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2. Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals

Author

Timur Liwinski, Matthias K. Auer, Johanna Schröder, Ina Pieknik, Christian Casar, Dorothee Schwinge, Lara Henze, Günter K. Stalla, Undine E. Lang, Alina von Klitzing, Peer Briken, Thomas Hildebrandt, Jeanne C. Desbuleux, Sarah V. Biedermann, Paul-Martin Holterhus, Corinna Bang, Christoph Schramm, and Johannes Fuss

Subjects
Gender-affirming hormonal therapy, Sex steroids, Microbiome, Microbiota, Metagenome, Trans women, Medicine
Abstract

Abstract Background Limited data exists regarding gender-specific microbial alterations during gender-affirming hormonal therapy (GAHT) in transgender individuals. This study aimed to investigate the nuanced impact of sex steroids on gut microbiota taxonomy and function, addressing this gap. We prospectively analyzed gut metagenome changes associated with 12 weeks of GAHT in trans women and trans men, examining both taxonomic and functional shifts. Methods Thirty-six transgender individuals (17 trans women, 19 trans men) provided pre- and post-GAHT stool samples. Shotgun metagenomic sequencing was used to assess the changes in gut microbiota structure and potential function following GAHT. Results While alpha and beta diversity remained unchanged during transition, specific species, including Parabacteroides goldsteinii and Escherichia coli, exhibited significant abundance shifts aligned with affirmed gender. Overall functional metagenome analysis showed a statistically significant effect of gender and transition (R 2 = 4.1%, P = 0.0115), emphasizing transitions aligned with affirmed gender, particularly in fatty acid-related metabolism. Conclusions This study provides compelling evidence of distinct taxonomic and functional profiles in the gut microbiota between trans men and women. GAHT induces androgenization in trans men and feminization in trans women, potentially impacting physiological and health-related outcomes. Trial registration Clinicaltrials.gov NCT02185274.

Published
2024
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3. Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals

Author

Liwinski, Timur, Auer, Matthias K., Schröder, Johanna, Pieknik, Ina, Casar, Christian, Schwinge, Dorothee, Henze, Lara, Stalla, Günter K., Lang, Undine E., von Klitzing, Alina, Briken, Peer, Hildebrandt, Thomas, Desbuleux, Jeanne C., Biedermann, Sarah V., Holterhus, Paul-Martin, Bang, Corinna, Schramm, Christoph, and Fuss, Johannes

Published
2024
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4. Next-generation large-scale binary protein interaction network for Drosophila melanogaster.

Author

Tang, Hong-Wen, Spirohn, Kerstin, Hu, Yanhui, Hao, Tong, Kovács, István, Gao, Yue, Binari, Richard, Yang-Zhou, Donghui, Wan, Kenneth, Bader, Joel, Balcha, Dawit, Bian, Wenting, Booth, Benjamin, Coté, Atina, de Rouck, Steffi, Desbuleux, Alice, Goh, Kah, Kim, Dae-Kyum, Knapp, Jennifer, Lee, Wen, Lemmens, Irma, Li, Cathleen, Li, Mian, Li, Roujia, Lim, Hyobin, Liu, Yifang, Luck, Katja, Markey, Dylan, Pollis, Carl, Rangarajan, Sudharshan, Rodiger, Jonathan, Schlabach, Sadie, Shen, Yun, Sheykhkarimli, Dayag, TeeKing, Bridget, Roth, Frederick, Tavernier, Jan, Calderwood, Michael, Hill, David, Celniker, Susan, Vidal, Marc, Perrimon, Norbert, and Mohr, Stephanie

Subjects
Animals, Protein Interaction Maps, Drosophila melanogaster, Drosophila, Saccharomyces cerevisiae, Drosophila Proteins, Protein Interaction Mapping, Two-Hybrid System Techniques
Abstract

Generating reference maps of interactome networks illuminates genetic studies by providing a protein-centric approach to finding new components of existing pathways, complexes, and processes. We apply state-of-the-art methods to identify binary protein-protein interactions (PPIs) for Drosophila melanogaster. Four all-by-all yeast two-hybrid (Y2H) screens of > 10,000 Drosophila proteins result in the FlyBi dataset of 8723 PPIs among 2939 proteins. Testing subsets of data from FlyBi and previous PPI studies using an orthogonal assay allows for normalization of data quality; subsequent integration of FlyBi and previous data results in an expanded binary Drosophila reference interaction network, DroRI, comprising 17,232 interactions among 6511 proteins. We use FlyBi data to generate an autophagy network, then validate in vivo using autophagy-related assays. The deformed wings (dwg) gene encodes a protein that is both a regulator and a target of autophagy. Altogether, these resources provide a foundation for building new hypotheses regarding protein networks and function.

Published
2023

5. Next-generation large-scale binary protein interaction network for Drosophila melanogaster

Author

Hong-Wen Tang, Kerstin Spirohn, Yanhui Hu, Tong Hao, István A. Kovács, Yue Gao, Richard Binari, Donghui Yang-Zhou, Kenneth H. Wan, Joel S. Bader, Dawit Balcha, Wenting Bian, Benjamin W. Booth, Atina G. Coté, Steffi de Rouck, Alice Desbuleux, Kah Yong Goh, Dae-Kyum Kim, Jennifer J. Knapp, Wen Xing Lee, Irma Lemmens, Cathleen Li, Mian Li, Roujia Li, Hyobin Julianne Lim, Yifang Liu, Katja Luck, Dylan Markey, Carl Pollis, Sudharshan Rangarajan, Jonathan Rodiger, Sadie Schlabach, Yun Shen, Dayag Sheykhkarimli, Bridget TeeKing, Frederick P. Roth, Jan Tavernier, Michael A. Calderwood, David E. Hill, Susan E. Celniker, Marc Vidal, Norbert Perrimon, and Stephanie E. Mohr

Subjects
Science
Abstract

Abstract Generating reference maps of interactome networks illuminates genetic studies by providing a protein-centric approach to finding new components of existing pathways, complexes, and processes. We apply state-of-the-art methods to identify binary protein-protein interactions (PPIs) for Drosophila melanogaster. Four all-by-all yeast two-hybrid (Y2H) screens of > 10,000 Drosophila proteins result in the ‘FlyBi’ dataset of 8723 PPIs among 2939 proteins. Testing subsets of data from FlyBi and previous PPI studies using an orthogonal assay allows for normalization of data quality; subsequent integration of FlyBi and previous data results in an expanded binary Drosophila reference interaction network, DroRI, comprising 17,232 interactions among 6511 proteins. We use FlyBi data to generate an autophagy network, then validate in vivo using autophagy-related assays. The deformed wings (dwg) gene encodes a protein that is both a regulator and a target of autophagy. Altogether, these resources provide a foundation for building new hypotheses regarding protein networks and function.

