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109. integration on smooth rigid varieties and invariants of degenerations

Author

SEBAG, Julien, LOESER, F., Sebag, Julien, Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Département de Mathématiques et Applications - ENS Paris (DMA), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut de Mathématiques de Jussieu (IMJ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de Mathématiques Laurent Schwartz (CMLS), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure - Paris (ENS Paris)

Subjects
[MATH.MATH-AG] Mathematics [math]/Algebraic Geometry [math.AG], [MATH.MATH-AG]Mathematics [math]/Algebraic Geometry [math.AG], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2003

110. Motivic Integration and its Interactions with Model Theory and Non-Archimedean Geometry. Volume1

Author

Cluckers, Raf, Nicaise, Johannes, Sebag, Julien, Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Raf Cluckers, Johannes Nicaise, Julien Sebag, Laboratoire Paul Painlevé - UMR 8524 ( LPP ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Raf Cluckers, Johannes Nicaise, Julien Sebag, Laboratoire Paul Painlevé - UMR 8524 (LPP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Published
2011

111. Motivic Integration and its Interactions with Model Theory and Non-Archimedean Geometry. Volume 2

Author

Cluckers, Raf, Nicaise, Johannes, Sebag, Julien, Laboratoire Paul Painlevé - UMR 8524 (LPP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Institut de Recherche Mathématique de Rennes (IRMAR), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Raf Cluckers, Johannes Nicaise, Julien Sebag, Laboratoire Paul Painlevé - UMR 8524 ( LPP ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Raf Cluckers, Johannes Nicaise, Julien Sebag, Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Published
2011

115. A note on motivic integration in mixed characteristic

Author

Nicaise , Johannes, Sebag , Julien, Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire Paul Painlevé - UMR 8524 ( LPP ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Paul Painlevé - UMR 8524 (LPP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
Mathematics - Algebraic Geometry, FOS: Mathematics, [MATH.MATH-AG]Mathematics [math]/Algebraic Geometry [math.AG], Algebraic Geometry (math.AG), [ MATH.MATH-AG ] Mathematics [math]/Algebraic Geometry [math.AG]
Abstract

We introduce a quotient of the Grothendieck ring of varieties by identifying classes of universally homeomorphic varieties. We show that the standard realization morphisms factor through this quotient, and we argue that it is the correct value ring for the theory of motivic integration on formal schemes and rigid varieties in mixed characteristic. The present note is an excerpt of a detailed survey paper which will be published in the proceedings of the conference "Motivic integration and its interactions with model theory and non-archimedean geometry" (ICMS, 2008).

Published
2009

117. Nilpotency in arc scheme of plane curves.

Author

Kpognon, Kodjo and Sebag, Julien

Subjects
DIFFERENTIAL dimension polynomials, NILPOTENT groups, PLANE curves, IDEALS (Algebra), RING theory
Abstract

Letkbe a field of characteristic 0. Letbe a non-constant reduced polynomial. In this article we study the differential idealof the differential ring. We introduce theS-algorithm which allows, for every differential polynomial, to test if it belongs or not to the differential ideal. Another consequence of this study is to establish a precise characterization of the reducedness of the arc scheme associated with a plane curveX, defined overk, in terms of the geometry ofX. [ABSTRACT FROM AUTHOR]

Published
2017
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118. Structure of the Melanocortin-2 Receptor Accessory Protein MRAP and its Roles in the Regulation of Melanocortin Receptors Trafficking and Signaling

Author

Sebag, Julien A., Hinkle, Patricia M., Sebag, Julien A., and Hinkle, Patricia M.

