Mental Retardation and Development Disabilities Research

Summary

Principal Investigator: M Yudkoff
Affiliation: The Children's Hospital of Philadelphia
Country: USA
Abstract: The proposed Mental Retardation and Developmental Disabilities Research Center (MRDDRC) was established in 1990 and renewed in 1995 and 1999. It represents the collaboration of the Children's Hospital of Philadelphia and the University of Pennsylvania (Penn). In this renewal application, funds are requested to support five core facilities and New Program Development projects. The cores are: (A) Administrative Core, which provides overall management of the MRDDRC. It administers all educational programs, lecture series, and the New Program Development projects. It also oversees the proposed Mid-Atlantic Research Consortium, a new venture that would encourage more joint research at the MRDDRCs at Penn, Johns Hopkins, and Children's National Medical Center. (B) Biostatistics and Bioinformatics, which provides consultation with regard to study design, statistical analysis, and database design. A new emphasis is bioinformatics, which is crucial to the interpretation of data culled from chip array analysis of DNA. (C) Molecular Genetics, which provides a centralized facility for DNA sequencing, fluorescent fragment analysis, mutation detection with cosmig contigs, screen of YAC libraries, quantitative PCR analysis, gene mapping, cell culture, etc. (D) Analytical Neurochemistry and Spectroscopy, which provides expert and support with regard to biochemical analyses. The core facilitates a wide spectrum of neurochemical analysis, from brain tissue to living cells in vitro to the intact organism. It combines mass spectrometric analysis of stable isotopes, HPLC of biogenic amines and amino acids, positron emission tomography (PET) services and fluorescent assays in live cells. A new component is the proposed Proteomics Subcore that facilitates characterization of proteins of neurochemical interest. (E) Cellular Neuroscience, which provides support and advice with regard to confocal microscopy, cytoarchitectural analysis, and cell culture. A new component is the availability of techniques for optically imaging circuit function in slice preparations using voltage sensitive dyes. Finally, the core proposes to provide users with expertise for the development and preservation of mouse models (transgenic and knock-outs). These units service more than 96 NIH -funded projects with an aggregate annual value of more than $12 million (greater than $1.5 million from NICHD). The Center includes more than 60 Penn faculty members representing 15 departments at the School of Medicine, School of Veterinary Medicine, The School of Nursing, the Wistar Institute, and the College of Arts and Sciences.
Funding Period: 1997-08-01 - 2010-06-30
more information: NIH RePORT

Top Publications

  1. pmc Two-year neurodevelopmental outcomes of ventilated preterm infants treated with inhaled nitric oxide
    Michele C Walsh
    Case Western Reserve University, Cleveland, OH, USA
    J Pediatr 156:556-61.e1. 2010
  2. pmc Variable bandwidth filtering for improved sensitivity of cross-frequency coupling metrics
    Jeffrey I Berman
    Department of Radiology, Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Brain Connect 2:155-63. 2012
  3. pmc Striatum specific protein, Rhes regulates AKT pathway
    Sookhee Bang
    Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, 125 S 31st St, TRL Rm 2207, Philadelphia, PA 19104, United States
    Neurosci Lett 521:142-7. 2012
  4. pmc Delayed myelination in an intrauterine growth retardation model is mediated by oxidative stress upregulating bone morphogenetic protein 4
    Mary V Reid
    Department of Neurology, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Neuropathol Exp Neurol 71:640-53. 2012
  5. pmc NMNAT1 mutations cause Leber congenital amaurosis
    Marni J Falk
    Department of Pediatrics, Division of Human Genetics, The Children s Hospital of Philadelphia, Pennsylvania, USA
    Nat Genet 44:1040-5. 2012
  6. pmc Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid identity of a small region within the GluN1 amino terminal domain
    Amy J Gleichman
    Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 32:11082-94. 2012
  7. pmc Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma
    Sharon J Diskin
    Division of Oncology, Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Genet 44:1126-30. 2012
  8. pmc Neurovascular coupling varies with level of global cerebral ischemia in a rat model
    Wesley B Baker
    Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cereb Blood Flow Metab 33:97-105. 2013
  9. pmc Maturation and activity of sterol regulatory element binding protein 1 is inhibited by acyl-CoA binding domain containing 3
    Yong Chen
    Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 7:e49906. 2012
  10. pmc Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months
    Tracy A Glauser
    Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Epilepsia 54:141-55. 2013

Scientific Experts

Detail Information

Publications127 found, 100 shown here

  1. pmc Two-year neurodevelopmental outcomes of ventilated preterm infants treated with inhaled nitric oxide
    Michele C Walsh
    Case Western Reserve University, Cleveland, OH, USA
    J Pediatr 156:556-61.e1. 2010
    ..Because some preventative BPD treatments are associated with neurodevelopmental impairment, we designed a follow-up study to assess the safety of nitric oxide...
