Digital Commons Network^™

Maternal Separation Affects Dopamine Transporter Function In The Spontaneously Hypertensive Rat: An In Vivo Electrochemical Study, Jacqueline S. Womersley, Jennifer H. Hsieh, Lauriston A. Kellaway, Greg A. Gerhardt, Vivienne A. Russell

Neuroscience Faculty Publications

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT) in ways that distinguish SHR …

A Brief Overview Of Adolescent Developmental Problems In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun

Pediatrics Faculty Publications

Several adolescent developmental problems in Hong Kong are briefly reviewed in this paper. First, rising adolescent substance abuse trends are described. Second, Internet use problems and Internet addiction among young people are examined. Third, worrying trends in adolescent sexuality are identified. Fourth, phenomena on bullying among young people are reviewed. Finally, phenomena related to adolescent materialistic orientation are focused upon. With reference to these adolescent developmental problems, possible solutions are briefly discussed particularly with reference to the ecological perspective. It is argued that the related scientific literature provides useful pointers for designing the curriculum in the extension phase of the …

Age-Associated Disruption Of Molecular Clock Expression In Skeletal Muscle Of The Spontaneously Hypertensive Rat, Mitsunori Miyazaki, Elizabeth Schroder, Stephanie E. Edelmann, Michael E. Hughes, Karl Kornacker, C. William Balke, Karyn A. Esser

Physiology Faculty Publications

It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including …

A Work In Progress: The Lived Experiences Of Black Male Undergraduates At One Predominantly White University, Wayne D. Lewis, Steven Thurston Oliver, Jennifer L. Burris

Kentucky Journal of Higher Education Policy and Practice

This exploratory study examines the lived academic and social experiences of current black male undergraduate students, including their perceived barriers and their strategies for persistence and achieving success. Study participants included black male undergraduate students at one predominantly white, four-year, public research university. Data collection methods included two focus group interviews with a purposeful sample of 12 undergraduate, black male students. Students reported that explicit and implicit messages of racial hatred have contributed to a general campus atmosphere of discomfort for black male students. The students described an environment where they continually encounter racial micro aggressions and prejudice. Students reported …

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Thrombospondin1 Deficiency Reduces Obesity-Associated Inflammation And Improves Insulin Sensitivity In A Diet-Induced Obese Mouse Model, Yanzhang Li, Xiaopeng Tong, Courtney Rumala, Kate Clemons, Shuxia Wang

Graduate Center for Nutritional Sciences Faculty Publications

BACKGROUND: Obesity is prevalent worldwide and is associated with insulin resistance. Advanced studies suggest that obesity-associated low-grade chronic inflammation contributes to the development of insulin resistance and other metabolic complications. Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue. A recent study suggests a positive correlation of TSP1 with obesity, adipose inflammation, and insulin resistance. However, the direct effect of TSP1 on obesity and insulin resistance is not known. Therefore, we investigated the role of TSP1 in mediating obesity-associated inflammation and insulin resistance by using TSP1 knockout mice.

METHODOLOGY/PRINCIPAL FINDINGS: Male TSP1-/- mice …

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 …

Wolbachia Infections That Reduce Immature Insect Survival: Predicted Impacts On Population Replacement, Philip R. Crain, James W. Mains, Eunho Suh, Yunxin Huang, Philip H. Crowley, Stephen L. Dobson

Entomology Faculty Publications

BACKGROUND: The evolutionary success of Wolbachia bacteria, infections of which are widespread in invertebrates, is largely attributed to an ability to manipulate host reproduction without imposing substantial fitness costs. Here, we describe a stage-structured model with deterministic immature lifestages and a stochastic adult female lifestage. Simulations were conducted to better understand Wolbachia invasions into uninfected host populations. The model includes conventional Wolbachia parameters (the level of cytoplasmic incompatibility, maternal inheritance, the relative fecundity of infected females, and the initial Wolbachia infection frequency) and a new parameter termed relative larval viability (RLV), which is the survival of infected larvae relative to …

Functional Plasticity Of Central Trpv1 Receptors In Brainstem Dorsal Vagal Complex Circuits Of Streptozotocin-Treated Hyperglycemic Mice, Andrea Zsombok, Muthu D. Bhaskaran, Hong Gao, Andrei V. Derbenev, Bret N. Smith

Physiology Faculty Publications

Emerging data indicate that central neurons participate in diabetic processes by modulating autonomic output from neurons in the dorsal motor nucleus of the vagus (DMV). We tested the hypothesis that synaptic modulation by transient receptor potential vanilloid type 1 (TRPV1) receptors is reduced in the DMV in slices from a murine model of type 1 diabetes. The TRPV1 agonist capsaicin robustly enhanced glutamate release onto DMV neurons by acting at preterminal receptors in slices from intact mice, but failed to do so in slices from diabetic mice. TRPV1 receptor protein expression in the vagal complex was unaltered. Brief insulin preapplication …

