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107. Risk factors for injury in high school football players

Author

Turbeville, Sean D., Cowan, Linda D., Owen, Willis L., Asal, Nabih R., and Anderson, Mark A.

Subjects
Football players -- Injuries, Teenage athletes -- Injuries, Wounds and injuries -- Prevention, Health, Sports and fitness
Published
2003

108. Risk factors for injury in middle school football players

Author

Turbeville, Sean D., Cowan, Linda D., Asal, Nabih R., Owen, Willis L., and Anderson, Mark A.

Subjects
Junior high school students -- Injuries, Football players -- Injuries, Health, Sports and fitness
Published
2003

113. Kinetic study of folding and misfolding of diacylglycerol kinase in model membranes

Author

Nagy, Joanna K., Lonzer, Willis L., and Sanders, Charles R.

Subjects
Biochemistry -- Research, Glycerol kinase -- Physiological aspects, Membrane proteins -- Research, Protein folding -- Research, Cystic fibrosis -- Causes of, Biological sciences, Chemistry
Abstract

Research has been conducted on the folding and misfolding of the membrane proteins. The kinetics of the membrane insertion and folding of the homotrimeric integral membrane protein diacylglycerol kinase has been investigated.

Published
2001

118. Teaching Biology through Creative Writing.

Author

Kirkland, Willis L.

Abstract

Describes a course that integrates abstract biological concepts into narrative contexts to make science come alive for apprehensive nonmajors. Simple and creative methods of conveying information--such as humorous, light-hearted analogies to lighten the mood--reduce the abstractness of the material and alone can effectively relieve anxiety and facilitate learning. Students then become active learners through creative writing assignments. (PVD)

Published
1997

119. Reconstitutive refolding of diacylglycerol kinase, an integral membrane protein

Author

Gorzelle, Bonnie M., Nagy, Joanna K., Oxenoid, Kirill, Lonzer, Willis L., Cafiso, David S., and Sanders, Charles R.

Subjects
Protein folding -- Research, Protein kinases -- Research, Membrane proteins -- Research, Biological sciences, Chemistry
Abstract

Researchers report a technique for refolding misfolded diacylglycerol kinase. The activity of this membrane protein increased when it was refolded. Misfolded membrane proteins have been linked to some diseases.

Published
1999

122. Effect of Experience on Medical Students' Attitudes toward Animal Laboratories in Pharmacology Education.

Author

Willis, L. R. and Besch, Henry R.

Abstract

Students (n=143) at the Indiana University School of Medicine were surveyed--before and after pharmacology laboratory experiences using dogs--for their assessments of educational and moral aspects of animal laboratories. Most students indicated that the laboratory experiences did not involve immoral use of animals and were preferable to alternatives that did not use animals. (JDD)

Published
1995

129. Does money still matter?

Author

Peterson, Willis L.

Subjects
Quantity theory of money -- Research, Monetary policy -- Research, Fiscal policy -- Research, Political science
Abstract

The validity of the quantity theory, which states that an empirical relationship exists between money and economic activity, has been attacked by economists such as Kenneth Kuttner, Benjamin Friedman, Robert Litterman and Laurence Weiss. Statistical analysis of economic indicators would show that both fiscal and monetary policies are unnecessary in combating problems such as unemployment.