Abstract

Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Pharmacology and Physiology, 2008., The melanocortin-2 receptor or adrenocorticotropic hormone (ACTH) receptor is the main regulator of glucocorticoid synthesis. Loss of function of MC2 receptors causes a severe glucocorticoid deficiency that, if not treated, results in death. Interestingly, the MC2 receptor requires the MC2 receptor accessory protein (MRAP) for proper trafficking to the plasma membrane. These studies were performed to better understand the structure of the single transmembrane spanning protein MRAP and how it regulates melanocortin receptor trafficking and function. We show that MRAP displays a previously uncharacterized topology. Epitopes on both the N- and C-terminal ends of MRAP were localized on the external face of CHO cells at comparable levels. Using antibodies raised against N- and C-terminal MRAP peptides, we demonstrated that both ends of endogenous MRAP face the outside in adrenal cells. Nearly half of MRAP was glycosylated at the single endogenous N-terminal glycosylation site, and over half was glycosylated when the natural glycosylation site was replaced by one in the C-terminal domain. Coimmunoprecipitation of differentially tagged MRAPs established that MRAP is a dimer. By selectively immunoprecipitating cell surface MRAP in one or the other orientation, we showed that MRAP homodimers are antiparallel and form a stable complex with MC2 receptor. In the absence of MRAP, MC2 receptor was trapped in the endoplasmic reticulum, but with MRAP, the MC2 receptor was glycosylated and localized on the plasma membrane, where it signaled in response to ACTH. MRAP is the first eukaryotic membrane protein identified with an antiparallel homodimeric structure. We also showed that an epitope-tagged chaperone for odorant and taste receptors, Receptor Transporting Protein-1S (RTP-1S), also displayed dual topology, suggesting that this unusual structure may be common to several GPCR accessory proteins. We used bimolecular fluorescence complementation to ask where MRAP achieves dual topo

Published
2011

135. Neutrophils Alter DNA Repair Landscape to Impact Survival and Shape Distinct Therapeutic Phenotypes of Colorectal Cancer.

Author

Bui, Triet M., Butin-Israeli, Veronika, Wiesolek, Hannah L., Zhou, Meredith, Rehring, Jake F., Wiesmüller, Lisa, Wu, Jennifer D., Yang, Guang-Yu, Hanauer, Stephen B., Sebag, Julien A., and Sumagin, Ronen

Abstract

Tumor-infiltrating neutrophils (polymorphonuclear neutrophils [PMNs]) are a prominent feature of colorectal cancer (CRC), where they can promote cytotoxicity or exacerbate disease outcomes. We recently showed that in acute colon injury, PMNs can increase DNA double-strand break (DSB) burden and promote genomic instability via microRNA-dependent inhibition of homologous recombination (HR) repair. In this study, we aimed to establish whether in inflamed colon, neutrophils shape the DSB-repair responses to impact CRC progression and sensitivity/resistance to DNA-repair targeted therapy. Human sporadic CRC biopsies, The Cancer Genome Atlas gene expression analyses, tumor xenografts, and murine CRC models, as well as small-molecule inhibition of key DSB-repair factors were leveraged to investigate changes in the DSB-repair landscape and identify unique CRC responses with/without tumor infiltration by PMNs. We reveal that neutrophils exert a functional dualism in cancer cells, driving temporal modulation of the DNA damage landscape and resolution of DSBs. PMNs were found to promote HR deficiency in low-grade CRC by miR-155-dependent downregulation of RAD51, thus attenuating tumor growth. However, neutrophil-mediated genotoxicity due to accumulation of DSBs led to the induction of non-homologous end-joining (NHEJ), allowing for survival and growth of advanced CRC. Our findings identified a PMN-induced HR-deficient CRC phenotype, featuring low RAD51 and low Ku70 levels, rendering it susceptible to synthetic lethality induced by clinically approved PARP1 inhibitor Olaparib. We further identified a distinct PMN-induced HR-deficient CRC phenotype, featuring high Ku70 and heightened NHEJ, which can be therapeutically targeted by specific inhibition of NHEJ. Our work delineates 2 mechanism-based translatable therapeutic interventions in sporadic CRC. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2021
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137. MRAP2 inhibits β-arrestin recruitment to the ghrelin receptor by preventing GHSR1a phosphorylation.

Author

Rouault, Alix A. J., Buscaglia, Paul, and Sebag, Julien A.

