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102. Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden

Author

Hakkarainen, Katja Marja, primary, Juuti, Rosa, additional, Burkill, Sarah, additional, Geissbühler, Yvonne, additional, Sabidó, Meritxell, additional, Popescu, Catrinel, additional, Suzart-Woischnik, Kiliana, additional, Hillert, Jan, additional, Artama, Miia, additional, Verkkoniemi-Ahola, Auli, additional, Myhr, Kjell-Morten, additional, Mehtälä, Juha, additional, Bahmanyar, Shahram, additional, Montgomery, Scott, additional, Korhonen, Pasi, additional, Adamo, Alessandra, additional, Wicklein, Eva-Maria, additional, Akbaba, Metin, additional, Borghesi, Gustavo, additional, Köfüncü, Evra, additional, Everage, Nicholas, additional, Pandhi, Avni, additional, Naylor, Maria, additional, Ly, Anh, additional, Jack, Dominic, additional, Todorovic, Milorad, additional, Issard, Delphine, additional, Macklin, Alexandra, additional, Primatesta, Paola, additional, Weitzman, Richard, additional, Klement, Riho, additional, Vehkala, Minna, additional, Vattulainen, Pia, additional, Korjagina, Marta, additional, and Gyllensten, Hanna, additional

Published
2020
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103. The association between exposure to interferon-beta during pregnancy and birth measurements in offspring of women with multiple sclerosis

Author

Burkill, Sarah, primary, Vattulainen, Pia, additional, Geissbuehler, Yvonne, additional, Sabido Espin, Meritxell, additional, Popescu, Catrinel, additional, Suzart-Woischnik, Kiliana, additional, Hillert, Jan, additional, Artama, Miia, additional, Verkkoniemi-Ahola, Auli, additional, Myhr, Kjell-Morten, additional, Cnattingius, Sven, additional, Korhonen, Pasi, additional, Montgomery, Scott, additional, and Bahmanyar, Shahram, additional

Published
2019
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105. The association between exposure to interferon-beta during pregnancy and birth measurements in offspring of women with multiple sclerosis

Author

Burkill, Sarah, Vattulainen, Pia, Geissbuehler, Yvonne, Sabido Espin, Meritxell, Popescu, Catrinel, Suzart-Woischnik, Kiliana, Hillert, Jan, Artama, Miia, Verkkoniemi-Ahola, Auli, Myhr, Kjell-Morten, Cnattingius, Sven, Korhonen, Pasi, Montgomery, Scott, Bahmanyar, Shahram, Burkill, Sarah, Vattulainen, Pia, Geissbuehler, Yvonne, Sabido Espin, Meritxell, Popescu, Catrinel, Suzart-Woischnik, Kiliana, Hillert, Jan, Artama, Miia, Verkkoniemi-Ahola, Auli, Myhr, Kjell-Morten, Cnattingius, Sven, Korhonen, Pasi, Montgomery, Scott, and Bahmanyar, Shahram

Abstract

BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference., Funding Agencies:Bayer AG Biogen Netherlands B.V. Merck KGaA Novartis Europharm Limited

Published
2019
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106. Whole-genome sequence of the bovine blood fluke Schistosoma bovis supports interspecific hybridization with S. haematobium

Author

Oleaga, Ana [0000-0002-8019-7354], Oey, Harald, Zakrzewski, Martha, Gravermann, Kerstin, Young, Neil D., Korhonen, Pasi K., Gobert, Geoffrey N., Nawaratna, Sujeevi, Hasan, Shihab, Martínez, David M., You, Hong, Lavin, Martin, Jones, Malcolm K., Ragan, Mark A., Stoye, Jens, Oleaga, Ana, Emery, Aidan M., Webster, Bonnie L., Rollinson, David, Gasser, Robin B., McManus, Donald P., Krause, Lutz, Oleaga, Ana [0000-0002-8019-7354], Oey, Harald, Zakrzewski, Martha, Gravermann, Kerstin, Young, Neil D., Korhonen, Pasi K., Gobert, Geoffrey N., Nawaratna, Sujeevi, Hasan, Shihab, Martínez, David M., You, Hong, Lavin, Martin, Jones, Malcolm K., Ragan, Mark A., Stoye, Jens, Oleaga, Ana, Emery, Aidan M., Webster, Bonnie L., Rollinson, David, Gasser, Robin B., McManus, Donald P., and Krause, Lutz

