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2. Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host

Author

Paula Josefina Gómez-González, Anna D. Grabowska, Leopold D. Tientcheu, Anthony G. Tsolaki, Martin L. Hibberd, Susana Campino, Jody E. Phelan, and Taane G. Clark

Subjects
Mycobacerium tuberculosis, genomics, MTBC, diversity, pe/ppe family of genes, Microbiology, QR1-502
Abstract

IntroductionAround 10% of the coding potential of Mycobacterium tuberculosisis constituted by two poorly understood gene families, the pe and ppe loci, thought to be involved in host-pathogen interactions. Their repetitive nature and high GC content have hindered sequence analysis, leading to exclusion from whole-genome studies. Understanding the genetic diversity of pe/ppe families is essential to facilitate their potential translation into tools for tuberculosis prevention and treatment.MethodsTo investigate the genetic diversity of the 169 pe/ppe genes, we performed a sequence analysis across 73 long-read assemblies representing seven different lineages of M. tuberculosis and M. bovis BCG. Individual pe/ppe gene alignments were extracted and diversity and conservation across the different lineages studied.ResultsThe pe/ppe genes were classified into three groups based on the level of protein sequence conservation relative to H37Rv, finding that >50% were conserved, with indels in pe_pgrs and ppe_mptr sub-families being major drivers of structural variation. Gene rearrangements, such as duplications and gene fusions, were observed between pe and pe_pgrs genes. Inter-lineage diversity revealed lineage-specific SNPs and indels.DiscussionThe high level of pe/ppe genes conservation, together with the lineage-specific findings, suggest their phylogenetic informativeness. However, structural variants and gene rearrangements differing from the reference were also identified, with potential implications for pathogenicity. Overall, improving our knowledge of these complex gene families may have insights into pathogenicity and inform the development of much-needed tools for tuberculosis control.

Published
2023
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4. CTA contributions to the 33rd International Cosmic Ray Conference (ICRC2013)