  2. pmc Variable bandwidth filtering for improved sensitivity of cross-frequency coupling metrics
    Jeffrey I Berman
    Department of Radiology, Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Brain Connect 2:155-63. 2012
    ..The variable bandwidth method of filtering an amplitude modulated signal is proposed to preserve amplitude modulation and enable accurate CFC measurements...
  3. pmc Striatum specific protein, Rhes regulates AKT pathway
    Sookhee Bang
    Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, 125 S 31st St, TRL Rm 2207, Philadelphia, PA 19104, United States
    Neurosci Lett 521:142-7. 2012
    ..These findings suggest that Rhes is a novel striatal regulator of the AKT-mediated pathway in the striatum...
  4. pmc Delayed myelination in an intrauterine growth retardation model is mediated by oxidative stress upregulating bone morphogenetic protein 4
    Mary V Reid
    Department of Neurology, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Neuropathol Exp Neurol 71:640-53. 2012
    ..Together, these findings suggest that IUGR results in delayed myelination through the generation of oxidative stress that leads to BMP4 upregulation...
  5. pmc NMNAT1 mutations cause Leber congenital amaurosis
    Marni J Falk
    Department of Pediatrics, Division of Human Genetics, The Children s Hospital of Philadelphia, Pennsylvania, USA
    Nat Genet 44:1040-5. 2012
    ..These results are the first to link an NMNAT isoform to disease in humans and indicate that NMNAT1 mutations cause LCA...
  6. pmc Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid identity of a small region within the GluN1 amino terminal domain
    Amy J Gleichman
    Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 32:11082-94. 2012
    ..These findings provide tools for detailed comparison of antibodies across patients and suggest an interaction between antibody binding and channel function...
  7. pmc Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma
    Sharon J Diskin
    Division of Oncology, Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Genet 44:1126-30. 2012
    ..008 and 0.014, respectively). Taken together, these data show that common variants in HACE1 and LIN28B influence neuroblastoma susceptibility and indicate that both genes likely have a role in disease progression...
  8. pmc Neurovascular coupling varies with level of global cerebral ischemia in a rat model
    Wesley B Baker
    Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cereb Blood Flow Metab 33:97-105. 2013
    ....
  9. pmc Maturation and activity of sterol regulatory element binding protein 1 is inhibited by acyl-CoA binding domain containing 3
    Yong Chen
    Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 7:e49906. 2012
    ..These findings suggest that ACBD3 plays an essential role in maintaining lipid homeostasis via regulating SREBP1's processing pathway and thus impacting cellular lipogenesis...
  10. pmc Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months
    Tracy A Glauser
    Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Epilepsia 54:141-55. 2013
    ..Determine the optimal initial monotherapy for children with newly diagnosed childhood absence epilepsy (CAE) based on 12 months of double-blind therapy...
  11. pmc The glutamate transporter, GLAST, participates in a macromolecular complex that supports glutamate metabolism
    DEBORAH E BAUER
    Children s Hospital of Philadelphia Research Institute, University of Pennsylvania, Philadelphia, PA 19104, United States
    Neurochem Int 61:566-74. 2012
    ..Our data support a model in which GLAST exists in a macromolecular complex that allows transported glutamate to be metabolized in mitochondria to support energy production...
  12. pmc Resting-state oscillatory activity in autism spectrum disorders
    Lauren Cornew
    Lurie Family Foundations MEG Imaging Center, Department of Radiology, Children s Hospital of Philadelphia, 2nd Floor Wood Bldg, Room 2115, Mail Stop W02 1010, Philadelphia, PA 19104 4399, USA
    J Autism Dev Disord 42:1884-94. 2012
    ..Increased temporal and parietal alpha power was associated with greater symptom severity and thus is of particular interest...
  13. pmc Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria
    Elizabeth N Genda
    Children s Hospital of Philadelphia Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 31:18275-88. 2011
    ....
  14. pmc N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia
    Nicholas Ah Mew
    Research Center for Genetic Medicine, Children s National Medical Center, George Washington University, Washington, DC 20010, USA
    Pediatrics 126:e208-14. 2010
    ..The objective of this study was to determine whether N-carbamylglutamate (NCG) reduces plasma levels of ammonia and glutamine and increases the rate of ureagenesis in patients with propionic acidemia (PA)...
  15. pmc Facial diagnosis of mild and variant CdLS: Insights from a dysmorphologist survey
    Sarika Rohatgi
    Division of Genetics, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Am J Med Genet A 152:1641-53. 2010
    ..This work underscores the difficulty in diagnosing patients with mild and variant CdLS and serves to objectively classify both useful and misleading features in the diagnosis of CdLS...
  16. pmc EphB receptors couple dendritic filopodia motility to synapse formation
    Matthew S Kayser
    Department of Neuroscience, University of Pennsylvania School of Medicine, 1114 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Neuron 59:56-69. 2008
    ..Our findings provide a mechanistic link between dendritic filopodia motility and synapse differentiation...
