Medicine and Health Sciences Commons^™

The Relationship Between Marital Status And Psychological Resilience In Chronic Pain, James B. Wade, Robert P. Hart, James H. Wade, Jasmohan S. Bajaj, Donald D. Price

Psychiatry Publications

We examined the relationship between marital status and a 2-stage model of pain-related effect, consisting of pain unpleasantness and suffering. We studied 1914 chronic pain patients using multivariate analysis of covariance (MANCOVA) to clarify whether marital status was a determinant factor in the emotional or ideational suffering associated with chronic pain after controlling for pain sensation intensity, age, and ethnicity. Marital status was unrelated to immediate unpleasantness (). We found a strong association with emotional suffering () but not with negative illness beliefs (). Interestingly, widowed subjects experienced significantly less frustration, fear, and anger than all other groups (married, divorced, …

Improved Detection Of Common Variants Associated With Schizophrenia And Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate, Ole A. Andreassen, Wesley K. Thompson, Andrew J. Schork, Stephan Ripke, Morten Mattingsdal, John R. Kelsoe, Kenneth S. Kendler, Michael C. O'Donovan, Dan Rujescu, Thomas Werge, Pamela Sklar, J. Cooper Roddey, Chi-Hua Chen, Linda Mcevoy, Rahul S. Desikan, Srdjan Djurovic, Anders M. Dale

Psychiatry Publications

Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disease risk are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability. Epidemiological and clinical evidence suggest similar disease characteristics and overlapping genes between SCZ and BD. Here, we computed conditional …

Ethanol Regulation Of Serum Glucocorticoid Kinase 1 Expression In Dba2/J Mouse Prefrontal Cortex, Blair N. Costin, Seth M. Dever, Michael F. Miles

Pharmacology and Toxicology Publications

Background

We previously identified a group of glucocorticoid-responsive genes, including Serum Glucocorticoid kinase 1 (Sgk1), regulated by acute ethanol in prefrontal cortex of DBA2/J mice. Acute ethanol activates the hypothalamic pituitary adrenal axis (HPA) causing release of glucocorticoids. Chronic ethanol dysregulates the HPA response in both humans and rodents, possibly contributing to important interactions between stress and alcoholism. Because Sgk1regulates ion channels and learning and memory, we hypothesized that Sgk1 contributes to HPA-dependent acute and adaptive neuronal responses to ethanol. These studies characterized acute and chronic ethanol regulation of Sgk1 mRNA and protein and their relationship with ethanol actions …

Fyn-Dependent Gene Networks In Acute Ethanol Sensitivity, Sean P. Farris, Michael F. Miles

Pharmacology and Toxicology Publications

Studies in humans and animal models document that acute behavioral responses to ethanol are predisposing factor for the risk of long-term drinking behavior. Prior microarray data from our laboratory document strain- and brain region-specific variation in gene expression profile responses to acute ethanol that may be underlying regulators of ethanol behavioral phenotypes. The non-receptor tyrosine kinase Fyn has previously been mechanistically implicated in the sedative-hypnotic response to acute ethanol. To further understand how Fyn may modulate ethanol behaviors, we used whole-genome expression profiling. We characterized basal and acute ethanol-evoked (3 g/kg) gene expression patterns in nucleus accumbens (NAC), prefrontal cortex …

Contribution Of Nadph Oxidase To Membrane Cd38 Internalization And Activation In Coronary Arterial Myocytes, Ming Xu, Xiao-Xue Li, Joseph K. Ritter, Justine M. Abais, Yang Zhang, Pin-Lan Li

Pharmacology and Toxicology Publications

The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase …

Cannabinoid Cb2 Receptors Regulate Central Sensitization And Pain Responses Associated With Osteoarthritis Of The Knee Joint, James J. Burston, David R. Sagar, Pin Shao, Mingfeng Bai, Emma King, Louis Brailsford, Jenna M. Turner, Gareth J. Hathway, Andrew J. Bennett, David A. Walsh, David A. Kendall, Aron H. Lichtman, Victoria Chapman

Pharmacology and Toxicology Publications

Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies.

Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that …

Mapping The Literature Of Allied Health: Healthcare Chaplaincy, Emily Johnson, Diane Dodd Mccue, Alexander Tartaglia, Jennifer A. Mcdaniel

VCU Libraries Faculty and Staff Publications

OBJECTIVE: This study examined citation patterns and indexing coverage from 2008 to 2010 to determine (1) the core literature of health care chaplaincy and (2) the resources providing optimum coverage for the literature.

METHODS: Citations from three source journals (2008-2010 inclusive) were collected and analyzed according to the protocol created for the Mapping the Literature of Allied Health Professions Project. An analysis of indexing coverage by five databases was conducted. A secondary analysis of self-citations by source journals was also conducted.

RESULTS: The 3 source journals--Chaplaincy Today, the Journal of Health Care Chaplaincy, and the Journal of Pastoral Care and …

Biological Characterization Of 3-(2-Amino-Ethyl)-5-[3-(4-Butoxyl-Phenyl)-Propylidene]-Thiazolidine-2,4-Dione (K145) As A Selective Sphingosine Kinase-2 Inhibitor And Anticancer Agent, Kai Liu, Tai L. Guo, Nitai C. Hait, Jeremy Allegood, Hardik I. Parikh, Wenfang Xu, Glen E. Kellogg, Steven Grant, Sarah Spiegel, Shijun Zhang

Medicinal Chemistry Publications

In our effort to develop selective sphingosine kinase-2 (SphK2) inhibitors as pharmacological tools, a thiazolidine-2,4-dione analogue, 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione(K145), was synthesized and biologically characterized. Biochemical assay results indicate that K145 is a selective SphK2 inhibitor. Molecular modeling studies also support this notion. In vitro studies using human leukemia U937 cells demonstrated that K145 accumulates in U937 cells, suppresses the S1P level, and inhibits SphK2. K145 also exhibited inhibitory effects on the growth of U937 cells as well as apoptotic effects in U937 cells, and that these effects may be through the inhibition of down-stream ERK and Akt signaling pathways. K145 also significantly …

A Hierarchical Method For Removal Of Baseline Drift From Biomedical Signals: Application In Ecg Analysis, Yurong Luo, Rosalyn H. Hargraves, Ashwin Belle, Ou Bai, Xuguang Qi, Kevin R. Ward, Michael Paul Pfaffenberger, Kayvan Najarian

Computer Science Publications

Noise can compromise the extraction of some fundamental and important features from biomedical signals and hence prohibit accurate analysis of these signals. Baseline wander in electrocardiogram (ECG) signals is one such example, which can be caused by factors such as respiration, variations in electrode impedance, and excessive body movements. Unless baseline wander is effectively removed, the accuracy of any feature extracted from the ECG, such as timing and duration of the ST-segment, is compromised. This paper approaches this filtering task from a novel standpoint by assuming that the ECG baseline wander comes from an independent and unknown source. The technique …

Genotype-Based Ancestral Background Consistently Predicts Efficacy And Side Effects Across Treatments In Catie And Star*D, Daniel E. Adkins, Renan P. Souza, Karolina A. Aberg, Shaunna L. Clark, Joseph L. Mcclay, Patrick F. Sullivan, Edwin J. C. G. Van Den Oord

Biomarker Research and Personalized Medicine Publications

Only a subset of patients will typically respond to any given prescribed drug. The time it takes clinicians to declare a treatment ineffective leaves the patient in an impaired state and at unnecessary risk for adverse drug effects. Thus, diagnostic tests robustly predicting the most effective and safe medication for each patient prior to starting pharmacotherapy would have tremendous clinical value. In this article, we evaluated the use of genetic markers to estimate ancestry as a predictive component of such diagnostic tests. We first estimated each patient’s unique mosaic of ancestral backgrounds using genome-wide SNP data collected in the Clinical …

Ethnicity And Gender Comparisons Of Health Consequences In Adults With Alcohol Dependence, Karen G. Chartier, Michie N. Hesselbrock, Victor M. Hesselbrock

Social Work Publications

The moderating effects of ethnicity and gender on factors associated with physical health consequences in adults with alcohol dependence was examined using data from the 2001–2002 U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Black and White respondents with a lifetime diagnosis of DSM-IV alcohol dependence were selected for the study (n = 3,852). A multiple-group structural equation model tested ethnicity, gender, and intervening variables as predictors of physical health status in alcohol dependent men and women. Study findings offer implications for clinical practice with alcohol dependent individuals by identifying likely target groups and problems for intervention.