Published
1996

131. Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Author

Wang, X. (Xinzhu), Nijman, R.G. (Ruud), Camuzeaux, S. (Stephane), Sands, C. (Caroline), Jackson, H. (Heather), Kaforou, M. (Myrsini), Emonts, M. (Marieke), Herberg, J.A. (Jethro A.), MacOnochie, I.K. (Ian), Carrol, E.D. (Enitan), Paulus, S.C. (Stephane C.), Zenz, W. (Werner), Flier, M. (Michiel) van der, Groot, R. (Ronald) de, Martinon-Torres, F. (Federico), Schlapbach, L.J. (Luregn), Pollard, A.J. (Andrew J.), Fink, C. (Colin), Kuijpers, T.T. (Taco T.), Anderson, S. (Suzanne), Lewis, M.R. (Matthew R.), Levin, M. (Michael), McClure, M. (Myra), Gormley, S. (Stuart), Hamilton, S. (Shea), Hourmat, B. (Bernardo), Hoggart, C. (Clive), Sancho-Shimizu, V. (Vanessa), Wright, V.J. (Victoria), Abdulla, A. (Amina), Agapow, P. (Paul), Bartlett, M. (Maeve), Bellos, E. (Evangelos), Eleftherohorinou, H. (Hariklia), Galassini, R. (Rachel), Inwald, D. (David), Mashbat, M. (Meg), Menikou, S. (Stefanie), Mustafa, S. (Sobia), Nadel, S. (Simon), Rahman, R. (Rahmeen), Thakker, C. (Clare), Coin, L.M.J. (Lachlan M. J.), Bokhandi, S. (S.), Power, S. (Sue), Barham, H. (Heather), Pathan, D.N. (Dr N), Ridout, J. (Jenna), White, D. (Deborah), Thurston, S. (Sarah), Faust, D. (Dominik), Patel, S.Y. (Smita Y.), McCorkell, J. (Jenni), Davies, P. (P.), Crate, L. (Lindsey), Navarra, H. (Helen), Carter, S. (Stephanie), Ramaiah, R. (R.), Patel, R. (Rekha), Tuffrey, C. (Catherine), Gribbin, A. (Andrew), McCready, S. (Sharon), Peters, M. (Mark), Hardy, K. (Katie), Standing, F. (Fran), O’Neill, L. (Lauren), Abelake, E. (Eugenia), Deep, A. (Akash), Nsirim, E. (Eniola), Willis, L. (Louise), Young, Z. (Zoe), Royad, C. (C.), White, S. (Sonia), Fortune, P.M. (P. M.), Hudnott, P. (Phil), González, F.Á. (Fernando Álvez), Barral-Arca, R. (Ruth), Cebey-López, M. (Miriam), Curras-Tuala, M.J. (María José), García, N. (Natalia), Vicente, L.G. (Luisa García), Gómez-Carballa, A. (Alberto), Rial, J.G. (Jose Gómez), Beiroa, A.G. (Andrea Grela), Grande, A.J. (Antonio Justicia), Iglesias, P.L. (Pilar Leboráns), Santos, A.E.M. (Alba Elena Martínez), Martinón-Torres, F. (Federico), MartinónTorres, N. (Nazareth), Sánchez, J.M.M. (José María Martinón), Gutiérrez, B.M. (Beatriz Morillo), Pérez, B.M. (Belén Mosquera), Pacheco, P.O. (Pablo Obando), Pardo-Seco, J. (Jacobo), Pischedda, S. (Sara), RiveroCalle, I. (Irene), Rodríguez-Tenreiro, C. (Carmen), Redondo-Collazo, L. (Lorenzo), Ellacuriagal, A.S. (Antonio Salas), Fernández, S.S. (Sonia Serén), Silva, M.S.P. (María del Sol Porto), Vega, A. (Ana), Trillo, L.V. (Lucía Vilanova), Salas, A. (Antonio), Reyes, S.B. (Susana Beatriz), León, M.C.L. (María Cruz León), Mingorance, Á.N. (Álvaro Navarro), Barrios, X.G. (Xavier Gabaldó), Vergara, E.O. (Eider Oñate), Torre, A.C. (Andrés Concha), Vivanco, A. (Ana), Fernández, R. (Reyes), Sánchez, F.G. (Francisco Giménez), Forte, M.S. (Miguel Sánchez), Rojo, P. (Pablo), Contreras, J.R. (J. Ruiz), Palacios, A. (Alba), Ibarrondo, C.E. (Cristina Epalza), Cooke, E.F. (Elizabeth Fernández), Navarro, M. (Marisa), Álvarez, C.