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Leor Weinberger, PhD

Title(s)Professor, Biochemistry and Biophysics
SchoolSchool of Medicine
Address1650 Owens St
San Francisco CA 94107
Phone415-734-4857
ORCID ORCID Icon0000-0002-9987-6357 Additional info
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    Collapse Biography 
    Collapse Education and Training
    Princeton UniversityLewis-Thomas Fellow2007Molecular Biology
    University of California, BerkeleyPh.D.2004Biophysics
    University of Maryland, College ParkB.Sc.1998Biology, Physics
    Collapse Awards and Honors
    2017William and Ute Bowes Distinguished Professor
    2016Blavatnik Scholar
    2016Senior Investigator, Gladstone Institutes
    2013NIH Director's Pioneer Award
    2015American Institute for Mechanical and Biological Engineering (AIMBE), College of Fellows
    2013NIH/NIDA Avant Garde Award for HIV Research (deferred)
    2011Alfred P. Sloan Research Fellow
    2009NIH Director's New Innovator Award
    2009Bill & Melinda Gates Foundation, Grand Challenges Award
    2009W.M. Keck Foundation, Research Excellence Award
    2009California HIV/AIDS Foundation, Young Investigator Innovative Development Award
    2008NIH K25 Career Development Award
    2008Pew Scholar in the Biomedical Sciences
    2004Lewis Thomas Fellowship, Princeton University
    1999E. Cota-Robles Fellowship, UC Berkeley
    1999Howard Hughes Medical Institute (HHMI) Pre-Doctoral Fellowship
    1997John Prost Award, University of Maryland
    1997HHMI Undergraduate Research Fellowship, 2nd Award
    1996Maryland Distinguished Scholar
    1995HHMI Undergraduate Research Fellowship
    1993NIH FAES Fellow

    Collapse Overview 
    Collapse Overview
    Dr. Weinberger and colleagues pioneered the study of HIV’s decision circuit and demonstrated that stochastic ‘noise’ in gene expression—Brownian fluctuations arising from diffusion-limited reactions—can drive fate-selection decisions. The lab’s studies identified the molecular sources of noise in HIV, exposed the mechanisms regulating noise, and determined how feedback architectures tune noise for fate selection. The techniques developed for HIV also enabled the lab’s discovery of the first transcriptional accelerator circuit—a high-cooperativity feedback motif that enables signaling systems (e.g. inflammatory responses) to overcome a fundamental tradeoff wherein increased speed generates higher/toxic amplitude. These accelerator circuits in herpesviruses are being exploited for a new class of antiviral target.

    Collectively, the lab’s studies overturned dogma that HIV latency was a deterministic cell-driven artifact and instead showed that HIV encodes a ‘hardwired’ latency program that is evolutionarily optimized to harness noise. Gene-expression noise is now acknowledged as a major clinical barrier to reversing HIV latency and curing HIV. These studies laid the foundation for new therapeutic strategies targeting the HIV-latency circuit, including the lab’s prediction and subsequent discovery of noise-enhancer molecules. Noise enhancers potentiate transcriptional activators, substantially increasing their efficacy and ability to activate persistent (i.e., latent) HIV.