Published
2023
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6. The Self-Reported Sexual Real-World Consequences of Sex Doll Use.

Author

Desbuleux, Jeanne C. and Fuss, Johannes

Subjects
*INTERPERSONAL relations, *SEX workers, *SEX dolls, *SEXUAL fantasies, *HUMAN sexuality, *SEX customs
Abstract

It is a growing concern that the use of sex dolls and robots could affect human sexuality. This concern has led to a ban of child-like sex dolls in several countries and a call to ban adult-like sex dolls and robots by some scholars. However, empirical data is largely missing supporting this claim. Here, we present retrospective self-reported quantitative and qualitative data of a large sample (N = 224, 90.5% men, Mean age = 31 years, SD = 14.2) of teleiophilic (i.e., sexual orientation toward adults) and pedo-hebephilic participants. Using an online survey, we found that users reported an overall reduction in sexuality-related behaviors (e.g., porn consumption or visiting of sex workers) in response to doll ownership. Users in a relationship with a human were less affected by doll use, while those in a relationship with a doll reported greater effects. Interestingly, pedo-hebephilic users reported a greater reduction of sexual compulsivity compared to teleiophilic participants following doll use. Additionally, pedo-hebephilic participants more often reported acting out of illegal sexual fantasies with their dolls and a loss of interest in (sexual) intimacy with real children through doll use in the qualitative data. These self-reported data challenge the view that doll use is dangerously affecting human sexuality and instead suggest that dolls may be used as a sexual outlet for potentially dangerous and illegal (sexual) fantasies. [ABSTRACT FROM AUTHOR]

Published
2024
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8. A reference map of the human binary protein interactome

Author

Luck, Katja, Kim, Dae-Kyum, Lambourne, Luke, Spirohn, Kerstin, Begg, Bridget E., Bian, Wenting, Brignall, Ruth, Cafarelli, Tiziana, Campos-Laborie, Francisco J., Charloteaux, Benoit, Choi, Dongsic, Coté, Atina G., Daley, Meaghan, Deimling, Steven, Desbuleux, Alice, Dricot, Amélie, Gebbia, Marinella, Hardy, Madeleine F., Kishore, Nishka, Knapp, Jennifer J., Kovács, István A., Lemmens, Irma, Mee, Miles W., Mellor, Joseph C., Pollis, Carl, Pons, Carles, Richardson, Aaron D., Schlabach, Sadie, Teeking, Bridget, Yadav, Anupama, Babor, Mariana, Balcha, Dawit, Basha, Omer, Bowman-Colin, Christian, Chin, Suet-Feung, Choi, Soon Gang, Colabella, Claudia, Coppin, Georges, D’Amata, Cassandra, De Ridder, David, De Rouck, Steffi, Duran-Frigola, Miquel, Ennajdaoui, Hanane, Goebels, Florian, Goehring, Liana, Gopal, Anjali, Haddad, Ghazal, Hatchi, Elodie, Helmy, Mohamed, Jacob, Yves, Kassa, Yoseph, Landini, Serena, Li, Roujia, van Lieshout, Natascha, MacWilliams, Andrew, Markey, Dylan, Paulson, Joseph N., Rangarajan, Sudharshan, Rasla, John, Rayhan, Ashyad, Rolland, Thomas, San-Miguel, Adriana, Shen, Yun, Sheykhkarimli, Dayag, Sheynkman, Gloria M., Simonovsky, Eyal, Taşan, Murat, Tejeda, Alexander, Tropepe, Vincent, Twizere, Jean-Claude, Wang, Yang, Weatheritt, Robert J., Weile, Jochen, Xia, Yu, Yang, Xinping, Yeger-Lotem, Esti, Zhong, Quan, Aloy, Patrick, Bader, Gary D., De Las Rivas, Javier, Gaudet, Suzanne, Hao, Tong, Rak, Janusz, Tavernier, Jan, Hill, David E., Vidal, Marc, Roth, Frederick P., and Calderwood, Michael A.

Published
2020
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9. The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.

Author

Charlotte Vandermeulen, Tina O'Grady, Jerome Wayet, Bartimee Galvan, Sibusiso Maseko, Majid Cherkaoui, Alice Desbuleux, Georges Coppin, Julien Olivet, Lamya Ben Ameur, Keisuke Kataoka, Seishi Ogawa, Olivier Hermine, Ambroise Marcais, Marc Thiry, Franck Mortreux, Michael A Calderwood, Johan Van Weyenbergh, Jean-Marie Peloponese, Benoit Charloteaux, Anne Van den Broeke, David E Hill, Marc Vidal, Franck Dequiedt, and Jean-Claude Twizere

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome.

Published
2021
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13. Neuroendocrine processing of the baby schema in pedophilia

Author

Zannoni, Ronja, Hempelmann, Annika, Holtfrerich, Sarah, Keil, Julian, Fuss, Johannes, Desbuleux-Rettel, Jeanne, Diekhof, Esther, Briken, Peer, Stirn, Aglaja, and Ponseti, Jorge

Subjects
FOS: Psychology, Psychological Phenomena and Processes, Biological Psychology, Medicine and Health Sciences, Psychology, Psychiatry and Psychology, Experimental Analysis of Behavior, pedophilia eeg, Social and Behavioral Sciences
Abstract

Although the etiology of pedophilia is largely unknown, there is first evidence that pedophilia could be at least in part caused by an overactive neural nurturing system (Ponseti, Bruhn, Nolting et al., 2018). To investigate this connection, we compare behavioral, hormonal, and neurobiological factors between pedophilic and teleiophilic participants that might be involved in the response to the baby schema, which plays an important role in the human nurturing system.

Published
2022
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14. Next-generation large-scale binary protein interaction network for Drosophila

Author

Hong-Wen Tang, Kerstin Spirohn, Yanhui Hu, Tong Hao, István A. Kovács, Yue Gao, Richard Binari, Donghui Yang-Zhou, Kenneth H. Wan, Joel S. Bader, Dawit Balcha, Wenting Bian, Benjamin W. Booth, Atina G. Cote, Steffi De Rouck, Alice Desbuleux, Dae-Kyum Kim, Jennifer J. Knapp, Wen Xing Lee, Irma Lemmens, Cathleen Li, Mian Li, Roujia Li, Hyobin Julianne Lim, Katja Luck, Dylan Markey, Carl Pollis, Sudharshan Rangarajan, Jonathan Rodiger, Sadie Schlabach, Yun Shen, Bridget TeeKing, Frederick P. Roth, Jan Tavernier, Michael A. Calderwood, David E. Hill, Susan E. Celniker, Marc Vidal, Norbert Perrimon, and Stephanie E. Mohr