Á. (Cristina Álvarez), Lozano, M.J. (María José), Carreras, E. (Eduardo), Sanagustín, S.B. (Sonia Brió), Neth, O. (Olaf), Padilla, M.C.M. (Ma del Carmen Martínez), Tato, L.M.P. (Luis Manuel Prieto), Guillén, S. (Sara), Silveira, L.F. (Laura Fernández), Moreno, D. (David), van Furth, A.M.T. (A. M. Tutu), Boeddha, N.P. (Navin), Driessen, G.J.A. (Gertjan), Hazelzet, J.A. (Jan), Pajkrt, D. (D.), Sanders, E.A.M. (E. A.M.), van de Beek, D. (D.), Ende, A. (A.) van der, Philipsen, H.L.A. (H. L.A.), Adeel, A.O.A. (A. O.A.), Breukels, M.A. (M. A.), Brinkman, D.M.C., de Korte, C.C.M.M. (C. C.M.M.), de Vries, E. (E.), Waal, W.J. (Wouter) de, Dekkers, R. (R.), Dings-Lammertink, A. (A.), Doedens, R.A. (R. A.), Donker, A.E. (A.), Dousma, M. (M.), Faber, T.E. (T. E.), Gerrit, G.P.J.M. (Gerardus), Gerver, J.A.M. (J. A.M.), Heidema, J. (Jojanneke), Veen, J.H.-V. (J. Homan-van der), Jacobs, M.A.M. (M. A.M.), Jansen, N.J.G. (N. J.G.), Kawczynski, P. (P.), Klucovska, K. (K.), Kneyber, M.C.J. (M. C.J.), Koopman-Keemink, Y. (Yvonne), Langenhorst, V.J. (V. J.), Leusink, J. (J.), Loza, B.F. (Bettina F.), Merth, I.T. (I. T.), Miedema, C.J. (C. J.), Neeleman, C. (C.), Noordzij, J.G. (Jeroen), Obihara, C.C. (Charlie C.), van Overbeek – van Gils, A.L.T. (A. L.T.), Poortman, G.H. (G. H.), Potgieter, S.T. (S. T.), Potjewijd, J. (J.), Rosias, P.P.R. (Philippe), Sprong, T. (Tom), ten Tussher, G.W. (G. W.), Thio, B.J. (B. J.), Tramper-Stranders, G.A. (Gerdien), Deuren, M. (Marcel) van, van der Meer, H. (H.), van Kuppevelt, A.J.M. (A. J.M.), van Wermeskerken, A.M. (A. M.), Verwijs, W.A. (W. A.), Wolfs, T.F.W. (T. F.W.), Agyeman, P. (Philipp), Aebi, C. (Christoph), Berger, C. (Christoph), Giannoni, P., Stocker, M. (Martin), Posfay-Barbe, K.M. (Klara M.), Heininger, U. (Ulrich), Bernhard-Stirnemann, S. (Sara), Niederer-Loher, A. (Anita), Kahlert, C. (Christian), Hasters, P. (Paul), Relly, C. (Christa), Baer, W. (Walter), Frederick, H. (Hannah), Jennings, R. (Rebecca), Johnston, J. (Joanne), Kenwright, R. (Rhian), Pinnock, E. (Elli), Agbeko, R. (Rachel), Secka, F. (Fatou), Bojang, K. (Kalifa), Sarr, I. (Isatou), Kebbeh, N. (Ngange), Sey, G. (Gibbi), Momodou, (), khan, S. (Saidy), Cole, F. (Fatoumata), Thomas, G. (Gilleh), Antonio, M. (Martin), Klobassa, D.S. (Daniela S.), Binder, A. (Alexander), Schweintzger, N.A. (Nina A.), Sagmeister, M. (Manfred), Baumgart, H. (Hinrich), Baumgartner, M. (Markus), Behrends, U. (Uta), Biebl, A. (Ariane), Birnbacher, R. (Robert), Blanke, J.-G. (Jan-Gerd), Boelke, C. (Carsten), Breuling, K. (Kai), Brunner, J. (Jürgen), Buller, M. (Maria), Dahlem, P. (Peter), Dietrich, B. (Beate), Eber, E. (Ernst), Elias, J. (Johannes), Emhofer, J. (Josef), Etschmaier, R. (Rosa), Farr, S. (Sebastian), Girtler, Y. (Ylenia), Grigorow, I. (Irina), Heimann, K. (Konrad), Ihm, U. (Ulrike), Jaros, Z. (Zdenek), Kalhoff, H. (Hermann), Kaulfersch, W. (Wilhelm), Kemen, C. (Christoph), Klocker, N. (Nina), Köster, B. (Bernhard), Kohlmaier, B. (Benno), Komini, E. (Eleni), Kramer, L. (Lydia), Neubert, A. (Antje), Ortner, D. (Daniel), Pescollderungg, L. (Lydia), Pfurtscheller, K. (Klaus), Reiter, K. (Karl), Ristic, G. (Goran), Rödl, S. (Siegfried), Sellner, A. (Andrea), Sonnleitner, A. (Astrid), Sperl, M. (Matthias), Stelzl, W. (Wolfgang), Till, H. (Holger), Trobisch, A. (Andreas), Vierzig, A. (Anne), Vogel, U. (Ulrich), Weingarten, C. (Christina), Welke, S. (Stefanie), Wimmer, A. (Andreas), Wintergerst, U. (Uwe), Wüller, D. (Daniel), Zaunschirm, A. (Andrew), Ziuraite, I. (Ieva), Žukovskaja, V. (Veslava), Wang, X. (Xinzhu), Nijman, R.G. (Ruud), Camuzeaux, S. (Stephane), Sands, C. (Caroline), Jackson, H. (Heather), Kaforou, M. (Myrsini), Emonts, M. (Marieke), Herberg, J.A. (Jethro