Author

Consortium, The CTA, Abril, O., Acharya, B. S., Actis, M., Agnetta, G., Aguilar, J. A., Aharonian, F., Ajello, M., Akhperjanian, A., Alcubierre, M., Aleksic, J., Alfaro, R., Aliu, E., Allafort, A. J., Allan, D., Allekotte, I., Aloisio, R., Amato, E., Ambrosi, G., Ambrosio, M., Anderson, J., Angüner, E. O., Antonelli, L. A., Antonuccio, V., Antonucci, M., Antoranz, P., Aravantinos, A., Argan, A., Arlen, T., Aramo, C., Armstrong, T., Arnaldi, H., Arrabito, L., Asano, K., Ashton, T., Asorey, H. G., Aune, T., Awane, Y., Baba, H., Babic, A., Baby, N., Bähr, J., Bais, A., Baixeras, C., Bajtlik, S., Balbo, M., Balis, D., Balkowski, C., Ballet, J., Bamba, A., Bandiera, R., Barber, A., Barbier, C., Barceló, M., Barnacka, A., Barnstedt, J., de Almeida, U. Barres, Barrio, J. A., Basili, A., Basso, S., Bastieri, D., Bauer, C., Baushev, A., Becciani, U., Becerra, J., Becherini, Y., Bechtol, K. C., Tjus, J. Becker, Beckmann, V., Bednarek, W., Behera, B., Belluso, M., Benbow, W., Berdugo, J., Berge, D., Berger, K., Bernard, F., Bernardino, T., Bernlöhr, K., Bertucci, B., Bhat, N., Bhattacharyya, S., Biasuzzi, B., Bigongiari, C., Biland, A., Billotta, S., Bird, T., Birsin, E., Bissaldi, E., Biteau, J., Bitossi, M., Blake, S., Bigas, O. Blanch, Blasi, P., Bobkov, A., Boccone, V., Böttcher, M., Bogacz, L., Bogart, J., Bogdan, M., Boisson, C., Gargallo, J. Boix, Bolmont, J., Bonanno, G., Bonardi, A., Bonev, T., Bonifacio, P., Bonnoli, G., Bordas, P., Borgland, A., Borkowski, J., Bose, R., Botner, O., Bottani, A., Bouchet, L., Bourgeat, M., Boutonnet, C., Bouvier, A., Brau-Nogué, S., Braun, I., Bretz, T., Briggs, M., Brigida, M., Bringmann, T., Britto, R., Brook, P., Brun, P., Brunetti, L., Bruno, P., Bucciantini, N., Buanes, T., Buckley, J., Bühler, R., Bugaev, V., Bulgarelli, A., Bulik, T., Busetto, G., Buson, S., Byrum, K., Cailles, M., Cameron, R., Camprecios, J., Canestrari, R., Cantu, S., Capalbi, M., Caraveo, P., Carmona, E., Carosi, A., Carosi, R., Carr, J., Carter, J., Carton, P. -H., Caruso, R., Casanova, S., Cascone, E., Casiraghi, M., Castellina, A., Catalano, O., Cavazzani, S., Cazaux, S., Cerchiara, P., Cerruti, M., Chabanne, E., Chadwick, P., Champion, C., Chaves, R., Cheimets, P., Chen, A., Chiang, J., Chiappetti, L., Chikawa, M., Chitnis, V. R., Chollet, F., Christof, A., Chudoba, J., Cieślar, M., Cillis, A., Cilmo, M., Codino, A., Cohen-Tanugi, J., Colafrancesco, S., Colin, P., Colome, J., Colonges, S., Compin, M., Conconi, P., Conforti, V., Connaughton, V., Conrad, J., Contreras, J. L., Coppi, P., Coridian, J., Corona, P., Corti, D., Cortina, J., Cossio, L., Costa, A., Costantini, H., Cotter, G., Courty, B., Couturier, S., Covino, S., Crimi, G., Criswell, S. J., Croston, J., Cusumano, G., Dafonseca, M., Dale, O., Daniel, M., Darling, J., Davids, I., Dazzi, F., de Angelis, A., De Caprio, V., De Frondat, F., Pino, E. M. de Gouveia Dal, de la Calle, I., De La Vega, G. A., Lopez, R. de los Reyes, de Lotto, B., De Luca, A., de Naurois, M., de Oliveira, Y., Wilhelmi, E. de Oña, de Palma, F., de Souza, V., Decerprit, G., Decock, G., Deil, C., Delagnes, E., Deleglise, G., Delgado, C., della Volpe, D., Demange, P., Depaola, G., Dettlaff, A., Di Girolamo, T., Di Giulio, C., Di Paola, A., Di Pierro, F., di Sciascio, G., Díaz, C., Dick, J., Dickherber, R., Dickinson, H., Diez-Blanco, V., Digel, S., Dimitrov, D., Disset, G., Djannati-Ataï, A., Doert, M., Dohmke, M., Domainko, W., Prester, D. Dominis, Donat, A., Dorner, D., Doro, M., Dournaux, J. -L., Drake, G., Dravins, D., Drury, L., Dubois, F., Dubois, R., Dubus, G., Dufour, C., Dumas, D., Dumm, J., Durand, D., Dwarkadas, V., Dyks, J., Dyrda, M., Ebr, J., Edy, E., Egberts, K., Eger, P., Einecke, S., Eleftheriadis, C., Elles, S., Emmanoulopoulos, D., Engelhaupt, D., Enomoto, R., Ernenwein, J. -P., Errando, M., Etchegoyen, A., Evans, P. A., Falcone, A., Faltenbacher, A., Fantinel, D., Farakos, K., Farnier, C., Farrell, E., Fasola, G., Favill, B. W., Fede, E., Federici, S., Fegan, S., Feinstein, F., Ferenc, D., Ferrando, P., Fesquet, M., Fetfatzis, P., Fiasson, A., Fillin-Martino, E., Fink, D., Finley, C., Finley, J. P., Fiorini, M., Curcoll, R. Firpo, Flandrini, E., Fleischhack, H., Flores, H., Florin, D., Focke, W., Föhr, C., Fokitis, E., Font, L., Fontaine, G., Fornasa, M., Förster, A., Fortson, L., Fouque, N., Franckowiak, A., Franco, F. J., Frankowski, A., Fransson, C., Fraser, G. W., Frei, R., Fresnillo, L., Fruck, C., Fugazza, D., Fujita, Y., Fukazawa, Y., Fukui, Y., Funk, S., Gäbele, W., Gabici, S., Gabriele, R., Gadola, A., Galante, N., Gall, D., Gallant, Y., Gámez-García, J., Garczarczyk, M., García, B., López, R. Garcia, Gardiol, D., Gargano, F., Garrido, D., Garrido, L., Gascon, D., Gaug, M., Gaweda, J., Gebremedhin, L., Geffroy, N., Gerard, L., Ghedina, A., Ghigo, M., Ghislain, P., Giannakaki, E., Gianotti, F., Giarrusso, S., Giavitto, G., Giebels, B., Giglietto, N., Gika, V., Giomi, M., Giommi, P., Giordano, F., Girard, N., Giro, E., Giuliani, A., Glanzman, T., Glicenstein, J. -F., Godinovic, N., Golev, V., Berisso, M. Gomez, Gómez-Ortega, J., Gonzalez, M. M., González, A., González, F., Muñoz, A. González, Gothe, K. S., Grabarczyk, T., Gougerot, M., Graciani, R., Grandi, P., Grañena, F., Granot, J., Grasseau, G., Gredig, R., Green, A., Greenshaw, T., Grégoire, T., Grillo, A., Grimm, O., Grondin, M. -H., Grube, J., Grudzinska, M., Gruev, V., Grünewald, S., Grygorczuk, J., Guarino, V., Gunji, S., Gyuk, G., Hadasch, D., Hagedorn, A., Hagiwara, R., Hahn, J., Hakansson, N., Hallgren, A., Heras, N. Hamer, Hara, S., Hardcastle, M. J., Harezlak, D., Harris, J., Hassan, T., Hatanaka, K., Haubold, T., Haupt, A., Hayakawa, T., Hayashida, M., Heller, R., Henault, F., Henri, G., Hermann, G., Hermel, R., Herrero, A., Hervet, O., Hidaka, N., Hinton, J. A., Hirotani, K., Hoffmann, D., Hofmann, W., Hofverberg, P., Holder, J., Hörandel, J. R., Horns, D., Horville, D., Houles, J., Hrabovsky, M., Hrupec, D., Huan, H., Huber, B., Huet, J. -M., Hughes, G., Humensky, T. B., Huovelin, J., Huppert, J. -F., Ibarra, A., Ikawa, D., Illa, J. M., Impiombato, D., Incorvaia, S., Inoue, S., Inoue, Y., Iocco, F., Ioka, K., Israel, G. L., Jablonski, C., Jacholkowska, A., Jacquemier, J., Jamrozy, M., Janiak, M., Jean, P., Jeanney, C., Jimenez, J. J., Jogler, T., Johnson, C., Johnson, T., Journet, L., Juffroy, C., Jung, I., Kaaret, P., Kabuki, S., Kagaya, M., Kakuwa, J., Kalkuhl, C., Kankanyan, R., Karastergiou, A., Kärcher, K., Karczewski, M., Karkar, S., Kasperek, J., Kastana, D., Katagiri, H., Kataoka, J., Katarzyński, K., Katz, U., Kawanaka, N., Kazanas, D., Kelley-Hoskins, N., Kellner-Leidel, B., Kelly, H., Kendziorra, E., Khélifi, B., Kieda, D. B., Kifune, T., Kihm, T., Kishimoto, T., Kitamoto, K., Kluźniak, W., Knapic, C., Knapp, J., Knödlseder, J., Köck, F., Kocot, J., Kodani, K., Köhne, J. -H., Kohri, K., Kokkotas, K., Kolitzus, D., Komin, N., Kominis, I., Konno, Y., Köppel, H., Korohoda, P., Kosack, K., Koss, G., Kossakowski, R., Koul, R., Kowal, G., Koyama, S., Kozioł, J., Krähenbühl, T., Krause, J., Krawzcynski, H., Krennrich, F., Krepps, A., Kretzschmann, A., Krobot, R., Krueger, P., Kubo, H., Kudryavtsev, V. A., Kushida, J., Kuznetsov, A., La Barbera, A., La Palombara, N., La Parola, V., La Rosa, G., Lacombe, K., Lamanna, G., Lande, J., Languignon, D., Lapington, J. S., Laporte, P., Laurent, B., Lavalley, C., Flour, T. Le, Padellec, A. Le, Lee, S. -H., Lee, W. H., Lefèvre, J. -P., Leich, H., de Oliveira, M. A. Leigui, Lelas, D., Lenain, J. -P., Leoni, R., Leopold, D. J., Lerch, T., Lessio, L., Leto, G., Lieunard, B., Lieunard, S., Lindemann, R., Lindfors, E., Liolios, A., Lipniacka, A., Lockart, H., Lohse, T., Lombardi, S., Longo, F., Lopatin, A., Lopez, M., López-Coto, R., López-Oramas, A., Lorca, A., Lorenz, E., Louis, F., Lubinski, P., Lucarelli, F., Lüdecke, H., Ludwin, J., Luque-Escamilla, P. L., Lustermann, W., Luz, O., Lyard, E., Maccarone, M. C., Maccarone, T. J., Madejski, G. M., Madhavan, A., Mahabir, M., Maier, G., Majumdar, P., Malaguti, G., Malaspina, G., Maltezos, S., Manalaysay, A., Mancilla, A., Mandat, D., Maneva, G., Mangano, A., Manigot, P., Mannheim, K., Manthos, I., Maragos, N., Marcowith, A., Mariotti, M., Marisaldi, M., Markoff, S., Marszałek, A., Martens, C., Martí, J., Martin, J. -M., Martin, P., Martínez, G., Martínez, F., Martínez, M., Massaro, F., Masserot, A., Mastichiadis, A., Mathieu, A., Matsumoto, H., Mattana, F., Mattiazzo, S., Maurer, A., Maurin, G., Maxfield, S., Maya, J., Mazin, D., Comb, L. Mc, McCann, A., McCubbin, N., McHardy, I., McKay, R., Meagher, K., Medina, C., Melioli, C., Melkumyan, D., Melo, D., Mereghetti, S., Mertsch, P., Meucci, M., Meyer, M., Michałowski, J., Micolon, P., Mihailidis, A., Mineo, T., Minuti, M., Mirabal, N., Mirabel, F., Miranda, J. M., Mirzoyan, R., Mistò, A., Mizuno, T., Moal, B., Moderski, R., Mognet, I., Molinari, E., Molinaro, M., Montaruli, T., Monte, C., Monteiro, I., Moore, P., Olaizola, A. Moralejo, Mordalska, M., Morello, C., Mori, K., Morlino, G., Morselli, A., Mottez, F., Moudden, Y., Moulin, E., Mrusek, I., Mukherjee, R., Munar-Adrover, P., Muraishi, H., Murase, K., Murphy, A. StJ., Nagataki, S., Naito, T., Nakajima, D., Nakamori, T., Nakayama, K., Naumann, C., Naumann, D., Naumann-Godo, M., Nayman, P., Nedbal, D., Neise, D., Nellen, L., Neronov, A., Neustroev, V., Neyroud, N., Nicastro, L., Nicolau-Kukliński, J., Niedźwiecki, A., Niemiec, J., Nieto, D., Nikolaidis, A., Nishijima, K., Nishikawa, K. -I., Noda, K., Nolan, S., Northrop, R., Nosek, D., Nowak, N., Nozato, A., Oakes, L., O'Brien, P. T., Ohira, Y., Ohishi, M., Ohm, S., Ohoka, H., Okuda, T., Okumura, A., Olive, J. -F., Ong, R. A., Orito, R., Orr, M., Osborne, J. P., Ostrowski, M., Otero, L. A., Otte, N., Ovcharov, E., Oya, I., Ozieblo, A., Padilla, L., Pagano, I., Paiano, S., Paillot, D., Paizis, A., Palanque, S., Palatka, M., Pallota, J., Palatiello, M., Panagiotidis, K., Panazol, J. -L., Paneque, D., Panter, M., Panzera, M. R., Paoletti, R., Papayannis, A., Papyan, G., Paredes, J. M., Pareschi, G., Parraud, J. -M., Parsons, D., Pauletta, G., Arribas, M. Paz, Pech, M., Pedaletti, G., Pelassa, V., Pelat, D., Perez, M. d. C., Persic, M., Petrucci, P. -O., Peyaud, B., Pichel, A., Pieloth, D., Pierre, E., Pita, S., Pivato, G., Pizzolato, F., Platino, M., Platos, Ł., Platzer, R., Podkladkin, S., Pogosyan, L., Pohl, M., Pojmanski, G., Ponz, J. D., Potter, W., Poutanen, J., Prandini, E., Prast, J., Preece, R., Profeti, F., Prokoph, H., Prouza, M., Proyetti, M., Puerto-Giménez, I., Pühlhofer, G., Puljak, I., Punch, M., Pyzioł, R., Quel, E. J., Quesada, J., Quinn, J., Quirrenbach, A., Racero, E., Rainò, S., Rajda, P. J., Rameez, M., Ramon, P., Rando, R., Rannot, R. 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Subjects
Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Instrumentation and Methods for Astrophysics, High Energy Physics - Experiment
Abstract

