B Perbal

Summary

Country: France

Publications

  1. pmc NOV story: the way to CCN3
    Bernard Perbal
    Laboratoire d Oncologie Virale et Moléculaire, Case 7048, UFR de Biochimie, Université Paris 7 D, Diderot, 2 place Jussieu, 75005 Paris France
    Cell Commun Signal 4:3. 2006
  2. ncbi request reprint CCN proteins: multifunctional signalling regulators
    Bernard Perbal
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, 75005, Paris, France
    Lancet 363:62-4. 2004
  3. ncbi request reprint The CCN3 (NOV) cell growth regulator: a new tool for molecular medicine
    Bernard Perbal
    Laboratoire d Oncologie, Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, 2 Place Jussieu 75 005, Paris, France
    Expert Rev Mol Diagn 3:597-604. 2003
  4. pmc Report on the second international workshop on the CCN family of genes
    B Perbal
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, 2 place Jussieu, 75005 Paris, France
    Mol Pathol 56:80-5. 2003
  5. pmc A potential splicing factor is encoded by the opposite strand of the trans-spliced c-myb exon
    M Vellard
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Centre Universitaire, Orsay, France
    Proc Natl Acad Sci U S A 89:2511-5. 1992
  6. pmc Alteration of C-MYB DNA binding to cognate responsive elements in HL-60 variant cells
    C Gaillard
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, 75005 Paris, France
    Mol Pathol 55:325-35. 2002
  7. ncbi request reprint [Genetic alterations associated with pathologic differentiation of Wilms' tumors]
    G Chevalier
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Orsay, France
    Bull Cancer 84:289-303. 1997
  8. pmc Characterization of multiple alternative RNAs resulting from antisense transcription of the PR264/SC35 splicing factor gene
    A Sureau
    Laboratoire d Oncologie Virale et Moléculaire, Unité de Formation et de Recherche de Biochimie, Université Paris 7 D Diderot, 2 place Jussieu, 75005 Paris, France
    Nucleic Acids Res 25:4513-22. 1997
  9. ncbi request reprint Regulation of nov by WT1: a potential role for nov in nephrogenesis
    C Martinerie
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Orsay, France
    Oncogene 12:1479-92. 1996
  10. pmc A role for CCN3 (NOV) in calcium signalling
    C L Li
    Laboratoire d Oncologie Virale et Moléculaire LOVM, UFR de Biochimie, Université Paris 7 D Diderot, 2 place Jussieu, 75005 Paris, France
    Mol Pathol 55:250-61. 2002

Collaborators

Detail Information

Publications53

  1. pmc NOV story: the way to CCN3
    Bernard Perbal
    Laboratoire d Oncologie Virale et Moléculaire, Case 7048, UFR de Biochimie, Université Paris 7 D, Diderot, 2 place Jussieu, 75005 Paris France
    Cell Commun Signal 4:3. 2006
    ..It is also a good opportunity to acknowledge the input of those who participated in the development of this scientific endeavour...
  2. ncbi request reprint CCN proteins: multifunctional signalling regulators
    Bernard Perbal
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, 75005, Paris, France
    Lancet 363:62-4. 2004
    ..This family participates in angiogenesis, chondrogenesis, and osteogenesis, and they are probably involved in the control of cell proliferation and differentiation...
  3. ncbi request reprint The CCN3 (NOV) cell growth regulator: a new tool for molecular medicine
    Bernard Perbal
    Laboratoire d Oncologie, Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, 2 Place Jussieu 75 005, Paris, France
    Expert Rev Mol Diagn 3:597-604. 2003
    ..In an attempt to evaluate the relevance of CCN3 as a useful tool in modern biomedical technologies, the biological properties of the CCN proteins and the data that established their potential usefulness will briefly be reviewed...
  4. pmc Report on the second international workshop on the CCN family of genes
    B Perbal
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, 2 place Jussieu, 75005 Paris, France
    Mol Pathol 56:80-5. 2003
    ..fr) as an important medium for the exchange of scientific knowledge and resources in the CCN field. Once more, the high quality of scientific communications and individual interactions set the stage for an extremely fruitful meeting...