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 …

Critical Role Of Pi3k/Akt/Gsk3Β In Motoneuron Specification From Human Neural Stem Cells In Response To Fgf2 And Egf, Luis Ojeda, Junling Gao, Kristopher G. Hooten, Enyin Wang, Jason R. Thonhoff, Tiffany J. Dunn, Tianyan Gao, Ping Wu

Markey Cancer Center Faculty Publications

Fibroblast growth factor (FGF) and epidermal growth factor (EGF) are critical for the development of the nervous system. We previously discovered that FGF2 and EGF had opposite effects on motor neuron differentiation from human fetal neural stem cells (hNSCs), but the underlying mechanisms remain unclear. Here, we show that FGF2 and EGF differentially affect the temporal patterns of Akt and glycogen synthase kinase 3 beta (GSK3β) activation. High levels of phosphatidylinositol 3-kinase (PI3K)/Akt activation accompanied with GSK3β inactivation result in reduction of the motor neuron transcription factor HB9. Inhibition of PI3K/Akt by chemical inhibitors or RNA interference or overexpression of …

Srt1720 Improves Survival And Healthspan Of Obese Mice, Robin K. Minor, Joseph A. Baur, Ana P. Gomes, Theresa M. Ward, Anna Csiszar, Evi M. Mercken, Kotb Abdelmohsen, Yu-Kyong Shin, Carles Canto, Morten Scheibye-Knudsen, Melissa Krawczyk, Pablo M. Irusta, Alejandro Martín-Montalvo, Basil P. Hubbard, Yongqing Zhang, Elin Lehrmann, Alexa A. White, Nathan L. Price, William R. Swindell, Kevin J. Pearson, Kevin G. Becker, Vilhelm A. Bohr, Myriam Gorospe, Josephine M. Egan, Mark I. Talan, Johan Auwerx, Christoph H. Westphal, James L. Ellis, Zoltan Ungvari, George P. Vlasuk, Peter J. Elliott, David A. Sinclair, Rafael De Cabo

Graduate Center for Nutritional Sciences Faculty Publications

Sirt1 is an NAD(+)-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and …

No Evidence Of Association Between Hiv-1 And Malaria In Populations With Low Hiv-1 Prevalence, Diego F. Cuadros, Adam J. Branscum, Gisela García-Ramos

Biology Faculty Publications

BACKGROUND: The geographic overlap between HIV-1 and malaria has generated much interest in their potential interactions. A variety of studies have evidenced a complex HIV-malaria interaction within individuals and populations that may have dramatic effects, but the causes and implications of this co-infection at the population level are still unclear. In a previous publication, we showed that the prevalence of malaria caused by the parasite Plasmodium falciparum is associated with HIV infection in eastern sub-Saharan Africa. To complement our knowledge of the HIV-malaria co-infection, the objective of this work was to assess the relationship between malaria and HIV prevalence in …

Effect Of Variable Transmission Rate On The Dynamics Of Hiv In Sub-Saharan Africa, Diego F. Cuadros, Phillip H. Crowley, Ben Augustine, Sarah L. Stewart, Gisela García-Ramos

Biology Faculty Publications

BACKGROUND: The cause of the high HIV prevalence in sub-Saharan Africa is incompletely understood, with heterosexual penile-vaginal transmission proposed as the main mechanism. Heterosexual HIV transmission has been estimated to have a very low probability; but effects of cofactors that vary in space and time may substantially alter this pattern.

METHODS: To test the effect of individual variation in the HIV infectiousness generated by co-infection, we developed and analyzed a mathematical sexual network model that simulates the behavioral components of a population from Malawi, as well as the dynamics of HIV and the co-infection effect caused by other infectious diseases, …

Targeted Over-Expression Of Glutamate Transporter 1 (Glt-1) Reduces Ischemic Brain Injury In A Rat Model Of Stroke, Brandon K. Harvey, Mikko Airavaara, Jason Michael Hinzman, Emily M. Wires, Matthew J. Chiocco, Douglas B. Howard, Hui Shen, Greg A. Gerhardt, Barry J. Hoffer, Yun Wang

Neuroscience Faculty Publications

Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV) vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV-GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical region of infarction 3 weeks prior …