Subjects
*GHRELIN receptors, *MELANOCORTIN receptors, *ARRESTINS, *PHOSPHORYLATION, *PROTEIN receptors
Abstract

The melanocortin receptor accessory protein 2 (MRAP2) is essential for several physiological functions of the ghrelin receptor growth hormone secretagogue receptor 1a (GHSR1a), including increasing appetite and suppressing insulin secretion. In the absence of MRAP2, GHSR1a displays high constitutive activity and a weak G-protein–mediated response to ghrelin and readily recruits β-arrestin. In the presence of MRAP2, however, G-protein–mediated signaling via GHSR1a is strongly dependent on ghrelin stimulation and the recruitment of β-arrestin is significantly diminished. To better understand how MRAP2 modifies GHSR1a signaling, here we investigated the role of several phosphorylation sites within the C-terminal tail and third intracellular loop of GHSR1a, as well as the mechanism behind MRAP2-mediated inhibition of β-arrestin recruitment. We show that Ser252 and Thr261 in the third intracellular loop of GHSR1a contribute to β-arrestin recruitment, whereas the Cterminal region is not essential for β-arrestin interaction. Additionally, we found that MRAP2 inhibits GHSR1a phosphorylation by blocking the interaction of GRK2 and PKC with the receptor. Taken together, these data suggest that MRAP2 alters GHSR1a signaling by directly impacting the phosphorylation state of the receptor and that the C-terminal tail of GHSR1a prevents rather than contribute to β- arrestin recruitment. [ABSTRACT FROM AUTHOR]

Published
2022
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138. A question of Joseph Ritt from the point of view of vertex algebras.

Author

Arakawa, Tomoyuki, Kawasetsu, Kazuya, and Sebag, Julien

Subjects
*ALGEBRA, *INTEGERS, *DIFFERENTIAL algebra
Abstract

Let k be a field of characteristic zero. This paper studies a problem proposed by Joseph F. Ritt in 1950. Precisely, we prove that (1) If p ⩾ 2 is an integer, for every integer i ∈ N , the nilpotency index of the image of T i in the ring k { T } / [ T p ] equals (i + 1) p − i. (2) For every pair of integers (i , j) , the nilpotency index of the image of T i U j in the ring k { T } / [ T U ] equals i + j + 1. [ABSTRACT FROM AUTHOR]

Published
2021
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139. ARC SCHEME AND HIGHER DIFFERENTIAL FORMS

Author

Le Dréau, Yann, Sebag, Julien, Le Dréau, Yann, and Sebag, Julien

Abstract

Let k be a field. In this article, we identify the component of weight 2 of the natural Gm,kgraduation on the k-algebra of the arc scheme attached to an affine algebraic variety X with the module of the 2-nd order derivations on X. We in particular deduce, from this property, characterizations of the geometry of hypersurfaces (in affine spaces) in terms of the nilpotency on arc scheme.

140. ARC SCHEME AND HIGHER DIFFERENTIAL FORMS

Author

Le Dréau, Yann, Sebag, Julien, Le Dréau, Yann, and Sebag, Julien

Abstract

Let k be a field. In this article, we identify the component of weight 2 of the natural Gm,kgraduation on the k-algebra of the arc scheme attached to an affine algebraic variety X with the module of the 2-nd order derivations on X. We in particular deduce, from this property, characterizations of the geometry of hypersurfaces (in affine spaces) in terms of the nilpotency on arc scheme.

141. Regions of MRAP2 required for the inhibition of orexin and prokineticin receptor signaling.

Author

Rouault, Alix A.J., Lee, Abigail A., and Sebag, Julien A.

