Medicine and Health Sciences Commons^™

A Selective Gβγ-Linked Intracellular Mechanism For Modulation Of A Ligand-Gated Ion Channel By Ethanol, Gonzalo E. Yevenes, Gustavo Moraga-Cid, Robert W. Peoples, Günther Schmalzing, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

The current understanding about ethanol effects on the ligand-gated ion channel (LGIC) superfamily has been restricted to identify potential binding sites within transmembrane (TM) domains in the Cys-loop family. Here, we demonstrate a key role of the TM3–4 intracellular loop and Gβγ signaling for potentiation of glycine receptors (GlyRs) by ethanol. We discovered 2 motifs within the large intracellular loop of the GlyR α₁ subunit that are critical for the actions of pharmacological concentrations of ethanol. Significantly, the sites were ethanol-specific because they did not alter the sensitivity to general anesthetics, neurosteroids, or longer n-alcohols. Furthermore, Gβγ scavengers …

Neural Substrates Of Sound–Touch Synesthesia After A Thalamic Lesion, Michael S. Beauchamp, Tony Ro

Publications and Research

Neural plasticity induced by stroke can mediate positive outcomes, such as recovery of function, but can also result in the formation of abnormal connections with negative consequences for perception and cognition. In three experiments using blood-oxygen level dependent (BOLD) functional magnetic resonance imaging, we examined the neural substrates of acquired auditory-tactile synesthesia, in which certain sounds can produce an intense somatosensory tingling sensation in a patient with a thalamic lesion. Compared with nine normal controls, the first experiment showed that the patient had a threefold greater BOLD response to sounds in the parietal operculum, the location of secondary somatosensory cortex. …

Torsina And The Pathophysiology Of Dyt1 Dystonia, Yu Zhao

Theses and Dissertations (ETD)

The goal of my dissertation work was to examine the systems biology of torsinA, a DYT1 dystonia-associated protein, by using rodent model systems. TorsinA is a putative ATPase associated with a variety of cellular activities (AAA+). Deletion of glutamic acid residue 302/303 in TOR1A is causally associated with many cases of early-onset primary dystonia.

In our work, transient forebrain ischemia and sciatic nerve transection were used as central and peripheral neural perturbations, respectively, to gain insight into the in vivo role(s) of torsinA. Moreover, transgenic mouse models that overexpress either human mutant torsinA (hMT) or wild-type torsinA (hWT) were used …

Fitness And Action Monitoring: Evidence For Improved Cognitive Flexibility In Young Adults, Jason R. Themanson, Matthew B. Pontifex, Charles H. Hillman

Jason R. Themanson, Ph.D

To improve behavior, one must detect errors and initiate subsequent corrective adaptations. This action monitoring process has been widely studied, but little is known about how one may improve this aspect of cognition. To examine the relationship between cardiorespiratory fitness and action monitoring, we recorded the error-related negativity (ERN), an event-related brain potential believed to index action monitoring, as well as post-error behavioral indices of action monitoring from healthy young adults (18–25 years) who varied in cardiorespiratory fitness. These measures were collected during the execution of flanker tasks emphasizing response accuracy or speed to better assess the specificity of any …

Focus On Rna Isolation: Obtaining Rna For Microrna (Mirna) Expression Profiling Analyses Of Neural Tissue, Wang-Xia Wang, Bernard R. Wilfred, Donald A. Baldwin, R. Benjamin Isett, Na Ren, Arnold J. Stromberg, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of 'upstream' variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional …

Technical Variables In High-Throughput Mirna Expression Profiling: Much Work Remains To Be Done, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Guiliang Tang

Pathology and Laboratory Medicine Faculty Publications

MicroRNA (miRNA) gene expression profiling has provided important insights into plant and animal biology. However, there has not been ample published work about pitfalls associated with technical parameters in miRNA gene expression profiling. One source of pertinent information about technical variables in gene expression profiling is the separate and more well-established literature regarding mRNA expression profiling. However, many aspects of miRNA biochemistry are unique. For example, the cellular processing and compartmentation of miRNAs, the differential stability of specific miRNAs, and aspects of global miRNA expression regulation require specific consideration. Additional possible sources of systematic bias in miRNA expression studies include …