Associations Of Occupational Attributes And Excessive Drinking, Andrew J. Barnes, Frederick J. Zimmerman

Health Behavior and Policy Publications

Numerous work-related drinking mechanisms have been posited and, oftentimes, examined in isolation. We combined data from over 100 occupational attributes into several factors and tested the association of these factors with measures of alcohol use. We used the NLSY79 2006 wave, a U.S. representative sample of 6,426 workers ages 41 to 49 and the 2006 Occupational Information Network database (O*NET), a nationally representative sample of nearly 1,000 occupations. We conducted exploratory factor analysis on 119 occupational attributes and found three independent workplace characteristics – physical demands, job autonomy, and social engagement - explained the majority of the variation. We then …

Association Study Of 167 Candidate Genes For Schizophrenia Selected By A Multi-Domain Evidence-Based Prioritization Algorithm And Neurodevelopmental Hypothesis, Zhongming Zhao, Bradley T. Webb, Peilin Jia, T. Bernard Bigdeli, Brion S. Maher, Edwin Van Den Oord, Sarah Bergen, Richard L. Amdur, Francis A. O'Neill, Dermot Walsh, Dawn L. Thiselton, Xianging Chen, Carlos N. Pato, The International Schizophrenia Consortium, Brien P. Riley, Kenneth S. Kendler, Ayman H. Fanous

Psychiatry Publications

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene …

Suicidal Risk Factors Of Recurrent Major Depression In Han Chinese Women, Yuzhang Zhu, Hongni Zhang, Shenxun Shi, Jingfang Gao, Youhui Li, Ming Tao, Kerang Zhang, Xumei Wang, Chengge Gao, Lijun Yang, Kan Li, Jiangguo Shi, Gang Wang, Lanfen Liu, Jinbei Zhang, Bo Du, Guoqing Jiang, Jianhua Shen, Zhen Zhang, Wei Liang, Jing Sun, Jian Hu, Tiebang Liu, Xueyi Wang, Guodong Miao, Huaqing Meng, Yi Li, Chunmei Hu, Yi Li, Guoping Huang, Gongying Li, Baowei Ha, Hong Deng, Qiyi Mei, Hui Zhong, Shugui Gao, Hong Sang, Yutang Zhang, Xiang Fang, Fengyu Yu, Donglin Yang, Tieqiao Liu, Yunchun Chen, Xiaohong Hong, Wenyuan Wu, Guibing Chen, Min Cai, Yan Song, Jiyang Pan, Jicheng Dong, Runde Pan, Wei Zhang, Zhenming Shen, Zhengrong Liu, Danhua Gu, Xiaoping Wang, Xiaojuan Liu, Qiwen Zhang, Yihan Li, Yiping Chen, Kenneth S. Kendler, Jonathan Flint, Ying Liu

Psychiatry Publications

The relationship between suicidality and major depression is complex. Socio- demography, clinical features, comorbidity, clinical symptoms, and stressful life events are important factors influencing suicide in major depression, but these are not well defined. Thus, the aim of the present study was to assess the associations between the above-mentioned factors and suicide ideation, suicide plan, and suicide attempt in 6008 Han Chinese women with recurrent major depression (MD). Patients with any suicidality had significantly more MD symptoms, a significantly greater number of stressful life events, a positive family history of MD, a greater number of episodes, a significant experience of …

Association Testing Strategy For Data From Dense Marker Panels, Donghyung Lee, Silviu-Alin Bacanu

Psychiatry Publications

Genome wide association studies have been usually analyzed in a univariate manner. The commonly used univariate tests have one degree of freedom and assume an additive mode of inheritance. The experiment-wise significance of these univariate statistics is obtained by adjusting for multiple testing. Next generation sequencing studies, which assay 10-20 million variants, are beginning to come online. For these studies, the strategy of additive univariate testing and multiple testing adjustment is likely to result in a loss of power due to (1) the substantial multiple testing burden and (2) the possibility of a non-additive causal mode of inheritance. To reduce …

