Piali Sengupta

Summary

Affiliation: Brandeis University
Country: USA

Publications

  1. ncbi request reprint Generation and modulation of chemosensory behaviors in C. elegans
    Piali Sengupta
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    Pflugers Arch 454:721-34. 2007
  2. pmc Sensing temperature
    Piali Sengupta
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 23:R304-7. 2013
  3. pmc The belly rules the nose: feeding state-dependent modulation of peripheral chemosensory responses
    Piali Sengupta
    Department of Biology and the National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, United States
    Curr Opin Neurobiol 23:68-75. 2013
  4. pmc Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans
    Sarah L Bauer Huang
    Howard Hughes Medical Institute and Rockefeller University, New York, NY 10065, USA
    Neural Dev 2:24. 2007
  5. ncbi request reprint Chemosensation: tasting with the tail
    Piali Sengupta
    Department of Biology, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 12:R386-8. 2002
  6. pmc Caenorhabditis elegans: a model system for systems neuroscience
    Piali Sengupta
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, United States
    Curr Opin Neurobiol 19:637-43. 2009
  7. doi request reprint Cellular reprogramming: chromatin puts on the brake
    Piali Sengupta
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 21:R157-9. 2011
  8. pmc Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans
    Saikat Mukhopadhyay
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Dev Cell 14:762-74. 2008
  9. pmc The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans
    Kyuhyung Kim
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Development 137:963-74. 2010
  10. pmc KIN-29 SIK regulates chemoreceptor gene expression via an MEF2 transcription factor and a class II HDAC
    Alexander M van der Linden
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    EMBO J 26:358-70. 2007

Collaborators

  • James H Thomas
  • CRAIG PATRICK HUNTER
  • Sarah E Hall
  • Saikat Mukhopadhyay
  • Aravinthan D T Samuel
  • Yun Lu
  • Shai Shaham
  • William S Ryu
  • Oliver E Blacque
  • Cornelia I Bargmann
  • Young jai You
  • Leon Avery
  • John S Satterlee
  • K Touhara
  • Nelson C Lau
  • I Mori
  • Hitoshi Inada
  • Kyuhyung Kim
  • Alexander M van der Linden
  • Anne Lanjuin
  • David Biron
  • Matthew Beverly
  • Marc E Colosimo
  • Martin Wojtyniak
  • Inna V Nechipurenko
  • Damon A Clark
  • Sara M Wasserman
  • Tali Melkman
  • Mayumi Shibuya
  • Scott J Neal
  • Anique Olivier-Mason
  • Katherine M Nolan
  • Paul A Garrity
  • Eva B Nokes
  • Sara Wasserman
  • Yoshihiro Omori
  • Cynthia A Chi
  • Sarah L Bauer Huang
  • Miri K VanHoven
  • Adam Brown
  • Christopher Gabel
  • Manabi Fujiwara
  • Damien M O'Halloran
  • David B Doroquez
  • Rachel V Bowie
  • Andrea G Brear
  • Harold W Bell
  • Sriram Anbil
  • Miriam B Goodman
  • Joseph Rodriguez
  • Sebastian Kadener
  • Michael Rosbash
  • Rinho Kim
  • Koji Sato
  • Jon Clardy
  • Caron Winslow
  • Kristin Ma
  • Justin R Ragains
  • Danna M Zeiger
  • Rebecca A Butcher
  • Takahisa Furukawa
  • Chengtian Zhao
  • Alexey Veraksa
  • Jarema Malicki
  • Woong Kim
  • Scott Wiener
  • Arunesh Saras
  • Alexander van der Linden
  • Linjiao Luo
  • Takeshi Ishihara
  • Jeffrey Brown
  • Christopher V Gabel
  • Ichiro Torayama
  • Stella Lee
  • Yasunori Saheki
  • Isao Katsura
  • Julia Claggett
  • Helen Yeung
  • Anne E Lanjuin
  • Susan Tran
  • Julia K Thompson
  • Adam M Saffer
  • Steven L McIntire
  • Trina R Sarafi-Reinach
  • Jennifer G Horne