Abstract

Generating reference maps of the interactome networks underlying most cellular functions can greatly illuminate genetic studies by providing a protein-centric approach to finding new components of existing pathways, complexes, and processes. Here, we applied state-of-the-art experimental and bioinformatics methods to identify high-confidence binary protein-protein interactions (PPIs) for Drosophila melanogaster. We performed four all-by-all yeast two-hybrid (Y2H) screens of >10,000 Drosophila proteins, resulting in the ‘FlyBi’ dataset of 8,723 PPIs among 2,939 proteins. As part of this effort, we tested subsets of our data and data from previous PPI datasets using an orthogonal assay, which allowed us to normalize data quality across datasets. Next, we integrated our FlyBi data with previous PPI data, resulting in an expanded, high-confidence binary Drosophila reference interaction network, DroRI, comprising 17,232 interactions among 6,511 proteins. These data are accessible through the Molecular Interaction Search Tool (MIST) and other databases. To assess the utility of the PPI resource, we used novel interactions from the FlyBi dataset to generate an autophagy interaction network that we validated in vivo using two different autophagy-related assays. We found that deformed wings (dwg) encodes a protein that is both a regulator and a target of autophagy. Altogether, the resources generated in this project provide a strong foundation for building high-confidence new hypotheses regarding protein networks and function.

Published
2022

15. Next-generation large-scale binary protein interaction network for Drosophila

Author

Tang, Hong-Wen, primary, Spirohn, Kerstin, additional, Hu, Yanhui, additional, Hao, Tong, additional, Kovács, István A., additional, Gao, Yue, additional, Binari, Richard, additional, Yang-Zhou, Donghui, additional, Wan, Kenneth H., additional, Bader, Joel S., additional, Balcha, Dawit, additional, Bian, Wenting, additional, Booth, Benjamin W., additional, Cote, Atina G., additional, De Rouck, Steffi, additional, Desbuleux, Alice, additional, Kim, Dae-Kyum, additional, Knapp, Jennifer J., additional, Lee, Wen Xing, additional, Lemmens, Irma, additional, Li, Cathleen, additional, Li, Mian, additional, Li, Roujia, additional, Lim, Hyobin Julianne, additional, Luck, Katja, additional, Markey, Dylan, additional, Pollis, Carl, additional, Rangarajan, Sudharshan, additional, Rodiger, Jonathan, additional, Schlabach, Sadie, additional, Shen, Yun, additional, TeeKing, Bridget, additional, Roth, Frederick P., additional, Tavernier, Jan, additional, Calderwood, Michael A., additional, Hill, David E., additional, Celniker, Susan E., additional, Vidal, Marc, additional, Perrimon, Norbert, additional, and Mohr, Stephanie E., additional

Published
2022
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17. Binary Interactome Models of Inner- Versus Outer-Complexome Organization

Author

Thomas Rolland, Atina G. Cote, Marc Vidal, Michael E. Cusick, Alice Desbuleux, István Kovács, Michael A. Calderwood, Kerstin Spirohn, Sadie Schlabach, Jan Tavernier, Jüri Reimand, Irma Lemmens, Jean-Claude Twizere, Patrick Aloy, Pascal Falter-Braun, David E. Hill, Jennifer K. Knapp, Carles Pons, Noor Jailkhani, Yang Wang, Luke Lambourne, Yves Jacob, Tiziana M. Cafarelli, Marinella Gebbia, Nishka Kishore, Tong Hao, David De Ridder, Quan Zhong, Wenting Bian, Benoit Charloteaux, Mohamed Helmy, Katja Luck, Joseph C. Mellor, Dae-Kyum Kim, Frederick P. Roth, Anupama Yadav, Miles W. Mee, Yun Shen, Dana-Farber Cancer Institute [Boston], Université de Liège, University of Toronto, Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Physics, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Homogeneous, Structural plasticity, Binary number, Computational biology, Interactome, Functional similarity, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

SummaryHundreds of different protein complexes that perform important functions across all cellular processes, collectively comprising the “complexome” of an organism, have been identified1. However, less is known about the fraction of the interactome that exists outside the complexome, in the “outer-complexome”. To investigate features of “inner”- versus outer-complexome organisation in yeast, we generated a high-quality atlas of binary protein-protein interactions (PPIs), combining three previous maps2–4 and a new reference all-by-all binary interactome map. A greater proportion of interactions in our map are in the outer-complexome, in comparison to those found by affinity purification followed by mass spectrometry5–7 or in literature curated datasets8–11. In addition, recent advances in deep learning predictions of PPI structures12 mirror the existing experimentally resolved structures in being largely focused on the inner complexome and missing most interactions in the outer-complexome. Our new PPI network suggests that the outer-complexome contains considerably more PPIs than the inner-complexome, and integration with functional similarity networks13–15 reveals that interactions in the inner-complexome are highly detectable and correspond to pairs of proteins with high functional similarity, while proteins connected by more transient, harder-to-detect interactions in the outer-complexome, exhibit higher functional heterogeneity.

Published
2021

18. Is the Anthropomorphization of Sex Dolls Associated with Objectification and Hostility Toward Women? A Mixed Method Study among Doll Users.

Author

Desbuleux, Jeanne C. and Fuss, Johannes

Subjects
*SEX dolls, *SEX toys, *ROBOTS, *HUMANOID robots, *ATTITUDE (Psychology)
Abstract

Both the ownership and development of sex dolls and robots are passionately debated, with skeptics suspecting that their increasing human-likeness and the accompanying anthropomorphization (i.e., attributing human-likeness) reinforce the objectification of, and hostility toward, women. As empirical data are largely lacking, we scrutinized this hypothesis in a pre-registered study among doll owners (N = 217), comparing two user groups: "toy group" (n = 104; doll as sex toy) and "partner group" (n = 113; doll as partner). We related their objectification tendencies (i.e., seeing women merely as objects, e.g., to promote sexual desire) as well as their hostility toward women, to the anthropomorphization of their doll. Additionally, we collected qualitative data on how participants perceived their doll usage affected their attitudes toward women. The partner group expressed greater levels of hostility and anthropomorphization, moderate in magnitude. Objectification mediated the influence of anthropomorphization on hostility and a higher percentage described a change in attitudes toward women in response to doll use. These data provide the first empirical evidence that the tendency to anthropomorphize dolls is related to negative attitudes toward women. Given the ongoing development of sex robots designed to surpass dolls in human-likeness and anthropomorphization, this finding seems highly significant. [ABSTRACT FROM AUTHOR]

Published
2023
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19. The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape

Author

Vandermeulen, Charlotte, primary, O’Grady, Tina, additional, Wayet, Jerome, additional, Galvan, Bartimee, additional, Maseko, Sibusiso, additional, Cherkaoui, Majid, additional, Desbuleux, Alice, additional, Coppin, Georges, additional, Olivet, Julien, additional, Ben Ameur, Lamya, additional, Kataoka, Keisuke, additional, Ogawa, Seishi, additional, Hermine, Olivier, additional, Marcais, Ambroise, additional, Thiry, Marc, additional, Mortreux, Franck, additional, Calderwood, Michael A., additional, Van Weyenbergh, Johan, additional, Peloponese, Jean-Marie, additional, Charloteaux, Benoit, additional, Van den Broeke, Anne, additional, Hill, David E., additional, Vidal, Marc, additional, Dequiedt, Franck, additional, and Twizere, Jean-Claude, additional

Published
2021
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20. miRNA expression in anaplastic thyroid carcinomas.