Abstract

Mesenteric infection by the parasitic blood fluke Schistosoma bovis is a common veterinary problem in Africa and the Middle East and occasionally in the Mediterranean Region. The species also has the ability to form interspecific hybrids with the human parasite S. haematobium with natural hybridisation observed in West Africa, presenting possible zoonotic transmission. Additionally, this exchange of alleles between species may dramatically influence disease dynamics and parasite evolution. We have generated a 374 Mb assembly of the S. bovis genome using Illumina and PacBio-based technologies. Despite infecting different hosts and organs, the genome sequences of S. bovis and S. haematobium appeared strikingly similar with 97% sequence identity. The two species share 98% of protein-coding genes, with an average sequence identity of 97.3% at the amino acid level. Genome comparison identified large continuous parts of the genome (up to several 100 kb) showing almost 100% sequence identity between S. bovis and S. haematobium. It is unlikely that this is a result of genome conservation and provides further evidence of natural interspecific hybridization between S. bovis and S. haematobium. Our results suggest that foreign DNA obtained by interspecific hybridization was maintained in the population through multiple meiosis cycles and that hybrids were sexually reproductive, producing viable offspring. The S. bovis genome assembly forms a highly valuable resource for studying schistosome evolution and exploring genetic regions that are associated with species-specific phenotypic traits.

Published
2019

114. Abstract LB-251: The cancer clinical trial landscape in the EU and the Nordic countries

Author

Pouwels, Jeroen, primary, Soidinsalo, Sebastian, additional, Haikala, Heidi, additional, Jaakola, Panu, additional, Jalava, Tarja, additional, Joensuu, Heikki, additional, Mustonen, Mika, additional, Korhonen, Pasi, additional, Kovanen, Panu, additional, Lehtonen, Anne, additional, Mattson, Johanna, additional, Monni, Outi, additional, Westermarck, Jukka, additional, and Klefström, Juha, additional

Published
2019
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119. Whole-genome sequence of the bovine blood fluke Schistosoma bovis supports interspecific hybridization with S. haematobium

Author

Oey, Harald, primary, Zakrzewski, Martha, additional, Gravermann, Kerstin, additional, Young, Neil D., additional, Korhonen, Pasi K., additional, Gobert, Geoffrey N., additional, Nawaratna, Sujeevi, additional, Hasan, Shihab, additional, Martínez, David M., additional, You, Hong, additional, Lavin, Martin, additional, Jones, Malcolm K., additional, Ragan, Mark A., additional, Stoye, Jens, additional, Oleaga, Ana, additional, Emery, Aidan M., additional, Webster, Bonnie L., additional, Rollinson, David, additional, Gasser, Robin B., additional, McManus, Donald P., additional, and Krause, Lutz, additional

Published
2019
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121. Best practice data life cycle approaches for the life sciences

