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157. Development and Application of a Multilocus Sequence Analysis Method for the Identification of Genotypes Within Genus Bradyrhizobium and for Establishing Nodule Occupancy of Soybean (Glycine max L. Merr)

Author

Peter van Berkum, Patrick Elia, Qijian Song, and Bertrand D. Eardly

Subjects
Microbiology, QR1-502, Botany, QK1-989
Abstract

A multilocus sequence typing (MLST) method based on allelic variation of seven chromosomal loci was developed for characterizing genotypes (GT) within the genus Bradyrhizobium. With the method, 29 distinct multilocus GT were identified among 190 culture collection soybean strains. The occupancy of 347 nodules taken from uninoculated field-grown soybean plants also was determined. The bacteroid GT were either the same as or were closely related to GT identified among strains in the culture collection. Double-nodule occupancy estimates of 2.9% were much lower than values published based on serology. Of the 347 nodules examined, 337 and 10 were occupied by Bradyrhizobium japonicum and B. elkanii, respectively. The collection strains within the species B. japonicum and B. elkaniialso were compared with Bradyrhizobium cultures from other legumes. In many cases, the observed GT varied more according to their geographic origin than by their trap hosts of isolation. In other cases, there were no apparent relationships with either the legume or geographic source. The MLST method that was developed should be a useful tool in determining the influence of geographic location, temperature, season, soil type, and host plant cultivar on the distribution of GT of Bradyrhizobium spp.

Published
2012
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160. Search for neutrino-induced cascades with five years of AMANDA data

Author

Abbasi, R., Abdou, Y., Abu-Zayyad, T., Actis, O., Adams, J., Aguilar, J.A., Ahlers, M., Andeen, K., Auffenberg, J., Bai, X., Baker, M., Barwick, S.W., Bay, R., Bazo Alba, J.L., Beattie, K., Beatty, J.J., Bechet, S., Becker, J.K., Becker, K.-H., Benabderrahmane, M.L., Berdermann, J., Berghaus, P., Berley, D., Bernardini, E., Bertrand, D., Besson, D.Z., Bissok, M., Blaufuss, E., Boersma, D.J., Bohm, C., Böser, S., Botner, O., Bradley, L., Braun, J., Buitink, S., Carson, M., Chirkin, D., Christy, B., Clem, J., Clevermann, F., Cohen, S., Colnard, C., Cowen, D.F., D’Agostino, M.V., Danninger, M., Davis, J.C., De Clercq, C., Demirörs, L., Depaepe, O., Descamps, F., Desiati, P., de Vries-Uiterweerd, G., DeYoung, T., Díaz-Vélez, J.C., Dreyer, J., Dumm, J.P., Duvoort, M.R., Ehrlich, R., Eisch, J., Ellsworth, R.W., Engdegård, O., Euler, S., Evenson, P.A., Fadiran, O., Fazely, A.R., Feusels, T., Filimonov, K., Finley, C., Foerster, M.M., Fox, B.D., Franckowiak, A., Franke, R., Gaisser, T.K., Gallagher, J., Ganugapati, R., Geisler, M., Gerhardt, L., Gladstone, L., Glüsenkamp, T., Goldschmidt, A., Goodman, J.A., Grant, D., Griesel, T., Groß, A., Grullon, S., Gunasingha, R.M., Gurtner, M., Ha, C., Hallgren, A., Halzen, F., Han, K., Hanson, K., Helbing, K., Herquet, P., Hickford, S., Hill, G.C., Hoffman, K.D., Homeier, A., Hoshina, K., Hubert, D., Huelsnitz, W., Hülß, J.-P., Hulth, P.O., Hultqvist, K., Hussain, S., Imlay, R.L., Ishihara, A., Jacobsen, J., Japaridze, G.S., Johansson, H., Joseph, J.M., Kampert, K.-H., Kappes, A., Karg, T., Karle, A., Kelley, J.L., Kemming, N., Kenny, P., Kiryluk, J., Kislat, F., Klein, S.R., Knops, S., Köhne, J.-H., Kohnen, G., Kolanoski, H., Köpke, L., Koskinen, D.J., Kowalski, M., Kowarik, T., Krasberg, M., Krings, T., Kroll, G., Kuehn, K., Kuwabara, T., Labare, M., Lafebre, S., Laihem, K., Landsman, H., Lauer, R., Lehmann, R., Lennarz, D., Lünemann, J., Madsen, J., Majumdar, P., Maruyama, R., Mase, K., Matis, H.S., Matusik, M., Meagher, K., Merck, M., Mészáros, P., Meures, T., Middell, E., Milke, N., Miller, J., Montaruli, T., Morse, R., Movit, S.M., Nahnhauer, R., Nam, J.W., Naumann, U., Nießen, P., Nygren, D.R., Odrowski, S., Olivas, A., Olivo, M., Ono, M., Panknin, S., Paul, L., Pérez de los Heros, C., Petrovic, J., Piegsa, A., Pieloth, D., Porrata, R., Posselt, J., Price, P.B., Prikockis, M., Przybylski, G.T., Rawlins, K., Redl, P., Resconi, E., Rhode, W., Ribordy, M., Rizzo, A., Rodrigues, J.P., Roth, P., Rothmaier, F., Rott, C., Roucelle, C., Ruhe, T., Rutledge, D., Ruzybayev, B., Ryckbosch, D., Sander, H.-G., Sarkar, S., Schatto, K., Schlenstedt, S., Schmidt, T., Schneider, D., Schukraft, A., Schultes, A., Schulz, O., Schunck, M., Seckel, D., Semburg, B., Seo, S.H., Sestayo, Y., Seunarine, S., Silvestri, A., Slipak, A., Spiczak, G.M., Spiering, C., Stamatikos, M., Stanev, T., Stephens, G., Stezelberger, T., Stokstad, R.G., Stoyanov, S., Strahler, E.A., Straszheim, T., Sullivan, G.W., Swillens, Q., Taboada, I., Tamburro, A., Tepe, A., Ter-Antonyan, S., Tilav, S., Toale, P.A., Tosi, D., Turčan, D., van Eijndhoven, N., Vandenbroucke, J., Van Overloop, A., van Santen, J., Voigt, B., Walck, C., Waldenmaier, T., Wallraff, M., Walter, M., Wendt, C., Westerhoff, S., Whitehorn, N., Wiebe, K., Wiebusch, C.H., Wikström, G., Williams, D.R., Wischnewski, R., Wissing, H., Woschnagg, K., Xu, C., Xu, X.W., Yodh, G., Yoshida, S., and Zarzhitsky, P.

Published
2011
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161. Measurement of acoustic attenuation in South Pole ice

Author

Abbasi, R., Abdou, Y., Abu-Zayyad, T., Adams, J., Aguilar, J.A., Ahlers, M., Andeen, K., Auffenberg, J., Bai, X., Baker, M., Barwick, S.W., Bay, R., Bazo Alba, J.L., Beattie, K., Beatty, J.J., Bechet, S., Becker, J.K., Becker, K.-H., Benabderrahmane, M.L., Berdermann, J., Berghaus, P., Berley, D., Bernardini, E., Bertrand, D., Besson, D.Z., Bissok, M., Blaufuss, E., Boersma, D.J., Bohm, C., Böser, S., Botner, O., Bradley, L., Braun, J., Buitink, S., Carson, M., Chirkin, D., Christy, B., Clem, J., Clevermann, F., Cohen, S., Colnard, C., Cowen, D.F., D’Agostino, M.V., Danninger, M., De Clercq, C., Demirörs, L., Depaepe, O., Descamps, F., Desiati, P., de Vries-Uiterweerd, G., DeYoung, T., Díaz-Vélez, J.C., Dreyer, J., Dumm, J.P., Duvoort, M.R., Ehrlich, R., Eisch, J., Ellsworth, R.W., Engdegård, O., Euler, S., Evenson, P.A., Fadiran, O., Fazely, A.R., Feusels, T., Filimonov, K., Finley, C., Foerster, M.M., Fox, B.D., Franckowiak, A., Franke, R., Gaisser, T.K., Gallagher, J., Ganugapati, R., Geisler, M., Gerhardt, L., Gladstone, L., Glüsenkamp, T., Goldschmidt, A., Goodman, J.A., Grant, D., Griesel, T., Groß, A., Grullon, S., Gunasingha, R.M., Gurtner, M., Gustafsson, L., Ha, C., Hallgren, A., Halzen, F., Han, K., Hanson, K., Helbing, K., Herquet, P., Hickford, S., Hill, G.C., Hoffman, K.D., Homeier, A., Hoshina, K., Hubert, D., Huelsnitz, W., Hülß, J.-P., Hulth, P.O., Hultqvist, K., Hussain, S., Imlay, R.L., Ishihara, A., Jacobsen, J., Japaridze, G.S., Johansson, H., Joseph, J.M., Kampert, K.-H., Kappes, A., Karg, T., Karle, A., Kelley, J.L., Kemming, N., Kenny, P., Kiryluk, J., Kislat, F., Klein, S.R., Knops, S., Köhne, J.-H., Kohnen, G., Kolanoski, H., Köpke, L., Koskinen, D.J., Kowalski, M., Kowarik, T., Krasberg, M., Krings, T., Kroll, G., Kuehn, K., Kuwabara, T., Labare, M., Lafebre, S., Laihem, K., Landsman, H., Lauer, R., Lehmann, R., Lennarz, D., Lünemann, J., Madsen, J., Majumdar, P., Maruyama, R., Mase, K., Matis, H.S., Matusik, M., Meagher, K., Merck, M., Mészáros, P., Meures, T., Middell, E., Milke, N., Montaruli, T., Morse, R., Movit, S.M., Nahnhauer, R., Nam, J.W., Naumann, U., Nießen, P., Nygren, D.R., Odrowski, S., Olivas, A., Olivo, M., Ono, M., Panknin, S., Paul, L., Pérez de los Heros, C., Petrovic, J., Piegsa, A., Pieloth, D., Porrata, R., Posselt, J., Price, P.B., Prikockis, M., Przybylski, G.T., Rawlins, K., Redl, P., Resconi, E., Rhode, W., Ribordy, M., Rizzo, A., Rodrigues, J.P., Roth, P., Rothmaier, F., Rott, C., Roucelle, C., Ruhe, T., Rutledge, D., Ruzybayev, B., Ryckbosch, D., Sander, H.-G., Sarkar, S., Schatto, K., Schlenstedt, S., Schmidt, T., Schneider, D., Schukraft, A., Schultes, A., Schulz, O., Schunck, M., Seckel, D., Semburg, B., Seo, S.H., Sestayo, Y., Seunarine, S., Silvestri, A., Slipak, A., Spiczak, G.M., Spiering, C., Stamatikos, M., Stanev, T., Stephens, G., Stezelberger, T., Stokstad, R.G., Stoyanov, S., Strahler, E.A., Straszheim, T., Sullivan, G.W., Swillens, Q., Taboada, I., Tamburro, A., Tarasova, O., Tepe, A., Ter-Antonyan, S., Tilav, S., Toale, P.A., Tosi, D., Turčan, D., van Eijndhoven, N., Vandenbroucke, J., Van Overloop, A., van Santen, J., Voigt, B., Walck, C., Waldenmaier, T., Wallraff, M., Walter, M., Wendt, C., Westerhoff, S., Whitehorn, N., Wiebe, K., Wiebusch, C.H., Wikström, G., Williams, D.R., Wischnewski, R., Wissing, H., Woschnagg, K., Xu, C., Xu, X.W., Yanez, J.P., Yodh, G., Yoshida, S., and Zarzhitsky, P.

