle secretory pathway in PC12 cells.

Author

Duncan C, Bica L, Crouch PJ, Caragounis A, Lidgerwood GE, Parker SJ, Meyerowitz J, Volitakis I, Liddell JR, Raghupathi R, Paterson BM, Duffield MD, Cappai R, Donnelly PS, Grubman A, Camakaris J, Keating DJ, and White AR

Subjects
Animals, Biological Transport drug effects, Copper metabolism, PC12 Cells, Rats, Copper pharmacology, Secretory Pathway drug effects, Secretory Vesicles drug effects, Secretory Vesicles metabolism
Abstract

Copper (Cu) is an essential biometal involved in a number of cell functions. Abnormal Cu homeostasis has been identified as a major factor in a number of neurodegenerative disorders. However, little is known about how cells of brain origin maintain Cu homeostasis and in particular, how they respond to an elevated Cu environment. Understanding these processes is essential to obtaining a greater insight into the pathological changes in neurodegeneration and ageing. Although previous studies have shown that Cu in neurons can be associated with synaptic function, there is little understanding of how Cu modulates the regulated secretory vesicle pathways in these cells. In this study, we examined the effect of elevated intracellular Cu on proteins associated with the regulated secretory vesicle pathway in NGF-differentiated PC12 cells that exhibit neuronal-like properties. Increasing intracellular Cu with a cell-permeable Cu-complex (Cu(II)(gtsm)) resulted in increased expression of synaptophysin and robust translocation of this and additional vesicular proteins from synaptic-like microvesicle (SLMV) fractions to chromogranin-containing putative large dense core vesicle (LDCV) fractions in density gradient preparations. The LDCV fractions also contained substantially elevated Cu levels upon treatment of cells with Cu(II)(gtsm). Expression of the H(+) pump, V-ATPase, which is essential for vesicle maturation, was increased in Cu-treated cells while inhibition of V-ATPase prevented translocation of synaptophysin to LDCV fractions. Cu treatment was found to inhibit release of LDCVs in chromaffin cells due to reduced Ca(2+)-mediated vesicle exocytosis. Our findings demonstrate that elevated Cu can modulate LDCV metabolism potentially resulting in sequestration of Cu in this vesicle pool.

Published
2013
Full Text
View/download PDF

24. Diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)) protects against peroxynitrite-induced nitrosative damage and prolongs survival in amyotrophic lateral sclerosis mouse model.

Author

Soon CPW, Donnelly PS, Turner BJ, Hung LW, Crouch PJ, Sherratt NA, Tan JL, Lim NK, Lam L, Bica L, Lim S, Hickey JL, Morizzi J, Powell A, Finkelstein DI, Culvenor JG, Masters CL, Duce J, White AR, Barnham KJ, and Li QX

Subjects
Animals, Antioxidants chemistry, Astrocytes cytology, Coordination Complexes, Copper chemistry, DNA-Binding Proteins pharmacology, Disease Models, Animal, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microglia cytology, Neurodegenerative Diseases embryology, Neurons metabolism, Oxidative Stress, Oxygen chemistry, Spinal Cord pathology, Superoxide Dismutase-1, Transgenes, Amyotrophic Lateral Sclerosis metabolism, Organometallic Compounds chemistry, Peroxynitrous Acid metabolism, Superoxide Dismutase genetics, Thiosemicarbazones chemistry
Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which is an orally bioavailable, blood-brain barrier-permeable complex. In vitro the compound inhibits the action of peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) and subsequent nitration of cellular proteins. Oral treatment of transgenic SOD1G93A mice with CuII(atsm) at presymptomatic and symptomatic ages was performed. The mice were examined for improvement in lifespan and motor function, as well as histological and biochemical changes to key disease markers. Systemic treatment of SOD1G93A mice significantly delayed onset of paralysis and prolonged lifespan, even when administered to symptomatic animals. Consistent with the properties of this compound, treated mice had reduced protein nitration and carbonylation, as well as increased antioxidant activity in spinal cord. Treatment also significantly preserved motor neurons and attenuated astrocyte and microglial activation in mice. Furthermore, CuII(atsm) prevented the accumulation of abnormally phosphorylated and fragmented TAR DNA-binding protein-43 (TDP-43) in spinal cord, a protein pivotal to the development of ALS. CuII(atsm) therefore represents a potential new class of neuroprotective agents targeting multiple major disease pathways of motor neurons with therapeutic potential for ALS.

Published
2011
Full Text
View/download PDF

25. Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease.