    Collapse Research 
    Collapse Research Activities and Funding
    A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups
    NIH/NIDA DP1DA051144Apr 15, 2020 - Mar 31, 2025
    Role: Principal Investigator
    Development of a Technology Platform for Engineering Single-Administration HIV Therapeutics
    NIH/NIAID R56AI145018Jul 16, 2019 - Jun 30, 2020
    Role: Principal Investigator
    Experiment &Theory to Test an Evolutionary Fitness Role for Lentiviral Latency
    NIH/NIAID R21AI109611Jul 15, 2014 - Jun 30, 2016
    Role: Principal Investigator
    Stochastic Gene Expression in Retroviral Latency
    NIH/NIAID R01AI109593Jun 1, 2014 - May 31, 2019
    Role: Principal Investigator
    Evolvable 'Resistance-Proof' Therapies
    NIH/NIDCR DP1DE024408Sep 30, 2013 - Jul 31, 2018
    Role: Principal Investigator
    Martin Delaney Collaboratory to Eradicate HIV-1 Infection
    NIH U19AI096113Jul 8, 2011 - Jun 30, 2016
    Role: Co-Investigator
    Global innate immune responses to HIV-1 infection
    NIH P01AI090935Aug 15, 2010 - Jul 31, 2015
    Role: Co-Investigator
    Developing Transmissible Antivirals by Exploiting Gene-Expression Circuitry
    NIH DP2OD006677Sep 30, 2009 - Jul 31, 2011
    Role: Principal Investigator
    How Feedback Circuitry Drives Phenotype Switching in a Human Herpesvirus
    NIH/NIGMS K25GM083395Jun 5, 2008 - May 31, 2013
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Websites

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. A molecular mechanism for probabilistic bet hedging and its role in viral latency. Proc Natl Acad Sci U S A. 2020 07 21; 117(29):17240-17248. Chaturvedi S, Klein J, Vardi N, Bolovan-Fritts C, Wolf M, Du K, Mlera L, Calvert M, Moorman NJ, Goodrum F, Huang B, Weinberger LS. PMID: 32632017.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansCells
    2. The HSV-1 ICP4 Transcriptional Auto-Repression Circuit Functions as a Transcriptional "Accelerator" Circuit. Front Cell Infect Microbiol. 2020; 10:265. Chaturvedi S, Engel R, Weinberger L. PMID: 32670890.
      View in: PubMed   Mentions:    Fields:    
    3. Noise-driven cellular heterogeneity in circadian periodicity. Proc Natl Acad Sci U S A. 2020 05 12; 117(19):10350-10356. Li Y, Shan Y, Desai RV, Cox KH, Weinberger LS, Takahashi JS. PMID: 32358201.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCells
    4. HIV Latency: Stochastic across Multiple Scales. . 2019 12 11; 26(6):703-705. Hansen MMK, Martin B, Weinberger LS. PMID: 31951580.
      View in: PubMed   Mentions:
    5. Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform. Cell. 2019 10 31; 179(4):880-894.e10. Herzig E, Kim KC, Packard TA, Vardi N, Schwarzer R, Gramatica A, Deeks SG, Williams SR, Landgraf K, Killeen N, Martin DW, Weinberger LS, Greene WC. PMID: 31668804.
      View in: PubMed   Mentions: 13     Fields:    Translation:HumansAnimalsCells
    6. Post-Transcriptional Noise Control. Bioessays. 2019 07; 41(7):e1900044. Hansen MMK, Weinberger LS. PMID: 31222776.
      View in: PubMed   Mentions:    Fields:    Translation:HumansCells
    7. Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability. Cell Syst. 2018 10 24; 7(4):384-397.e6. Hansen MMK, Desai RV, Simpson ML, Weinberger LS. PMID: 30243562.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansAnimalsCells
    8. Feedback-mediated signal conversion promotes viral fitness. Proc Natl Acad Sci U S A. 2018 09 11; 115(37):E8803-E8810. Vardi N, Chaturvedi S, Weinberger LS. PMID: 30150412.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansCells
    9. A Post-Transcriptional Feedback Mechanism for Noise Suppression and Fate Stabilization. Cell. 2018 06 14; 173(7):1609-1621.e15. Hansen MMK, Wen WY, Ingerman E, Razooky BS, Thompson CE, Dar RD, Chin CW, Simpson ML, Weinberger LS. PMID: 29754821.
      View in: PubMed   Mentions: 13     Fields:    Translation:HumansCells
    10. A Bioreactor Method to Generate High-titer, Genetically Stable, Clinical-isolate Human Cytomegalovirus. Bio Protoc. 2017 Nov 05; 7(21). Saykally VR, Rast LI, Sasaki J, Jung SY, Bolovan-Fritts C, Weinberger LS. PMID: 29226181.