Published
2011
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165. Abstract 12020: Heterogeneity and Plasticity of Cardiac Fibroblasts Governing Reparative Lymphangiogenesis After Myocardial Infarction: A New Therapeutic Approach for Heart Failure

Author

Yuimi Matsuoka, Bertrand D Segard, Tomomi Imamura, Kodai Kimura, Ayana Ikeda, Makoto Matsuyama, Mami Arai, Takeshi Machino, Akira Sato, Nobuyuki Murakoshi, and Takahiro Iwamiya

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Cardiac lymphangiogenesis has attracted attention as a therapeutic target after myocardial infarction (MI). Lymphangiogenic remodeling has been observed after MI in adult and fetal hearts; however, reparative lymphangiogenic remodeling is only observed in fetal hearts. The factors that determine the fate of this phenomenon have not been fully elucidated. Hypothesis: We demonstrated that a specific population of VCAM1 + human fetal cardiac fibroblasts (fCFs) restore cardiac function post-MI by lymphangiogenesis. Thus, we hypothesize that adult cardiac fibroblasts (aCFs), compared to fCFs, possess a different distribution of fibroblasts with differing lymphangiogenic potential. Furthermore, we also hypothesize that aCFs can be exogenously manipulated to acquire fCFs-like reparative lymphangiogenic potential, which can be used as a cell therapy for heart failure. Methods: Flow cytometry assessed CD90 and VCAM1 expression of aCFs and fCFs. To shift aCFs towards a fCF phenotype, TNF-α and IL-4 were added to culture medium. aCF subpopulations were intramyocardially injected in nude rats and swine post-MI with subsequent echocardiography. Myocardial tissue staining (Sirius Red, LYVE1) and RNA-seq were performed to identify the molecular mechanism. Results: aCFs and fCFs exhibited different distributions of CD90 and VCAM1 expression, where aCFs showed lower CD90 and VCAM1 expression. The addition of TNF-α and IL-4 shifted the localization of VCAM1 + aCFs towards a fCF distribution by activation of NF-κB. VCAM1 + CD90 + fCFs-like aCFs provided a sustained improvement in left ventricular ejection fraction and showed reduced fibrosis and increased lymphangiogenesis. This effect was recapitulated in a large animal model. In terms of the molecular mechanism, 13 candidate genes were identified. Conclusions: These findings suggest that the heterogenous and plastic polarity of aCFs and fCFs determines the fate of the lymphangiogenic response after MI and that this response can be regulated by 13 genes. This artificial creation of the VCAM1 + fCFs-like fibroblast environment after MI has enabled a clinical trial for a new cell therapy for inducing reparative lymphangiogenesis (clinical trial ID: jRCT2033210078).

Published
2021

167. A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

Author

Huaying Zhao, Rodolfo Ghirlando, Carlos Alfonso, Fumio Arisaka, Ilan Attali, David L Bain, Marina M Bakhtina, Donald F Becker, Gregory J Bedwell, Ahmet Bekdemir, Tabot M D Besong, Catherine Birck, Chad A Brautigam, William Brennerman, Olwyn Byron, Agnieszka Bzowska, Jonathan B Chaires, Catherine T Chaton, Helmut Cölfen, Keith D Connaghan, Kimberly A Crowley, Ute Curth, Tina Daviter, William L Dean, Ana I Díez, Christine Ebel, Debra M Eckert, Leslie E Eisele, Edward Eisenstein, Patrick England, Carlos Escalante, Jeffrey A Fagan, Robert Fairman, Ron M Finn, Wolfgang Fischle, José García de la Torre, Jayesh Gor, Henning Gustafsson, Damien Hall, Stephen E Harding, José G Hernández Cifre, Andrew B Herr, Elizabeth E Howell, Richard S Isaac, Shu-Chuan Jao, Davis Jose, Soon-Jong Kim, Bashkim Kokona, Jack A Kornblatt, Dalibor Kosek, Elena Krayukhina, Daniel Krzizike, Eric A Kusznir, Hyewon Kwon, Adam Larson, Thomas M Laue, Aline Le Roy, Andrew P Leech, Hauke Lilie, Karolin Luger, Juan R Luque-Ortega, Jia Ma, Carrie A May, Ernest L Maynard, Anna Modrak-Wojcik, Yee-Foong Mok, Norbert Mücke, Luitgard Nagel-Steger, Geeta J Narlikar, Masanori Noda, Amanda Nourse, Tomas Obsil, Chad K Park, Jin-Ku Park, Peter D Pawelek, Erby E Perdue, Stephen J Perkins, Matthew A Perugini, Craig L Peterson, Martin G Peverelli, Grzegorz Piszczek, Gali Prag, Peter E Prevelige, Bertrand D E Raynal, Lenka Rezabkova, Klaus Richter, Alison E Ringel, Rose Rosenberg, Arthur J Rowe, Arne C Rufer, David J Scott, Javier G Seravalli, Alexandra S Solovyova, Renjie Song, David Staunton, Caitlin Stoddard, Katherine Stott, Holger M Strauss, Werner W Streicher, John P Sumida, Sarah G Swygert, Roman H Szczepanowski, Ingrid Tessmer, Ronald T Toth, Ashutosh Tripathy, Susumu Uchiyama, Stephan F W Uebel, Satoru Unzai, Anna Vitlin Gruber, Peter H von Hippel, Christine Wandrey, Szu-Huan Wang, Steven E Weitzel, Beata Wielgus-Kutrowska, Cynthia Wolberger, Martin Wolff, Edward Wright, Yu-Sung Wu, Jacinta M Wubben, and Peter Schuck

Subjects
Medicine, Science
Abstract

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.

Published
2015
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168. Ectomycorrhizal diversity on the roots of Pitch pine (Pinus rigida Mill.) saplings as influenced by remediation and soil metal content.

Author

Eardly, Bertrand D., Cloutier, Mara, Chung, Taejung, Roitman, Sofia, Vieira, Fabricio R., and Bruns, Mary Ann V.

Subjects
*METAL content of soils, *SOIL remediation, *COMMUNITIES, *PINE, *FUNGAL communities
Abstract

From 1913 to 1980, two zinc smelters in Palmerton, Pennsylvania, emitted large quantities of atmospheric pollutants nearly eliminating forests along a ridge above the town. In 2008, a remediation treatment was applied to the land above one of the smelters that included the planting of several locally adapted plant species. It also included mineral fertilization and mycorrhizal inoculation. One of the species, the Pitch pine (Pinus rigida, Mill.), is a native tree that is both tolerant of metalliferous soils and obligatorily ectomycorrhizal. This report summarizes the results of two observational studies conducted 5 years after the remediation treatment. The first study's objective was to compare ectomycorrhizal communities on treated Pitch pine saplings, with communities on naturally regenerating saplings in an adjacent non‐remediated area. The second study's objective was to determine if the composition of the fungal communities on root tips of naturally regenerating Pitch pine saplings differed with distance from the smelters. Fungal community compositions were determined using internal transcribed spacer rRNA sequences. Comparisons of sequences from the remediated and non‐remediated sites revealed that communities at the remediated sites had lower taxonomic diversity and were dominated by members of a genus in the remediation inoculant. The results of the smelter‐proximity study indicated that although fungal diversity did not differ markedly with distance from the smelters, the relative abundances of some taxa were greater on saplings growing directly above the smelters, where the soils contained highest concentrations of zinc and cadmium. [ABSTRACT FROM AUTHOR]

