A5019647640- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Obsessive-Compulsive Spectrum Disorders
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Ergonomics and Musculoskeletal Disorders
- CRISPR and Genetic Engineering
- Musculoskeletal pain and rehabilitation
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Autism Spectrum Disorder Research
- Animal Genetics and Reproduction
- Heart Rate Variability and Autonomic Control
- DNA and Nucleic Acid Chemistry
- Marriage and Sexual Relationships
- DNA Repair Mechanisms
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Nail Diseases and Treatments
- Parkinson's Disease Mechanisms and Treatments
- Protein Degradation and Inhibitors
- Sexuality, Behavior, and Technology
- Heat shock proteins research
- Phosphodiesterase function and regulation
- Fibromyalgia and Chronic Fatigue Syndrome Research
Massachusetts Institute of Technology
1994-2012
University of Minnesota
2006-2011
Institute of Human Genetics
2011
Center for Cancer Research
2008
University of California, Berkeley
1996-2001
Howard Hughes Medical Institute
1996
Texas College
1993
University of Minnesota Medical Center
1991
University of North Texas
1980-1989
To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results these inconsistent, likely as a consequence small sample sizes variable methodologies. Furthermore, data concerning heritability factors are limited. Item category-level YBOCS-CL items from 1224 OCD subjects were followed by in 52 OCD-affected...
The sterol regulatory element binding proteins (SREBP-1 and -2) activate transcription of genes whose products are involved in the cellular uptake synthesis cholesterol. Although considerable effort has been exerted to define events regulating levels active SREBP, little is known about transcriptional cofactors mediating SREBP function. In an unbiased search for potential coactivators we isolated a protein 265 kD from HeLa cells that directly bound SREBP-1 SREBP-2. Peptide sequencing Western...
Summary Age of onset for Huntington's disease (HD) varies inversely with the length disease‐causing CAG repeat expansion in HD gene. A simple exponential regression model yielded adjusted R‐squared values 0.728 a large set Venezuelan kindreds and 0.642 North American, European, Australian sample (the MAPS cohort). We present evidence that two‐segment curve provides significantly better fit than regression. plot natural log‐transformed age against reveals this segmental relationship. This on...
The major determinant of age onset in Huntington's disease is the length causative triplet CAG repeat. Significant variance remains, however, residual even after repeat factored out. Many genetic polymorphisms have previously shown evidence association with several different populations.To replicate these tests 443 affected people from a large set kindreds Venezuela.Previously tested were analysed HD gene itself (HD), GluR6 kainate glutamate receptor (GRIK2), apolipoprotein E (APOE),...
The age of onset Huntington's disease (HD) is inversely correlated with the CAG length in HD gene. repeat accounts for 70% variability onset. However, 90% individuals worldwide expanded alleles possess between 40 and 50 lengths their For these people, size only determines 44% Once effect has been accounted for, residual variance a heritable trait. Targeted candidate gene studies genome scan have suggested some loci as potential modifiers HD. We analyzed large Venezuelan kindreds which was...
Spinocerebellar ataxia type 1 (SCA1) is one of nine dominantly inherited neurodegenerative diseases caused by polyglutamine tract expansion. In SCA1, the expanded in ataxin-1 (ATXN1) protein. ATXN1 part an vivo complex with retinoid acid receptor-related orphan receptor alpha (Rora) and acetyltransferase tat-interactive protein 60 kDa (Tip60). Tip60 interact directly via HMG-box (AXH) domain ATXN1. Moreover, phospho-mimicking Asp amino at position 776, previously shown to enhance...
Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited neurodegenerative disorders caused by a mutant protein with an expanded polyglutamine tract. Phosphorylation ataxin-1 (ATXN1) at serine 776 implicated in SCA1 pathogenesis. Previous studies, utilizing transfected cell lines and Drosophila photoreceptor model SCA1, suggest that phosphorylating ATXN1 S776 renders it less susceptible to degradation. This work also indicated oncogene from AKR mouse thymoma (Akt) promotes the...
