Medicine and Health Sciences Commons^™

Biological Diversity Of Prokaryotic Type Iv Secretion Systems, Cristina E Alvarez-Martinez, Peter J Christie

Faculty, Staff and Student Publications

Type IV secretion systems (T4SS) translocate DNA and protein substrates across prokaryotic cell envelopes generally by a mechanism requiring direct contact with a target cell. Three types of T4SS have been described: (i) conjugation systems, operationally defined as machines that translocate DNA substrates intercellularly by a contact-dependent process; (ii) effector translocator systems, functioning to deliver proteins or other macromolecules to eukaryotic target cells; and (iii) DNA release/uptake systems, which translocate DNA to or from the extracellular milieu. Studies of a few paradigmatic systems, notably the conjugation systems of plasmids F, R388, RP4, and pKM101 and the Agrobacterium tumefaciens VirB/VirD4 system, …

Dopamine-Stimulated Dephosphorylation Of Connexin 36 Mediates Aii Amacrine Cell Uncoupling, W Wade Kothmann, Stephen C Massey, John O'Brien

Faculty, Staff and Student Publications

Gap junction proteins form the substrate for electrical coupling between neurons. These electrical synapses are widespread in the CNS and serve a variety of important functions. In the retina, connexin 36 (Cx36) gap junctions couple AII amacrine cells and are a requisite component of the high-sensitivity rod photoreceptor pathway. AII amacrine cell coupling strength is dynamically regulated by background light intensity, and uncoupling is thought to be mediated by dopamine signaling via D(1)-like receptors. One proposed mechanism for this uncoupling involves dopamine-stimulated phosphorylation of Cx36 at regulatory sites, mediated by protein kinase A. Here we provide evidence against this hypothesis …

5-Ht And Gaba Modulate Intrinsic Excitability Of Type I Interneurons In Hermissenda, Nan Ge Jin, Lian-Ming Tian, Terry Crow

Faculty, Staff and Student Publications

The sensory neurons (photoreceptors) in the visual system of Hermissenda are one site of plasticity produced by Pavlovian conditioning. A second site of plasticity produced by conditioning is the type I interneurons in the cerebropleural ganglia. Both photoreceptors and statocyst hair cells of the graviceptive system form monosynaptic connections with identified type I interneurons. Two proposed neurotransmitters in the graviceptive system, serotonin (5-HT) and gamma-aminobutyric acid (GABA), have been shown to modify synaptic strength and intrinsic neuronal excitability in identified photoreceptors. However, the potential role of 5-HT and GABA in plasticity of type I interneurons has not been investigated. Here …

Comparing Clinician Knowledge And Online Information Regarding Alli (Orlistat), Stuart Nelson, Kevin O Hwang, Elmer V Bernstam

Faculty, Staff and Student Publications

BACKGROUND: Many consumers join online communities focused on health. Online forums are a popular medium for the exchange of health information between consumers, so it is important to determine the accuracy and completeness of information posted to online forums.

OBJECTIVE: We compared the accuracy and completeness of information regarding the FDA-approved over-the counter weight-loss drug Alli (Orlistat) from forums and from clinicians.

METHODS: We identified Alli-related questions posted on online forums and then posed the questions to 11 primary care providers. We then compared the clinicians' answers to the answers given on the forums. A panel of blinded experts evaluated …

Cross Currents In Protein Misfolding Disorders: Interactions And Therapy, Rodrigo Morales, Kristi M Green, Claudio Soto

Faculty, Staff and Student Publications

Protein Misfolding Disorders (PMDs) are a group of diseases characterized by the accumulation of abnormally folded proteins. Despite the wide range of proteins and tissues involved, PMDs share similar molecular and pathogenic mechanisms. Several epidemiological, clinical and experimental reports have described the co-existence of PMDs, suggesting a possible cross-talk between them. A better knowledge of the molecular basis of PMDs could have important implications for understanding the mechanism by which these diseases appear and progress and ultimately to develop novel strategies for treatment. Due to their similar molecular mechanisms, common therapeutic strategies could be applied for the diseases in this …

Adherence To Host Extracellular Matrix And Serum Components By Enterococcus Faecium Isolates Of Diverse Origin, Meng Zhao, Jouko Sillanpää, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium has emerged as an important cause of nosocomial infections over the last two decades. We recently demonstrated collagen type I (CI) as a common adherence target for some E. faecium isolates and a significant correlation was found to exist between acm-mediated CI adherence and clinical origin. Here, we evaluated 60 diverse E. faecium isolates for their adherence to up to 15 immobilized host extracellular matrix and serum components. Adherence phenotypes were most commonly observed to fibronectin (Fn) (20% of the 60 isolates), fibrinogen (17%) and laminin (Ln) (13%), while only one or two of the isolates adhered to …