  17. pmc Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites
    M A Posencheg
    Department of Pediatrics, University of Pennsylvania School of Medicine and The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    J Perinatol 30:275-80. 2010
    ..Inhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery...
  18. pmc Down-regulation of hepatic urea synthesis by oxypurines: xanthine and uric acid inhibit N-acetylglutamate synthase
    Itzhak Nissim
    Division of Child Development, Rehabilitation Medicine, and Metabolic Disease, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:22055-68. 2011
    ..An important and novel concept emerging from this study is that xanthine and/or uric acid may have a role in the regulation of ureagenesis and, thus, nitrogen homeostasis in normal and disease states...
  19. pmc Canonical Wnt signalling requires the BMP pathway to inhibit oligodendrocyte maturation
    Keith Feigenson
    Department of Neurology, Childrens Hospital of Philadelphia, Philadelphia, PA, U S A
    ASN Neuro 3:e00061. 2011
    ..Our results indicate that the BMP signalling pathway is necessary for the canonical Wnt signalling pathway to exert its effects on OL development, but not vice versa, suggesting that Wnt signals upstream of BMP...
  20. pmc N-carbamylglutamate enhancement of ureagenesis leads to discovery of a novel deleterious mutation in a newly defined enhancer of the NAGS gene and to effective therapy
    Sandra K Heibel
    Research Center for Genetic Medicine, Children s National Medical Center, The George Washington University, Washington, DC, USA
    Hum Mutat 32:1153-60. 2011
    ..Oral daily NCG therapy restored ureagenesis in this patient, normalizing her biochemical markers, and allowing discontinuation of alternate pathway therapy and normalization of her diet with no recurrence of hyperammonemia. Inc...
  21. pmc Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression
    Teresa L Mastracci
    Department of Genetics and Development, Russ Berrie Medical Pavilion, Columbia University, 1150 St Nicholas Ave, New York, NY 10032, USA
    Dev Biol 359:1-11. 2011
    ..Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells...
  22. pmc Differential effects of a polyalanine tract expansion in Arx on neural development and gene expression
    MacLean Pancoast Nasrallah
    Neuroscience Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Hum Mol Genet 21:1090-8. 2012
    ..Our data demonstrate a novel mechanism for poly-A expansion diseases: the misregulation of a subset of target genes normally regulated by a transcription factor...
  23. pmc Regulation of glucagon secretion in normal and diabetic human islets by γ-hydroxybutyrate and glycine
    Changhong Li
    Division of Endocrinology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 288:3938-51. 2013
    ..The results suggest that glycine and GHB provide a counterbalancing receptor-based mechanism for controlling α-cell secretory responses to metabolic fuels...
  24. pmc Protracted postnatal development of sparse, specific dentate granule cell activation in the mouse hippocampus
    Esther P Yu
    Division of Neurology and the Pediatric Regional Epilepsy Program, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 33:2947-60. 2013
    ....
  25. pmc Noninvasive optical quantification of cerebral venous oxygen saturation in humans
    Jennifer M Lynch
    University of Pennsylvania, Department of Physics and Astronomy, 209 South 33rd St, Philadelphia, PA 19104 Electronic address
    Acad Radiol 21:162-7. 2014
    ....
  26. pmc In vivo metabolic flux profiling with stable isotopes discriminates sites and quantifies effects of mitochondrial dysfunction in C. elegans
    Samantha Schrier Vergano
    Division of Human Genetics, The Children s Hospital of Philadelphia, and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA Division of Metabolic Disease, The Children s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA Children s Hospital of The King s Daughters, Division of Medical Genetics and Metabolism, Norfolk, VA, USA
    Mol Genet Metab 111:331-41. 2014
    ..elegans, to interrogate in vivo differences in metabolic flux among distinct genetic models of primary RC defects and closely related metabolic disorders...
  27. pmc Neuronal activity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters
    Joshua G Jackson
    Children s Hospital of Philadelphia Research Institute, Department of Pediatrics, Department of Pharmacology, and Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104
    J Neurosci 34:1613-24. 2014
    ....
  28. pmc Arx is required for specification of the zona incerta and reticular nucleus of the thalamus
    C Nicole Sunnen
    From the Department of Pathology, Children s Hospital of Philadelphia CNS Penn PORT Program CNS, and Department of Cell and Developmental Biology JCS, University of Pennsylvania and Department of Neurology, Children s Hospital of Philadelphia EDM, Philadelphia, Pennsylvania and Department of Pathology, Brigham Women and Children s Hospital, Boston, Massachusetts JAG
    J Neuropathol Exp Neurol 73:253-61. 2014
    ..Because the ZI and A13 regions make connections to several hypothalamic nuclei, such misspecification may contribute to the "hypothalamic dysfunction" observed in some patients. ..
  29. pmc The molecular and metabolic influence of long term agmatine consumption
    Itzhak Nissim
    From The Children s Hospital of Philadelphia
    J Biol Chem 289:9710-29. 2014
    ..The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming. ..