Compilation of CTA contributions to the proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), which took place in 2-9 July, 2013, in Rio de Janeiro, Brazil, Comment: Index of CTA conference proceedings at the ICRC2013, Rio de Janeiro (Brazil). v1: placeholder with no arXiv links yet, to be replaced once individual contributions have been all submitted. v2: final with arXiv links to all CTA contributions and full author list

Published
2013

5. Classical Marxism: an intellectual history

Author

Leopold, D

Abstract

The Invention of Marxism is a rich group biography of the founding generation of European socialists who introduced millions to Karl Marx’s ideas. But it doesn’t identify this generation’s core theoretical and philosophical unities.

Published
2023

8. Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host.

Author

Josefina Gómez-González, Paula, Grabowska, Anna D., Tientcheu, Leopold D., Tsolaki, Anthony G., Hibberd, Martin L., Campino, Susana, Phelan, Jody E., and Clark, Taane G.

Subjects
MYCOBACTERIUM tuberculosis, GENETIC variation, GENE rearrangement, GENE families, SOCIAL interaction, PERSONAL protective equipment
Abstract

Introduction: Around 10% of the coding potential of Mycobacterium tuberculosisis constituted by two poorly understood gene families, the pe and ppe loci, thought to be involved in host-pathogen interactions. Their repetitive nature and high GC content have hindered sequence analysis, leading to exclusion from whole-genome studies. Understanding the genetic diversity of pe/ppe families is essential to facilitate their potential translation into tools for tuberculosis prevention and treatment. Methods: To investigate the genetic diversity of the 169 pe/ppe genes, we performed a sequence analysis across 73 long-read assemblies representing seven different lineages of M. tuberculosis and M. bovis BCG. Individual pe/ppe gene alignments were extracted and diversity and conservation across the different lineages studied. Results: The pe/ppe genes were classified into three groups based on the level of protein sequence conservation relative to H37Rv, finding that >50% were conserved, with indels in pe_pgrs and ppe_mptr sub-families being major drivers of structural variation. Gene rearrangements, such as duplications and gene fusions, were observed between pe and pe_pgrs genes. Inter-lineage diversity revealed lineage-specific SNPs and indels. Discussion: The high level of pe/ppe genes conservation, together with the lineage-specific findings, suggest their phylogenetic informativeness. However, structural variants and gene rearrangements differing from the reference were also identified, with potential implications for pathogenicity. Overall, improving our knowledge of these complex gene families may have insights into pathogenicity and inform the development of much-needed tools for tuberculosis control. [ABSTRACT FROM AUTHOR]

Published
2023
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9. David Robertson, Sir Charles Eastlake and the Victorian Art World

Author

Ettlinger, Leopold D.

Abstract

Rezension zu: David Robertson, Sir Charles Eastlake and the Victorian Art World. Princeton University Press, Princeton, New Jersey, 1978, 468 pp. 200 ills., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Bd. 34 Nr. 3 (1981): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2023
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13. Analytical Marxism

Author

Leopold, D

Abstract

Analytical Marxism is a predominantly Anglophone variety of Marxism that emerged in the late 1970s, and whose leading proponents are located in philosophy and social science departments in US and European universities. It can be distinguished from certain classical forms of Marxism by its openness to analytical methods, its critical attitude to certain substantive Marxist claims, its acknowledgement of its own normative commitments, and its assertion of the need for socialist design.

Published
2022

14. Host Immune Responses Differ between M. africanum- and M. tuberculosis-Infected Patients following Standard Anti-tuberculosis Treatment.

