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9. A jump to the left and a step to the right: A test of two accounts of peak shift

Author

Gallaghar NJ, Provost S, and Bizo LA

Subjects
1701 Psychology, 1702 Cognitive Sciences, Behavioral Science & Comparative Psychology
Abstract

© 2019, The Author(s). “Peak Shift” usually occurs following intradimensional-discrimination training and involves a shift of the peak of the generalization gradient away from the original discriminative stimulus (S+) in a direction away from an S-. Two theoretical accounts of peak shift, the gradient interaction theory (GIT) and adaptation level theory (ALT), were compared. The effects of asymmetric test stimuli and the impact of instructions to participants for them to treat stimuli as members of categories on generalization gradients were investigated. In Experiment 1, the relation between peak shifts obtained when an extended asymmetric set of test stimuli was employed and the occurrence of categorization of the stimuli involved was investigated in four separate conditions. Two involved temporal discrimination, one involved line-angle discrimination, and one involved a compound line-angle and temporal cue discrimination. If participants treated the stimuli as belonging to discrete categories, such as hands-on a clock, rather than as being on continuous dimensions then responding to the compound cue was expected to result in attenuation of blocking of a peak shift. However, the peak shift obtained to the three cue types were the same. In Experiment 2, an independent group of participants was given explicit instructions to treat the line angles as if they were the hands of a clock face and this eliminated peak shift. The results from the present experiments support an ALT interpretation, although the peak shifts were significantly smaller in magnitude than predicted by this account.

Published
2020

10. Oncogenic cooperation between TCF7-SPI1 and NRAS(G12D) requires β-catenin activity to drive T-cell acute lymphoblastic leukemia

Author

Van Thillo, Q, De Bie, J, Seneviratne, JA, Demeyer, S, Omari, S, Balachandran, A, Zhai, V, Tam, WL, Sweron, B, Geerdens, E, Gielen, O, Provost, S, Segers, H, Boeckx, N, Marshall, GM, Cheung, BB, Isobe, K, Kato, I, Takita, J, Amos, TG, Deveson, IW, McCalmont, H, Lock, RB, Oxley, EP, Garwood, MM, Dickins, RA, Uyttebroeck, A, Carter, DR, Cools, J, de Bock, CE, Van Thillo, Q, De Bie, J, Seneviratne, JA, Demeyer, S, Omari, S, Balachandran, A, Zhai, V, Tam, WL, Sweron, B, Geerdens, E, Gielen, O, Provost, S, Segers, H, Boeckx, N, Marshall, GM, Cheung, BB, Isobe, K, Kato, I, Takita, J, Amos, TG, Deveson, IW, McCalmont, H, Lock, RB, Oxley, EP, Garwood, MM, Dickins, RA, Uyttebroeck, A, Carter, DR, Cools, J, and de Bock, CE

Abstract

Spi-1 Proto-Oncogene (SPI1) fusion genes are recurrently found in T-cell acute lymphoblastic leukemia (T-ALL) cases but are insufficient to drive leukemogenesis. Here we show that SPI1 fusions in combination with activating NRAS mutations drive an immature T-ALL in vivo using a conditional bone marrow transplant mouse model. Addition of the oncogenic fusion to the NRAS mutation also results in a higher leukemic stem cell frequency. Mechanistically, genetic deletion of the β-catenin binding domain within Transcription factor 7 (TCF7)-SPI1 or use of a TCF/β-catenin interaction antagonist abolishes the oncogenic activity of the fusion. Targeting the TCF7-SPI1 fusion in vivo with a doxycycline-inducible knockdown results in increased differentiation. Moreover, both pharmacological and genetic inhibition lead to down-regulation of SPI1 targets. Together, our results reveal an example where TCF7-SPI1 leukemia is vulnerable to pharmacological targeting of the TCF/β-catenin interaction.