  5. pmc A potential splicing factor is encoded by the opposite strand of the trans-spliced c-myb exon
    M Vellard
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Centre Universitaire, Orsay, France
    Proc Natl Acad Sci U S A 89:2511-5. 1992
    ..Furthermore, we show that PR264-specific mRNAs are expressed in normal hematopoietic cells of chicken and human origin and that the relative proportion of the PR264 transcripts is developmentally regulated in chicken...
  6. pmc Alteration of C-MYB DNA binding to cognate responsive elements in HL-60 variant cells
    C Gaillard
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, 75005 Paris, France
    Mol Pathol 55:325-35. 2002
    ..In addition, to determine whether alterations in the binding of the MYB protein to MREs affects HL-60 cell proliferation and differentiation...
  7. ncbi request reprint [Genetic alterations associated with pathologic differentiation of Wilms' tumors]
    G Chevalier
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Orsay, France
    Bull Cancer 84:289-303. 1997
    ..Our observations also indicate that nov could be involved in the development of Wilms' tumors, and represent a marker of their differentiation state...
  8. pmc Characterization of multiple alternative RNAs resulting from antisense transcription of the PR264/SC35 splicing factor gene
    A Sureau
    Laboratoire d Oncologie Virale et Moléculaire, Unité de Formation et de Recherche de Biochimie, Université Paris 7 D Diderot, 2 place Jussieu, 75005 Paris, France
    Nucleic Acids Res 25:4513-22. 1997
    ..Northern blot analyses performed with several murine tissues confirmed the differential expression of the ET gene and revealed that it is predominantly expressed in the testis...
  9. ncbi request reprint Regulation of nov by WT1: a potential role for nov in nephrogenesis
    C Martinerie
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Orsay, France
    Oncogene 12:1479-92. 1996
    ..The downregulation of novH expression by WT1 might represent a key element in normal and tumoral nephrogenesis...
  10. pmc A role for CCN3 (NOV) in calcium signalling
    C L Li
    Laboratoire d Oncologie Virale et Moléculaire LOVM, UFR de Biochimie, Université Paris 7 D Diderot, 2 place Jussieu, 75005 Paris, France
    Mol Pathol 55:250-61. 2002
    ....
  11. ncbi request reprint Pathogenic potential of myeloblastosis-associated virus: implication of env proteins for osteopetrosis induction
    V Joliot
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Centre Universitaire, Orsay, France
    Virology 195:812-9. 1993
    ..These results, together with sequence comparisons between the MAV strains examined, suggest that subtle changes in the primary structure of the TM env protein's extracellular domain are likely to affect the tumorigenic potential of MAV...
  12. pmc Chromosomal mapping and expression of the human cyr61 gene in tumour cells from the nervous system
    C Martinerie
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Universite, Paris, Diderot, France
    Mol Pathol 50:310-6. 1997
    ....
  13. pmc Characterization of SRp46, a novel human SR splicing factor encoded by a PR264/SC35 retropseudogene
    J Soret
    Laboratoire d Oncologie Virale et Moléculaire, INSERM U142, Bâtiment Kourilsky, Hopital Saint Antoine, Paris 75571 Cedex 12, France
    Mol Cell Biol 18:4924-34. 1998
    ..These results demonstrate, for the first time, that an SR splicing factor, which represents a novel member of the SR family, is encoded by a functional retropseudogene...
  14. pmc NOV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues
    B Perbal
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D, Diderot, France
    Mol Pathol 54:57-79. 2001
    ..In this model, disruption of the secondary structure of the CCN proteins induced by deletions of either terminus is expected to confer on the truncated polypeptide constitutive positive or negative activities...
  15. pmc The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling
    B Perbal
    Laboratoire d Oncologie Virale et Moléculaire, Institut National de la Santé et de la Recherche Médicale U142, Hopital Saint Antoine, 75012 Paris, France
    Proc Natl Acad Sci U S A 96:869-74. 1999
    ..These results set the stage for a study of NOVH-fibulin 1C interactions and their potential significance in cell-adhesion signaling in normal and pathological conditions...
  16. pmc Several mRNAs with variable 3' untranslated regions and different stability encode the human PR264/SC35 splicing factor
    A Sureau
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Orsay, France
    Proc Natl Acad Sci U S A 91:932-6. 1994
    ....
