18 results on '"B. Lebeau"'
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2. Echinocandins Susceptibility Patterns of 2,787 Yeast Isolates: Importance of the Thresholds for the Detection of FKS Mutations
- Author
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Desnos-Ollivier, Marie, Bretagne, Stéphane, Lortholary, Olivier, Dromer, Françoise, French Mycoses Study Group, The, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This work was supported by Santé Publique France and Institut Pasteur., Members of the French Mycoses Study Group who contributed to the data are, in alphabetical order of the cities, all the French microbiologists and mycologists who sent isolates for characterization of unusual antifungal susceptibility profiles or to contribute to the ongoing surveillance program on the epidemiology of invasive fungal infections in France (YEASTS and RESSIF programs): N. Brieu (CH Aix), T. Chouaki, C. Damiani, A. Totet (CHU Amiens), J. P. Bouchara, D. Chabasse, M. Pihet (CHU Angers), S. Bland (CH Annecy), V. Blanc (CH Antibes), S. Branger (CH Avignon), A. P. Bellanger, L. Millon (CHU Besançon), C. Plassart (CH Beauvais), I. Poilane (Hôpital Jean Verdier, Bondy), I. Accoceberry, L. Delhaes, B. Couprie, F. Gabriel (CH Bordeaux), J. Dunand, A. L. Roux, V. Sivadon-Tardy (Hôpital Ambroise Paré, Boulogne Billancourt), F. Laurent (CH, Bourg en Bresse), S. Legal, E. Moalic, G. Nevez, D. Quinio (CHU Brest), M. Cariou (CH Bretagne Sud), J. Bonhomme, C. Duhamel (CHU, Caen), B. Podac (CH, Chalon sur Saône), S. Lechatch (CH, Charleville-Mézières), C. Soler (Hopital d’Instruction des armées, Clamart), M. Cambon, C. Nourrisson, P. Poirier, D. Pons (CHU, Clermont Ferrand), O. Augereau, I. Grawey (CH, Colmar), N. Fauchet (CHIC, Créteil), A. Bonnin, F. Dalle (CHU, Dijon), P. Cahen, P. Honderlick (CMC, Foch), N. Desbois, C. Miossec (CHU, Fort de France), J. L. Hermann (Hôpital Raymond Poincaré, Garches), M. Cornet, R. Grillot, B. Lebeau, D. Maubon, H. Pelloux (CHU, Grenoble), M. Nicolas (CHU, Guadeloupe), C. Aznar, D. Blanchet, J. F. Carod, M. Demar, (CHU, Guyane), A. Angoulvant (Hôpital Bicêtre, le Kremlin Bicêtre), C. Ciupek (CH, Le Mans), A. Gigandon (Hôpital Marie Lannelongue, Le Plessis Robinson), B. Bouteille (CH Limoges), E. Frealle, D. Poulain, B. Sendid (CHU Lille), D. Dupont, J. Menotti, F. Persat, M.-A. Piens, M. Wallon (CHU, Lyon), C. Cassagne, S. Ranque (CHU, Marseille), T. Benoit-Cattin, L. Collet (CH Mayotte), A. Fiacre (CH Meaux), N. Bourgeois, L. Lachaud, P. Rispail, Y. Sterkers (CHU, Montpellier), M. Machouart (CHU, Nancy), F. Gay-Andrieu, P. Lepape, F. Morio (CHU, Nantes), O. Moquet (CH, Nevers), S. Lefrançois (Hôpital Américain, Neuilly), M. Sasso (CHU, Nimes), F. Reibel (GH, Nord-Essone), M. Gari-Toussaint, L. Hasseine (CHU Nice), L. Bret, D. Poisson (CHR Orléans), S. Brun (Hôpital Avicenne, Paris), C. Bonnal, C. Chochillon, S. Houzé (Hôpital Bichat, Paris), A. Paugam (Hôpital Cochin, Paris), N. Ait-Ammar, F. Botterel, R. Chouk (CHU Henri Mondor, Paris), M. E. Bougnoux, E. Sitterle (Hôpital Necker, Paris), A. Fekkar, R. Piarroux (Hôpital Pitié Salpêtrière, Paris), J. Guitard, C. Hennequin, J.-L. Poirot (Hôpital St Antoine, Paris), M. Gits-Muselli, S. Hamane, C. Lacroix (Hôpital Saint Louis, Paris), S. Bonacorsi, P. Mariani (Hôpital Robert Debré, Paris), D. Moissenet (Hôpital Trousseau, Paris), C. Kauffmann-Lacroix, A. Minoza, E. Perraud, M. H. Rodier (CHU Poitiers), G. Colonna (CH, Porto Vecchio), A. Huguenin, D. Toubas (CHU Reims), S. Chevrier, J. P. Gangneux, F. Robert-Gangneux, C. Guigen (CHU Rennes), O. Belmonte, G. Hoarau, M. C. Jaffar Bandjee, J. Jaubert, S. Picot, N. Traversier (CHU Réunion), L. Favennec, G. Gargala (CHU, Rouen), N. Godineau, C. Tournus (CH, St Denis), C. Mahinc, H. Raberin (CHU, St Etienne), V. Letscher Bru (CHU, Strasbourg), S. Cassaing (CHU, Toulouse), P. Patoz (CH Tourcoing), E. Bailly, J. Chandenier, G. Desoubeaux (CHU Tours), F. Moreau (CH Troyes), P. Munier (CH Valence), E. Mazars (CH Valenciennes), O. Eloy (CH Versailles), E. Chachaty (Institut Gustave Roussy, Villejuif), and and members of the NRCMA (Institut Pasteur, Paris): A. Bertho, C. Blanc, A. Boullié, C. Gautier, V. Geolier, D. Hoinard, and D. Raoux-Barbot for technical help, and K. Boukris-Sitbon, F. Lanternier, A. Alanio, and D. Garcia-Hermoso for their expertise and contribution to the surveillance programs.
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Pharmacology ,Antifungal Agents ,[SDV]Life Sciences [q-bio] ,yeasts ,Microbial Sensitivity Tests ,antifungal resistance ,Anidulafungin ,bacterial infections and mycoses ,rare yeast ,common yeast ,Echinocandins ,Lipopeptides ,Infectious Diseases ,Susceptibility ,Caspofungin ,Drug Resistance, Fungal ,Mutation ,Micafungin ,polycyclic compounds ,FKS mutation ,Humans ,Candidiasis, Invasive ,Pharmacology (medical) ,MIC distribution - Abstract
International audience; Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.
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- 2022
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3. Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth.
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Zhang Y, Chen K, Tang SC, Cai Y, Nambu A, See YX, Fu C, Raju A, Lebeau B, Ling Z, Chan JJ, Tay Y, Mutwil M, Lakshmanan M, Tucker-Kellogg G, Chng WJ, Tenen DG, Osato M, Tergaonkar V, and Fullwood MJ
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- Humans, Animals, Cell Line, Tumor, Mice, CCCTC-Binding Factor metabolism, CCCTC-Binding Factor genetics, DNA Topoisomerases, Type II metabolism, DNA Topoisomerases, Type II genetics, Gene Expression Regulation, Neoplastic, Poly-ADP-Ribose Binding Proteins metabolism, Poly-ADP-Ribose Binding Proteins genetics, Neoplasms genetics, Neoplasms pathology, Neoplasms metabolism, Cell Proliferation, Apoptosis, Indazoles, Pyridones, Enhancer of Zeste Homolog 2 Protein metabolism, Enhancer of Zeste Homolog 2 Protein genetics, Enhancer of Zeste Homolog 2 Protein antagonists & inhibitors, Chromatin metabolism, Repressor Proteins metabolism, Repressor Proteins genetics
- Abstract
Human silencers have been shown to regulate developmental gene expression. However, the functional importance of human silencers needs to be elucidated, such as whether they can form 'super-silencers' and whether they are linked to cancer progression. Here, we show two silencer components of the FGF18 gene can cooperate through compensatory chromatin interactions to form a super-silencer. Double knockout of two silencers exhibited synergistic upregulation of FGF18 expression and changes in cell identity. To perturb the super-silencers, we applied combinational treatment of an enhancer of zeste homolog 2 inhibitor GSK343, and a repressor element 1-silencing transcription factor inhibitor, X5050 ('GR'). Interestingly, GR led to severe loss of topologically associated domains and loops, which were associated with reduced CTCF and TOP2A mRNA levels. Moreover, GR synergistically upregulated super-silencer-controlled genes related to cell cycle, apoptosis and DNA damage, leading to anticancer effects in vivo. Overall, our data demonstrated a super-silencer example and showed that GR can disrupt super-silencers, potentially leading to cancer ablation., Competing Interests: Competing interests: M.J.F. declares seven patents held related to ChIA-PET and nucleic acid molecular biology methods. The other authors declare no competing interests., (© 2024. The Author(s).)
