Digital Commons Network^™

Margaret Mitchell's Lost Letter To A Kansas Horse Buggy Doctor., Jane F. Knapp, Robert Schremmer

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Combined Fluorescence And Reflectance Spectroscopy For In Vivo Quantification Of Cancer Biomarkers In Low- And High-Grade Glioma Surgery, Pablo A. ValdéS, Anthony Kim, Keith D. Paulsen, Frederic Leblond, Olga M. Conde, Brent T. Harris, David W. Roberts

Dartmouth Scholarship

Biomarkers are indicators of biological processes and hold promise for the diagnosis and treatment of disease. Gliomas represent a heterogeneous group of brain tumors with marked intra- and inter-tumor variability. The extent of surgical resection is a significant factor influencing post-surgical recurrence and prognosis. Here, we used fluorescence and reflectance spectral signatures for in vivo quantification of multiple biomarkers during glioma surgery, with fluorescence contrast provided by exogenously-induced protoporphyrin IX (PpIX) following administration of 5-aminolevulinic acid. We performed light-transport modeling to quantify multiple biomarkers indicative of tumor biological processes, including the local concentration of PpIX and associated photoproducts, total hemoglobin …

The Raf/Mek/Extracellular Signal-Regulated Kinase 1/2 Pathway Can Mediate Growth Inhibitory And Differentiation Signaling Via Androgen Receptor Downregulation In Prostate Cancer Cells., Seung-Keun Hong, Jin-Hwan Kim, Ming-Fong Lin, Jong-In Park

Journal Articles: Biochemistry & Molecular Biology

Upregulated ERK1/2 activity is correlated with androgen receptor (AR) downregulation in certain prostate cancer (PCa) that exhibits androgen deprivation-induced neuroendocrine differentiation, but its functional relevance requires elucidation. We found that sustained ERK1/2 activation using active Raf or MEK1/2 mutants is sufficient to induce AR downregulation at mRNA and protein levels in LNCaP. Downregulation of AR protein, but not mRNA, was blocked by proteasome inhibitors, MG132 and bortezomib, indicating that the pathway regulation is mediated at multiple points. Ectopic expression of a constitutively active AR inhibited Raf/MEK/ERK-mediated regulation of the differentiation markers, neuron-specific enolase and neutral endopeptidase, and the cyclin-dependent kinase …

An Engineered Approach To Stem Cell Culture: Automating The Decision Process For Real-Time Adaptive Subculture Of Stem Cells, Dai Fei Elmer Ker, Lee E. Weiss, Silvina N. Junkers, Mei Chen, Zhaozheng Yin, Mike F. Sandbothe, Seungil Huh, Sungeun Eom, Ryoma Bise, Elvira Osuna-Highley, Takeo Kanade, Phil Gordon Campbell

Computer Science Faculty Research & Creative Works

Current cell culture practices are dependent upon human operators and remain laborious and highly subjective, resulting in large variations and inconsistent outcomes, especially when using visual assessments of cell confluency to determine the appropriate time to subculture cells. Although efforts to automate cell culture with robotic systems are underway, the majority of such systems still require human intervention to determine when to subculture. Thus, it is necessary to accurately and objectively determine the appropriate time for cell passaging. Optimal stem cell culturing that maintains cell pluripotency while maximizing cell yields will be especially important for efficient, cost-effective stem cell-based therapies. …

Childhood Obesity And Blood Pressure: Back To The Future?, Bonita Falkner, Samuel Gidding

Department of Pediatrics Faculty Papers

The prevalence of childhood hypertension is increasing.^{1, 2} Studies that apply the 95^th percentile definition and repeat measurements on three separate visits, report a pediatric hypertension prevalence of approximately 3.5%^{3, 4}, and among obese children and adolescents the prevalence of both hypertension and prehypertension is even greater. The recently documented increase in hypertension among the young is due largely to the childhood obesity epidemic and possibly other secular changes in lifestyles. These publications and others confirm that hypertension is a prevalent child health condition, especially among overweight and obese children. A consistent positive association between body …

Differential Il-21 Signaling In Apcs Leads To Disparate Th17 Differentiation In Diabetes-Susceptible Nod And Diabetes-Resistant Nod.Idd3 Mice., Sue M. Liu, David H. Lee, Jenna M. Sullivan, Denise Chung, Anneli Jäger, Bennett O V. Shum, Nora E. Sarvetnick, Ana C. Anderson, Vijay K. Kuchroo

