Eva Feldman

Personal Information
Title Professor
Expertise Neuropathy & Neurocognition
Institution University of Michigan
Data Summary
TypeCount
Grants/SubContracts 3
Progress Reports 10
Presentations 6
Publications 66
Protocols 10
Committees 2
Experiments 0
Strains 12
Models 9

Mitochondrial SOD as a Target for Diabetic Neuropathy
Grant Number: DK076160

Abstract: In response to the request for applications DK-05-011, entitled Animal Models of Diabetic Complications Consortium (AMDCC), the Investigators from the current AMDCC Neuropathy Phenotyping Core are proposing to develop 2 new mouse models of diabetic neuropathy (DN) targeting the biochemical pathways of oxidative stress. Our general strategic approach is to accelerate glucose-mediated oxidative injury in neurons in genetic models of type 2 diabetes. While many gene products participate in this process, we will concentrate on targeting 2 enzymes involved in superoxide detoxification: mitochondrial superoxide dismutase 2 (SOD2) and catalase. Our initial approach will concentrate on developing 2 Cre-loxP models on a susceptible genetic background. In parallel, we propose 2 hypothesis-driven specific aims for discovering the basic pathophysiologic mechanisms underlying DN. Aim 1 will test the hypothesis that decreased catalase activity in sensory neurons will make these neurons more susceptible to glucose-mediated injury. Aim 2 will test the hypothesis that animal models with DN have morphological and biochemical markers of increased oxidative stress in the peripheral nervous system. Information gained from this application will lead to new insights into the pathogenesis of DN and allow for the development of more relevant murine models of this disabling complication. Relevance to Public Health: 20 million Americans are diabetic and the incidence is increasing by 5% each year. Although DN is a common and highly morbid condition, there are no treatments for DN outside of control of the diabetic condition itself. Our studies will identify cellular targets for treatment of DN and have the potential to benefit all patients with diabetes.


Institution: University of Michigan
3003 SOUTH STATE STREET
ANN ARBOR, MI
Fiscal Year:2006
Department:NEUROLOGY
Project Start: 9/30/2006
Project End: 8/31/2011
ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

SubContract(s)


A Centralized Data Mining and Analysis Portal for Diabetic Neuropathy Research
Diabetic neuropathy (DN) is the most common complication of diabetes with significant morbidity, mortality and cost. 60% - 70% of diabetic patients have neuropathy often resulting in poor quality of life. Better understanding of the molecular mechanism of development and progression of DN is crucial for designing mechanism based therapies. Genome-wide molecular studies in animal models are integral to understanding human disease pathogenesis. Diabetic Complications Consortium (DCC) has extensively characterized mouse models of human DN. Integrating high-throughput gene expression data in human DN with those in the animal models is critical in delineating species-specific as well as shared mechanisms between human and mouse. Our group has developed a database system that integrates transcriptomics data from our studies in mouse models and human DN. Goal of this proposal is to extend the existing system to form a centralized repository for publicly available transcriptomics data sets of DN and to provide a data-mining and data-analysis portal to the diabetes complications research community. Specific aims of the project are: Aim 1. Identify and annotate human and mouse DN gene expression data sets in the DCC data repository, National Center for Biotechnology Information (NCBI) Gene Expression Omnibus and European Bioinformatics Institute (EBI) ArrayExpress; process data using our established data processing pipeline to achieve consistency. Aim 2. Extend the existing database to efficiently store large transcriptomics data sets and upload processed data into the database; develop and implement data mining and data analysis tools with a user friendly web-based interface. Making this centralized data repository and analysis portal available to the research community at large will aid investigators in generating hypotheses and designing future experiments. Comparing gene regulation in the well characterized DCC murine models and human DN will facilitate selection of models that best recapitulate human disease mechanism for further exploration.

