Michael Schwartz, PhD
Research & Publications
Biography
News
Locations
Research Summary
The research in my laboratory is concerned with the organization and development of the mammalian cerebral cortex, the influence of prenatal and neonatal experiences on the final organization of these regions and the impact on behavioral function. Studies in non-human primates focus on the organization and synaptic features of cortical areas in developing and mature monkeys, with particular emphasis on cortico-cortical, cortical-thalamic, and local circuit neurons. Studies in mice focus on the impact of perinatal hypoxia on brain development, behavioral maturation and mechanisms of recovery using a variety of wild type, knockout and overexpressing mouse models.
Studies currently in progress in the laboratory include:
- Examination of the expression of neurotransmitter substances in the cerebral cortex of fetal and postnatal monkeys;
- Analysis of the role of GABA and FGF on neuronal proliferation and transmitter phenotype;
- The impact of prenatal ultrasound exposure on brain development and behavioral function in non-human primates and mice;
- The impact of hypoxia on the emergence of cortical connectivity and behavioral function.
The studies in the lab utilize a variety of techniques including fetal and adult neurosurgery, light (LM) and electron microscopy (EM), immunocytochemistry, tract tracing methods, and behavioral analysis techniques.
Specialized Terms: Mammalian cerebral cortex
Coauthors
Research Interests
Hypoxia, Brain; Cerebral Cortex; Education, Medical; Neurobiology; Neurosciences
Selected Publications
- Stitching a solution to the addiction epidemic: A longitudinal addiction curricular thread across four years of medical training.Muvvala SB, Schwartz ML, Petrakis I, O'Connor PG, Tetrault JM. Stitching a solution to the addiction epidemic: A longitudinal addiction curricular thread across four years of medical training. Substance Abuse : Official Publication Of The Association For Medical Education And Research In Substance Abuse 2020, 41: 475-479. PMID: 31951809, DOI: 10.1080/08897077.2019.1709606.
- Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (KNa1.1) Na+-activated K+ channels.Quraishi IH, Mercier MR, McClure H, Couture RL, Schwartz ML, Lukowski R, Ruth P, Kaczmarek LK. Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (KNa1.1) Na+-activated K+ channels. Scientific Reports 2020, 10: 3213. PMID: 32081855, PMCID: PMC7035262, DOI: 10.1038/s41598-020-60028-z.
- Echo-Focusing in Transcranial Focused Ultrasound Thalamotomy for Essential Tremor: A Feasibility Study.Jones RM, Huang Y, Meng Y, Scantlebury N, Schwartz ML, Lipsman N, Hynynen K. Echo-Focusing in Transcranial Focused Ultrasound Thalamotomy for Essential Tremor: A Feasibility Study. Movement Disorders : Official Journal Of The Movement Disorder Society 2020, 35: 2327-2333. PMID: 32815611, DOI: 10.1002/mds.28226.
- Suspending Medical Student Clerkships Due to COVID-19.Goldenberg MN, Hersh DC, Wilkins KM, Schwartz ML. Suspending Medical Student Clerkships Due to COVID-19. Medical Science Educator 2020, 1-4. PMID: 32837784, PMCID: PMC7266676, DOI: 10.1007/s40670-020-00994-1.
- The Use of Mobile Devices to Enhance Engagement and Integration with Curricular Content.Leydon GB, Schwartz ML. The Use of Mobile Devices to Enhance Engagement and Integration with Curricular Content. The Yale Journal Of Biology And Medicine 2020, 93: 453-460. PMID: 32874152, PMCID: PMC7448388.
- Twelve tips for incorporating and teaching sexual and gender minority health in medical school curricula.Solotke M, Sitkin NA, Schwartz ML, Encandela JA. Twelve tips for incorporating and teaching sexual and gender minority health in medical school curricula. Medical Teacher 2019, 41: 141-146. PMID: 29179617, DOI: 10.1080/0142159X.2017.1407867.
- Principles and Practices for Developing an Integrated Medical School Curricular Sequence About Sexual and Gender Minority Health.Encandela J, Zelin NS, Solotke M, Schwartz ML. Principles and Practices for Developing an Integrated Medical School Curricular Sequence About Sexual and Gender Minority Health. Teaching And Learning In Medicine 2019, 31: 319-334. PMID: 30661414, DOI: 10.1080/10401334.2018.1559167.
- Using learning analytics to evaluate a video-based lecture series.Lau KHV, Farooque P, Leydon G, Schwartz ML, Sadler RM, Moeller JJ. Using learning analytics to evaluate a video-based lecture series. Medical Teacher 2018, 40: 91-98. PMID: 29113565, DOI: 10.1080/0142159X.2017.1395001.