Journal Articles: Regenerative Medicine

Type 1 diabetes (T1D) is an autoimmune disease that shows familial aggregation in humans and likely has genetic determinants. Disease linkage studies have revealed many susceptibility loci for T1D in mice and humans. The mouse T1D susceptibility locus insulin-dependent diabetes susceptibility 3 (Idd3), which has a homologous genetic interval in humans, encodes cytokine genes Il2 and Il21 and regulates diabetes and other autoimmune diseases; however, the cellular and molecular mechanisms of this regulation are still being elucidated. Here we show that T cells from NOD mice produce more Il21 and less Il2 and exhibit enhanced Th17 cell generation compared with …

Non-Geometric Echocardiographic Indices Of Ventricular Function In Patients With A Fontan Circulation., Jonathan Rhodes, Renee Margossian, Lynn A. Sleeper, Piers Barker, Timothy J. Bradley, Minmin Lu, Mark Fogel, Matthew A. Harris, Wyman W. Lai, Andrew J. Powell, Michael D. Puchalski, Girish S. Shirali, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Complex anatomy and limited windows complicate echocardiographic assessments of ventricular function in Fontan patients. For the Pediatric Heart Network Fontan Cross-Sectional Study, data were acquired from which mean ventricular pressure change during isovolumetric contraction (dP/dt(ic)), Tei index, and maximal systolic annular velocity (S') could be measured. The purpose of this study was to compare these nongeometric indices of ventricular function to cardiac magnetic resonance (CMR) measurements of ventricular ejection fraction (EF).

METHODS: Echocardiographic and CMR studies were performed prospectively using standardized protocols; measurements were completed by core laboratories. Data from both modalities were available from 137 patients.

RESULTS: A …

Characterization Of Street Food Consumption In Palermo: Possible Effects On Health, Silvio Buscemi, Annamaria Barile, Vincenza Maniaci, John A. Batsis

Dartmouth Scholarship

Background: Street Food (SF) consists of out-of-home food consumption and has old, historical roots with complex social-economic and cultural implications. Despite the emergence of modern fast food, traditional SF persists worldwide, but the relationship of SF consumption with overall health, well-being, and obesity is unknown.

Methods: This is an observational, cross-sectional study. The study was performed in Palermo, the largest town of Sicily, Italy. Two groups were identified: consumers of SF (n = 687) and conventional restaurant food (RES) consumers (n = 315). Study subjects answered a questionnaire concerning their health conditions, nutritional preferences, frequency of consumption of SF and …

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation: A Phase 1/2 Trial Performed With Optimized T-Cell Dosing., Dolores Gross, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg …

Manganese Superoxide Dismutase: Guardian Of The Powerhouse, Aaron K. Holley, Vasudevan Bakthavatchalu, Joyce M. Velez-Roman, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese …

Cardiovascular Magnetic Resonance Myocardial Feature Tracking Detects Quantitative Wall Motion During Dobutamine Stress., Andreas Schuster, Shelby Kutty, Asif Padiyath, Victoria Parish, Paul Gribben, David A. Danford, Marcus R. Makowski, Boris Bigalke, Philipp Beerbaum, Eike Nagel

Journal Articles: Pediatrics

BACKGROUND: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) is an established tool to assess hibernating myocardium and ischemia. Analysis is typically based on visual assessment with considerable operator dependency. CMR myocardial feature tracking (CMR-FT) is a recently introduced technique for tissue voxel motion tracking on standard steady-state free precession (SSFP) images to derive circumferential and radial myocardial mechanics.We sought to determine the feasibility and reproducibility of CMR-FT for quantitative wall motion assessment during intermediate dose DS-CMR.

METHODS: 10 healthy subjects were studied at 1.5 Tesla. Myocardial strain parameters were derived from SSFP cine images using dedicated CMR-FT software (Diogenes MRI prototype; …

Duration Of Symptoms Resulting From Lumbar Disc Herniation: Effect On Treatment Outcomes: Analysis Of The Spine Patient Outcomes Research Trial (Sport)., Jeffrey A Rihn, Alan Hilibrand, Kristen Radcliff, Mark Kurd, Jon Lurie, Emily Blood, Todd J Albert, James N Weinstein

Rothman Institute Papers

BACKGROUND: The purpose of the present study was to determine if the duration of symptoms affects outcomes following the treatment of intervertebral lumbar disc herniation.