  30. pmc Behavioral changes and dopaminergic dysregulation in mice lacking the nuclear receptor Rev-erbα
    Jennifer Jager
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism J J, B F, Z G H, M A L, Department of Neurosciences W T O, J M, and Division of Hematology Oncology, Department of Medicine P S K, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104 and Children s Hospital of Philadelphia Research Institute E N K, M B R, Departments of Pediatrics and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
    Mol Endocrinol 28:490-8. 2014
    ..These findings reveal a novel, nonredundant function for Rev-erbα that links a core component of the circadian gene-regulatory network to the control of dopaminergic and hippocampus-dependent behaviors. ..
  31. pmc Integrated transcriptome analysis across mitochondrial disease etiologies and tissues improves understanding of common cellular adaptations to respiratory chain dysfunction
    Zhe Zhang
    Center for Biomedical Informatics, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, United States
    Int J Biochem Cell Biol 50:106-11. 2014
    ..Overall, transcriptome analyses provide a useful means to survey cellular adaptation to mitochondrial diseases. ..
  32. pmc Rare variants in TP53 and susceptibility to neuroblastoma
    Sharon J Diskin
    Affiliations of authors Division of Oncology SJD, MDI, DAO, KC, KRB, MRR, JMM, Center for Childhood Cancer Research SJD, MDI, DAO, KC, KRB, MRR, JMM, Center for Applied Genomics HH, and Division of Genetics HH, MDe Children s Hospital of Philadelphia, Philadelphia, PA Department of Pediatrics SJD, DAO, KRB, HH, MDE, JMM, Abramson Cancer Center SJD, JMM, Genomics and Computational Biology, Biomedical Graduate Studies SJD, DAO, JMM, and Department of Biostatistics and Epidemiology MDe, Perelman School of Medicine
    J Natl Cancer Inst 106:dju047. 2014
    ..Future studies using whole-genome sequencing data are likely to reveal additional rare variants with large effect sizes contributing to neuroblastoma tumorigenesis. ..
  33. pmc SDF1 reduces interneuron leading process branching through dual regulation of actin and microtubules
    Daniel E Lysko
    Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, and Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104
    J Neurosci 34:4941-62. 2014
    ....
  34. pmc Spectro-temporal correlates of lexical access during auditory lexical decision
    Jonathan Brennan
    University of Michigan, Department of Linguistics, United States Electronic address
    Brain Lang 133:39-46. 2014
    ..These findings suggest that alpha de-synchronization during auditory word processing is associated with early stages of lexical access...
  35. pmc Dorsal raphe neuroinflammation promotes dramatic behavioral stress dysregulation
    Alexis R Howerton
    Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
    J Neurosci 34:7113-23. 2014
    ..Behavioral changes were rescued by acute selective serotonin reuptake inhibitor treatment, supporting the hypothesis that serotonin dysregulation stemming from neuroinflammation in the DR underlies manic-like behaviors. ..
  36. pmc Cortical synaptic NMDA receptor deficits in α7 nicotinic acetylcholine receptor gene deletion models: Implications for neuropsychiatric diseases
    Hong Lin
    Departments of Pediatrics and Neurology, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Neurobiol Dis 63:129-40. 2014
    ....
  37. pmc Maturational differences in thalamocortical white matter microstructure and auditory evoked response latencies in autism spectrum disorders
    Timothy P L Roberts
    Lurie Family Foundation s MEG Imaging Center, Department of Radiology, The Children s Hospital of Philadelphia, Wood Building, Suite 2115, 34th Street and Civic Center Boulevard, Philadelphia, PA, USA Electronic address
    Brain Res 1537:79-85. 2013
    ....
  38. pmc High angular resolution diffusion imaging probabilistic tractography of the auditory radiation
    J I Berman
    Department of Radiology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    AJNR Am J Neuroradiol 34:1573-8. 2013
    ..This study investigates whether HARDI fiber tracking can be used to robustly delineate the full extent of the tract...
  39. pmc Transplantation of CD15-enriched murine neural stem cells increases total engraftment and shifts differentiation toward the oligodendrocyte lineage
    Sushma Chaubey
    Research Institute of the Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Stem Cells Transl Med 2:444-54. 2013
    ..This strategy may allow better delivery of therapeutic cells to the developing central nervous system and may be particularly useful for treating diseases involving white matter lesions...
  40. pmc Evidence for a motor gamma-band network governing response interference
    W Gaetz
    Lurie Family Foundations MEG Imaging Center, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Neuroimage 74:245-53. 2013
    ..Together, these data provide evidence for a motor gamma-band network for response selection and maintenance of planned behavior...
  41. pmc Cell-type-specific activation of the oligoadenylate synthetase-RNase L pathway by a murine coronavirus
    Ling Zhao
    Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    J Virol 87:8408-18. 2013
    ..Thus, RNase L activation during MHV infection is cell type specific and correlates with relatively high levels of expression of OAS genes, which are necessary but not sufficient for induction of an effective RNase L antiviral response. ..
