165 results on '"Leduc BE"'
Search Results
2. Characterization of neural mechanotransduction response in human traumatic brain injury organoid model
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Beltrán, Susana M., Bobo, Justin, Habib, Ahmed, Kodavali, Chowdari V., Edwards, Lincoln, Mamindla, Priyadarshini, Taylor, Rebecca E., LeDuc, Philip R., and Zinn, Pascal O.
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- 2023
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3. Comparison of the neuromuscular response to three different Turkish, semi-professional football training sessions typically used within the tactical periodization training model
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Garrett, Joel M., Leduc, Cedric, Akyildiz, Zeki, van den Hoek, Daniel J., Clemente, Filipe Manuel, Yildiz, Mehmet, and Nobari, Hadi
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- 2023
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4. Characterization of neural mechanotransduction response in human traumatic brain injury organoid model
- Author
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Susana M. Beltrán, Justin Bobo, Ahmed Habib, Chowdari V. Kodavali, Lincoln Edwards, Priyadarshini Mamindla, Rebecca E. Taylor, Philip R. LeDuc, and Pascal O. Zinn
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Medicine ,Science - Abstract
Abstract The ability to model physiological systems through 3D neural in-vitro systems may enable new treatments for various diseases while lowering the need for challenging animal and human testing. Creating such an environment, and even more impactful, one that mimics human brain tissue under mechanical stimulation, would be extremely useful to study a range of human-specific biological processes and conditions related to brain trauma. One approach is to use human cerebral organoids (hCOs) in-vitro models. hCOs recreate key cytoarchitectural features of the human brain, distinguishing themselves from more traditional 2D cultures and organ-on-a-chip models, as well as in-vivo animal models. Here, we propose a novel approach to emulate mild and moderate traumatic brain injury (TBI) using hCOs that undergo strain rates indicative of TBI. We subjected the hCOs to mild (2 s−1) and moderate (14 s−1) loading conditions, examined the mechanotransduction response, and investigated downstream genomic effects and regulatory pathways. The revealed pathways of note were cell death and metabolic and biosynthetic pathways implicating genes such as CARD9, ENO1, and FOXP3, respectively. Additionally, we show a steeper ascent in calcium signaling as we imposed higher loading conditions on the organoids. The elucidation of neural response to mechanical stimulation in reliable human cerebral organoid models gives insights into a better understanding of TBI in humans.
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- 2023
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5. Comparison of the neuromuscular response to three different Turkish, semi-professional football training sessions typically used within the tactical periodization training model
- Author
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Joel M. Garrett, Cedric Leduc, Zeki Akyildiz, Daniel J. van den Hoek, Filipe Manuel Clemente, Mehmet Yildiz, and Hadi Nobari
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Medicine ,Science - Abstract
Abstract This study examined the neuromuscular responses to three typical football (soccer) training sessions and the reliability of peak speed (PS) measured during a submaximal running test (SRT) for identifying neuromuscular fatigue (NMF) status. Jump height (CMJH) and peak velocity (CMJPV) were collected from a CMJ test, while peak speed (PS) was collected during an SRT before and after each training session. Large effect size (ES) decreases were observed in each variable post-training (ES; − 1.42 to − 2.32). Significant differences (> 0.001) were detected between each football session's external load variables. Coefficients of variations were small (
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- 2023
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6. Author Correction: Characterization of neural mechanotransduction response in human traumatic brain injury organoid model
- Author
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Susana M. Beltrán, Justin Bobo, Ahmed Habib, Chowdari V. Kodavali, Lincoln Edwards, Priyadarshini Mamindla, Rebecca E. Taylor, Philip R. LeDuc, and Pascal O. Zinn
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Medicine ,Science - Published
- 2024
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7. Milk proteins as a feed restriction signature indicating the metabolic adaptation of dairy cows
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A. Leduc, S. Le Guillou, L. Bianchi, L. Oliveira Correia, M. Gelé, J. Pires, P. Martin, C. Leroux, F. Le Provost, and M. Boutinaud
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Medicine ,Science - Abstract
Abstract Milk production in dairy cows is affected by numerous factors, including diet. Feed restriction is known to have little impact on milk total protein content but its effect on the fine protein composition is still poorly documented. The objective of this study was to describe the effects of two feed restriction trials of different intensities on the milk protein composition of Holstein cows. One restriction trial was of high intensity (H: 8 mid-lactation Holstein cows) and the second of moderate intensity (M: 19 peak lactation Holstein cows). Feed restriction decreased the milk protein yield for caseins under the M trial and of all six major milk proteins under the H trial. These decreased yields lead to lower concentrations of αs1-, αs2- and β-caseins during the H trial. The milk proteome, analyzed on 32 milk samples, was affected as a function of restriction intensity. Among the 345 proteins identified eight varied under the M trial and 160 under the H trial. Ontology analyses revealed their implication in carbohydrate, lipid and protein metabolisms as well as in the immune system. These proteins reflected adaptations of the animal and mammary gland physiology to feed restriction and constituted a signature of this change.
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- 2022
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8. Milk proteins as a feed restriction signature indicating the metabolic adaptation of dairy cows
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Leduc, A., Le Guillou, S., Bianchi, L., Correia, L. Oliveira, Gelé, M., Pires, J., Martin, P., Leroux, C., Le Provost, F., and Boutinaud, M.
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- 2022
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9. Intra- and inter-spatial variability of meiofauna in hadal trenches is linked to microbial activity and food availability
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Shimabukuro, M., Zeppilli, D., Leduc, D., Wenzhöfer, F., Berg, P., Rowden, A. A., and Glud, R. N.
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- 2022
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10. Variability in frost occurrence under climate change and consequent risk of damage to trees of western Quebec, Canada
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Marquis, Benjamin, Bergeron, Yves, Houle, Daniel, Leduc, Martin, and Rossi, Sergio
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- 2022
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11. A refined proposal for the origin of dogs: the case study of Gnirshöhle, a Magdalenian cave site
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Baumann, Chris, Pfrengle, Saskia, Münzel, Susanne C., Molak, Martyna, Feuerborn, Tatiana R., Breidenstein, Abagail, Reiter, Ella, Albrecht, Gerd, Kind, Claus-Joachim, Verjux, Christian, Leduc, Charlotte, Conard, Nicholas J., Drucker, Dorothée G., Giemsch, Liane, Thalmann, Olaf, Bocherens, Hervé, and Schuenemann, Verena J.