Subjects
*MELANOCORTIN receptors, *OREXINS, *PROKINETICINS, *FOOD consumption, *CALORIC expenditure, *CELLULAR signal transduction, *PROTEIN expression
Abstract

The Melanocortin Receptor Accessory Protein 2 (MRAP2) regulates the activity of several GPCRs involved in the control of food intake and energy expenditure. While MRAP2 was originally thought to exclusively interact with melanocortin receptors we have recently shown that it interacts with and inhibits the trafficking and signaling of the prokineticin receptor 1 (PKR1). In this study we demonstrate a new role of MRAP2 in the regulation of the orexin receptor 1 (OX1R) and identify the specific regions of MRAP2 required for the regulation of OX1R and PKR1. Importantly, like MC4R and PKRs, OX1R is predominately expressed in the brain where it regulates food intake. By demonstrating that MRAP2 modulates the activity of OX1R we further establish the critical role of MRAP2 in the control of energy homeostasis. [ABSTRACT FROM AUTHOR]

Published
2017
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142. Activation of amygdala prokineticin receptor 2 neurons drives the anorexigenic activity of the neuropeptide PK2.

Author

Yin, Terry C., Mittal, Ayushi, Buscaglia, Paul, Wenxian Li, and Sebag, Julien A.

Subjects
*HYPOTHALAMUS, *AMYGDALOID body, *NEURONS, *MELANOCORTIN receptors, *TRAFFIC signs & signals, *FOOD consumption
Abstract

Energy homeostasis is a complex system involving multiple hormones, neuropeptides, and receptors. Prokineticins (PK1 and PK2) are agonists to two G protein--coupled receptors, prokineticin receptor 1 and 2 (PKR1 and PKR2), which decrease food intake when injected in rodents. The relative contribution of PKR1 and PKR2 to the anorexigenic effect of PK2 and their site of action in the brain have not yet been elucidated. While PKR1 and PKR2 are both expressed in the hypothalamus, a central region involved in the control of energy homeostasis, PKR2 is also present in the amygdala, which has recently been shown to regulate food intake in response to several anorexigenic signals. PKR trafficking and signaling are inhibited by the melanocortin receptor accessory protein 2 (MRAP2), thus suggesting that MRAP2 has the potential to alter the anorexigenic activity of PK2 in vivo. In this study, we investigated the importance of PKR1 and PKR2 for PK2- mediated inhibition of food intake, the brain region involved in this function, and the effect of MRAP2 on PK2 action in vivo. Using targeted silencing of PKR2 and chemogenetic manipulation of PKR2 neurons, we show that the anorexigenic effect of PK2 is mediated by PKR2 in the amygdala and that altering MRAP2 expression in PKR2 neurons modulates the activity of PK2. Collectively, our results provide evidence that inhibition of food intake by PKs is not mediated through activation of hypothalamic neurons but rather amygdala PKR2 neurons and further establishes the importance of MRAP2 in the regulation of energy homeostasis. [ABSTRACT FROM AUTHOR]

Published
2023
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143. Insulin sensitization by small molecules enhancing GLUT4 translocation.

Author

Yin, Terry C., Van Vranken, Jonathan G., Srivastava, Dhiraj, Mittal, Ayushi, Buscaglia, Paul, Moore, Autumn E., Verdinez, Jissele A., Graham, Aschleigh E., Walsh, Susan A., Acevedo, Michael A., Kerns, Robert J., Artemyev, Nikolai O., Gygi, Steven P., and Sebag, Julien A.

Subjects
*SMALL molecules, *TYPE 2 diabetes, *GLUCOSE transporters, *INSULIN, *INSULIN sensitivity, *PROTEIN structure
Abstract

Insulin resistance (IR) is the root cause of type II diabetes, yet no safe treatment is available to address it. Using a high throughput compatible assay that measures real-time translocation of the glucose transporter glucose transporter 4 (GLUT4), we identified small molecules that potentiate insulin action. In vivo , these insulin sensitizers improve insulin-stimulated GLUT4 translocation, glucose tolerance, and glucose uptake in a model of IR. Using proteomic and CRISPR-based approaches, we identified the targets of those compounds as Unc119 proteins and solved the structure of Unc119 bound to the insulin sensitizer. This study identifies compounds that have the potential to be developed into diabetes treatment and establishes Unc119 proteins as targets for improving insulin sensitivity. [Display omitted] • HiBiT-GLUT4 can be used to monitor GLUT4 translocation in real time • HTS identified small molecules that increase insulin-stimulated GLUT4 translocation • Unc119B regulates GLUT4 translocation • Targeting Unc119B has the potential to improve insulin sensitivity Reversing insulin resistance is a promising approach for the treatment of type II diabetes. Yin et al. identified compounds that improve insulin sensitivity and promote glucose uptake in storage tissues. These insulin sensitizers act by binding to Unc119B, identifying this protein as a regulator of glucose homeostasis. [ABSTRACT FROM AUTHOR]

