Medicine and Health Sciences Commons^™

Influence Of Age, Sex And Genetic Factors On The Human Brain, D Reese Mckay, Anderson M. Winkler, Rene L. Olvera, Joanne E. Curran, Harald H. H. Goring, Thomas D. Dyer, Ravi Duggirala, Laura Almasy, John Blangero, David C. Glahn

School of Medicine Publications

We report effects of age, age(2), sex and additive genetic factors on variability in gray matter thickness, surface area and white matter integrity in 1,010 subjects from the Genetics of Brain Structure and Function Study. Age was more strongly associated with gray matter thickness and fractional anisotropy of water diffusion in white matter tracts, while sex was more strongly associated with gray matter surface area. Widespread heritability of neuroanatomic traits was observed, suggesting that brain structure is under strong genetic control. Furthermore, our findings indicate that neuroimaging-based measurements of cerebral variability are sensitive to genetic mediation. Fundamental studies of genetic …

Ambulatory Hypertension Subtypes And 24-Hour Systolic And Diastolic Blood Pressure As Distinct Outcome Predictors In 8341 Untreated People Recruited From 12 Populations, Yan Li, Fang-Fei Wei, Lutgarde Thijs, José Boggia, Kei Asayama, Tine W. Hansen, Masahiro Kikuya, Kristina Björklund-Bodegård, Takayoshi Ohkubo, Gladys E. Maestre

School of Medicine Publications

Background—Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce.

Methods and Results—We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a …

Permutation Inference For The General Linear Model, Anderson M. Winkler, Gerard R. Ridgway, Matthew A. Webster, Stephen M. Smith, Thomas E. Nichols

School of Medicine Publications

Permutation methods can provide exact control of false positives and allow the use of non-standard statistics, making only weak assumptions about the data. With the availability of fast and inexpensive computing, their main limitation would be some lack of flexibility to work with arbitrary experimental designs. In this paper we report on results on approximate permutation methods that are more flexible with respect to the experimental design and nuisance variables, and conduct detailed simulations to identify the best method for settings that are typical for imaging research scenarios. We present a generic framework for permutation inference for complex general linear …

Toxoplasmosis Gondii: An Atypical Presentation Of Optic Neuritis, Nicky R. Holdeman, Steven Burnham, Roberto A. Cruz, Rosa A. Tang

School of Medicine Publications

Toxoplasmosis gondii is a parasite whose natural host is the cat. Ocular toxoplasmosis can be categorized into two forms of infections: congenital, where an infant is infected in utero; and acquired, where an individual is typically infected by ingesting food contaminated with T. Gondii oocytes. Although acquired infections are rare in the United States, they can occur and toxoplasmosis should be in the differential diagnosis of an infectious optic neuritis.

The typical manifestation of toxoplasmosis is a retinochoroiditis, with a “headlight in the fog” appearance, due to dense inflammation of the vitreous; consequently, the diagnosis is often made clinically. This …

A Dna Microarray-Based Assay To Detect Dual Infection With Two Dengue Virus Serotypes, Alvaro Diaz-Badillo, María De Lourdes Muñoz, Gerardo Pérez-Ramírez, Victor Altuzar, Juan Burgueño, Julio G. Mendoza-Alvarez, Jorge P. Martínez-Muñoz, Alejandro Cisneros, Joel Navarrete-Espinosa, Feliciano Sanchez-Sinencio

School of Medicine Publications

Here; we have described and tested a microarray based-method for the screening of dengue virus (DENV) serotypes. This DNA microarray assay is specific and sensitive and can detect dual infections with two dengue virus serotypes and single-serotype infections. Other methodologies may underestimate samples containing more than one serotype. This technology can be used to discriminate between the four DENV serotypes. Single-stranded DNA targets were covalently attached to glass slides and hybridised with specific labelled probes. DENV isolates and dengue samples were used to evaluate microarray performance. Our results demonstrate that the probes hybridized specifically to DENV serotypes; with no detection …

Cortical Volume Alterations In Conduct Disordered Adolescents With And Without Bipolar Disorder, Rene L. Olvera, David C. Glahn, Louise O'Donnell, Carrie E. Bearden, Jair C. Soares, Anderson M. Winkler, Steven R. Pliszka

School of Medicine Publications

Background: There is increasing evidence that bipolar disorder (BD) and conduct disorder (CD) are co-occurring disorders. Magnetic resonance imaging has revealed differences in the structure and function of the frontal cortex in these disorders when studied separately; however, the impact of BD comorbidity on brain structure in adolescents with CD has not yet been examined.