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- 2025
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4. PlantEMS: A comprehensive database of epigenetic modification sites across multiple plant species.
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Dao F, Xie X, Zhang H, Guan Z, Wu C, Su W, Wei Y, Hong F, Luo X, Xie S, Lai H, Gao D, Yang Y, Zhang Y, Ning L, Li S, Hao Y, Lebeau B, Ling CCY, Huang J, Fullwood MJ, Lin H, and Lv H
- Abstract
In summary, PlantEMS is designed to advance plant epigenetics research by providing a comprehensive repository of multi-omics and multi-modification data. This resource enables detailed investigations into the epigenetic regulatory mechanisms underlying essential plant traits and responses, potentially informing innovative strategies for crop management, monitoring, and development., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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5. Combined Inhibition of MNK Signaling and BET Proteins Reveals TGM2 as a Novel Vulnerability in Melanoma.
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Méant A, Moussa O, Lebeau B, Gonçalves C, Richard VR, Cai F, Prabhu SA, Langke M, Guettler EM, Su J, Gagnon N, Zahedi RP, Borchers CH, Miller WH Jr, Del Rincón SV, and Witcher M
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- 2024
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6. Quantum-confined bismuth iodide perovskite nanocrystals in mesoporous matrices.
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Dupé S, Liu D, Ghosh A, Vasenko AS, Pouget S, Schlutig S, Vidal M, Lebeau B, Ling WL, Reiss P, Prezhdo OV, Ryzhikov A, and Aldakov D
- Abstract
Bismuth iodide perovskite nanocrystals are considered a viable alternative to the Pb halide ones due to their reduced toxicity and increased stability. However, it is still challenging to fabricate nanocrystals with a small and controlled size, and their electronic properties are not well understood. Here, we propose the growth of Bi iodide perovskite nanocrystals using different mesoporous silica with ordered pores of controlled diameter as templates. We obtain a series of confined Cs
3 Bi2 I9 and MA3 Bi2 I9 perovskites with diameters of 2.3, 3.7, 7.4, and 9.2 nm, and precise size control. The complex absorption spectra of the encapsulated perovskites cannot be properly fitted using classical Tauc or Elliott formalisms. By fitting the spectra with a modified Elliott formula, the bandgap values and exciton binding energies (70-400 meV) could be extracted. The calculated bandgaps scale with the pore sizes. Using a combined experimental and theoretical approach, we demonstrate for the first time quantum confinement in 0D Bi-iodide perovskite nanocrystals.- Published
- 2024
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7. Reactive and control processes in the development of internalizing and externalizing problems across early childhood to adolescence.
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Harris JL, LeBeau B, and Petersen IT
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Reactive and control processes - e.g., negative emotionality and immediacy preference - may predict distinct psychopathology trajectories. However, externalizing and internalizing problems change in behavioral manifestation across development and across contexts, thus necessitating the use of different measures and informants across ages. This is the first study that created developmental scales for both internalizing and externalizing problems by putting scores from different informants and measures onto the same scale to examine temperament facets as risk factors. Multidimensional linking allowed us to examine trajectories of internalizing and externalizing problems from ages 2 to 15 years ( N = 1,364) using near-annual ratings by mothers, fathers, teachers, other caregivers, and self report. We examined reactive and control processes in early childhood as predictors of the trajectories and as predictors of general versus specific psychopathology in adolescence. Negative emotionality at age 4 predicted general psychopathology and unique externalizing problems at age 15. Wait times on an immediacy preference task at age 4 were negatively associated with age 15 general psychopathology, and positively associated with unique internalizing problems. Findings demonstrate the value of developmental scaling for examining development of psychopathology across a lengthy developmental span and the importance of considering reactive and control processes in development of psychopathology.