Published
2023
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144. Quasi-unipotent motives and motivic nearby sheaves

Author

Julien Sebag, Florian Ivorra, Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche Mathématique de Rennes (IRMAR), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Sebag, Julien

Subjects
[ MATH ] Mathematics [math], Pure mathematics, Applied Mathematics, General Mathematics, 010102 general mathematics, [MATH] Mathematics [math], [MATH]Mathematics [math], 0101 mathematics, Unipotent, 01 natural sciences, ComputingMilieux_MISCELLANEOUS, Mathematics
Abstract

International audience

Published
2018

145. On logarithmic differential operators and equations in the plane

Author

Julien Sebag, Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Sebag, Julien, AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
[ MATH ] Mathematics [math], 14B05, Logarithm, Plane (geometry), General Mathematics, 010102 general mathematics, Mathematical analysis, [MATH] Mathematics [math], Differential operator, 01 natural sciences, 14H50, 13N05, 0103 physical sciences, 14E18, 010307 mathematical physics, 13N10, 0101 mathematics, [MATH]Mathematics [math], 13N15, ComputingMilieux_MISCELLANEOUS, Mathematics
Abstract

Let $k$ be a field of characteristic zero. Let $f\in k[x_{0},y_{0}]$ be an irreducible polynomial. In this article, we study the space of polynomial partial differential equations of order one in the plane, which admit $f$ as a solution. We provide algebraic characterizations of the associated graded $k[x_{0},y_{0}]$-module (by degree) of this space. In particular, we show that it defines the general component of the tangent space of the curve $\{f=0\}$ and connect it to the $V$-filtration of the logarithmic differential operators of the plane along $\{f=0\}$.

Published
2018

146. On torsion Kähler differential forms

Author

Julien Sebag, David Bourqui, Institut de Recherche Mathématique de Rennes (IRMAR), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Sebag, Julien

Subjects
Pure mathematics, Kähler differential, Algebra and Number Theory, Mathematics::Complex Variables, 010102 general mathematics, Mathematical analysis, [MATH] Mathematics [math], 0102 computer and information sciences, 01 natural sciences, Hypersurface, 010201 computation theory & mathematics, Torsion (algebra), 0101 mathematics, Locus (mathematics), 14F40, 13N05, 14B10, 14R05, [MATH]Mathematics [math], ComputingMilieux_MISCELLANEOUS, Mathematics
Abstract

Let k be a field of characteristic zero. Let V V be an integral affine k -variety. We prove that any torsion Kahler differential form ω ∈ Ω V / k 1 ( V ) vanishes at every formal germ of curve on V V . If V V is an integral hypersurface of A k N ( N≥1 N ≥ 1 ), we also prove that the non-cylindrical singular points of V V belong to the singular locus of any torsion Kahler differential forms.

Published
2018

147. Smooth arcs on algebraic varieties

Author

David Bourqui, Julien Sebag, Institut de Recherche Mathématique de Rennes (IRMAR), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Sebag, Julien, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
[ MATH ] Mathematics [math], Pure mathematics, Applied Mathematics, 010102 general mathematics, Algebraic variety, [MATH] Mathematics [math], 01 natural sciences, 0103 physical sciences, 010307 mathematical physics, Geometry and Topology, 0101 mathematics, [MATH]Mathematics [math], ComputingMilieux_MISCELLANEOUS, Mathematics
Abstract