A.), MacOnochie, I.K. (Ian), Carrol, E.D. (Enitan), Paulus, S.C. (Stephane C.), Zenz, W. (Werner), Flier, M. (Michiel) van der, Groot, R. (Ronald) de, Martinon-Torres, F. (Federico), Schlapbach, L.J. (Luregn), Pollard, A.J. (Andrew J.), Fink, C. (Colin), Kuijpers, T.T. (Taco T.), Anderson, S. (Suzanne), Lewis, M.R. (Matthew R.), Levin, M. (Michael), McClure, M. (Myra), Gormley, S. (Stuart), Hamilton, S. (Shea), Hourmat, B. (Bernardo), Hoggart, C. (Clive), Sancho-Shimizu, V. (Vanessa), Wright, V.J. (Victoria), Abdulla, A. (Amina), Agapow, P. (Paul), Bartlett, M. (Maeve), Bellos, E. (Evangelos), Eleftherohorinou, H. (Hariklia), Galassini, R. (Rachel), Inwald, D. (David), Mashbat, M. (Meg), Menikou, S. (Stefanie), Mustafa, S. (Sobia), Nadel, S. (Simon), Rahman, R. (Rahmeen), Thakker, C. (Clare), Coin, L.M.J. (Lachlan M. J.), Bokhandi, S. (S.), Power, S. (Sue), Barham, H. (Heather), Pathan, D.N. (Dr N), Ridout, J. (Jenna), White, D. (Deborah), Thurston, S. (Sarah), Faust, D. (Dominik), Patel, S.Y. (Smita Y.), McCorkell, J. (Jenni), Davies, P. (P.), Crate, L. (Lindsey), Navarra, H. (Helen), Carter, S. (Stephanie), Ramaiah, R. (R.), Patel, R. (Rekha), Tuffrey, C. (Catherine), Gribbin, A. (Andrew), McCready, S. (Sharon), Peters, M. (Mark), Hardy, K. (Katie), Standing, F. (Fran), O’Neill, L. (Lauren), Abelake, E. (Eugenia), Deep, A. (Akash), Nsirim, E. (Eniola), Willis, L. (Louise), Young, Z. (Zoe), Royad, C. (C.), White, S. (Sonia), Fortune, P.M. (P. M.), Hudnott, P. (Phil), González, F.Á. (Fernando Álvez), Barral-Arca, R. (Ruth), Cebey-López, M. (Miriam), Curras-Tuala, M.J. (María José), García, N. (Natalia), Vicente, L.G. (Luisa García), Gómez-Carballa, A. (Alberto), Rial, J.G. (Jose Gómez), Beiroa, A.G. (Andrea Grela), Grande, A.J. (Antonio Justicia), Iglesias, P.L. (Pilar Leboráns), Santos, A.E.M. (Alba Elena Martínez), Martinón-Torres, F. (Federico), MartinónTorres, N. (Nazareth), Sánchez, J.M.M. (José María Martinón), Gutiérrez, B.M. (Beatriz Morillo), Pérez, B.M. (Belén Mosquera), Pacheco, P.O. (Pablo Obando), Pardo-Seco, J. (Jacobo), Pischedda, S. (Sara), RiveroCalle, I. (Irene), Rodríguez-Tenreiro, C. (Carmen), Redondo-Collazo, L. (Lorenzo), Ellacuriagal, A.S. (Antonio Salas), Fernández, S.S. (Sonia Serén), Silva, M.S.P. (María del Sol Porto), Vega, A. (Ana), Trillo, L.V. (Lucía Vilanova), Salas, A. (Antonio), Reyes, S.B. (Susana Beatriz), León, M.C.L. (María Cruz León), Mingorance, Á.N. (Álvaro Navarro), Barrios, X.G. (Xavier Gabaldó), Vergara, E.O. (Eider Oñate), Torre, A.C. (Andrés Concha), Vivanco, A. (Ana), Fernández, R. (Reyes), Sánchez, F.G. (Francisco Giménez), Forte, M.S. (Miguel Sánchez), Rojo, P. (Pablo), Contreras, J.R. (J. Ruiz), Palacios, A. (Alba), Ibarrondo, C.E. (Cristina Epalza), Cooke, E.F. (Elizabeth Fernández), Navarro, M. (Marisa), Álvarez, C.