Detail Information

Publications46

  1. ncbi request reprint Generation and modulation of chemosensory behaviors in C. elegans
    Piali Sengupta
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    Pflugers Arch 454:721-34. 2007
    ..This review summarizes the current knowledge on the molecular and neuronal substrates of chemosensory behaviors and chemosensory behavioral plasticity in C. elegans...
  2. pmc Sensing temperature
    Piali Sengupta
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 23:R304-7. 2013
    ....
  3. pmc The belly rules the nose: feeding state-dependent modulation of peripheral chemosensory responses
    Piali Sengupta
    Department of Biology and the National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, United States
    Curr Opin Neurobiol 23:68-75. 2013
    ..Focusing primarily on recent work in C. elegans and Drosophila, I describe the neuromodulatory mechanisms that translate feeding state information into changes in chemosensory neuron response properties and behavioral output...
  4. pmc Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans
    Sarah L Bauer Huang
    Howard Hughes Medical Institute and Rockefeller University, New York, NY 10065, USA
    Neural Dev 2:24. 2007
    ..Signaling between AWC neurons induces left-right asymmetry through a gap junction network and a claudin-related protein, which inhibit a calcium-regulated MAP kinase pathway in the neuron that becomes AWCON...
  5. ncbi request reprint Chemosensation: tasting with the tail
    Piali Sengupta
    Department of Biology, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 12:R386-8. 2002
    ..Recent work suggests that Caenorhabditis elegans uses chemosensory information provided by spatially distinct sensilla to generate a sensory map of its environment and to avoid noxious compounds...
  6. pmc Caenorhabditis elegans: a model system for systems neuroscience
    Piali Sengupta
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, United States
    Curr Opin Neurobiol 19:637-43. 2009
    ....
  7. doi request reprint Cellular reprogramming: chromatin puts on the brake
    Piali Sengupta
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 21:R157-9. 2011
    ..A recent study demonstrates that efficient reprogramming of Caenorhabditis elegans germ cells into neurons can be achieved by knocking down a histone chaperone gene and ectopic expression of a terminal selector transcription factor...
  8. pmc Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans
    Saikat Mukhopadhyay
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Dev Cell 14:762-74. 2008
    ..Our results suggest that compensatory mechanisms in response to altered levels of sensory activity modulate AWB cilia architecture, revealing remarkable plasticity in the regulation of cilia structure...
  9. pmc The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans
    Kyuhyung Kim
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Development 137:963-74. 2010
    ....
  10. pmc KIN-29 SIK regulates chemoreceptor gene expression via an MEF2 transcription factor and a class II HDAC
    Alexander M van der Linden
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    EMBO J 26:358-70. 2007
    ..elegans...
  11. ncbi request reprint Identification of thermosensory and olfactory neuron-specific genes via expression profiling of single neuron types
    Marc E Colosimo
    Department of Biology, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 14:2245-51. 2004
    ..Expression profiling of single neuron types provides a rapid, powerful, and unbiased method for identifying neuron-specific genes whose functions can then be investigated in vivo...
  12. pmc The EGL-4 PKG acts with KIN-29 salt-inducible kinase and protein kinase A to regulate chemoreceptor gene expression and sensory behaviors in Caenorhabditis elegans
    Alexander M van der Linden
    Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA
    Genetics 180:1475-91. 2008
    ..Our results suggest that integration of complex sensory inputs via multiple signaling pathways allows animals to precisely regulate sensory gene expression, thereby appropriately modulating physiology and behavior...
  13. ncbi request reprint The UNC-3 Olf/EBF protein represses alternate neuronal programs to specify chemosensory neuron identity
    Kyuhyung Kim
    Department of Biology and Volen Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    Dev Biol 286:136-48. 2005
    ....
  14. ncbi request reprint Regulation of neuronal lineage decisions by the HES-related bHLH protein REF-1
    Anne Lanjuin
    Department of Biology, Brandeis University, Waltham, MA 02454, USA
    Dev Biol 290:139-51. 2006
    ..These results indicate that REF-1 functions in both Notch-dependent and independent pathways to regulate multiple developmental decisions in different neuronal sublineages...
  15. doi request reprint Two chemoreceptors mediate developmental effects of dauer pheromone in C. elegans
    Kyuhyung Kim
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Science 326:994-8. 2009
    ..Identification of dauer pheromone receptors will allow a better understanding of the signaling cascades that transduce the context-dependent effects of ecologically important chemical signals...
  16. doi request reprint Cis-regulatory mechanisms of gene expression in an olfactory neuron type in Caenorhabditis elegans
    Eva B Nokes
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454, USA
    Dev Dyn 238:3080-92. 2009
    ..Our results provide insights into the cis-regulatory logic driving cell-specific gene expression, and suggest that variations in this logic contribute to the generation of functional diversity...
  17. ncbi request reprint Otx/otd homeobox genes specify distinct sensory neuron identities in C. elegans