METHODS: An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial (SPORT) for the treatment of intervertebral lumbar disc herniation. Randomized and observational cohorts were combined. A comparison was made between patients who had had symptoms for six months or less (n = 927) and those who had had symptoms for more than six months (n = 265). Primary and secondary outcomes were measured at baseline and at regular follow-up …

Duration Of Symptoms Resulting From Lumbar Disc Herniation: Effect On Treatment Outcomes: Analysis Of The Spine Patient Outcomes Research Trial (Sport)., Jeffrey A Rihn, Alan S Hilibrand, Kristen Radcliff, Mark Kurd, Jon Lurie, Emily Blood, Todd J Albert, James N Weinstein

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The purpose of the present study was to determine if the duration of symptoms affects outcomes following the treatment of intervertebral lumbar disc herniation.

METHODS: An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial (SPORT) for the treatment of intervertebral lumbar disc herniation. Randomized and observational cohorts were combined. A comparison was made between patients who had had symptoms for six months or less (n = 927) and those who had had symptoms for more than six months (n = 265). Primary and secondary outcomes were measured at baseline and at regular follow-up …

Pre- And Post-Bronchodilator Lung Function As Predictors Of Mortality In The Lung Health Study, David M. Mannino, Enrique Diaz-Guzman, Sonia Buist

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is supposed to be classified on the basis of post-bronchodilator lung function. Most longitudinal studies of COPD, though, do not have post-bronchodilator lung function available. We used pre-and post bronchodilator lung function data from the Lung Health Study to determine whether these measures differ in their ability to predict mortality.

METHODS: We limited our analysis to subjects who were of black or white race, on whom we had complete data, and who participated at either the 1 year or the 5 year follow-up visit. We classified subjects based on their baseline lung function, according …

Regional Gray Matter Correlates Of Perceived Emotional Intelligence, Nancy S. Koven, Robert M. Roth, Matthew A. Garlinghouse, Laura A. Flashman, Andrew J. Saykin

Dartmouth Scholarship

Coping with stressful life events requires a degree of skill in the ability to attend to, comprehend, label, communicate and regulate emotions. Individuals vary in the extent to which these skills are developed, with the term ‘alexithymia’ often applied in the clinical and personality literature to those individuals most compromised in these skills. Although a frontal lobe model of alexithymia is emerging, it is unclear whether such a model satisfactorily reflects brain-related patterns associated with perceived emotional intelligence at the facet level. To determine whether these trait meta-mood facets (ability to attend to, have clarity of and repair emotions) have …

Microarray-Based Cancer Prediction Using Single Genes., Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Although numerous methods of using microarray data analysis for cancer classification have been proposed, most utilize many genes to achieve accurate classification. This can hamper interpretability of the models and ease of translation to other assay platforms. We explored the use of single genes to construct classification models. We first identified the genes with the most powerful univariate class discrimination ability and then constructed simple classification rules for class prediction using the single genes.

RESULTS: We applied our model development algorithm to eleven cancer gene expression datasets and compared classification accuracy to that for standard methods including Diagonal Linear …

Demasculinization And Feminization Of Male Gonads By Atrazine: Consistent Effects Across Vertebrate Classes, Krista A. Mccoy

Integrative Biology Faculty and Staff Publications

Atrazine is the most commonly detected pesticide contaminant of ground water, surface water, and precipitation. Atrazine is also an endocrine disruptor that, among other effects, alters male reproductive tissues when animals are exposed during development. Here, we apply the nine so-called “Hill criteria” (Strength, Consistency, Specificity, Temporality, Biological Gradient, Plausibility, Coherence, Experiment, and Analogy) for establishing cause–effect relationships to examine the evidence for atrazine as an endocrine disruptor that demasculinizes and feminizes the gonads of male vertebrates. We present experimental evidence that the effects of atrazine on male development are consistent across all vertebrate classes examined and we present a …

Ethics And The 'Seasons Of My Life' As A Dental Educator, David A. Nash

Oral Health Science Faculty Publications

Perhaps the first comprehensive ethics program in American dental schools was created in 1990 at the University of Kentucky by then dean David Nash. Nash recounts the emergence of his personal and professional interest in ethics using the structure of Daniel Levinson's book The Seasons of a Man's Life. Each season brings tasks of evolving and deepening ethical engagement. Being ethical is important; helping others to be so is special. Nash still teaches the course.

