̽»¨¾«Ñ¡

Chemical and functional neuroanatomy of pain and stress systems – Tomas Hökfelt group

Our research involves studies of neuropeptides and their receptors in the nervous and endocrine systems, mainly based on histochemical techniques such as immunohistochemistry and in situ hybridization, but also molecular biological methods. During recent years focus has been on the analysis of human postmortem tissues.

Immunofluorescence micrograph of human dorsal root ganglion after incubation with antiserum to the neuropeptide calcitonin gene-related peptide (CGRP).

Research focus

Chemical Neurotransmission Research

Our research is focused on chemical messengers in the nervous and endocrine systems, mainly based on histochemical techniques: immunohistochemistry and in situ hybridiza­tion. We also use molecular biological approaches including RT-PCR and have created some transgenic animals.

We are interested in the concept that a neuron produces and re­leases more than one transmitter substance. In particular, our work has focused on the role of neuropeptides in the central and peripheral nervous system, including substance P, cholecystokinin (CCK), galanin and neuropeptide Y (NPY), four peptides that have been discovered by scientists at ̽»¨¾«Ñ¡. These peptides often have a modulating role, exerting their effects via 7-transmembrane, G-protein-coupled receptors. The peptide systems are involved in numerous functions, for example control of food intake, as well as in various diseases such as obesity, anorexia nervosa, pain and depression.

We are now particularly interested in studying human tissues to validate hypotheses based on rodent experiments with the aim to understand mechanisms underlying pain and depression and to develop novel strategies for treatment of these disorders .