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- 2021
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12. Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
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Leduc, Alexandre, Chaouni, Samia, Pouzoulet, Frédéric, De Marzi, Ludovic, Megnin-Chanet, Frédérique, Corre, Erwan, Stefan, Dinu, Habrand, Jean-Louis, Sichel, François, and Laurent, Carine
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- 2021
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13. Author Correction: Bones geometric morphometrics illustrate 10th millennium cal. BP domestication of autochthonous Cypriot wild boar (Sus scrofa circeus nov. ssp)
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Cucchi, Thomas, Domont, Auriale, Harbers, Hugo, Evin, Allowen, Alcàntara Fors, Roger, Saña, Maria, Leduc, Charlotte, Guidez, Aurélie, Bridault, Anne, Hongo, Hitomi, Price, Max, Peters, Joris, Briois, François, Guilaine, Jean, and Vigne, Jean‑Denis
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- 2021
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14. Bones geometric morphometrics illustrate 10th millennium cal. BP domestication of autochthonous Cypriot wild boar (Sus scrofa circeus nov. ssp)
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Cucchi, Thomas, Domont, Auriale, Harbers, Hugo, Evin, Allowen, Alcàntara Fors, Roger, Saña, Maria, Leduc, Charlotte, Guidez, Aurélie, Bridault, Anne, Hongo, Hitomi, Price, Max, Peters, Joris, Briois, François, Guilaine, Jean, and Vigne, Jean-Denis
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- 2021
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15. Publisher Correction: Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
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Leduc, Alexandre, Chaouni, Samia, Pouzoulet, Frédéric, De Marzi, Ludovic, Megnin-Chanet, Frédérique, Corre, Erwan, Stefan, Dinu, Habrand, Jean-Louis, Sichel, François, and Laurent, Carine
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- 2021
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16. Characteristics and comparative clinical outcomes of prisoner versus non-prisoner populations hospitalized with COVID-19
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Altibi, Ahmed M., Pallavi, Bhargava, Liaqat, Hassan, Slota, Alexander A., Sheth, Radhika, Al Jebbawi, Lama, George, Matthew E., LeDuc, Allison, Abdallah, Enas, Russell, Luke R., Jain, Saniya, Shirvanian, Nariné, Masri, Ahmad, and Kak, Vivek
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- 2021
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17. Probing coordinated co-culture cancer related motility through differential micro-compartmentalized elastic substrates
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Chou, Szu-Yuan, Lin, Chang-You, Cassino, Theresa, Wan, Li, and LeDuc, Philip R.
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- 2020
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18. Fatty acid mimetic PBI-4547 restores metabolic homeostasis via GPR84 in mice with non-alcoholic fatty liver disease
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Simard, Jean-Christophe, Thibodeau, Jean-François, Leduc, Martin, Tremblay, Mikael, Laverdure, Alexandre, Sarra-Bournet, François, Gagnon, William, Ouboudinar, Jugurtha, Gervais, Liette, Felton, Alexandra, Letourneau, Sylvie, Geerts, Lilianne, Cloutier, Marie-Pier, Hince, Kathy, Corpuz, Ramon, Blais, Alexandra, Quintela, Vanessa Marques, Duceppe, Jean-Simon, Abbott, Shaun D., Blais, Amélie, Zacharie, Boulos, Laurin, Pierre, Laplante, Steven R., Kennedy, Christopher R. J., Hébert, Richard L., Leblond, François A., Grouix, Brigitte, and Gagnon, Lyne
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- 2020
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19. Matriptase processing of APLP1 ectodomain alters its homodimerization
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Lanchec, Erwan, Désilets, Antoine, Béliveau, François, Fontaine-Carbonneau, Cloé, Laniel, Andréanne, Leduc, Richard, and Lavoie, Christine
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- 2020
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20. Frequency and consequences of the collection of already parasitized caterpillars by a potter wasp
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Segoli, Michal, Leduc, Sarah, Meng, Fengqun, Hoffmann, Ishai, Kishinevsky, Miriam, and Rozenberg, Tamir
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- 2020
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21. Scintigraphic Investigations of the Deep and Superficial Lymphatic Systems in the Evaluation of Lower Limb Oedema
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Barbieux, Romain, Roman, Mirela Mariana, Rivière, Fanny, Leduc, Olivier, Leduc, Albert, Bourgeois, Pierre, and Provyn, Steven
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- 2019
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22. Characterization of Holstein and Normande whole milk miRNomes highlights breed specificities
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Le Guillou, S., Leduc, A., Laubier, J., Barbey, S., Rossignol, M.-N., Lefebvre, R., Marthey, S., Laloë, D., and Le Provost, F.
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- 2019
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23. Brain lateralization probed by water diffusion at the atomic to micrometric scale
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Natali, F., Dolce, C., Peters, J., Stelletta, C., Demé, B., Ollivier, J., Leduc, G., Cupane, A., and Barbier, E. L.
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- 2019
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24. Pleiotropic effects of rfa-gene mutations on Escherichia coli envelope properties
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Pagnout, Christophe, Sohm, Bénédicte, Razafitianamaharavo, Angélina, Caillet, Céline, Offroy, Marc, Leduc, Marjorie, Gendre, Héloïse, Jomini, Stéphane, Beaussart, Audrey, Bauda, Pascale, and Duval, Jérôme F. L.
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- 2019
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25. Author Correction: Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling
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Wan, L., Skoko, J., Yu, J., Ozdoganlar, O. B., LeDuc, P. R., and Neumann, C. A.
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- 2019
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26. Transgenic substitution with Greater Amberjack Seriola dumerili fish insulin 2 in NOD mice reduces beta cell immunogenicity
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Foo, Kylie S., Skowronski, Alicja A., Baum, Danielle, Firdessa-Fite, Rebuma, Thams, Sebastian, Shang, Linshan, Creusot, Rémi J., LeDuc, Charles A., Egli, Dieter, and Leibel, Rudolph L.
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- 2019
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27. Bones geometric morphometrics illustrate 10th millennium cal. BP domestication of autochthonous Cypriot wild boar (Sus scrofa circeus nov. ssp)
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Jean Guilaine, Hugo Harbers, Roger Alcàntara Fors, Charlotte Leduc, François Briois, Max Price, Aurélie Guidez, Allowen Evin, Jean-Denis Vigne, Joris Peters, Maria Saña, Anne Bridault, Auriale Domont, Hitomi Hongo, Thomas Cucchi, Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Archéologies environnementales, Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Autonomous University of Barcelona, Faculty of Education, Trajectoires - UMR 8215, Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Archéologie et histoire ancienne : Méditerranée - Europe (ARCHIMEDE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF (institution)), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)
- Subjects
0106 biological sciences ,0301 basic medicine ,[SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory ,Evolution ,Lineage (evolution) ,[SDE.MCG]Environmental Sciences/Global Changes ,Science ,Sus scrofa ,Zoology ,010603 evolutionary biology ,01 natural sciences ,Article ,Domestication ,03 medical and health sciences ,Wild boar ,biology.animal ,Animals ,Animal Husbandry ,Author Correction ,History, Ancient ,Morphometrics ,Multidisciplinary ,Epipaleolithic ,biology ,030104 developmental biology ,Geography ,Geographic origin ,[SHS.ENVIR]Humanities and Social Sciences/Environmental studies ,Medicine ,[SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology - Abstract
Epipaleolithic hunter-gatherers from the Near East introduced wild boars (Sus scrofa) to Cyprus, with the Early Pre-Pottery Neolithic (PPN) settlers hunting the wild descendants of these boars. However, the geographic origin of the Cypriot boar and how they were integrated into the earliest forms of pig husbandry remain unsolved. Here, we present data on 11,000 to 9000 cal. BP Sus scrofa from the PPN sites of Klimonas and Shillourokambos. We compared them to contemporaneous populations from the Near East and to Neolithic and modern populations in Corsica, exploring their origin and evolution using biosystematic signals from molar teeth and heel bones (calcanei), using 2D and 3D geometric morphometrics. We found that the Cypriot PPN lineage of Sus scrofa originates from the Northern Levant. Yet, their phenotypic idiosyncrasy suggest that they evolved into an insular sub-species that we named Sus scrofa circeus, referring to Circe, the metamorphosis goddess that changed Ulysses companions into pigs. The phenotypic homogeneity among PPNA Klimonas wild boars and managed populations of PPNB Shillourokambos suggests that local domestication has been undertaken on the endemic S. s. circeus, strengthening the idea that Cyprus was integrated into the core region of animal domestication.