  42. pmc GABA estimation in the brains of children on the autism spectrum: measurement precision and regional cortical variation
    W Gaetz
    Lurie Family Foundations MEG Imaging Center, Children s Hospital of Philadelphia, Philadelphia, PA, USA Electronic address
    Neuroimage 86:1-9. 2014
    ..Our novel findings support the model of regional differences in GABA+/Cr in the ASD brain, primarily in Auditory and to a lesser extent Motor but not Visual areas. ..
  43. pmc Mitochondrial respiratory chain disease discrimination by retrospective cohort analysis of blood metabolites
    Colleen Clarke
    Division of Human Genetics, Department of Pediatrics, The Children s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
    Mol Genet Metab 110:145-52. 2013
    ....
  44. pmc PKA modulates iron trafficking in the striatum via small GTPase, Rhes
    B R Choi
    Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, The Perlman School of Medicine at the University of Pennsylvania, 125 S 31st St TRL Rm 2207, Philadelphia, PA 19104, United States
    Neuroscience 253:214-20. 2013
    ..These findings suggest that Rhes may play a crucial role in striatal iron homeostasis...
  45. pmc Dexras1, a small GTPase, is required for glutamate-NMDA neurotoxicity
    Yong Chen
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 33:3582-7. 2013
    ..Deletion of Dexras1 in mice attenuates NO-mediated cell death in dissociated primary cortical neurons and retinal ganglion cells in vivo. Thus, Dexras1 appears to mediate NMDA-elicited neurotoxicity via NO and iron influx...
  46. doi The effects of healthy aging on cerebral hemodynamic responses to posture change
    Brian L Edlow
    Department of Neurology, University of Pennsylvania, Philadelphia, USA
    Physiol Meas 31:477-95. 2010
    ..23) and was associated with a smaller magnitude of decline in HbO(2) (p < 0.05) during supine-to-standing posture change. We conclude that healthy aging does not alter postural changes in frontal cortical perfusion...
  47. pmc Measuring in vivo ureagenesis with stable isotopes
    Marc Yudkoff
    Children s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Genet Metab 100:S37-41. 2010
    ..Finally, the use of isotopes affords an ideal tool with which to gauge the efficacy of therapeutic interventions to augment residual flux through the cycle...
  48. ncbi Intracerebral microdialysis during deep brain stimulation surgery
    Michaux Kilpatrick
    Department of Neurological Surgery, Gaston Memorial Hospital, Gastonia, NC, USA
    J Neurosci Methods 190:106-11. 2010
    ..Measurement of neurotransmitter levels within the BG may provide insight into mechanisms of DBS, but such an approach presents technical challenges...
  49. pmc Leading process branch instability in Lis1+/- nonradially migrating interneurons
    Pallavi P Gopal
    University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cereb Cortex 20:1497-505. 2010
    ..These data highlight a role for Lis1, acting through the PAF pathway, in leading process branching and microtubule stabilization...
  50. pmc Methyl-CpG-binding protein 2 is phosphorylated by homeodomain-interacting protein kinase 2 and contributes to apoptosis
    Giorgia Bracaglia
    Department of Experimental Oncology, Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Rome 00158, Italy
    EMBO Rep 10:1327-33. 2009
    ..These data are, to our knowledge, the first that describe a kinase associating with MeCP2, causing its specific phosphorylation in vivo and, furthermore, they reinforce the role of MeCP2 in regulating cell growth...
  51. pmc Molecular profiling of mitochondrial dysfunction in Caenorhabditis elegans
    Erzsebet Polyak
    Division of Human Genetics, Department of Pediatrics, The Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Methods Mol Biol 837:241-55. 2012
    ..elegans, qRT-PCR analysis of both nuclear and mitochondrial genes, and global nuclear genome expression profiling using the Affymetrix GeneChip C. elegans Genome Array...
  52. pmc Optical measurement of cerebral hemodynamics and oxygen metabolism in neonates with congenital heart defects
    Turgut Durduran
    ICFO Institut de Ciencies Fotoniques, Av Canal Olimpic s n, Castelldefels 08860, Spain
    J Biomed Opt 15:037004. 2010
    ..7, p=0.01). The study demonstrates use of NIRS-DCS on a critically ill neonatal population, and the results indicate that the optical technology is a promising clinical method for monitoring this population...
  53. pmc A palindrome-mediated recurrent translocation with 3:1 meiotic nondisjunction: the t(8;22)(q24.13;q11.21)
    Molly B Sheridan
    The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Am J Hum Genet 87:209-18. 2010
    ..Furthermore, demonstration that de novo PATRR8-to-PATRR11 translocations occur in sperm suggests that palindrome-mediated translocation is a universal mechanism producing chromosomal rearrangements...