Identifying Alterations in Mitochondrial Dynamics Associate
Diabetes is a growing epidemic, affecting more than 387 million individuals worldwide. Up to 60% of diabetic patients have diabetic neuropathy (DN), a debilitating microvascular complication that results in the progressive loss of sensory nerve function in the extremities. Despite the deleterious impact of DN, therapies for the disease are limited to symptomatic relief. To develop effective treatments that specifically target DN, a mechanistic understanding of molecular pathways that result in neurological dysfunction associated with diabetes is needed. Recent evidence suggests that dyslipidemia, rather than hyperglycemia, is the clinical parameter that correlates with the progression of DN. Since metabolic pathways converge on the mitochondria (Mt), these organelles play a central role in maintaining neuronal cellular function and energy homeostasis through mitochondrial (Mtl) trafficking mechanisms and endoplasmic reticulum (ER)-mediated calcium signaling pathways. However, metabolic overload associated with diabetes may result in aberrant calcium dynamics in the primary sensory neurons of the nervous system, the dorsal root ganglia (DRG), resulting in diminished Mtl trafficking and cell death induced by ER-Mt contact sites. We hypothesize that hyperlipidemia increases the level of ER-Mt contact sites in DRG neurons, creating a localized calcium flux which triggers Mtl apoptosis and halts Mtl trafficking. We will test this hypothesis by 1) evaluating the role of ER-Mt interactions in Mtl dysfunction and neuronal cell death in the DRG and sural nerve of a high fat (HF)-fed mouse model, and 2) identifying changes in calcium dynamics that impair Mtl trafficking in hyperlipidemic DRG neurons. These studies will provide important insight into the role of Mtl dynamics in DN and thereby support our long-term goal of identifying therapeutic targets that specifically improve Mtl function and restore nerve function to patients with DN.


Progress Reports

Annual Reports

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Feldman, Eva (2004)
2004Annual Report
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Feldman, Eva (2005)
2005Annual Report
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Feldman, Eva (2006)
2006Annual Report
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Feldman, Eva (2007)
2007Annual Report
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Feldman, Eva (2008)
2008Annual Report
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Feldman, Eva (2009)
2009Annual Report
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Feldman, Eva (2010)
2010Annual Report
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Feldman, Eva (2011)
2011Annual Report
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 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2017; Items: 2

 
Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.
Hinder LM, Park M, Rumora AE, Hur J, Eichinger F, Pennathur S, Kretzler M, Brosius FC, Feldman EL
Journal of cellular and molecular medicine, 2017
28272773
Published
 
Dyslipidemia impairs mitochondrial trafficking and function in sensory neurons.
Rumora AE, Lentz SI, Hinder LM, Jackson SW, Valesano A, Levinson GE, Feldman EL
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2017
28904018
Published

Year: 2016; Items: 2

 
The evaluation of distal symmetric polyneuropathy: utilisation and expenditures by community neurologists.
Callaghan BC, Kerber KA, Banerjee M, Feldman EL, Morgenstern LB, Longoria R, Rodgers A, Longwell P, Lisabeth LD
Journal of neurology, neurosurgery, and psychiatry, 2016 (87), 113 - 4
25604430
Published
 
Tissue-specific metabolic reprogramming drives nutrient flux in diabetic complications.
Sas KM, Kayampilly P, Byun J, Nair V, Hinder LM, Hur J, Zhang H, Lin C, Qi NR, Michailidis G, Groop PH, Nelson RG, Darshi M, Sharma K, Schelling JR, Sedor JR, Pop-Busui R, Weinberg JM, Soleimanpour SA, Abcouwer SF, Gardner TW, Burant CF, Feldman EL, Kretzler M, Brosius FC, Pennathur S
JCI insight, 2016 (1), e86976
27699244
Published

Year: 2014; Items: 5

 
ER Stress in Diabetic Peripheral Neuropathy: A New Therapeutic Target.
O'Brien PD, Hinder LM, Sakowski SA, Feldman EL
Antioxidants & redox signaling, 2014 (21), 621 - 633
24382087
Published
 