      View in: PubMed   Mentions:
    11. Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean. PLoS Biol. 2017 Oct; 15(10):e2000841. Razooky BS, Cao Y, Hansen MMK, Perelson AS, Simpson ML, Weinberger LS. PMID: 29045398.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansCells
    12. Fate-Regulating Circuits in Viruses: From Discovery to New Therapy Targets. Annu Rev Virol. 2017 09 29; 4(1):469-490. Pai A, Weinberger LS. PMID: 28800289.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansCells
    13. Transient Thresholding: A Mechanism Enabling Noncooperative Transcriptional Circuitry to Form a Switch. Biophys J. 2017 Jun 06; 112(11):2428-2438. Aull KH, Tanner EJ, Thomson M, Weinberger LS. PMID: 28591615.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansCells
    14. Transcriptional Bursting Explains the Noise-Versus-Mean Relationship in mRNA and Protein Levels. PLoS One. 2016; 11(7):e0158298. Dar RD, Shaffer SM, Singh A, Razooky BS, Simpson ML, Raj A, Weinberger LS. PMID: 27467384.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansCells
    15. The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7. J Biol Chem. 2016 07 29; 291(31):16240-8. Ali I, Ramage H, Boehm D, Dirk LM, Sakane N, Hanada K, Pagans S, Kaehlcke K, Aull K, Weinberger L, Trievel R, Schnoelzer M, Kamada M, Houtz R, Ott M. PMID: 27235396.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansCells
    16. Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals. PLoS Comput Biol. 2016 05; 12(5):e1004799. Rast LI, Rouzine IM, Rozhnova G, Bishop L, Weinberger AD, Weinberger LS. PMID: 27152856.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansCells
    17. Exploiting Genetic Interference for Antiviral Therapy. PLoS Genet. 2016 05; 12(5):e1005986. Tanner EJ, Kirkegaard KA, Weinberger LS. PMID: 27149616.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansCells
    18. A minimal fate-selection switch. Curr Opin Cell Biol. 2015 Dec; 37:111-8. Weinberger LS. PMID: 26611210.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansCells
    19. The Low Noise Limit in Gene Expression. PLoS One. 2015; 10(10):e0140969. Dar RD, Razooky BS, Weinberger LS, Cox CD, Simpson ML. PMID: 26488303.
      View in: PubMed   Mentions: 8     Fields:    Translation:Cells
    20. A hardwired HIV latency program. Cell. 2015 Feb 26; 160(5):990-1001. Razooky BS, Pai A, Aull K, Rouzine IM, Weinberger LS. PMID: 25723172.
      View in: PubMed   Mentions: 84     Fields:    Translation:HumansCells
    21. An evolutionary role for HIV latency in enhancing viral transmission. Cell. 2015 Feb 26; 160(5):1002-1012. Rouzine IM, Weinberger AD, Weinberger LS. PMID: 25723173.
      View in: PubMed   Mentions: 44     Fields:    Translation:HumansAnimalsCells
    22. Spatial tuning of acoustofluidic pressure nodes by altering net sonic velocity enables high-throughput, efficient cell sorting. Lab Chip. 2015 Feb 21; 15(4):1000-3. Jung SY, Notton T, Fong E, Shusteff M, Weinberger LS. PMID: 25563937.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansCells
    23. Stochastic variability in HIV affects viral eradication. Proc Natl Acad Sci U S A. 2014 Sep 16; 111(37):13251-2. Rouzine IM, Razooky BS, Weinberger LS. PMID: 25201951.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansCellsPHPublic Health
    24. The case for transmissible antivirals to control population-wide infectious disease. Trends Biotechnol. 2014 Aug; 32(8):400-5. Notton T, Sardanyés J, Weinberger AD, Weinberger LS. PMID: 25017994.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansPHPublic Health
    25. Screening for noise in gene expression identifies drug synergies. Science. 2014 Jun 20; 344(6190):1392-6. Dar RD, Hosmane NN, Arkin MR, Siliciano RF, Weinberger LS. PMID: 24903562.
      View in: PubMed   Mentions: 80     Fields:    Translation:HumansCells
    26. Fifteen years later: hard and soft selection sweeps confirm a large population number for HIV in vivo. PLoS Genet. 2014 Feb; 10(2):e1004179. Rouzine IM, Coffin JM, Weinberger LS. PMID: 24586204.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansCells
    27. Acoustic focusing with engineered node locations for high-performance microfluidic particle separation. Analyst. 2014 Mar 07; 139(5):1192-200. Fong EJ, Johnston AC, Notton T, Jung SY, Rose KA, Weinberger LS, Shusteff M. PMID: 24448925.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    28. Altering Stochastic Noise in Gene Expression for HIV Therapy. Biophysical Journal. 2014 Jan 1; 106(2):374a. Roy D. Dar, Leor S. Weinberger. .