Publications

All publications from group members

  • Article: NATURE COMMUNICATIONS. 2024;15(1):2762
    Hevesi Z; Bakker J; Tretiakov EO; Adori C; Raabgrund A; Barde SS; Caramia M; Krausgruber T; Ladstaetter S; Bock C; Hoekfelt T; Harkany T
  • Article: PROCEEDINGS OF THE ESTONIAN ACADEMY OF SCIENCES. 2024;73(3):170-192
    Hokfelt T; Barde S; Zhong W; Xu Z-QD; Alberts P
  • Article: EUROPEAN NEUROPSYCHOPHARMACOLOGY. 2024;78:54-63
    Barde S; Aguila J; Zhong W; Solarz A; Mei I; Prud'homme J; Palkovits M; Turecki G; Mulder J; Uhlen M; Nagy C; Mechawar N; Hedlund E; Hokfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2022;119(33):e2123146119
    Zhong W; Barde S; Mitsios N; Adori C; Oksvold P; von Feilitzen K; O'Learyd L; Csiba L; Hortobagyi T; Szocsics P; Mechawar N; Magloczky Z; Renner E; Palkovits M; Uhlen M; Mulder J; Hokfelt T
  • Article: BRAIN, BEHAVIOR, AND IMMUNITY. 2022;101:214-230
    Su J; Krock E; Barde S; Delaney A; Ribeiro J; Kato J; Agalave N; Wigerblad G; Matteo R; Sabbadini R; Josephson A; Chun J; Kultima K; Peyruchaud O; Hokfelt T; Svensson CI
  • Article: SCIENCE ADVANCES. 2021;7(30):eabg5733
    Adori C; Daraio T; Kuiper R; Barde S; Horvathova L; Yoshitake T; Ihnatko R; Valladolid-Acebes I; Vercruysse P; Wellendorf AM; Gramignoli R; Bozoky B; Kehr J; Theodorsson E; Cancelas JA; Mravec B; Jorns C; Ellis E; Mulder J; Uhlen M; Bark C; Hokfelt T
  • Article: NEUROPEPTIDES. 2020;79:102000
    Lyu C; Xia S; Lyu G-W; Dun X-P; Zheng K; Su J; Barde S; Xu Z-QD; Hokfelt T; Shi T-JS
  • Article: BRAIN STRUCTURE AND FUNCTION. 2019;224(6):2061-2078
    Zahola P; Hanics J; Pinter A; Mate Z; Gaspardy A; Hevesi Z; Echevarria D; Adori C; Barde S; Torocsik B; Erdelyi F; Szabo G; Wagner L; Kovacs GG; Hokfelt T; Harkany T; Alpar A
  • Review: FRONTIERS IN NEURAL CIRCUITS. 2018;12:106
    Hokfelt T; Barde S; Xu Z-QD; Kuteeva E; Ruegg J; Le Maitre E; Risling M; Kehr J; Ihnatko R; Theodorsson E; Palkovits M; Deakin W; Bagdy G; Juhasz G; Prud'homme HJ; Mechawar N; Diaz-Heijtz R; Ogren SO
  • Article: BIOLOGICAL CHEMISTRY. 2017;398(3):331-340
    Yang Y; Li Y; Di F; Cui J; Wang Y; David Xu Z-Q
  • Article: AGING AND DISEASE. 2017;8(1):85-100
    Li Y; Mei Z; Liu S; Wang T; Li H; Li X-X; Han S; Yang Y; Li J; Xu Z-QD
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2016;113(52):E8472-E8481
    Barde S; Ruegg J; Prud'homme J; Ekstrom TJ; Palkovits M; Turecki G; Bagdy G; Ihnatko R; Theodorsson E; Juhasz G; Diaz-Heijtz R; Mechawar N; Hokfelt TGM
  • Thesis / dissertation: 2016
    Barde, Swapnali
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2016;113(43):E6686-E6695
    Zhang M-D; Barde S; Yang T; Lei B; Eriksson LI; Mathew JP; Andreska T; Akassoglou K; Harkany T; Hokfelt TGM; Terrando N
  • Corrigendum: BRAIN STRUCTURE AND FUNCTION. 2016;221(7):3843
    Zhang M-D; Barde S; Szodorai E; Josephson A; Mitsios N; Watanabe M; Attems J; Lubec G; Kovacs GG; Uhlen M; Mulder J; Harkany T; Hokfelt T
  • Article: BRAIN STRUCTURE AND FUNCTION. 2016;221(7):3803-3823
    Zhang M-D; Barde S; Szodorai E; Josephson A; Mitsios N; Watanabe M; Attems J; Lubec G; Kovacs GG; Uhlen M; Mulder J; Harkany T; Hokfelt T
  • Article: BRAIN STRUCTURE AND FUNCTION. 2016;221(7):3521-3546
    Adori C; Barde S; Vas S; Ebner K; Su J; Svensson C; Mathe AA; Singewald N; Reinscheid RR; Uhlen M; Kultima K; Bagdy G; Hokfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2016;113(32):E4726-E4735
    Wang P; Li H; Barde S; Zhang M-D; Sun J; Wang T; Zhang P; Luo H; Wang Y; Yang Y; Wang C; Svenningsson P; Theodorsson E; Hokfelt TGM; Xu Z-QD
  • Article: NUTRITION. 2016;32(6):709-715