Male Mating Competitiveness Of A Wolbachia-Introgressed Aedes Polynesiensis Strain Under Semi-Field Conditions, Eric W. Chambers, Limb Hapairai, Bethany A. Peel, Hervé Bossin, Stephen L. Dobson

Entomology Faculty Publications

BACKGROUND: Lymphatic filariasis (LF), a global public health problem affecting approximately 120 million people worldwide, is a leading cause of disability in the developing world including the South Pacific. Despite decades of ongoing mass drug administration (MDA) in the region, some island nations have not yet achieved the threshold levels of microfilaremia established by the World Health Organization for eliminating transmission. Previously, the generation of a novel Aedes polynesiensis strain (CP) infected with an exogenous type of Wolbachia has been described. The CP mosquito is cytoplasmically incompatible (i.e., effectively sterile) when mated with wildtype mosquitoes, and a strategy was proposed …

Epigenetic Silencing Of Nucleolar Rrna Genes In Alzheimer's Disease, Maciej Pietrzak, Grzegorz Rempala, Peter T. Nelson, Jing-Juan Zheng, Michal Hetman

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer's disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation.

METHODOLOGY/PRINCIPAL FINDINGS: To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter …

Sr-A Ligand And M-Csf Dynamically Regulate Sr-A Expression And Function In Primary Macrophages Via P38 Mapk Activation, Dejan Nikolic, Lindsay Calderon, Liqin Du, Steven R. Post

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Inflammation is characterized by dynamic changes in the expression of cytokines, such as M-CSF, and modifications of lipids and proteins that result in the formation of ligands for Class A Scavenger Receptors (SR-A). These changes are associated with altered SR-A expression in macrophages; however, the intracellular signal pathways involved and the extent to which SR-A ligands regulate SR-A expression are not well defined. To address these questions, SR-A expression and function were examined in resident mouse peritoneal macrophages incubated with M-CSF or the selective SR-A ligand acetylated-LDL (AcLDL).

RESULTS: M-CSF increased SR-A expression and function, and required the specific …

Microglial P38Α Mapk Is A Key Regulator Of Proinflammatory Cytokine Up-Regulation Induced By Toll-Like Receptor (Tlr) Ligands Or Beta-Amyloid (Aβ), Adam D. Bachstetter, Bin Xing, Lucia De Almeida, Edgardo R. Dimayuga, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical to elucidate intracellular signaling pathways that are significant contributors to cytokine overproduction in microglia exposed to specific stressors, especially pathways amenable to drug interventions. The serine/threonine protein kinase p38α MAPK is a key enzyme in the parallel and convergent intracellular signaling pathways involved in stressor-induced production of IL-1β and TNFα in peripheral tissues, and is a drug development target for peripheral inflammatory diseases. However, much less is known about the quantitative …

Osler Came To Boston, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Farmwork-Related Injury Among Farmers 50 Years Of Age And Older In Kentucky And South Carolina: A Cohort Study, 2002-2005, Jennifer L. Marcum, Steven R. Browning, Deborah B. Reed, Richard Charnigo

Epidemiology and Environmental Health Faculty Publications

Farmers in the U.S. are becoming more diverse; the average age of the farmer is increasing, as is the number of women and minority farm operators. There is limited research on injury risk factors in these special populations of farmers. It is especially important to study the risk factors for injury in these growing and at-risk groups. A longitudinal survey was conducted of farmers (n = 1,394) age 50 and older who resided in Kentucky and South Carolina. The questionnaire was administered by telephone and mail surveys four times between 2002 and 2005 to the fixed cohort of farmers, obtained …

Cooperative And Antagonistic Contributions Of Two Heterochromatin Proteins To Transcriptional Regulation Of The Drosophila Sex Determination Decision, Hui Li, Janel Rodriguez, Youngdong Yoo, Momin Mohammed Shareef, Ramakrishna Badugu, Jamila I. Horabin, Rebecca Kellum

Biology Faculty Publications

Eukaryotic nuclei contain regions of differentially staining chromatin (heterochromatin), which remain condensed throughout the cell cycle and are largely transcriptionally silent. RNAi knockdown of the highly conserved heterochromatin protein HP1 in Drosophila was previously shown to preferentially reduce male viability. Here we report a similar phenotype for the telomeric partner of HP1, HOAP, and roles for both proteins in regulating the Drosophila sex determination pathway. Specifically, these proteins regulate the critical decision in this pathway, firing of the establishment promoter of the masterswitch gene, Sex-lethal (Sxl). Female-specific activation of this promoter, Sxl(Pe), is essential to females, as it provides SXL …