Published
2021

12. Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

Author

Webb, T.R., Erdmann, J., Stirrups, K.E., Stitziel, N.O., Masca, N.G.D., Jansen, H., Kanoni, S., Nelson, C.P., Ferrario, P.G., Konig, I.R., Eicher, J.D., Johnson, A.D., Hamby, S.E., Betsholtz, C., Ruusalepp, A., Franzen, O., Schadt, E.E., Bjorkegren, J.L.M., Weeke, P.E., Auer, P.L., Schick, U.M., Lu, Y.C., Zhang, H., Dube, M.P., Goel, A., Farrall, M., Peloso, G.M., Won, H.H., R. do, Iperen, E. van, Kruppa, J., Mahajan, A., Scott, R.A., Willenborg, C., Braund, P.S., Capelleveen, J.C. van, Doney, A.S.F., Donnelly, L.A., Asselta, R., Merlini, P.A., Duga, S., Marziliano, N., Denny, J.C., Shaffer, C., El-Mokhtari, N.E., Franke, A., Heilmann, S., Hengstenberg, C., Hoffmann, P., Holmen, O.L., Hveem, K., Jansson, J.H., Jockel, K.H., Kessler, T., Kriebel, J., Laugwitz, K.L., Marouli, E., Martinelli, N., McCarthy, M.I., Zuydam, N.R. van, Meisinger, C., Esko, T., Mihailov, E., Escher, S.A., Alver, M., Moebus, S., Morris, A.D., Virtamo, J., Nikpay, M., Olivieri, O., Provost, S., AlQarawi, A., Robertson, N.R., Akinsansya, K.O., Reilly, D.F., Vogt, T.F., Yin, W., Asselbergs, F.W., Kooperberg, C., Jackson, R.D., Stahl, E., Muller-Nurasyid, M., Strauch, K., Varga, T.V., Waldenberger, M., Zeng, L.Y., Chowdhury, R., Salomaa, V., Ford, I., Jukema, J.W., Amouyel, P., Kontto, J., Nordestgaard, B.G., Ferrieres, J., Saleheen, D., Sattar, N., Surendran, P., Wagner, A., Young, R., Howson, J.M.M., Butterworth, A.S., Danesh, J., Ardissino, D., Bottinger, E.P., Erbel, R., Franks, P.W., Girelli, D., Hall, A.S., Hovingh, G.K., Kastrati, A., Lieb, W., Meitinger, T., Kraus, W.E., Shah, S.H., McPherson, R., Orho-Melander, M., Melander, O., Metspalu, A., Palmer, C.N.A., Peters, A., Rader, D.J., Reilly, M.P., Loos, R.J.F., Reiner, A.P., Roden, D.M., Tardif, J.C., Thompson, J.R., Wareham, N.J., Watkins, H., Willer, C.J., Samani, N.J., Schunkert, H., Deloukas, P., Kathiresan, S., Wellcome Trust Case Control, MORGAM Investigators, and Myocardial Infarction Genetics

Subjects
expression quantitative trait loci, single nucleotide polymorphism, cholesteryl ester transfer protein, genome-wide association, genetics
Abstract

BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10(-4) with a range of other diseases/traits. CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.

Published
2017

19. A PROSPECTIVE INVESTIGATION OF THE IMPACT OF AGTR1 A1166C ON THE NEUROHORMONAL AND HEMODYNAMIC EFFECTS OF CANDESARTAN IN HEART FAILURE PATIENTS

Author

de Denus, S., primary, Dubé, M.P., additional, Fouodjio, R., additional, Huynh, T., additional, Leblanc, M.H., additional, Lepage, S., additional, Sheppard, R., additional, Giannetti, N., additional, Lavoie, J., additional, Mansour, A., additional, Phillips, M.S., additional, Turgeon, J., additional, Provost, S., additional, Normand, V., additional, Mongrain, I., additional, Langlois, M., additional, O'Meara, E., additional, Ducharme, A., additional, Racine, N., additional, Guertin, M.C., additional, Tardif, J.C., additional, Rouleau, J.L., additional, and White, M., additional

Published
2016
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20. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials

Author

de Denus, S, primary, Rouleau, J L, additional, Mann, D L, additional, Huggins, G S, additional, Cappola, T P, additional, Shah, S H, additional, Keleti, J, additional, Zada, Y F, additional, Provost, S, additional, Bardhadi, A, additional, Phillips, M S, additional, Normand, V, additional, Mongrain, I, additional, and Dubé, M-P, additional

Published
2016
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22. Les 'GASC' (GBM-associated stromal cells): mise en évidence et rôle dans la croissance des cellules tumorales

Author

Menei, Philippe, Clavreul, Anne, Etcheverry, A, Chassevent, Agnès, Quillien, V, Avril, Tony, Jourdan, Marie-Lise, Michalack-Provost, S, François, Patrick, Carré, JL, Mosser, Jean, Network, Great, Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Centre Paul Papin, CRLCC Paul Papin, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Genomic Research Laboratory, Service of Infectious Diseases, Hôpitaux Universitaires de Genève (HUG), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Génétique moléculaire et Génomique [CHU Rennes], CHU Pontchaillou [Rennes], Univ Angers, Okina, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service de Génétique moléculaire et Génomique [CHU Rennes]

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2012

24. Primary healthcare solo practices: homogeneous or heterogeneous?

Author

Pineault, R., Silva, R. de, Provost, S., Beaulieu, M.D., Boivin, A., Couture, A., Prud'homme, A., Pineault, R., Silva, R. de, Provost, S., Beaulieu, M.D., Boivin, A., Couture, A., and Prud'homme, A.