    Anne Lanjuin
    Department of Biology and Volen Center for Complex Systems, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    Dev Cell 5:621-33. 2003
    ..Misexpression experiments indicate that although the specific identity adopted upon expression of an Otx gene may be constrained by the cellular context, individual Otx genes preferentially promote distinct neuronal identities...
  18. ncbi request reprint Regulation of chemosensory and GABAergic motor neuron development by the C. elegans Aristaless/Arx homolog alr-1
    Tali Melkman
    Department of Biology, Brandeis University, 415 South Street, Brandeis, MA 02454, USA
    Development 132:1935-49. 2005
    ..Investigating ALR-1 functions in C. elegans may yield insights into the role of this important protein in neuronal development and the etiology of mental retardation...
  19. pmc An olfactory neuron responds stochastically to temperature and modulates Caenorhabditis elegans thermotactic behavior
    David Biron
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Proc Natl Acad Sci U S A 105:11002-7. 2008
    ..Our observations suggest that the AFD and AWC neurons encode thermal stimuli via distinct strategies to regulate C. elegans thermotactic behavior...
  20. pmc Genome-wide analysis of light- and temperature-entrained circadian transcripts in Caenorhabditis elegans
    Alexander M van der Linden
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts, United States of America
    PLoS Biol 8:e1000503. 2010
    ..Together, these findings demonstrate circadian-regulated transcriptional rhythms in C. elegans and suggest that further analyses in this organism will provide new information about the evolution and function of this biological clock...
  21. pmc Regulation of response properties and operating range of the AFD thermosensory neurons by cGMP signaling
    Sara M Wasserman
    Department of Biology, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 21:353-62. 2011
    ..However, because AFD thermosensory responses appear to be similar at all examined temperatures above T∗(AFD), the mechanisms that generate specific behaviors in defined temperature ranges remain to be determined...
  22. ncbi request reprint The CMK-1 CaMKI and the TAX-4 Cyclic nucleotide-gated channel regulate thermosensory neuron gene expression and function in C. elegans
    John S Satterlee
    Department of Biology and Volen Center for Complex Systems, Brandeis University, MS 008, Waltham, Massachusetts 02454, USA
    Curr Biol 14:62-8. 2004
    ..We propose that the activation of distinct programs of AFD-specific gene expression at different temperatures by CMK-1 and TAX-4 enables C. elegans to sense and/or encode a memory for the T(c)...
  23. pmc Transmembrane protein OSTA-1 shapes sensory cilia morphology via regulation of intracellular membrane trafficking in C. elegans
    Anique Olivier-Mason
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Development 140:1560-72. 2013
    ..Our findings suggest that regulation of transport pathways in a cell type-specific manner contributes to diversity in sensory cilia structure and might allow dynamic remodeling of ciliary architecture via multiple inputs...
  24. pmc RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans
    Sarah E Hall
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454, USA
    RNA 19:306-19. 2013
    ....
  25. pmc The divergent orphan nuclear receptor ODR-7 regulates olfactory neuron gene expression via multiple mechanisms in Caenorhabditis elegans
    Marc E Colosimo
    Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA
    Genetics 165:1779-91. 2003
    ..The odr-7 ortholog in the closely related nematode C. briggsae can fully substitute for all ODR-7-mediated functions, indicating conservation of function across 25-120 million years of divergence...
  26. pmc The DAF-7 TGF-beta signaling pathway regulates chemosensory receptor gene expression in C. elegans
    Katherine M Nolan
    Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA
    Genes Dev 16:3061-73. 2002
    ..elegans is subject to multiple modes of regulation, thereby ensuring that animals exhibit the responses most appropriate for their developmental stage and environmental conditions...
  27. pmc Distinct IFT mechanisms contribute to the generation of ciliary structural diversity in C. elegans
    Saikat Mukhopadhyay
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, 415 South Street, Waltham, MA 2454, USA
    EMBO J 26:2966-80. 2007
    ..Our results suggest that cell-specific regulation of IFT contributes to the generation of ciliary diversity, and provide insights into the networks coupling the acquisition of ciliary specializations with other aspects of cell fate...
  28. ncbi request reprint Specification of chemosensory neuron subtype identities in Caenorhabditis elegans
    Anne Lanjuin
    Department of Biology, Brandeis University, MS008, 415 South Street, Waltham, MA 02454, USA
    Curr Opin Neurobiol 14:22-30. 2004
    ..Additional cellular complexity is generated by novel mechanisms that further diversify the identities of the left and right members of a bilateral sensory neuron pair...
  29. doi request reprint Quantitative assessment of pheromone-induced Dauer formation in Caenorhabditis elegans
    Scott J Neal
    Department of Biology, Brandeis University, Waltham, MA, USA
    Methods Mol Biol 1068:273-83. 2013
    ..Here, we describe a quantitative dauer formation assay that provides a measure of the potency of single or mixtures of pheromone components in regulating this critical developmental decision. ..
  30. pmc Degeneracy and neuromodulation among thermosensory neurons contribute to robust thermosensory behaviors in Caenorhabditis elegans
    Matthew Beverly