Author

Adlard PA, Bica L, White AR, Nurjono M, Filiz G, Crouch PJ, Donnelly PS, Cappai R, Finkelstein DI, and Bush AI

Subjects
Alzheimer Disease metabolism, Animals, Cells, Cultured, Clioquinol analogs & derivatives, Disease Models, Animal, Female, Hippocampus drug effects, Hippocampus pathology, Ionophores administration & dosage, Memory drug effects, Metals administration & dosage, Mice, Mice, Transgenic, Neurites drug effects, Neurites metabolism, Neurogenesis drug effects, Alzheimer Disease pathology, Dendritic Spines drug effects, Dendritic Spines pathology, Ionophores pharmacology, Metals pharmacology, Nerve Tissue Proteins metabolism, Synapses metabolism
Abstract

We have previously demonstrated that brief treatment of APP transgenic mice with metal ionophores (PBT2, Prana Biotechnology) rapidly and markedly improves learning and memory. To understand the potential mechanisms of action underlying this phenomenon we examined hippocampal dendritic spine density, and the levels of key proteins involved in learning and memory, in young (4 months) and old (14 months) female Tg2576 mice following brief (11 days) oral treatment with PBT2 (30 mg/kg/d). Transgenic mice exhibited deficits in spine density compared to littermate controls that were significantly rescued by PBT2 treatment in both the young (+17%, p<0.001) and old (+32%, p<0.001) animals. There was no effect of PBT2 on spine density in the control animals. In the transgenic animals, PBT2 treatment also resulted in significant increases in brain levels of CamKII (+57%, p = 0.005), spinophilin (+37%, p = 0.04), NMDAR1A (+126%, p = 0.02), NMDAR2A (+70%, p = 0.05), pro-BDNF (+19%, p = 0.02) and BDNF (+19%, p = 0.04). While PBT2-treatment did not significantly alter neurite-length in vivo, it did increase neurite outgrowth (+200%, p = 0.006) in cultured cells, and this was abolished by co-incubation with the transition metal chelator, diamsar. These data suggest that PBT2 may affect multiple aspects of snaptic health/efficacy. In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular β-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function.

Published
2011
Full Text
View/download PDF

26. Cell cycle arrest in cultured neuroblastoma cells exposed to a bis(thiosemicarbazonato) metal complex.

Author

Bica L, Meyerowitz J, Parker SJ, Caragounis A, Du T, Paterson BM, Barnham KJ, Crouch PJ, White AR, and Donnelly PS

Subjects
Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Cycle drug effects, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Flow Cytometry, Humans, Molecular Structure, Organometallic Compounds chemical synthesis, Organometallic Compounds chemistry, Stereoisomerism, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Copper chemistry, Neuroblastoma drug therapy, Neuroblastoma pathology, Organometallic Compounds pharmacology, Thiosemicarbazones chemistry
Abstract

Brain tumors such as neuroblastomas and gliomas are often refractory to current treatments. Development of metal-based drugs may offer an alternative approach due to the ability to deliver radionuclides or cytotoxic metals to the tumor. Previous studies have shown that diacetyl-bis(N(4)-methylthiosemicarbazonato)-copper(II) (Cu(II)(atsm)) can selectively target hypoxic tumors and this feature has been utilized for development of imaging and radiotherapy. However, we have recently shown that glyoxal-bis(N(4)-methylthiosemicarbazonato)-copper(II) (Cu(II)(gtsm)) can target the brain in animal models of neurodegeneration. Unlike Cu(II)(atsm), Cu(II)(gtsm) is able to release Cu intracellularly under normoxic conditions. Glyoxal-bis(thiosemicarbazones) have reported anticancer effects but little is known about the cellular mechanisms involved. Therefore, in this study, we used protein microarray analysis to investigate the effect of Cu(II)(gtsm) on neuroblastoma cell growth in vitro. Treatment of the human neuroblastoma cell line BE(2)-M17, resulted in cell cycle arrest as assessed by fluorescent activated cell sorting (FACS) analysis. Rapidly arrested growth was not associated with onset of apoptosis. Instead, protein microarray analysis revealed that Cu(II)(gtsm) rapidly and potently reduced cyclin D1 expression, while increasing Kip2 expression. Other changes observed were decreased Cdk7 expression and activation of CHK2. These changes may be associated with the cell cycle arrest. We also observed a potent decrease of total and phosphorylated insulin-like growth factor receptor (IGF-IR) by Cu(II)(gtsm) which is associated with modulation of cyclin D1 expression. Our studies reveal important insights into the potential anticancer activity of Cu(II)(gtsm). Further studies are needed to examine the therapeutic potential of Cu(II)(gtsm) and other bis(thiosemicarbazonato) metal complexes as metallo-drugs for treatment of systemic or brain tumors.