Method: We conducted an optimized voxel based morphometry (VBM) study of juvenile offenders with the following diagnoses: conduct disorder with comorbid bipolar disorder (CD-BD; n = 24), conduct disorder without bipolar disorder (CD; n = 24) and healthy controls (HC, n = 24). Participants were …

Edentulism Associates With Worse Cognitive Performance In Community-Dwelling Elders In Rural Ecuador: Results Of The Atahualpa Project, Oscar H. Del Brutto, Hannah Gardener, Victor J. Del Brutto, Gladys E. Maestre, Mauricio Zambrano, Jipson E. Montenegro, Clinton B. Wright

School of Medicine Publications

Studies in industrialized nations suggest that severe edentulism correlates with cognitive impairment, but there is little information on this association in underserved populations. We conducted a community-based study to assess whether edentulism associates with cognitive impairment in elders living in rural Ecuador. Atahualpa residents aged ≥60 years were identified during a door-to-door census and evaluated using the Montreal Cognitive Assessment (MoCA). Persons were classified into two groups according to whether they have severe edentulism (teeth) or not. In addition, a questionnaire allowed self-rating of oral health. A total of 274 persons (mean age 69.6 ± 7.7 years; 59 % women) …

Developmental Origins Of Cardiovascular Disease, Edwina H. Yeung, Candace Robledo, Nansi S. Boghossian, Cuilin Zhang, Pauline Mendola

School of Medicine Publications

Although cardiovascular disease has traditionally been viewed as a condition of aging individuals, increasing focus has turned to its developmental origins. Since birthweight has been related to cardiovascular disease risk, research into factors such as gravid conditions that affect fetal growth have grown. Associations between maternal diabetes and childhood obesity from sibling studies suggest a causal role but prospective studies of gestational diabetes remain mixed. Preeclampsia and increased offspring blood pressure has been consistently observed but evidence for other cardiovascular outcomes is lacking. While maternal obesity is associated with childhood obesity, causality remains unclear and paternal obesity should be investigated …

Galvanic Vestibular Stimulator For Fmri Studies, Hellen M. Della-Justina, Tiago Manczak, Anderson M. Winkler, Dráulio Barros De Araújo, Mauren Abreu De Souza, Edson Amaro Junior, Humberto Remigio Gamba

School of Medicine Publications

INTRODUCTION: Areas of the brain that are associated with the vestibular system can be activated using galvanic vestibular stimulation. These areas can be studied through a combination of galvanic vestibular stimulation with functional magnetic resonance imaging (fMRI). In order to provide an appropriate sequence of galvanic stimulation synchronous with the MRI pulse sequence, a specific electronic device that was built and assessed is presented.

METHODS: The electronic project of the GVS is divided in analog and digital circuits. The analog circuits are mounted in an aluminum case, supplied by sealed batteries, and goes inside the MRI room near to the …

Mindfulness-Oriented Recovery Enhancement For Chronic Pain And Prescription Opioid Misuse: Results From An Early Stage Randomized Controlled Trial, Eric L. Garland, Eron G. Manusov, Brett Froeliger, Amber Kelly, Jaclyn M. Williams, Matthew O. Howard

School of Medicine Publications

Objective: Opioid pharmacotherapy is now the leading treatment for chronic pain, a problem that affects nearly one third of the U.S. population. Given the dramatic rise in prescription opioid misuse and opioid-related mortality, novel behavioral interventions are needed. The purpose of this study was to conduct an early-stage randomized controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE), a multimodal intervention designed to simultaneously target mechanisms underpinning chronic pain and opioid misuse.