Author

Leopold D Tientcheu, Mariëlle C Haks, Schadrac C Agbla, Jayne S Sutherland, Ifedayo M Adetifa, Simon Donkor, Edwin Quinten, Mohammed Daramy, Martin Antonio, Beate Kampmann, Tom H M Ottenhoff, Hazel M Dockrell, and Martin O Ota

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberculosis (Mtb)-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10-, whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively). In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and MIP-1α were higher in Mtb-infected patients. Overnight stimulation with ESAT-6/CFP-10 induced significantly higher levels of IFN-γ and TNF-α production, as well as gene expression of CCL4, IL1B and TLR4 in Mtb- compared to Maf-infected patients. Our study confirms differences in clinical features and immune genes expression and concentration of proteins associated with inflammatory processes between Mtb- and Maf-infected patients following anti-tuberculosis treatment These findings have public health implications for treatment regimens, and biomarkers for tuberculosis diagnosis and susceptibility.

Published
2016
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17. Association of slow recovery of Mycobacterium africanum-infected patients posttreatment with high content of Persister-Like bacilli in pretreatment sputum

Author

Leopold D Tientcheu, Andrew Bell, Oumie Secka, Abigail Ayorinde, Jacob Otu, Nathalie J Garton, Jayne S Sutherland, Martin O Ota, Martin Antonio, H M Dockrell, Beate Kampmann, and Michael R Barer

Subjects
Drug tolerance, Lipid body, Mycobacterium africanum, Tuberculosis treatment, Microbiology, QR1-502
Abstract

Objectives/Background: Mycobacterium africanum that causes 40% of tuberculosis (TB) in West Africa grows more slowly in culture and has similar transmission capacity compared with Mycobacterium tuberculosis, but M. africanum-exposed contacts progress more slowly to active disease. The presence of lipid body (LB) containing M. tuberculosis complex (MTBC) cells in sputum samples has been associated with mycobacterial transcriptomes indicating slow or no growth and persister-like antibiotic tolerance. Slow-growing bacilli have been found to display a persister-like phenotype with the accumulation of LBs and drug tolerance. Our previous study showed that the body mass index and lung damage resolution on chest X-ray were significantly improved slower in M. africanum-infected patients posttreatment than in M. tuberculosis-infected patients; however, the reason for this remains unclear. Therefore, we hypothesized that these differences could be either due to significant differences in drug resistance between the MTBC lineages or a difference in their content of persisters, as indicated by the percentage of LP-positive bacilli in sputum. Methods: Sputum isolates collected before treatment from patients with TB were subjected to drug susceptibility testing using the BD BACTEC MGIT 960 SIRE kit. The percentage of acid-fast bacilli (AFB) and LB-positive bacilli in pretreatment sputum was determined by a dual staining procedure using Auramine O and LipidTOX Red neutral lipid stain, respectively, and fluorescence microscopy imaging. Results: Out of the 77 isolates tested, 9 showed resistance to at least one drug and only 2 showed multidrug (rifampicin and isoniazid) resistance among M. tuberculosis-infected patients. The percentage of AFB-positive smears was similar between the two groups (p = 0.821), whereas that of LP-positive bacilli was significantly higher (p = 0.0059) in M. africanum-infected patients' sputa (n = 24) than in M. tuberculosis-infected patients' sputa (n = 36). In addition, the bacillary lengths were significantly higher in M. africanum-infected patients' sputa than in M. tuberculosis-infected patients' sputa (p = 0.0007). A high frequency of LP-positive bacilli in pretreatment sputum was associated with a poor body mass index and lung damage on chest X-ray improvement following anti-TB treatment in both the groups (r2 = 0.022; p = 0.017). Conclusion: The slow clinical recovery of M. africanum-infected patients compared with M. tuberculosis-infected patients posttreatment may be at least partially associated with the persistence of drug-tolerant “fat and lazy” bacilli.

Published
2016
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18. Etiology of Pediatric Bacterial Meningitis Pre- and Post-PCV13 Introduction Among Children Under 5 Years Old in Lomé, Togo

Author

Joseph Nsiari-Muzeyi Biey, Mawussi Godonou, Abdul Karim Sesay, Novissi Tsogbale, Martin Antonio, Leopold D. Tientcheu, Bernard Ntsama, Peter Sylvanus Ndow, Dadja Essoya Landoh, Segla D. Tigossou, Madikay Senghore, Archibald Worwui, Brenda Kwambana-Adams, Yawo Dzayissè Atakouma, Djatougbe Ayaovi Elie Akolly, Rowan E Bancroft, Jason M. Mwenda, Anoumou Dagnra, Enyonam Tsolenyanu, and M Fiawoo

Subjects
Male, 0301 basic medicine, Microbiology (medical), Pediatrics, medicine.medical_specialty, vaccine impact, 030106 microbiology, Supplement Articles, Neisseria meningitidis, Serogroup, medicine.disease_cause, Meningitis, Bacterial, Haemophilus influenzae, Hospitals, University, Pneumococcal Vaccines, 03 medical and health sciences, 0302 clinical medicine, Streptococcus pneumoniae, Prevalence, medicine, Humans, 030212 general & internal medicine, Whole Genome Sequencing, business.industry, Incidence, Vaccination, Infant, Newborn, meningitis, Infant, Outbreak, Pneumococcus, medicine.disease, 3. Good health, Bacterial vaccine, pediatric, Infectious Diseases, Togo, Child, Preschool, Female, business, Sentinel Surveillance, Meningitis, MenAfriVac
Abstract

Background Pediatric bacterial meningitis (PBM) causes severe morbidity and mortality within Togo. Thus, as a member of the World Health Organization coordinated Invasive Bacterial Vaccine Preventable Diseases network, Togo conducts surveillance targeting Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae, at a sentinel hospital within the capital city, Lomé, in the southernmost Maritime region. Methods Cerebrospinal fluid was collected from children, Streptococcus pneumoniae was the predominant pathogen responsible for pediatric bacterial meningitis during longitudinal sentinel surveillance within Togo, from 2010 to 2016. However, pneumococcal meningitis cases decreased by 88.1% (52/59) postvaccine introduction; from 59 cases prevaccine introduction to 7 cases postvaccine introduction.