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- 2021
28. Functional diversity of TMPRSS6 isoforms and variants expressed in hepatocellular carcinoma cell lines
- Author
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Dion, Sébastien P., Béliveau, François, Morency, Louis-Philippe, Désilets, Antoine, Najmanovich, Rafaël, and Leduc, Richard
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- 2018
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29. GRK2 knockdown in mice exacerbates kidney injury and alters renal mechanisms of blood pressure regulation
- Author
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Tutunea-Fatan, Elena, Abd-Elrahman, Khaled S., Thibodeau, Jean-Francois, Holterman, Chet E., Holleran, Brian J., Leduc, Richard, Kennedy, Christopher R. J., Gros, Robert, and Ferguson, Stephen S. G.
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- 2018
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30. Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling
- Author
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Wan, L., Skoko, J., Yu, J., Ozdoganlar, O. B., LeDuc, P. R., and Neumann, C. A.
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- 2017
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31. Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
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Frederic Pouzoulet, Jean-Louis Habrand, François Sichel, Alexandre Leduc, Ludovic De Marzi, Carine Laurent, Erwan Corre, Frédérique Mégnin-Chanet, Dinu Stefan, Samia Chaouni, Aliments Bioprocédés Toxicologie Environnements (ABTE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)
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Cancer therapy ,[SDV]Life Sciences [q-bio] ,Science ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Article ,Non-coding RNAs ,Transcriptome ,03 medical and health sciences ,Gene expression analysis ,0302 clinical medicine ,Transcription (biology) ,Complementary DNA ,microRNA ,Gene expression ,Keratin ,Transcriptomics ,Gene ,Proton therapy ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Multidisciplinary ,Cell biology ,chemistry ,030220 oncology & carcinogenesis ,Medicine - Abstract
Proton therapy allows to avoid excess radiation dose on normal tissues. However, there are some limitations. Indeed, passive delivery of proton beams results in an increase in the lateral dose upstream of the tumor and active scanning leads to strong differences in dose delivery. This study aims to assess possible differences in the transcriptomic response of skin in C57BL/6 mice after TBI irradiation by active or passive proton beams at the dose of 6 Gy compared to unirradiated mice. In that purpose, total RNA was extracted from skin samples 3 months after irradiation and RNA-Seq was performed. Results showed that active and passive delivery lead to completely different transcription profiles. Indeed, 140 and 167 genes were differentially expressed after active and passive scanning compared to unirradiated, respectively, with only one common gene corresponding to RIKEN cDNA 9930021J03. Moreover, protein–protein interactions performed by STRING analysis showed that 31 and 25 genes are functionally related after active and passive delivery, respectively, with no common gene between both types of proton delivery. Analysis showed that active scanning led to the regulation of genes involved in skin development which was not the case with passive delivery. Moreover, 14 ncRNA were differentially regulated after active scanning against none for passive delivery. Active scanning led to 49 potential mRNA-ncRNA pairs with one ncRNA mainly involved, Gm44383 which is a miRNA. The 43 genes potentially regulated by the miRNA Gm44393 confirmed an important role of active scanning on skin keratin pathway. Our results demonstrated that there are differences in skin gene expression still 3 months after proton irradiation versus unirradiated mouse skin. And strong differences do exist in late skin gene expression between scattered or scanned proton beams. Further investigations are strongly needed to understand this discrepancy and to improve treatments by proton therapy.
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- 2021
32. Probing coordinated co-culture cancer related motility through differential micro-compartmentalized elastic substrates
- Author
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Chang-You Lin, Szu-Yuan Chou, Li Wan, Philip R. LeDuc, and Theresa R. Cassino
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0301 basic medicine ,Cancer microenvironment ,Cell type ,Science ,Cell ,Motility ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,medicine ,Substrate stiffness ,Tumor Microenvironment ,Humans ,Dimethylpolysiloxanes ,Cells, Cultured ,Multidisciplinary ,Lab-on-a-chip ,Chemistry ,Cell growth ,Substrate (chemistry) ,Cancer ,Cell Differentiation ,Epithelial Cells ,Fibroblasts ,medicine.disease ,Coculture Techniques ,Elasticity ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,A549 Cells ,030220 oncology & carcinogenesis ,Medicine ,Co-Culture - Abstract
Cell development and behavior are driven by internal genetic programming, but the external microenvironment is increasingly recognized as a significant factor in cell differentiation, migration, and in the case of cancer, metastatic progression. Yet it remains unclear how the microenvironment influences cell processes, especially when examining cell motility. One factor that affects cell motility is cell mechanics, which is known to be related to substrate stiffness. Examining how cells interact with each other in response to mechanically differential substrates would allow an increased understanding of their coordinated cell motility. In order to probe the effect of substrate stiffness on tumor related cells in greater detail, we created hard–soft–hard (HSH) polydimethylsiloxane (PDMS) substrates with alternating regions of different stiffness (200 and 800 kPa). We then cultured WI-38 fibroblasts and A549 epithelial cells to probe their motile response to the substrates. We found that when the 2 cell types were exposed simultaneously to the same substrate, fibroblasts moved at an increased speed over epithelial cells. Furthermore, the HSH substrate allowed us to physically guide and separate the different cell types based on their relative motile speed. We believe that this method and results will be important in a diversity of areas including mechanical microenvironment, cell motility, and cancer biology.
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- 2020
33. Matriptase processing of APLP1 ectodomain alters its homodimerization
- Author
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François Béliveau, Christine Lavoie, Richard Leduc, Antoine Désilets, Cloé Fontaine-Carbonneau, Andréanne Laniel, and Erwan Lanchec
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Proteases ,Amyloid beta ,lcsh:Medicine ,Article ,Amyloid beta-Protein Precursor ,mental disorders ,Amyloid precursor protein ,Humans ,Matriptase ,APLP1 ,lcsh:Science ,Serine protease ,Amyloid beta-Peptides ,Multidisciplinary ,biology ,Chemistry ,Serine Endopeptidases ,lcsh:R ,Alzheimer's disease ,Cell biology ,HEK293 Cells ,Ectodomain ,biology.protein ,lcsh:Q ,Amyloid Precursor Protein Secretases ,Dimerization ,Amyloid precursor protein secretase - Abstract
The amyloid beta peptide (Aβ) is derived from the amyloid precursor protein (APP) by secretase processing. APP is also cleaved by numerous other proteases, such as the type II transmembrane serine protease matriptase, with consequences on the production of Aβ. Because the APP homolog protein amyloid-like protein 1 (APLP1) shares similarities with APP, we sought to determine if matriptase also plays a role in its processing. Here, we demonstrate that matriptase directly interacts with APLP1 and that APLP1 is cleaved in cellulo by matriptase in its E1 ectodomains at arginine 124. Replacing Arg124 with Ala abolished APLP1 processing by matriptase. Using a bioluminescence resonance energy transfer (BRET) assay we found that matriptase reduces APLP1 homodimeric interactions. This study identifies matriptase as the first protease cleaving APLP1 in its dimerization domain, potentially altering the multiple functions associated with dimer formation.
