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2,068 results on '"Stevens, E."'

102. Social interaction and sensorimotor gating abnormalities in mice lacking Dv/1

Author

Lijam, Nardos, Paylor, Richard, McDonald, Michael P., Crawley, Jacqueline N., Deng, Chu-Xia, Herrup, Karl, Stevens, E Karen, Maccaferri, Gianmaria, McBain, Chris J., Sussman, Daniel J., and Wynshaw-Boris, Anthony

Subjects
Mice, mutant strains -- Observations, Mental health -- Research, Biological sciences
Abstract

Gene targeting was used to create mice completely deficient for Dv/1, a mouse homolog of the Drosphila segment polarity gene Dishevelled. The mice were viable, fertile and structurally normal, but showed reduced social interaction. Such mutants could therefore act as models for certain human psychiatric disorders.

Published
1997

103. Enzyme deprivation along a heterothermic tissue: the visceral retia mirabilia of the bluefin tuna

Author

Fudge, Douglas S., Stevens, E. Don, and Ballantyne, James S.

Subjects
Enzyme kinetics -- Physiological aspects, Bluefin tuna -- Physiological aspects, Body temperature -- Regulation, Metabolism -- Physiological aspects, Biological sciences
Abstract

The activity of several enzymes in the visceral retia of Thunnus thynnus bluefin tuna was analyzed to characterize the patterns of enzyme compensation. Quantitative analysis of the enzymes involved in amino acid metabolism and anaerobic carbohydrate metabolism indicated the positive correlation between adaptation temperature and the enthalpy of activation. The positive thermal compensation that was exhibited by the enzymes was also achieved via differences in enzyme concentration along the visceral retia.

Published
1997

110. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author

Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), Pourcain, B.S. (Beate), Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), and Pourcain, B.S. (Beate)

Abstract

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for lowfrequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carrie

Published
2019
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117. Proteomics in cancer

Author

Stevens, E. V., Posadas, E. M., Davidson, B., and Kohn, E. C.

Published
2004

128. Ruptured Anterior Spinal Artery Aneurysm: A Case Report

Author

Pollock, Jeffrey M., Powers, Alexander K., Stevens, E. Andrew, Sanghvi, Amit N., Wilson, John A., and Morris, Pearse P.

Subjects
Aneurysms, Health
Abstract

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1552-6569.2008.00287.x Byline: Jeffrey M. Pollock (1), Alexander K. Powers (1), E. Andrew Stevens (1), Amit N. Sanghvi (1), John A. Wilson (1), Pearse P. Morris (1) Keywords: Anterior spinal artery; aneurysm; Chiari malformation Abstract: ABSTRACT We present a case of a subarachnoid hemorrhage and vasospasm secondary to a ruptured anterior spinal artery aneurysm associated with a Chiari 1 malformation. To our knowledge this is the first reported spinal artery aneurysm with this association. Author Affiliation: (1)Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC (JMP, ANS, PPM); and Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (AKP, JAW).[Correction added after online publication 10-June-2009: Received date has been corrected.] Article History: Acceptance: Received February 19, 2008, and in revised form May 19, 2008. Accepted for publication June 11, 2008. Article note: Correspondence: Address correspondence to Jeffrey M. Pollock, MD, Wake Forest University, Department of Radiology, Medical Center Boulevard, Winston-Salem, NC. E-mail: jeffmpollock@gmail.com.

Published
2009

130. The influence of starvation and predators on the mating behavior of a semiaquatic insect

Author

Travers, Stevens E. and Sih, Andrew

Subjects
Insects -- Behavior, Predation (Biology) -- Research, Sex ratio -- Research, Reproduction -- Research, Biological sciences, Environmental issues
Abstract

Few experimental studies of mating behavior have examined mating behavior shifts in response to ecological factors (e.g., predators, starvation). We conducted experiments designed to: (1) examine multiple trade-offs between predator avoidance, feeding behavior, and copulation duration in a semiaquatic insect (Microvelia austrina); and (2) address the influence of altered copulation duration on male reproductive success. To examine multiple trade-offs, we used a 2 x 2 factorial design where we measured the amount of time that mating microveliids remained in tandem, for starved and fed microveliids in the presence and absence vs. absence of predaceous water striders (Gerris remigis). We also looked at the effects of presence vs. absence of green sunfish (Lepomis cyanellus) on microveliid tandem duration. To address the impact of premature pair separation on male mating success, we separated paired microveliids in field populations and measured the time required for each sex to find new mates. To examine the effects of local sex ratio on remating times of males and females, we quantified the sex ratio of field populations via periodic censuses and correlated local sex ratio with remating times. Finally, to address oviposition rates while pairs are in tandem, we measured female oviposition patterns relative to tandem duration for poorly fed and well-fed females. Both starvation and gerrid presence significantly reduced tandem duration. As a result of male-biased sex ratios, males that prematurely separated from females often faced long search times before securing a new mate. Females oviposited at a constant rate while in tandem. A simple computer simulation incorporating the above observations suggests that reductions in tandem duration can decrease fertilization rates.

Published
1991

134. 137A trial to evaluate an eXTended RehAbilitation service for Stroke patients (EXTRAS): main patient results

Author

Rodgers, H, primary, Shaw, L, additional, Bhattarai, N, additional, Cant, R, additional, Drummond, A, additional, Ford, G A, additional, Forster, A, additional, Francis, R, additional, Hills, K, additional, Howel, D, additional, Laverty, A M, additional, McKevitt, C, additional, McMeekin, P, additional, Price, C, additional, Stamp, E, additional, Stevens, E, additional, and Vale, L, additional

Published
2019
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144. Ervaringen met mestschuif en mestrobots op Hooibeekhoeve

Author

Stevens, E. and Stevens, E.

Abstract

Het ‘mestvrij’ maken van de stalvloeren is een erg belangrijke hygiënemaatregel in de melkveestal. Hooibeekhoeve heeft in het verleden ervaring opgebouwd met een mestschuif en intussen beschikt het bedrijf over twee types mestrobots. In dit artikel geven we een beschrijving van de werking, alsook de voor- en nadelen van zowel de mestschuif als de mestrobots.

Published
2018

145. Clube Nexus

Author

Stevens, E. J., Colombini, Renan, Stevens, E. J., and Colombini, Renan

Subjects
Young adult fiction, American--Translations into Portuguese, Psychic ability--Fiction, Fairies--Fiction, Private investigators--Fiction
Abstract

Finalista do RPG Reviewer's Choice Award por Melhor Série de Fantasia Urbana. Um demônio, uma humana, uma fada Unseelie, e um vampiro entraram num bar... Este especial da série Ivy Granger contém contos ambientados no Clube Nexus, uma rave oculta do submundo paranormal de Harborsmouth. CONGELADA Uma barganha destinada a dar errado levou uma fada da nobreza Unseelie a ser escravizada por toda a vida como uma bartender com anseios de vingança. PULVERIZADO Ser um predador de grande haabilidade não te coloca necessariamente no topo da cadeia alimentar no Clube Nexus. Um vampiro sulista com desejos mórbido por sangue e violência pode ter dado uma mordida maior que a boca. ENDIABRADO O advogado demônio que mais amamos odiar está de olho em uma certa humana com jeito de roqueira gótica. Uma pena que ela trouxe uma besta carregada com dardos mergulhados em água benta para passar a noite na cidade. AZARADA Bem quando Jinx precisa de uma'noite das garotas'despreocupada com Ivy, um demônio gostosão tenta pagar uma bebida para ela. Ela realmente é a humana mais azarada do planeta. Clube Nexus (Ivy Granger, Detetive Paranomral #2.5) é uma noveleta que se passa na série de fantasia urbana premiada de Ivy Granger, de E.J. Stevens. O mundo de Ivy Granger, onde se passam as séries'Ivy Grander, Detetive Paranormal'e'Guilda dos Caçadores', é recheada de ação, mistérios paranormais, humor negro, personagens peculiares, vampiros sanguessugas, demônios coquetes, gárgolas sarcásticas, transmorfos sexies, bruxas temperamentais, fadas psicopátas e heroínas fortes de lingua afiada. As séries de Ivy Granger ganharam numerosos prêmios, incluindo o BTS Red Carpet Award por Melhor Romance, o RPG Reviewer's Choice Award por Melhor Fantasia Paranormal, Melhor Fantasia Urbana e finalista em Melhor Série de Fantasia Urbana.