Published
2011
Full Text
View/download PDF

27. Metallo-complex activation of neuroprotective signalling pathways as a therapeutic treatment for Alzheimer's disease.

Author

Bica L, Crouch PJ, Cappai R, and White AR

Subjects
Amyloid beta-Peptides metabolism, Animals, Extracellular Signal-Regulated MAP Kinases metabolism, Glycogen Synthase Kinase 3 metabolism, Humans, Ligands, Oxidative Stress, Oxyquinoline pharmacology, Phosphorylation, Signal Transduction, Zinc chemistry, tau Proteins chemistry, Alzheimer Disease metabolism, Alzheimer Disease therapy, Metals chemistry, Neuroprotective Agents pharmacology
Abstract

Alzheimer's disease is the most common neurodegenerative disease of the elderly and although some drugs may delay cognitive impairment, an effective treatment has not yet been found. Extracellular deposition of amyloid-beta (Abeta) plaques, intracellular hyperphosphorylation of the microtubule associated protein, tau and elevated oxidative stress have long been a focus for neurotherapeutic strategies. More recently biometal interactions with Abeta have become a feasible target as they appear to play a significant role in the pathogenesis of this devastating disease. Metal ligands such as 8-hydroxyquinoline derivatives have been developed that alter these interactions and promote clearance of amyloid deposits. A novel neurotherapeutic approach may involve activation of neuronal cell signalling mechanisms using metallo-complexes. Copper or zinc complexes can activate phosphoinositol-3-kinase leading to downstream modulation of glycogen synthase kinase-3 and extracellular signal regulated kinase and this results in decreased tau and Abeta levels. These approaches may offer a new strategy for treating AD. Further in vivo investigation is required to elucidate the mechanism of action of these metallo-complexes in vivo and determine their efficacy and safety as potential treatments of neurodegenerative diseases.

Published
2009
Full Text
View/download PDF

28. Clioquinol inhibits peroxide-mediated toxicity through up-regulation of phosphoinositol-3-kinase and inhibition of p53 activity.

Author

Filiz G, Caragounis A, Bica L, Du T, Masters CL, Crouch PJ, and White AR

Subjects
Animals, Cell Line, Tumor, Humans, Hydrogen Peroxide toxicity, Mice, Up-Regulation, Clioquinol pharmacology, Hydrogen Peroxide antagonists & inhibitors, Neuroprotective Agents pharmacology, Oxidative Stress drug effects, Phosphatidylinositol 3-Kinases metabolism, Tumor Suppressor Protein p53 antagonists & inhibitors
Abstract

A growing body of evidence supports a central role for biometals in neurodegenerative disorders. Biometals induce oxidative stress through the generation of reactive oxygen species and contribute to neuronal cell dysfunction in Alzheimer's disease (AD), prion disorders and Parkinson's disease (PD). Therapies based on modulation of biometal metabolism are currently being developed and the metal ligand, 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol or CQ) has been investigated for the treatment of AD. CQ has also shown therapeutic benefits in an animal model of PD. However, little is known about the neuroprotective processes of CQ in vivo. In this study, we examined the effect of CQ in BE(2)-M17 human neuroblastoma cells exposed to increased oxidative stress (hydrogen peroxide (H2O2) treatment). Although CQ alone induced a moderate toxic effect on cells, when added to H2O2-treated M17 cells, CQ induced a significant inhibition of H2O2 toxicity. This correlated with up-regulation of phosphoinositol-3-kinase (PI3K) activity in CQ-treated cells. The protective action of CQ was not observed in murine N2a neuroblastoma cells treated with H2O2 and this cell-line did not reveal CQ-mediated increases in PI3K activation. The protective effect was specific for CQ and was not induced by a number of different metal ligands. Inhibition of PI3K activity with LY294002 prevented CQ protection against H2O2 toxicity, demonstrating a crucial role for CQ activation of PI3K in protection against oxidative stress. Furthermore, CQ inhibited H2O2-mediated up-regulation of p53 activity in the M17 cells and this was dependent on PI3K activation. Our studies demonstrate that in human M17 cells, CQ can protect against oxidative stress by activating the PI3K-dependent survival pathway and blocking p53-mediated cell death. These findings have important implications for the development of protective metal ligand-based therapies for treatment of disorders involving oxidative stress.

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results