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- 2020
34. Frequency and consequences of the collection of already parasitized caterpillars by a potter wasp
- Author
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Sarah Leduc, Michal Segoli, Fengqun Meng, Ishai Hoffmann, Tamir Rozenberg, and Miriam Kishinevsky
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0106 biological sciences ,food.ingredient ,Offspring ,Evolution ,Zoology ,lcsh:Medicine ,Biology ,010603 evolutionary biology ,01 natural sciences ,Copidosoma ,Article ,Predation ,Parasitoid ,food ,Nest ,Potter wasp ,lcsh:Science ,Multidisciplinary ,Ecology ,fungi ,lcsh:R ,biology.organism_classification ,Delta dimidiatipenne ,Pupa ,010602 entomology ,lcsh:Q - Abstract
Maladaptive behaviors reflecting a “bad” choice of habitat or resource have been widely documented; however, their persistence is often difficult to interpret. The potter wasp Delta dimidiatipenne constructs mud cells, in each of which it lays a single egg and places several caterpillars to feed its offspring. Preliminary observations indicated that a portion of these caterpillars were already parasitized and contained the offspring of the gregarious parasitoid Copidosoma primulum. As a result, the offspring of the potter wasp often failed to develop. To characterize the distribution, frequency and consequences of this intriguing phenomenon, we surveyed potter wasp nests throughout the Negev Desert. Evidence for parasitized caterpillars (mummies) was found in ~85% of the sampled sites, in ~20% of previous years’ nest cells and in ~70–80% of the same year’s cells. The survival and pupal mass of the potter wasp offspring were negatively associated with the presence and number of parasitized caterpillars inside the cells. We concluded that the collection of parasitized caterpillars by D. dimidiantipenne is frequent and costly. The persistence of this behavior may result from limited discrimination ability against parasitized prey by female potter wasps, or by their limited ability to exhibit choosiness under field conditions.
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- 2020
35. Publisher Correction: Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
- Author
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Erwan Corre, Jean-Louis Habrand, Samia Chaouni, Carine Laurent, Frederic Pouzoulet, Dinu Stefan, François Sichel, Alexandre Leduc, Ludovic De Marzi, and Frédérique Mégnin-Chanet
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RNA, Untranslated ,Proton ,Science ,Nuclear magnetic resonance ,Animals ,Protein Interaction Maps ,RNA, Messenger ,Irradiation ,Skin ,Multidisciplinary ,Chemistry ,Gene Expression Profiling ,Body Weight ,Dose-Response Relationship, Radiation ,Total body ,Publisher Correction ,Mice, Inbred C57BL ,Gene Ontology ,Gene Expression Regulation ,Keratins ,Medicine ,Protons ,Transcriptome ,Normal skin ,Whole-Body Irradiation - Abstract
Proton therapy allows to avoid excess radiation dose on normal tissues. However, there are some limitations. Indeed, passive delivery of proton beams results in an increase in the lateral dose upstream of the tumor and active scanning leads to strong differences in dose delivery. This study aims to assess possible differences in the transcriptomic response of skin in C57BL/6 mice after TBI irradiation by active or passive proton beams at the dose of 6 Gy compared to unirradiated mice. In that purpose, total RNA was extracted from skin samples 3 months after irradiation and RNA-Seq was performed. Results showed that active and passive delivery lead to completely different transcription profiles. Indeed, 140 and 167 genes were differentially expressed after active and passive scanning compared to unirradiated, respectively, with only one common gene corresponding to RIKEN cDNA 9930021J03. Moreover, protein-protein interactions performed by STRING analysis showed that 31 and 25 genes are functionally related after active and passive delivery, respectively, with no common gene between both types of proton delivery. Analysis showed that active scanning led to the regulation of genes involved in skin development which was not the case with passive delivery. Moreover, 14 ncRNA were differentially regulated after active scanning against none for passive delivery. Active scanning led to 49 potential mRNA-ncRNA pairs with one ncRNA mainly involved, Gm44383 which is a miRNA. The 43 genes potentially regulated by the miRNA Gm44393 confirmed an important role of active scanning on skin keratin pathway. Our results demonstrated that there are differences in skin gene expression still 3 months after proton irradiation versus unirradiated mouse skin. And strong differences do exist in late skin gene expression between scattered or scanned proton beams. Further investigations are strongly needed to understand this discrepancy and to improve treatments by proton therapy.
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- 2021
36. Variability in frost occurrence under climate change and consequent risk of damage to trees of western Quebec, Canada
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Benjamin Marquis, Yves Bergeron, Daniel Houle, Martin Leduc, and Sergio Rossi
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Multidisciplinary ,Climate Change ,Quebec ,Seasons ,Ecosystem ,Trees - Abstract
Climate change affects timings, frequency, and intensity of frost events in northern ecosystems. However, our understanding of the impacts that frost will have on growth and survival of plants is still limited. When projecting the occurrence of frost, the internal variability and the different underlying physical formulations are two major sources of uncertainty of climate models. We use 50 climate simulations produced by a single-initial large climate ensemble and five climate simulations produced by different pairs of global and regional climate models based on the concentration pathway (RCP 8.5) over a latitudinal transect covering the temperate and boreal ecosystems of western Quebec, Canada, during 1955–2099 to provide a first-order estimate of the relative importance of these two sources of uncertainty on the occurrence of frost, i.e. when air temperature is
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- 2021
37. A refined proposal for the origin of dogs: the case study of Gnirshöhle, a Magdalenian cave site
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Charlotte Leduc, Olaf Thalmann, Nicholas J. Conard, Christian Verjux, Chris Baumann, Abagail M. Breidenstein, Martyna Molak, Dorothée G. Drucker, Susanne C. Münzel, Ella Reiter, Saskia Pfrengle, Claus-Joachim Kind, Liane Giemsch, Verena J. Schuenemann, Hervé Bocherens, Gerd Albrecht, Tatiana R. Feuerborn, University of Tübingen, Universität Zürich [Zürich] = University of Zurich (UZH), University of Warsaw (UW), Markgräflerland-Museum Society, State Office for Cultural Heritage Baden-Württemberg, Direction Régionale des Affaires Culturelles Centre-Val de Loire (DRAC Centre-Val de Loire), Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives (Inrap), Trajectoires - UMR 8215, Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Archäologisches Museum Frankfurt, Poznan University of Medical Sciences [Poland] (PUMS), University of Zurich, Baumann, Chris, Pfrengle, Saskia, and Schuenemann, Verena J
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0106 biological sciences ,0301 basic medicine ,[SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory ,Protein diet ,Evolution ,Science ,610 Medicine & health ,Morphology (biology) ,Biology ,DNA, Mitochondrial ,010603 evolutionary biology ,01 natural sciences ,Article ,Domestication ,03 medical and health sciences ,Dogs ,Cave ,Genetics ,Animals ,Restricted diet ,Magdalenian ,Phylogeny ,Canidae ,1000 Multidisciplinary ,geography ,Genetic diversity ,Wolves ,Multidisciplinary ,geography.geographical_feature_category ,Ecology ,Phylogenetic tree ,Fossils ,Caves ,030104 developmental biology ,Evolutionary biology ,11294 Institute of Evolutionary Medicine ,Medicine ,Switzerland - Abstract
Dogs are known to be the oldest animals domesticated by humans. Although many studies have examined wolf domestication, the geographic and temporal origin of this process is still being debated. To address this issue, our study sheds new light on the early stages of wolf domestication during the Magdalenian period (16–14 ka cal BP) in the Hegau Jura region (Southwestern Germany and Switzerland). By combining morphology, genetics, and isotopes, our multidisciplinary approach helps to evaluate alternate processes driving the early phases of domestication. The isotope analysis uncovered a restricted, low δ15N protein diet for all analyzed Gnirshöhle specimens, while morphological examinations and phylogenetic relationships did not unequivocally assign them to one or the other canid lineage. Intriguingly, the newly generated mitochondrial canid genomes span the entire genetic diversity of modern dogs and wolves. Such high mitochondrial diversity could imply that Magdalenian people tamed and reared animals originating from different wolf lineages. We discuss our results in light of three ecological hypotheses and conclude that both domestication and the existence of a specialized wolf ecomorph are highly probable. However, due to their proximity to humans and a restricted diet, we propose domestication as the most likely scenario explaining the patterns observed herein.