  54. pmc mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal dendrites in vitro and dramatically increases in vivo after a seizure
    John R Ross
    Department of Pediatrics, Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104 4318, USA
    Neurochem Int 58:366-75. 2011
    ..These studies provide the first evidence that EAAC1 mRNA localizes to dendrites and suggest that dendritic targeting of EAAC1 mRNA is increased by seizure activity and may be regulated by neuronal activity/depolarization...
  55. pmc The incidence of thrombocytopenia in children with Cornelia de Lange syndrome
    Michele P Lambert
    Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, USA
    Am J Med Genet A 155:33-7. 2011
    ..Although further studies are needed to better define the scope of the problem and to define the mechanisms of thrombocytopenia in CdLS, we would recommend screening for thrombocytopenia upon diagnosis and at 5-year intervals thereafter...
  56. pmc Group I mGluR-regulated translation of the neuronal glutamate transporter, excitatory amino acid carrier 1
    John R Ross
    Departments of Pediatrics and Pharmacology, Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Neurochem 117:812-23. 2011
    ..These studies provide the first evidence EAAC1 translation can be regulated, and they show that regulated translation of EAAC1 is up-regulated after SE...
  57. pmc Effects of a glucokinase activator on hepatic intermediary metabolism: study with 13C-isotopomer-based metabolomics
    Itzhak Nissim
    Division of Child Development and Metabolic Disease, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Biochem J 444:537-51. 2012
    ..GKA improved hepatic bioenergetics, ureagenesis and glycogenesis, but decreased gluconeogenesis with a potential risk of lactic acidosis and fatty liver...
  58. pmc Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses
    Darren Goffin
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Nat Neurosci 15:274-83. 2012
    ....
  59. pmc In vitro stretch injury induces time- and severity-dependent alterations of STEP phosphorylation and proteolysis in neurons
    Mahlet N Mesfin
    Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Neurotrauma 29:1982-98. 2012
    ....
  60. pmc Phase measurement of cognitive impairment specific to radiotherapy
    Carol L Armstrong
    Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Int J Radiat Oncol Biol Phys 83:e319-24. 2012
    ..The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain...
  61. pmc Rare structural variation of synapse and neurotransmission genes in autism
    X Gai
    Center for Biomedical Informatics, Children s Hospital of Philadelphia, Philadelphia, PA 19104 4318, USA
    Mol Psychiatry 17:402-11. 2012
    ..These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology and suggest a sizable pool of additional potential ASD risk loci...
  62. pmc Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in an RNA interference model of methyl-CpG-binding protein 2 deficiency
    Lydia Wood
    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    J Neurosci 29:12440-8. 2009
    ..These studies indicate that MeCP2 deficiency in individual postsynaptic cortical pyramidal neurons is sufficient to induce a pathological synaptic defect in excitatory intracortical circuits...
  63. pmc SDF1 regulates leading process branching and speed of migrating interneurons
    Daniel E Lysko
    Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 31:1739-45. 2011
    ....
  64. pmc Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes
    J Elia
    Department of Child and Adolescent Psychiatry, The Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Mol Psychiatry 15:637-46. 2010
    ..Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD...
  65. ncbi Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders
    Susan E Levy
    Division of Child Development and Rehabilitation, Children s Seashore House of The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Biol Psychiatry 61:492-7. 2007
    ..The purpose of this study was to 1) describe dietary intake of a cohort of children with ASD compared with normative data and 2) determine whether GI symptoms and stool consistency are related to dietary intake...
  66. pmc Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation
    Rifat J Hussain
    Department of Psychiatry, University of Pennsylvania School of Medicine, Clinical Research Building, Philadelphia, Pennsylvania, USA
    Hippocampus 16:495-503. 2006
    ..The implications of these findings for the role of the mossy fiber-CA3 pathway in hippocampus-dependent learning processes are discussed...
  67. ncbi Inflammatory markers and mediators in tracheal fluid of premature infants treated with inhaled nitric oxide
    William E Truog
    Department of Pediatrics, Section of Neonatology, Children s Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, 2401 Gillham Rd, Kansas City, MO 64108, USA
    Pediatrics 119:670-8. 2007
    ..We investigated relationships between respiratory severity scores and airway concentrations of inflammatory markers/mediators...
  68. ncbi Effects of a GTP-insensitive mutation of glutamate dehydrogenase on insulin secretion in transgenic mice
    Changhong Li
    Division of Endocrinology, The Children s Hospital of Philadelphia and Diabetes Center, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 281:15064-72. 2006
    ..This study suggests that GDH functions predominantly in the direction of glutamate oxidation rather than glutamate synthesis in mouse islets and that this flux is tightly controlled by glucose...
  69. ncbi Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays
    Jeffrey E Ming
    Division of Human Genetics, Stokes Research Institute, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Hum Mutat 27:467-73. 2006
    ..Their higher resolution and commercial availability make this type of microarray highly desirable for application in the diagnosis of patients with multiple congenital defects...
  70. ncbi Analysis of non-radial interneuron migration dynamics and its disruption in Lis1+/- mice
    Ilya M Nasrallah
    Neuroscience Program, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    J Comp Neurol 496:847-58. 2006
    ..These data provide insight into NRCM and practical methods for future studies on the role(s) of specific genes in interneuron migration...