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- 2024
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8. MTOR modulation induces selective perturbations in histone methylation which influence the anti-proliferative effects of mTOR inhibitors.
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Kim H, Lebeau B, Papadopoli D, Jovanovic P, Russo M, Avizonis D, Morita M, Afzali F, Ursini-Siegel J, Postovit LM, Witcher M, and Topisirovic I
- Abstract
Emerging data suggest a significant cross-talk between metabolic and epigenetic programs. However, the relationship between the mechanistic target of rapamycin (mTOR), which is a pivotal metabolic regulator, and epigenetic modifications remains poorly understood. Our results show that mTORC1 activation caused by the abrogation of its negative regulator tuberous sclerosis complex 2 (TSC2) coincides with increased levels of the histone modification H3K27me3 but not H3K4me3 or H3K9me3. This selective H3K27me3 induction was mediated via 4E-BP-dependent increase in EZH2 protein levels. Surprisingly, mTOR inhibition also selectively induced H3K27me3. This was independent of TSC2, and was paralleled by reduced EZH2 and increased EZH1 protein levels. Notably, the ability of mTOR inhibitors to induce H3K27me3 levels was positively correlated with their anti-proliferative effects. Collectively, our findings demonstrate that both activation and inhibition of mTOR selectively increase H3K27me3 by distinct mechanisms, whereby the induction of H3K27me3 may potentiate the anti-proliferative effects of mTOR inhibitors., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)
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- 2024
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9. Cobalt Stabilization through Mesopore Confinement on TiO 2 Support for Fischer-Tropsch Reaction.
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Platero F, Todorova S, Aoudjera L, Michelin L, Lebeau B, Blin JL, Holgado JP, Caballero A, and Colón G
- Abstract
Cobalt supported on mesostructured TiO
2 catalysts has been prepared by a wet-impregnation method. The Co/TiO2 catalytic system showed better catalytic performance after support calcination at 380 °C. Co nanoparticles appeared well distributed along the mesopore channels of TiO2 . After reduction pretreatment and reaction, a drastic structural change leads to mesopore structure collapse and the dispersion of the Co nanoparticles on the external surface. Along this complex process, Co species first form discrete nanoparticles inside the pore and then diffuse out as the pore collapses. Through this confinement, a strong metal-support interaction effect is hindered, and highly stable metal active sites lead to better performance for Fischer-Tropsch synthesis reaction toward C5+ products., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)- Published
- 2023
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10. Black women's distress matters: Examining gendered racial disparities in psycho-oncology referral rates.
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Aburizik A, Brindle M, Johnson E, Provencio A, Kivlighan M, and LeBeau B
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- Female, Humans, Male, Racial Groups, Referral and Consultation, White People, Black People psychology, Neoplasms therapy, Neoplasms psychology, Psycho-Oncology, Psychological Distress
- Abstract
Objective: Presently, there is a lack of research examining gendered racial disparities in psycho-oncology referral rates for Black women with cancer. Informed by intersectionality, gendered racism, and the Strong Black Woman framework, this study sought to examine the possibility that Black women are adversely affected by such phenomena as evidenced by lower probability of being referred to psycho-oncology services compared to Black men, White women and White men., Methods: Data for this study consisted of 1598 cancer patients who received psychosocial distress screening at a comprehensive cancer center in a large Midwest teaching hospital. Multilevel logistic modeling was used to examine the probability of referral to psycho-oncology services for Black women, Black men, White women, and White men while controlling for patient-reported emotional and practical problems and psychosocial distress., Results: Results indicated that Black women had the lowest probability of being referred to psycho-oncology services (2%). In comparison, the probability of being referred to psycho-oncology were 10% for White women, 9% for Black men, and 5% for White men. Additionally, as nurses' patient caseload decreased, the probability of being referred to psycho-oncology increased for Black men, White men, and White women. In contrast, nurses' patient caseload had little effect on the probability of being referred to psycho-oncology for Black women., Conclusions: These findings suggest unique factors influence psycho-oncology referral rates for Black women. Findings are discussed with particular focus on how to enhance equitable care for Black women with cancer., (© 2023 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)
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- 2023
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11. TiO 2 -SiO 2 Self-Standing Materials bearing Hierarchical Porosity: MUB-200(x) Series toward 3D-Efficient VOC Photoabatement Properties.