Author

Aline Hébrant, Sébastien Floor, Manuel Saiselet, Aline Antoniou, Alice Desbuleux, Bérengère Snyers, Caroline La, Nicolas de Saint Aubain, Emmanuelle Leteurtre, Guy Andry, and Carine Maenhaut

Subjects
Medicine, Science
Abstract

Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents an end stage of thyroid tumor progression. No effective treatment exists so far. In this study, we analyzed the miRNA expression profiles of 11 ATC by microarrays and their relationship with the mRNA expression profiles of the same 11 ATC samples. ATC show distinct miRNA expression profiles compared to other less aggressive thyroid tumor types. ATC show 18 commonly deregulated miRNA compared to normal thyroid tissue (17 downregulated and 1 upregulated miRNA). First, the analysis of a combined approach of the mRNA gene expression and of the bioinformatically predicted mRNA targets of the deregulated miRNA suggested a role for these regulations in the epithelial to mesenchymal transition (EMT) process in ATC. Second, the direct interaction between one of the upregulated mRNA target, the LOX gene which is an EMT key player, and a downregulated miRNA, the miR-29a, was experimentally validated by a luciferase assay in HEK cell. Third, we confirmed that the ATC tissue is composed of about 50% of tumor associated macrophages (TAM) and suggested, by taking into account our data and published data, their most likely direct or paracrine intercommunication between them and the thyroid tumor cells, amplifying the tumor aggressiveness. Finally, we demonstrated by in situ hybridization a specific thyrocyte localization of 3 of the deregulated miRNA: let-7g, miR-29a and miR-30e and we pointed out the importance of identifying the cell type localization before drawing any conclusion on the physiopathological role of a given gene.

Published
2014
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21. The viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape

Author

Georges Coppin, Alice Desbuleux, Lamya Ben Ameur, Charlotte Vandermeulen, Franck Dequiedt, Benoit Charloteaux, Michael A. Calderwood, Bartimée Galvan, Marc Vidal, Keisuke Kataoka, Majid Cherkaoui, Jean-Claude Twizere, Tina O'Grady, Marc Thiry, Julien Olivet, Johan Van Weyenbergh, David E. Hill, Franck Mortreux, and Seishi Ogawa

Subjects
U2AF2, Spliceosome, Exon, Transcription (biology), RNA splicing, Alternative splicing, Translation (biology), Biology, Transcription factor, Cell biology
Abstract

SUMMARYWhile viral infections are known to hijack the transcription and translation of the host cell, the extent to which encoded viral proteins coordinate these perturbations remains unclear. Here we demonstrate that the oncoviral proteins Tax and HBZ interact with specific components of the spliceosome machinery, including the U2 auxiliary factor large subunit (U2AF2), and the complementary factor for APOBEC-1 (A1CF), respectively. Tax and HBZ perturb the splicing landscape in T-cells by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia (ATL) patients, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinately used by Tax and HBZ to reprogram the transcriptome.HighlightsTax and HBZ interact with RNA-binding proteins as well as transcription factorsHTLV-1 encoded proteins Tax and HBZ alter the splicing landscape in T-cellsTax and HBZ expression affect alternative splicing of 33 and 63 cancer genes, respectivelyOpposing roles for Tax and HBZ in deregulation of gene expressionGraphical abstract

Published
2021

22. The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape

Author

Vandermeulen, Charlotte, O’Grady, Tina, Wayet, Jérôme, Galvan, Bartimee, Maseko, Sibusiso, Cherkaoui, Majid, Desbuleux, Alice, Coppin, Georges, Olivet, Julien, Ameur, Lamya Ben, Kataoka, Keisuke, Ogawa, Seishi, Hermine, Olivier, Marçais, Ambroise, Thiry, Marc, Mortreux, Franck, Calderwood, Michael A, van Weyenbergh, Johan, Peloponese, Jean Marie, Charloteaux, Benoît, Van Den Broeke, Anne, Hill, David D.E., Vidal, Marc, Dequiedt, Franck, Twizere, Jean-Claude, Vandermeulen, Charlotte, O’Grady, Tina, Wayet, Jérôme, Galvan, Bartimee, Maseko, Sibusiso, Cherkaoui, Majid, Desbuleux, Alice, Coppin, Georges, Olivet, Julien, Ameur, Lamya Ben, Kataoka, Keisuke, Ogawa, Seishi, Hermine, Olivier, Marçais, Ambroise, Thiry, Marc, Mortreux, Franck, Calderwood, Michael A, van Weyenbergh, Johan, Peloponese, Jean Marie, Charloteaux, Benoît, Van Den Broeke, Anne, Hill, David D.E., Vidal, Marc, Dequiedt, Franck, and Twizere, Jean-Claude

Abstract

Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

24. Binary interactome models of inner- versus outer-complexome organisation

Author

Lambourne, Luke, primary, Yadav, Anupama, additional, Wang, Yang, additional, Desbuleux, Alice, additional, Kim, Dae-Kyum, additional, Cafarelli, Tiziana, additional, Pons, Carles, additional, Kovács, István A., additional, Jailkhani, Noor, additional, Schlabach, Sadie, additional, Ridder, David De, additional, Luck, Katja, additional, Bian, Wenting, additional, Shen, Yun, additional, Yang, Zhipeng, additional, Mee, Miles W., additional, Helmy, Mohamed, additional, Jacob, Yves, additional, Lemmens, Irma, additional, Rolland, Thomas, additional, Coté, Atina G., additional, Gebbia, Marinella, additional, Kishore, Nishka, additional, Knapp, Jennifer J., additional, Mellor, Joseph C., additional, Reimand, Jüri, additional, Tavernier, Jan, additional, Cusick, Michael E., additional, Falter-Braun, Pascal, additional, Spirohn, Kerstin, additional, Zhong, Quan, additional, Aloy, Patrick, additional, Hao, Tong, additional, Charloteaux, Benoit, additional, Roth, Frederick P., additional, Hill, David E., additional, Calderwood, Michael A., additional, Twizere, Jean-Claude, additional, and Vidal, Marc, additional

Published
2021
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25. A reference map of the human binary protein interactome