Clinical Features Of Patients With Dysthymia In A Large Cohort Of Han Chinese Women With Recurrent Major Depression, Wenqing Wu, Zhoubing Wang, Yan Wei, Guanghua Zhang, Shenxun Shi, Jingfang Gao, Youhui Li, Ming Tao, Kerang Zhang, Xumei Wang, Chengge Gao, Lijun Yang, Kan Li, Jianguo Shi, Gang Wang, Lanfen Liu, Jinbei Zhang, Bo Du, Guoqing Jiang, Jianhua Shen, Ying Liu, Wei Liang, Jing Sun, Jian Hu, Tiebang Liu, Xueyi Wang, Guodong Miao, Huaqing Meng, Yi Li, Guoping Huang, Gongying Li, Baowei Ha, Hong Deng, Qiyi Mei, Hui Zhong, Shugui Gao, Hong Sang, Yutang Zhang, Xiang Fang, Fengyu Yu, Donglin Yang, Tieqiao Liu, Yunchun Chen, Xiaohong Hong, Wenyuan Wu, Guibing Chen, Min Cai, Yan Song, Jiyang Pan, Jicheng Dong, Runde Pan, Wei Zhang, Zhenming Shen, Zhengrong Liu, Danhua Gu, Xiaoping Wang, Xiaojuan Liu, Qiwen Zhang, Yihan Li, Yiping Chen, Kenneth S. Kendler, Jonathan Flint, Zhen Zhang

Psychiatry Publications

Background

Dysthymia is a form of chronic mild depression that has a complex relationship with major depressive disorder (MDD). Here we investigate the role of environmental risk factors, including stressful life events and parenting style, in patients with both MDD and dysthymia. We ask whether these risk factors act in the same way in MDD with and without dysthymia.

Results

We examined the clinical features in 5,950 Han Chinese women with MDD between 30–60 years of age across China. We confirmed earlier results by replicating prior analyses in 3,950 new MDD cases. There were no significant differences between the two …

Microglial Activation Decreases Retention Of The Protease Inhibitor Saquinavir: Implications For Hiv Treatment, Shannon Dallas, Michelle L. Block, Deborah M. Thompson, Marcelo G. Bonini, Patrick T. Ronaldson, Reina Bendayan, David S. Miller

Anatomy and Neurobiology Publications

Background

Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide.

Methods

To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent …

Physical Activity And Sedentary Behavior Of Cancer Survivors And Non-Cancer Individuals: Results From A National Survey, Roy B. Kim, Allison Phillips, Kirsten Herrick, Marieka Helou, Carlin Rafie, Mitchell S. Anscher, Ross B. Mikkelsen, Yi Ning

Anatomy and Neurobiology Publications

Increasing physical activity and decreasing sedentary behavior are associated with a higher quality of life and lower mortality rates for cancer survivors, a growing population group. Studies detailing the behavior of cancer survivors are limited. Therefore, we investigated physical activity and sedentary behavior of cancer survivors using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Participants were those who provided physical activity and sedentary behavior data. Those who were pregnant,old, or10,472 non-cancer participants. After adjustment for age, race, gender, education status, body mass index, and smoking status, cancer survivors (n = 10,472) reported significantly longer duration of …

Contributions Of Vldlr And Lrp8 In The Establishment Of Retinogeniculate Projections, Jianmin Su, Michael A. Klemm, Anne M. Josephson, Michael A. Fox

Anatomy and Neurobiology Publications

Background

Retinal ganglion cells (RGCs), the output neurons of the retina, project to over 20 distinct brain nuclei, including the lateral geniculate nucleus (LGN), a thalamic region comprised of three functionally distinct subnuclei: the ventral LGN (vLGN), the dorsal LGN (dLGN) and the intergeniculate leaflet (IGL). We previously identified reelin, an extracellular glycoprotein, as a critical factor that directs class-specific targeting of these subnuclei. Reelin is known to bind to two receptors: very-low-density lipoprotein receptor (VLDLR) and low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2). Here we examined the roles of these canonical reelin …

Paclitaxel-Induced Apoptosis Is Bak-Dependent, But Bax And Bim-Independent In Breast Tumor, Anna V. Miller, Mark A. Hicks, Wataru Nakajima, Amanda C. Richardson, Jolene J. Windle, Hisashi Harada