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454, USA
    J Neurosci 31:11718-27. 2011
    ....
  31. ncbi request reprint The worm's sense of smell. Development of functional diversity in the chemosensory system of Caenorhabditis elegans
    Tali Melkman
    Department of Biology, Brandeis University, Waltham, MA 02454, USA
    Dev Biol 265:302-19. 2004
    ..Such a complete description may be possible in C. elegans...
  32. ncbi request reprint Regulation of chemosensory receptor expression and sensory signaling by the KIN-29 Ser/Thr kinase
    Anne Lanjuin
    Department of Biology and Volen Center for Complex Systems, Brandeis University, MS 008, 415 South Street, Waltham, MA 02454, USA
    Neuron 33:369-81. 2002
    ....
  33. pmc A cellular memory of developmental history generates phenotypic diversity in C. elegans
    Sarah E Hall
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    Curr Biol 20:149-55. 2010
    ..Modifications to the epigenome as a consequence of early experience may contribute in part to a memory of early experience and generate phenotypic variation in an isogenic population...
  34. pmc Running hot and cold: behavioral strategies, neural circuits, and the molecular machinery for thermotaxis in C. elegans and Drosophila
    Paul A Garrity
    Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA
    Genes Dev 24:2365-82. 2010
    ..Here, we discuss the role of thermosensation in the development and survival of C. elegans and Drosophila, and review the behavioral strategies, neuronal circuits, and molecular networks responsible for thermotaxis behavior...
  35. pmc Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization in C. elegans
    Martin Wojtyniak
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
    J Cell Sci 126:4381-95. 2013
    ..Our results uncover unexpected diversity in the mechanisms that traffic and localize CNG channel subunits to cilia both within and across cell types, highlighting the essential contribution of this process to cellular functions...
  36. pmc Primary cilia and dendritic spines: different but similar signaling compartments
    Inna V Nechipurenko
    Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA, 02454, USA
    Mol Cells 36:288-303. 2013
    ....
  37. ncbi request reprint A diacylglycerol kinase modulates long-term thermotactic behavioral plasticity in C. elegans
    David Biron
    Department of Physics, Harvard University, 17 Oxford Street, Cambridge, Massachusetts 02138, USA
    Nat Neurosci 9:1499-505. 2006
    ..These results provide the first mechanistic insight into the basis of experience-dependent plasticity in this complex behavior...
  38. ncbi request reprint Regulation of body size and behavioral state of C. elegans by sensory perception and the EGL-4 cGMP-dependent protein kinase
    Manabi Fujiwara
    Ernest Gallo Clinic and Research Center and Department of Neurology, Programs in Neuroscience and Biomedical Science, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA
    Neuron 36:1091-102. 2002
    ..elegans to regulate multiple developmental and behavioral processes including the orchestrated growth of the animal and the expression of particular behavioral states...
  39. ncbi request reprint The AFD sensory neurons encode multiple functions underlying thermotactic behavior in Caenorhabditis elegans
    Damon A Clark
    Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA
    J Neurosci 26:7444-51. 2006
    ..Encoding multiple functions in individual sensory neurons may enable C. elegans to perform complex behaviors with simple neuronal circuits...
  40. ncbi request reprint Temperature and food mediate long-term thermotactic behavioral plasticity by association-independent mechanisms in C. elegans
    Cynthia A Chi
    Department of Physics, Harvard University, Cambridge, MA 02138, USA
    J Exp Biol 210:4043-52. 2007
    ..Mutation in the tax-6 calcineurin gene abolishes thermotactic behavior altogether. In summary, we do not find evidence that long-term plasticity requires association between temperature and the presence or absence of bacterial food...
  41. ncbi request reprint Sensorimotor integration: locating locomotion in neural circuits
    Aravinthan D T Samuel
    Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA
    Curr Biol 15:R341-3. 2005
    ..Several recent studies have now functionally mapped the sensorimotor circuits responsible for locomotion behaviors under defined environmental conditions in the nematode Caenorhabditis elegans...
  42. ncbi request reprint Taking sides in the nervous system with miRNA
    Piali Sengupta
    Nat Neurosci 7:100-2. 2004
  43. ncbi request reprint Smell: the worm turns
    Piali Sengupta
    Nature 450:35-6. 2007
  44. pmc Identification of guanylyl cyclases that function in thermosensory neurons of Caenorhabditis elegans
    Hitoshi Inada
    Group of Molecular Neurobiology, Department of Molecular Biology, Graduate School of Science, Nagoya University, Japan
    Genetics 172:2239-52. 2006
    ..These results suggest that three guanylyl cyclases function redundantly in the AFD neurons to mediate thermosensation by C. elegans...
  45. doi request reprint Elipsa is an early determinant of ciliogenesis that links the IFT particle to membrane-associated small GTPase Rab8
    Yoshihiro Omori
    Department of Ophthalmology, Harvard Medical School, MEEI, R513, 243 Charles St Boston, MA 02114, USA
    Nat Cell Biol 10:437-44. 2008
    ..We show that Rabaptin5 binds to both Elipsa and Rab8, suggesting that these proteins provide a bridging mechanism between the IFT particle and protein complexes that assemble at the ciliary membrane...
  46. ncbi request reprint From eye of newt to chemical structure
    Piali Sengupta
    Nat Chem Biol 3:368-9. 2007