Method: Chronic pain patients (N = 115; mean age = 48 ± 14 years; 68% female) were randomized to 8 weeks of MORE or a support group (SG). Outcomes were …

Outcome-Driven Thresholds For Ambulatory Pulse Pressure In 9938 People Recruited From 11 Populations, Yu-Mei Gu, Lutgarde Thijs, Yan Li, Kei Asayama, José Boggia, Tine W. Hansen, Yan-Ping Liu, Takayoshi Ohkubo, Kristina Björklund-Bodegård, Gladys E. Maestre

School of Medicine Publications

Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24–h ambulatory PP, we analyzed 9938 people randomly recruited from 11 populations (47.3% women). After age stratification (≥60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (HRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68,853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top …

Mycoplasma Genitalium Promotes Epithelial Crossing And Peripheral Blood Mononuclear Cell Infection By Hiv-1, Kishore Das, Georgina De La Garza, Edward B. Siwak, Virginia L. Scofield, Subramanian Dhandayuthapani

School of Medicine Publications

Background

Mycoplasma genitalium co-infection in HIV-infected individuals has been reported to increase the shedding of HIV in the urogenital region of females. To better understand this relationship, we investigated the influence of M. genitalium on the transmission and replication of HIV using an in vitro model.

Methods

The Transwell co-culture system was employed to assess the crossing of an endocervical cell barrier by HIV-1. Immunocytochemistry and confocal microscopy were used to assess the distribution of the nectin-1 molecule on M. genitalium -infected epithelial cells of the End1/E6E7 endocervical cell line, grown as monolayers in the insert wells. Peripheral blood mononuclear …

Titanium Dioxide Nanoparticles As Guardian Against Environmental Carcinogen Benzo[Alpha]Pyrene, Anupam Dhasmana, Qazi Mohd Sajid Jamal, Snober Shabnam Mir, Madan Lal Brahma Bhatt, Qamar Rahman, Richa Gupta, Mohd. Haris Siddiqui, Mohtashim Lohani

School of Medicine Publications

Polycyclic aromatic hydrocarbons (PAH), like Benzo[alpha]Pyrene (BaP) are known to cause a number of toxic manifestations including lung cancer. As Titanium dioxide Nanoparticles (TiO2 NPs) have recently been shown to adsorb a number of PAHs from soil and water, we investigated whether TiO2 NPs could provide protection against the BaP induced toxicity in biological system. A549 cells when co-exposed with BaP (25 µM, 50 µM and 75 µM) along with 0.1 µg/ml,0.5 µg/ml and 1 µg/ml of TiO2 NPs, showed significant reduction in the toxic effects of BaP, as measured by Micronucleus Assay, MTT Assay and ROS Assay. In order …

Age-Specific Differences Between Conventional And Ambulatory Daytime Blood Pressure Values, David Conen, Stefanie Aeschbacher, Lutgarde Thijs, Yan Li, José Boggia, Kei Asayama, Tine W. Hansen, Masahiro Kikuya, Kristina Björklund-Bodegård, Takayoshi Ohkubo, Gladys Maestre

School of Medicine Publications

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals < 50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P< 0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P< 0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P< 0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.

“Someone’S Got To Do It” – Primary Care Providers (Pcps) Describe Caring For Rural Women With Mental Health Problems, Maria C. Colon-Gonzalez, Jennifer S. Mccall-Hosenfeld, Carol S. Weisman, Marianne M. Hillemeier, Amanda N. Perry, Cynthia H. Chuang

School of Medicine Publications

Objective: Little is known about how primary care providers (PCPs) approach mental health care for low-income rural women. We developed a qualitative research study to explore the attitudes and practices of PCPs regarding the care of mood and anxiety disorders in rural women.