Neuroendocrine Peptides Neuropeptide-Y (Npy) And Peptide-Yy (Pyy) Suppress Cl- Secretion And K+ Secretion In Guinea Pig Distal Colon Through Action At Y2-Receptors, Susan T. Halm, Jin Zhang, Dan R. Halm

Neuroscience, Cell Biology & Physiology Faculty Publications

Electrogenic Cl^– and K⁺ secretion in isolated mucosa from guinea pig distal colon measured as short-circuit current (I_sc) and transepithelial conductance (G_t) were stimulated by epinephrine (epi), prostaglandin-E₂ (PGE₂) and carbachol (CCh). neuropeptide-Y (NPY) and peptide-YY (PYY) inhibited by 60% Cl^– secretion activated by either PGE₂ or PGE₂+CCh with EC₅₀’s of 16nM and 6nM, respectively. Neither peptide markedly inhibited the transient component of the PGE₂+CCh response. Immunoreactivity (IR) for NPY was present in enteric ganglia and in proximity with crypts. Basolateral membranes of …

Investigating Bimanual Coordination In Dominant And Non-Dominant Virtual Hands, Gavin Buckingham, David Carey

Gavin Buckingham

A bias in attention towards the dominant hand has been cited as a possible factor in the lateralisation of human bimanual coordination (Peters, 1981). A mirror was placed between the hands of 18 dextral participants performing rhythmic anti-phase movements. This set-up gave the appearance of a reflected virtual hand (moving in time with the un-occluded hand), in the same spatial location as the occluded left or right hand. This asymmetrical conflict between vision and action examined whether the left hand would show higher levels of error when replaced by a virtual right hand than the converse condition. Higher levels of …

Short-Term Memory, Working Memory, And Executive Functioning In Preschoolers: Longitudinal Predictors Of Mathematical Achievement At Age 7 Years, Rebecca Bull, Kimberly A. Espy, Sandra A. Wiebe

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

This study examined whether measures of short-term memory, working memory, and executive functioning in preschool children predict later proficiency in academic achievement at 7 years of age (third year of primary school). Children were tested in preschool (M age = 4 years, 6 months) on a battery of cognitive measures, and mathematics and reading outcomes (from standardized, norm-referenced school-based assessments) were taken on entry to primary school, and at the end of the first adn third year of primary school. Growth curve analyses examined predictors of math and reading achievement across the duration of the study and revealed that better …

Viral Vectors In The Research Laboratory: Just How Safe Are They?, Dawn P. Wooley, Kimberly Kay Morris, Robert Mcrae, John C. Trefry

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.

The Ubiquitin-Proteasome System Is Necessary For Long-Term Synaptic Depression In Aplysia, Diasinou Fioravante, Rong-Yu Liu, John H. Byrne

Journal Articles

The neuropeptide Phe-Met-Arg-Phe-NH(2) (FMRFa) can induce transcription-dependent long-term synaptic depression (LTD) in Aplysia sensorimotor synapses. We investigated the role of the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to presynaptic inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by CREB2, which is generally regarded as a transcription repressor. Binding of CREB2 to the promoter region of ap-uch was accompanied by histone hyperacetylation, suggesting that CREB2 cannot only inhibit but also promote gene expression. CREB2 was phosphorylated …

Evidence That Α2-Antiplasmin Becomes Covalently Ligated To Plasma Fibrinogen In The Circulation: A New Role For Plasma Factor Xiii In Fibrinolysis Regulation, Michael W. Mosesson, Kevin R. Siebenlist, Irene Hernandez, K. N. Lee, V. J. Christiansen, P. A. Mckee

Biomedical Sciences Faculty Research and Publications

Background:

Plasma alpha₂-antiplasmin (α₂AP) is a rapid and effective inhibitor of the fibrinolytic enzyme plasmin. Congenital α₂AP deficiency results in a severe hemorrhagic disorder due to accelerated fibrinolysis. It is well established that in the presence of thrombin-activated factor XIII (FXIIIa), α₂AP becomes covalently ligated to the distal α chains of fibrin or fibrinogen at lysine 303 (two potential sites per molecule). Some time ago we showed that α₂AP is covalently linked to plasma fibrinogen . That singular observation led to our hypothesis that native plasma factor XIII (FXIII), …

Blunted Cystine–Glutamate Antiporter Function In The Nucleus Accumbens Promotes Cocaine-Induced Drug Seeking, Kristen S. Kau, Aric Madayag, John R. Mantsch, Mark D. Grier, Omer Abdulhameed, David A. Baker

Biomedical Sciences Faculty Research and Publications

Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine–glutamate exchange via system x_c−, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system x_c−. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system x_c−. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0–60 mg/kg, i.p.) in the …

Neutralization Of Botulinum Neurotoxin By A Human Monoclonal Antibody Specific For The Catalytic Light Chain., Sharad P Adekar, Tsuyoshi Takahashi, R Mark Jones, Fetweh H Al-Saleem, Denise M Ancharski, Michael J Root, B P Kapadnis, Lance L Simpson, Scott K Dessain

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Botulinum neurotoxins (BoNT) are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC), a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored.

METHODS AND FINDINGS: We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A). The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for …

Transcriptional Regulation Network Analysis Of The Hypertension-Perturbed Nucleus Tractus Solitarius, Gregory E. Gonye, Rajanikanth Vadigepalli, Haiping Hao, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Poster Presentation.

Freesurfer-Initiated Fully-Automated Subcortical Brain Segmentation In Mri Using Large Deformation Diffeomorphic Metric Mapping., Ali R Khan, Lei Wang, Mirza Faisal Beg

Brain and Mind Institute Researchers' Publications

Fully-automated brain segmentation methods have not been widely adopted for clinical use because of issues related to reliability, accuracy, and limitations of delineation protocol. By combining the probabilistic-based FreeSurfer (FS) method with the Large Deformation Diffeomorphic Metric Mapping (LDDMM)-based label-propagation method, we are able to increase reliability and accuracy, and allow for flexibility in template choice. Our method uses the automated FreeSurfer subcortical labeling to provide a coarse-to-fine introduction of information in the LDDMM template-based segmentation resulting in a fully-automated subcortical brain segmentation method (FS+LDDMM). One major advantage of the FS+LDDMM-based approach is that the automatically generated segmentations generated are …

El Virus De La Diarrea Viral En Bovinos Criollos De La Provincia De Melgar, Puno, Q. Richard Quispe, Ccama Albert S., Hermelinda G. Rivera, Mariluz Araínga

Journal Articles: Pharmacology & Experimental Neuroscience

The prevalence of bovine viral diarrhea virus (BVDV) infection in 347 evaluated was criollo cattle of both sexes and older than 6 months of age in small herds of the province of Melgar, Puno. Serum samples were tested for antibodies against BVDV using the viral neutralization test. The 48.7 ± 0.1% (166/347) of the samples had antibodies against BVDV. Animals carrying on the virus, virus were not detected. Antibodies were detected in all sampled herds and the prevalence varied from 15.7 to 94.1%. Antibodies titers varied from 2 to >256, showing that BVDV infection is widespread in the local cattle …

Self-Efficacy Effects On Neuroelectric And Behavioral Indices Of Action Monitoring In Older Adults, Jason R. Themanson, Charles H. Hillman, Edward Mcauley, Sarah M. Buck, Shawna E. Doerksen, Katherine S. Morris, Matthew B. Pontifex