Keap1 E3 Ligase-Mediated Downregulation Of Nf-Kappab Signaling By Targeting Ikkbeta, Dung-Fang Lee, Hsu-Ping Kuo, Mo Liu, Chao-Kai Chou, Weiya Xia, Yi Du, Jia Shen, Chun-Te Chen, Longfei Huo, Ming-Chuan Hsu, Chia-Wei Li, Qingqing Ding, Tsai-Lien Liao, Chien-Chen Lai, Ann-Chi Lin, Ya-Hui Chang, Shih-Feng Tsai, Long-Yuan Li, Mien-Chie Hung

Faculty, Staff and Student Publications

IkappaB kinase beta (IKKbeta) is involved in tumor development and progression through activation of the nuclear factor (NF)-kappaB pathway. However, the molecular mechanism that regulates IKKbeta degradation remains largely unknown. Here, we show that a Cullin 3 (CUL3)-based ubiquitin ligase, Kelch-like ECH-associated protein 1 (KEAP1), is responsible for IKKbeta ubiquitination. Depletion of KEAP1 led to the accumulation and stabilization of IKKbeta and to upregulation of NF-kappaB-derived tumor angiogenic factors. A systematic analysis of the CUL3, KEAP1, and RBX1 genomic loci revealed a high percentage of genome loss and missense mutations in human cancers that failed to facilitate IKKbeta degradation. Our …

Intracranial Eeg Reveals A Time- And Frequency-Specific Role For The Right Inferior Frontal Gyrus And Primary Motor Cortex In Stopping Initiated Responses, Nicole Swann, Nitin Tandon, Ryan Canolty, Timothy M Ellmore, Linda K Mcevoy, Stephen Dreyer, Michael Disano, Adam R Aron

Faculty, Staff and Student Publications

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band ( approximately 16 Hz) …

Ethnic Differences In Do-Not-Resuscitate Orders After Intracerebral Hemorrhage, Darin B Zahuranec, Devin L Brown, Lynda D Lisabeth, Nicole R Gonzales, Paxton J Longwell, Melinda A Smith, Nelda M Garcia, Lewis B Morgenstern

Faculty, Staff and Student Publications

OBJECTIVE: To explore ethnic differences in do-not-resuscitate orders after intracerebral hemorrhage.

DESIGN: Population-based surveillance.

SETTING: Corpus Christi, Texas.

PATIENTS: All cases of intracerebral hemorrhage in the community of Corpus Christi, TX were ascertained as part of the Brain Attack Surveillance in Corpus Christi (BASIC) project.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for do-not-resuscitate orders. Unadjusted and multivariable logistic regression were used to test for associations between ethnicity and do-not-resuscitate orders, both overall ("any do-not-resuscitate") and within 24 hrs of presentation ("early do-not-resuscitate"), adjusted for age, gender, Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage, infratentorial hemorrhage, …

Clinical Decision Support Capabilities Of Commercially-Available Clinical Information Systems, Adam Wright, Dean F Sittig, Joan S Ash, Sapna Sharma, Justine E Pang, Blackford Middleton

Faculty, Staff and Student Publications

BACKGROUND: The most effective decision support systems are integrated with clinical information systems, such as inpatient and outpatient electronic health records (EHRs) and computerized provider order entry (CPOE) systems. Purpose The goal of this project was to describe and quantify the results of a study of decision support capabilities in Certification Commission for Health Information Technology (CCHIT) certified electronic health record systems.

METHODS: The authors conducted a series of interviews with representatives of nine commercially available clinical information systems, evaluating their capabilities against 42 different clinical decision support features.

RESULTS: Six of the nine reviewed systems offered all the applicable …

Advances In Progenitor Cell Therapy Using Scaffolding Constructs For Central Nervous System Injury, Peter A Walker, Kevin R Aroom, Fernando Jimenez, Shinil K Shah, Matthew T Harting, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and …

Modern Approaches To Pediatric Brain Injury Therapy, Peter A Walker, Matthew T Harting, James E Baumgartner, Stephen Fletcher, Nathan Strobel, Charles S Cox