  17. ncbi request reprint Chromosomal reallocation of the chicken c-myb locus and organization of 3'-proximal coding exons
    J Soret
    Laboratoire d Oncologie Virale et Moléculaire, Centre Universitaire, Orsay, France
    FEBS Lett 263:254-60. 1990
    ..Our sequencing data also indicate that the 3'-proximal noncoding sequences represented in c-myb mRNA species are derived from non-contiguous exons...
  18. pmc Nuclear localisation of NOVH protein: a potential role for NOV in the regulation of gene expression
    B Perbal
    UFR de Biochimie, Universite, Paris, France
    Mol Pathol 52:84-91. 1999
    ....
  19. pmc The noncoding and surface envelope coding sequences of myeloblastosis-associated virus are respectively responsible for nephroblastoma development and renal hyperplasia
    V Joliot
    Laboratoire d Oncologie Virale et Moléculaire, Centre National de la Recherche Scientifique UMR 146, Institut Curie, Centre Universitaire, Orsay, France
    J Virol 70:2576-80. 1996
    ....
  20. pmc Alterations of the MDV oncogenic regions in an MDV transformed lymphoblastoid cell line
    E Le Rouzic
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, Paris, France
    Mol Pathol 55:262-72. 2002
    ..In an attempt to define the respective participation of c-myb and MDV in the transformed phenotype of T9 cells, an analysis of MDV oncogenic sequences (BamHI-H, BamHI-A, and EcoQ fragments) was performed in these cells...
  21. ncbi request reprint Contribution of MAV-1-induced nephroblastoma to the study of genes involved in human Wilms' tumor development
    B Perbal
    UFR de Biochimie, Université Paris 7 D Diderot, France
    Crit Rev Oncog 5:589-613. 1994
    ..The recent data that are discussed in this review strongly suggest that the nov protein might play a critical role in normal and pathological nephrogenesis...
  22. pmc Induction of nephroblastoma by myeloblastosis-associated virus type 1: state of proviral DNAs in tumor cells
    J Soret
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Orsay, France
    J Virol 63:1803-7. 1989
    ..Rearrangements occur preferentially in the gag-pol region of the MAV1 proviral genome, and similar rearrangements can be detected in well-developed independent tumors...
  23. ncbi request reprint Physical mapping of human loci homologous to the chicken nov proto-oncogene
    C Martinerie
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Orsay, France
    Oncogene 7:2529-34. 1992
    ..1. The chromosomal assignment of nov and CTGF proximal to c-myc and c-myb respectively is of interest because chromosomal abnormalities involving these regions have been associated with different human tumors including Wilms'...
  24. ncbi request reprint Pathogenic potential of myeloblastosis-associated viruses
    B Perbal
    UFR de Biochimie, Université Paris 7 D Diderot, France
    Infect Agents Dis 4:212-27. 1995
    ....
  25. ncbi request reprint Structural analysis of the human nov proto-oncogene and expression in Wilms tumor
    C Martinerie
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Orsay, France
    Oncogene 9:2729-32. 1994
    ..Our results suggest that the regulation of IGFII expression by WT1 and increase of novH in Wilms tumors might be interrelated and represent a key element in tumor development in human...
  26. ncbi request reprint Antiproliferative activity of CCN3: involvement of the C-terminal module and post-translational regulation
    A M Bleau
    Université Paris7 D Diderot, UFR de Biochimie, Laboratoire d Oncologie Virale et Moléculaire, 2 place Jussieu, 75005 Paris, France
    J Cell Biochem 101:1475-91. 2007
    ..The use of several clones expressing various portions of CCN3 established that the CT module of CCN3 is sufficient to induce cell growth inhibition...
  27. pmc The PR264/c-myb connection: expression of a splicing factor modulated by a nuclear protooncogene
    A Sureau
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Centre Universitaire, Orsay, France
    Proc Natl Acad Sci U S A 89:11683-7. 1992
    ..Moreover, expression from the PR264 promoter is transactivated, both in vitro and in cultured cells, by different c-myb products. Thus, the PR264 gene is most likely a physiological target for the c-myb family of transcription factors...
  28. ncbi request reprint Nuclear addressing provides a clue for the transforming activity of amino-truncated CCN3 proteins
    Nathalie Planque
    Université Paris7 D Diderot, UFR de Biochimie, Laboratoire d Oncologie Virale et Moléculaire, 2 place Jussieu, 75005 Paris, France
    J Cell Biochem 99:105-16. 2006
    ..In this context, the CT module confers on nuclear CCN3 proteins a negative regulatory effect on transcription. We propose that the nuclear localization of amino-truncated CCN3 proteins be correlated to oncogenicity...