Mouse models of diabetic neuropathy.
O'Brien PD, Sakowski SA, Feldman EL
ILAR journal / National Research Council, Institute of Laboratory Animal Resources, 2014 (54), 259 - 272
24615439
Published
 
How neurologists can choose (even more) wisely: prioritizing waste reduction targets and identifying gaps in knowledge.
Callaghan BC, Burke JF, Feldman EL
JAMA : the journal of the American Medical Association, 2014 (311), 1607 - 1608
24756505
Published
 
Role of neurologists and diagnostic tests on the management of distal symmetric polyneuropathy.
Callaghan BC, Kerber KA, Lisabeth LL, Morgenstern LB, Longoria R, Rodgers A, Longwell P, Feldman EL
JAMA neurology, 2014 (71), 1143 - 1149
25048157
Published
 
BTBR ob/ob mice as a novel diabetic neuropathy model: Neurological characterization and gene expression analyses.
O'Brien PD, Hur J, Hayes JM, Backus C, Sakowski SA, Feldman EL
Neurobiology of disease, 2014 (73C), 348 - 355
25447227
Published

Year: 2013; Items: 10

 
Apolipoprotein E knockout as the basis for mouse models of dyslipidemia-induced neuropathy.
Hinder LM, Vincent AM, Hayes JM, McLean LL, Feldman EL
Experimental neurology, 2013 (239), 102 - 110
23059459
Published
 
Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes.
Hinder LM, Vivekanandan-Giri A, McLean LL, Pennathur S, Feldman EL
The Journal of endocrinology, 2013 (216), 1 - 11
23086140
Published
 
Hyperglycemia-induced Tau cleavage in vitro and in vivo: a possible link between diabetes and Alzheimer's disease.
Kim B, Backus C, Oh S, Feldman EL
Journal of Alzheimer's disease : JAD, 2013 (34), 727 - 739
23254634
Published
 
Diabetic cardiac autonomic neuropathy: insights from animal models.
Stables CL, Glasser RL, Feldman EL
Autonomic neuroscience : basic & clinical, 2013 (177), 74 - 80
23562143
Published
 
Increased axonal regeneration and swellings in intraepidermal nerve fibers characterize painful phenotypes of diabetic neuropathy.
Cheng HT, Dauch JR, Porzio MT, Yanik BM, Hsieh W, Smith AG, Singleton JR, Feldman EL
The journal of pain : official journal of the American Pain Society, 2013 (14), 941 - 947
23685187
Published
 
The role of oxidative stress in nervous system aging.
Sims-Robinson C, Hur J, Hayes JM, Dauch JR, Keller PJ, Brooks SV, Feldman EL
PLoS ONE, 2013 (8), e68011
23844146
Published
 
Biology of diabetic neuropathy.
Vincent AM, Calabek B, Roberts L, Feldman EL
Handbook of clinical neurology, 2013 (115), 591 - 606
23931804
Published
 
Long-Chain Acyl Coenzyme A Synthetase 1 Overexpression in Primary Cultured Schwann Cells Prevents Long Chain Fatty Acid-Induced Oxidative Stress and Mitochondrial Dysfunction.
Hinder LM, Figueroa-Romero C, Pacut C, Hong Y, Vivekanandan-Giri A, Pennathur S, Feldman EL
Antioxidants & redox signaling, 2013 (21), 588 - 600
23991914
Published
 
Identification of factors associated with sural nerve regeneration and degeneration in diabetic neuropathy.
Hur J, Sullivan KA, Callaghan BC, Pop-Busui R, Feldman EL
Diabetes care, 2013 (36), 4043 - 4049
24101696
Published
 
Peripheral neuropathy in adolescents and young adults with type 1 and type 2 diabetes from the SEARCH for Diabetes in Youth follow-up cohort: a pilot study.
Jaiswal M, Lauer A, Martin CL, Bell RA, Divers J, Dabelea D, Pettitt DJ, Saydah S, Pihoker C, Standiford DA, Rodriguez BL, Pop-Busui R, Feldman EL
Diabetes care, 2013 (36), 3903 - 3908
24144652
Published