      View in: Publisher Site   Mentions:
    29. Structure and Function of a Transcriptional ‘Accelerator’ Circuit. Biophysical Journal. 2014 Jan 1; 106(2):375a. Roy Dar, Cynthia Bolovan-Fritts, Melissa Teng, Brian Linhares, Michael Simpson, Leor S. Weinberger. .
      View in: Publisher Site   Mentions:
    30. Stochastic fate selection in HIV-infected patients. Cell. 2013 Oct 24; 155(3):497-9. Weinberger AD, Weinberger LS. PMID: 24243007.
      View in: PubMed   Mentions: 24     Fields:    Translation:Cells
    31. Reply to "Coadaptive stability of interfering particles with HIV-1 when there is an evolutionary conflict". J Virol. 2013 Sep; 87(17):9960-2. Rouzine IM, Weinberger LS. PMID: 23943740.
      View in: PubMed   Mentions: 3     Fields:    Translation:Cells
    32. Development of a high-throughput assay to measure the neutralization capability of anti-cytomegalovirus antibodies. Clin Vaccine Immunol. 2013 Apr; 20(4):540-50. Gardner TJ, Bolovan-Fritts C, Teng MW, Redmann V, Kraus TA, Sperling R, Moran T, Britt W, Weinberger LS, Tortorella D. PMID: 23389931.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansCells
    33. An Endogenous Accelerator for Viral Gene Expression Confers a Fitness Advantage. Cell. 2013 Feb 1; 152(5):1195. Melissa W. Teng, Cynthia Bolovan-Fritts, Roy D. Dar, Andrew Womack, Michael L. Simpson, Thomas Shenk, Leor S. Weinberger. .
      View in: Publisher Site   Mentions:
    34. The quantitative theory of within-host viral evolution. Journal of Statistical Mechanics Theory and Experiment. 2013 Jan 16; 2013(01):p01009. Igor M Rouzine, Leor S Weinberger. .
      View in: Publisher Site   Mentions:
    35. An endogenous accelerator for viral gene expression confers a fitness advantage. Cell. 2012 Dec 21; 151(7):1569-80. Teng MW, Bolovan-Fritts C, Dar RD, Womack A, Simpson ML, Shenk T, Weinberger LS. PMID: 23260143.
      View in: PubMed   Mentions: 30     Fields:    Translation:HumansCells
    36. Design requirements for interfering particles to maintain coadaptive stability with HIV-1. J Virol. 2013 Feb; 87(4):2081-93. Rouzine IM, Weinberger LS. PMID: 23221552.
      View in: PubMed   Mentions: 10     Fields:    Translation:Cells
    37. Microwell devices with finger-like channels for long-term imaging of HIV-1 expression kinetics in primary human lymphocytes. Lab Chip. 2012 Nov 07; 12(21):4305-12. Razooky BS, Gutierrez E, Terry VH, Spina CA, Groisman A, Weinberger LS. PMID: 22976503.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansCells
    38. Transcriptional burst frequency and burst size are equally modulated across the human genome. Proc Natl Acad Sci U S A. 2012 Oct 23; 109(43):17454-9. Dar RD, Razooky BS, Singh A, Trimeloni TV, McCollum JM, Cox CD, Simpson ML, Weinberger LS. PMID: 23064634.
      View in: PubMed   Mentions: 131     Fields:    Translation:HumansCells
    39. BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism. . 2013 Feb 01; 12(3):452-62. Boehm D, Calvanese V, Dar RD, Xing S, Schroeder S, Martins L, Aull K, Li PC, Planelles V, Bradner JE, Zhou MM, Siliciano RF, Weinberger L, Verdin E, Ott M. PMID: 23255218.
      View in: PubMed   Mentions:
    40. Dynamics of protein noise can distinguish between alternate sources of gene-expression variability. Mol Syst Biol. 2012; 8:607. Singh A, Razooky BS, Dar RD, Weinberger LS. PMID: 22929617.
      View in: PubMed   Mentions: 35     Fields:    Translation:HumansCells
    41. Autonomous targeting of infectious superspreaders using engineered transmissible therapies. PLoS Comput Biol. 2011 Mar; 7(3):e1002015. Metzger VT, Lloyd-Smith JO, Weinberger LS. PMID: 21483468.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansPHPublic Health
    42. Lentiviral vectors to study stochastic noise in gene expression. Methods Enzymol. 2011; 497:603-22. Franz K, Singh A, Weinberger LS. PMID: 21601105.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansCells
    43. Mapping the architecture of the HIV-1 Tat circuit: A decision-making circuit that lacks bistability and exploits stochastic noise. Methods. 2011 Jan; 53(1):68-77. Razooky BS, Weinberger LS. PMID: 21167940.