Jason R. Themanson, Ph.D

The relationships between self-efficacy (SE), i.e., beliefs in personal capabilities, and behavioral and neuroelectric (i.e., ERN, Pe) indices of action monitoring were investigated in 40 older adults (13 male) during the completion of a flanker paradigm performed under task conditions emphasizing either accuracy or speed. SE relative to task performance during both conditions was assessed prior to each cognitive task. Results indicated that high-SE older adults exhibited larger ERN and Pe amplitudes compared to low-SE older adults under the accuracy instruction condition. Additionally, a moderating effect of SE on the relationship between ERN and post-error response accuracy was revealed in …

Three-Dimensional Arm Movements At Constant Equi-Affine Speed, Frank E. Pollick, Uri Maoz, Amir A. Handzel, Peter J. Giblin, Guillermo Sapiro, Tamar Flash

Psychology Faculty Articles and Research

It has long been acknowledged that planar hand drawing movements conform to a relationship between movement speed and shape, such that movement speed is inversely proportional to the curvature to the power of one-third. Previous literature has detailed potential explanations for the power-law’s existence as well as systematic deviations from it. However, the case of speed-shape relations for three-dimensional (3D) drawing movements has remained largely unstudied. In this paper we first derive a generalization of the planar power law to 3D movements, which is based on the principle that this power law implies motion at constant equi-affine speed. This generalization …

The Role Of Extracellular Matrix And Matrix-Degrading Proteases In Neonatal Hypoxic-Ischemic Injury, Christopher C. Leonardo

USF Tampa Graduate Theses and Dissertations

Improvements in medical care over recent decades have increased the number of premature and low birth weight infants that survive hypoxic-ischemic (H-I) insults. Because there is a rising incidence in diseases associated with these events, it is critical to develop effective therapies to treat the various resulting neuropathies. Extracellular matrix constitutes the majority of brain parenchyma. Lecticans and matrix-degrading proteases including ADAMTSs (a disintegrin and metalloproteinase with thrombospondin repeats) and matrix metalloproteinases (MMPs) exert effects on cell viability and may be associated with either protective or destructive processes after H-I. Both ADAMTSs (Cross et al. 2006; Tian et al. 2007) …

Effects Of Acute Ethyl Alcohol Consumption On A Psychophysical Measure Of Lateral Inhibition In Human Vision., Kevin D Johnston, Brian Timney

Brain and Mind Institute Researchers' Publications

Acute consumption of ethyl alcohol affects a variety of visual functions. However, there have been few systematic attempts to investigate the neural mechanisms underlying these effects. Here, we employed the Westheimer paradigm to investigate the hypothesis that alcohol reduces lateral inhibition within human "perceptive fields", the psychophysical analogue of physiological receptive fields. Westheimer functions obtained under alcohol and no-alcohol conditions at photopic, mesopic, and scotopic levels of adaptation showed changes consistent with an alcohol-induced decrease in lateral inhibition. We conclude that this decrease in lateral inhibition may be responsible for some of the changes in visual perception that result from …

Factors Influencing Topotecan Cns Penetration In Mouse Models, Jun Shen

Theses and Dissertations (ETD)

Camptothecin analogs such as topotecan are currently tested in clinical trials for brain tumors. However the clinical outcome is far below the expectations, which are derived from the promising preclinical studies. This discrepancy could be partially attributed to the presence of two barrier systems in the brain, the blood brain barrier (BBB) and blood cerebrospinal fluid (CSF) barrier (BCB). Further investigations have demonstrated multiple ATP-binding cassette (ABC) transporters are present at the two barriers. Camptothecin analogs are well known substrates for several of the transporters. This work defined the role of two ABC transporters, Bcrp1 and P-gp in determination of …

Changing The Rules At The Drop Of A Hat: An Erp Study Of Preschoolers' Set-Shifting Ability, Sandra A. Wiebe, Daniel J. Carroll, Megan Herrington, Sari Raber, Kimberly A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

We examined the neural correlates of set-shifting in 5-year-old children and examined whether the ease of switching was affected by varying the number of non-switch trials preceding a switch.