- Loss of TrkB Signaling in Parvalbumin-Expressing Basket Cells Results in Network Activity Disruption and Abnormal Behavior.Xenos D, Kamceva M, Tomasi S, Cardin JA, Schwartz ML, Vaccarino FM. Loss of TrkB Signaling in Parvalbumin-Expressing Basket Cells Results in Network Activity Disruption and Abnormal Behavior. Cerebral Cortex (New York, N.Y. : 1991) 2018, 28: 3399-3413. PMID: 28968898, PMCID: PMC6132287, DOI: 10.1093/cercor/bhx173.
- When patients hurt us.Cyrus KD, Angoff NR, Illuzzi JL, Schwartz ML, Wilkins KM. When patients hurt us. Medical Teacher 2018, 40: 1308-1309. PMID: 29375008, DOI: 10.1080/0142159X.2018.1428291.
- MMP-2: A modulator of neuronal precursor activity and cognitive and motor behaviors.Li Q, Michaud M, Shankar R, Canosa S, Schwartz M, Madri JA. MMP-2: A modulator of neuronal precursor activity and cognitive and motor behaviors. Behavioural Brain Research 2017, 333: 74-82. PMID: 28666838, DOI: 10.1016/j.bbr.2017.06.041.
- The role of endothelial HIF-1 αin the response to sublethal hypoxia in C57BL/6 mouse pups.Li Q, Michaud M, Park C, Huang Y, Couture R, Girodano F, Schwartz ML, Madri JA. The role of endothelial HIF-1 αin the response to sublethal hypoxia in C57BL/6 mouse pups. Laboratory Investigation; A Journal Of Technical Methods And Pathology 2017, 97: 356-369. PMID: 28092362, DOI: 10.1038/labinvest.2016.154.
- Why Not Wait? Eight Institutions Share Their Experiences Moving United States Medical Licensing Examination Step 1 After Core Clinical Clerkships.Daniel M, Fleming A, Grochowski CO, Harnik V, Klimstra S, Morrison G, Pock A, Schwartz ML, Santen S. Why Not Wait? Eight Institutions Share Their Experiences Moving United States Medical Licensing Examination Step 1 After Core Clinical Clerkships. Academic Medicine : Journal Of The Association Of American Medical Colleges 2017, 92: 1515-1524. PMID: 28422816, DOI: 10.1097/ACM.0000000000001714.
- A Video-Based Introductory EEG Curriculum for Neurology Residents and Other EEG Learners.Moeller JJ, Farooque P, Leydon G, Dominguez M, Schwartz ML, Sadler RM. A Video-Based Introductory EEG Curriculum for Neurology Residents and Other EEG Learners. MedEdPORTAL : The Journal Of Teaching And Learning Resources 2017, 13: 10570. PMID: 30800772, PMCID: PMC6342517, DOI: 10.15766/mep_2374-8265.10570.
- Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus.Varela L, Schwartz ML, Horvath TL. Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus. Neurobiology Of Disease 2016, 90: 68-74. PMID: 26777666, DOI: 10.1016/j.nbd.2016.01.004.
- Fibroblast Growth Factor 2 Modulates Hypothalamic Pituitary Axis Activity and Anxiety Behavior Through Glucocorticoid Receptors.Salmaso N, Stevens HE, McNeill J, ElSayed M, Ren Q, Maragnoli ME, Schwartz ML, Tomasi S, Sapolsky RM, Duman R, Vaccarino FM. Fibroblast Growth Factor 2 Modulates Hypothalamic Pituitary Axis Activity and Anxiety Behavior Through Glucocorticoid Receptors. Biological Psychiatry 2016, 80: 479-489. PMID: 27133954, PMCID: PMC8009045, DOI: 10.1016/j.biopsych.2016.02.026.
- Online Learning Tools as Supplements for Basic and Clinical Science Education.Ellman MS, Schwartz ML. Online Learning Tools as Supplements for Basic and Clinical Science Education. Journal Of Medical Education And Curricular Development 2016, 3 PMID: 29349323, PMCID: PMC5736292, DOI: 10.4137/JMECD.S18933.
- Modulation of Sox10, HIF-1α, Survivin, and YAP by Minocycline in the Treatment of Neurodevelopmental Handicaps following Hypoxic Insult.Li Q, Tsuneki M, Krauthammer M, Couture R, Schwartz M, Madri JA. Modulation of Sox10, HIF-1α, Survivin, and YAP by Minocycline in the Treatment of Neurodevelopmental Handicaps following Hypoxic Insult. The American Journal Of Pathology 2015, 185: 2364-78. PMID: 26209807, PMCID: PMC5801488, DOI: 10.1016/j.ajpath.2015.05.016.