Year: 2012; Items: 11

 
Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities in painful neuropathy of type 2 diabetes.
Cheng HT, Dauch JR, Hayes JM, Yanik BM, Feldman EL
Neurobiology of disease, 2012 (45), 280 - 287
21872660
Published
 
Insulin resistance in the nervous system.
Kim B, Feldman EL
Trends in endocrinology and metabolism: TEM, 2012 (23), 133 - 141
22245457
Published
 
Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications.
Herman WH, Pop-Busui R, Braffett BH, Martin CL, Cleary PA, Albers JW, Feldman EL
Diabetic medicine : a journal of the British Diabetic Association, 2012 (29), 937 - 944
22417277
Published
 
Altered excitation-inhibition balance in the brain of patients with diabetic neuropathy.
Petrou M, Pop-Busui R, Foerster BR, Edden RA, Callaghan BC, Harte SE, Harris RE, Clauw DJ, Feldman EL
Academic radiology, 2012 (19), 607 - 612
22463961
Published
 
Neurodegeneration and early lethality in superoxide dismutase 2-deficient mice: a comprehensive analysis of the central and peripheral nervous systems.
Oh SS, Sullivan KA, Wilkinson JE, Backus C, Hayes JM, Sakowski SA, Feldman EL
Neuroscience, 2012 (212), 201 - 213
22516022
Published
 
Bioenergetics in diabetic neuropathy: what we need to know.
Hinder LM, Vincent AM, Burant CF, Pennathur S, Feldman EL
Journal of the peripheral nervous system : JPNS, 2012 (17 Suppl 2), 10 - 14
22548617
Published
 
Central nervous system endoplasmic reticulum stress in a murine model of type 2 diabetes.
Sims-Robinson C, Zhao S, Hur J, Feldman EL
Diabetologia, 2012 (55), 2276 - 2284
22581041
Published
 
Diabetic neuropathy: clinical manifestations and current treatments.
Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL
Lancet neurology, 2012 (11), 521 - 534
22608666
Published
 
Enhanced glucose control for preventing and treating diabetic neuropathy.
Callaghan BC, Little AA, Feldman EL, Hughes RA
Cochrane database of systematic reviews (Online), 2012 (6), CD007543
22696371
Published
 
Diabetic neuropathy: one disease or two?
Callaghan BC, Hur J, Feldman EL
Current opinion in neurology, 2012 (25), 536 - 541
22892951
Published
 
Capturing cases of distal symmetric polyneuropathy in a community.
Callaghan B, Kerber K, Longoria R, Feldman E, Lisabeth L
Muscle & nerve, 2012 (46), 943 - 947
23042289
Published

Year: 2011; Items: 8

 
21194385
Published
 
Triglycerides and amputation risk in patients with diabetes: ten-year follow-up in the DISTANCE study.
Callaghan BC, Feldman E, Liu J, Kerber K, Pop-Busui R, Moffet H, Karter AJ
Diabetes care, 2011 (34), 635 - 640
21285390
Published
 
21484835
Published
 
Transcriptional profiling of diabetic neuropathy in the BKS db/db mouse: a model of type 2 diabetes.
Pande M, Hur J, Hong Y, Backus C, Hayes JM, Oh SS, Kretzler M, Feldman EL
Diabetes, 2011 (60), 1981 - 1989
21617178
Published
 
Hyperinsulinemia induces insulin resistance in dorsal root ganglion neurons.
Kim B, McLean LL, Philip SS, Feldman EL
Endocrinology, 2011 (152), 3638 - 3647
21810948
Published
 
Diabetic neuropathy: cellular mechanisms as therapeutic targets.
Vincent AM, Callaghan BC, Smith AL, Feldman EL
Nature reviews. Neurology, 2011 (7), 573 - 583
21912405
Published
 