Published
2017

146. Visão de Veras

Author

Stevens, E. J., Colombini, Renan, Stevens, E. J., and Colombini, Renan

Subjects
Psychic ability--Fiction, Fairies--Fiction, Private investigators--Fiction
Abstract

Vencedor do PRG Review's Choice Award do Melhor Romance de Fantasia Paranormal e finalista da Melhor Série de Fantasia Urbana. Bem-vindo a Harborsmouth, onde os monstros caminham pelas ruas invisíveis pelos seres humanos... exceto aqueles com visão de veras, como Ivy Granger. Há coisas melhores não vistas... A visão de veras de Ivy Granger finalmente está dando propósito a sua vida. Ivy e sua melhor amiga Jinx talvez não estejam ficando ricas, mas sua agência de detetive psíquica paga as contas - na maioria das vezes. Sua única preocupação é o tédio de um dia lento e o ocasional cliente louco - até que um demônio passe pela porta delas. Demônios nunca são coisa boa... Um advogado demônio que representa as fae aquáticas? Coisas mais estranhas já aconteceram. E as coisas estão prestes a ficar muito, mas muito estranhas mesmo quanto um pesadelo sangrento começa a caçar na cidade de Harborsmouth. Há sangue na água... Kelpies tem reputação de comer humanos. Infelizmente, os kelpies são os clientes. Quando fadas Unseelie más desse jeito perambulam as vias da sua cidade, você precisa fazer escolhas difíceis. O menor dos dois males... Visão de Veras é o primeira livro da série de fantasia urbana Ivy Granger, bestseller de E.J. Stevens. O mundo de Ivy Granger, incluindo a série Ivy Granger, Detetive Paranormal e a série Hunter's Guild, é recheada de ação, mistério paranormal, magia, humor pesado, personagens peculiares, vampiros sanguinolentos, demônios que flertam, gárgulas sarcásticas, transmorfos sexy, bruxas temperamentais, fadas psicóticas e heroínas irritadiças.'Stevens nos convence instantaneamente com personagens bem desenvolvidos e agradáveis'. -Ted Fauster, autor da série World of Faerel'Este é um começo maravilhoso para uma série que o deixa querendo mais!'-Miranda Shanklin, autor da série Soul

Published
2017

147. Uses and Doses of Local Anesthetics in Fish, Amphibians, and Reptiles

Author

Chatigny, Frederic, Kamunde, Collins, Creighton, Catherine M, and Stevens, E Don

Subjects
Amphibians, Analgesics, Overview, Fishes, Animals, Lidocaine, Pain, Reptiles, Guidelines as Topic, Anesthetics, Local, Animal Welfare
Abstract

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly benefit from those drugs. Some recommendations are currently available in the literature concerning analgesic use in these animals. However the pharmacological properties, safety and often efficacy of local anesthetic drugs have not been investigated yet in fish, amphibians, or reptiles. This review compiled current information concerning the use of those agents in fish, reptiles and amphibians to help clinicians make an informed decision as to which dose and drug to use. The resulting literature search showed that the literature concerning use of local analgesics in fish and amphibians is very limited while the literature for reptiles is more extensive. We found few experimental studies evaluating the efficacy of local anesthetics. Further studies would provide additional information for developing guidelines to improve the welfare of fish, amphibians and reptiles.