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Layan E, Gupta J, Ly I, Nallet F, Bentaleb A, Laurichesse E, Vallée R, Blin JL, Lebeau B, Louërat F, Le Bechec M, Moonen P, Toupance T, Pigot T, and Backov R
- Abstract
Three-dimensional photoactive self-standing porous materials have been synthesized through the integration of soft chemistry and colloids (emulsions, lyotrope mesophases, and P25 titania nanoparticles). Final multiscale porous ceramics bear 700-1000 m
2 g-1 of micromesoporosity depending on the P25 nanoparticle contents. The applied thermal treatment does not affect the P25 anatase/rutile allotropic phase ratio. Photonic investigations correlated with the foams' morphologies suggest that the larger amount of TiO2 that is introduced, the larger the walls' density and the smaller the mean size of the void macroscopic diameters, with both effects inducing a reduction of the photon transport mean free path ( lt ) with the P25 content increase. A light penetration depth in the range of 6 mm is reached, thus depicting real 3D photonic scavenger behavior. The 3D photocatalytic properties of the MUB-200(x) series, studied in a dynamic "flow-through" configuration, show that the highest photoactivity (concentration of acetone ablated and concentration of CO2 formed) is obtained with the highest monolith height (volume) while providing an average of 75% mineralization. These experimental results validate the fact that these materials, bearing 3D photoactivity, are paving the path for air purification operating with self-standing porous monolith-type materials, which are much easier to handle than powders. As such, the photocatalytic systems can now be advantageously miniaturized, thereby offering indoor air treatment within vehicles/homes while drastically limiting the associated encumbrance. This volumetric counterintuitive acting mode for light-induced reactions may find other relevant advanced applications for photoinduced water splitting, solar fuel, and dye-sensitized solar cells while both optimizing photon scavenging and opening the path for the miniaturization of the processes where encumbrance or a foot-print penalty would be advantageously circumvented.- Published
- 2023
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12. Heterogeneous Photoredox Catalysis Based on Silica Mesoporous Material and Eosin Y: Impact of Material Support on Selectivity of Radical Cyclization.
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Mahmoud N, Awassa J, Toufaily J, Lebeau B, Daou TJ, Cormier M, and Goddard JP
- Abstract
Heterogenization of the photocatalyst appears to be a valuable solution to reach sustainable processes. Rapid and efficient synthesis of supported photocatalyst is still a remaining challenge and the choice of the support material is crucial. The present study aims at preparing a new generation of hybrid inorganic/organic photocatalysts based on silica mesoporous material and Eosin Y. These results highlight the influence of non-covalent interactions between the material support and the reagent impacting the selectivity of the reaction.
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- 2023
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13. Studying children's growth in self-regulation using changing measures to account for heterotypic continuity: A Bayesian approach to developmental scaling.
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Hosch A, Oleson JJ, Harris JL, Goeltz MT, Neumann T, LeBeau B, Hazeltine E, and Petersen IT
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- Child, Humans, Child, Preschool, Longitudinal Studies, Bayes Theorem, Mathematics, Individuality, Self-Control
- Abstract
Self-regulation is thought to show heterotypic continuity-its individual differences endure but its behavioral manifestations change across development. Thus, different measures across time may be necessary to account for heterotypic continuity of self-regulation. This longitudinal study examined children's (N = 108) self-regulation development using 17 measures, including 15 performance-based measures, two questionnaires, and three raters across seven time points. It is the first to use different measures of self-regulation over time to account for heterotypic continuity while using developmental scaling to link the measures onto the same scale for more accurate growth estimates. Assessed facets included inhibitory control, delayed gratification, sustained attention, and executive functions. Some measures differed across ages to retain construct validity and account for heterotypic continuity. A Bayesian longitudinal mixed model for developmental scaling was developed to link the differing measures onto the same scale. This allowed charting children's self-regulation growth across ages 3-7 years and relating it to both predictors and outcomes. Rapid growth occurred from ages 3-6. As a validation of the developmental scaling approach, greater self-regulation was associated with better school readiness (math and reading skills) and fewer externalizing problems. Our multi-wave, multi-facet, multi-method, multi-measure, multi-rater, developmental scaling approach is the most comprehensive to date for assessing the development of self-regulation. This approach demonstrates that developmental scaling may enable studying development of self-regulation across the lifespan., (© 2022 The Authors. Developmental Science published by John Wiley & Sons Ltd.)