Research Grants23

  1. GENETIC ANALYSIS OF SENSORY SPECIFICATION IN C ELEGANS
    Piali Sengupta; Fiscal Year: 2001
    ..Our long-term goals are to elucidate the pathways in which odr-7-like genes act in the development and function of sensory neuron types. ..
  2. Genetic analysis of sensory specification in C.elegans
    Piali Sengupta; Fiscal Year: 2009
    ..elegans model system. We expect that this information will inform experiments aimed at driving the differentiation of defined cell types from multipotent precursors such as stem cells. ..
  3. Genetic analysis of sensory specification in C.elegans
    Piali Sengupta; Fiscal Year: 2009
    ..elegans model system. We expect that this information will inform experiments aimed at driving the differentiation of defined cell types from multipotent precursors such as stem cells. ..
  4. Molecular and neuronal mechanisms of thermosensory behavior
    Piali Sengupta; Fiscal Year: 2009
    ..elegans model system. Many of these genes are expected to be conserved in other organisms including humans, and to play important roles in regulating neuron functions. ..
  5. Genetic analyses of Arx homeobox gene function in neurodevelopmental disorders
    Piali Sengupta; Fiscal Year: 2007
    ..elegans, to investigate how Arx gene mutations affect brain development. This work may allow us to rapidly identify potential new targets for rational drug design. ..
  6. Genetic analysis of sensory specification in C.elegans
    Piali Sengupta; Fiscal Year: 2005
    ....
  7. Molecular and neuronal mechanisms of thermosensory behavior
    Piali Sengupta; Fiscal Year: 2010
    ..elegans model system. Many of these genes are expected to be conserved in other organisms including humans, and to play important roles in regulating neuron functions. ..