We examined the aortic baroreflex control of heart rate (HR) in seven healthy young men average fitness (AF) and high (HF). The level was determined by maximal oxygen uptake (AF = 42.9 +/- 1.1, HF 62.3 1.8 ml.kg-1.min-1). Aortic HR during a steady-state increase mean arterial pressure (MAP; AF, +15.0 2.1 HF, +18.3 0.8 mmHg) with phenylephrine (PE) infusion combined positive neck (NP; 18 2.0 20 to counteract increased carotid sinus low levels lower body negative central venous pressure. There...
Abstract Objective To screen a library of potential therapeutic compounds for woman with Lennox‐Gastaut syndrome due to Y302C GABRB3 (c.905A>G) mutation. Methods We compared the electrophysiological properties cells wild‐type or pathogenic Results Among 1320 compounds, multiple candidates enhanced channel conductance in cell models. Vinpocetine, an alkaloid derived from periwinkle plant anti‐inflammatory and ability modulate sodium channels, was lead candidate based on efficacy safety...
Abstract The instability of the CAG repeat size HD gene when transmitted intergenerationally has critical implications for genetic counseling practices. In particular, repeats between 27 and 35 have been subject debate based on small samples. To address this issue, we analyzed allelic in Venezuelan kindreds, largest most informative families ascertained HD. We identified 647 transmissions. Our results indicate that 27‐35 range are highly stable. Out 69 alleles range, none expand into any...
We have developed a low stringency polymerase chain reaction (LSPCR) to isolate the unknown neighboring region around known DNA sequence, thus allowing efficient targeted gene walking. The method involves (PCR) with single primer under conditions of for annealing (40 degrees C) first few cycles followed by more at high (55 C). This enables amplification fragment along other nontargeted fragments. High nested PCRs end-labeled primers are then used generate ladder radioactive bands, which...
We have identified four putative human sodium channel gene sequences, 55 bp each, using the polymerase chain reaction (PCR) on total placental DNA with primers specific for cDNA sequence of rat brain Iα <i>(Scn1a</i>) gene. One these sequences was extended bidirectionally by genomic inverse-PCR to obtain a 1.6-kb fragment. Sequencing this 1,556-bp fragment showed 282-bp complete exon, which has 95% and 94% homology at nucleotide amino acid levels, respectively, <i>Scn1a...
The sites of action for somatostatin and epinephrine to inhibit insulin secretion have been reported be exclusively in the exocytotic pathway. We used HIT cells, a clonal line β-cells, examine whether these hormones might as yet undescribed, nonexocytotic effects on messenger RNA levels. observed that both not only (53 ± 2% 50 control, respectively) but also decrease mRNA levels (54 5% 66 content cells (61 51 1% respectively). latter two are discernible by 24 h, maximal 48 prevented...
Abstract Spinocerebellar ataxia type 1 (SCA1) is an inherited neurodegenerative disorder. The mutation causing SCA1 expansion in the polyglutamine tract of ATXN1 protein. Previous work demonstrated that phosphorylation mutant at serine 776 (S776), a putative Akt site, critical for pathogenesis. To examine this pathway further, we utilized cell‐transfection system allowed targeting to either cytoplasm or nucleus. In contrast HeLa cells, found targeted increased degradation Chinese hamster...
Propeptide processing occurs in specific compartments of the secretory pathway, but how these processing-competent organelles are generated from their processing-incompetent precursor is unknown. To dissect process biochemically, we have developed a novel cell-free system reconstituting production granules AtT-20 cells. Using donor membranes containing [35S]sulfate labeled pro-opiomelanocortin (POMC)5 trans-Golgi, can reconstitute cytosol- and ATP-dependent prohormone as well incorporation...
Smith, J. C.; Davis, G. M. FACSM; Dobson, E.; Andresen, J.; Shelton, H.; Simmons, Author Information