    Francois M; Barde S; Legrand R; Lucas N; Azhar S; el Dhaybi M; Guerin C; Hokfelt T; Dechelotte P; Coeffier M; Fetissov SO
  • Article: EXPERIMENTAL NEUROLOGY. 2016;279:159-167
    Kawa L; Barde S; Arborelius UP; Theodorsson E; Agoston D; Risling M; Hokfelt T
  • Article: JOURNAL OF CHILD NEUROLOGY. 2016;31(5):613-620
    Li L; Liu C-Q; Li T-F; Guan Y-G; Zhou J; Qi X-L; Yang Y-T; Deng J-H; Xu Z-QD; Luan G-M
  • Article: STEM CELL RESEARCH. 2016;16(2):236-242
    Tang X; Wang S; Bai Y; Wu J; Fu L; Li M; Xu Q; Xu Z-QD; Alex Zhang Y; Chen Z
  • Article: MOLECULAR NEUROBIOLOGY. 2016;53(2):1266-1278
    Yang Y; Cui J; Xue F; Overstreet A-M; Zhan Y; Shan D; Li H; Li H; Wang Y; Zhang M; Yu C; Xu Z-QD
  • Article: MOLECULAR PAIN. 2015;11:44
    Lyu C; Mulder J; Barde S; Sahlholm K; Zeberg H; Nilsson J; Arhem P; Hokfelt T; Fried K; Shi T-JS
  • Article: NEUROPEPTIDES. 2015;51:17-23
    Francois M; Barde S; Achamrah N; Breton J; do Rego J-C; Coeffier M; Hokfelt T; Dechelotte P; Fetissov SO
  • Article: ACTA NEUROPATHOLOGICA. 2015;129(4):541-563
    Adori C; Glueck L; Barde S; Yoshitake T; Kovacs GG; Mulder J; Magloczky Z; Havas L; Boelcskei K; Mitsios N; Uhlen M; Szolcsanyi J; Kehr J; Ronnback A; Schwartz T; Rehfeld JF; Harkany T; Palkovits M; Schulz S; Hokfelt T
  • Article: SCIENTIFIC REPORTS. 2015;5:9232
    Wang S; Wang B; Pan N; Fu L; Wang C; Song G; An J; Liu Z; Zhu W; Guan Y; Xu Z-QD; Chan P; Chen Z; Zhang YA
  • Article: BIOCHIMICA ET BIOPHYSICA ACTA: INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND BIOPHYSICS. 2015;1849(3):270-281
    Yang Y; Cui J; Xue F; Zhang C; Mei Z; Wang Y; Bi M; Shan D; Meredith A; Li H; Xu Z-QD
  • Article: FRONTIERS IN NEUROANATOMY. 2015;9:126
    Adori C; Barde S; Bogdanovic N; Uhlen M; Reinscheid RR; Kovacs GG; Hokfelt T
  • Article: CEREBRAL CORTEX. 2014;24(12):3277-3288
    Keimpema E; Zheng K; Barde SS; Berghuis P; Dobszay MB; Schnell R; Mulder J; Luiten PGM; Xu ZD; Runesson J; Langel U; Lu B; Hokfelt T; Harkany T
  • Published conference paper: JOURNAL OF MOLECULAR NEUROSCIENCE. 2014;53(3):345-351
    Liu LN; Zhu FP; Song MY; Kang XJ; Shang SJ; Zhang XY; Xu HD; Teng SS; Liu B; Kuo ST; Liu W; Li ML; Zhou L; Jiao RY; Wang CH; Wang SR; Yang H; Zhang B; Zhou Z; Xu ZQD
  • Article: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 2014;446(1):316-321
    Pan NC; Bai Y-F; Yang Y; Hokfelt T; Xu Z-QD
  • Article: MOLECULAR PAIN. 2014;10:12
    Shi T-JS; Xiang Q; Zhang M-D; Barde S; Kai-Larsen Y; Fried K; Josephson A; Glueck L; Deyev SM; Zvyagin AV; Schulz S; Hokfelt T
  • Article: PLOS ONE. 2014;9(1):e85885
    Zhang Y; Lu L; Jia J; Jia L; Geula C; Pei J; Xu Z; Qin W; Liu R; Li D; Pan N
  • Article: INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE. 2014;48(2):109-119
    Wang Y-J; Yang Y-T; Li H; Liu P-Z; Wang C-Y; Xu Z-QD
  • Article: JOURNAL OF NEUROCHEMISTRY. 2013;127(2):209-220
    Mansouri S; Barde S; Ortsater H; Eweida M; Darsalia V; Langel U; Sjoholm A; Hokfelt T; Patrone C
  • Article: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY AND BIOLOGICAL PSYCHIATRY. 2013;45:7-10
    Li H; Wang Y-J; Hua L; Yang Y-T; Zhang M; Zhang D; Wang C; Xu Z-QD
  • Article: NEUROPEPTIDES. 2013;47(2):133-137
    Darsalia V; Mansouri S; Wolbert P; Barde S; Sjoholm A; Patrone C
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2013;110(6):E536-E545
    Le Maitre E; Barde SS; Palkovits M; Diaz-Heijtz R; Hokfelt TGM
  • Article: PLOS ONE. 2013;8(2):e57042
    Wang Y; Yang Y; Hui L; Tie C; Li F; Xu Z-QD; Wang C
  • Article: PLOS ONE. 2013;8(5):e64617
    Wang Y-J; Li H; Yang Y-T; Tie C-L; Li F; Xu Z-QD; Wang C-Y