Published
2019

22. Use of resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

Author

Luc Kestens, Leopold D. Tientcheu, M. Coninx, Beate Kampmann, Dawda Jobe, Marie P. Gomez, Jayne S. Sutherland, Kees L. M. C. Franken, Tom H. M. Ottenhoff, and W. van Loon

Subjects
0301 basic medicine, Male, 0302 clinical medicine, Medicine, Mass Screening, Interferon gamma, 030212 general & internal medicine, Child, Diagnostics, Family Characteristics, IGRA, biology, Infectious Diseases, Mycobacterium tuberculosis complex, Child, Preschool, Population study, Cytokines, Female, Gambia, medicine.symptom, medicine.drug, Research Article, Tuberculosis, Immunology, Tuberculin, Enzyme-Linked Immunosorbent Assay, Asymptomatic, Sensitivity and Specificity, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Interferon-gamma, Bacterial Proteins, Latent Tuberculosis, Humans, lcsh:RC109-216, Immunodiagnostics, Antigens, Bacterial, Interferon-gamma production, business.industry, Tuberculin Test, Mycobacterium tuberculosis, medicine.disease, biology.organism_classification, Pediatric tuberculosis, 030104 developmental biology, Human medicine, RpfB, business, RpfD, Interferon-gamma Release Tests
Abstract

Background Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children. Methods Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-γ level and calculate sensitivity and specificity. Results Interferon gamma production was significantly higher in infected (IGRA+, n=45) than in uninfected (IGRA-, n=20) children after stimulation with RpfA, B, C, and D (P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cut-offs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73%-92% and 77%-72% respectively, which was similar to and better than 65%-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n=28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P = 0.02 and 0.03, respectively). Conclusion RpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.

Published
2020

23. Performance of metabonomic serum analysis for diagnostics in paediatric tuberculosis

Author

Joram M. Posma, Matthew R. Lewis, Robindra Basu Roy, Leopold D. Tientcheu, Uzochukwu Egere, María Gómez-Romero, Elaine Holmes, Nicholas J. Andreas, Beate Kampmann, Toyin Togun, Verena Horneffer-van der Sluis, Stephane Camuzeaux, Abdou K. Sillah, and Beatriz Jiménez

Subjects
Male, 0301 basic medicine, Multivariate analysis, lcsh:Medicine, Diagnostic accuracy, CHILDREN, ACTIVATION, 0302 clinical medicine, Medicine, Prospective Studies, 030212 general & internal medicine, Child, lcsh:Science, Multidisciplinary, SPECTROSCOPY, Molecular medicine, PLASMA, Area under the curve, Multidisciplinary Sciences, TB, Child, Preschool, Metabolome, Science & Technology - Other Topics, Female, EXPRESSION, medicine.medical_specialty, Tuberculosis, Adolescent, PULMONARY TUBERCULOSIS, BIOMARKERS, METABOLISM, Paediatric research, Article, CLASSIFICATION, 03 medical and health sciences, Internal medicine, Humans, Metabolomics, Nuclear Magnetic Resonance, Biomolecular, Tuberculosis, Pulmonary, Science & Technology, Receiver operating characteristic, business.industry, lcsh:R, Infant, Diagnostic markers, medicine.disease, Confidence interval, 030104 developmental biology, Lipidomics, lcsh:Q, business, Validation cohort
Abstract

We applied a metabonomic strategy to identify host biomarkers in serum to diagnose paediatric tuberculosis (TB) disease. 112 symptomatic children with presumptive TB were recruited in The Gambia and classified as bacteriologically-confirmed TB, clinically diagnosed TB, or other diseases. Sera were analysed using 1H nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Multivariate data analysis was used to distinguish patients with TB from other diseases. Diagnostic accuracy was evaluated using Receiver Operating Characteristic (ROC) curves. Model performance was tested in a validation cohort of 36 children from the UK. Data acquired using 1H NMR demonstrated a sensitivity, specificity and Area Under the Curve (AUC) of 69% (95% confidence interval [CI], 56–73%), 83% (95% CI, 73–93%), and 0.78 respectively, and correctly classified 20% of the validation cohort from the UK. The most discriminatory MS data showed a sensitivity of 67% (95% CI, 60–71%), specificity of 86% (95% CI, 75–93%) and an AUC of 0.78, correctly classifying 83% of the validation cohort. Amongst children with presumptive TB, metabolic profiling of sera distinguished bacteriologically-confirmed and clinical TB from other diseases. This novel approach yielded a diagnostic performance for paediatric TB comparable to that of Xpert MTB/RIF and interferon gamma release assays.