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- 2021
38. Characteristics and comparative clinical outcomes of prisoner versus non-prisoner populations hospitalized with COVID-19
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Saniya Jain, Vivek Kak, Alexander A. Slota, Matthew E. George, Radhika Sheth, Lama Al Jebbawi, Hassan Liaqat, Ahmed M Altibi, Allison LeDuc, Enas Abdallah, Nariné Shirvanian, Bhargava Pallavi, Luke R. Russell, and Ahmad Masri
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Male ,Diseases ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,law ,Vasoconstrictor Agents ,030212 general & internal medicine ,Hospital Mortality ,Aged, 80 and over ,Multidisciplinary ,Hazard ratio ,Middle Aged ,Intensive care unit ,Hospitalization ,Survival Rate ,Intensive Care Units ,Cohort ,Medicine ,population characteristics ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,Science ,Tachypnea ,Article ,03 medical and health sciences ,Medical research ,mental disorders ,medicine ,Humans ,Survival rate ,Aged ,Proportional Hazards Models ,Ventilators, Mechanical ,Proportional hazards model ,business.industry ,SARS-CoV-2 ,Prisoners ,COVID-19 ,Odds ratio ,social sciences ,Confidence interval ,United States ,Black or African American ,Logistic Models ,Risk factors ,Emergency medicine ,business - Abstract
Prisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were used to investigate primary outcomes. Of the 706 hospitalized COVID-19 patients (mean age 66.7 ± 16.1 years, 57% males, and 44% black), 108 were prisoners and 598 were non-prisoners. Compared to non-prisoners, prisoners were more likely to present with fever, tachypnea, hypoxemia, and markedly elevated inflammatory markers. Prisoners were more commonly admitted to the intensive care unit (ICU) (26.9% vs. 18.7%), required vasopressors (24.1% vs. 9.9%), and intubated (25.0% vs. 15.2%). Prisoners had higher unadjusted inpatient mortality (29.6% vs. 20.1%) and 30-day mortality (34.3% vs. 24.6%). In the adjusted models, prisoner status was associated with higher in-hospital death (odds ratio, 2.32; 95% confidence interval (CI), 1.33 to 4.05) and 30-day mortality (hazard ratio, 2.00; 95% CI, 1.33 to 3.00). In this cohort of hospitalized COVID-19 patients, prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, in-hospital mortality, and 30-day mortality.
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- 2021
39. Author Correction: Bones geometric morphometrics illustrate 10th millennium cal. BP domestication of autochthonous Cypriot wild boar (Sus scrofa circeus nov. ssp)
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Roger Alcàntara Fors, Jean-Denis Vigne, Auriale Domont, Allowen Evin, Aurélie Guidez, François Briois, Joris Peters, Anne Bridault, Maria Saña, Charlotte Leduc, Hitomi Hongo, Jean Guilaine, Hugo Harbers, Max Price, and Thomas Cucchi
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Morphometrics ,Multidisciplinary ,Wild boar ,biology.animal ,Science ,Zoology ,Medicine ,Biology ,Domestication - Published
- 2021
40. Fatty acid mimetic PBI-4547 restores metabolic homeostasis via GPR84 in mice with non-alcoholic fatty liver disease
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Jugurtha Ouboudinar, Ramon Corpuz, Martin Leduc, Jean-Simon Duceppe, Alexandre Laverdure, Mikaël Tremblay, Kathy Hince, Amélie Blais, Marie-Pier Cloutier, Richard L. Hébert, Christopher R.J. Kennedy, Alexandra Blais, Liette Gervais, Lilianne Geerts, Lyne Gagnon, Pierre Laurin, Jean-Christophe Simard, Steven R. LaPlante, Sylvie Létourneau, Jean-Francois Thibodeau, François A. Leblond, Brigitte Grouix, Shaun D. Abbott, Boulos Zacharie, Alexandra Felton, Vanessa Marques Quintela, William Gagnon, and François Sarra-Bournet
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0301 basic medicine ,Male ,Magnetic Resonance Spectroscopy ,Molecular biology ,Physiology ,lcsh:Medicine ,Diseases ,Biosensing Techniques ,Acetates ,Ligands ,Receptors, G-Protein-Coupled ,Liver disease ,Mice ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Drug Discovery ,Homeostasis ,lcsh:Science ,Receptor ,Beta oxidation ,chemistry.chemical_classification ,Multidisciplinary ,Fatty liver ,Fatty Acids ,Gastroenterology ,GPR120 ,Mitochondria ,Cholesterol ,Disease Progression ,030211 gastroenterology & hepatology ,Female ,Plasmids ,Protein Binding ,medicine.medical_specialty ,Cell biology ,Binding, Competitive ,Article ,03 medical and health sciences ,Free fatty acid receptor 1 ,Internal medicine ,medicine ,Animals ,Humans ,Metabolomics ,Obesity ,business.industry ,lcsh:R ,Fatty acid ,Glucose Tolerance Test ,medicine.disease ,Oxygen ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Glucose ,HEK293 Cells ,chemistry ,lcsh:Q ,Steatosis ,business - Abstract
Non-alcoholic Fatty Liver Disease (NAFLD) is the most common form of liver disease and is associated with metabolic dysregulation. Although G protein-coupled receptor 84 (GPR84) has been associated with inflammation, its role in metabolic regulation remains elusive. The aim of our study was to evaluate the potential of PBI-4547 for the treatment of NAFLD and to validate the role of its main target receptor, GPR84. We report that PBI-4547 is a fatty acid mimetic, acting concomitantly as a GPR84 antagonist and GPR40/GPR120 agonist. In a mouse model of diet-induced obesity, PBI-4547 treatment improved metabolic dysregulation, reduced hepatic steatosis, ballooning and NAFLD score. PBI-4547 stimulated fatty acid oxidation and induced gene expression of mitochondrial uncoupling proteins in the liver. Liver metabolomics revealed that PBI-4547 improved metabolic dysregulation induced by a high-fat diet regimen. In Gpr84−/− mice, PBI-4547 treatment failed to improve various key NAFLD-associated parameters, as was observed in wildtype littermates. Taken together, these results highlight a detrimental role for the GPR84 receptor in the context of meta-inflammation and suggest that GPR84 antagonism via PBI-4547 may reflect a novel treatment approach for NAFLD and its related complications.