Store-Operated Ca(2+) Entry (Soce) Contributes To Normal Skeletal Muscle Contractility In Young But Not In Aged Skeletal Muscle, Angela M. Thornton, Xiaoli Zhao, Noah Weisleder, Leticia S. Brotto, Sylvain Bougoin, Thomas M. Nosek, Michael B. Reid, Brian Hardin, Zui Pan, Jianjie Ma, Jerome Parness, Marco Brotto

Physiology Faculty Publications

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular …

Patient Discomfort Associated With The Use Of Intra-Arterial Iodinated Contrast Media: A Meta-Analysis Of Comparative Randomized Controlled Trials, Peter A. Mccullough, Patrizio Capasso

Radiology Faculty Publications

BACKGROUND: Discomfort characterized by pain and warmth are common adverse effects associated with the use of intra-arterial iodinated contrast media (CM). The objective of this review was to pool patient-reported outcomes available from head-to-head randomized controlled trials (RCTs) and to compare the discomfort rates associated with iso-osmolar contrast media (IOCM; i.e., iodixanol) to those reported with various low-osmolar contrast media (LOCM).

METHODS: A review of the literature published between 1990 and 2009 available through Medline, Medline Preprints, Embase, Biological Abstracts, BioBase, Cab Abstracts, International Pharmaceutical Abstracts, Life Sciences Collection, Inside Conferences, Energy Database, Engineering Index and Technology Collection was performed …

Synaptic Reorganization Of Inhibitory Hilar Interneuron Circuitry After Traumatic Brain Injury In Mice, Robert F. Hunt, Stephen W. Scheff, Bret N. Smith

Physiology Faculty Publications

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found …

Oxidative Stress Accumulates In Adipose Tissue During Aging And Inhibits Adipogenesis, Hannes M. Findeisen, Kevin J. Pearson, Florence Gizard, Yue Zhao, Hua Qing, Karrie L Jones, Dianne Cohn, Elizabeth B. Heywood, Rafael De Cabo, Dennis Bruemmer

Saha Cardiovascular Research Center Faculty Publications

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at …

Phenethyl Isothiocyanate Exhibits Antileukemic Activity In Vitro And In Vivo By Inactivation Of Akt And Activation Of Jnk Pathways, N. Gao, Amit Budhraja, S. Cheng, E.-H. Liu, J. Chen, Z. Yang, D. Chen, Zhuo Zhang, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively …

Deep Sleep And Parietal Cortex Gene Expression Changes Are Related To Cognitive Deficits With Age, Heather M. Buechel, Jelena Popovic, James L. Searcy, Nada M. Porter, Olivier Thibault, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. Despite sleep disruption's well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleep's relationship to cognitive aging.

METHODOLOGY: We measured sleep stages in young adult and aged F344 rats during inactive (enhanced sleep) and active (enhanced wake) periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken.

PRINCIPAL FINDINGS: Water maze performance was impaired, and inactive period deep sleep was decreased with age. However, increased deep sleep during the …

Common And Distinct Mechanisms Of Cognitive Flexibility In Prefrontal Cortex, Chobok Kim, Nathan F. Johnson, Sara E. Cilles, Brian T. Gold

Neuroscience Faculty Publications

The human ability to flexibly alternate between tasks represents a central component of cognitive control. Neuroimaging studies have linked task switching with a diverse set of prefrontal cortex (PFC) regions, but the contributions of these regions to various forms of cognitive flexibility remain largely unknown. Here, subjects underwent functional brain imaging while they completed a paradigm that selectively induced stimulus, response, or cognitive set switches in the context of a single task decision performed on a common set of stimuli. Behavioral results indicated comparable reaction time costs associated with each switch type. Domain-general task-switching activation was observed in the inferior …

Aspirin Treatment Of Mice Infected With Trypanosoma Cruzi And Implications For The Pathogenesis Of Chagas Disease, Shankar Mukherjee, Fabiana S. Machado, Huang Huang, Helieh S. Oz, Linda A. Jelicks, Cibele M. Prado, Wade Koba, Eugene J. Fine, Dazhi Zhao, Stephen M. Factor, J. Elias Collado, Louis M. Weiss, Herbert B. Tanowitz, Anthony W. Ashton

Center for Oral Health Research Faculty Publications

Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T. cruzi infection (Brazil strain) beginning 5 days post infection (dpi) with aspirin (ASA) increased mortality (2-fold) and parasitemia (12-fold). However, there were no differences regarding histopathology or cardiac structure or function. Delayed treatment with ASA (20 mg/kg) beginning 60 dpi did not increase parasitemia or mortality but improved ejection fraction. ASA treatment diminished the profile of parasite- and host-derived circulating prostaglandins in infected …