- Contribution of maternal oxygenic state to the effects of chronic postnatal hypoxia on mouse body and brain development.Salmaso N, Dominguez M, Kravitz J, Komitova M, Vaccarino FM, Schwartz ML. Contribution of maternal oxygenic state to the effects of chronic postnatal hypoxia on mouse body and brain development. Neuroscience Letters 2015, 604: 12-7. PMID: 26222256, PMCID: PMC4568169, DOI: 10.1016/j.neulet.2015.07.033.
- Hypoxia-induced developmental delays of inhibitory interneurons are reversed by environmental enrichment in the postnatal mouse forebrain.Komitova M, Xenos D, Salmaso N, Tran KM, Brand T, Schwartz ML, Ment L, Vaccarino FM. Hypoxia-induced developmental delays of inhibitory interneurons are reversed by environmental enrichment in the postnatal mouse forebrain. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2013, 33: 13375-87. PMID: 23946395, PMCID: PMC3742925, DOI: 10.1523/JNEUROSCI.5286-12.2013.
- Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory.D'Agostino G, Kim JD, Liu ZW, Jeong JK, Suyama S, Calignano A, Gao XB, Schwartz M, Diano S. Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory. Cerebral Cortex (New York, N.Y. : 1991) 2013, 23: 2007-14. PMID: 22767632, PMCID: PMC3841400, DOI: 10.1093/cercor/bhs199.
- Learning and memory depend on fibroblast growth factor receptor 2 functioning in hippocampus.Stevens HE, Jiang GY, Schwartz ML, Vaccarino FM. Learning and memory depend on fibroblast growth factor receptor 2 functioning in hippocampus. Biological Psychiatry 2012, 71: 1090-8. PMID: 22541947, PMCID: PMC3371339, DOI: 10.1016/j.biopsych.2012.03.013.
- Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice.Müller Smith K, Williamson TL, Schwartz ML, Vaccarino FM. Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice. Brain Research 2012, 1460: 12-24. PMID: 22578469, PMCID: PMC3361544, DOI: 10.1016/j.brainres.2012.04.002.
- Species-dependent posttranscriptional regulation of NOS1 by FMRP in the developing cerebral cortex.Kwan KY, Lam MM, Johnson MB, Dube U, Shim S, Rašin MR, Sousa AM, Fertuzinhos S, Chen JG, Arellano JI, Chan DW, Pletikos M, Vasung L, Rowitch DH, Huang EJ, Schwartz ML, Willemsen R, Oostra BA, Rakic P, Heffer M, Kostović I, Judaš M, Sestan N. Species-dependent posttranscriptional regulation of NOS1 by FMRP in the developing cerebral cortex. Cell 2012, 149: 899-911. PMID: 22579290, PMCID: PMC3351852, DOI: 10.1016/j.cell.2012.02.060.
- Environmental enrichment increases the GFAP+ stem cell pool and reverses hypoxia-induced cognitive deficits in juvenile mice.Salmaso N, Silbereis J, Komitova M, Mitchell P, Chapman K, Ment LR, Schwartz ML, Vaccarino FM. Environmental enrichment increases the GFAP+ stem cell pool and reverses hypoxia-induced cognitive deficits in juvenile mice. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2012, 32: 8930-9. PMID: 22745493, PMCID: PMC3399175, DOI: 10.1523/JNEUROSCI.1398-12.2012.
- Cortical glial fibrillary acidic protein-positive cells generate neurons after perinatal hypoxic injury.Bi B, Salmaso N, Komitova M, Simonini MV, Silbereis J, Cheng E, Kim J, Luft S, Ment LR, Horvath TL, Schwartz ML, Vaccarino FM. Cortical glial fibrillary acidic protein-positive cells generate neurons after perinatal hypoxic injury. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2011, 31: 9205-21. PMID: 21697371, PMCID: PMC3142780, DOI: 10.1523/JNEUROSCI.0518-11.2011.
- Yale University School of Medicine.Belitsky R, Weissbach-Licht G, Schwartz M. Yale University School of Medicine. Academic Medicine : Journal Of The Association Of American Medical Colleges 2010, 85: S124-6. PMID: 20736529, DOI: 10.1097/ACM.0b013e3181e86cab.
- Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome.Kataoka Y, Kalanithi PS, Grantz H, Schwartz ML, Saper C, Leckman JF, Vaccarino FM. Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. The Journal Of Comparative Neurology 2010, 518: 277-91. PMID: 19941350, PMCID: PMC2846837, DOI: 10.1002/cne.22206.