Author

Eyal Simonovsky, Joseph C. Mellor, Amélie Dricot, Marc Vidal, Liana Goehring, Miquel Duran-Frigola, Florian Goebels, Dayag Sheykhkarimli, Thomas Rolland, Murat Tasan, John Rasla, Steffi De Rouck, Carles Pons, Sadie Schlabach, Yoseph Kassa, Claudia Colabella, Dong-Sic Choi, Yves Jacob, Joseph N. Paulson, Javier De Las Rivas, Madeleine F. Hardy, Francisco J. Campos-Laborie, Xinping Yang, Soon Gang Choi, Frederick P. Roth, Kerstin Spirohn, Nishka Kishore, Luke Lambourne, Cassandra D’Amata, Dawit Balcha, Adriana San-Miguel, Anupama Yadav, Anjali Gopal, Suet-Feung Chin, Suzanne Gaudet, Yang Wang, István Kovács, Elodie Hatchi, Natascha van Lieshout, Michael A. Calderwood, Yu Xia, Gloria M. Sheynkman, Robert J. Weatheritt, Marinella Gebbia, Atina G. Cote, Bridget E. Begg, Mohamed Helmy, Katja Luck, Bridget Teeking, Quan Zhong, Serena Landini, David E. Hill, Sudharshan Rangarajan, Georges Coppin, Ghazal Haddad, Omer Basha, Carl Pollis, Dylan Markey, Alice Desbuleux, Hanane Ennajdaoui, Dae-Kyum Kim, Vincent Tropepe, Roujia Li, Steven Deimling, Jennifer J. Knapp, Jan Tavernier, Mariana Babor, Benoit Charloteaux, Gary D. Bader, Alexander O. Tejeda, Aaron Richardson, Ruth Brignall, Ashyad Rayhan, Irma Lemmens, Tong Hao, Christian Bowman-Colin, Janusz Rak, David De Ridder, Jochen Weile, Wenting Bian, Jean-Claude Twizere, Patrick Aloy, Esti Yeger-Lotem, Meaghan Daley, Tiziana M. Cafarelli, Andrew MacWilliams, Miles W. Mee, Yun Shen, National Institutes of Health (US), National Human Genome Research Institute (US), Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fonds de la Recherche Scientifique (Fédération Wallonie-Bruxelles), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris], Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Toronto, Mount Sinai Health System, Canadian Institute for Advanced Research (CIFAR), and This work was primarily supported by the National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI) grant U41HG001715 (M.V., F.P.R., D.E.H., M.A.C., G.D.B. and J.T.) with additional support from NIH grants P50HG004233 (M.V. and F.P.R.), U01HL098166 (M.V.), U01HG007690 (M.V.), R01GM109199 (M.A.C.), Canadian Institute for Health Research (CIHR) Foundation Grants (F.P.R. and J. Rak), the Canada Excellence Research Chairs Program (F.P.R.) and an American Heart Association grant 15CVGPS23430000 (M.V.). D.-K.K. was supported by a Banting Postdoctoral Fellowship through the Natural Sciences and Engineering Research Council (NSERC) of Canada and by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2017R1A6A3A03004385). C. Pons was supported by a Ramon Cajal fellowship (RYC-2017-22959). G.M.S. was supported by NIH Training Grant T32CA009361. M.V. is a Chercheur Qualifié Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium).

Subjects
0301 basic medicine, Multidisciplinary, Proteome, [SDV]Life Sciences [q-bio], Computational biology, Biology, Genome, Phenotype, Interactome, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Article, Protein–protein interaction, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Organ Specificity, Protein Interaction Mapping, Reference map, Humans, Cellular organization, Extracellular Space, 030217 neurology & neurosurgery, Function (biology)
Abstract

et al., Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype–phenotype relationships1,2. Here we present a human ‘all-by-all’ reference interactome map of human binary protein interactions, or ‘HuRI’. With approximately 53,000 protein–protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome3, transcriptome4 and proteome5 data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein–protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes., This work was primarily supported by the National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI) grant U41HG001715 (M.V., F.P.R., D.E.H., M.A.C., G.D.B. and J.T.) with additional support from NIH grants P50HG004233 (M.V. and F.P.R.), U01HL098166 (M.V.), U01HG007690 (M.V.), R01GM109199 (M.A.C.), Canadian Institute for Health Research (CIHR) Foundation Grants (F.P.R. and J. Rak), the Canada Excellence Research Chairs Program (F.P.R.) and an American Heart Association grant 15CVGPS23430000 (M.V.). D.-K.K. was supported by a Banting Postdoctoral Fellowship through the Natural Sciences and Engineering Research Council (NSERC) of Canada and by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2017R1A6A3A03004385). C. Pons was supported by a Ramon Cajal fellowship (RYC-2017-22959). G.M.S. was supported by NIH Training Grant T32CA009361. M.V. is a Chercheurv Qualifié Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium).

Published
2020

26. The viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape

Author

Vandermeulen, Charlotte, primary, O’Grady, Tina, additional, Galvan, Bartimee, additional, Cherkaoui, Majid, additional, Desbuleux, Alice, additional, Coppin, Georges, additional, Olivet, Julien, additional, Ameur, Lamya Ben, additional, Kataoka, Keisuke, additional, Ogawa, Seishi, additional, Thiry, Marc, additional, Mortreux, Franck, additional, Calderwood, Michael A., additional, Hill, David E., additional, Van Weyenbergh, Johan, additional, Charloteaux, Benoit, additional, Vidal, Marc, additional, Dequiedt, Franck, additional, and Twizere, Jean-Claude, additional

Published
2021
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27. A reference map of the human protein interactome