  29. ncbi request reprint CCN proteins and cancer: two to tango
    Anne Marie Bleau
    Université Paris 7 D Diderot, Laboratoire d Oncologie Virale et Moléculaire, 2 place Jussieu, Case 7048, 75251 Paris Cedex France
    Front Biosci 10:998-1009. 2005
    ..The possible opposite functions of CCN1 and CCN3 in tumorigenesis, and the relevance of the distinct expression profiles of these two genes observed in many cancers are discussed below...
  30. pmc Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas
    V Joliot
    Laboratoire d Oncologie Virale et Moléculaire, Institut Curie, Centre Universitaire, Orsay, France
    Mol Cell Biol 12:10-21. 1992
    ..We also showed that the expression of an amino-terminal-truncated nov product in chicken embryo fibroblasts was sufficient to induce their transformation...
  31. ncbi request reprint The CCN3 protein and cancer
    Bernard Perbal
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, Case 7048 2 Place Jussieu 75, 005 Paris, France
    Adv Exp Med Biol 587:23-40. 2006
    ..Identifying the pathways in which the CCN proteins act and establishing the role of these proteins in intercellular communication will constitute new promising avenues among the trends for 21st century in cancer research...
  32. doi request reprint Differential expression of CCN1/CYR61, CCN3/NOV, CCN4/WISP1, and CCN5/WISP2 in neurofibromatosis type 1 tumorigenesis
    Eric Pasmant
    UMR745 INSERM, Universite Paris Descartes, Faculte des Sciences Pharmaceutiques et Biologiques, Paris, France
    J Neuropathol Exp Neurol 69:60-9. 2010
    ..Some of the genes identified, particularly CCN1, might be useful diagnostic or prognostic markers or form the basis for novel therapeutic strategies...
  33. ncbi request reprint Deletions within the U3 long terminal repeat alter the tumorigenic potential of myeloblastosis associated virus type 1(N)
    Chéraz Khelifi-Younes
    Laboratoire d Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7 D Diderot, Paris, France
    Virology 316:84-9. 2003
    ..The results obtained indicated that deletions of the LTRs resulted in a modification of the pathogenic spectrum of MAV-1(N) and a decreased efficiency for nephroblastoma induction...
  34. ncbi request reprint CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible mechanism of connexin-mediated growth suppression
    Christine T Fu
    Department of Anatomy and Cell Biology, University of British Columbia, Vancouver V6T 1Z3, British Columbia, Canada
    J Biol Chem 279:36943-50. 2004
    ..Taken together, these data support an interaction of CCN3 with the C terminus of Cx43, which could play an important role in mediating growth control induced by specific gap junction proteins...
  35. doi request reprint Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1
    Yuko Katsuki
    Maxillofacial Surgery, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan
    Biochem Biophys Res Commun 368:808-14. 2008
    ..These results suggest that CCN3 employs Notch and BMP pathways in anti-osteogenic activity while it inhibits cell proliferation uniquely by Notch/p21 pathway...
  36. doi request reprint Prognostic value of CCN3 in osteosarcoma
    Bernard Perbal
    Laboratorio di Ricerca Oncologica and Laboratorio di Rigenerazione Tissutale Ossea, Istituti Ortopedici Rizzoli, Bologna, Italy
    Clin Cancer Res 14:701-9. 2008
    ..We assessed the prognostic value of CCN1, CCN2, and CCN3 genes, involved in fundamental biological processes...
  37. ncbi request reprint Expression of CCN3 protein in human Wilms' tumors: immunohistochemical detection of CCN3 variants using domain-specific antibodies
    Manish Mani Subramaniam
    Department of Pathology, Medical School, University of Valencia, Valencia, Spain
    Virchows Arch 452:33-9. 2008
    ..Thus, the domain-specific antibodies represent valuable tools for detecting CCN3 protein variants in normal and neoplastic kidneys...
  38. ncbi request reprint The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway
    Kei Sakamoto
    Department of Molecular Pathology, Graduate School of Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8549, Japan
    J Biol Chem 277:29399-405. 2002
    ..These results indicate that NOV-Notch1 association exerts a positive effect on Notch signaling and consequently suppresses myogenesis...