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- 2022
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14. Developmental milestones as early indicators of twice-exceptionality.
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LeBeau B, Schabilion K, Assouline SG, Foley Nicpon M, Doobay AF, and Mahatmya D
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- Bayes Theorem, Cognition, Humans, Attention Deficit Disorder with Hyperactivity diagnosis, Autism Spectrum Disorder diagnosis, Autism Spectrum Disorder psychology
- Abstract
Twice-exceptional individuals are those who have high cognitive ability in one or more areas, but also have a diagnosed disability. The needs of these individuals likely differ from those with high cognitive ability without a disability and those who solely have a disability. Intervening early can offer exceptional benefits for twice-exceptional individuals, but this has proved challenging due to the high cognitive abilities masking disabilities. This study explores if parent-reported developmental milestones can predict the number of disabilities diagnosed for an individual, including Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), and Specific Learning Disorder (SLD). Using a clinical sample of about 1,300 individuals, we used a Bayesian cumulative logistic model to explore if developmental milestones can predict the number of diagnoses after controlling for IQ and age. Study results showed that when an individual began to count and read informed predictions for the number of future diagnoses in the clinical sample. Implications for future study and practitioners are discussed in further detail., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)
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- 2022
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15. 3D chromatin remodeling potentiates transcriptional programs driving cell invasion.
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Lebeau B, Jangal M, Zhao T, Wong CK, Wong N, Cañedo EC, Hébert S, Aguilar-Mahecha A, Chabot C, Buchanan M, Catterall R, McCaffrey L, Deblois G, Kleinman C, Park M, Basik M, and Witcher M
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- CCCTC-Binding Factor metabolism, Carcinogenesis genetics, Chromatin genetics, Chromatin metabolism, Humans, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Promoter Regions, Genetic, Chromatin Assembly and Disassembly, Gene Expression Regulation, Neoplastic, Neoplasm Invasiveness genetics, Neoplasm Invasiveness pathology
- Abstract
The contribution of deregulated chromatin architecture, including topologically associated domains (TADs), to cancer progression remains ambiguous. CCCTC-binding factor (CTCF) is a central regulator of higher-order chromatin structure that undergoes copy number loss in over half of all breast cancers, but the impact of this defect on epigenetic programming and chromatin architecture remains unclear. We find that under physiological conditions, CTCF organizes subTADs to limit the expression of oncogenic pathways, including phosphatidylinositol 3-kinase (PI3K) and cell adhesion networks. Loss of a single CTCF allele potentiates cell invasion through compromised chromatin insulation and a reorganization of chromatin architecture and histone programming that facilitates de novo promoter-enhancer contacts. However, this change in the higher-order chromatin landscape leads to a vulnerability to inhibitors of mTOR. These data support a model whereby subTAD reorganization drives both modification of histones at de novo enhancer-promoter contacts and transcriptional up-regulation of oncogenic transcriptional networks.
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- 2022
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16. Single base-pair resolution analysis of DNA binding motif with MoMotif reveals an oncogenic function of CTCF zinc-finger 1 mutation.