Author

Madeleine F. Hardy, Bridget Teeking, Francisco J. Campos-Laborie, Dayag Sheykhkarimli, Dawit Balcha, Anjali Gopal, Marinella Gebbia, Ashyad Rayhan, Carles Pons, Gloria M. Sheynkman, Yves Jacob, Suzanne Gaudet, Aaron Richardson, Yoseph Kassa, Elodie Hatchi, Kerstin Spirohn, Dong-Sic Choi, Yu Xia, Eyal Simonovsky, David E. Hill, Hanane Ennajdaoui, Steven Deimling, Joseph N. Paulson, Natascha van Lieshout, Vincent Tropepe, Michael A. Calderwood, István Kovács, Gary D. Bader, Luke Lambourne, Sudharshan Rangarajan, Tiziana M. Cafarelli, Carl Pollis, Suet-Feung Chin, Alice Desbuleux, Andrew MacWilliams, Amélie Dricot, Jean-Claude Twizere, Patrick Aloy, Atina G. Cote, Marc Vidal, Jan Tavernier, Javier De Las Rivas, Cassandra D’Amata, Alexander O. Tejeda, Esti Yeger-Lotem, Liana Goehring, Joseph C. Mellor, Meaghan Daley, Irma Lemmens, Soon Gang Choi, Christian Bowman-Colin, Ghazal Haddad, Janusz Rak, Florian Goebels, Robert J. Weatheritt, Mariana Babor, Yang Wang, Thomas Rolland, Steffi De Rouck, Jochen Weile, Serena Landini, John Rasla, Sadie Schlabach, Nishka Kishore, Bridget E. Begg, Ruth Brignall, Quan Zhong, Tong Hao, David De Ridder, Claudia Colabella, Frederick P. Roth, Anupama Yadav, Mohamed Helmy, Katja Luck, Omer Basha, Dae-Kyum Kim, Benoit Charloteaux, Georges Coppin, Dylan Markey, Roujia Li, Miquel Duran-Frigola, Adriana San-Miguel, Wenting Bian, Miles W. Mee, Jennifer J. Knapp, Yun Shen, Murat Tasan, Xinping Yang, Dana-Farber Cancer Institute [Boston], Division of Medical Physics in Radiology [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Cancer Research UK Cambridge Institute (CRUK), University of Cambridge [UK] (CAM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Harvard Medical School [Boston] (HMS), University of Toronto, Universidad de Salamanca, McGill University Health Center [Montreal] (MUHC), Mount Sinai Hospital [Toronto, Canada] (MSH), Université de Liège, Wigner Research Centre for Physics [Budapest], Hungarian Academy of Sciences (MTA), Northeastern University [Boston], Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Universiteit Gent = Ghent University [Belgium] (UGENT), Barcelona Institute of Science and Technology (BIST), Ben-Gurion University of the Negev (BGU), Università degli Studi di Perugia (UNIPG), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Canadian Institute for Advanced Research (CIFAR), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Perugia = University of Perugia (UNIPG), and Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Context (language use), Computational biology, Biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Genome, Interactome, Human genetics, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Human interactome, Proteome, 030217 neurology & neurosurgery, Function (biology), 030304 developmental biology
Abstract

Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence revolutionized human genetics, a reference map of the human interactome network is critical to fully understand genotype-phenotype relationships. Here we present the first human “all-by-all” binary reference interactome map, or “HuRI”. With ~53,000 high-quality protein-protein interactions (PPIs), HuRI is approximately four times larger than the information curated from small-scale studies available in the literature. Integrating HuRI with genome, transcriptome and proteome data enables the study of cellular function within essentially any physiological or pathological cellular context. We demonstrate the use of HuRI in identifying specific subcellular roles of PPIs and protein function modulation via splicing during brain development. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms underlying tissue-specific phenotypes of Mendelian diseases. HuRI thus represents an unprecedented, systematic reference linking genomic variation to phenotypic outcomes.

Published
2019

28. Prostitution/ Sex work in Sweden and Germany : A Study of Former Research

Author

Desbuleux-Rettel, Juliette

Subjects
Sweden, prostitution, Other Social Sciences not elsewhere specified, Germany, sex work, sexköpslagen, Prostituiertenschutzgesetz, Övrig annan samhällsvetenskap
Abstract

This thesis deals with part of the current research about prostitution/ sex work in Sweden and Germany. While prostitution/ sex work is partly criminalized in Sweden, the German law is currently designed to improve the legal situation of prostitutes/ sex worker. Both countries offer a different range of research on the topic with Sweden having several scholars who focused their research on the field compared to rather little research in Germany. Assistant Professor at the Social Work Department at the University of Wisconsin-Madison, Lara Gerassi, argues that besides the general lack of research on the field of prostitution/ sex work, the research that exists focuses more on the macro level perspectives and leaves the micro level with not a lot of research. Existing research, she claims, then shows little empirical support. The thesis will conclude that there is indeed too little research in both countries, especially within the micro level perspective and that the field needs an increased amount of research to help understand the field better and to be able to adapt the laws and regulations according to the needs.

Published
2019

29. A reference map of the human protein interactome

Author

Luck, Katja, primary, Kim, Dae-Kyum, additional, Lambourne, Luke, additional, Spirohn, Kerstin, additional, Begg, Bridget E., additional, Bian, Wenting, additional, Brignall, Ruth, additional, Cafarelli, Tiziana, additional, Campos-Laborie, Francisco J., additional, Charloteaux, Benoit, additional, Choi, Dongsic, additional, Cote, Atina G., additional, Daley, Meaghan, additional, Deimling, Steven, additional, Desbuleux, Alice, additional, Dricot, Amélie, additional, Gebbia, Marinella, additional, Hardy, Madeleine F., additional, Kishore, Nishka, additional, Knapp, Jennifer J., additional, Kovács, István A., additional, Lemmens, Irma, additional, Mee, Miles W., additional, Mellor, Joseph C., additional, Pollis, Carl, additional, Pons, Carles, additional, Richardson, Aaron D., additional, Schlabach, Sadie, additional, Teeking, Bridget, additional, Yadav, Anupama, additional, Babor, Mariana, additional, Balcha, Dawit, additional, Basha, Omer, additional, Bowman-Colin, Christian, additional, Chin, Suet-Feung, additional, Choi, Soon Gang, additional, Colabella, Claudia, additional, Coppin, Georges, additional, D’Amata, Cassandra, additional, De Ridder, David, additional, De Rouck, Steffi, additional, Duran-Frigola, Miquel, additional, Ennajdaoui, Hanane, additional, Goebels, Florian, additional, Goehring, Liana, additional, Gopal, Anjali, additional, Haddad, Ghazal, additional, Hatchi, Elodie, additional, Helmy, Mohamed, additional, Jacob, Yves, additional, Kassa, Yoseph, additional, Landini, Serena, additional, Li, Roujia, additional, van Lieshout, Natascha, additional, MacWilliams, Andrew, additional, Markey, Dylan, additional, Paulson, Joseph N., additional, Rangarajan, Sudharshan, additional, Rasla, John, additional, Rayhan, Ashyad, additional, Rolland, Thomas, additional, San-Miguel, Adriana, additional, Shen, Yun, additional, Sheykhkarimli, Dayag, additional, Sheynkman, Gloria M., additional, Simonovsky, Eyal, additional, Taşan, Murat, additional, Tejeda, Alexander, additional, Twizere, Jean-Claude, additional, Wang, Yang, additional, Weatheritt, Robert J., additional, Weile, Jochen, additional, Xia, Yu, additional, Yang, Xinping, additional, Yeger-Lotem, Esti, additional, Zhong, Quan, additional, Aloy, Patrick, additional, Bader, Gary D., additional, De Las Rivas, Javier, additional, Gaudet, Suzanne, additional, Hao, Tong, additional, Rak, Janusz, additional, Tavernier, Jan, additional, Tropepe, Vincent, additional, Hill, David E., additional, Vidal, Marc, additional, Roth, Frederick P., additional, and Calderwood, Michael A., additional

Published
2019
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30. Network Analysis of UBE3A/E6AP-Associated Proteins Provides Connections to Several Distinct Cellular Processes