The identification of gene expression profiles associated with progression of human diabetic neuropathy.
Hur J, Sullivan KA, Pande M, Hong Y, Sima AA, Jagadish HV, Kretzler M, Feldman EL
Brain : a journal of neurology, 2011 (134), 3222 - 3235
21926103
Published
 
The Evaluation of Distal Symmetric Polyneuropathy: A Physician Survey of Clinical Practice.
Callaghan BC, Kerber K, Smith AL, Fendrick AM, Feldman EL
Archives of neurology, 2011
22083798
Published

Year: 2010; Items: 8

 
Mitochondrial DNA (mtDNA) biogenesis: visualization and duel incorporation of BrdU and EdU into newly synthesized mtDNA in vitro.
Lentz SI, Edwards JL, Backus C, McLean LL, Haines KM, Feldman EL
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2010 (58), 207 - 218
19875847
Published
 
The management of diabetic neuropathy in CKD.
Pop-Busui R, Roberts L, Pennathur S, Kretzler M, Brosius FC, Feldman EL
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2010 (55), 365 - 385
20042258
Published
 
Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy.
Vincent AM, Edwards JL, McLean LL, Hong Y, Cerri F, Lopez I, Quattrini A, Feldman EL
Acta Neuropathologica, 2010 (120), 477 - 489
20473509
Published
 
Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice.
Kakoki M, Sullivan KA, Backus C, Hayes JM, Oh SS, Hua K, Gasim AM, Tomita H, Grant R, Nossov SB, Kim HS, Jennette JC, Feldman EL, Smithies O
Proceedings of the National Academy of Sciences of the United States of America, 2010 (107), 10190 - 10195
20479236
Published
 
The effects of anesthesia on measures of nerve conduction velocity in male C57Bl6/J mice.
Oh SS, Hayes JM, Sims-Robinson C, Sullivan KA, Feldman EL
Neuroscience letters, 2010 (483), 127 - 131
20691755
Published
 
How does diabetes accelerate Alzheimer disease pathology?
Sims-Robinson C, Kim B, Rosko A, Feldman EL
Nature reviews. Neurology, 2010 (6), 551 - 559
20842183
Published
 
Literature-based discovery of diabetes- and ROS-related targets.
Hur J, Sullivan KA, Schuyler AD, Hong Y, Pande M, States DJ, Jagadish HV, Feldman EL
BMC medical genomics, 2010 (3), 49
20979611
Published
 
Visualization of mitochondrial DNA replication in individual cells by EdU signal amplification.
Haines KM, Feldman EL, Lentz SI
Journal of visualized experiments : JoVE, 2010
21113116
Published

Year: 2009; Items: 9

 
Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy.
Dowling JJ, Vreede AP, Low SE, Gibbs EM, Kuwada JY, Bonnemann CG, Feldman EL
PLoS genetics, 2009 (5(2)), e1000372
19197364
Published
 
Disorders of cranial nerves IX and X.
Erman AB, Kejner AE, Hogikyan ND, Feldman EL
Seminars in neurology, 2009 (29), 85 - 92
19214937
Published
 
Hydrogen peroxide-induced Akt phosphorylation regulates Bax activation.
Sadidi M, Lentz SI, Feldman EL
Biochimie, 2009 (91(5)), 577 - 585
19278624
Published
 
Computational methods for predicting sites of functionally important dynamics.
Schuyler AD, Carlson HA, Feldman EL
The journal of physical chemistry. B, 2009 (113(19)), 6613 - 6622
19378962
Published
 
Dyslipidemia-Induced Neuropathy in Mice: the Role of oxLDL/LOX-1
Andrea M. Vincent, John M. Hayes, Lisa L. McLean, Anuradha Vivekanandan-Giri, Subramaniam Pennathur, and Eva L. Feldman
Diabetes, 2009 (58(10)), 2376 - 2385
19592619
Published
 
SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle.
Figueroa-Romero C, Iñiguez-Lluhí JA, Stadler J, Chang CR, Arnoult D, Keller PJ, Hong Y, Blackstone C, Feldman EL
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009 (23(11)), 3917 - 3927
19638400
Published
 