- Strain differences in behavioral and cellular responses to perinatal hypoxia and relationships to neural stem cell survival and self-renewal: Modeling the neurovascular niche.Li Q, Liu J, Michaud M, Schwartz ML, Madri JA. Strain differences in behavioral and cellular responses to perinatal hypoxia and relationships to neural stem cell survival and self-renewal: Modeling the neurovascular niche. The American Journal Of Pathology 2009, 175: 2133-46. PMID: 19815710, PMCID: PMC2774076, DOI: 10.2353/ajpath.2009.090354.
- Hypoxic injury during neonatal development in murine brain: correlation between in vivo DTI findings and behavioral assessment.Chahboune H, Ment LR, Stewart WB, Rothman DL, Vaccarino FM, Hyder F, Schwartz ML. Hypoxic injury during neonatal development in murine brain: correlation between in vivo DTI findings and behavioral assessment. Cerebral Cortex (New York, N.Y. : 1991) 2009, 19: 2891-901. PMID: 19380380, PMCID: PMC2774398, DOI: 10.1093/cercor/bhp068.
- Deficiency in inhibitory cortical interneurons associates with hyperactivity in fibroblast growth factor receptor 1 mutant mice.Müller Smith K, Fagel DM, Stevens HE, Rabenstein RL, Maragnoli ME, Ohkubo Y, Picciotto MR, Schwartz ML, Vaccarino FM. Deficiency in inhibitory cortical interneurons associates with hyperactivity in fibroblast growth factor receptor 1 mutant mice. Biological Psychiatry 2008, 63: 953-62. PMID: 17988653, DOI: 10.1016/j.biopsych.2007.09.020.
- Modeling the neurovascular niche: murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn.Li Q, Michaud M, Stewart W, Schwartz M, Madri JA. Modeling the neurovascular niche: murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn. Journal Of Neuroscience Research 2008, 86: 1227-42. PMID: 18092360, PMCID: PMC2644407, DOI: 10.1002/jnr.21597.
- Astroglial cells in development, regeneration, and repair.Vaccarino FM, Fagel DM, Ganat Y, Maragnoli ME, Ment LR, Ohkubo Y, Schwartz ML, Silbereis J, Smith KM. Astroglial cells in development, regeneration, and repair. The Neuroscientist : A Review Journal Bringing Neurobiology, Neurology And Psychiatry 2007, 13: 173-85. PMID: 17404377, DOI: 10.1177/1073858406298336.
- Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function.Andrews ZB, Rivera A, Elsworth JD, Roth RH, Agnati L, Gago B, Abizaid A, Schwartz M, Fuxe K, Horvath TL. Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function. The European Journal Of Neuroscience 2006, 24: 32-6. PMID: 16882005, DOI: 10.1111/j.1460-9568.2006.04906.x.
- Midline radial glia translocation and corpus callosum formation require FGF signaling.Smith KM, Ohkubo Y, Maragnoli ME, Rasin MR, Schwartz ML, Sestan N, Vaccarino FM. Midline radial glia translocation and corpus callosum formation require FGF signaling. Nature Neuroscience 2006, 9: 787-97. PMID: 16715082, DOI: 10.1038/nn1705.
- Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome.Kalanithi PS, Zheng W, Kataoka Y, DiFiglia M, Grantz H, Saper CB, Schwartz ML, Leckman JF, Vaccarino FM. Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13307-12. PMID: 16131542, PMCID: PMC1201574, DOI: 10.1073/pnas.0502624102.
- Neonatal hypoxia suppresses oligodendrocyte Nogo-A and increases axonal sprouting in a rodent model for human prematurity.Weiss J, Takizawa B, McGee A, Stewart WB, Zhang H, Ment L, Schwartz M, Strittmatter S. Neonatal hypoxia suppresses oligodendrocyte Nogo-A and increases axonal sprouting in a rodent model for human prematurity. Experimental Neurology 2004, 189: 141-9. PMID: 15296844, DOI: 10.1016/j.expneurol.2004.05.018.
- Chronic neonatal hypoxia leads to long term decreases in the volume and cell number of the rat cerebral cortex.Schwartz ML, Vaccarino F, Chacon M, Yan WL, Ment LR, Stewart WB. Chronic neonatal hypoxia leads to long term decreases in the volume and cell number of the rat cerebral cortex. Seminars In Perinatology 2004, 28: 379-88. PMID: 15693394, DOI: 10.1053/j.semperi.2004.10.009.