Author

Marc Vidal, Katja Luck, Flavian Leclere, Diana Rodriguez, Jeffrey T. Galligan, Simone Kühnle, Quan Zhong, David E. Hill, Patricia Szajner, Gustavo Martínez-Noël, Kathleen A. Boyland, Alice Desbuleux, Peter M. Howley, and Leon Zheng

Subjects
0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Proteasome Endopeptidase Complex, Ubiquitin-Protein Ligases, Computational biology, Biology, Proteomics, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, Structural Biology, Angelman syndrome, Ca2+/calmodulin-dependent protein kinase, Protein Interaction Mapping, UBE3A, medicine, Humans, Molecular Biology, DNA replication, Translation (biology), medicine.disease, Crosstalk (biology), 030104 developmental biology, HEK293 Cells, biology.protein, Calcium-Calmodulin-Dependent Protein Kinase Type 2, 030217 neurology & neurosurgery
Abstract

Perturbations in activity and dosage of the UBE3A ubiquitin-ligase have been linked to Angelman syndrome and autism spectrum disorders. UBE3A was initially identified as the cellular protein hijacked by the human papillomavirus E6 protein to mediate the ubiquitylation of p53, a function critical to the oncogenic potential of these viruses. Although a number of substrates have been identified, the normal cellular functions and pathways affected by UBE3A are largely unknown. Previously, we showed that UBE3A associates with HERC2, NEURL4, and MAPK6/ERK3 in a high-molecular-weight complex of unknown function that we refer to as the HUN complex (HERC2, UBE3A, and NEURL4). In this study, the combination of two complementary proteomic approaches with a rigorous network analysis revealed cellular functions and pathways in which UBE3A and the HUN complex are involved. In addition to finding new UBE3A-associated proteins, such as MCM6, SUGT1, EIF3C, and ASPP2, network analysis revealed that UBE3A-associated proteins are connected to several fundamental cellular processes including translation, DNA replication, intracellular trafficking, and centrosome regulation. Our analysis suggests that UBE3A could be involved in the control and/or integration of these cellular processes, in some cases as a component of the HUN complex, and also provides evidence for crosstalk between the HUN complex and CAMKII interaction networks. This study contributes to a deeper understanding of the cellular functions of UBE3A and its potential role in pathways that may be affected in Angelman syndrome, UBE3A-associated autism spectrum disorders, and human papillomavirus-associated cancers.

Published
2017

31. Mapping, modeling, and characterization of protein-protein interactions on a proteomic scale

Author

Yang Wang, Marc Vidal, Alice Desbuleux, Tiziana M. Cafarelli, David De Ridder, and Soon Gang Choi

Subjects
0301 basic medicine, Models, Molecular, Proteomics, Cell signaling, Scale (chemistry), Computational biology, Biology, Bioinformatics, Interactome, Protein–protein interaction, 03 medical and health sciences, 030104 developmental biology, Structural Biology, Interaction network, Protein Interaction Mapping, Humans, Protein–protein interaction prediction, Computer Simulation, Cellular organization, Molecular Biology, Function (biology)
Abstract

Proteins effect a number of biological functions, from cellular signaling, organization, mobility, and transport to catalyzing biochemical reactions and coordinating an immune response. These varied functions are often dependent upon macromolecular interactions, particularly with other proteins. Small-scale studies in the scientific literature report protein–protein interactions (PPIs), but slowly and with bias towards well-studied proteins. In an era where genomic sequence is readily available, deducing genotype–phenotype relationships requires an understanding of protein connectivity at proteome-scale. A proteome-scale map of the protein–protein interaction network provides a global view of cellular organization and function. Here, we discuss a summary of methods for building proteome-scale interactome maps and the current status and implications of mapping achievements. Not only do interactome maps serve as a reference, detailing global cellular function and organization patterns, but they can also reveal the mechanisms altered by disease alleles, highlight the patterns of interaction rewiring across evolution, and help pinpoint biologically and therapeutically relevant proteins. Despite the considerable strides made in proteome-wide mapping, several technical challenges persist. Therefore, future considerations that impact current mapping efforts are also discussed.

Published
2017

33. Double radial immunodiffusion as a tool to identify pregnancy-associated glycoproteins in ruminant and nonruminant placentae

Author

Henri Banga-Mboko, Noelita Melo de Sousa, Jean-François Beckers, Henri Desbuleux, Khira Mecif, and Bouchra El Amiri

Subjects
Immunodiffusion, medicine.medical_specialty, Swine, Placenta, Pregnancy Proteins, Biology, Mice, Food Animals, Antigen, Pregnancy, Internal medicine, medicine, Placental Extracts, Animals, Aspartic Acid Endopeptidases, Small Animals, chemistry.chemical_classification, Antiserum, Radial immunodiffusion, Sheep, Equine, Goats, Trophoblast, Ruminants, medicine.disease, Molecular biology, Endocrinology, medicine.anatomical_structure, chemistry, Cats, Cattle, Female, Animal Science and Zoology, Rabbits, Glycoprotein
Abstract

Pregnancy-associated glycoproteins (PAGs) are antigens synthesized in the superficial layers of the ruminant trophoblast. Initially, they were identified either as proteins released into the maternal bloodstream (where they have applications in pregnancy diagnosis) (PAG1) or as molecules binding to the LH receptor (PAG2). In this study, double radial immunodiffusion was used to test the ability of antisera raised against different PAG molecules (bovine, ovine and caprine) to react with placental extracts from nonruminants (rabbit, cat, mouse, pig, and wild pig) and ruminants (cow, ewe, and goat). Placental extracts from all nonruminants tested except rabbit reacted with anti bovine PAG2 (anti-boPAG2). Extracts of ruminant placentas reacted with different antisera, confirming the expression of various PAG molecules. According to the time at which the placentas were collected (early or middle pregnancy), the reaction differed as regards the thickness, position, and number of precipitation lines, suggesting that PAG expression varies as pregnancy progresses. Bos indicus and Bos taurus placental extracts exhibited different reactions with anti-boPAG2: a single precipitation line in the former case and two lines in the latter. This suggests differential expression of boPAG2 related glycoproteins in these two subspecies.