Author

Griffin, Philippa C, Khadake, Jyoti, LeMay, Kate S, Lewis, Suzanna E, Orchard, Sandra, Pask, Andrew, Pope, Bernard, Roessner, Ute, Russell, Keith, Seemann, Torsten, Treloar, Andrew, Tyagi, Sonika, Christiansen, Jeffrey H, Dayalan, Saravanan, Gladman, Simon, Hangartner, Sandra B, Hayden, Helen L, Ho, William WH, Keeble-Gagnère, Gabriel, Korhonen, Pasi K, Neish, Peter, Prestes, Priscilla R, Richardson, Mark F, Watson-Haigh, Nathan S, Wyres, Kelly L, Young, Neil D, Schneider, Maria Victoria, Griffin, Philippa C, Khadake, Jyoti, LeMay, Kate S, Lewis, Suzanna E, Orchard, Sandra, Pask, Andrew, Pope, Bernard, Roessner, Ute, Russell, Keith, Seemann, Torsten, Treloar, Andrew, Tyagi, Sonika, Christiansen, Jeffrey H, Dayalan, Saravanan, Gladman, Simon, Hangartner, Sandra B, Hayden, Helen L, Ho, William WH, Keeble-Gagnère, Gabriel, Korhonen, Pasi K, Neish, Peter, Prestes, Priscilla R, Richardson, Mark F, Watson-Haigh, Nathan S, Wyres, Kelly L, Young, Neil D, and Schneider, Maria Victoria

Published
2018

122. Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain

Author

Preston, Sarah, Korhonen, Pasi K., Mouchiroud, Laurent, Cornaglia, Matteo, Mcgee, Sean L., Young, Neil D., Davis, Rohan A., Crawford, Simon, Nowell, Cameron, Ansell, Brendan R. E., Fisher, Gillian M., Andrews, Katherine T., Chang, Bill C. H., Gijs, Martin A. M., Sternberg, Paul W., Auwerx, Johan, Baell, Jonathan, Hofmann, Andreas, Jabbar, Abdul, and Gasser, Robin B.

Subjects
natural product, transcriptomics, nematode, oxidative phosphorylation, anthelmintic activity
Abstract

As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mito-ribosomal protein production before inhibiting motility. Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In accordance, real-time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic (Haemonchus contortus) and free-living (Caenorhabditis elegans) nematodes. Consequently, we hypothesize that deguelin is exerting its toxic effect on nematodes as a modulator of oxidative phosphorylation. This study highlights the dynamic biologic response of multicellular organisms to deguelin perturbation.—Preston, S., Korhonen, P. K., Mouchiroud, L., Cornaglia, M., McGee, S. L., Young, N. D., Davis, R. A., Crawford, S., Nowell, C., Ansell, B. R. E., Fisher, G. M., Andrews, K. T., Chang, B. C. H., Gijs, M. A. M., Sternberg, P. W., Auwerx, J., Baell, J., Hofmann, A., Jabbar, A., Gasser, R. B. Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain.

Published
2017

124. Additional file 2: Figure S1. of Use of a bioinformatic-assisted primer design strategy to establish a new nested PCR-based method for Cryptosporidium

Author

Koehler, Anson, Korhonen, Pasi, Hall, Ross, Young, Neil, Wang, Tao, Haydon, Shane, and Gasser, Robin

Abstract

Alignment of sequences of the variable D8 domain of the large subunit of nuclear ribosomal RNA gene (LSU) representing Cryptosporidium and closely related apicomplexans, alveolates and dinoflagellates. Oligonucleotide primers (LSU2040F, LSU3020R; LSU2065F and LSU2557R) designed specifically to regions flanking the variable D8 domain are indicated in green. Nucleotide differences from the majority consensus of the alignment are highlighted. Figure S2. Alignment of sequences of the variable D8 domain of the large subunit of nuclear ribosomal RNA gene (LSU) representing Cryptosporidium derived from 45 faecal DNA samples. Nucleotide differences from the majority consensus of the alignment are highlighted. Colpodella angusta was included as an outgroup. (PDF 222 kb)

Published
2017
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125. Gene Content Evolution in the Arthropods