Á. (Cristina Álvarez), Lozano, M.J. (María José), Carreras, E. (Eduardo), Sanagustín, S.B. (Sonia Brió), Neth, O. (Olaf), Padilla, M.C.M. (Ma del Carmen Martínez), Tato, L.M.P. (Luis Manuel Prieto), Guillén, S. (Sara), Silveira, L.F. (Laura Fernández), Moreno, D. (David), van Furth, A.M.T. (A. M. Tutu), Boeddha, N.P. (Navin), Driessen, G.J.A. (Gertjan), Hazelzet, J.A. (Jan), Pajkrt, D. (D.), Sanders, E.A.M. (E. A.M.), van de Beek, D. (D.), Ende, A. (A.) van der, Philipsen, H.L.A. (H. L.A.), Adeel, A.O.A. (A. O.A.), Breukels, M.A. (M. A.), Brinkman, D.M.C., de Korte, C.C.M.M. (C. C.M.M.), de Vries, E. (E.), Waal, W.J. (Wouter) de, Dekkers, R. (R.), Dings-Lammertink, A. (A.), Doedens, R.A. (R. A.), Donker, A.E. (A.), Dousma, M. (M.), Faber, T.E. (T. E.), Gerrit, G.P.J.M. (Gerardus), Gerver, J.A.M. (J. A.M.), Heidema, J. (Jojanneke), Veen, J.H.-V. (J. Homan-van der), Jacobs, M.A.M. (M. A.M.), Jansen, N.J.G. (N. J.G.), Kawczynski, P. (P.), Klucovska, K. (K.), Kneyber, M.C.J. (M. C.J.), Koopman-Keemink, Y. (Yvonne), Langenhorst, V.J. (V. J.), Leusink, J. (J.), Loza, B.F. (Bettina F.), Merth, I.T. (I. T.), Miedema, C.J. (C. J.), Neeleman, C. (C.), Noordzij, J.G. (Jeroen), Obihara, C.C. (Charlie C.), van Overbeek – van Gils, A.L.T. (A. L.T.), Poortman, G.H. (G. H.), Potgieter, S.T. (S. T.), Potjewijd, J. (J.), Rosias, P.P.R. (Philippe), Sprong, T. (Tom), ten Tussher, G.W. (G. W.), Thio, B.J. (B. J.), Tramper-Stranders, G.A. (Gerdien), Deuren, M. (Marcel) van, van der Meer, H. (H.), van Kuppevelt, A.J.M. (A. J.M.), van Wermeskerken, A.M. (A. M.), Verwijs, W.A. (W. A.), Wolfs, T.F.W. (T. F.W.), Agyeman, P. (Philipp), Aebi, C. (Christoph), Berger, C. (Christoph), Giannoni, P., Stocker, M. (Martin), Posfay-Barbe, K.M. (Klara M.), Heininger, U. (Ulrich), Bernhard-Stirnemann, S. (Sara), Niederer-Loher, A. (Anita), Kahlert, C. (Christian), Hasters, P. (Paul), Relly, C. (Christa), Baer, W. (Walter), Frederick, H. (Hannah), Jennings, R. (Rebecca), Johnston, J. (Joanne), Kenwright, R. (Rhian), Pinnock, E. (Elli), Agbeko, R. (Rachel), Secka, F. (Fatou), Bojang, K. (Kalifa), Sarr, I. (Isatou), Kebbeh, N. (Ngange), Sey, G. (Gibbi), Momodou, (), khan, S. (Saidy), Cole, F. (Fatoumata), Thomas, G. (Gilleh), Antonio, M. (Martin), Klobassa, D.S. (Daniela S.), Binder, A. (Alexander), Schweintzger, N.A. (Nina A.), Sagmeister, M. (Manfred), Baumgart, H. (Hinrich), Baumgartner, M. (Markus), Behrends, U. (Uta), Biebl, A. (Ariane), Birnbacher, R. (Robert), Blanke, J.-G. (Jan-Gerd), Boelke, C. (Carsten), Breuling, K. (Kai), Brunner, J. (Jürgen), Buller, M. (Maria), Dahlem, P. (Peter), Dietrich, B. (Beate), Eber, E. (Ernst), Elias, J. (Johannes), Emhofer, J. (Josef), Etschmaier, R. (Rosa), Farr, S. (Sebastian), Girtler, Y. (Ylenia), Grigorow, I. (Irina), Heimann, K. (Konrad), Ihm, U. (Ulrike), Jaros, Z. (Zdenek), Kalhoff, H. (Hermann), Kaulfersch, W. (Wilhelm), Kemen, C. (Christoph), Klocker, N. (Nina), Köster, B. (Bernhard), Kohlmaier, B. (Benno), Komini, E. (Eleni), Kramer, L. (Lydia), Neubert, A. (Antje), Ortner, D. (Daniel), Pescollderungg, L. (Lydia), Pfurtscheller, K. (Klaus), Reiter, K. (Karl), Ristic, G. (Goran), Rödl, S. (Siegfried), Sellner, A. (Andrea), Sonnleitner, A. (Astrid), Sperl, M. (Matthias), Stelzl, W. (Wolfgang), Till, H. (Holger), Trobisch, A. (Andreas), Vierzig, A. (Anne), Vogel, U. (Ulrich), Weingarten, C. (Christina), Welke, S. (Stefanie), Wimmer, A. (Andreas), Wintergerst, U. (Uwe), Wüller, D. (Daniel), Zaunschirm, A. (Andrew), Ziuraite, I. (Ieva), and Žukovskaja, V. (Veslava)