Drd2 Genotype And Prenatal Exposure To Tobacco Interact To Influence Infant Attention And Reactivity, Sandra A. Wiebe, Kimberly A. Espy, Christian Stopp, Jennifer Respass, Travis Jameson, Jodi Huggenvik

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

The present study examined the effects of dopamine receptor D2 genotype and PTE status on early infant neurobehavior.

Using Confirmatory Factor Analysis To Understand Executive Control In Preschool Children: I. Latent Structure, Sandra A. Wiebe, Kimberly A. Espy, David Charak

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

*This article may not exactly replicate the final version published in the APA journal. It is not the copy of record. http://content.apa.org/journals/0012-1649 Although many tasks have been developed recently to study executive control in the preschool years, the constructs that underlie performance on these tasks are poorly understood. In particular, it is unclear whether executive control is comprised of multiple, separable cognitive abilities (e.g., inhibition and working memory) or whether it is unitary in nature. A sample of 243 normally developing children between 2.25 and 6 years of age completed a battery of ageappropriate executive control tasks. Confirmatory factor analysis …

Functional Interactions Of Alcohol-Sensitive Sites In The N-Methyl-D-Aspartate Receptor M3 And M4 Domains, Hong Ren, Abdelghaffar K. Salous, Jaclyn M. Paul, Kaitlin A. Lamb, Donard S. Dwyer, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The N-methyl-d-aspartate receptor is an important mediator of the behavioral effects of ethanol in the central nervous system. Previous studies have demonstrated sites in the third and fourth membrane-associated (M) domains of the N-methyl-d-aspartate receptor NR2A subunit that influence alcohol sensitivity and ion channel gating. We investigated whether two of these sites, Phe-637 in M3 and Met-823 in M4, interactively regulate the ethanol sensitivity of the receptor by testing dual substitution mutants at these positions. A majority of the mutations decreased steady-state glutamate EC₅₀ values and maximal steady-state to peak current ratios (I_ss/I …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Gene Expression Profile Of Neuronal Progenitor Cells Derived From Hescs: Activation Of Chromosome 11p15.5 And Comparison To Human Dopaminergic Neurons., William J Freed, Jia Chen, Cristina M Bäckman, Catherine M Schwartz, Tandis Vazin, Jingli Cai, Charles E Spivak, Carl R Lupica, Mahendra S Rao, Xianmin Zeng

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription.

METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined.

PRINCIPAL FINDINGS: A number of genes known to be involved in the …

Incorporating Information From Neuroscience And Endocrinology Regarding Sexual Orientation Into Social Work Education, Jill Littrell

SW Publications

The brains of heterosexual males and heterosexual females are different. Moreover, the brains of gay men are similar to heterosexual females whereas the brains of lesbians are similar to heterosexual males. Neuroscience research supporting these postulates is reviewed. The gestational processes that might explain the differences in brain structure and function corresponding with gender are reviewed. Following a discussion of the physiological bases for sexual orientation, a discussion of the physiological bases for the expression of gender related traits and a discussion of factors contributing to sexual identity are provided. Throughout the article, alternative ways to think about gender are …

Mechanisms Underlying Inspiratory Burst Generation In Prebotzinger Complex Neurons Of Neonatal Mice, Ryland Weed Pace

Dissertations, Theses, and Masters Projects

Understanding how molecular and cellular events integrate into a physiological behavior is a major question in neuroscience. Breathing can be easily studied using rhythmically active in vitro models that provide experimental access to perform cellular- and synapse-level experiments. While it is widely accepted that breathing depends on a specific region of the brainstem dubbed the preBotzinger complex (preBotC), the mechanisms responsible for rhythm generation remain unclear. In Chapter 1, we examine the pacemaker hypothesis, which posits that pacemaker properties and/or the persistent sodium current (/NaP) are obligatory for rhythm generation. We found that neither pacemaker properties nor /NaP are essential …