  • Article: NEUROPEPTIDES. 2012;46(5):195-201
    Tofighi R; Barde S; Palkovits M; Hoog A; Hokfelt T; Ceccatelli S; Hulting A-L
  • Review: FRONTIERS IN MOLECULAR NEUROSCIENCE. 2012;5:29
    Huang H-P; Zhu F-P; Chen X-W; Xu Z-QD; Zhang CX; Zhou Z
  • Article: NEUROSCIENCE. 2011;190:270-288
    Le Maitre TW; Xia S; Le Maitre E; Dun X-P; Lu J; Theodorsson E; Ogren SO; Hokfelt T; Xu Z-QD
  • Article: METHODS IN MOLECULAR BIOLOGY. 2011;789:181-189
    Xu Z-QD
  • Article: JOURNAL OF COMPARATIVE NEUROLOGY. 2010;518(17):3464-3494
    Fu W; Le Maitre E; Fabre V; Bernard J-F; Xu Z-QD; Hokfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2008;105(50):20004-20008
    Shi T-JS; Liu S-XL; Hammarberg H; Watanabe M; Xu Z-QD; Hokfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2008;105(14):5609-5613
    Xia S; Dun X-P; Hu P-S; Kjaer S; Zheng K; Qian Y; Solen C; Xu T; Fredholm B; Hokfelt T; Xu Z-QD
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2008;105(7):2717-2722
    Tofighi R; Joseph B; Xia S; Xu Z-QD; Hamberger B; Hokfelt T; Ceccatelli S
  • Published conference paper: ACTA PHYSIOLOGICA. 2007;190(1):39-45
    Xu Z-QD; Zhang X; Scott L
  • Corrigendum: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2006;103(40):14978
    Swanson CJ; Blackburn TP; Zhang X; Zheng K; Xu Z-QD; Hokfelt T; Wolinsky TD; Konkel MJ; Chen H; Zhong H; Walker MW; Craig DA; Gerald CPG; Branchek TA
  • Corrigendum: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2006;103(14):5632
    Swanson CJ; Blackburn TP; Zhang XX; Zheng K; Xu ZQD; Hökfelt T; Wolinsky TD; Konkel MJ; Chen H; Zhong HL; Walker MW; Craig DA; Gerald CPG; Branchek TA
  • Published conference paper: NEUROPEPTIDES. 2005;39(3):269-275
    Xu ZQD; Zheng K; Hökfelt T
  • Published conference paper: NEUROPEPTIDES. 2005;39(3):259-267
    Zheng K; Kuteeva E; Xia S; Bartfai T; Hökfelt T; Xu ZQD
  • Published conference paper: NEUROPEPTIDES. 2005;39(3):173-178
    Xia S; Kjaer S; Zheng K; Hu PS; Xu T; Hökfelt T; Xu ZQD
  • Article: INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS. 2005;11(1):17-27
    Lundström L; Sollenberg U; Brewer A; Kouya PF; Zheng K; Xu XJ; Sheng X; Robinson JK; Wiesenfeld-Hallin Z; Xu ZQ; Hökfelt T; Bartfai T; Langel Ü
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2004;101(42):15207-15212
    Xia S; Kjær S; Zheng K; Hu PS; Bai L; Jia JY; Rigler R; Pramanik A; Xu T; Hökfelt T; Xu ZQD
  • Article: JOURNAL OF NEUROENDOCRINOLOGY. 2003;15(8):754-760
    Fetissov SO; Xu ZQ; Byrne LC; Hassani H; Ernfors P; Hökfelt T
  • Review: NEUROSCIENCE. 2002;111(3):443-532
    Kopp J; Xu ZQ; Zhang X; Pedrazzini T; Herzog H; Kreese A; Wong H; Walsh JH; Hökfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2001;98(24):14006-14011
    Kokaia M; Holmberg K; Nanobashvili A; Xu ZQD; Kokaia Z; Lendahl U; Hilke S; Theodorsson E; Kahl U; Bartfai T; Lindvall O; Hökfelt T
  • Article: BRAIN RESEARCH. 2001;919(1):169-174
    Ma XS; Tong YG; Schmidt R; Brown W; Payza K; Hodzic L; Pou C; Godbout C; Hökfelt T; Xu ZQD
  • Article: NEUROREPORT. 2001;12(8):1779-1782
    Xu ZQD; Tong YG; Hökfelt T
  • Article: EUROPEAN JOURNAL OF NEUROSCIENCE. 2001;13(4):773-780
    Lindgren N; Xu ZQD; Herrera-Marschitz M; Haycock J; Hökfelt T; Fisone G
  • Article: NEUROSCIENCE. 2001;105(1):249-263
    Shi TJS; Tandrup T; Bergman E; Xu ZQD; Ulfhake B; Hökfelt T
  • Review: NEUROPHARMACOLOGY. 2000;39(8):1337-1356
    Hökfelt T; Broberger C; Xu ZQD; Sergeyev V; Ubink R; Diez M
  • Article: JOURNAL OF NEUROCHEMISTRY. 2000;74(6):2470-2477
    Lindgren N; Xu ZQD; Lindskog M; Herrera-Marschitz M; Goiny M; Haycock J; Goldstein M; Hökfelt T; Fisone G