      View in: PubMed   Mentions: 12     Fields:    Translation:HumansCells
    44. Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression. Biophys J. 2010 Apr 21; 98(8):L32-4. Singh A, Razooky B, Cox CD, Simpson ML, Weinberger LS. PMID: 20409455.
      View in: PubMed   Mentions: 76     Fields:    Translation:HumansCells
    45. Accelerated immunodeficiency by anti-CCR5 treatment in HIV infection. PLoS Comput Biol. 2009 Aug; 5(8):e1000467. Weinberger AD, Perelson AS, Ribeiro RM, Weinberger LS. PMID: 19680436.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansCells
    46. Stochastic gene expression as a molecular switch for viral latency. Curr Opin Microbiol. 2009 Aug; 12(4):460-6. Singh A, Weinberger LS. PMID: 19595626.
      View in: PubMed   Mentions: 44     Fields:    Translation:Cells
    47. Negative Feedback Speeds Transcriptional Response-Time In Human Cytomegalovirus. Biophysical Journal. 2009 Feb 1; 96(3):305a. Melissa L. Wong, Cynthia Bolovan-Fritts, Leor S. Weinberger. .
      View in: Publisher Site   Mentions:
    48. Transient-mediated fate determination in a transcriptional circuit of HIV. Nat Genet. 2008 Apr; 40(4):466-70. Weinberger LS, Dar RD, Simpson ML. PMID: 18344999.
      View in: PubMed   Mentions: 89     Fields:    Translation:HumansCells
    49. An HIV feedback resistor: auto-regulatory circuit deactivator and noise buffer. PLoS Biol. 2007 Jan; 5(1):e9. Weinberger LS, Shenk T. PMID: 17194214.
      View in: PubMed   Mentions: 39     Fields:    Translation:Cells
    50. Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell. 2005 Jul 29; 122(2):169-82. Weinberger LS, Burnett JC, Toettcher JE, Arkin AP, Schaffer DV. PMID: 16051143.
      View in: PubMed   Mentions: 272     Fields:    Translation:HumansCells
    51. Theoretical design of a gene therapy to prevent AIDS but not human immunodeficiency virus type 1 infection. J Virol. 2003 Sep; 77(18):10028-36. Weinberger LS, Schaffer DV, Arkin AP. PMID: 12941913.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansCells
    52. Early hepatitis C viral kinetics correlate with long-term outcome in patients receiving high dose induction followed by combination interferon and ribavirin therapy. J Hepatol. 2002 Jul; 37(1):124-30. Rosen HR, Ribeiro RR, Weinberger L, Wolf S, Chung M, Gretch DR, Perelson AS. PMID: 12076871.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansCellsCTClinical Trials
    53. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J Exp Med. 2001 Nov 05; 194(9):1277-87. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, Markowitz M, Kost R, Hurley A, Weinberger L, Cesar D, Hellerstein MK, Ho DD. PMID: 11696593.
      View in: PubMed   Mentions: 122     Fields:    Translation:HumansCells
    54. Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta. J Hepatol. 2000 Aug; 33(2):313-22. Shiratori Y, Perelson AS, Weinberger L, Imazeki F, Yokosuka O, Nakata R, Ihori M, Hirota K, Ono N, Kuroda H, Motojima T, Nishigaki M, Omata M. PMID: 10952250.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansCellsCTClinical Trials
    55. Rapid turnover rate of hepatitis C virus clearance by the twice-a-day treatment regimen using interferon-beta. Gastroenterology. 2000 Apr 1; 118(4):a1488. Yasushi Shiratori, As Perelson, L. Weinberger, F. Imazeki, O. Yokosuka, R. Nakata, M. Omata. .
      View in: Publisher Site   Mentions:
    56. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med. 1999 Mar 15; 189(6):991-8. Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, Blanchard J, Irwin CE, Safrit JT, Mittler J, Weinberger L, Kostrikis LG, Zhang L, Perelson AS, Ho DD. PMID: 10075982.
      View in: PubMed   Mentions: 559     Fields:    Translation:AnimalsCells
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