Abstract

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are

Published
2019
Full Text
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132. Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Author

Borghini, L, Png, E, Binder, A, Wright, VJ, Pinnock, E, de Groot, R, Hazelzet, J, Emonts, M, Van der Flier, M, Schlapbach, LJ, Anderson, S, Secka, F, Salas, A, Fink, C, Carrol, ED, Pollard, AJ, Coin, LJ, Kuijpers, TW, Martinon-Torres, F, Zenz, W, Levin, M, Hibberd, ML, Davila, S, Gormley, S, Hamilton, S, Herberg, J, Hourmat, B, Hoggart, C, Kaforou, M, Sancho-Shimizu, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Bokhandi, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Cratev, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, Martinon-Torres, N, Martinon Sanchez, JM, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, Rivero Calle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, van der Flier, M, Boeddha, NP, Driessen, GJA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Paulus, S, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Agbeko, R, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Saidykhan, M, Cole, F, Thomas, G, Antonio, M, Walcher, W, Geishofer, G, Klobassa, D, Martin, M, Pfurtscheller, K, Reiter, K, Roedl, S, Zobel, G, Zoehrer, B, Toepke, B, Fucik, P, Gabriel, M, Penzien, JM, Diab, G, Miething, R, Deeg, KH, Hammer, J, Varnholt, V, Schmidt, A, Bindl, L, Sillaber, U, Huemer, C, Meier, P, Simic-Schleicher, G, Markart, M, Pfau, E, Broede, H, Ausserer, B, Kalhoff, H, Arpe, V, Schweitzer-Krantz, S, Kasper, J-M, Loranth, K, Bittrich, HJ, Simma, B, Klinge, J, Fedlmaier, M, Weigand, N, Herting, E, Grube, R, Fusch, C, Gruber, A, Schimmel, U, Knaufer-Schiefer, S, Laessig, W, Hennenberger, A, von der Wense, A, Tillmann, R, Schwarick, J, Sitzmann, FC, Streif, W, Mueller, H, Kurnik, P, Groneck, P, Weiss, U, Groeblacher-Roth, H, Bensch, J, Moser, R, Schwarz, R, Lenz, K, Hofmann, T, Goepel, W, Schulz, D, Berger, T, Hauser, E, Foerster, KM, Peters, J, Nicolai, TH, Kumlien, B, Beckmann, R, Seitz, C, Hueseman, D, Schuermann, R, Ta, VH, Weikmann, E, Evert, W, Hautz, J, Seidenberg, J, Wocko, L, Luigs, P, Reiter, H-L, Quietzach, J, Koenig, M, Herrmann, J, Mitter, H, Seidler, E, Maak, B, Sperl, W, Zwiauer, K, Meissl, M, Koch, R, Cremer, M, Breuer, HA, Goerke, W, Nossal, R, Pernice, W, Brangenberg, R, Salzer, HR, Koch, H, Schaller, G, Paky, F, Strasser, F, Eitelberger, F, Sontheimer, D, Lischka, A, Kronberger, M, Dilch, A, Scheibenpflug, C, Bruckner, R, Mahler, K, Runge, K, Kunze, W, Schermann, P, Borghini, L, Png, E, Binder, A, Wright, VJ, Pinnock, E, de Groot, R, Hazelzet, J, Emonts, M, Van der Flier, M, Schlapbach, LJ, Anderson, S, Secka, F, Salas, A, Fink, C, Carrol, ED, Pollard, AJ, Coin, LJ, Kuijpers, TW, Martinon-Torres, F, Zenz, W, Levin, M, Hibberd, ML, Davila, S, Gormley, S, Hamilton, S, Herberg, J, Hourmat, B, Hoggart, C, Kaforou, M, Sancho-Shimizu, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Bokhandi, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Cratev, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, Martinon-Torres, N, Martinon Sanchez, JM, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, Rivero Calle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, van der Flier, M, Boeddha, NP, Driessen, GJA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Paulus, S, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Agbeko, R, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Saidykhan, M, Cole, F, Thomas, G, Antonio, M, Walcher, W, Geishofer, G, Klobassa, D, Martin, M, Pfurtscheller, K, Reiter, K, Roedl, S, Zobel, G, Zoehrer, B, Toepke, B, Fucik, P, Gabriel, M, Penzien, JM, Diab, G, Miething, R, Deeg, KH, Hammer, J, Varnholt, V, Schmidt, A, Bindl, L, Sillaber, U, Huemer, C, Meier, P, Simic-Schleicher, G, Markart, M, Pfau, E, Broede, H, Ausserer, B, Kalhoff, H, Arpe, V, Schweitzer-Krantz, S, Kasper, J-M, Loranth, K, Bittrich, HJ, Simma, B, Klinge, J, Fedlmaier, M, Weigand, N, Herting, E, Grube, R, Fusch, C, Gruber, A, Schimmel, U, Knaufer-Schiefer, S, Laessig, W, Hennenberger, A, von der Wense, A, Tillmann, R, Schwarick, J, Sitzmann, FC, Streif, W, Mueller, H, Kurnik, P, Groneck, P, Weiss, U, Groeblacher-Roth, H, Bensch, J, Moser, R, Schwarz, R, Lenz, K, Hofmann, T, Goepel, W, Schulz, D, Berger, T, Hauser, E, Foerster, KM, Peters, J, Nicolai, TH, Kumlien, B, Beckmann, R, Seitz, C, Hueseman, D, Schuermann, R, Ta, VH, Weikmann, E, Evert, W, Hautz, J, Seidenberg, J, Wocko, L, Luigs, P, Reiter, H-L, Quietzach, J, Koenig, M, Herrmann, J, Mitter, H, Seidler, E, Maak, B, Sperl, W, Zwiauer, K, Meissl, M, Koch, R, Cremer, M, Breuer, HA, Goerke, W, Nossal, R, Pernice, W, Brangenberg, R, Salzer, HR, Koch, H, Schaller, G, Paky, F, Strasser, F, Eitelberger, F, Sontheimer, D, Lischka, A, Kronberger, M, Dilch, A, Scheibenpflug, C, Bruckner, R, Mahler, K, Runge, K, Kunze, W, and Schermann, P

