Medical Physiology Commons^™

Learning From Mistakes: Improving Initial Fingertip Force Scaling By Observing Lifting Errors, Gavin Buckingham, Minnie Tang, Paul Gribble, Melvyn A. Goodale

Psychology Presentations

• When lifting objects that are lighter or heaver than we expect them to be, individuals typically misapply forces in a way that reflects their prior expectations of heaviness.

• Because we lift in this predictive way, large and small cubes elicit these characteristic errors even when they are adjusted to have equal mass. Lifters will apply too much force to a large cube and substantially less force to a small cube – errors that are rapidly corrected with repeated lifts (Flanagan & Beltzner, 2000).

• When watching others lift objects, an observer’s motor system automatically reacts in a way …

Lesion Of Cholinergic Neurons In Nucleus Basalis Enhances Response To General Anesthetics, Leung L. Stan

Physiology and Pharmacology Publications

Acetylcholine in the brain has been associated with consciousness and general anesthesia effects. We tested the hypothesis that the integrity of the nucleus basalis magnocellularis (NBM) affects the response to general anesthetics. Cholinergic neurons in NBM were selectively lesioned by bilateral infusion of 192IgG-saporin in adult, male Long–Evans rats, and control rats were infused with saline. Depletion of choline-acetyltransferase (ChAT)-immunoreactive cells in the NBM and decrease in optical density of acetylcholinesterase (AChE) staining in the frontal and visual cortices confirmed a significant decrease in NBM cholinergic neurons in lesioned as compared to control rats. AChE staining in the hippocampus and …

Toward A Mechanistic Understanding Of Narcolepsy With Cataplexy, William Mccurdy

McNair Poster Presentations

Narcolepsy (hypersomnolence) is a disorder that affects 1 in 2000 individuals in the United States and it is characterized by excessive daytime sleepiness (EDS) and catalepsy, which is a sudden loss of muscle tone. As of relatively recent years, there has been a general consensus amongst the scientific community concerning the etiology of narcolepsy as numerous studies suggest that it is caused by the deficiency of neurotransmitters called orexin-A and orexin-B (or hypocretin-1 and hypocretin-2). Research suggests that deficiencies of these proteins are related to a mutation on chromosome 6 in the human leukocyte antigen (HLA) complex which is a …

Lysophosphatidic Acid Production And Signaling In Platelets, Zachary Bennett Fulkerson

Theses and Dissertations--Physiology

Lysophosphatidic acid (LPA) belongs to a class of extracellular lipid signaling molecules. In the vasculature, LPA may regulate platelet activation and modulate endothelial and smooth muscle cell function. LPA has therefore been proposed as a mediator of cardiovascular disease.

The bulk of circulating LPA is produced from plasma lysophosphatidylcholine (LPC) by autotaxin (ATX), a secreted lysophospholipase D (lysoPLD). Early studies suggest that some of the production of circulating LPA is platelet-dependent. ATX possesses an N-terminal somatomedin B-like domain suggesting the hypothesis that ATX interacts with platelet integrins which may localize ATX to substrate in the membrane and/or alter the catalytic …

Effect Of Type 2 Diabetes On The Dynamic Response Characteristics Of Leg Vascular Conductance During Exercise, Oscar Mac Ananey, H Reilly, D O'Shea, M Egana, S Green

Articles

Abstract

In this study we tested the hypothesis that type 2 diabetes impairs the dynamic response of leg vascular conductance (LVC) during exercise. LVC (leg blood flow/mean arterial pressure) responses were studied during intermittent contractions of the calf muscle in subjects with type 2 diabetes (n = 9), heavy controls (n = 10) and lean controls (n = 8) using a biexponential function and an estimate of the mean response time (MRT). The time constant of the second phase of LVC was significantly greater in type 2 diabetes (66.4 ± 29.2 s) than the heavy (22.2 ± 13.4 s) and …

Strategies For Targeting Lentiviral Vectors, Christopher Matthew Trimby

University of Kentucky Doctoral Dissertations

Lentiviral gene therapy has held great promise for treating a wide range of neurological disorders due to its ability to stably integrate into the genome of nondividing cells like neurons, in addition to dividing cells. The nervous system is a complex and highly heterogeneous system, and while a therapeutic intervention may have beneficial effects in one population of cells it may have severe side effects in another. For this reason, specific targeting of lentiviral vectors is crucial for their ultimate utility for research and clinical research use.

Two different approaches for focusing the targeting of lentiviral vectors were employed in …

Genome-Wide Association Studies At The Interface Of Alzheimer’S Disease And Epidemiologically Related Disorders, Christopher Ryan Simmons

University of Kentucky Doctoral Dissertations

Genome-wide association studies (GWAS)s provide an unbiased means of exploring the landscape of complex genetic disease. As such, these studies have identified genetic variants that are robustly associated with a multitude of conditions. I hypothesize that these genetic variants serve as excellent tools for evaluation of the genetic interface between epidemiologically related conditions. Herein, I test the association between SNPs associated with either (i) plasma lipids, (ii) rheumatoid arthritis (RA) or (iii) diabetes mellitus (DM) and late-onset Alzheimer’s disease (AD) to identify shared genetic variants. Regarding the most significantly AD-associated variants, I have also attempted to elucidate their molecular function. …

Von Willebrand Factor Expression In Vascular Endothelial Cells Of Cage Control And Antiorthostatic Cage Suspension Golden Hamster Ovaries., Kristan Provchy