Author

Thomas, Gregg W.C., primary, Dohmen, Elias, additional, Hughes, Daniel S.T., additional, Murali, Shwetha C., additional, Poelchau, Monica, additional, Glastad, Karl, additional, Anstead, Clare A., additional, Ayoub, Nadia A., additional, Batterham, Phillip, additional, Bellair, Michelle, additional, Binford, Gretta J., additional, Chao, Hsu, additional, Chen, Yolanda H., additional, Childers, Christopher, additional, Dinh, Huyen, additional, Doddapaneni, HarshaVardhan, additional, Duan, Jian J., additional, Dugan, Shannon, additional, Esposito, Lauren A., additional, Friedrich, Markus, additional, Garb, Jessica, additional, Gasser, Robin B., additional, Goodisman, Michael A.D., additional, Gundersen-Rindal, Dawn E., additional, Han, Yi, additional, Handler, Alfred M., additional, Hatakeyama, Masatsugu, additional, Hering, Lars, additional, Hunter, Wayne B., additional, Ioannidis, Panagiotis, additional, Jayaseelan, Joy C., additional, Kalra, Divya, additional, Khila, Abderrahman, additional, Korhonen, Pasi K., additional, Lee, Carol Eunmi, additional, Lee, Sandra L., additional, Li, Yiyuan, additional, Lindsey, Amelia R.I., additional, Mayer, Georg, additional, McGregor, Alistair P., additional, McKenna, Duane D., additional, Misof, Bernhard, additional, Munidasa, Mala, additional, Munoz-Torres, Monica, additional, Muzny, Donna M., additional, Niehuis, Oliver, additional, Osuji-Lacy, Nkechinyere, additional, Palli, Subba R., additional, Panfilio, Kristen A., additional, Pechmann, Matthias, additional, Perry, Trent, additional, Peters, Ralph S., additional, Poynton, Helen C., additional, Prpic, Nikola-Michael, additional, Qu, Jiaxin, additional, Rotenberg, Dorith, additional, Schal, Coby, additional, Schoville, Sean D., additional, Scully, Erin D., additional, Skinner, Evette, additional, Sloan, Daniel B., additional, Stouthamer, Richard, additional, Strand, Michael R., additional, Szucsich, Nikolaus U., additional, Wijeratne, Asela, additional, Young, Neil D., additional, Zattara, Eduardo E., additional, Benoit, Joshua B., additional, Zdobnov, Evgeny M., additional, Pfrender, Michael E., additional, Hackett, Kevin J., additional, Werren, John H., additional, Worley, Kim C., additional, Gibbs, Richard A., additional, Chipman, Ariel D., additional, Waterhouse, Robert M., additional, Bornberg-Bauer, Erich, additional, Hahn, Matthew W., additional, and Richards, Stephen, additional

Published
2018
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127. Best practice data life cycle approaches for the life sciences

Author

Griffin, Philippa C., primary, Khadake, Jyoti, additional, LeMay, Kate S., additional, Lewis, Suzanna E., additional, Orchard, Sandra, additional, Pask, Andrew, additional, Pope, Bernard, additional, Roessner, Ute, additional, Russell, Keith, additional, Seemann, Torsten, additional, Treloar, Andrew, additional, Tyagi, Sonika, additional, Christiansen, Jeffrey H., additional, Dayalan, Saravanan, additional, Gladman, Simon, additional, Hangartner, Sandra B., additional, Hayden, Helen L., additional, Ho, William W.H., additional, Keeble-Gagnère, Gabriel, additional, Korhonen, Pasi K., additional, Neish, Peter, additional, Prestes, Priscilla R., additional, Richardson, Mark F., additional, Watson-Haigh, Nathan S., additional, Wyres, Kelly L., additional, Young, Neil D., additional, and Schneider, Maria Victoria, additional

Published
2018
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128. The small RNA complement of adult Schistosoma haematobium

Author

Stroehlein, Andreas J., primary, Young, Neil D., additional, Korhonen, Pasi K., additional, Hall, Ross S., additional, Jex, Aaron R., additional, Webster, Bonnie L., additional, Rollinson, David, additional, Brindley, Paul J., additional, and Gasser, Robin B., additional

Published
2018
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132. Comparative Transcriptomic Exploration Reveals Unique Molecular Adaptations of Neuropathogenic Trichobilharzia to Invade and Parasitize Its Avian Definitive Host

Author

Leontovyč, Roman, Young, Neil D., Korhonen, Pasi K., Hall, Ross S., Tan, Patrick, Mikeš, Libor, Kašný, Martin, Horák, Petr, and Gasser, Robin B.