Food Insecurity And Sexual Risk In An Hiv Endemic Community In Uganda, Cari L. Miller, David R. Bangsberg, David M. Tuller, Jude Senkungu, Annet Kawuma, Edward A. Frongillo Jr., Sheri D. Weiser

Faculty Publications

Food insecurity has been linked to high-risk sexual behavior in sub-Saharan Africa, but there are limited data on these links among people living with HIV/AIDS, and on the mechanisms for how food insecurity predisposes individuals to risky sexual practices. We undertook a series of in-depth open-ended interviews with 41 individuals living with HIV/AIDS to understand the impact of food insecurity on sexual-risk behaviors. Participants were recruited from the Immune Suppression Clinic at the Mbarara University of Science and Technology in Mbarara, Uganda. Interviews were recorded, transcribed verbatim, translated, and coded following the strategy of grounded theory. Four major themes emerged …

A Tool To Measure The Attributes Of Receiving Iv Therapy In A Home Versus Hospital Setting: The Multiple Sclerosis Relapse Management Scale (Msrms)., Afsane Riazi, Bernadette Porter, Jeremy Chataway, Alan J. Thompson, Jeremy C. Hobart

Peninsula Medical School

BACKGROUND: Intravenous steroids are routinely used to treat disabling relapses in multiple sclerosis (MS). Theoretically, the infusion could take place at home, rather than in hospital. Findings from other patient populations suggest that patients may find the experiences of home relapse management more desirable. However, formal comparison of these two settings, from the patients' point of view, was prevented by the lack of a clinical scale. We report the development of a rating scale to measure patient's experiences of relapse management that allowed this question to be answered confidently. METHODS: Scale development had three stages. First, in-depth interviews of 21 …

Strain-Dependent Variation In The Early Transcriptional Response To Cns Injury Using A Cortical Explant System, David J. Graber, Brent T. Harris, William F. Hickey

Dartmouth Scholarship

While it is clear that inbred strains of mice have variations in immunological responsiveness, the influence of genetic background following tissue damage in the central nervous system is not fully understood. A cortical explant system was employed as a model for injury to determine whether the immediate transcriptional response to tissue resection revealed differences among three mouse strains. Immunological mRNAs were measured in cerebral cortex from SJL/J, C57BL/6J, and BALB/cJ mice using real time RT-PCR. Freshly isolated cortical tissue and cortical sections incubated in explant medium were examined. Levels of mRNA, normalized to β-actin, were compared using one way analysis …

Rna Oxidation Adducts 8-Ohg And 8-Oha Change With Aβ42 Levels In Late-Stage Alzheimer's Disease, Adam M. Weidner, Melissa A. Bradley, Tina L. Beckett, Dana M. Niedowicz, Amy L.S. Dowling, Sergey V. Matveev, Harry Levine, Mark A. Lovell, M. Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain …

In Vivo Microdialysis Reveals Age-Dependent Decrease Of Brain Interstitial Fluid Tau Levels In P301s Human Tau Transgenic Mice, Kaoru Yamada, John R. Cirrito, Floy R. Stewart, Hong Jiang, Mary Beth Finn, Brandon B. Holmes, Lester I. Binder, Eva-Maria Mandelkow, Marc I. Diamond, Virginia M.-Y. Lee, David M. Holtzman

Open Access Publications

Although tau is a cytoplasmic protein, it is also found in brain extracellular fluids, e.g., CSF. Recent findings suggest that aggregated tau can be transferred between cells and extracellular tau aggregates might mediate spread of tau pathology. Despite these data, details of whether tau is normally released into the brain interstitial fluid (ISF), its concentration in ISF in relation to CSF, and whether ISF tau is influenced by its aggregation are unknown. To address these issues, we developed a microdialysis technique to analyze monomeric ISF tau levels within the hippocampus of awake, freely moving mice. We detected tau in ISF …

Activation Of Matrix Metalloproteinases Following Anti-Aβ Immunotherapy; Implications For Microhemorrhage Occurrence, Donna M. Wilcock, Dave Morgan, Marcia N. Gordon, Tiffany L. Taylor, Lisa A. Ridnour, David A. Wink, Carol A. Colton

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s) by which they occur.

METHODS: We have examined the matrix metalloproteinase (MMP) protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which …

The Meaning Of Breast Cancer Risk For African American Women., Janice Phillips, Marlene Z. Cohen

Journal Articles: College of Nursing

PURPOSE: To describe African American women's experience of being at high risk for breast cancer.

DESIGN: A hermeneutic phenomenological approach was used to guide in-depth interviews and analysis. Methods to ensure trustworthiness and rigor were included.

METHODS: Open interviews were conducted with 20 African American women who were at high risk for breast cancer (family history, personal history, genetic mutation). They were recruited from a cancer risk clinic and community-based settings. Data were transcribed verbatim, and themes were labeled among and between all interviews.