Abstract

Contains fulltext : 138974.pdf (publisher's version ) (Open Access), Introduction. Solo practices have generally been viewed as forming a homogeneous group. However, they may differ on many characteristics. The objective of this paper is to identify different forms of solo practice and to determine the extent to which they are associated with patient experience of care. Methods. Two surveys were carried out in two regions of Quebec in 2010: a telephone survey of 9180 respondents from the general population and a postal survey of 606 primary healthcare (PHC) practices. Data from the two surveys were linked through the respondent's usual source of care. A taxonomy of solo practices was constructed (n = 213), using cluster analysis techniques. Bivariate and multilevel analyses were used to determine the relationship of the taxonomy with patient experience of care. Results. Four models were derived from the taxonomy. Practices in the "resourceful networked" model contrast with those of the "resourceless isolated" model to the extent that the experience of care reported by their patients is more favorable. Conclusion. Solo practice is not a homogeneous group. The four models identified have different organizational features and their patients' experience of care also differs. Some models seem to offer a better organizational potential in the context of current reforms.

Published
2014

26. University students' views on the nature of science and psychology

Author

Provost, S., Martin, F., Peacock, A., Lipp, Ottmar, Bath, D., Hannan, G., Provost, S., Martin, F., Peacock, A., Lipp, Ottmar, Bath, D., and Hannan, G.

Abstract

Students' understanding of the nature of science (NOS), and the degree to which they perceive their discipline to be part of science, are critical to their academic development in psychology. In Study 1, 650 first-year psychology students from three universities in Australia completed the Psychology as a Science (PAS) questionnaire, an adjective checklist relating to science and psychology, and the Science Knowledge and Attitudes (SKA) scale. Results confirmed the limited value of the PAS to identify components of the NOS, but indicated that students view psychology to be a science within a few weeks of the commencement of their study at university. Three factors underlying the SKA scale were identified: naïve view of science (NVS), social and cultural perspective (SCP), and knowledge of refutability (KR). In Study 2, 622 students at the University of Tasmania completed the SKA and items relating to their beliefs about studying. Scores on the three factors were correlated with beliefs about studying, scores on KR increased with years of study, and scores on NVS decreased with years of study. These data suggest that our educational practices do in fact lead to appropriate changes in students' NOS understanding in a manner consistent with the learning outcomes underpinning psychology graduate attributes.

Published
2011

34. Predictors of pretravel consultation in tourists from Quebec (Canada).

Author

Provost S, Soto JC, Provost, S, and Soto, J C

Abstract

Background: Although many tourists from Quebec (Canada) each year visit destinations at risk for infectious diseases, only a few of them seek travel health advice. To identify the determinants of travel health consultation, we conducted a study among Quebec's tourists visiting two popular sun destinations.Methods: A conceptual model based on psychosocial determinants of human behavior was constructed. A cross-sectional survey was carried out, from January to April 1999, on two samples of travelers planning to visit Mexico and the Dominican Republic. One sample was composed of people who did not consult a travel clinic (cluster sampling in seven flights), and the other sample was one of clients of travel clinics (purposive selection of 13 specialized clinics located in Quebec). A 34-item self-administered bilingual questionnaire was distributed to travelers. Statistical analysis included a multivariate approach (logistic regression).Results: A total of 2,242 travelers were surveyed (response rate in flight 75% and in clinics 99%). We present only results reported by French-speaking tourists: 1,152 who did not consult a travel clinic and were reached in flight, and 449 who were reached in clinics. Multivariate analyses indicated that travel agent recommendation was the most important predictor of consultation among travelers (OR 8.0, 95% CI 5.1-13), especially among those under 45 years of age and those who never sought pretravel consultation before (OR 21, 95% CI 11-41). Other important predictors were: traveling for the first time, traveling with children, previous consultation, perception about efficacy of immunization, risk perception, and information from travel agent, family doctor, and pharmacist.Conclusions: Despite its limitations, this study provides data that should help improve public health interventions aimed at encouraging travelers to get a pretravel consultation. [ABSTRACT FROM AUTHOR]

Published
2001

35. CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas

Author

Riant, F., primary, Bergametti, F., additional, Fournier, H.-D., additional, Chapon, F., additional, Michalak-Provost, S., additional, Cecillon, M., additional, Lejeune, P., additional, Hosseini, H., additional, Choe, C., additional, Orth, M., additional, Bernreuther, C., additional, Boulday, G., additional, Denier, C., additional, Labauge, P., additional, and Tournier-Lasserve, E., additional

Published
2013
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37. G.P.126 “Strongman syndrome”: A new autosomal dominant herculean painful myopathy