International audience

Published
2017

148. A putative long noncoding RNA-encoded micropeptide maintains cellular homeostasis in pancreatic β cells.

Author

Li M, Shao F, Qian Q, Yu W, Zhang Z, Chen B, Su D, Guo Y, Phan AV, Song LS, Stephens SB, Sebag J, Imai Y, Yang L, and Cao H

Abstract

Micropeptides (microproteins) encoded by transcripts previously annotated as long noncoding RNAs (lncRNAs) are emerging as important mediators of fundamental biological processes in health and disease. Here, we applied two computational tools to identify putative micropeptides encoded by lncRNAs that are expressed in the human pancreas. We experimentally verified one such micropeptide encoded by a β cell- and neural cell-enriched lncRNA TCL1 Upstream Neural Differentiation-Associated RNA ( TUNAR , also known as TUNA , HI-LNC78 , or LINC00617 ). We named this highly conserved 48-amino-acid micropeptide beta cell- and neural cell-regulin (BNLN). BNLN contains a single-pass transmembrane domain and localizes at the endoplasmic reticulum (ER) in pancreatic β cells. Overexpression of BNLN lowered ER calcium levels, maintained ER homeostasis, and elevated glucose-stimulated insulin secretion in pancreatic β cells. We further assessed the BNLN expression in islets from mice fed a high-fat diet and a regular diet and found that BNLN is suppressed by diet-induced obesity (DIO). Conversely, overexpression of BNLN enhanced insulin secretion in islets from lean and obese mice as well as from humans. Taken together, our study provides the first evidence that lncRNA-encoded micropeptides play a critical role in pancreatic β cell functions and provides a foundation for future comprehensive analyses of micropeptide function and pathophysiological impact on diabetes., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Published
2021
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149. The Insulinostatic Effect of Ghrelin Requires MRAP2 Expression in δ Cells.

Author

Yin TC, Bauchle CJ, Rouault AAJ, Stephens SB, and Sebag JA

Abstract

Ghrelin regulates both energy intake and glucose homeostasis. In the endocrine pancreas, ghrelin inhibits insulin release to prevent hypoglycemia during fasting. The mechanism through which this is accomplished is unclear, but recent studies suggest that ghrelin acts on δ cells to stimulate somatostatin release, which in turn inhibits insulin release from β cells. Recently, the Melanocortin Receptor Accessory Protein 2 (MRAP2) was identified as an essential partner of the ghrelin receptor (GHSR1a) in mediating the central orexigenic action of ghrelin. In this study we show that MRAP2 is expressed in islet δ cells and is required for ghrelin to elicit a calcium response in those cells. Additionally, we show that both global and δ cell targeted deletion of MRAP2 abrogates the insulinostatic effect of ghrelin. Together, these findings establish that ghrelin signaling within δ cells is essential for the inhibition of insulin release and identify MRAP2 as a regulator of insulin secretion., Competing Interests: Declaration of Interests The authors declare no competing interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2020
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150. [G-protein-coupled receptors targeting: the allosteric approach].

Author

Sebag JA and Pantel J

Subjects
Allosteric Regulation, Animals, High-Throughput Screening Assays, Humans, Models, Biological, Allosteric Site physiology, Drug Design, Molecular Targeted Therapy methods, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled antagonists & inhibitors, Receptors, G-Protein-Coupled metabolism
Abstract

G-protein-coupled receptors (GPCR) are a major family of drug targets. Essentially all drugs targeting these receptors on the market compete with the endogenous ligand (agonists or antagonists) for binding the receptor. Recently, non-competitive compounds binding to distinct sites from the cognate ligand were documented in various classes of these receptors. These compounds, called allosteric modulators, generally endowed of a better selectivity are able to modulate specifically the endogenous signaling of the receptor. To better understand the promising potential of this class of GPCRs targeting compounds, this review highlights the properties of allosteric modulators, the strategies used to identify them and the challenges associated with the development of these compounds., (© 2012 médecine/sciences – Inserm / SRMS.)

Published
2012
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