Published
2017

148. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author

Hendricks, A.E. Bochukova, E.G. Marenne, G. Keogh, J.M. Atanassova, N. Bounds, R. Wheeler, E. Mistry, V. Henning, E. Körner, A. Muddyman, D. McCarthy, S. Hinney, A. Hebebrand, J. Scott, R.A. Langenberg, C. Wareham, N.J. Surendran, P. Howson, J.M. Butterworth, A.S. Danesh, J. Nordestgaard, Bø.G. Nielsen, S.F. Afzal, S. Papadia, S. Ashford, S. Garg, S. Millhauser, G.L. Palomino, R.I. Kwasniewska, A. Tachmazidou, I. O'Rahilly, S. Zeggini, E. Barroso, I. Farooqi, I.S. Benzeval, M. Burton, J. Buck, N. Jäckle, A. Kumari, M. Laurie, H. Lynn, P. Pudney, S. Rabe, B. Wolke, D. Overvad, K. Tjønneland, A. Clavel-Chapelon, F. Kaaks, R. Boeing, H. Trichopoulou, A. Ferrari, P. Palli, D. Krogha, V. Panico, S. Tuminoa, R. Matullo, G. Boer, J. Van Der Schouw, Y. Weiderpass, E. Quiros, J.R. Sánchez, M.-J. Navarro, C. Moreno-Iribas, C. Arriola, L. Melander, O. Wennberg, P. Key, T.J. Riboli, E. Turki, S.A. Anderson, C.A. Anney, R. Antony, D. Soler Artigas, M. Ayub, M. Bala, S. Barrett, J.C. Beales, P. Bentham, J. Bhattacharyaa, S. Birney, E. Blackwooda, D. Bobrow, M. Bolton, P.F. Boustred, C. Breen, G. Calissanoa, M. Carss, K. Charlton, R. Chatterjee, K. Chen, L. Ciampia, A. Cirak, S. Clapham, P. Clement, G. Coates, G. Coccaa, M. Collier, D.A. Cosgrove, C. Coxa, T. Craddock, N. Crooks, L. Curran, S. Curtis, D. Daly, A. Danecek, P. Day, I.N.M. Day-Williams, A. Dominiczak, A. Down, T. Du, Y. Dunham, I. Durbin, R. Edkins, S. Ekong, R. Ellis, P. Evansa, D.M. Fitzpatrick, D.R. Flicek, P. Floyd, J. Foley, A.R. Franklin, C.S. Futema, M. Gallagher, L. Gaunt, T.R. Geihs, M. Geschwind, D. Greenwood, C.M.T. Griffin, H. Grozeva, D. Guo, X. Guo, X. Gurling, H. Hart, D. Holmans, P. Howie, B. Huang, J. Huang, L. Hubbard, T. Humphries, S.E. Hurles, M.E. Hysi, P. Iotchkova, V. Jackson, D.K. Jamshidi, Y. Joyce, C. Karczewski, K.J. Kaye, J. Keane, T. Kemp, J.P. Kennedy, K. Kent, A. Khawaja, F. Van Kogelenberg, M. Kolb-Kokocinski, A. Lachance, G. Langford, C. Lawson, D. Lee, I. Lek, M. Li, R. Li, Y. Liang, J. Lin, H. Liu, R. Lönnqvist, J. Lopes, L.R. Lopes, M. MacArthur, D.G. Mangino, M. Marchini, J. Maslen, J. Mathieson, I. McGuffin, P. McIntosh, A.M. McKechanie, A.G. McQuillin, A. Memari, Y. Metrustry, S. Migone, N. Min, J.L. Mitchison, H.M. Moayyeri, A. Morris, A. Morris, J. Muntoni, F. Northstone, K. O'Donovan, M.C. Onoufriadis, A. Oualkacha, K. Owen, M.J. Palotie, A. Panoutsopoulou, K. Parker, V. Parr, J.R. Paternoster, L. Paunio, T. Payne, F. Payne, S.J. Perry, J.R.B. Pietilainen, O. Plagnol, V. Pollitt, R.C. Porteous, D.J. Povey, S. Quail, M.A. Quaye, L. Raymond, F.L. Rehnström, K. Richards, J.B. Ridout, C.K. Ring, S. Ritchie, G.R.S. Roberts, N. Robinson, R.L. Savage, D.B. Scambler, P. Schiffels, S. Schmidts, M. Schoenmakers, N. Scott, R.H. Semple, R.K. Serra, E. Sharp, S.I. Shaw, A. Shihab, H.A. Shin, S.-Y. Skuse, D. Small, K.S. Smee, C. Smith, B.H. Davey Smith, G. Soranzo, N. Southam, L. Spasic-Boskovic, O. Spector, T.D. St Clair, D. St Pourcain, B. Stalker, J. Stevens, E. Sun, J. Surdulescu, G. Suvisaari, J. Syrris, P. Taylor, R. Tian, J. Timpson, N.J. Tobin, M.D. Valdes, A.M. Vandersteen, A.M. Vijayarangakannan, P. Visscher, P.M. Wain, L.V. Walter, K. Walters, J.T.R. Wang, G. Wang, J. Wang, Y. Ward, K. Whyte, T. Williams, H.J. Williamson, K.A. Wilson, C. Wilson, S.G. Wong, K. Xu, C. Yang, J. Zhang, F. Zhang, P. Zheng, H.-F.