  71. ncbi Identification of a submicroscopic deletion of SHH associated with the holoprosencephaly spectrum by array-based CGH
    Jia Huang
    Clin Genet 69:367-9. 2006
  72. ncbi Chronic ibuprofen administration worsens cognitive outcome following traumatic brain injury in rats
    Kevin D Browne
    Department of Neurosurgery, Center for Brain Injury and Repair, University of Pennsylvania, Philadelphia, PA 19104, USA
    Exp Neurol 201:301-7. 2006
    ..These data may have important implications for TBI patients who are often prescribed NSAIDs for chronic pain...
  73. ncbi Mouse Piwi-interacting RNAs are 2'-O-methylated at their 3' termini
    Yohei Kirino
    Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nat Struct Mol Biol 14:347-8. 2007
    ..Here we report that the 3' termini of piRNAs are 2'-O-methylated; this modification may have important implications for the biogenesis and function of piRNAs...
  74. pmc MLPA: a rapid, reliable, and sensitive method for detection and analysis of abnormalities of 22q
    J A S Vorstman
    Division of Human Genetics, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Hum Mutat 27:814-21. 2006
    ..2 region, making it a fast and economic alternative to currently used methods. The current study provides valuable and detailed information on the characteristics of this novel method...
  75. pmc Evaluation of potential modifiers of the palatal phenotype in the 22q11.2 deletion syndrome
    Deborah A Driscoll
    Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, USA
    Cleft Palate Craniofac J 43:435-41. 2006
    ..To evaluate potential modifiers of the palatal phenotype in individuals with the 22q11.2 deletion syndrome...
  76. ncbi Inhaled nitric oxide in preterm infants undergoing mechanical ventilation
    Roberta A Ballard
    Children s Hospital of Philadelphia, Philadelphia 19104, USA
    N Engl J Med 355:343-53. 2006
    ..In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial...
  77. ncbi Intracellular and trans-synaptic regulation of glutamatergic synaptogenesis by EphB receptors
    Matthew S Kayser
    Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 26:12152-64. 2006
    ..These results demonstrate that EphB2 acts to control the organization of specific classes of mature glutamatergic synapses...
  78. pmc Chronically increased Gsalpha signaling disrupts associative and spatial learning
    Rusiko Bourtchouladze
    Center for Neurobiology and Behavior and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Learn Mem 13:745-52. 2006
    ..The learning deficits observed in these transgenic mice suggest that associative and spatial learning requires regulated Gsalpha protein signaling, much as does olfactory learning in Drosophila...
  79. ncbi A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon
    Zongming Pan
    Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 26:2599-613. 2006
    ..This includes the historical period when myelin also evolved...
  80. ncbi Short-term fasting, seizure control and brain amino acid metabolism
    Marc Yudkoff
    Department of Pediatrics, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 19104, USA
    Neurochem Int 48:650-6. 2006
    ....
  81. pmc Array based CGH and FISH fail to confirm duplication of 8p22-p23.1 in association with Kabuki syndrome
    J D Hoffman
    Division of Human Genetics, Department of Pediatrics, The Children s Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Med Genet 42:49-53. 2005
    ..A recent report described a duplication of 8p22-p23.1 in 13/13 patients...
  82. ncbi Visuospatial and numerical cognitive deficits in children with chromosome 22q11.2 deletion syndrome
    Tony J Simon
    University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    Cortex 41:145-55. 2005
    ..Instead, our findings are supportive of the hypothesis that visuospatial and numerical deficits in children with the chromosome 22q11.2 deletion are due, at least in part, to posterior parietal dysfunction...
  83. ncbi Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study
    Tony J Simon
    Children s Hospital of Philadelphia, 3535 Market Street, Room 1425, Philadelphia, PA 19104, USA
    Neuroimage 25:169-80. 2005
    ....
  84. ncbi Altered BMP signaling disrupts chick diencephalic development
    Youngshin Lim
    Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
    Mech Dev 122:603-20. 2005
    ..In summary, our data indicate that while not necessary, BMP signaling via Bmpr1a and Bmpr1b, is sufficient to modify nuclear organization in the chick diencephalon...
  85. ncbi Response of brain amino acid metabolism to ketosis
    Marc Yudkoff
    Department of Pediatrics, University of Pennsylvania School of Medicine, Children s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA
    Neurochem Int 47:119-28. 2005
    ....
  86. ncbi Effect of myristoylated alanine-rich C kinase substrate (MARCKS) overexpression on hippocampus-dependent learning and hippocampal synaptic plasticity in MARCKS transgenic mice
    Robert K McNamara
    Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0559, USA
    Hippocampus 15:675-83. 2005
    ..Collectively, these results indicate that elevations in MARCKS expression are detrimental to specific aspects of hippocampal function...