Faculty, Staff and Student Publications

Each year, pediatric traumatic brain injury (TBI) accounts for 435,000 emergency department visits, 37,000 hospital admissions, and approximately 2,500 deaths in the United States. TBI results in immediate injury from direct mechanical force and shear. Secondary injury results from the release of biochemical or inflammatory factors that alter the loco-regional milieu in the acute, subacute, and delayed intervals after a mechanical insult. Preliminary preclinical and clinical research is underway to evaluate the benefit from progenitor cell therapeutics, hypertonic saline infusion, and controlled hypothermia. However, all phase III clinical trials investigating pharmacologic monotherapy for TBI have shown no benefit. A recent …

Dicer Is Required For Female Reproductive Tract Development And Fertility In The Mouse, Gabriel Gonzalez, Richard R Behringer

Faculty, Staff and Student Publications

Dicer encodes a riboendonuclease required for microRNA biosynthesis. Dicer was inactivated in Müllerian duct mesenchyme-derived tissues of the reproductive tract of the mouse, using an Amhr2-Cre allele. Although Amhr2-Cre; Dicer conditional mutant males appeared normal and were fertile, mutant females were infertile. In adult mutant females, there was a reduction in the size of the oviducts and uterine horns. The oviducts were less coiled compared to controls and cysts formed at the isthmus near the uterotubal junction. Unfertilized, degenerate oocytes were commonly found within these cysts, indicating a defect in embryo transit. Beads transferred into the mutant oviduct failed to …

Improving Clinical Quality Indicators Through Electronic Health Records: It Takes More Than Just A Reminder, Dean F Sittig, Jonathan M Teich, Jerome A Osheroff, Hardeep Singh

Faculty, Staff and Student Publications

No abstract provided.

Therapeutic Targeting Of Atp7b In Ovarian Carcinoma, Lingegowda S Mangala, Vesna Zuzel, Rosemarie Schmandt, Erik S Leshane, Jyotsna B Halder, Guillermo N Armaiz-Pena, Whitney A Spannuth, Takemi Tanaka, Mian M K Shahzad, Yvonne G Lin, Alpa M Nick, Christopher G Danes, Jeong-Won Lee, Nicholas B Jennings, Pablo E Vivas-Mejia, Judith K Wolf, Robert L Coleman, Zahid H Siddik, Gabriel Lopez-Berestein, Svetlana Lutsenko, Anil K Sood

Faculty, Staff and Student Publications

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models.

EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).

RESULTS: ATP7A …

Antibodies Targeting Hepatoma-Derived Growth Factor As A Novel Strategy In Treating Lung Cancer, Hening Ren, Zuoming Chu, Li Mao

Faculty, Staff and Student Publications

Hepatoma-derived growth factor (HDGF) is overexpressed in lung cancer and the overexpression correlates with aggressive biological behaviors and poor clinical outcomes. We developed anti-HDGF monoclonal antibodies and tested their antitumor activity in lung cancer xenograft models. We also determined biological effects in tumors treated with the antibody alone or in combination with bevacizumab/avastin (an anti-vascular endothelial growth factor antibody) and/or gemcitabine (a chemotherapeutic agent). We found the anti-HDGF was effective to inhibit tumor growth in non-small cell lung cancer xenograft models. In the A549 model, compared with control IgG, tumor growth was substantially inhibited in animals treated with anti-HDGF antibodies, …

Evaluating Statistical Methods Used To Estimate The Number Of Postsynaptic Receptors, Georgios Kalantzis, Yoshira Kubota, Harel Z Shouval

Faculty, Staff and Student Publications

Calcium levels in spines play a significant role in determining the sign and magnitude of synaptic plasticity. The magnitude of calcium influx into spines is highly dependent on influx through N-methyl D-aspartate (NMDA) receptors, and therefore depends on the number of postsynaptic NMDA receptors in each spine. We have calculated previously how the number of postsynaptic NMDA receptors determines the mean and variance of calcium transients in the postsynaptic density, and how this alters the shape of plasticity curves. However, the number of postsynaptic NMDA receptors in the postsynaptic density is not well known. Anatomical methods for estimating the number …

Physical And Functional Interaction Between The Dopamine Transporter And The Synaptic Vesicle Protein Synaptogyrin-3, Loreto A Egaña, Rolando A Cuevas, Tracy B Baust, Leonardo A Parra, Rehana K Leak, Sarah Hochendoner, Karina Peña, Marisol Quiroz, Weimin C Hong, Mario M Dorostkar, Roger Janz, Harald H Sitte, Gonzalo E Torres