Abstract

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.

Published
2019

133. Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Author

Wang, X, Nijman, R, Camuzeaux, S, Sands, C, Jackson, H, Kaforou, M, Emonts, M, Herberg, JA, Maconochie, I, Carrol, ED, Paulus, SC, Zenz, W, Van der Flier, M, de Groot, R, Martinon-Torres, F, Schlapbach, LJ, Pollard, AJ, Fink, C, Kuijpers, TT, Anderson, S, Lewis, MR, Levin, M, McClure, M, Gormley, S, Hamilton, S, Hourmat, B, Hoggart, C, Sancho-Shimizu, V, Wright, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Coin, LMJ, Bokhand, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Crate, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, MartinonTorres, N, Martinon Sanchez, JM, Morillo Gutierrez, B, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, RiveroCalle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Salas Ellacuriagal, A, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Vilanova Trillo, L, Salas, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Epalza Ibarrondo, C, Fernandez Cooke, E, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, Boeddha, NP, Driessen, GJA, Hazelzet, JA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Pinnock, E, Agbeko, R, Secka, F, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Momodou, SK, Cole, F, Thomas, G, Antonio, M, Klobassa, DS, Binder, A, Schweintzger, NA, Sagmeister, M, Baumgart, H, Baumgartner, M, Behrends, U, Biebl, A, Birnbacher, R, Blanke, J-G, Boelke, C, Breuling, K, Brunner, J, Buller, M, Dahlem, P, Dietrich, B, Eber, E, Elias, J, Emhofer, J, Etschmaier, R, Farr, S, Girtler, Y, Grigorow, I, Heimann, K, Ihm, U, Jaros, Z, Kalhoff, H, Kaulfersch, W, Kemen, C, Klocker, N, Koester, B, Kohlmaier, B, Komini, E, Kramer, L, Neubert, A, Ortner, D, Pescollderungg, L, Pfurtscheller, K, Reiter, K, Ristic, G, Roedl, S, Sellner, A, Sonnleitner, A, Sperl, M, Stelzl, W, Till, H, Trobisch, A, Vierzig, A, Vogel, U, Weingarten, C, Welke, S, Wimmer, A, Wintergerst, U, Wueller, D, Zaunschirm, A, Ziuraite, I, Zukovskaja, V, Wang, X, Nijman, R, Camuzeaux, S, Sands, C, Jackson, H, Kaforou, M, Emonts, M, Herberg, JA, Maconochie, I, Carrol, ED, Paulus, SC, Zenz, W, Van der Flier, M, de Groot, R, Martinon-Torres, F, Schlapbach, LJ, Pollard, AJ, Fink, C, Kuijpers, TT, Anderson, S, Lewis, MR, Levin, M, McClure, M, Gormley, S, Hamilton, S, Hourmat, B, Hoggart, C, Sancho-Shimizu, V, Wright, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Coin, LMJ, Bokhand, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Crate, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, MartinonTorres, N, Martinon Sanchez, JM, Morillo Gutierrez, B, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, RiveroCalle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Salas Ellacuriagal, A, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Vilanova Trillo, L, Salas, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Epalza Ibarrondo, C, Fernandez Cooke, E, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, Boeddha, NP, Driessen, GJA, Hazelzet, JA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Pinnock, E, Agbeko, R, Secka, F, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Momodou, SK, Cole, F, Thomas, G, Antonio, M, Klobassa, DS, Binder, A, Schweintzger, NA, Sagmeister, M, Baumgart, H, Baumgartner, M, Behrends, U, Biebl, A, Birnbacher, R, Blanke, J-G, Boelke, C, Breuling, K, Brunner, J, Buller, M, Dahlem, P, Dietrich, B, Eber, E, Elias, J, Emhofer, J, Etschmaier, R, Farr, S, Girtler, Y, Grigorow, I, Heimann, K, Ihm, U, Jaros, Z, Kalhoff, H, Kaulfersch, W, Kemen, C, Klocker, N, Koester, B, Kohlmaier, B, Komini, E, Kramer, L, Neubert, A, Ortner, D, Pescollderungg, L, Pfurtscheller, K, Reiter, K, Ristic, G, Roedl, S, Sellner, A, Sonnleitner, A, Sperl, M, Stelzl, W, Till, H, Trobisch, A, Vierzig, A, Vogel, U, Weingarten, C, Welke, S, Wimmer, A, Wintergerst, U, Wueller, D, Zaunschirm, A, Ziuraite, I, and Zukovskaja, V