Published
2023
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169. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, Bosdriesz, E, Bougouffa, S, Bounova, G, Brouwer, T, Bryant, B, Calaza, M, Calderone, A, Calza, S, Capuzzi, S, Carbonell-Caballero, J, Carlin, D, Carter, H, Castagnoli, L, Celebi, R, Cesareni, G, Chang, H, Chen, G, Chen, H, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, Gestraud, P, Ghosh, S, Gillberg, J, Godoy-Lorite, A, Godynyuk, L, Godzik, A, Goldenberg, A, Gomez-Cabrero, D, Gonen, M, de Graaf, C, Gray, H, Grechkin, M, Guimera, R, Guney, E, Haibe-Kains, B, Han, Y, Hase, T, He, D, He, L, Heath, L, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Hu, Z, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, Moerbeke, M, Moo, K, Motsinger-Reif, A, Movva, R, Muraru, S, Muratov, E, Mushthofa, M, Nagarajan, N, Nakken, S, Nath, A, Neuvial, P, Newton, R, Ning, Z, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, Park, S, Pawitan, Y, Peluso, D, Pendyala, S, Peng, J, Perfetto, L, Pirro, S, Plevritis, S, Politi, R, Poon, H, Porta, E, Prellner, I, Preuer, K, Pujana, M, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden M. P., Wang D., Mason M. J., Szalai B., Bulusu K. C., Guan Y., Yu T., Kang J., Jeon M., Wolfinger R., Nguyen T., Zaslavskiy M., Abante J., Abecassis B. S., Aben N., Aghamirzaie D., Aittokallio T., Akhtari F. S., Al-lazikani B., Alam T., Allam A., Allen C., de Almeida M. P., Altarawy D., Alves V., Amadoz A., Anchang B., Antolin A. A., Ash J. R., Aznar V. R., Ba-alawi W., Bagheri M., Bajic V., Ball G., Ballester P. J., Baptista D., Bare C., Bateson M., Bender A., Bertrand D., Wijayawardena B., Boroevich K. A., Bosdriesz E., Bougouffa S., Bounova G., Brouwer T., Bryant B., Calaza M., Calderone A., Calza S., Capuzzi S., Carbonell-Caballero J., Carlin D., Carter H., Castagnoli L., Celebi R., Cesareni G., Chang H., Chen G., Chen H., Cheng L., Chernomoretz A., Chicco D., Cho K. -H., Cho S., Choi D., Choi J., Choi K., Choi M., Cock M. D., Coker E., Cortes-Ciriano I., Cserzo M., Cubuk C., Curtis C., Daele D. V., Dang C. C., Dijkstra T., Dopazo J., Draghici S., Drosou A., Dumontier M., Ehrhart F., Eid F. -E., ElHefnawi M., Elmarakeby H., van Engelen B., Engin H. B., de Esch I., Evelo C., Falcao A. O., Farag S., Fernandez-Lozano C., Fisch K., Flobak A., Fornari C., Foroushani A. B. K., Fotso D. C., Fourches D., Friend S., Frigessi A., Gao F., Gao X., Gerold J. M., Gestraud P., Ghosh S., Gillberg J., Godoy-Lorite A., Godynyuk L., Godzik A., Goldenberg A., Gomez-Cabrero D., Gonen M., de Graaf C., Gray H., Grechkin M., Guimera R., Guney E., Haibe-Kains B., Han Y., Hase T., He D., He L., Heath L. S., Hellton K. H., Helmer-Citterich M., Hidalgo M. R., Hidru D., Hill S. M., Hochreiter S., Hong S., Hovig E., Hsueh Y. -C., Hu Z., Huang J. K., Huang R. S., Hunyady L., Hwang J., Hwang T. H., Hwang W., Hwang Y., Isayev O., Don't Walk O. B., Jack J., Jahandideh S., Ji J., Jo Y., Kamola P. J., Kanev G. K., Karacosta L., Karimi M., Kaski S., Kazanov M., Khamis A. M., Khan S. A., Kiani N. A., Kim A., Kim J., Kim K., Kim S., Kim Y., Kirk P. D. W., Kitano H., Klambauer G., Knowles D., Ko M., Kohn-Luque A., Kooistra A. J., Kuenemann M. A., Kuiper M., Kurz C., Kwon M., van Laarhoven T., Laegreid A., Lederer S., Lee H., Lee J., Lee Y. W., Lepp_aho E., Lewis R., Li J., Li L., Liley J., Lim W. K., Lin C., Liu Y., Lopez Y., Low J., Lysenko A., Machado D., Madhukar N., Maeyer D. D., Malpartida A. B., Mamitsuka H., Marabita F., Marchal K., Marttinen P., Mason D., Mazaheri A., Mehmood A., Mehreen A., Michaut M., Miller R. A., Mitsopoulos C., Modos D., Moerbeke M. V., Moo K., Motsinger-Reif A., Movva R., Muraru S., Muratov E., Mushthofa M., Nagarajan N., Nakken S., Nath A., Neuvial P., Newton R., Ning Z., Niz C. D., Oliva B., Olsen C., Palmeri A., Panesar B., Papadopoulos S., Park J., Park S., Pawitan Y., Peluso D., Pendyala S., Peng J., Perfetto L., Pirro S., Plevritis S., Politi R., Poon H., Porta E., Prellner I., Preuer K., Pujana M. A., Ramnarine R., Reid J. E., Reyal F., Richardson S., Ricketts C., Rieswijk L., Rocha M., Rodriguez-Gonzalvez C., Roell K., Rotroff D., de Ruiter J. R., Rukawa P., Sadacca B., Safikhani Z., Safitri F., Sales-Pardo M., Sauer S., Schlichting M., Seoane J. A., Serra J., Shang M. -M., Sharma A., Sharma H., Shen Y., Shiga M., Shin M., Shkedy Z., Shopsowitz K., Sinai S., Skola D., Smirnov P., Soerensen I. F., Soerensen P., Song J. -H., Song S. O., Soufan O., Spitzmueller A., Steipe B., Suphavilai C., Tamayo S. P., Tamborero D., Tang J., Tanoli Z. -U. -R., Tarres-Deulofeu M., Tegner J., Thommesen L., Tonekaboni S. A. M., Tran H., Troyer E. D., Truong A., Tsunoda T., Turu G., Tzeng G. -Y., Verbeke L., Videla S., Vis D., Voronkov A., Votis K., Wang A., Wang H. -Q. H., Wang P. -W., Wang S., Wang W., Wang X., Wennerberg K., Wernisch L., Wessels L., van Westen G. J. P., Westerman B. A., White S. R., Willighagen E., Wurdinger T., Xie L., Xie S., Xu H., Yadav B., Yau C., Yeerna H., Yin J. W., Yu M., Yu M. H., Yun S. J., Zakharov A., Zamichos A., Zanin M., Zeng L., Zenil H., Zhang F., Zhang P., Zhang W., Zhao H., Zhao L., Zheng W., Zoufir A., Zucknick M., Jang I. S., Ghazoui Z., Ahsen M. E., Vogel R., Neto E. C., Norman T., Tang E. K. Y., Garnett M. J., Veroli G. Y. D., Fawell S., Stolovitzky G., Guinney J., Dry J. R., Saez-Rodriguez J., Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, Bosdriesz, E, Bougouffa, S, Bounova, G, Brouwer, T, Bryant, B, Calaza, M, Calderone, A, Calza, S, Capuzzi, S, Carbonell-Caballero, J, Carlin, D, Carter, H, Castagnoli, L, Celebi, R, Cesareni, G, Chang, H, Chen, G, Chen, H, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, Gestraud, P, Ghosh, S, Gillberg, J, Godoy-Lorite, A, Godynyuk, L, Godzik, A, Goldenberg, A, Gomez-Cabrero, D, Gonen, M, de Graaf, C, Gray, H, Grechkin, M, Guimera, R, Guney, E, Haibe-Kains, B, Han, Y, Hase, T, He, D, He, L, Heath, L, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Hu, Z, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, Moerbeke, M, Moo, K, Motsinger-Reif, A, Movva, R, Muraru, S, Muratov, E, Mushthofa, M, Nagarajan, N, Nakken, S, Nath, A, Neuvial, P, Newton, R, Ning, Z, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, Park, S, Pawitan, Y, Peluso, D, Pendyala, S, Peng, J, Perfetto, L, Pirro, S, Plevritis, S, Politi, R, Poon, H, Porta, E, Prellner, I, Preuer, K, Pujana, M, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden M. P., Wang D., Mason M. J., Szalai B., Bulusu K. C., Guan Y., Yu T., Kang J., Jeon M., Wolfinger R., Nguyen T., Zaslavskiy M., Abante J., Abecassis B. S., Aben N., Aghamirzaie D., Aittokallio T., Akhtari F. S., Al-lazikani B., Alam T., Allam A., Allen C., de Almeida M. P., Altarawy D., Alves V., Amadoz A., Anchang B., Antolin A. A., Ash J. R., Aznar V. R., Ba-alawi W., Bagheri M., Bajic V., Ball G., Ballester P. J., Baptista D., Bare C., Bateson M., Bender A., Bertrand D., Wijayawardena B., Boroevich K. A., Bosdriesz E., Bougouffa S., Bounova G., Brouwer T., Bryant B., Calaza M., Calderone A., Calza S., Capuzzi S., Carbonell-Caballero J., Carlin D., Carter H., Castagnoli L., Celebi R., Cesareni G., Chang H., Chen G., Chen H., Cheng L., Chernomoretz A., Chicco D., Cho K. -H., Cho S., Choi D., Choi J., Choi K., Choi M., Cock M. D., Coker E., Cortes-Ciriano I., Cserzo M., Cubuk C., Curtis C., Daele D. V., Dang C. C., Dijkstra T., Dopazo J., Draghici S., Drosou A., Dumontier M., Ehrhart F., Eid F. -E., ElHefnawi M., Elmarakeby H., van Engelen B., Engin H. B., de Esch I., Evelo C., Falcao A. O., Farag S., Fernandez-Lozano C., Fisch K., Flobak A., Fornari C., Foroushani A. B. K., Fotso D. C., Fourches D., Friend S., Frigessi A., Gao F., Gao X., Gerold J. M., Gestraud P., Ghosh S., Gillberg J., Godoy-Lorite A., Godynyuk L., Godzik A., Goldenberg A., Gomez-Cabrero D., Gonen M., de Graaf C., Gray H., Grechkin M., Guimera R., Guney E., Haibe-Kains B., Han Y., Hase T., He D., He L., Heath L. S., Hellton K. H., Helmer-Citterich M., Hidalgo M. R., Hidru D., Hill S. M., Hochreiter S., Hong S., Hovig E., Hsueh Y. -C., Hu Z., Huang J. K., Huang R. S., Hunyady L., Hwang J., Hwang T. H., Hwang W., Hwang Y., Isayev O., Don't Walk O. B., Jack J., Jahandideh S., Ji J., Jo Y., Kamola P. J., Kanev G. K., Karacosta L., Karimi M., Kaski S., Kazanov M., Khamis A. M., Khan S. A., Kiani N. A., Kim A., Kim J., Kim K., Kim S., Kim Y., Kirk P. D. W., Kitano H., Klambauer G., Knowles D., Ko M., Kohn-Luque A., Kooistra A. J., Kuenemann M. A., Kuiper M., Kurz C., Kwon M., van Laarhoven T., Laegreid A., Lederer S., Lee H., Lee J., Lee Y. W., Lepp_aho E., Lewis R., Li J., Li L., Liley J., Lim W. K., Lin C., Liu Y., Lopez Y., Low J., Lysenko A., Machado D., Madhukar N., Maeyer D. D., Malpartida A. B., Mamitsuka H., Marabita F., Marchal K., Marttinen P., Mason D., Mazaheri A., Mehmood A., Mehreen A., Michaut M., Miller R. A., Mitsopoulos C., Modos D., Moerbeke M. V., Moo K., Motsinger-Reif A., Movva R., Muraru S., Muratov E., Mushthofa M., Nagarajan N., Nakken S., Nath A., Neuvial P., Newton R., Ning Z., Niz C. D., Oliva B., Olsen C., Palmeri A., Panesar B., Papadopoulos S., Park J., Park S., Pawitan Y., Peluso D., Pendyala S., Peng J., Perfetto L., Pirro S., Plevritis S., Politi R., Poon H., Porta E., Prellner I., Preuer K., Pujana M. A., Ramnarine R., Reid J. E., Reyal F., Richardson S., Ricketts C., Rieswijk L., Rocha M., Rodriguez-Gonzalvez C., Roell K., Rotroff D., de Ruiter J. R., Rukawa P., Sadacca B., Safikhani Z., Safitri F., Sales-Pardo M., Sauer S., Schlichting M., Seoane J. A., Serra J., Shang M. -M., Sharma A., Sharma H., Shen Y., Shiga M., Shin M., Shkedy Z., Shopsowitz K., Sinai S., Skola D., Smirnov P., Soerensen I. F., Soerensen P., Song J. -H., Song S. O., Soufan O., Spitzmueller A., Steipe B., Suphavilai C., Tamayo S. P., Tamborero D., Tang J., Tanoli Z. -U. -R., Tarres-Deulofeu M., Tegner J., Thommesen L., Tonekaboni S. A. M., Tran H., Troyer E. D., Truong A., Tsunoda T., Turu G., Tzeng G. -Y., Verbeke L., Videla S., Vis D., Voronkov A., Votis K., Wang A., Wang H. -Q. H., Wang P. -W., Wang S., Wang W., Wang X., Wennerberg K., Wernisch L., Wessels L., van Westen G. J. P., Westerman B. A., White S. R., Willighagen E., Wurdinger T., Xie L., Xie S., Xu H., Yadav B., Yau C., Yeerna H., Yin J. W., Yu M., Yu M. H., Yun S. J., Zakharov A., Zamichos A., Zanin M., Zeng L., Zenil H., Zhang F., Zhang P., Zhang W., Zhao H., Zhao L., Zheng W., Zoufir A., Zucknick M., Jang I. S., Ghazoui Z., Ahsen M. E., Vogel R., Neto E. C., Norman T., Tang E. K. Y., Garnett M. J., Veroli G. Y. D., Fawell S., Stolovitzky G., Guinney J., Dry J. R., and Saez-Rodriguez J.

Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

Published
2019

172. Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment

Author

Chng K. R., Li C., Bertrand D., Ng A. H. Q., Kwah J. S., Low H. M., Tong C., Natrajan M., Zhang M. H., Xu L., Ko K. K. K., Ho E. X. P., Av-Shalom T. V., Teo J. W. P., Khor C. C., Danko D., Bezdan D., Afshinnekoo E., Ahsanuddin S., Bhattacharya C., Butler D. J., De Filippis F., Hecht J., Kahles A., Karasikov M., Kyrpides N. C., Leung M. H. Y., Meleshko D., Mustafa H., Mutai B., Neches R. Y., Ng A., Nieto-Caballero M., Nikolayeva O., Nikolayeva T., Png E., Sanchez J. L., Shaaban H., Sierra M. A., Tong X., Young B., Alicea J., Bhattacharyya M., Blekhman R., Castro-Nallar E., Canas A. M., Chatziefthimiou A. D., Crawford R. W., Deng Y., Desnues C., Dias-Neto E., Donnellan D., Dybwad M., Elhaik E., Ercolini D., Frolova A., Graf A. B., Green D. C., Hajirasouliha I., Hernandez M., Iraola G., Jang S., Jones A., Kelly F. J., Knights K., Labaj P. P., Lee P. K. H., Shawn L., Ljungdahl P., Lyons A., Mason-Buck G., McGrath K., Mongodin E. F., Moraes M. O., Nagarajan N., Noushmehr H., Oliveira M., Ossowski S., Osuolale O. O., Ozcan O., Paez-Espino D., Rascovan N., Richard H., Ratsch G., Schriml L. M., Semmler T., Sezerman O. U., Shi L., Song L. H., Suzuki H., Court D. S., Thomas D., Tighe S. W., Udekwu K. I., Ugalde J. A., Valentine B., Vassilev D. I., Vayndorf E., Velavan T. P., Zambrano M. M., Zhu J., Zhu S., Mason C. E., Chen S. L., Ng O. T., Marimuthu K., Ang B., Genome Institute of Singapore (GIS), Singapore University of Technology and Design (SUTD), Singapore General Hospital, National University Hospital [Singapore] (NUH), Weill Cornell Medicine [Cornell University], Cornell University [New York], Nanyang Technological University [Singapour], Tan Tock Seng Hospital, Department of Computational and Systems Biology [Singapore], Funding for this work was provided by A*STAR (N.N.), and we are grateful for support from NMRC (NMRC CGAug16C005: O.T.N. and K.M.). C.E.M. acknowledges support from the WorldQuant Foundation, the Bill and Melinda Gates Foundation (OPP1151054) and the Alfred P. Sloan Foundation (G-2015-13964). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. We would like to thank J. Gilbert for insightful comments and feedback on this work., MetaSUB Consortium: David Danko, Daniela Bezdan, Ebrahim Afshinnekoo, Sofia Ahsanuddin, Chandrima Bhattacharya, Daniel J. Butler, Kern Rei Chng, Francesca De Filippis, Jochen Hecht, Andre Kahles, Mikhail Karasikov, Nikos C. Kyrpides, Marcus H. Y. Leung, Dmitry Meleshko, Harun Mustafa, Beth Mutai, Russell Y. Neches, Amanda Ng, Marina Nieto-Caballero, Olga Nikolayeva, Tatyana Nikolayeva, Eileen Png, Jorge L. Sanchez, Heba Shaaban, Maria A. Sierra, Xinzhao Tong, Ben Young, Josue Alicea, Malay Bhattacharyya, Ran Blekhman, Eduardo Castro-Nallar, Ana M. Cañas, Aspassia D. Chatziefthimiou, Robert W. Crawford, Youping Deng, Christelle Desnues, Emmanuel Dias-Neto, Daisy Donnellan, Marius Dybwad, Eran Elhaik, Danilo Ercolini, Alina Frolova, Alexandra B. Graf, David C. Green, Iman Hajirasouliha, Mark Hernandez, Gregorio Iraola, Soojin Jang, Angela Jones, Frank J. Kelly, Kaymisha Knights, Paweł P. Łabaj, Patrick K. H. Lee, Levy Shawn, Per Ljungdahl, Abigail Lyons, Gabriella Mason-Buck, Ken McGrath, Emmanuel F. Mongodin, Milton Ozorio Moraes, Niranjan Nagarajan, Houtan Noushmehr, Manuela Oliveira, Stephan Ossowski, Olayinka O. Osuolale, Orhan Özcan, David Paez-Espino, Nicolas Rascovan, Hugues Richard, Gunnar Rätsch, Lynn M. Schriml, Torsten Semmler, Osman U. Sezerman, Leming Shi, Le Huu Song, Haruo Suzuki, Denise Syndercombe Court, Dominique Thomas, Scott W. Tighe, Klas I. Udekwu, Juan A. Ugalde, Brandon Valentine, Dimitar I. Vassilev, Elena Vayndorf, Thirumalaisamy P. Velavan, María M. Zambrano, Jifeng Zhu, Sibo Zhu & Christopher E. Mason, Weill Cornell Medicine [New York], Chng, K. R., Li, C., Bertrand, D., Ng, A. H. Q., Kwah, J. S., Low, H. M., Tong, C., Natrajan, M., Zhang, M. H., Xu, L., Ko, K. K. K., Ho, E. X. P., Av-Shalom, T. V., Teo, J. W. P., Khor, C. C., Danko, D., Bezdan, D., Afshinnekoo, E., Ahsanuddin, S., Bhattacharya, C., Butler, D. J., De Filippis, F., Hecht, J., Kahles, A., Karasikov, M., Kyrpides, N. C., Leung, M. H. Y., Meleshko, D., Mustafa, H., Mutai, B., Neches, R. Y., Ng, A., Nieto-Caballero, M., Nikolayeva, O., Nikolayeva, T., Png, E., Sanchez, J. L., Shaaban, H., Sierra, M. A., Tong, X., Young, B., Alicea, J., Bhattacharyya, M., Blekhman, R., Castro-Nallar, E., Canas, A. M., Chatziefthimiou, A. D., Crawford, R. W., Deng, Y., Desnues, C., Dias-Neto, E., Donnellan, D., Dybwad, M., Elhaik, E., Ercolini, D., Frolova, A., Graf, A. B., Green, D. C., Hajirasouliha, I., Hernandez, M., Iraola, G., Jang, S., Jones, A., Kelly, F. J., Knights, K., Labaj, P. P., Lee, P. K. H., Shawn, L., Ljungdahl, P., Lyons, A., Mason-Buck, G., Mcgrath, K., Mongodin, E. F., Moraes, M. O., Nagarajan, N., Noushmehr, H., Oliveira, M., Ossowski, S., Osuolale, O. O., Ozcan, O., Paez-Espino, D., Rascovan, N., Richard, H., Ratsch, G., Schriml, L. M., Semmler, T., Sezerman, O. U., Shi, L., Song, L. H., Suzuki, H., Court, D. S., Thomas, D., Tighe, S. W., Udekwu, K. I., Ugalde, J. A., Valentine, B., Vassilev, D. I., Vayndorf, E., Velavan, T. P., Zambrano, M. M., Zhu, J., Zhu, S., Mason, C. E., Chen, S. L., Ng, O. T., Marimuthu, K., Ang, B., and Acibadem University Dspace