Subjects
Metabolic Processes, Schistosoma Mansoni, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Molecular Sequence Data, Adaptation, Biological, Pathogenesis, Pathology and Laboratory Medicine, Biochemistry, Helminths, Schistosomatidae, parasitic diseases, Genetics, Medicine and Health Sciences, Animals, Life Cycle Stages, Gene Expression Profiling, lcsh:Public aspects of medicine, Organisms, Biology and Life Sciences, Computational Biology, Proteins, lcsh:RA1-1270, Genomics, Proteases, Sequence Analysis, DNA, Genome Analysis, Invertebrates, Enzymes, Metabolism, Ducks, Host-Pathogen Interactions, Enzymology, Carbohydrate Metabolism, Schistosoma, Metabolic Pathways, Transcriptome Analysis, Metabolic Networks and Pathways, Research Article
Abstract

To date, most molecular investigations of schistosomatids have focused principally on blood flukes (schistosomes) of humans. Despite the clinical importance of cercarial dermatitis in humans caused by Trichobilharzia regenti and the serious neuropathologic disease that this parasite causes in its permissive avian hosts and accidental mammalian hosts, almost nothing is known about the molecular aspects of how this fluke invades its hosts, migrates in host tissues and how it interacts with its hosts’ immune system. Here, we explored selected aspects using a transcriptomic-bioinformatic approach. To do this, we sequenced, assembled and annotated the transcriptome representing two consecutive life stages (cercariae and schistosomula) of T. regenti involved in the first phases of infection of the avian host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for taxonomically related blood flukes of the genus Schistosoma. Detailed comparative analyses revealed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during their invasion and in growth and development, as well as the roles of cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation), peptidases (cathepsins) and other histolytic and lysozomal proteins in schistosomula during their particular migration in neural tissues of the avian host. In conclusion, the present transcriptomic exploration provides new and significant insights into the molecular biology of T. regenti, which should underpin future genomic and proteomic investigations of T. regenti and, importantly, provides a useful starting point for a range of comparative studies of schistosomatids and other trematodes., Author Summary Despite the clinical importance of Trichobilharzia regenti in bird hosts and as a cause of cercarial dermatitis in humans, almost nothing is known about the molecular aspects of this fluke and its interactions with its hosts. Here, we sequenced, assembled and annotated the transcriptome representing two life stages (cercariae and schistosomula) of T. regenti involved in the first phases of infection of the bird host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for related flukes. Detailed analyses showed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during invasion and in growth and development, as well as cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation), peptidases (cathepsins) and other histolytic and lysozomal proteins in schistosomula during migration in neural tissues. These molecular insights into T. regenti biology should support future genomic and proteomic investigations of T. regenti, and comparative studies of flatworms.

Published
2016

133. Additional file 2: of Pipeline for the identification and classification of ion channels in parasitic flatworms

Author

Bahiyah Nor, Young, Neil, Korhonen, Pasi, Hall, Ross, Tan, Patrick, Lonie, Andrew, and Gasser, Robin

Abstract

Figure S1. The number of conserved domains common to >75 % of the sequences in each ion channel subfamily within the training dataset. The proportion of the sequences in the subfamilies that share the number of domains is given in the graph. The number of conserved domains is grouped according to the ion channel families. Figure S2. The range of transmembrane domains predicted in training dataset ion channel proteins. Range of transmembrane domains per subfamily, grouped according to each ion channel family. Figure S3. Receiver operating characteristic (ROC) curves for each probabilistic classification method. Figure S4. Probability values of each ion channel subfamilies computed during classification of sequences in the test dataset. Figure A shows the relation between the probability values and classifications made by SVM classifier. Figure B shows average probability values for individual ion channel subfamilies. The average values were grouped according to the ion channel families. Figure S5. Characteristics of putative ion channels identified and classified from the test dataset (human and C. elegans proteins). Panel A: Test sequences ordered by their SVM probability value, with their identification grouping presented on the second y-axis. Most of the sequences classified using high probability values were classified in Groups 1 and 2. Panel B: Confidence in test data ion channel classifications by group and classification category. (DOCX 1083 kb)