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 1999;96(25):14583-14587
    Xu ZQD; Ma XS; Soomets U; Langel U; Hökfelt T
  • Published conference paper: HORMONE AND METABOLIC RESEARCH. 1999;31(5):330-334
    Hökfelt T; Broberger C; Diez M; Xu ZQ; Shi T; Kopp J; Zhang X; Holmberg K; Landry M; Koistinaho J
  • Published conference paper: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. 1998;863:459-465
    Xu ZQD; Bartfai T; Langel Ü; Hökfelt T
  • Published conference paper: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. 1998;863:402-413
    Zhang X; Xu ZQ; Shi TJ; Landry M; Holmberg K; Ju G; Tong YG; Bao L; Cheng XP; Wiesenfeld-Hallin Z; Lozano A; Dostrovsky J; Hökfelt T
  • Published conference paper: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. 1998;863:252-263
    Hökfelt T; Xu ZQD; Shi TJ; Holmberg K; Zhang X
  • Article: PAIN. 1998;78(3):171-180
    Shi TJS; Holmberg K; Xu ZQD; Steinbusch H; de Vente J; Hökfelt T
  • Article: EUROPEAN JOURNAL OF NEUROSCIENCE. 1998;10(11):3508-3516
    Xu ZQD; de Vente J; Steinbusch H; Grillner S; Hökfelt T
  • Article: NEUROSCIENCE. 1998;87(1):79-94
    Xu ZQD; Zhang X; Pieribone VA; Grillner S; Hokfelt T
  • Published conference paper: BRAIN RESEARCH REVIEWS. 1998;26(2-3):154-166
    Hökfelt T; Broberger C; Zhang X; Diez M; Kopp J; Xu ZQ; Landry M; Bao L; Schalling M; Koistinaho J; DeArmond SJ; Prusiner S; Gong J; Walsh JH
  • Review: JOURNAL OF COMPARATIVE NEUROLOGY. 1998;392(2):227-251
    Xu ZQD; Shi TJS; Hökfelt T
  • Article: NEUROSCIENCE. 1998;82(3):727-738
    Xu ZQ; Lew JY; Harada K; Aman K; Goldstein M; Deutch A; Haycock JW; Hokfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 1997;94(24):13262-13266
    Xu ZQD; Zhang X; Grillner S; Hokfelt T
  • Article: NEUROSCIENCE LETTERS. 1997;237(2-3):57-60
    Shi TJS; Zhang X; Holmberg K; Xu ZQD; Hökfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 1997;94(23):12661-12666
    Bao L; Kopp J; Zhang X; Xu ZQD; Zhang LF; Wong H; Hokfelt T
  • Review: JOURNAL OF CHEMICAL NEUROANATOMY. 1997;13(3):169-187
    Xu ZQD; Hokfelt T
  • Review: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS. 1997;21(4):489-495
    HerreraMarschitz M; Goiny M; You ZB; Meana JJ; Pettersson E; RodriguezPuertas R; Xu ZQ; Terenius L; Hokfelt T; Ungerstedt U
  • Article: NEUROENDOCRINOLOGY. 1997;65(2):147-156
    Yamada K; Xu ZQ; Zhang X; Gustafsson L; Hulting AL; deVente J; Steinbusch HWM; Hokfelt T
  • Article: NEUROREPORT. 1996;8(1):237-242
    Xu ZQ; Shi TJ; Landry M; Hokfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 1996;93(25):14901-14905
    Xu ZQ; Shi TJ; Hokfelt T
  • Article: EXPERIMENTAL BRAIN RESEARCH. 1996;112(1):79-88
    Corness J; Shi TJ; Xu ZQ; Brulet P; Hokfelt T
  • Article: NEUROSCIENCE. 1996;74(1):51-66
    Pettersson E; HerreraMarschitz M; RodriguezPuertas R; Xu ZQ; You ZB; Hughes J; Elde RP; Ungerstedt U; Hokfelt T
  • Article: NEUROSCIENCE RESEARCH. 1996;25(4):359-369
    Zhang X; Bao L; Xu ZQ; Diez M; Frey P; Hokfelt T
  • Article: BRAIN RESEARCH. 1996;721(1-2):167-173
    Ji RR; Shi TJ; Xu ZQ; Zhang Q; Sakagami H; Tsubochi H; Kondo H; Hokfelt T
  • Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 1995;92(25):11819-11823
    MORALES MA; HOLMBERG K; XU ZQ; COZZARI C; HARTMAN BK; EMSON P; GOLDSTEIN M; ELFVIN LG; HOKFELT T
  • Article: JOURNAL OF NEUROSCIENCE. 1995;15(4):2733-2747
    ZHANG X; XU ZQ; BAO L; DAGERLIND A; HOKFELT T
  • Article: NEUROSCIENCE. 1995;64(4):861-874
    PIERIBONE VA; XU ZQ; ZHANG X; GRILLNER S; BARTFAI T; HOKFELT T
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