Nerve Growth Factor Mediates Mechanical Allodynia in a Mouse Model of Type 2 Diabetes
Hsinlin T Cheng, John M Hayes, Yu Hong and Eva L Feldman
Journal of neuropathology and experimental neurology, 2009
19816194
Published
 
Increased tau phosphorylation and cleavage in mouse models of type 1 and type 2 diabetes.
Kim B, Backus C, Oh S, Hayes JM, Feldman EL
Endocrinology, 2009 (150(12)), 5294 - 5301
19819959
Published
 
Hyperlipidemia: a new therapeutic target for diabetic neuropathy.
Vincent AM, Hinder LM, Pop-Busui R, Feldman EL
Journal of the peripheral nervous system : JPNS, 2009 (14(4)), 257 - 267
20021567
Published

Year: 2008; Items: 9

 
Criteria for creating and assessing mouse models of diabetic neuropathy.
Sullivan KA, Lentz SI, Roberts JL, Feldman EL
Current drug targets, 2008 (9(1)), 3
18220709
Published
 
Membrane traffic and muscle: lessons from human disease.
Dowling JJ, Gibbs EM, Feldman EL
Traffic (Copenhagen, Denmark), 2008 (9(7)), 1035 - 1043
18266915
Published
 
18413183
Published
 
From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy.
Qian Y, Feldman E, Pennathur S, Kretzler M, Brosius FC
Diabetes, 2008 (57(6)), 1439 - 1445
18511444
Published
 
Rosiglitazone Treatment Reduces Diabetic Neuropathy in STZ treated DBA/2J mice
Timothy D Wiggin, Matthias Kretzler, Subramaniam Pennathur, Kelli A. Sullivan, Frank C Brosius, Eva L Feldman
Endocrinology, 2008 (149(10)), 4928 - 4937
18583417
Published
 
Kindlin-2 is required for myocyte elongation and is essential for myogenesis.
Dowling JJ, Vreede AP, Kim S, Golden J, Feldman EL
BMC cell biology, 2008 (9), 36
18611274
Published
 
Rosiglitazone reduces renal and plasma markers of oxidative injury and reverses urinary metabolite abnormalities in the amelioration of diabetic nephropathy
Hongyu Zhang, Jharna Saha, MaryLee Schin, Jaeman Byun, Matthias Kretzler, Eva L. Feldman, David A. Weild, Subramaniam Pennathur, Frank C. Brosius III
American journal of physiology. Renal physiology, 2008 (295(4)), F1071 - F1081
18667486
Published
 
Mechanisms of disease: the oxidative stress theory of diabetic neuropathy.
Figueroa-Romero C, Sadidi M, Feldman EL
Reviews in endocrine & metabolic disorders, 2008 (9(4)), 301 - 314
18709457
Published
 
Insulin-like growth factors in the peripheral nervous system.
Sullivan KA, Kim B, Feldman EL
Endocrinology, 2008 (149(12)), 5963 - 5971
18719018
Published

Year: 2007; Items: 2

 
Mouse models of diabetic neuropathy.
Sullivan KA, Hayes JM, Wiggin TD, Backus C, Su Oh S, Lentz SI, Brosius F, Feldman EL
Neurobiology of disease, 2007 (28(3)), 276 - 285
17804249
Published
 
SOD2 Protects Neurons from Injury in Cell Culture and Animal Models of Diabetic Neuropathy
Andrea M. Vincent, James W. Russell, Kelli A. Sullivan, Carey Backus, John M. Hayes, Lisa L. McLean and Eva L. Feldman
Experimental neurology, 2007 (208), 216 - 227
17927981
Published

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Feldman, Eva (02/2004)
2004Presentation
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Feldman, Eva (10/19/2004)
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Feldman, Eva (2005)
2005Presentation
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Feldman, Eva (2006)
2006Presentation
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Feldman, Eva (2007)
2007Presentation
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Feldman, Eva (2009)
2009Presentation
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No experiments found.