Abstract

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies. © 2017 The Author(s).

Published
2017

149. Evaluation of optical localization in the visible band for ultrasound guidance in radiotherapy using a robotic arm

Author

Camps, S.M., Costa, M., Stevens, E., Sanches, P.G., Paiva Fonesca, G., Bellezzo, M., Verhaegen, F., and Video Coding & Architectures

Abstract

In many medical fields, spatial localization of devices is of paramount importance to e.g. deliver treatments correctly or to perform accurate diagnostic evaluations. Among the different technologies available, optical localization in the visible band of the spectrum offers many advantages: minimum interference with other instruments, flexibility in position of the devices used and extra features such as patient/operator surface tracking or vital signs monitoring. Its application in the domain of radiotherapy is novel, and potentially very beneficial. In this work we introduced a workflow to test the reliability of one of these systems, developed in house, to localize an ultrasound transducer for ultrasound guided radiation therapy (USgRT). Accuracy, precision, latency, sensitive volume and sensitivity to light intensity were evaluated. The workflow we proposed allowed us to establish that, while all the clinically relevant parameters of the system are acceptable, accuracy in locating the transducer could be as poor as 7-8 mm, therefore not acceptable for the intended purpose of the system. Evaluation of optical localization in the visible band for ultrasound guidance in radiotherapy using a robotic arm. Available from: https://www.researchgate.net/publication/319954001_Evaluation_of_optical_localization_in_the_visible_band_for_ultrasound_guidance_in_radiotherapy_using_a_robotic_arm [accessed Oct 25 2017].

Published
2017

150. CXCR4-Targeted and MMP-Responsive Iron Oxide Nanoparticles for Enhanced Magnetic Resonance Imaging

Author

Gallo, J, Kamaly, N, Lavdas, I, Stevens, E, Nguyen, Q, Wylezinska-Arridge, M, Aboagye, EO, Long, NJ, Cancer Research UK, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), National Institute for Health Research, Scottish Power Foundation, Engineering & Physical Science Research Council (EPSRC), Commission of the European Communities, GlaxoSmithKline Services Unlimited, and US Army (US)

Subjects
EXPRESSION, Azides, Receptors, CXCR4, RELAXIVITY, Chemistry, Multidisciplinary, Contrast Media, Mice, Nude, NANOCARRIER, Tumor Imaging, FREE CLICK CHEMISTRY, Mice, Animals, Magnetite Nanoparticles, CXCR4, Mice, Inbred BALB C, Science & Technology, tumor targeting, Communication, Organic Chemistry, MRI CONTRAST AGENTS, IN-VITRO, self-assembly, Neoplasms, Experimental, General Medicine, CANCER, Magnetic Resonance Imaging, Matrix Metalloproteinases, imaging agents, Chemistry, Alkynes, Physical Sciences, METASTASIS, click chemistry, nanoparticles, 03 Chemical Sciences
Abstract

MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivity and the commonly administered contrast agents lack specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were synthesized that were designed to selectively undergo copper-free click conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby leading to a self-assembled superparamagnetic nanocluster network with T2 signal enhancement properties. For this purpose, IONPs with bioorthogonal azide and alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4-targeted peptide ligands were synthesized and characterized. The IONPs were tested in vitro and T2 signal enhancements of around 160 % were measured when the IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous systemic administration of the bioorthogonal IONPs in tumor-bearing mice demonstrated the signal-enhancing ability of these ‘smart’ self-assembling nanomaterials.

Published
2014

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