Author

Al-Bustani, N., primary, Tétreault, M., additional, Provost, S., additional, Bolduc, V., additional, Srour, M., additional, O’Ferrall, E.K., additional, Dubé, M.P., additional, Bouchard, J.P., additional, Ravenscroft, G., additional, Laing, N.G., additional, Bignell, D., additional, Lamont, P.J., additional, Mathieu, J., additional, and Brais, B., additional

Published
2012
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38. Methylomic changes during conversion to psychosis

Author

Kebir, O, Chaumette, B, Rivollier, F, Miozzo, F, Lemieux Perreault, L P, Barhdadi, A, Provost, S, Plaze, M, Bourgin, J, Gaillard, R, Mezger, V, Dubé, M-P, and Krebs, M-O

Abstract

The onset of psychosis is the consequence of complex interactions between genetic vulnerability to psychosis and response to environmental and/or maturational changes. Epigenetics is hypothesized to mediate the interplay between genes and environment leading to the onset of psychosis. We believe we performed the first longitudinal prospective study of genomic DNA methylation during psychotic transition in help-seeking young individuals referred to a specialized outpatient unit for early detection of psychosis and enrolled in a 1-year follow-up. We used Infinium HumanMethylation450 BeadChip array after bisulfite conversion and analyzed longitudinal variations in methylation at 411 947 cytosine–phosphate–guanine (CpG) sites. Conversion to psychosis was associated with specific methylation changes. Changes in DNA methylation were significantly different between converters and non-converters in two regions: one located in 1q21.1 and a cluster of six CpG located in GSTM5 gene promoter. Methylation data were confirmed by pyrosequencing in the same population. The 100 top CpGs associated with conversion to psychosis were subjected to exploratory analyses regarding the related gene networks and their capacity to distinguish between converters and non-converters. Cluster analysis showed that the top CpG sites correctly distinguished between converters and non-converters. In this first study of methylation during conversion to psychosis, we found that alterations preferentially occurred in gene promoters and pathways relevant for psychosis, including oxidative stress regulation, axon guidance and inflammatory pathways. Although independent replications are warranted to reach definitive conclusions, these results already support that longitudinal variations in DNA methylation may reflect the biological mechanisms that precipitate some prodromal individuals into full-blown psychosis, under the influence of environmental factors and maturational processes at adolescence.

Published
2017
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39. GR.2 A deep intronic FGF14 GAA repeat expansion causes late-onset cerebellar ataxia

Author

Pellerin, D, Danzi, MC, Wilke, C, Renaud, M, Fazal, S, Dicaire, M, Scriba, CK, Ashton, C, Yanick, C, Beijer, D, Rebelo, A, Rocca, C, Jaunmuktane, Z, Sonnen, JA, Larivière, R, Genis, D, Porcel, L, Choquet, K, Sakalla, R, Provost, S, Tétreault, M, Reiling, SJ, Nagy, S, Nishadham, V, Purushottam, M, Vengalil, S, Bardhan, M, Nalini, A, Chen, Z, Mathieu, J, Massie, R, Chalk, CH, Lafontaine, A, Evoy, F, Rioux, M, Ragoussis, J, Boycott, KM, Dubé, M, Duquette, A, Houlden, H, Ravenscroft, G, Laing, NG, Lamont, P, Saporta, MA, Schüle, R, Schöls, L, La Piana, R, Synofzik, M, Zuchner, S, and Brais, B

Abstract

Background: The late-onset cerebellar ataxias (LOCAs) have until recently resisted molecular diagnosis. Contributing to this diagnostic gap is that non-coding structural variations, such as repeat expansions, are not fully accessible to standard short-read sequencing analysis. Methods: We combined bioinformatics analysis of whole-genome sequencing and long-read sequencing to search for repeat expansions in patients with LOCA. We enrolled 66 French-Canadian, 228 German, 20 Australian and 31 Indian patients. Pathogenic mechanisms were studied in post-mortem cerebellum and induced pluripotent stem cell (iPSC)-derived motor neurons from 2 patients. Results: We identified 128 patients who carried an autosomal dominant GAA repeat expansion in the first intron of the FGF14gene. The expansion was present in 61%, 18%, 15% and 10% of patients in the French-Canadian, German, Australian and Indian cohorts, respectively. The pathogenic threshold was determined to be (GAA)≥250, although incomplete penetrance was observed in the (GAA)250-300range. Patients developed a slowly progressive cerebellar syndrome at an average age of 59 years. Patient-derived post-mortem cerebellum and induced motor neurons both showed reduction in FGF14RNA and protein expression compared to controls. Conclusions: This intronic, dominantly inherited GAA repeat expansion in FGF14represents one of the most common genetic causes of LOCA uncovered to date.

Published
2023
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