  39. ncbi request reprint Connexin43 interacts with NOV: a possible mechanism for negative regulation of cell growth in choriocarcinoma cells
    Alexandra Gellhaus
    Institute of Anatomy and Cell Biology, University Hospital Essen, 55 Hufelandstrasse, 45122 Essen, Germany
    J Biol Chem 279:36931-42. 2004
    ..We suggest that Cx43 is able to regulate cell growth via an up-regulation of NOV transcription, a change in localization of the NOV protein and a binding of NOV to the C terminus of Cx43...
  40. ncbi request reprint CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways
    Tokutaro Minamizato
    Section of Oral Pathology, Graduate School of Tokyo Medical and Dental University, 1 5 45 Yushima, Tokyo 113 8549, Japan
    Biochem Biophys Res Commun 354:567-73. 2007
    ..These results indicate that CCN3 exerts inhibitory effects on BMP-2-induced osteoblast differentiation by its involvement of the BMP and Notch signaling pathways...
  41. pmc CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1
    Mizuho Fukunaga-Kalabis
    Molecular and Cellular Oncogenesis Program and 2Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA
    J Cell Biol 175:563-9. 2006
    ..These results demonstrate an intricate and necessary communication between keratinocytes and melanocytes in maintaining normal epidermal homeostasis...
  42. ncbi request reprint NOV (CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia
    Chunying Yu
    Program in Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada
    J Pathol 201:609-15. 2003
    ..As identification of the grade of cartilage neoplasia can sometimes be difficult using histology alone, the level of expression of CCN family members could be a useful adjunct in the determination of tumour grade...
  43. ncbi request reprint A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation
    Lynn McCallum
    Department of Haematology, Centre for Cancer Research and Cell Biology, Queen s University Belfast, University Floor, Tower Block, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, United Kingdom
    Blood 108:1716-23. 2006
    ..CCN3 plays an important role in internal and external cell-signaling pathways. Thus, BCR-ABL can regulate protein levels by governing secretion, a novel mechanism for this tyrosine kinase...
  44. ncbi request reprint Connective tissue growth factor induces c-fos gene activation and cell proliferation through p44/42 MAP kinase in primary rat hepatic stellate cells
    Runping Gao
    Laboratoire d Oncologie Virale et Moléculaire, Universite Paris 7, Diderot 75005, France
    J Hepatol 40:431-8. 2004
    ..Connective tissue growth factor (CCN2) is expressed during activation of hepatic stellate cells (HSC) and promotes HSC proliferation, adhesion, and collagen production. The aim of the study was to investigate CCN2 signaling pathways in HSC...
  45. ncbi request reprint A male infant case of lipofibromatosis in the submental region exhibited the expression of the connective tissue growth factor
    Yuhji Kabasawa
    Graduate School of Tokyo Medical and Dental University, Tokyo, Japan
    Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103:677-82. 2007
    ..We encountered a case of lipofibromatosis in a 21-month-old male patient and examined its histopathologic properties...
  46. ncbi request reprint The aminoterminal insulin-like growth factor (IGF) binding domain of IGF binding protein-3 cannot be functionally substituted by the structurally homologous domain of CCN3
    Xiaolang Yan
    Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia
    Endocrinology 147:5268-74. 2006
    ....
  47. doi request reprint CCN3/nephroblastoma overexpressed matricellular protein regulates integrin expression, adhesion, and dissemination in melanoma
    Viviana Vallacchi
    Unit of Immunotherapy of Human Tumors, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
    Cancer Res 68:715-23. 2008
    ..Together, these data indicate a role for CCN3 in melanoma cell interaction with the ECM by regulating integrin expression, resulting in altered cell adhesion and leading melanoma progression to aggressive disease...
  48. pmc The expression of ccn3(nov) gene in musculoskeletal tumors
    Maria Cristina Manara
    Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy
    Am J Pathol 160:849-59. 2002
    ..Further studies will help to clarify the biological role of this protein in musculoskeletal neoplasms...
  49. ncbi request reprint In Ewing's sarcoma CCN3(NOV) inhibits proliferation while promoting migration and invasion of the same cell type
    Stefania Benini
    Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, 40136 Bologna, Italy
    Oncogene 24:4349-61. 2005
    ..However, the underlying molecular mechanisms appear to be different, further highlighting the importance of the cellular context in the regulation of function of CCN proteins...