  87. ncbi Neuronal migration in developmental disorders
    Matthew F McManus
    Neuroscience Program, University of Pennsylvania School of Medicine, USA
    J Child Neurol 20:280-6. 2005
    ..Herein we discuss the role of normal non-radial cell migration in cortical development, as well as how perturbations in both radial and nonradial migration result in developmental anomalies...
  88. ncbi Brain amino acid requirements and toxicity: the example of leucine
    Marc Yudkoff
    Children s Hospital of Philadelphia, Division of Child Development, Rehabilitation and Metabolic Disease, Department of Pediatrics, University of Pennsylvania School of Medicine, 19104, USA
    J Nutr 135:1531S-8S. 2005
    ..The result is a compromise of energy metabolism because of a failure of the malate-aspartate shuttle and a diminished rate of protein synthesis...
  89. pmc Palindromic AT-rich repeat in the NF1 gene is hypervariable in humans and evolutionarily conserved in primates
    Hidehito Inagaki
    Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, 1 98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470 1192, Japan
    Hum Mutat 26:332-42. 2005
    ..Although such palindromic regions are usually unstable and disappear rapidly due to deletion, the 17PATRR in the NF1 gene was stably conserved during evolution for reasons that are still unknown...
  90. ncbi Genotypically defined lissencephalies show distinct pathologies
    Mark S Forman
    Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA, and Department of Neurology, Radcliffe Infirmary, Oxford, UK
    J Neuropathol Exp Neurol 64:847-57. 2005
    ..Based on these data, a new classification for lissencephaly is proposed that incorporates both pathologic and genetic findings...
  91. ncbi Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy
    A G Christina Bergqvist
    Division of Neurology, The Children s Hospital of Philadelphia, Pennsylvania 19104, USA
    Epilepsia 46:1810-9. 2005
    ..The purpose of the study was to compare the efficacy of a gradual KD initiation with the standard KD initiation preceded by a 24- to 48-h fast...
  92. pmc A human, ATP-independent, RISC assembly machine fueled by pre-miRNA
    Elisavet Maniataki
    Department of Pathology, Division of Neuropathology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    Genes Dev 19:2979-90. 2005
    ..We suggest that the miRLC couples the processing of the pre-miRNA substrate to the unwinding of the product and that after loading of the mature miRNA to Ago2, the miRLC disassembles and the miRNP is released...
  93. pmc RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain
    Peter T Nelson
    Division of Neuropathology and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 605A Stellar Chance Bldg, 421 Curie Blvd, Philadelphia, PA 19104, USA
    RNA 12:187-91. 2006
    ..The ability to profile miRNAs from archival tissues at the tissue level, by RAKE microarrays, and at the cellular level by LNA-ISH, will accelerate studies of miRNAs in human diseases...
  94. ncbi Behavioral and neurochemical alterations in mice lacking the RNA-binding protein translin
    Joel M Stein
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 26:2184-96. 2006
    ..Our results in mice indicate that mutations in translin may contribute to fragile X-like syndromes, mental retardation, attention deficit hyperactivity disorder, epilepsy, and autism spectrum disorders in humans...
  95. ncbi An mRNA m7G cap binding-like motif within human Ago2 represses translation
    Marianthi Kiriakidou
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 129:1141-51. 2007
    ..We propose that Ago2 represses the initiation of mRNA translation by binding to the m(7)G cap of mRNA targets, thus likely precluding the recruitment of eIF4E...
  96. ncbi Pax6-/- mice have a cell nonautonomous defect in nonradial interneuron migration
    Pallavi P Gopal
    Neuroscience Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cereb Cortex 18:752-62. 2008
    ..Further, our data indicate that the known axonal disorganization in Sey-/- mice contributes to the observed reduced distance of NRCM...
  97. pmc One-year respiratory outcomes of preterm infants enrolled in the Nitric Oxide (to prevent) Chronic Lung Disease trial
    Anna Maria Hibbs
    Department of Pediatrics, Rainbow Babies and Children s Hospital, Case Western Reserve University, Cleveland, OH 44106 6010, USA
    J Pediatr 153:525-9. 2008
    ..To identify whether inhaled nitric oxide treatment decreased indicators of long-term pulmonary morbidities after discharge from the neonatal intensive care unit...
  98. ncbi Gambling initiation in preadolescents
    Hallam Hurt
    Neonatology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Adolesc Health 43:91-3. 2008
    ..Gamblers were more likely to be white, have tried alcohol, have positive affect toward gambling, and have friends who gamble...
  99. pmc Identification of Arx transcriptional targets in the developing basal forebrain
    Carl T Fulp
    Neuroscience Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Hum Mol Genet 17:3740-60. 2008
    ....
  100. pmc Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction
    David R Wise
    Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Proc Natl Acad Sci U S A 105:18782-7. 2008
    ..These data suggest that oncogenic levels of Myc induce a transcriptional program that promotes glutaminolysis and triggers cellular addiction to glutamine as a bioenergetic substrate...