Abstract

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics.

Published
2019

149. We should not up the ante in Syria

Author

Krumholz, Willis L.

Subjects
Syrian Uprising, 2011-, Aerial bombing, Military intervention, Chemical weapons -- Usage -- International aspects, News, opinion and commentary
Abstract

Byline: Willis L. Krumholz Americans understandably reacted with horror to the reported chemical weapons attack in Syria last weekend. This act is only the latest in a long list of [...]

Published
2018

150. Cell size and growth regulation in the $\textit{Arabidopsis thaliana}$ apical stem cell niche

Author

Willis, L, Refahi, Y, Wightman, R, Landrein, B, Teles, J, Huang, KC, Meyerowitz, EM, Jönsson, H, Wightman, Raymond [0000-0003-1295-4875], Landrein, Benoit [0000-0002-2371-9996], Jonsson, Henrik [0000-0003-2340-588X], and Apollo - University of Cambridge Repository

Subjects
cell size, homeostasis, plant stem cells, cell growth, cell cycle
Abstract

Cell size and growth kinetics are fundamental cellular properties with important physiological implications. Classical studies on yeast, and recently on bacteria, have identified rules for cell size regulation in single cells, but in the more complex environment of multicellular tissues, data have been lacking. In this study, to characterize cell size and growth regulation in a multicellular context, we developed a 4D imaging pipeline and applied it to track and quantify epidermal cells over 3-4 d in $\textit{Arabidopsis thaliana}$ shoot apical meristems. We found that a cell size checkpoint is not the trigger for G2/M or cytokinesis, refuting the unexamined assumption that meristematic cells trigger cell cycle phases upon reaching a critical size. Our data also rule out models in which cells undergo G2/M at a fixed time after birth, or by adding a critical size increment between G2/M transitions. Rather, cell size regulation was intermediate between the critical size and critical increment paradigms, meaning that cell size fluctuations decay by ∼75% in one generation compared with 100% (critical size) and 50% (critical increment). Notably, this behavior was independent of local cell-cell contact topologies and of position within the tissue. Cells grew exponentially throughout the first >80% of the cell cycle, but following an asymmetrical division, the small daughter grew at a faster exponential rate than the large daughter, an observation that potentially challenges present models of growth regulation. These growth and division behaviors place strong constraints on quantitative mechanistic descriptions of the cell cycle and growth control.

Published
2017
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