Published
2020

26. Scientific Socialism: The Case of Robert Owen

Author

Leopold, D, Demetriou, K, and Loizides, A

Abstract

At the same time, the contributors of this volume take up the theme of how particular ideas such as political wisdom and political leadership as well as the nature of political science itself have been addressed in the history of Western political philosophy—that is, in what ways the elements that constitute statesmanship have over the centuries undergone several transformations and ramifications to fit within certain contexts and historical developments. Hence, the volume neither ...

Published
2019

29. Optimising the biosynthesis of oxygenated and acetylated Taxol precursors in Saccharomyces cerevisiae using advanced bioprocessing strategies

Author

Walls, Laura, primary, Malci, Koray, additional, Nowrouzi, Behnaz, additional, Li, Rachel, additional, Espaux, Leopold d, additional, Wong, Jeff, additional, Dennis, Jonathan, additional, Semiao, Andrea, additional, Wallace, Stephen, additional, Martinez, Jos, additional, Keasling, Jay, additional, and Solis, Leonardo Rios, additional

Published
2020
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34. Thalamus exhibits less sensory variability quenching than cortex

Author

Poland, E., Donner, T. H., Müller, K. -M., Leopold, D. A., and Wilke, M.

Subjects
genetic structures, Thalamus, Computational neuroscience, cortex, Article
Abstract

Spiking activity exhibits a large degree of variability across identical trials, which has been shown to be significantly reduced by stimulus onset in a wide range of cortical areas. Whether similar dynamics apply to the thalamus and in particular to the pulvinar is largely unknown. Here, we examined electrophysiological recordings from two adult rhesus macaques performing a perceptual task and comparatively investigated trial-to-trial variability in higher-order thalamus (ventral and dorsal pulvinar), the lateral geniculate nucleus (LGN) and visual cortex (area V4) prior to and following the presentation of a visual stimulus. We found spiking variability during stable fixation prior to stimulus onset to be considerably lower in both pulvinar and the LGN as compared to area V4. In contrast to the prominent variability reduction in V4 upon stimulus onset, variability in the thalamic nuclei was largely unaffected by visual stimulation. There was a small but significant variability decrease in the dorsal pulvinar, but not in the ventral portion of the pulvinar, which is closely connected to visual cortices and would thus have been expected to reflect cortical response properties. This dissociation did not stem from differences in response strength or mean firing rates and indicates fundamental differences in variability quenching between thalamus and cortex. Open-Access-Publikationsfonds 2019 peerReviewed

Published
2019

35. Methylation in Mycobacterium tuberculosis is lineage specific with associated mutations present globally

Author

Ruth McNerney, Paola Florez de Sessions, Taane G. Clark, Susana Campino, Martin L. Hibberd, Richard M. Anthony, Martin Antonio, Diana Machado, João Perdigão, Isabel Portugal, Jody Phelan, Miguel Viveiros, Zahra Hasan, Leopold D. Tientcheu, Indra Bergval, Rumina Hasan, Global Health and Tropical Medicine (GHTM), and Instituto de Higiene e Medicina Tropical (IHMT)

Subjects
0301 basic medicine, Methyltransferase, Tuberculosis, lcsh:Medicine, Genome, Biochemistry, Genetics and Molecular Biology (miscellaneous), Microbiology, Article, Mycobacterium tuberculosis, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Epigenetics, Nucleotide Motifs, lcsh:Science, Phylogeny, Genetics, Multidisciplinary, biology, lcsh:R, Computational Biology, Methyltransferases, Methylation, DNA Methylation, medicine.disease, biology.organism_classification, 3. Good health, 030104 developmental biology, Infectious Diseases, Mycobacterium tuberculosis complex, Mutation, DNA methylation, lcsh:Q, Genome, Bacterial
Abstract

DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M. tuberculosis and 2 lineages of M. africanum, the leading causes of tuberculosis disease in humans. We reveal lineage-specific methylated motifs and strain-specific mutations that are abundant globally and likely to explain loss of function in the respective methyltransferases. Our work provides a set of sixteen new complete reference genomes for the Mycobacterium tuberculosis complex, including complete lineage 5 genomes. Insights into lineage-specific methylomes will further elucidate underlying biological mechanisms and other important phenotypes of the epi-genome.

Published
2018

36. Hercules Florentinus

Author

Ettlinger, Leopold D.

Abstract

Mitteilungen des Kunsthistorischen Institutes in Florenz, Bd. 16, Nr. 2 (1972): Mitteilungen des Kunsthistorischen Institutes in Florenz

Published
2018
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39. Comparison of TB-LAMP, GeneXpert MTB/RIF and culture for diagnosis of pulmonary tuberculosis in The Gambia

Author

Francis S. Mendy, Martin Antonio, Adama L. Bojang, Jacob Otu, Schadrac C. Agbla, Leopold D. Tientcheu, Jayne S. Sutherland, and Beate Kampmann

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Tuberculosis, Adolescent, Liquid culture, 030106 microbiology, Mycobacterium, Sputum culture, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pulmonary tuberculosis, Internal medicine, parasitic diseases, medicine, Humans, 030212 general & internal medicine, Child, Tuberculosis, Pulmonary, Aged, Bacteriological Techniques, GeneXpert MTB/RIF, medicine.diagnostic_test, biology, business.industry, Sputum, Middle Aged, biology.organism_classification, medicine.disease, Virology, Cross-Sectional Studies, Infectious Diseases, Molecular Diagnostic Techniques, Mycobacterium tuberculosis complex, Child, Preschool, Cohort, Female, Gambia, medicine.symptom, business
Abstract