Method: We conducted semi-structured interviews with 19 family physicians, internists, and obstetrician-gynecologists (OBGYNs) in office-based practices in rural central Pennsylvania. Using thematic analysis, investigators developed a coding scheme. Questions focused on 1) screening and diagnosis of mental health conditions, 2) barriers to treatment among rural women, 3) management of mental illnesses in rural women, and 4) ideas …

Genetic Disruption Of Sod1 Gene Causes Glucose Intolerance And Impairs Β-Cell Function, Giovanna Muscogiuri, Adam B. Salmon, Cristina Aguayo-Mazzucato, Mengyao Li, Bogdan Balas, Rodolfo Guardado-Mendoza, Andrea Giaccari, Robert L. Reddick, Sara M. Reyna, Gordon Weir

School of Medicine Publications

Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of …

Genetic Basis Of Neurocognitive Decline And Reduced White-Matter Integrity In Normal Human Brain Aging, David C. Glahn, Jack W. Kent, Vincent P. Diego, Anderson M. Winkler, Joanne E. Curran, Harald Hh Goring, Thomas D. Dyer, Laura Almasy, Ravi Duggirala, John Blangero

School of Medicine Publications

Identification of genes associated with brain aging should markedly improve our understanding of the biological processes that govern normal age-related decline. However, challenges to identifying genes that facilitate successful brain aging are considerable, including a lack of established phenotypes and difficulties in modeling the effects of aging per se, rather than genes that influence the underlying trait. In a large cohort of randomly selected pedigrees (n = 1,129 subjects), we documented profound aging effects from young adulthood to old age (18-83 y) on neurocognitive ability and diffusion-based white-matter measures. Despite significant phenotypic correlation between white-matter integrity and tests of processing …

Reduced White Matter Integrity In Sibling Pairs Discordant For Bipolar Disorder, Emma Sprooten, Margaret S. Brumbaugh, Emma E. Knowles, D Reese Mckay, John Lewis, Jennifer Barrett, Stefanie Landau, Lindsay Cyr, Peter Kochunov, Anderson M. Winkler

School of Medicine Publications

Objective

Several lines of evidence indicate that white matter integrity is compromised in bipolar disorder, but the nature, extent, and biological causes remain elusive. To determine the extent to which white matter deficits in bipolar disorder are familial, the authors investigated white matter integrity in a large sample of bipolar patients, unaffected siblings, and healthy comparison subjects.

Method

The authors collected diffusion imaging data for 64 adult bipolar patients, 60 unaffected siblings (including 54 discordant sibling pairs), and 46 demographically matched comparison subjects. Fractional anisotropy was compared between the groups using voxel-wise tract-based spatial statistics and by extracting mean fractional …

Horner's Syndrome Secondary To Neuroblastoma, Roberto A. Cruz, T. K. Tran, Nicky R. Holdeman, Christian Cajavilca, Rosa A. Tang

School of Medicine Publications

Horner’s syndrome is classically characterized by a triad of miosis, partial ptosis and anhidrosis. The etiology is due to an interruption in the sympathetic innervation to the eye. A prompt diagnosis is crucial, given that Horner’s syndrome could be a manifestation of a life-threatening condition. A thorough case history and clinical evaluation must be employed to arrive at the diagnosis. An important means for confirming Horner’s syndrome is pharmacological testing, which is also used to localize the level where the sympathetic chain is compromised. Following the diagnosis and localization of the lesion, an algorithm should be followed to determine the …

Mobile Personal Health System For Ambulatory Blood Pressure Monitoring, Luis J. Mena, Vanessa G. Felix, Rodolfo Ostos, Jesus A. Gonzalez, Armando Cervantes, Armando Ochoa, Carlos Ruiz, Roberto Ramos, Gladys E. Maestre

School of Medicine Publications

The ARVmobile v1.0 is a multiplatform mobile personal health monitor (PHM) application for ambulatory blood pressure (ABP) monitoring that has the potential to aid in the acquisition and analysis of detailed profile of ABP and heart rate (HR), improve the early detection and intervention of hypertension, and detect potential abnormal BP and HR levels for timely medical feedback. The PHM system consisted of ABP sensor to detect BP and HR signals and smartphone as receiver to collect the transmitted digital data and process them to provide immediate personalized information to the user. Android and Blackberry platforms were developed to detect …