FINDINGS: Five themes were identified: (a) life-changing experience; (b) relationships: fears, support, and concerns; (c) the …

John H. Gibbon, Jr., M.D.: Surgical Innovator, Pioneer, And Inspiration., Jordan P. Bloom, B.S., Charles J. Yeo, Md, Herbert E. Cohn, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Throughout history there have been many discoveries that have changed the world, including Albert Einstein’s theory of relativity, Alexander Graham Bell’s telephone, and Jack Kilby and Robert Noyce’s microchip. There are a few analogous contributions that have been made in medicine: Sir Alexander’s discovery of penicillin, Lister’s principles of antiseptic technique, Salk and Sabin’s vaccines for polio, as well as numerous others. These innovative thinkers all had two factors in common. First, they were pioneers who faced problems that had no solutions at the time and who refused to accept the status quo in the face of great scrutiny and …

Mechanisms Of Resistance To Raf Inhibitors In Melanoma., A E Aplin, Fred M Kaplan, Yongping Shao

Department of Cancer Biology Faculty Papers

The recent RAF inhibitor trial with PLX4032/RG7204 in late-stage mutant B-RAF melanoma patients has been lauded as a success story for personalized cancer therapy since short-term clinical responses were observed in the majority of patients. However, initial responses were followed by subsequent tumor re-growth, and a subset of patients showed intrinsic resistance. Bi-directional translational efforts are now essential to determine the mechanisms underlying acquired/secondary and intrinsic resistance to RAF inhibitors.

Scleroderma Renal Crisis-Like Acute Renal Failure Associated With Mucopolysaccharide Accumulation In Renal Vessels In A Patient With Scleromyxedema., Young H Lee, Joya Sahu, Marie S O'Brien, Vivette D D'Agati, Sergio A. Jimenez

Scleroderma Center Faculty Papers

Scleromyxedema is a systemic disease characterized by lichenoid papules, nodules, and plaques on the skin and often diffuse skin induration resembling the cutaneous involvement of systemic sclerosis. The systemic involvement affects the musculoskeletal, pulmonary, cardiovascular, gastrointestinal, and central nervous systems, and the disorder is commonly associated with a paraproteinemia. Involvement of the kidney is rare and not considered a feature of the disease. Here, we describe an unusual case of scleromyxedema complicated by the development of scleroderma renal crisis-like acute renal failure with a marked intimal deposition of mucin, mucopolysaccharides, and hyaluronic acid in the intrarenal vessels.

Protoporphyrin Ix Fluorescence Contrast In Invasive Glioblastomas Is Linearly Correlated With Gd Enhanced Magnetic Resonance Image Contrast But Has Higher Diagnostic Accuracy, Kimberley S. Samkoe, Summer L. Gibbs-Strauss, Harold H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, Julia A. O'Hara, Risto A. Kauppinen, Brian W. Pogue

Dartmouth Scholarship

The sensitivity and specificity of in vivo magnetic resonance (MR) imaging is compared with production of protoporphyrin IX (PpIX), determined ex vivo, in a diffusely infiltrating glioma. A human glioma transfected with green fluorescent protein, displaying diffuse, infiltrative growth, was implanted intracranially in athymic nude mice. Image contrast from corresponding regions of interest (ROIs) in in vivo MR and ex vivo fluorescence images was quantified. It was found that all tumor groups had statistically significant PpIX fluorescence contrast and that PpIX contrast demonstrated the best predictive power for tumor presence. Contrast from gadolinium enhanced T1-weighted (T1W+Gd) and absolute T2 …

Laforin, A Dual Specificity Phosphatase Involved In Lafora Disease, Is Present Mainly As Monomeric Form With Full Phosphatase Activity, Vikas V. Dukhande, Devin M. Rogers, Carlos Romá-Mateo, Jordi Donderis, Alberto Marina, Adam O. Taylor, Pascual Sanz, Matthew S. Gentry

Molecular and Cellular Biochemistry Faculty Publications

Lafora Disease (LD) is a fatal neurodegenerative epileptic disorder that presents as a neurological deterioration with the accumulation of insoluble, intracellular, hyperphosphorylated carbohydrates called Lafora bodies (LBs). LD is caused by mutations in either the gene encoding laforin or malin. Laforin contains a dual specificity phosphatase domain and a carbohydrate-binding module, and is a member of the recently described family of glucan phosphatases. In the current study, we investigated the functional and physiological relevance of laforin dimerization. We purified recombinant human laforin and subjected the monomer and dimer fractions to denaturing gel electrophoresis, mass spectrometry, phosphatase assays, protein-protein interaction assays, …