Subjects
0301 basic medicine, Disease prevention, 030106 microbiology, Geographic Mapping, Drug resistance, Beds, Biology, Opportunistic Infections, Genome, General Biochemistry, Genetics and Molecular Biology, Article, Tertiary Care Centers, 03 medical and health sciences, Plasmid, Antibiotic resistance, Spatio-Temporal Analysis, Drug Resistance, Multiple, Bacterial, Drug Resistance, Bacterial, Patients' Rooms, Humans, Microbiome, Equipment and Supplies, Hospital, Genetics, Cross Infection, Infection Control, Singapore, Microbiota, General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Resistome, Disinfection, 030104 developmental biology, Metagenomics, Biofilms, Equipment Contamination, Mobilome, Microbial genetics
Abstract

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections., Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.

Published
2020

173. The energy spectrum of atmospheric neutrinos between 2 and 200 TeV with the AMANDA-II detector

Author

Abbasi, R., Abdou, Y., Abu-Zayyad, T., Adams, J., Aguilar, J.A., Ahlers, M., Andeen, K., Auffenberg, J., Bai, X., Baker, M., Barwick, S.W., Bay, R., Bazo Alba, J.L., Beattie, K., Beatty, J.J., Bechet, S., Becker, J.K., Becker, K.-H., Benabderrahmane, M.L., Berdermann, J., Berghaus, P., Berley, D., Bernardini, E., Bertrand, D., Besson, D.Z., Bissok, M., Blaufuss, E., Boersma, D.J., Bohm, C., Böser, S., Botner, O., Bradley, L., Braun, J., Buitink, S., Carson, M., Chirkin, D., Christy, B., Clem, J., Clevermann, F., Cohen, S., Colnard, C., Cowen, D.F., D’Agostino, M.V., Danninger, M., De Clercq, C., Demirörs, L., Depaepe, O., Descamps, F., Desiati, P., de Vries-Uiterweerd, G., DeYoung, T., Díaz-Vélez, J.C., Dreyer, J., Dumm, J.P., Duvoort, M.R., Ehrlich, R., Eisch, J., Ellsworth, R.W., Engdegård, O., Euler, S., Evenson, P.A., Fadiran, O., Fazely, A.R., Fedynitch, A., Feusels, T., Filimonov, K., Finley, C., Foerster, M.M., Fox, B.D., Franckowiak, A., Franke, R., Gaisser, T.K., Gallagher, J., Ganugapati, R., Geisler, M., Gerhardt, L., Gladstone, L., Glüsenkamp, T., Goldschmidt, A., Goodman, J.A., Grant, D., Griesel, T., Groß, A., Grullon, S., Gunasingha, R.M., Gurtner, M., Ha, C., Hallgren, A., Halzen, F., Han, K., Hanson, K., Helbing, K., Herquet, P., Hickford, S., Hill, G.C., Hoffman, K.D., Homeier, A., Hoshina, K., Hubert, D., Huelsnitz, W., Hülß, J.-P., Hulth, P.O., Hultqvist, K., Hussain, S., Imlay, R.L., Ishihara, A., Jacobsen, J., Japaridze, G.S., Johansson, H., Joseph, J.M., Kampert, K.-H., Kappes, A., Karg, T., Karle, A., Kelley, J.L., Kemming, N., Kenny, P., Kiryluk, J., Kislat, F., Klein, S.R., Knops, S., Köhne, J.-H., Kohnen, G., Kolanoski, H., Köpke, L., Koskinen, D.J., Kowalski, M., Kowarik, T., Krasberg, M., Krings, T., Kroll, G., Kuehn, K., Kuwabara, T., Labare, M., Lafebre, S., Laihem, K., Landsman, H., Lauer, R., Lehmann, R., Lennarz, D., Lünemann, J., Madsen, J., Majumdar, P., Maruyama, R., Mase, K., Matis, H.S., Matusik, M., Meagher, K., Merck, M., Mészáros, P., Meures, T., Middell, E., Milke, N., Montaruli, T., Morse, R., Movit, S.M., Münich, K., Nahnhauer, R., Nam, J.W., Naumann, U., Nießen, P., Nygren, D.R., Odrowski, S., Olivas, A., Olivo, M., Ono, M., Panknin, S., Paul, L., Pérez de los Heros, C., Petrovic, J., Piegsa, A., Pieloth, D., Porrata, R., Posselt, J., Price, P.B., Prikockis, M., Przybylski, G.T., Rawlins, K., Redl, P., Resconi, E., Rhode, W., Ribordy, M., Rizzo, A., Rodrigues, J.P., Roth, P., Rothmaier, F., Rott, C., Roucelle, C., Ruhe, T., Rutledge, D., Ruzybayev, B., Ryckbosch, D., Sander, H.-G., Sarkar, S., Schatto, K., Schlenstedt, S., Schmidt, T., Schneider, D., Schukraft, A., Schultes, A., Schulz, O., Schunck, M., Seckel, D., Semburg, B., Seo, S.H., Sestayo, Y., Seunarine, S., Silvestri, A., Slipak, A., Spiczak, G.M., Spiering, C., Stamatikos, M., Stanev, T., Stephens, G., Stezelberger, T., Stokstad, R.G., Stoyanov, S., Strahler, E.A., Straszheim, T., Sullivan, G.W., Swillens, Q., Taboada, I., Tamburro, A., Tarasova, O., Tepe, A., Ter-Antonyan, S., Tilav, S., Toale, P.A., Tosi, D., Turčan, D., van Eijndhoven, N., Vandenbroucke, J., Van Overloop, A., van Santen, J., Voigt, B., Walck, C., Waldenmaier, T., Wallraff, M., Walter, M., Wendt, C., Westerhoff, S., Whitehorn, N., Wiebe, K., Wiebusch, C.H., Wikström, G., Williams, D.R., Wischnewski, R., Wissing, H., Woschnagg, K., Xu, C., Xu, X.W., Yodh, G., Yoshida, S., and Zarzhitsky, P.