Published
2003

34. microRNA expression in autonomous thyroid adenomas: Correlation with mRNA regulation

Author

Matteo Capello, Guy Andry, Aline Hebrant, Frédérick Libert, Carine Maenhaut, Wilma C G van Staveren, Christophe Trésallet, Catherine Hoang, Alice Desbuleux, and Sebastien Floor

Subjects
Adenoma, Adult, Male, Down-Regulation, Biology, Bioinformatics, Biochemistry, Extracellular matrix, Endocrinology, Downregulation and upregulation, microRNA, medicine, Humans, RNA, Messenger, Thyroid Neoplasms, Molecular Biology, Aged, Aged, 80 and over, Messenger RNA, Microarray analysis techniques, Gene Expression Profiling, Middle Aged, medicine.disease, Cyclic Nucleotide Phosphodiesterases, Type 4, Gene Expression Regulation, Neoplastic, MicroRNAs, Tissue Array Analysis, Cancer research, cAMP-dependent pathway, Female, Extracellular matrix organization, Signal Transduction
Abstract

The objective of the study was to identify the deregulated miRNA in autonomous adenoma and to correlate the data with mRNA regulation. Seven autonomous adenoma with adjacent healthy thyroid tissues were investigated. Twelve miRNAs were downregulated and one was upregulated in the tumors. Combining bioinformatic mRNA target prediction and microarray data on mRNA regulations allowed to identify mRNA targets of our deregulated miRNAs. A large enrichment in mRNA encoding proteins involved in extracellular matrix organization and different phosphodiesterases were identified among these putative targets. The direct interaction between miR-101-3p and miR-144-3p and PDE4D mRNA was experimentally validated. The global miRNA profiles were not greatly modified, confirming the definition of these tumors as minimal deviation tumors. These results support a role for miRNA in the regulation of extracellular matrix proteins and tissue remodeling occurring during tumor development, and in the important negative feedback of the cAMP pathway, which limits the consequences of its constitutive activation in these tumors.

Published
2014

35. microRNA expression in autonomous thyroid adenomas: Correlation with mRNA regulation.

Author

Floor, Sebastien, Trésallet, Christophe, Hebrant, Aline, Desbuleux, Alice, Libert, Frédérick, Hoang, Catherine, Cappello, Matteo, Andry, Guy, van Staveren, Wilma C G, Maenhaut, Carine, Floor, Sebastien, Trésallet, Christophe, Hebrant, Aline, Desbuleux, Alice, Libert, Frédérick, Hoang, Catherine, Cappello, Matteo, Andry, Guy, van Staveren, Wilma C G, and Maenhaut, Carine

Abstract

The objective of the study was to identify the deregulated miRNA in autonomous adenoma and to correlate the data with mRNA regulation. Seven autonomous adenoma with adjacent healthy thyroid tissues were investigated. Twelve miRNAs were downregulated and one was upregulated in the tumors. Combining bioinformatic mRNA target prediction and microarray data on mRNA regulations allowed to identify mRNA targets of our deregulated miRNAs. A large enrichment in mRNA encoding proteins involved in extracellular matrix organization and different phosphodiesterases were identified among these putative targets. The direct interaction between miR-101-3p and miR-144-3p and PDE4D mRNA was experimentally validated. The global miRNA profiles were not greatly modified, confirming the definition of these tumors as minimal deviation tumors. These results support a role for miRNA in the regulation of extracellular matrix proteins and tissue remodeling occurring during tumor development, and in the important negative feedback of the cAMP pathway, which limits the consequences of its constitutive activation in these tumors., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

37. miRNA expression in anaplastic thyroid carcinomas.

Author

Hebrant, Aline, Floor, Sebastien, Saiselet, Manuel, Antoniou, Aline, Desbuleux, Alice, Snyers, Bérengère, La, Caroline, De Saint Aubain, Nicolas, Leteurtre, Emmanuelle, Andry, Guy, Maenhaut, Carine, Hebrant, Aline, Floor, Sebastien, Saiselet, Manuel, Antoniou, Aline, Desbuleux, Alice, Snyers, Bérengère, La, Caroline, De Saint Aubain, Nicolas, Leteurtre, Emmanuelle, Andry, Guy, and Maenhaut, Carine

Abstract

Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents an end stage of thyroid tumor progression. No effective treatment exists so far. In this study, we analyzed the miRNA expression profiles of 11 ATC by microarrays and their relationship with the mRNA expression profiles of the same 11 ATC samples. ATC show distinct miRNA expression profiles compared to other less aggressive thyroid tumor types. ATC show 18 commonly deregulated miRNA compared to normal thyroid tissue (17 downregulated and 1 upregulated miRNA). First, the analysis of a combined approach of the mRNA gene expression and of the bioinformatically predicted mRNA targets of the deregulated miRNA suggested a role for these regulations in the epithelial to mesenchymal transition (EMT) process in ATC. Second, the direct interaction between one of the upregulated mRNA target, the LOX gene which is an EMT key player, and a downregulated miRNA, the miR-29a, was experimentally validated by a luciferase assay in HEK cell. Third, we confirmed that the ATC tissue is composed of about 50% of tumor associated macrophages (TAM) and suggested, by taking into account our data and published data, their most likely direct or paracrine intercommunication between them and the thyroid tumor cells, amplifying the tumor aggressiveness. Finally, we demonstrated by in situ hybridization a specific thyrocyte localization of 3 of the deregulated miRNA: let-7g, miR-29a and miR-30e and we pointed out the importance of identifying the cell type localization before drawing any conclusion on the physiopathological role of a given gene., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2014

38. miRNA Expression in Anaplastic Thyroid Carcinomas

Author

Hébrant, Aline, primary, Floor, Sébastien, additional, Saiselet, Manuel, additional, Antoniou, Aline, additional, Desbuleux, Alice, additional, Snyers, Bérengère, additional, La, Caroline, additional, de Saint Aubain, Nicolas, additional, Leteurtre, Emmanuelle, additional, Andry, Guy, additional, and Maenhaut, Carine, additional

Published
2014
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39. Side effets of repeated treatments with exogenous gonadotropins in cattle, sheep and goats

Author

Drion, P.V., Rémy, Brigitte, McNamara, M., Baril, Gérard, Heyman, Yvan, Leboeuf, B., Theau-Clement, M.C., DESBULEUX, H., Ectors, F.J., Ectors, F., BECKERS, J.F., ProdInra, Migration, Unité de recherche Physiologie de la reproduction des mammifères domestiques, Nouzilly, Institut National de la Recherche Agronomique (INRA), Unité de biologie cellulaire et moléculaire, Insémination Caprine et Porcine (ICP), and Station d'Amélioration Génétique des Animaux (SAGA)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], HORMONE GONADOTROPE, [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
1997

41. READERS REPORT.

Author

Smith, Barrie T., Blanchard, Don, Lyons, Walter, Desbuleux, Ch., Gadell, John E., Prasad, S. Benjamin, Freedman, Walter, and Marx Jr., Leonard

Subjects
LETTERS to the editor, FREIGHT cars, RAILROAD cars, AUTOMOBILE restoration, AERONAUTICS safety appliances
Abstract

Several letters to the editor are presented in response to articles in previous issues including "Doubling the freight car's workday" in the December 18, 1965 issue, "Back on the road--and purring" in the December 15, 1965 issue and "Still seeking air safety" in the December 11, 1965 issue.

Published
1966

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