Faculty, Staff and Student Publications

Uptake through the dopamine transporter (DAT) represents the primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that dopamine (DA) taken up by the transporter is used to replenish synaptic vesicle stores for subsequent release, the molecular details of this mechanism are not completely understood. Here, we identified the synaptic vesicle protein synaptogyrin-3 as a DAT interacting protein using the split ubiquitin system. This interaction was confirmed through coimmunoprecipitation experiments using heterologous cell lines and mouse brain. DAT and synaptogyrin-3 colocalized at presynaptic terminals from mouse striatum. Using fluorescence resonance energy transfer microscopy, we show …

Use Of Instructional Video To Prepare Parents For Learning Infant Cardiopulmonary Resuscitation, Timothy S. Brannon, Lisa A. White, Julie N. Kilcrease, Lashawn D. Richard, Jana G. Spillers, Cynthia L. Phelps

Faculty, Staff and Student Publications

Parents of premature infants often receive infant cardiopulmonary resuscitation (CPR) training prior to discharge from the hospital, but one study showed that 27.5% of parents could not demonstrate adequate CPR skills after completing an instructor-led class. We hypothesized that parents who viewed an instructional video on infant CPR before attending the class would perform better on a standardized skills test than parents who attended the class with no preparation. Parents randomized to the intervention (video) group viewed the video within 48 hours of the CPR class. Parents in the control group attended the class with no special preparation. All parents …

Long-Term Survival After Multidisciplinary Management Of Resected Pancreatic Adenocarcinoma, Matthew H G Katz, Huamin Wang, Jason B Fleming, Charlotte C Sun, Rosa F Hwang, Robert A Wolff, Gauri Varadhachary, James L Abbruzzese, Christopher H Crane, Sunil Krishnan, Jean-Nicolas Vauthey, Eddie K Abdalla, Jeffrey E Lee, Peter W T Pisters, Douglas B Evans

Faculty, Staff and Student Publications

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.

METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed.

RESULTS: …

Comorbidities, Patient Knowledge, And Disease Management In A National Sample Of Patients With Copd, R Graham Barr, Bartolome R Celli, David M Mannino, Thomas Petty, Stephen I Rennard, Frank C Sciurba, James K Stoller, Byron M Thomashow, Gerard M Turino

Faculty, Staff and Student Publications

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States but is often undertreated. COPD often overlaps with other conditions such as hypertension and osteoporosis, which are less morbid but may be treated more aggressively. We evaluated the prevalence of these comorbid conditions and compared testing, patient knowledge, and management in a national sample of patients with COPD.

METHODS: A survey was administered by telephone in 2006 to 1003 patients with COPD to evaluate the prevalence of comorbid conditions, diagnostic testing, knowledge, and management using standardized instruments. The completion rate was 87%.

RESULTS: …

Antibiotic Resistance In Staphylococcus Aureus-Containing Cutaneous Abscesses Of Patients With Hiv, Gus W Krucke, Deanna E Grimes, Richard M Grimes, Thai D Dang

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to document the resistance patterns found in exudates from cutaneous abscesses of HIV-infected persons.

BASIC PROCEDURES: Patient records were reviewed on 93 culture and sensitivity tests performed on exudates taken from incised and drained abscesses of HIV-infected persons.

MAIN FINDINGS: Of the specimens, 84.6% were Staphylococcus aureus. Of these, 93.5% were penicillin resistant, 87% oxacillin resistant, 84.4% cephazolin resistant, 84.4% erythromycin resistant, 52.2% ciprofloxacin resistant, and 15.6% tetracycline resistant. Fifty-eight specimens were tested for clindamycin with 29.3% found resistant; 85.7% were methicillin-resistant S aureus (MRSA) (defined as resistant to both penicillin G and …

Creb Mediates Prostaglandin F2alpha-Induced Muc5ac Overexpression, Wen-Cheng Chung, Seung-Hee Ryu, Hongxia Sun, Darryl C Zeldin, Ja Seok Koo

Faculty, Staff and Student Publications

Mucus secretion is an important protective mechanism for the luminal lining of open tubular organs, but mucin overproduction in the respiratory tract can exacerbate the inflammatory process and cause airway obstruction. Production of MUC5AC, a predominant gel-forming mucin secreted by airway epithelia, can be induced by various inflammatory mediators such as prostaglandins. The two major prostaglandins involved in inflammation are PGE(2) and PGF(2alpha). PGE(2)-induced mucin production has been well studied, but the effect of PGF(2alpha) on mucin production remains poorly understood. To elucidate the effect and underlying mechanism of PGF(2alpha) on MUC5AC production, we investigated the signal transduction of PGF(2alpha) …