Published
2016
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134. Additional file 1: of Molecular characterization of the Haemonchus contortus phosphoinositide-dependent protein kinase-1 gene (Hc-pdk-1)

Author

Fa-Cai Li, Gasser, Robin, Lok, James, Korhonen, Pasi, He, Li, Di, Wen-Da, Fang-Yuan Yin, Zhou, Rui, Zhou, Yan-Qin, Zhao, Jun-Long, and Hu, Min

Subjects
parasitic diseases
Abstract

Primers used to isolate Hc-pdk-1 of Haemonchus contortus and to make constructs for green fluorescent protein (GFP) localization in Caenorhabditis elegans . (DOC 32Â kb)

Published
2016
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135. Additional file 2: of Molecular characterization of the Haemonchus contortus phosphoinositide-dependent protein kinase-1 gene (Hc-pdk-1)

Author

Fa-Cai Li, Gasser, Robin, Lok, James, Korhonen, Pasi, He, Li, Di, Wen-Da, Fang-Yuan Yin, Zhou, Rui, Zhou, Yan-Qin, Zhao, Jun-Long, and Hu, Min

Abstract

Cloning strategy for reporter constructs. The constructs containing the Caenorhabditis elegans Ce-pdk-1 and the Haemonchus contortus Hc-pdk-1 promoters (pL-Cepdk and pL-Hcpdk) were made in the vector pPV199 [34]. Briefly, the Ce-pdk-1 promoter region was cloned into pPV199 (BamH1 and Age1 sites). The Hc-pdk-1 promoter region was cloned into pPV199 by homologous recombination. (DOC 127Â kb)

Published
2016
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137. Best practice data life cycle approaches for the life sciences

Author

Griffin, Philippa C., primary, Khadake, Jyoti, additional, LeMay, Kate S., additional, Lewis, Suzanna E., additional, Orchard, Sandra, additional, Pask, Andrew, additional, Pope, Bernard, additional, Roessner, Ute, additional, Russell, Keith, additional, Seemann, Torsten, additional, Treloar, Andrew, additional, Tyagi, Sonika, additional, Christiansen, Jeffrey H., additional, Dayalan, Saravanan, additional, Gladman, Simon, additional, Hangartner, Sandra B., additional, Hayden, Helen L., additional, Ho, William W.H., additional, Keeble-Gagnère, Gabriel, additional, Korhonen, Pasi K., additional, Neish, Peter, additional, Prestes, Priscilla R., additional, Richardson, Mark F., additional, Watson-Haigh, Nathan S., additional, Wyres, Kelly L., additional, Young, Neil D., additional, and Schneider, Maria Victoria, additional

Published
2017
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138. Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain

Author

Preston, Sarah, primary, Korhonen, Pasi K., additional, Mouchiroud, Laurent, additional, Cornaglia, Matteo, additional, McGee, Sean L., additional, Young, Neil D., additional, Davis, Rohan A., additional, Crawford, Simon, additional, Nowell, Cameron, additional, Ansell, Brendan R. E., additional, Fisher, Gillian M., additional, Andrews, Katherine T., additional, Chang, Bill C. H., additional, Gijs, Martin A. M., additional, Sternberg, Paul W., additional, Auwerx, Johan, additional, Baell, Jonathan, additional, Hofmann, Andreas, additional, Jabbar, Abdul, additional, and Gasser, Robin B., additional