- Fibroblast growth factor 2 is necessary for the growth of glutamate projection neurons in the anterior neocortex.Korada S, Zheng W, Basilico C, Schwartz ML, Vaccarino FM. Fibroblast growth factor 2 is necessary for the growth of glutamate projection neurons in the anterior neocortex. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2002, 22: 863-75. PMID: 11826116, PMCID: PMC6758485.
- Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone.Ganat Y, Soni S, Chacon M, Schwartz ML, Vaccarino FM. Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone. Neuroscience 2002, 112: 977-91. PMID: 12088755.
- A1 adenosine receptor activation induces ventriculomegaly and white matter loss.Turner CP, Yan H, Schwartz M, Othman T, Rivkees SA. A1 adenosine receptor activation induces ventriculomegaly and white matter loss. Neuroreport 2002, 13: 1199-204. PMID: 12151769, DOI: 10.1097/00001756-200207020-00026.
- Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex.Raballo R, Rhee J, Lyn-Cook R, Leckman JF, Schwartz ML, Vaccarino FM. Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2000, 20: 5012-23. PMID: 10864959.
- Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis.Vaccarino FM, Schwartz ML, Raballo R, Nilsen J, Rhee J, Zhou M, Doetschman T, Coffin JD, Wyland JJ, Hung YT. Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nature Neuroscience 1999, 2: 246-53. PMID: 10195217, DOI: 10.1038/6350.
- Fibroblast growth factor signaling regulates growth and morphogenesis at multiple steps during brain development.Vaccarino FM, Schwartz ML, Raballo R, Rhee J, Lyn-Cook R. Fibroblast growth factor signaling regulates growth and morphogenesis at multiple steps during brain development. Current Topics In Developmental Biology 1999, 46: 179-200. PMID: 10417880, DOI: 10.1016/s0070-2153(08)60329-4.
- Cholinergic innervation of the mediodorsal thalamic nucleus in the monkey: ultrastructural evidence supportive of functional diversity.Schwartz ML, Mrzljak L. Cholinergic innervation of the mediodorsal thalamic nucleus in the monkey: ultrastructural evidence supportive of functional diversity. The Journal Of Comparative Neurology 1993, 327: 48-62. PMID: 8432908, DOI: 10.1002/cne.903270105.
- Early expression of GABA-containing neurons in the prefrontal and visual cortices of rhesus monkeys.Schwartz ML, Meinecke DL. Early expression of GABA-containing neurons in the prefrontal and visual cortices of rhesus monkeys. Cerebral Cortex (New York, N.Y. : 1991) 1992, 2: 16-37. PMID: 1633406.
- Early phenotype expression of cortical neurons: evidence that a subclass of migrating neurons have callosal axons.Schwartz ML, Rakic P, Goldman-Rakic PS. Early phenotype expression of cortical neurons: evidence that a subclass of migrating neurons have callosal axons. Proceedings Of The National Academy Of Sciences Of The United States Of America 1991, 88: 1354-8. PMID: 1705036, PMCID: PMC51016.
- Yale University School of Medicine.Belitsky R, Schwartz ML, Larkin SE, Roth A. Yale University School of Medicine. Academic Medicine : Journal Of The Association Of American Medical Colleges 2020, 95: S83-S86. PMID: 33626652, DOI: 10.1097/ACM.0000000000003458.
- Readiness for Medical School: a Radical Proposal.Angoff NR, Schwartz ML. Readiness for Medical School: a Radical Proposal. Medical Science Educator 2020, 30: 573-576. PMID: 34457704, PMCID: PMC8368260, DOI: 10.1007/s40670-019-00858-3.
- Burnout Among Beginning First-Year Students from Three Health Professional Training Programs.Roberts A, Angoff NR, Brissette D, Dupee D, Fahs D, Honan L, Korbey S, Roessler E, Schwartz M, Shabanova V, Tetrault J, Wu B, Colson E, Encandela J. Burnout Among Beginning First-Year Students from Three Health Professional Training Programs. Medical Science Educator 2020, 30: 879-883. PMID: 34457745, PMCID: PMC8368543, DOI: 10.1007/s40670-020-00969-2.
- Virtual Telesimulation for Medical Students During the COVID-19 Pandemic.Ray JM, Wong AH, Yang TJ, Buck S, Joseph M, Bonz JW, Auerbach MA, Couturier K, Tomassoni AJ, Schwartz ML, Evans LV. Virtual Telesimulation for Medical Students During the COVID-19 Pandemic. Academic Medicine : Journal Of The Association Of American Medical Colleges 2021, 96: 1431-1435. PMID: 33883398, PMCID: PMC8475640, DOI: 10.1097/ACM.0000000000004129.