Detailed Analysis Of Sequence Changes Occurring During Vlse Antigenic Variation In The Mouse Model Of Borrelia Burgdorferi Infection, Loïc Coutte, Douglas J. Botkin, Lihui Gao, Steven J. Norris

Faculty, Staff and Student Publications

Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion. Gene conversion between vls silent cassettes and the vlsE expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the VlsE product. In this study, we examined vlsE sequence variation in B. burgdorferi B31 during mouse infection by analyzing 1,399 clones isolated from bladder, heart, joint, ear, and skin tissues of mice infected for 4 …

Proton Magnetic Resonance Spectroscopy In Multiple Sclerosis, Balasrinivasa R Sajja, Jerry S Wolinsky, Ponnada A Narayana

Faculty, Staff and Student Publications

Proton magnetic resonance spectroscopy ((1)H-MRS) provides tissue metabolic information in vivo. This article reviews the role of MRS-determined metabolic alterations in lesions, normal-appearing white matter, gray matter, and spinal cord in advancing our knowledge of pathologic changes in multiple sclerosis (MS). In addition, the role of MRS in objectively evaluating therapeutic efficacy is reviewed. This potential metabolic information makes MRS a unique tool to follow MS disease evolution, understand its pathogenesis, evaluate the disease severity, establish a prognosis, and objectively evaluate the efficacy of therapeutic interventions.

Gstm1 And Gstt1 Null Polymorphisms And Risk Of Salivary Gland Carcinoma, Sayaka Kondo, Erich M. Sturgis, Fanglin Li, Qingyi Wei, Guojun Li

Faculty, Staff and Student Publications

Glutathione S-transferase (GST) genes detoxify and metabolize carcinogens, including oxygen free radicals which may contribute to salivary gland carcinogenesis. This cancer center-based case-control association study included 166 patients with incident salivary gland carcinoma (SGC) and 511 cancer-free controls. We performed multiplex polymerase chain reaction-based polymorphism genotyping assays for GSTM1 and GSTT1 null genotypes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with multivariable logistic regression analyses adjusted for age, sex, ethnicity, tobacco use, family history of cancer, alcohol use and radiation exposure. In our results, 27.7% of the SGC cases and 20.6% of the controls were null for …

Mutual Information For Testing Gene-Environment Interaction, Xuesen Wu, Li Jiin, Momiao Xiong

Faculty, Staff and Student Publications

Despite current enthusiasm for investigation of gene-gene interactions and gene-environment interactions, the essential issue of how to define and detect gene-environment interactions remains unresolved. In this report, we define gene-environment interactions as a stochastic dependence in the context of the effects of the genetic and environmental risk factors on the cause of phenotypic variation among individuals. We use mutual information that is widely used in communication and complex system analysis to measure gene-environment interactions. We investigate how gene-environment interactions generate the large difference in the information measure of gene-environment interactions between the general population and a diseased population, which motives …

Enhanced Estrogen-Induced Proliferation In Obese Rat Endometrium, Qian Zhang, Qi Shen, Joseph Celestino, Michael R Milam, Shannon N Westin, Robin A Lacour, Larissa A Meyer, Gregory L Shipley, Peter J A Davies, Lei Deng, Adrienne S Mccampbell, Russell R Broaddus, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: We tested the hypothesis that the proliferative estrogen effect on the endometrium is enhanced in obese vs lean animals.

STUDY DESIGN: Using Zucker fa/fa obese rats and lean control, we examined endometrial cell proliferation and the expression patterns of certain estrogen-regulated proproliferative and antiproliferative genes after short-term treatment with estradiol.

RESULTS: No significant morphologic/histologic difference was seen between the obese rats and the lean rats. Estrogen-induced proproliferative genes cyclin A and c-Myc messenger RNA expression were significantly higher in the endometrium of obese rats compared with those of the lean control. Expression of the antiproliferative gene p27Kip1 was suppressed …

Multiple Independent Genetic Factors At Nos1ap Modulate The Qt Interval In A Multi-Ethnic Population, Dan E. Arking, Amit Khera, Chao Xing, W H Linda Kao, Wendy Post, Eric Boerwinkle, Aravinda Chakravarti

Faculty, Staff and Student Publications

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples …

Genetic And Hormonal Factors Modulate Spreading Depression And Transient Hemiparesis In Mouse Models Of Familial Hemiplegic Migraine Type 1, Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I Savitz, Christian Waeber, Michael J Baum, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Michael A Moskowitz, Cenk Ayata

Faculty, Staff and Student Publications

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have …