Published
2017
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140. Pioglitazone and risk of mortality in patients with type 2 diabetes: results from a European multidatabase cohort study

Author

Strongman, Helen, primary, Korhonen, Pasi, additional, Williams, Rachael, additional, Bahmanyar, Shahram, additional, Hoti, Fabian, additional, Christopher, Solomon, additional, Majak, Maila, additional, Kool-Houweling, Leanne, additional, Linder, Marie, additional, Dolin, Paul, additional, and Heintjes, Edith M, additional

Published
2017
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145. Additional file 2: Figure S1. of The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery

Author

Stroehlein, Andreas, Young, Neil, Korhonen, Pasi, Jabbar, Abdul, Hofmann, Andreas, Sternberg, Paul, and Gasser, Robin

Subjects
parasitic diseases
Abstract

Transcription profiles for kinase genes in all key developmental stages (egg, L1, L2, L3, L4 and adult) and both sexes (L4 and adult) of Haemonchus contortus for eleven individual kinase groups. Figure S2. All clusters of transcription profiles for Haemonchus contortus kinase genes based on the Ward-clustering method (kâ =â 15). (DOCX 222 kb)

Published
2015
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146. COPD Patients Initiating Roflumilast in Sweden, Germany and the United States : Findings from the Roflumilast PASS Study

Author

Hoti, Fabian, Mushnikov, Vasili, Mehtala, Juha, Wentzell, Nadine, Kollhorst, Bianca, Schink, Tania, Garbe, Edeltraut, Mountford, William K., Knox, Caitlin, Kaufman, Elise, Johansson, Gunnar, Korhonen, Pasi, Hoti, Fabian, Mushnikov, Vasili, Mehtala, Juha, Wentzell, Nadine, Kollhorst, Bianca, Schink, Tania, Garbe, Edeltraut, Mountford, William K., Knox, Caitlin, Kaufman, Elise, Johansson, Gunnar, and Korhonen, Pasi

Published
2016
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147. Divergent Transcriptional Responses to Physiological and Xenobiotic Stress in Giardia duodenalis

Author

Ansell, Brendan R. E., McConville, Malcolm J., Baker, Louise, Korhonen, Pasi K., Emery, Samantha J., Svärd, Staffan G, Gasser, Robin B., Jex, Aaron R., Ansell, Brendan R. E., McConville, Malcolm J., Baker, Louise, Korhonen, Pasi K., Emery, Samantha J., Svärd, Staffan G, Gasser, Robin B., and Jex, Aaron R.

Abstract

Understanding how parasites respond to stress can help to identify essential biological processes. Giardia duodenalis is a parasitic protist that infects the human gastrointestinal tract and causes 200 to 300 million cases of diarrhea annually. Metronidazole, a major antigiardial drug, is thought to cause oxidative damage within the infective trophozoite form. However, treatment efficacy is suboptimal, due partly to metronidazole-resistant infections. To elucidate conserved and stress-specific responses, we calibrated sublethal metronidazole, hydrogen peroxide, and thermal stresses to exert approximately equal pressure on trophozoite growth and compared transcriptional responses after 24 h of exposure. We identified 252 genes that were differentially transcribed in response to all three stressors, including glycolytic and DNA repair enzymes, a mitogen-activated protein (MAP) kinase, high-cysteine membrane proteins, flavin adenine dinucleotide (FAD) synthetase, and histone modification enzymes. Transcriptional responses appeared to diverge according to physiological or xenobiotic stress. Downregulation of the antioxidant system and alpha-giardins was observed only under metronidazole-induced stress, whereas upregulation of GARP-like transcription factors and their subordinate genes was observed in response to hydrogen peroxide and thermal stressors. Limited evidence was found in support of stress-specific response elements upstream of differentially transcribed genes; however, antisense derepression and differential regulation of RNA interference machinery suggest multiple epigenetic mechanisms of transcriptional control.

Published
2016
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