Summary Background Diagnosis of tuberculosis (TB) remains difficult, particularly in resource-limited settings. The development of nucleic acid-based tests for detection of Mycobacterium tuberculosis complex (MTBC) has significantly increased sensitivity compared to conventional smear microscopy and provides results within a matter of hours compared to weeks for the current gold-standard, liquid culture. Methods In this study we performed side-by-side comparison of mycobacterial detection assays on sputum samples from 285 subjects presenting with symptoms suggestive of TB in The Gambia and a cross-sectional cohort of 156 confirmed TB patients with a median of 2 months of treatment. A novel assay, Loop-Mediated Amplification test for TB (TB-LAMP), was compared to smear microscopy, MGIT culture and GeneXpert MTB/RIF for all samples. Results When culture was used as the reference standard, we found an overall sensitivity for TB-LAMP of 99% (95% CI: 94.5–99.8) and specificity of 94% (95% CI: 89.3–96.7). When latent class analysis was performed, TB-LAMP had 98.6% (95% CI: 95.9–100) sensitivity and 99% (95% CI: 98.2–100) specificity compared to 91.1% (95% CI: 86.1–96) sensitivity and 100% (95% CI: 98.2–100) specificity for MGIT culture. GeneXpert had the highest sensitivity 99.1% (95% CI: 97.1–100) but the lowest specificity 96% (95% CI: 92.6–98.3). Both TB-LAMP and GeneXpert showed high sensitivity and specificity regardless of age or strain of infection. Conclusion Our findings show the diagnostic utility of both GeneXpert and TB-LAMP in The Gambia. Whilst TB-LAMP requires less infrastructure, it is unable to detect drug-resistant patterns and therefore would be most suitable as a screening test for new TB cases in peripheral health clinics.

Published
2016

40. The Experimental Watershed Liming Study: Comparison of lake and watershed neutralization strategies

Author

Driscoll, C. T., primary, Cirmo, C. P., additional, Fahey, T. J., additional, Blette, V. L., additional, Bukaveckas, P. A., additional, Burns, D. A., additional, Gubala, C. P., additional, Leopold, D. J., additional, Newton, R. M., additional, Raynal, D. J., additional, Schofield, C. L., additional, Yavitt, J. B., additional, and Porcella, D. B., additional

Published
1996
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44. Late Pleistocene Interstadial Environment on Faddeyevskiy Island, East-Siberian Sea, Russia

Author

Andreev, Andrei A, Peteet, Dorothy M, Romanenko, Fedor A, Filimonova, Ludmila V, Sulerzhitsky, Leopold D, and Tarasov, Pavel E

Subjects
Environment Pollution
Abstract

Pollen, plant macrofossil, LOI and radiocarbon analyses of a 1.4-m section from Faddeyevskiy Island, Novosibirskie Ostrova archipelago (75 deg 20 min N, 143 deg 50 min E, 30m elevation) provide new information on the Late Pleistocene interstadial environmental history of this high Arctic region. Bulk radiocarbon dates of 25,700 +/- 1000, 32,780 +/- 500, 35,200 +/- 650 and two AMS dates of 29,950 +/- 660 and 42,990 +/- 1280 indicate that the deposits accumulated during the Kargian (Boutellier) interval. Numerous mammoth (Mammuthus primigenius) remains collected in the vicinity of the site were radiocarbon dated to 36,700-18,500 yr. BP. Rare bison (Bison priscus) bones were dated to 32,200 +/- 600 and 33,100 +/- 320. Poaceae, Cyperaceae, and Artemisia pollen dominate the pollen spectra with some Ranunculaceae, Caryophyllaceae, Rosaceae, and Compositae. These pollen spectra reflect a tundra-steppe vegetation which probably was dominant on the exposed shelf of the Arctic Ocean. The presence of Carex macrofossils infer a summer climate two degrees warmer than today. The productivity of this local vegetation during the Kargian interstadial was apparently high enough to feed the grass-eater herds.

Published
1999

46. Contribution of Xpert® MTB/RIF to the diagnosis of pulmonary tuberculosis among TB-exposed children in The Gambia

Author

Abigail Ayorinde, Philip C. Hill, Martin Antonio, Jayne S. Sutherland, Abdou K. Sillah, Jacob Otu, Uzochukwu Egere, Francis S. Mendy, Toyin Togun, Leopold D. Tientcheu, and Beate Kampmann

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Tuberculosis, biology, business.industry, Mycobacterial culture, Induced sputum, Diagnostic accuracy, biology.organism_classification, medicine.disease, Mycobacterium tuberculosis, Infectious Diseases, Pulmonary tuberculosis, Internal medicine, medicine, Sputum, medicine.symptom, business, Reference standards
Abstract

SETTING Greater Banjul Area, The Gambia. OBJECTIVE To conduct a pragmatic evaluation of the Xpert(®) MTB/RIF assay in the diagnosis of tuberculosis (TB) among child contacts. DESIGN In this prospective study, one induced sputum sample was obtained from TB contacts aged

Published
2015

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