Published
2010
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174. Measurement of sound speed vs. depth in South Pole ice for neutrino astronomy

Author

Abbasi, R., Abdou, Y., Ackermann, M., Adams, J., Aguilar, J.A., Ahlers, M., Andeen, K., Auffenberg, J., Bai, X., Baker, M., Barwick, S.W., Bay, R., Bazo Alba, J.L., Beattie, K., Beatty, J.J., Bechet, S., Becker, J.K., Becker, K.-H., Benabderrahmane, M.L., Berdermann, J., Berghaus, P., Berley, D., Bernardini, E., Bertrand, D., Besson, D.Z., Bissok, M., Blaufuss, E., Boersma, D.J., Bohm, C., Bolmont, J., Böser, S., Botner, O., Bradley, L., Braun, J., Breder, D., Castermans, T., Chirkin, D., Christy, B., Clem, J., Cohen, S., Cowen, D.F., D’Agostino, M.V., Danninger, M., Day, C.T., De Clercq, C., Demirörs, L., Depaepe, O., Descamps, F., Desiati, P., de Vries-Uiterweerd, G., DeYoung, T., Diaz-Velez, J.C., Dreyer, J., Dumm, J.P., Duvoort, M.R., Edwards, W.R., Ehrlich, R., Eisch, J., Ellsworth, R.W., Engdegård, O., Euler, S., Evenson, P.A., Fadiran, O., Fazely, A.R., Feusels, T., Filimonov, K., Finley, C., Foerster, M.M., Fox, B.D., Franckowiak, A., Franke, R., Gaisser, T.K., Gallagher, J., Ganugapati, R., Gerhardt, L., Gladstone, L., Goldschmidt, A., Goodman, J.A., Gozzini, R., Grant, D., Griesel, T., Groß, A., Grullon, S., Gunasingha, R.M., Gurtner, M., Ha, C., Hallgren, A., Halzen, F., Han, K., Hanson, K., Hasegawa, Y., Heise, J., Helbing, K., Herquet, P., Hickford, S., Hill, G.C., Hoffman, K.D., Hoshina, K., Hubert, D., Huelsnitz, W., Hülß, J.-P., Hulth, P.O., Hultqvist, K., Hussain, S., Imlay, R.L., Inaba, M., Ishihara, A., Jacobsen, J., Japaridze, G.S., Johansson, H., Joseph, J.M., Kampert, K.-H., Kappes, A., Karg, T., Karle, A., Kelley, J.L., Kenny, P., Kiryluk, J., Kislat, F., Klein, S.R., Klepser, S., Knops, S., Kohnen, G., Kolanoski, H., Köpke, L., Kowalski, M., Kowarik, T., Krasberg, M., Kuehn, K., Kuwabara, T., Labare, M., Lafebre, S., Laihem, K., Landsman, H., Lauer, R., Leich, H., Lennarz, D., Lucke, A., Lundberg, J., Lünemann, J., Madsen, J., Majumdar, P., Maruyama, R., Mase, K., Matis, H.S., McParland, C.P., Meagher, K., Merck, M., Mészáros, P., Middell, E., Milke, N., Miyamoto, H., Mohr, A., Montaruli, T., Morse, R., Movit, S.M., Münich, K., Nahnhauer, R., Nam, J.W., Nießen, P., Nygren, D.R., Odrowski, S., Olivas, A., Olivo, M., Ono, M., Panknin, S., Patton, S., Pérez de los Heros, C., Petrovic, J., Piegsa, A., Pieloth, D., Pohl, A.C., Porrata, R., Potthoff, N., Price, P.B., Prikockis, M., Przybylski, G.T., Rawlins, K., Redl, P., Resconi, E., Rhode, W., Ribordy, M., Rizzo, A., Rodrigues, J.P., Roth, P., Rothmaier, F., Rott, C., Roucelle, C., Rutledge, D., Ryckbosch, D., Sander, H.-G., Sarkar, S., Satalecka, K., Schlenstedt, S., Schmidt, T., Schneider, D., Schukraft, A., Schulz, O., Schunck, M., Seckel, D., Semburg, B., Seo, S.H., Sestayo, Y., Seunarine, S., Silvestri, A., Slipak, A., Spiczak, G.M., Spiering, C., Stamatikos, M., Stanev, T., Stephens, G., Stezelberger, T., Stokstad, R.G., Stoufer, M.C., Stoyanov, S., Strahler, E.A., Straszheim, T., Sulanke, K.-H., Sullivan, G.W., Swillens, Q., Taboada, I., Tarasova, O., Tepe, A., Ter-Antonyan, S., Terranova, C., Tilav, S., Tluczykont, M., Toale, P.A., Tosi, D., Turčan, D., van Eijndhoven, N., Vandenbroucke, J., Van Overloop, A., Vogt, C., Voigt, B., Walck, C., Waldenmaier, T., Walter, M., Wendt, C., Westerhoff, S., Whitehorn, N., Wiebusch, C.H., Wiedemann, A., Wikström, G., Williams, D.R., Wischnewski, R., Wissing, H., Woschnagg, K., Xu, X.W., Yodh, G., and Yoshida, S.

Published
2010
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175. Calibration and characterization of the IceCube photomultiplier tube

Author

Abbasi, R., Abdou, Y., Abu-Zayyad, T., Adams, J., Aguilar, J.A., Ahlers, M., Andeen, K., Auffenberg, J., Bai, X., Baker, M., Barwick, S.W., Bay, R., Bazo Alba, J.L., Beattie, K., Beatty, J.J., Bechet, S., Becker, J.K., Becker, K.-H., Benabderrahmane, M.L., Berdermann, J., Berghaus, P., Berley, D., Bernardini, E., Bertrand, D., Besson, D.Z., Bissok, M., Blaufuss, E., Boersma, D.J., Bohm, C., Botner, O., Bradley, L., Braun, J., Buitink, S., Carson, M., Chirkin, D., Christy, B., Clem, J., Cohen, S., Colnard, C., Cowen, D.F., D’Agostino, M.V., Danninger, M., De Clercq, C., Demirörs, L., Depaepe, O., Descamps, F., Desiati, P., de Vries-Uiterweerd, G., DeYoung, T., Díaz-Vélez, J.C., Dreyer, J., Dumm, J.P., Duvoort, M.R., Ehrlich, R., Eisch, J., Ellsworth, R.W., Engdegård, O., Euler, S., Evenson, P.A., Fadiran, O., Fazely, A.R., Feusels, T., Filimonov, K., Finley, C., Foerster, M.M., Fox, B.D., Franckowiak, A., Franke, R., Gaisser, T.K., Gallagher, J., Ganugapati, R., Geisler, M., Gerhardt, L., Gladstone, L., Goldschmidt, A., Goodman, J.A., Grant, D., Griesel, T., Groß, A., Grullon, S., Gunasingha, R.M., Gurtner, M., Ha, C., Hallgren, A., Halzen, F., Han, K., Hanson, K., Hasegawa, Y., Haugen, J., Helbing, K., Herquet, P., Hickford, S., Hill, G.C., Hoffman, K.D., Homeier, A., Hoshina, K., Hubert, D., Huelsnitz, W., Hülß, J.-P., Hulth, P.O., Hultqvist, K., Hussain, S., Imlay, R.L., Inaba, M., Ishihara, A., Jacobsen, J., Japaridze, G.S., Johansson, H., Joseph, J.M., Kampert, K.-H., Kappes, A., Karg, T., Karle, A., Kelley, J.L., Kemming, N., Kenny, P., Kiryluk, J., Kislat, F., Kitamura, N., Klein, S.R., Knops, S., Kohnen, G., Kolanoski, H., Köpke, L., Koskinen, D.J., Kowalski, M., Kowarik, T., Krasberg, M., Krings, T., Kroll, G., Kuehn, K., Kuwabara, T., Labare, M., Lafebre, S., Laihem, K., Landsman, H., Lauer, R., Laundrie, A., Lehmann, R., Lennarz, D., Lünemann, J., Madsen, J., Majumdar, P., Maruyama, R., Mase, K., Matis, H.S., Matusik, M., Meagher, K., Merck, M., Mészáros, P., Meures, T., Middell, E., Milke, N., Miyamoto, H., Montaruli, T., Morse, R., Movit, S.M., Nahnhauer, R., Nam, J.W., Naumann, U., Nießen, P., Nygren, D.R., Odrowski, S., Olivas, A., Olivo, M., Ono, M., Panknin, S., Paul, L., Pérez de los Heros, C., Petrovic, J., Piegsa, A., Pieloth, D., Pohl, A.C., Porrata, R., Posselt, J., Price, P.B., Prikockis, M., Przybylski, G.T., Rawlins, K., Redl, P., Resconi, E., Rhode, W., Ribordy, M., Rizzo, A., Robl, P., Rodrigues, J.P., Roth, P., Rothmaier, F., Rott, C., Roucelle, C., Rutledge, D., Ruzybayev, B., Ryckbosch, D., Sander, H.-G., Sandstrom, P., Sarkar, S., Schatto, K., Schlenstedt, S., Schmidt, T., Schneider, D., Schukraft, A., Schultes, A., Schulz, O., Schunck, M., Seckel, D., Semburg, B., Seo, S.H., Sestayo, Y., Seunarine, S., Silvestri, A., Slipak, A., Spiczak, G.M., Spiering, C., Stamatikos, M., Stanev, T., Stephens, G., Stezelberger, T., Stokstad, R.G., Stoyanov, S., Strahler, E.A., Straszheim, T., Sullivan, G.W., Swillens, Q., Taboada, I., Tamburro, A., Tarasova, O., Tepe, A., Ter-Antonyan, S., Terranova, C., Tilav, S., Toale, P.A., Tosi, D., Turčan, D., van Eijndhoven, N., Vandenbroucke, J., Van Overloop, A., van Santen, J., Voigt, B., Wahl, D., Walck, C., Waldenmaier, T., Wallraff, M., Walter, M., Wendt, C., Westerhoff, S., Whitehorn, N., Wiebe, K., Wiebusch, C.H., Wikström, G., Williams, D.R., Wischnewski, R., Wissing, H., Woschnagg, K., Xu, C., Xu, X.W., Yodh, G., Yoshida, S., and Zarzhitsky, P.