Philips Institute for Oral Health Research Publications

Paclitaxel (Taxol)-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death) plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim−/− MEFs (mouse embryonic fibroblasts), the bim−/− mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak−/− MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel …

Two-Component System Response Regulators Involved In Virulence Of Streptococcus Pneumoniae Tigr4 In Infective Endocarditis, My Trihn, Xiuchun Ge, Alleson Dobson, Todd Kitten, Cindy Munro, Ping Xu

Philips Institute for Oral Health Research Publications

Streptococci resident in the oral cavity have been linked to infective endocarditis (IE). While other viridans streptococci are commonly studied in relation to IE, less research has been focused on Streptococcus pneumoniae. We established for the first time an animal model of S. pneumoniae IE, and examined the virulence of the TIGR4 strain in this model. We hypothesized that two-component systems (TCS) may mediate S. pneumoniae TIGR4 strain virulence in IE and examined TCS response regulator (RR) mutants of TIGR4 in vivo with the IE model. Thirteen of the 14 RR protein genes were mutagenized, excluding only the essential …

Structure-Based Mechanism For Early Plp-Mediated Steps Of Rabbit Cytosolic Serine Hydroxymethyltransferase Reaction, Martino L. Di Salvo, J. Neel Scarsdale, Galina Kazanina, Roberto Contestabile, Verne Schirch, H. Tonie Wright

Biochemistry and Molecular Biology Publications

Serine hydroxymethyltransferase catalyzes the reversible interconversion of L-serine and glycine with transfer of one-carbon groups to and from tetrahydrofolate. Active site residue Thr254 is known to be involved in the transaldimination reaction, a crucial step in the catalytic mechanism of all pyridoxal 5′-phosphate- (PLP-) dependent enzymes, which determines binding of substrates and release of products. In order to better understand the role of Thr254, we have expressed, characterized, and determined the crystal structures of rabbit cytosolic serine hydroxymethyltransferase T254A and T254C mutant forms, in the absence and presence of substrates. These mutants accumulate a kinetically stable gem-diamine intermediate, and their …

Osu-03012 Sensitizes Breast Cancers To Lapatinib-Induced Cell Killing: A Role For Nck1 But Not Nck2, N. Winston West, Aileen Garcia-Vargas, Charles E. Chalfant, Margaret A. Park

Biochemistry and Molecular Biology Publications

Background

Lapatinib is characterized as an ErbB1/ErbB2 dual inhibitor and has recently been approved for the treatment of metastatic breast cancer. In this study, we examined mechanisms associated with enhancing the activity of lapatinib via combination with other therapies.

Methods

In the present studies, estrogen receptor (ER) positive and ER negative breast cancer cells were genetically manipulated to up- or downregulate eIF2-alpha, its phospho-mutant, Nck1, or Nck2, then treated with OSU-03012, lapatinib or the combination and assayed for cytotoxicity/cytostaticity using clonogenic assays.

Results

Treatment of breast cancer cell lines with lapatinib and OSU-03012 (a small molecule derivative of the Cox-2 …

A Networks Method For Ranking Microrna Dysregulation In Cancer, William Budd, Sarah Seashols, Danielle Weaver, Cyriac Joseph, Zendra E. Zehner

Biochemistry and Molecular Biology Publications

Background

Despite the lack of agreement on their exact roles, it is known that miRNAs contribute to cancer progression. Many studies utilize methods to detect differential regulation of miRNA expression. It is prohibitively expensive to examine all potentially dysregulated miRNAs and traditionally, researchers have focused their efforts on the most extremely dysregulated miRNAs. These methods may overlook the contribution of less differentially expressed but more functionally relevant miRNAs. The purpose of this study was to outline a method that not only utilizes differential expression but ranks miRNAs based on the functional relevance of their targets. This work uses a networks …

The Geometry Of Locomotive Behavioral States In C. Elegans, Thomas Gallagher, Theresa Bjorness, Robert Greene, Young-Jai You, Leon Avery

Biochemistry and Molecular Biology Publications

We develop a new hidden Markov model-based method to analyze C elegans locomotive behavior and use this method to quantitatively characterize behavioral states. In agreement with previous work, we find states corresponding to roaming, dwelling, and quiescence. However, we also find evidence for a continuum of intermediate states. We suggest that roaming, dwelling, and quiescence may best be thought of as extremes which, mixed in any proportion, define the locomotive repertoire of C elegans foraging and feeding behavior.