Global Prefrontal And Fronto-Amygdala Dysconnectivity In Bipolar I Disorder With Psychosis History, Alan Anticevic, Margaret S. Brumbaugh, Anderson M. Winkler, Lauren E. Lombardo, Jennifer Barrett, Phillip R. Corlett, Hedy Kober, June Gruber, Grega Repovs, Michael W. Cole

School of Medicine Publications

BACKGROUND: Pathophysiological models of bipolar disorder postulate that mood dysregulation arises from fronto-limbic dysfunction, marked by reduced prefrontal cortex (PFC) inhibitory control. This might occur due to both disruptions within PFC networks and abnormal inhibition over subcortical structures involved in emotional processing. However, no study has examined global PFC dysconnectivity in bipolar disorder and tested whether regions with within-PFC dysconnectivity also exhibit fronto-limbic connectivity deficits. Furthermore, no study has investigated whether such connectivity disruptions differ for bipolar patients with psychosis history, who might exhibit a more severe clinical course. METHODS: We collected resting-state functional magnetic resonance imaging at 3T in …

Testing The Hypothesis Of Accelerated Cerebral White Matter Aging In Schizophrenia And Major Depression, Peter Kochunov, David C. Glahn, Laura M. Rowland, Rene L. Olvera, Anderson M. Winkler, Hemalatha Sampath, Ravi Duggirala, Joanne E. Curran, John Blangero, L. Elliot Hong

School of Medicine Publications

Background

Elevated rate of aging-related biological and functional decline, termed “accelerated aging,” is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD.

Methods

The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20–60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20–79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 …

Management Options For Patients With Chronic Back Pain Without An Etiology, Lenny D. Salzberg, Eron G. Manusov

School of Medicine Publications

The treatment and management of low back pain is complex when there is no specific etiology such as cancer, fracture, or herniated disc. An organized approach to management that follows evidence based guidelines will facilitate care in a problem that reflects a lifetime prevalence of over 70 percent. The purpose of this review is to present a guideline to care for a common disabling process with a very heterogeneous etiology.

Proteomic Identification Of Dengue Virus Binding Proteins In Aedes Aegypti Mosquitoes And Aedes Albopictus Cells, Maria De Lourdes Muñoz, Gustavo Limón-Camacho, Rosalinda Tovar, Alvaro Diaz-Badillo, Guillermo Mendoza-Hernández, William C. Black

School of Medicine Publications

The main vector of dengue in America is the mosquito Aedes aegypti, which is infected by dengue virus (DENV) through receptors of midgut epithelial cells. The envelope protein (E) of dengue virus binds to receptors present on the host cells through its domain III that has been primarily recognized to bind cell receptors. In order to identify potential receptors, proteins from mosquito midgut tissue and C6/36 cells were purified by affinity using columns with the recombinant E protein domain III (rE-DIII) or DENV particles bound covalently to Sepharose 4B to compare and evaluate their performance to bind proteins including …

Identification Of Pleiotropic Genetic Effects On Obesity And Brain Anatomy, Joanne E. Curran, D Reese Mckay, Anderson M. Winkler, Rene L. Olvera, Thomas D. Dyer, Peter T. Fox, Laura Almasy, Ravi Duggirala, John Blangero, David C. Glahn

School of Medicine Publications

Background/aims: Obesity is a major contributor to the global burden of chronic disease and disability, though current knowledge of causal biologic underpinnings is lacking. Through the regulation of energy homeostasis and interactions with adiposity and gut signals, the brain is thought to play a significant role in the development of this disorder. While neuroanatomical variation has been associated with obesity, it is unclear if this relationship is influenced by common genetic mechanisms. In this study, we sought genetic components that influence both brain anatomy and body mass index (BMI) to provide further insight into the role of the brain in …

Is Bisphenol-A Exposure During Pregnancy Associated With Blood Glucose Levels Or Diagnosis Of Gestational Diabetes?, Candace A. Robledo, Jennifer D. Peck, Julie A. Stoner, Hélène Carabin, Linda Cowan, Holger M. Koch, Jean R. Goodman