Published
2010
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180. Abstract 12020: Heterogeneity and Plasticity of Cardiac Fibroblasts Governing Reparative Lymphangiogenesis After Myocardial Infarction: A New Therapeutic Approach for Heart Failure

Author

Matsuoka, Yuimi, primary, Segard, Bertrand D, additional, Imamura, Tomomi, additional, Kimura, Kodai, additional, Ikeda, Ayana, additional, Matsuyama, Makoto, additional, Arai, Mami, additional, Machino, Takeshi, additional, Sato, Akira, additional, Murakoshi, Nobuyuki, additional, and Iwamiya, Takahiro, additional

Published
2021
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182. Tapering of Etanercept is feasible in patients with Rheumatoid Arthritis in sustained remission: a pragmatic randomized controlled trial

Author

Bertrand, D, primary, Stouten, V, additional, De Cock, D, additional, Pazmino, S, additional, Doumen, M, additional, de Wergifosse, I, additional, Joly, J, additional, Badot, V, additional, Corluy, L, additional, Hoffman, I, additional, Taelman, V, additional, De Knop, K, additional, Geens, E, additional, Langenaken, C, additional, Lenaerts, JL, additional, Lenaerts, J, additional, Walschot, M, additional, Mannaerts, J, additional, Westhovens, R, additional, and Verschueren, P, additional

Published
2021
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183. When results matter: reliable creatinine concentrations in hyperbilirubinemia patients

Author

Bertrand D. van Zelst, Roseri J.A.C. Roelofsen-de Beer, Christian Ramakers, Yolanda B. de Rijke, Aram B Vroling, and Clinical Chemistry

Subjects
Creatinine, medicine.medical_specialty, business.industry, Bilirubin, Biochemistry (medical), Clinical Biochemistry, Limits of agreement, General Medicine, Gastroenterology, chemistry.chemical_compound, chemistry, Tandem Mass Spectrometry, Internal medicine, Lc ms ms, Humans, Medicine, business, Blood Chemical Analysis, Chromatography, Liquid, Hyperbilirubinemia
Abstract

Background Failure to report a creatinine concentration, especially in icteric patients who are eligible for a liver transplant, can result in a life-threatening situation. We assessed the influence of bilirubin interference on several creatinine assays and investigated ways to circumvent icteric interference without interfering with our normal automated sample logistics. Methods Using icteric patient sera (total bilirubin >255 μmol/L) we determined creatinine concentrations using an enzymatic and Jaffé assay (Roche Diagnostics) in both normal (i.e. undiluted) and decreased mode (i.e. diluted) as well as an enzyme-coupled amperometric assay on a Radiometer ABL837 FLEX analyzer. Creatinine concentrations from the five methods were compared with an in-house developed LC-MS/MS method. Passing and Bablok (proportional and constant bias) as well as difference plot parameters (bias and 95% limits of agreement [LoA]) were calculated. Interferograph-based regression analysis of the enzymatic and Jaffé results was used to investigate if such an approach could be used to report corrected creatinine concentrations in icteric patient sera. Results In icteric patient sera the enzyme-coupled amperometric assay was hardly influenced by icteric interference as shown by a difference plot bias of −1.5% (95% LoA −11.6 to +8.5%). The undiluted Jaffé method had a bias of −1.4% with a very broad 95% LoA (−35.1 to +32.2%) emphasizing the poor specificity of this method. The undiluted enzymatic method had the largest bias (−13.4%, 95% LoA −35.8 to +9.0%). Diluting sera in the enzymatic method did not improve the bias (−10.5%, 95% LoA −25.4 to 4.4%), while diluting the Jaffé method resulted in a bias increase (+11.4%, 95% LoA −14.7 to 37.5%). Using interferograph-based regression analysis we were able to reliably correct enzymatic creatinine concentrations in 97 out of 100 icteric patient sera. Conclusions Analytically, quantifying creatinine in icteric sera using the Radiometer ABL837 FLEX analyzer is the method of choice within our laboratory. However, not all laboratories are equipped with this method and even if available, the limited number of highly icteric patient sera makes this method costly. For those laboratories using the Roche enzymatic method, mathematically correcting an icteric creatinine concentration using an interferograph based on an LC-MS/MS reference method is a suitable alternative to report reliable creatinine results in icteric patients.

Published
2019

184. Association between methylation potential and nutrient metabolism throughout the reproductive cycle of sows

Author

Bertrand D. van Zelst, Karolien Langendries, Geert Janssens, Sam Millet, Miriam Van Riet, and Clinical Chemistry

Subjects
Litter (animal), Homocysteine, Swine, 040301 veterinary sciences, Biology, 0403 veterinary science, Andrology, chemistry.chemical_compound, Food Animals, Pregnancy, Lactation, Follicular phase, Blood plasma, medicine, Animals, Weaning, Methionine, Body Weight, 0402 animal and dairy science, Nutrients, 04 agricultural and veterinary sciences, Methylation, DNA Methylation, Animal Feed, 040201 dairy & animal science, Diet, medicine.anatomical_structure, chemistry, Body Composition, Animal Nutritional Physiological Phenomena, Female, Animal Science and Zoology
Abstract

DNA methylation is an important epigenetic strategy for embryo development and survival. The one-carbon metabolism can be disturbed by inadequate provision of dietary methyl donors. Because of the continuous selection for larger litters, it is relevant to explore if highly prolific sows might encounter periods of methyl donor deficiency throughout their reproductive cycles. This study, therefore, assesses the fluctuation(s) in methylation potential (MP) and aims to link possible methyl donor deficiencies to nutrient metabolism. In total, 15 hybrid sows were followed from weaning of the previous reproductive cycle (d-5) to weaning of the present cycle. Blood samples were taken at d-5, 0, 21, 42, 63, 84 and d108 of gestation, the day of parturition (d115), two weeks of lactation (d129) and at weaning (d143). Blood plasma samples were analysed for S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), free methionine, free glycine, acetylcarnitine and 3-hydroxybutyrylcarnitine. Serum samples were analysed for urea and creatinine. Generally, MP (i.e. ratio SAM:SAH) increased throughout gestation (p = 0.009), but strongly fluctuated in the period around parturition and weaning. From d108 to parturition, absolute plasma levels of SAM (p < 0.001), SAH (p = 0.031) and methionine (p = 0.001) increased. The first two weeks of lactation were characterised by an increase in MP (p = 0.039) due to a remaining high value of SAM and a distinct decrease in SAH (p = 0.008). During the last two weeks of lactation, MP decreased (p = 0.038) due to a decrease in SAM (p < 0.001) and a stable value for SAH. The methylation reactions seem to continue after weaning, a period crucial for the follicular and embryonic development of the subsequent litter. This study thus demonstrates that the methylation status fluctuates substantially throughout a sow's reproductive cycle, and further research is needed to identify the factors affecting methylation status.

Published
2019

187. The IceCube data acquisition system: Signal capture, digitization, and timestamping

Author

Abbasi, R., Ackermann, M., Adams, J., Ahlers, M., Ahrens, J., Andeen, K., Auffenberg, J., Bai, X., Baker, M., Barwick, S.W., Bay, R., Bazo Alba, J.L., Beattie, K., Becka, T., Becker, J.K., Becker, K.-H., Berghaus, P., Berley, D., Bernardini, E., Bertrand, D., Besson, D.Z., Bingham, B., Blaufuss, E., Boersma, D.J., Bohm, C., Bolmont, J., Böser, S., Botner, O., Braun, J., Breeder, D., Burgess, T., Carithers, W., Castermans, T., Chen, H., Chirkin, D., Christy, B., Clem, J., Cowen, D.F., D’Agostino, M.V., Danninger, M., Davour, A., Day, C.T., Depaepe, O., De Clercq, C., Demirörs, L., Descamps, F., Desiati, P., de Vries-Uiterweerd, G., DeYoung, T., Diaz-Velez, J.C., Dreyer, J., Dumm, J.P., Duvoort, M.R., Edwards, W.R., Ehrlich, R., Eisch, J., Ellsworth, R.W., Engdegård, O., Euler, S., Evenson, P.A., Fadiran, O., Fazely, A.R., Feusels, T., Filimonov, K., Finley, C., Foerster, M.M., Fox, B.D., Franckowiak, A., Franke, R., Gaisser, T.K., Gallagher, J., Ganugapati, R., Gerhardt, L., Gladstone, L., Glowacki, D., Goldschmidt, A., Goodman, J.A., Gozzini, R., Grant, D., Griesel, T., Groß, A., Grullon, S., Gunasingha, R.M., Gurtner, M., Ha, C., Hallgren, A., Halzen, F., Han, K., Hanson, K., Hardtke, R., Hasegawa, Y., Haugen, J., Hays, D., Heise, J., Helbing, K., Hellwig, M., Herquet, P., Hickford, S., Hill, G.C., Hodges, J., Hoffman, K.D., Hoshina, K., Hubert, D., Huelsnitz, W., Hughey, B., Hülß, J.-P., Hulth, P.O., Hultqvist, K., Hussain, S., Imlay, R.L., Inaba, M., Ishihara, A., Jacobsen, J., Japaridze, G.S., Johansson, H., Jones, A., Joseph, J.M., Kampert, K.-H., Kappes, A., Karg, T., Karle, A., Kawai, H., Kelley, J.L., Kiryluk, J., Kislat, F., Klein, S.R., Kleinfelder, S., Klepser, S., Kohnen, G., Kolanoski, H., Köpke, L., Kowalski, M., Kowarik, T., Krasberg, M., Kuehn, K., Kujawski, E., Kuwabara, T., Labare, M., Laihem, K., Landsman, H., Lauer, R., Laundrie, A., Leich, H., Leier, D., Lewis, C., Lucke, A., Ludvig, J., Lundberg, J., Lünemann, J., Madsen, J., Maruyama, R., Mase, K., Matis, H.S., McParland, C.P., Meagher, K., Meli, A., Merck, M., Messarius, T., Mészáros, P., Minor, R.H., Miyamoto, H., Mohr, A., Mokhtarani, A., Montaruli, T., Morse, R., Movit, S.M., Münich, K., Muratas, A., Nahnhauer, R., Nam, J.W., Nießen, P., Nygren, D.R., Odrowski, S., Olivas, A., Olivo, M., Ono, M., Panknin, S., Patton, S., Pérez de los Heros, C., Petrovic, J., Piegsa, A., Pieloth, D., Pohl, A.C., Porrata, R., Potthoff, N., Pretz, J., Price, P.B., Przybylski, G.T., Rawlins, K., Razzaque, S., Redl, P., Resconi, E., Rhode, W., Ribordy, M., Rizzo, A., Robbins, W.J., Rodrigues, J.P., Roth, P., Rothmaier, F., Rott, C., Roucelle, C., Rutledge, D., Ryckbosch, D., Sander, H.-G., Sarkar, S., Satalecka, K., Sandstrom, P., Schlenstedt, S., Schmidt, T., Schneider, D., Schulz, O., Seckel, D., Semburg, B., Seo, S.H., Sestayo, Y., Seunarine, S., Silvestri, A., Smith, A.J., Song, C., Sopher, J.E., Spiczak, G.M., Spiering, C., Stanev, T., Stezelberger, T., Stokstad, R.G., Stoufer, M.C., Stoyanov, S., Strahler, E.A., Straszheim, T., Sulanke, K.-H., Sullivan, G.W., Swillens, Q., Taboada, I., Tarasova, O., Tepe, A., Ter-Antonyan, S., Tilav, S., Tluczykont, M., Toale, P.A., Tosi, D., Turčan, D., van Eijndhoven, N., Vandenbroucke, J., Van Overloop, A., Viscomi, V., Vogt, C., Voigt, B., Vu, C.Q., Wahl, D., Walck, C., Waldenmaier, T., Waldmann, H., Walter, M., Wendt, C., Westerhof, S., Whitehorn, N., Wharton, D., Wiebusch, C.H., Wiedemann, C., Wikström, G., Williams, D.R., Wischnewski, R., Wissing, H., Woschnagg, K., Xu, X.W., Yodh, G., and Yoshida, S.