Light-Induced Translocation Of Rgs9-1 And Gβ5l In Mouse Rod Photoreceptors, Mei Tian, Marisa Zallocchi, Weimin Wang, Ching-Kang Chen, Krzysztof Palczewski, Duane Delimont, Dominic Cosgrove, You-Wei Peng

Biochemistry and Molecular Biology Publications

The transducin GTPase-accelerating protein complex, which determines the photoresponse duration of photoreceptors, is composed of RGS9-1, Gβ5L and R9AP. Here we report that RGS9-1 and Gβ5L change their distribution in rods during light/dark adaptation. Upon prolonged dark adaptation, RGS9-1 and Gβ5L are primarily located in rod inner segments. But very dim-light exposure quickly translocates them to the outer segments. In contrast, their anchor protein R9AP remains in the outer segment at all times. In the dark, Gβ5L's interaction with R9AP decreases significantly and RGS9-1 is phosphorylated at S475 to a significant degree. Dim light exposure leads to quick de-phosphorylation of …

Hif- And Non-Hif-Regulated Hypoxic Responses Require The Estrogen-Related Receptor In Drosophila Melanogaster, Yan Li, Divya Padmanabha, Luciana B. Gentile, Catherine I. Dumur, Robert B. Beckstead, Keith D. Baker

Biochemistry and Molecular Biology Publications

Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been determined. Here, we investigate how HIF influences hypoxic adaptation throughout Drosophila melanogaster development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in sima mutants and that these animals are unable to mobilize glycogen in hypoxia. …

Lipopolysaccharide-Induced Neuronal Activation In The Paraventricular And Dorsomedial Hypothalamus Depends On Ambient Temperature, Samuel P. Wanner, Kyoko Yoshida, Vladimir A. Kulchitsky, Andrei I. Ivanov, Kazuyuki Kanosue, Andrej A. Romanovsky

Human and Molecular Genetics Publications

Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS). To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.5 mg/kg, intravenously) either in a thermoneutral (30°C) or cool (24°C) environment. At 30°C, LPS caused fever; at 24°C, the same dose caused profound hypothermia. Both fever and hypothermia were …

Wicking: A Rapid Method For Manually Inserting Ion Channels Into Planar Lipid Bilayers, Justin A. Costa, Dac A. Nguyen, Egdar Leal-Pinto, Ronald E. Gordon, Basil Hanss

Physiology and Biophysics Publications

The planar lipid bilayer technique has a distinguished history in electrophysiology but is arguably the most technically difficult and time-consuming method in the field. Behind this is a lack of experimental consistency between laboratories, the challenges associated with painting unilamellar bilayers, and the reconstitution of ion channels into them. While there has be a trend towards automation of this technique, there remain many instances where manual bilayer formation and subsequent membrane protein insertion is both required and advantageous. We have developed a comprehensive method, which we have termed “wicking”, that greatly simplifies many experimental aspects of the lipid bilayer system. …

In Vivo Regulation Of Brain-Derived Neurotrophic Factor In Dorsal Root Ganglia Is Mediated By Nerve Growth Factor-Triggered Akt Activation During Cystitis, Li-Ya Qiao, Sharon Yu, Jarren C. Kay, Chun-Mei Xia

Physiology and Biophysics Publications

Abstract

The role of brain-derived neurotrophic factor (BDNF) in sensory hypersensitivity has been suggested; however the molecular mechanisms and signal transduction that regulate BDNF expression in primary afferent neurons during visceral inflammation are not clear. Here we used a rat model of cystitis and found that the mRNA and protein levels of BDNF were increased in the L6 dorsal root ganglia (DRG) in response to bladder inflammation. BDNF up-regulation in the L6 DRG was triggered by endogenous nerve growth factor (NGF) because neutralization of NGF with a specific NGF antibody reduced BDNF levels during cystitis. The neutralizing NGF antibody also …