School of Medicine Publications

Recent epidemiological studies indicate bisphenol A (BPA), an estrogenic chemical used in production of epoxy, polycarbonate, and plastic may increase risk of insulin resistance and type 2 diabetes. Exposure to BPA during pregnancy may contribute to development of gestational diabetes mellitus (GDM), a precursor to type 2 diabetes in women. This pilot study examined the association between BPA exposure, fasting blood glucose levels (FBG), and GDM diagnosis during pregnancy. Banked urine samples from 22 cases of GDM and 72 controls were analyzed for total (free BPA + conjugates) urinary BPA concentrations (μg/L). FBG levels (mg/dl) were obtained from 1-h 50-g …

Short-Term Exercise Training Improves Insulin Sensitivity But Does Not Inhibit Inflammatory Pathways In Immune Cells From Insulin-Resistant Subjects, Sara M. Reyna, Puntip Tantiwong, Eugenio Cersosimo, Ralph A. Defronzo, Apiradee Sriwijitkamol, Nicolas Musi

School of Medicine Publications

Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells.

Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC) were obtained for determination of Toll-like receptor (TLR) 2 and 4 protein content and mitogen-activated protein kinase phosphorylation.

Results. …

Genetic Architecture Of Declarative Memory: Implications For Complex Illnesses, Carrie E. Bearden, Katherine H. Karlsgodt, Peter Bachman, Theo G. Van Erp, Anderson M. Winkler, David C. Glahn

School of Medicine Publications

Why do memory abilities vary so greatly across individuals and cognitive domains? Although memory functions are highly heritable, what exactly is being genetically transmitted? Here we review evidence for the contribution of both common and partially independent inheritance of distinct aspects of memory function. We begin by discussing the assessment of long-term memory and its underlying neural and molecular basis. We then consider evidence for both specialist and generalist genes underlying individual variability in memory, indicating that carving memory into distinct subcomponents may yield important information regarding its genetic architecture. And finally we review evidence from both complex and single-gene …

Inhibition Of Neddylation Represses Lipopolysaccharide-Induced Proinflammatory Cytokine Production In Macrophage Cells, Fang-Mei Chang, Sara M. Reyna, Jose C. Granados, Sung-Jen Wei, Wendy Innis-Whitehouse, Shivani K. Maffi, Edward Rodriguez, Thomas J. Slaga, John D. Short

School of Medicine Publications

Background: Lipopolysaccharides (LPSs) up-regulate proinflammatory cytokines in macrophages, partly through a NF-κB-dependent process.

Results: Blocking neddylation, which helps regulate NF-κB, represses LPS-induced up-regulation of proinflammatory cytokines.

Conclusion: Neddylation plays a role in the up-regulation of NF-κB-regulated proinflammatory cytokines produced by macrophages in response to LPS.

Significance: Inhibition of neddylation represents a novel and effective method for the prevention of LPS-induced proinflammatory cytokines.

Association Of Differential Gene Expression With Imatinib Mesylate And Omacetaxine Mepesuccinate Toxicity In Lymphoblastoid Cell Lines, Hemant Kulkarni, Harald H. H. Goring, Vincent P. Diego, Shelley A. Cole, Ken R. Walder, Greg R. Collier, John Blangero, Melanie A. Carless

School of Medicine Publications

Background: Imatinib mesylate is currently the drug of choice to treat chronic myeloid leukemia. However, patient resistance and cytotoxicity make secondary lines of treatment, such as omacetaxine mepesuccinate, a necessity. Given that drug cytotoxicity represents a major problem during treatment, it is essential to understand the biological pathways affected to better predict poor drug response and prioritize a treatment regime.

Methods: We conducted cell viability and gene expression assays to determine heritability and gene expression changes associated with imatinib and omacetaxine treatment of 55 non-cancerous lymphoblastoid cell lines, derived from 17 pedigrees. In total, 48,803 transcripts derived from Illumina …