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- 2020
41. Proteomic analyses of decellularized porcine ovaries identified new matrisome proteins and spatial differences across and within ovarian compartments
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Kelly A. Even, Monica M. Laronda, Richard D. LeDuc, and Nathaniel F.C. Henning
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Proteomics ,0301 basic medicine ,Swine ,lcsh:Medicine ,Shotgun ,Primary Ovarian Insufficiency ,Biology ,Premature ovarian insufficiency ,Polymerase Chain Reaction ,Article ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Tandem Mass Spectrometry ,Animals ,Compartment (development) ,Tissue engineering ,lcsh:Science ,Extracellular Matrix Proteins ,030219 obstetrics & reproductive medicine ,Multidisciplinary ,Decellularization ,lcsh:R ,Cell Compartmentation ,Extracellular Matrix ,Cell biology ,Processing methods ,030104 developmental biology ,lcsh:Q ,Female ,Folliculogenesis ,Chromatography, Liquid - Abstract
Premature ovarian insufficiency (POI) affects approximately 1% of women. We aim to understand the ovarian microenvironment, including the extracellular matrix (ECM) and associated proteins (matrisome), and its role in controlling folliculogenesis. We mapped the composition of the matrisome of porcine ovaries through the cortical compartment, where quiescent follicles reside and the medullary compartment, where the larger follicles grow and mature. To do this we sliced the ovaries, uniformly in two anatomical planes, enriched for matrisome proteins and performed bottom-up shotgun proteomic analyses. We identified 42 matrisome proteins that were significantly differentially expressed across depths, and 11 matrisome proteins that have not been identified in previous ovarian protein analyses. We validated these data for nine proteins and confirmed compartmental differences with a second processing method. Here we describe a processing and proteomic analysis pipeline that revealed spatial differences and matrisome protein candidates that may influence folliculogenesis.
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- 2019
42. Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling
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John J. Skoko, Philip R. LeDuc, Carola A. Neumann, Jonelle Z. Yu, O. B. Ozdoganlar, and Lei Wan
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0301 basic medicine ,food.ingredient ,Cell ,Cell Culture Techniques ,Motility ,lcsh:Medicine ,Breast Neoplasms ,Matrix (biology) ,Gelatin ,Soft lithography ,Article ,Extracellular matrix ,03 medical and health sciences ,food ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Computer vision ,Author Correction ,lcsh:Science ,Multidisciplinary ,Tissue Engineering ,Chemistry ,business.industry ,lcsh:R ,Chemotaxis ,Microfluidic Analytical Techniques ,Chip ,Extracellular Matrix ,030104 developmental biology ,medicine.anatomical_structure ,Cross-Sectional Studies ,Biophysics ,Female ,lcsh:Q ,Artificial intelligence ,business - Abstract
The ability for cells to sense and respond to microenvironmental signals is influenced by their three dimensional (3D) surroundings, which includes the extracellular matrix (ECM). In the 3D environment, vascular structures supply cells with nutrients and oxygen thus affecting cell responses such as motility. Interpretation of cell motility studies though is often restricted by the applied approaches such as 2D conventional soft lithography methods that have rectangular channel cross-sectional morphology. To better simulate cell responses to vascular supply in 3D, we developed a cell on a chip system with microfluidic channels with curved cross-sections embedded within a 3D collagen matrix that emulates anatomical vasculature more closely than inorganic polymers, thus to mimic a more physiologically relevant 3D cellular environment. To accomplish this, we constructed perfusable microfluidic channels by embedding sacrificial circular gelatin vascular templates in collagen, which were removed through temperature control. Motile breast cancer cells were pre-seeded into the collagen matrix and when presented with a controlled chemical stimulation from the artificial vasculature, they migrated towards the vasculature structure. We believe this innovative vascular 3D ECM system can be used to provide novel insights into cellular dynamics during multidirectional chemokineses and chemotaxis that exist in cancer and other diseases.
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- 2017
43. Proteomic analyses of decellularized porcine ovaries identified new matrisome proteins and spatial differences across and within ovarian compartments
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Henning, Nathaniel F., primary, LeDuc, Richard D., additional, Even, Kelly A., additional, and Laronda, Monica M., additional
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- 2019
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44. Scintigraphic Investigations of the Deep and Superficial Lymphatic Systems in the Evaluation of Lower Limb Oedema
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Olivier Leduc, Fanny Rivière, Mirela Mariana Roman, Albert Leduc, Pierre Bourgeois, Steven Provyn, Romain Barbieux, Faculty of Physical Education and Physical Therapy, Anatomical Research and Clinical Studies, Physiotherapy, Human Physiology and Anatomy, and Vrije Universiteit Brussel
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,lcsh:Medicine ,Molecular imaging ,Lower limb ,Article ,030218 nuclear medicine & medical imaging ,Lymphatic System ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Lymphatic nodes ,Physical examination ,Phénomènes atmosphériques ,Medicine ,Humans ,In patient ,Lymphedema ,lcsh:Science ,Aged ,Retrospective Studies ,Multidisciplinary ,business.industry ,lcsh:R ,Lower limb oedema ,Middle Aged ,Lymphatic system ,Lower Extremity ,Risk factors ,030220 oncology & carcinogenesis ,lcsh:Q ,Female ,Radiology ,business ,Lymphoscintigraphy - Abstract
The lymphoscintigraphic investigation (LySc) of the superficial lymphatic system (SLS) remains the gold standard for the diagnosis of lower limb lymphoedema. However, LySc of the deep lymphatic system (DLS) may be useful for diagnosing deep lymphatic system insufficiency in patients with lower limb oedema (LLE) but normal and/or paradoxical LySc of the SLS. The purpose of this study was therefore to evaluate a new LySc of the deep lymphatic system in patients presenting with a normal and/or paradoxical SLS exam showing LLE. In all, 15 patients with unilateral and 17 with bilateral LLE underwent 3-phased deep LySc of the lower limb via the injection of 99 mTc-labelled human serum albumin (HSA) nanocolloids in the Kager’s triangle. The absence of popliteal lymphatic node visualization after phase 2 of DLS LySc to diagnose a deep lymphatic insufficiency has a specificity and a sensitivity of 89% in patients with unilateral LLE and without associated venous symptoms. An insufficiency of the DLS was observed in 67% of cases with unilateral LLE and 59% of patients with bilateral LLE of venous and/or lymphatic origin. In conclusion, the lymphoscintigraphic visualization of the popliteal lymphatic nodes after the injection of 99 mTc-labelled HSA nanocolloids in the Kager’s triangle seems to be an effective way to diagnose DLS insufficiency in patients with LLE but normal findings in the SLS., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2018
45. Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs
- Author
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Legendre, Florence, Ollitrault, David, Gómez-Leduc, Tangni, Bouyoucef, Mouloud, Hervieu, Magalie, Gruchy, Nicolas, Mallein-Gerin, Frédéric, Leclercq, Sylvain, Demoor, Magali, Galéra, Philippe, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
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Male ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Science ,Cell- and Tissue-Based Therapy ,Bone Morphogenetic Protein 2 ,Mice, Nude ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Mesenchymal Stem Cell Transplantation ,Collagen Type I ,Article ,Transforming Growth Factor beta1 ,Mice ,Chondrocytes ,Bone Marrow ,Osteoarthritis ,chondrogenesis ,Animals ,Humans ,RNA, Small Interfering ,Cells, Cultured ,Aged ,Aged, 80 and over ,Tissue Engineering ,hypoxia ,Cell Differentiation ,Mesenchymal Stem Cells ,High-Temperature Requirement A Serine Peptidase 1 ,Middle Aged ,BM-MSC ,Collagen Type I, alpha 1 Chain ,siRNA ,Medicine ,Female - Abstract
International audience; Mesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not uniformly positive for stem cell markers, and maintain their multilineage potential throughout multiple passages. The chondrogenic lineage of BM-MSCs was induced in collagen scaffolds, under normoxia or hypoxia, by BMP-2 and/or TGF-β1. The best chondrogenic induction, with the least hypertrophic induction, was obtained with the combination of BMP-2 and TGF-β1 under hypoxia. Differentiated BM-MSCs were then transfected with siRNAs targeting two markers overexpressed in OA chondrocytes, type I collagen and/or HtrA1 protease. siRNAs significantly decreased mRNA and protein levels of type I collagen and HtrA1, resulting in a more typical chondrocyte phenotype, but with frequent calcification of the subcutaneously implanted constructs in a nude mouse model. Our 3D culture model with BMP-2/TGF-β1 and COL1A1/HtrA1 siRNAs was not effective in producing a cartilage-like matrix in vivo. Further optimization is needed to stabilize the chondrocyte phenotype of differentiated BM-MSCs. Nevertheless, this study offers the opportunity to develop a combinatory cellular therapy strategy for cartilage tissue engineering.