Published
2009
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194. Tapering of Etanercept is feasible in patients with Rheumatoid Arthritis in sustained remission: a pragmatic randomized controlled trial.

Author

Bertrand, D, Stouten, V, De Cock, D, Pazmino, S, Doumen, M, de Wergifosse, I, Joly, J, Badot, V, Corluy, L, Hoffman, I, Taelman, V, De Knop, K, Geens, E, Langenaken, C, Lenaerts, JL, Lenaerts, J, Walschot, M, Mannaerts, J, Westhovens, R, and Verschueren, P

Abstract

In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. Patients with RA in 28-joint Disease Activity Score (DAS28) remission (≥ 6 months) and treated with etanercept 50 mg weekly (≥ 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28–C-reactive protein (CRP) ≥ 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0–6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission. [ABSTRACT FROM AUTHOR]

Published
2022
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197. Critical Assessment of Metagenome Interpretation - the second round of challenges

Author

Meyer, F., primary, Fritz, A., additional, Deng, Z.-L., additional, Koslicki, D., additional, Gurevich, A., additional, Robertson, G., additional, Alser, M., additional, Antipov, D., additional, Beghini, F., additional, Bertrand, D., additional, Brito, J. J., additional, Brown, C.T., additional, Buchmann, J., additional, Buluç, A., additional, Chen, B., additional, Chikhi, R., additional, Clausen, P. T., additional, Cristian, A., additional, Dabrowski, P. W., additional, Darling, A. E., additional, Egan, R., additional, Eskin, E., additional, Georganas, E., additional, Goltsman, E., additional, Gray, M. A., additional, Hansen, L. H., additional, Hofmeyr, S., additional, Huang, P., additional, Irber, L., additional, Jia, H., additional, Jørgensen, T. S., additional, Kieser, S. D., additional, Klemetsen, T., additional, Kola, A., additional, Kolmogorov, M., additional, Korobeynikov, A., additional, Kwan, J., additional, LaPierre, N., additional, Lemaitre, C., additional, Li, C., additional, Limasset, A., additional, Malcher-Miranda, F., additional, Mangul, S., additional, Marcelino, V. R., additional, Marchet, C., additional, Marijon, P., additional, Meleshko, D., additional, Mende, D. R., additional, Milanese, A., additional, Nagarajan, N., additional, Nissen, J., additional, Nurk, S., additional, Oliker, L., additional, Paoli, L., additional, Peterlongo, P., additional, Piro, V. C., additional, Porter, J. S., additional, Rasmussen, S., additional, Rees, E. R., additional, Reinert, K., additional, Renard, B., additional, Robertsen, E. M., additional, Rosen, G. L., additional, Ruscheweyh, H.-J., additional, Sarwal, V., additional, Segata, N., additional, Seiler, E., additional, Shi, L., additional, Sun, F., additional, Sunagawa, S., additional, Sørensen, S. J., additional, Thomas, A., additional, Tong, C., additional, Trajkovski, M., additional, Tremblay, J., additional, Uritskiy, G., additional, Vicedomini, R., additional, Wang, Zi., additional, Wang, Zhe., additional, Wang, Zho., additional, Warren, A., additional, Willassen, N. P., additional, Yelick, K., additional, You, R., additional, Zeller, G., additional, Zhao, Z., additional, Zhu, S., additional, Zhu, J., additional, Garrido-Oter, R., additional, Gastmeier, P., additional, Hacquard, S., additional, Häußler, S., additional, Khaledi, A., additional, Maechler, F., additional, Mesny, F., additional, Radutoiu, S., additional, Schulze-Lefert, P., additional, Smit, N., additional, Strowig, T., additional, Bremges, A., additional, Sczyrba, A., additional, and McHardy, A. C., additional

Published
2021
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198. Global DNA (hydroxy)methylation is stable over time under several storage conditions and temperatures

Author

Natanja Oosterom, Helen R. Gosselt, Sandra G. Heil, Robert de Jonge, Pieter H. Griffioen, Bertrand D. van Zelst, Clinical Chemistry, Laboratory Medicine, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
0301 basic medicine, DNA Hydroxymethylation, Cancer Research, epigenome, classification: DNA methylation, Biology, Tandem mass spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, SDG 3 - Good Health and Well-being, chromatography liquid, tandem mass spectrometry, Humans, Epigenetics, Molecular Biology, Cryopreservation, DNA methylation, Blood Cells, Chromatography liquid, Methylation, Molecular biology, 030104 developmental biology, chemistry, Blood Preservation, 030220 oncology & carcinogenesis, DNA, Research Article, Research Paper
Abstract

Background: Epigenetic markers are often quantified and related to disease in stored samples. While, effects of storage on stability of these markers have not been thoroughly examined. In this longitudinal study, we investigated the influence of storage time, material, temperature, and freeze-thaw cycles on stability of global DNA (hydroxy)methylation. Methods: EDTA blood was collected from 90 individuals. Blood (n = 30, group 1) and extracted DNA (n = 30, group 2) were stored at 4°C, −20°C and −80°C for 0, 1 (endpoint blood 4°C), 6, 12 or 18 months. Additionally, freeze-thaw cycles of blood and DNA samples (n = 30, group 3) were performed over three days. Global DNA methylation and hydroxymethylation (mean ± SD) were quantified using liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS) with between-run precision of 2.8% (methylation) and 6.3% (hydroxymethylation). Effects on stability were assessed using linear mixed models. Results: global DNA methylation was stable over 18 months in blood at −20°C and −80°C and DNA at 4°C and −80°C. However, at 18 months DNA methylation from DNA stored at −20°C relatively decreased −6.1% compared to baseline. Global DNA hydroxymethylation was more stable in DNA samples compared to blood, independent of temperature (p = 0.0131). Stability of global DNA methylation and hydroxymethylation was not affected up to three freeze – thaw cycles. Conclusion: Global DNA methylation and hydroxymethylation stored as blood and DNA can be used for epigenetic studies. The relevance of small differences occuring during storage depend on the expected effect size and research question.

Published
2021

199. Global DNA (hydroxy)methylation is stable over time under several storage conditions and temperatures

Author

Gosselt, Helen R., Griffioen, Pieter H., van Zelst, Bertrand D., Oosterom, Natanja, de Jonge, Robert, Heil, Sandra G., Gosselt, Helen R., Griffioen, Pieter H., van Zelst, Bertrand D., Oosterom, Natanja, de Jonge, Robert, and Heil, Sandra G.

Abstract

Background: Epigenetic markers are often quantified and related to disease in stored samples. While, effects of storage on stability of these markers have not been thoroughly examined. In this longitudinal study, we investigated the influence of storage time, material, temperature, and freeze-thaw cycles on stability of global DNA (hydroxy)methylation. Methods: EDTA blood was collected from 90 individuals. Blood (n = 30, group 1) and extracted DNA (n = 30, group 2) were stored at 4°C, −20°C and −80°C for 0, 1 (endpoint blood 4°C), 6, 12 or 18 months. Additionally, freeze-thaw cycles of blood and DNA samples (n = 30, group 3) were performed over three days. Global DNA methylation and hydroxymethylation (mean ± SD) were quantified using liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS) with between-run precision of 2.8% (methylation) and 6.3% (hydroxymethylation). Effects on stability were assessed using linear mixed models. Results: global DNA methylation was stable over 18 months in blood at −20°C and −80°C and DNA at 4°C and −80°C. However, at 18 months DNA methylation from DNA stored at −20°C relatively decreased −6.1% compared to baseline. Global DNA hydroxymethylation was more stable in DNA samples compared to blood, independent of temperature (p = 0.0131). Stability of global DNA methylation and hydroxymethylation was not affected up to three freeze–thaw cycles. Conclusion: Global DNA methylation and hydroxymethylation stored as blood and DNA can be used for epigenetic studies. The relevance of small differences occuring during storage depend on the expected effect size and research question.

Published
2021

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