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Lebeau B, Zhao K, Jangal M, Zhao T, Guerra M, Greenwood CMT, and Witcher M
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- CCCTC-Binding Factor genetics, CCCTC-Binding Factor metabolism, DNA chemistry, Mutation, Binding Sites, Zinc metabolism, Chromatin genetics
- Abstract
Defining the impact of missense mutations on the recognition of DNA motifs is highly dependent on bioinformatic tools that define DNA binding elements. However, classical motif analysis tools remain limited in their capacity to identify subtle changes in complex binding motifs between distinct conditions. To overcome this limitation, we developed a new tool, MoMotif, that facilitates a sensitive identification, at the single base-pair resolution, of complex, or subtle, alterations to core binding motifs, discerned from ChIP-seq data. We employed MoMotif to define the previously uncharacterized recognition motif of CTCF zinc-finger 1 (ZF1), and to further define the impact of CTCF ZF1 mutation on its association with chromatin. Mutations of CTCF ZF1 are exclusive to breast cancer and are associated with metastasis and therapeutic resistance, but the underlying mechanisms are unclear. Using MoMotif, we identified an extension of the CTCF core binding motif, necessitating a functional ZF1 to bind appropriately. Using a combination of ChIP-Seq and RNA-Seq, we discover that the inability to bind this extended motif drives an altered transcriptional program associated with the oncogenic phenotypes observed clinically. Our study demonstrates that MoMotif is a powerful new tool for comparative ChIP-seq analysis and characterising DNA-protein contacts., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2022
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17. Creating a developmental scale to chart the development of psychopathology with different informants and measures across time.
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Petersen IT and LeBeau B
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- Adolescent, Child, Child, Preschool, Female, Humans, Mothers, Parents, Self Report, Mental Disorders diagnosis, Psychopathology
- Abstract
Research Domain Criteria (RDoC) aims to advance a dimensional, multilevel understanding of psychopathology across the life span. Two key challenges exist in applying a developmental perspective to RDoC: First, the most accurate informants for assessing a person's psychopathology often differ across development (e.g., parents and teachers may be better informants of a person's externalizing problems in early childhood, whereas peer- and self-report may also be important to assess in adolescence). Second, many constructs change in their behavioral manifestation across development (i.e., heterotypic continuity). Thus, different informants and measures across time may be necessary to account for the construct's changing manifestation. The challenge of using different informants and measures of a construct across time is ensuring that the same construct is assessed in a comparable way across development. Vertical scaling creates a developmental scale to link scores from changing informants and measures to account for heterotypic continuity and study people's development of psychopathology across the life span. This is the first study that created a developmental scale to assess people's development by putting different informants and measures on the same scale. We examined the development of externalizing problems from ages 2 to 15 years (N = 1,364) using annual ratings by mothers, fathers, teachers, other caregivers, and self-report. The developmental scale linked different informants and measures on the same scale. This allowed us to chart people's growth trajectories and to identify multilevel risk factors, including poor verbal comprehension. Creating a developmental scale may be crucial to advance RDoC's goal of studying the development of psychopathology across the life span. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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- 2022
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18. Natural water defluoridation by adsorption on Laponite clay.
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Braik S, Amor TB, Michelin L, Rigolet S, Bonne M, Lebeau B, and Hafiane A
- Subjects
- Adsorption, Clay, Humans, Silicates, Thermodynamics, Fluorides
- Abstract
Safe drinking water is a necessity for every human being, but clean water is scarce and not easily available due to natural geochemical factors or industrial pollutant activity. Many issues involving water quality could be greatly improved using clays as adsorbents. We highlight for the first time, the uptake of fluoride from natural water by Laponite, synthetic hectorite clay, in raw and modified state. A series of batch adsorption experiments were carried out to evaluate the adsorption potential of the different parameters. The optimized parameters were: contact time, adsorbent dose and pH. It was found that fluoride uptake from natural water was better using raw Laponite and inorganic-modified Laponite than using organic-modified Laponite clays. Adsorbents were characterized before and after fluoride adsorption by X-ray diffraction, X-ray fluorescence, FTIR, thermo gravimetric analyses and
19 F solid state NMR spectroscopy. The experimental data showed that both Langmuir and Freundlich models fitted an adsorption isotherm well. Thermodynamic parameters such as Gibbs free energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) were calculated. These parameters indicated that fluoride adsorption onto Laponite was nonspontaneous and endothermic in temperature range between 25 and 45 °C.- Published
- 2022
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