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- 2017
46. Pleiotropic effects of rfa-gene mutations on Escherichia coli envelope properties
- Author
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Jérôme F. L. Duval, Pascale Bauda, Marc Offroy, Audrey Beaussart, Céline Caillet, Stéphane Jomini, Marjorie Leduc, Christophe Pagnout, Héloïse Gendre, Angelina Razafitianamaharavo, Bénédicte Sohm, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Plateforme protéomique 3P5 [Institut Cochin] (3P5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Duval, Jerome
- Subjects
Lipopolysaccharides ,0301 basic medicine ,Cell biology ,Cell Membrane Permeability ,Proteome ,[SDV]Life Sciences [q-bio] ,Mutant ,Antimicrobial peptides ,Population ,lcsh:Medicine ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Gene mutation ,Microscopy, Atomic Force ,medicine.disease_cause ,Article ,[PHYS] Physics [physics] ,03 medical and health sciences ,0302 clinical medicine ,Escherichia coli ,medicine ,lcsh:Science ,education ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,[PHYS]Physics [physics] ,education.field_of_study ,Multidisciplinary ,Chemistry ,Escherichia coli Proteins ,Cell Membrane ,lcsh:R ,Glycosyltransferases ,Membrane Proteins ,Bacteriology ,Anti-Bacterial Agents ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,Mutation ,lcsh:Q ,lipids (amino acids, peptides, and proteins) ,Cell envelope ,Bacterial outer membrane ,Biological physics ,030217 neurology & neurosurgery ,Isobaric tag for relative and absolute quantitation - Abstract
International audience; Mutations in the rfa operon leading to severely truncated lipopolysaccharide (LPS) structures are associated with pleiotropic effects on bacterial cells, which in turn generates a complex phenotype termed deep-rough. Literature reports distinct behavior of these mutants in terms of susceptibility to bacteriophages and to several antibacterial substances. There is so far a critical lack of understanding of such peculiar structure-reactivity relationships mainly due to a paucity of thorough biophysical and biochemical characterizations of the surfaces of these mutants. In the current study, the biophysicochemical features of the envelopes of Escherichia coli deep-rough mutants are identified from the molecular to the single cell and population levels using a suite of complementary techniques, namely microelectrophoresis, Atomic Force Microscopy (AFM) and Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) for quantitative proteomics. Electrokinetic, nanomechanical and proteomic analyses evidence enhanced mutant membrane destabilization/permeability, and differentiated abundances of outer membrane proteins involved in the susceptibility phenotypes of LPS-truncated mutants towards bacteriophages, antimicrobial peptides and hydrophobic antibiotics. In particular, inner-core LPS altered mutants exhibit the most pronounced heterogeneity in the spatial distribution of their Young modulus and stiffness, which is symptomatic of deep damages on cell envelope likely to mediate phage infection process and antibiotic action. Lipopolysaccharides (LPS) cover surface of the outer membrane of Gram-negative bacteria. They are tripar-tite molecules composed of lipid A, core oligosaccharides usually containing glucose, heptose, galactose, 2-keto-3-deoxyoctonate (KDO), and a highly variable O-antigen component (O-antigen is missing in Escherichia coli K-12). LPS act as a protective and permeable barrier against large molecules and hydrophobic compounds from the environment. They are positioned among phospholipids and proteins of the outer membrane, and contribute to the structural properties of the latter. In Escherichia coli, genes involved in the LPS synthesis are organized according to three operons in the rfa (also known as waa) locus (Fig. 1A). The first operon contains rfaD (or gmhD), rfaF, rfaC and rfaL genes. The three first genes encode proteins involved in the biosynthesis and transfer of the two first heptose residues in the inner core of LPS, whereas rfaL encodes a ligase required for the attachment of O-antigen. The second operon contains (i) rfaQ and rfaK (or waaU) that encodes the heptosyltransferases adding the third and fourth heptose residues, respectively, (ii) genes rfaG (or waaG), rfaI (or waaO) and rfaJ (or warR /waaJ) encoding the gluco-syltransferases that add the three glucose residues in the LPS outer core, (iii) rfaB that encodes the galactosyl-transferase adding the galactose residue to the first glucose, (iv) rfaY and rfaP that encodes kinases responsible for phosphorylation of heptoses, (v) rfaZ involved in the KDO attachment during LPS core biosynthesis, and finally (vi) rfaS that encodes a protein necessary for the attachment of rhamnose to the LPS core by linkage to the KDOII residue. The short kdtA operon contains kdtA (or waaA) that encodes the KDO transferase adding the two KDO residues to the lipid A and kdtB (or coaD) that is not involved in the LPS synthesis 1-3. A defining feature of E. coli LPS is the presence of phosphoryl substituents on the LPS core-heptose residues, essential for
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- 2019
47. Author Correction: Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling
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O. B. Ozdoganlar, Philip R. LeDuc, Jonelle Z. Yu, John J. Skoko, Carola A. Neumann, and Lei Wan
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Structure (mathematical logic) ,Multidisciplinary ,business.industry ,Computer science ,lcsh:R ,lcsh:Medicine ,Cancer ,medicine.disease ,Chip ,Text mining ,Computer architecture ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,medicine ,lcsh:Q ,lcsh:Science ,business - Abstract
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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- 2019
48. Transgenic substitution with Greater Amberjack Seriola dumerili fish insulin 2 in NOD mice reduces beta cell immunogenicity
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Rebuma Firdessa-Fite, Kylie S. Foo, Sebastian Thams, Remi J. Creusot, Alicja A. Skowronski, Rudolph L. Leibel, Charles A. LeDuc, Danielle Baum, Linshan Shang, and Dieter Egli
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,medicine.medical_specialty ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,lcsh:Medicine ,Mice, Transgenic ,Nod ,Biology ,Kidney ,Lymphocyte Activation ,Epitope ,Article ,Diabetes Mellitus, Experimental ,03 medical and health sciences ,Epitopes ,0302 clinical medicine ,Mice, Inbred NOD ,Internal medicine ,Insulin-Secreting Cells ,medicine ,Animals ,Humans ,Insulin ,Amino Acid Sequence ,lcsh:Science ,NOD mice ,Multidisciplinary ,Pancreatic islets ,Immunogenicity ,lcsh:R ,Transplantation ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,lcsh:Q ,Beta cell ,030217 neurology & neurosurgery - Abstract
Type I diabetes (T1D) is caused by immune-mediated destruction of pancreatic beta cells. This process is triggered, in part, by specific (aa 9–23) epitopes of the insulin Β chain. Previously, fish insulins were used clinically in patients allergic to bovine or porcine insulin. Fish and human insulin differ by two amino acids in the critical immunogenic region (aa 9–23) of the B chain. We hypothesized that β cells synthesizing fish insulin would be less immunogenic in a mouse model of T1D. Transgenic NOD mice in which Greater Amberjack fish (Seriola dumerili) insulin was substituted for the insulin 2 gene were generated (mouse Ins1−/− mouse Ins2−/− fish Ins2+/+). In these mice, pancreatic islets remained free of autoimmune attack. To determine whether such reduction in immunogenicity is sufficient to protect β cells from autoimmunity upon transplantation, we transplanted fish Ins2 transgenic (expressing solely Seriola dumerili Ins2), NOD, or B16:A-dKO islets under the kidney capsules of 5 weeks old female NOD wildtype mice. The B:Y16A Β chain substitution has been previously shown to be protective of T1D in NOD mice. NOD mice receiving Seriola dumerili transgenic islet transplants showed a significant (p = 0.004) prolongation of their euglycemic period (by 6 weeks; up to 18 weeks of age) compared to un-manipulated female NOD (diabetes onset at 12 weeks of age) and those receiving B16:A-dKO islet transplants (diabetes onset at 12 weeks of age). These data support the concept that specific amino acid sequence modifications can reduce insulin immunogenicity. Additionally, our study shows that alteration of a single epitope is not sufficient to halt an ongoing autoimmune response. Which, and how many, T cell epitopes are required and suffice to perpetuate autoimmunity is currently unknown. Such studies may be useful to achieve host tolerance to β cells by inactivating key immunogenic epitopes of stem cell-derived β cells intended for transplantation.
- Published
- 2019
49. Functional diversity of TMPRSS6 isoforms and variants expressed in hepatocellular carcinoma cell lines
- Author
-
Sébastien P. Dion, Rafael Najmanovich, François Béliveau, Richard Leduc, Louis-Philippe Morency, and Antoine Désilets
- Subjects
0301 basic medicine ,Gene isoform ,TMPRSS6 ,Carcinoma, Hepatocellular ,Iron ,Mutant ,lcsh:Medicine ,Article ,03 medical and health sciences ,Hepcidin ,Humans ,Protein Isoforms ,lcsh:Science ,Regulation of gene expression ,Multidisciplinary ,Anemia, Iron-Deficiency ,biology ,Liver cell ,Liver Neoplasms ,Serine Endopeptidases ,lcsh:R ,Membrane Proteins ,Hep G2 Cells ,Molecular biology ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Cell culture ,Mutation ,biology.protein ,lcsh:Q ,HAMP - Abstract
TMPRSS6, also known as matriptase-2, is a type II transmembrane serine protease that plays a major role in iron homeostasis by acting as a negative regulator of hepcidin production through cleavage of the BMP co-receptor haemojuvelin. Iron-refractory iron deficiency anaemia (IRIDA), an iron metabolism disorder, is associated with mutations in the TMPRSS6 gene. By analysing RNA-seq data encoding TMPRSS6 isoforms and other proteins involved in hepcidin production, we uncovered significant differences in expression levels between hepatocellular carcinoma (HCC) cell lines and normal human liver samples. Most notably, TMPRSS6 and HAMP expression was found to be much lower in HepG2 and Huh7 cells when compared to human liver samples. Furthermore, we characterized the common TMPRSS6 polymorphism V736A identified in Hep3B cells, the V795I mutation found in HepG2 cells, also associated with IRIDA, and the G603R substitution recently detected in two IRIDA patients. While variant V736A is as active as wild-type TMPRSS6, mutants V795I and G603R displayed significantly reduced proteolytic activity. Our results provide important information about commonly used liver cell models and shed light on the impact of two TMPRSS6 mutations associated with IRIDA.
- Published
- 2018
50. GRK2 knockdown in mice exacerbates kidney injury and alters renal mechanisms of blood pressure regulation
- Author
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Richard Leduc, Jean-Francois Thibodeau, Elena Tutunea-Fatan, Chet E. Holterman, Robert Gros, Stephen S. G. Ferguson, Brian J. Holleran, Khaled S. Abd-Elrahman, and Christopher R.J. Kennedy
- Subjects
Serum ,0301 basic medicine ,medicine.medical_specialty ,G-Protein-Coupled Receptor Kinase 2 ,Kidney Glomerulus ,lcsh:Medicine ,Renal function ,Kidney development ,Blood Pressure ,Kidney ,Losartan ,Receptor, Angiotensin, Type 1 ,Article ,03 medical and health sciences ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,lcsh:Science ,Gene knockdown ,Multidisciplinary ,biology ,business.industry ,Beta adrenergic receptor kinase ,lcsh:R ,Mice, Inbred C57BL ,Phenotype ,030104 developmental biology ,Blood pressure ,Endocrinology ,medicine.anatomical_structure ,Gene Knockdown Techniques ,biology.protein ,lcsh:Q ,Reactive Oxygen Species ,business ,Glomerular Filtration Rate ,medicine.drug - Abstract
The renin-angiotensin system regulates blood pressure and fluid balance in the body primarily via angiotensin receptor 1 (AT1R). Renal AT1R was found to be primarily responsible for Ang II-mediated hypertension. G protein-coupled receptor kinase 2 (GRK2) modulates AT1R desensitization and increased GRK2 protein expression is reported in hypertensive patients. However, the consequences of GRK2 inhibition on kidney functions remain unknown. We employed shGRK2 knockdown mice (shGRK2 mice) to test the role of GRK2 in kidney development and function that can be ultimately linked to the hypertensive phenotype detected in shGRK2 mice. GRK2 knockdown reduced kidney size, nephrogenesis and glomerular count, and impaired glomerular filtration. Glomerular damage in adult shGRK2 mice was associated with increased renin- and AT1R-mediated production of reactive oxygen species. The AT1R blocker, Losartan, normalized elevated blood pressure and markedly improved glomerular filtration in the shGRK2 knockdown mice. Our findings provide evidence for the crucial role of GRK2 in renal regulation of blood pressure. It also suggests that the detrimental outcomes of GRK2 inhibitors on the kidney should be carefully examined when used as antihypertensive.
- Published
- 2018
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