Undergraduate Honors Theses

The hamster estrous cycle lasts four days and is considered to be a physiological model for angiogenesis. Angiogenesis is the formation of new capillaries from preexisting vessels, and it occurs extensively during corpus luteum formation in the estrous cycle. Von Willebrand Factor (vWF) is a glycoprotein that is secreted uniquely in endothelial cells and megakaryocytes. It is frequently used as an endothelial cell marker and it is able to detect vessels within tissues when it is used in immunohistochemical staining techniques. This study explores von Willebrand Factor expression within Golden Hamster ovarian tissue. In particular, this study uses cage control …

Long-Term Hypoxia Regulates Cortisol Biosynthesis In The Ovine Fetal Adrenal Cortex, Vladimir Enrique Vargas

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies demonstrated enhanced fetal adrenal cortisol biosynthesis following exposure to long-term hypoxia (LTH). The studies presented here were designed to determine the mechanism(s) regulating this important adaptive endocrine response. Ewes were maintained at high altitude (3,820 m) from approximately day 40 to 138-141 of gestation. Fetal adrenal glands were then collected from LTH and age matched normoxic controls. Dispersed fetal adrenal cortical cells (FACs) were untreated, treated with ACTH, treated in combination with ACTH precursors (POMC and 22-kDa pro-ACTH), or pre-treated with H-89 and or UO126 followed by ACTH treatment. Following ACTH treatment, cortisol biosynthesis increased in both groups …

Analysis Of Β8 Integrin In Neurogenesis And Neurovascular Homeostasis, Aaron K. Mobley

Dissertations and Theses (Open Access)

Neurogenesis in the adult mouse brain occurs within the subventricular zone (SVZ) of the lateral ventricle. In the SVZ, neural stem cells (NSC) reside in a specialized microenvironment, or vascular niche, consisting of blood vessels and their basement membranes. Most NSCs in the SVZ differentiate into progenitor cells, which further differentiate to generate neuroblasts, which then migrate from the SVZ to the olfactory bulbs (OB) along the rostral migratory stream (RMS). ECM-mediated adhesion and signaling within the vascular niche likely contribute to proper NSC self-renewal, survival, differentiation and neuroblast motility. The mechanisms that control these events are poorly understood. Previous …

Quantification Of Localized Brain Iron Sources Using Magnetic Resonance Phase, Grant Alexander Mcauley

Loma Linda University Electronic Theses, Dissertations & Projects

Brain microbleeds (BMB), often present in cerebrovascular and neurodegenerative diseases and neurotrauma, are associated with both chronic and acute illness of significant social and economic impact. Because BMB present a source of potentially cyctotoxic iron to the brain proportional to the amount of extravasated blood, non-invasive quantification of this iron pool is potentially valuable both to assess tissue risk and as a biomarker to monitor disease progression, treatment efficacy, and inform treatment. Past efforts to quantify brain iron have focused on distributed (e.g., anatomical) brain regions. However, BMB represent localized sources of iron deposition. In addition, conventional "magnitude" MR images …

Cortisol Exerts Bi-Phasic Regulation Of Inflammation In Humans, Mark P. Yeager, Patricia Pioli, Paul M. Guyre

Dartmouth Scholarship

Natural and synthetic glucocorticoids (GCs) have been used for decades to suppress inflammation. In this paper, we re-examine the role of the endogenous GC, cortisol, as a primary homeostatic regulator of the human inflammatory response to injury. Our data show that cortisol regulation of innate immunity can be both pro-inflammatory and anti-inflammatory. Using a human model of in vivo cortisol depletion, we first show that baseline (diurnal) cortisol concentrations do not exert an anti-inflammatory effect. This is the first clue that cortisol regulation of inflammation is not represented by a linear dose-response relationship. We next show in surgical patients that …

Q-Ve-Oph, A Negative Control For O-Phenoxy-Conjugated Caspase Inhibitors, Benjamin Southerland, Kashmira Kulkarni-Datar, Chanel Keoni, Rebecca Bricker, William C. Grunwald Jr., Daniel M. Ketcha, Eugene Hern, David R. Cool, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

The broad-spectrum apoptosis (caspase) inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibi- tor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh, thereby retaining the identical charge and molecular properties with only the addition of an extra –CH2 group. The purity …

Optimal Bone Strength And Mineralization Requires The Type 2 Iodothyronine Deiodinase In Osteoblasts, J. H. D. Bassett, Alan Boyde, Peter G. T. Howell, Richard H. Bassett, Thomas M. Galliford, Marta Archanco, Holly Evans, Michelle A. Lawson, Peter Croucher, Donald L. St. Germain, Valerie A. Galton, Graham R. Williams

Dartmouth Scholarship

Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3'-L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone …

Bitc Sensitizes Pancreatic Adenocarcinomas To Trail-Induced Apoptosis, Christina A. Wicker, Ravi P. Sahu, Kashmira Kulkarni-Datar, Sanjay K. Srivastava, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is often associated with mutations in codon 12 of the K-Ras gene (K-Ras 12), which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC). BITC is a component of cruciferous vegetables and a cell cycle …

Electrospun Nanofibers For Neural Tissue Engineering, Jingwei Xie, Matthew R. Macewan, Andrea G. Schwartz, Younan Xia

MIIR Faculty Research

Biodegradable nanofibers produced by electrospinning represent a new class of promising scaffolds to support nerve regeneration. We begin with a brief discussion on electrospinning of nanofibers and methods for controlling the structure, porosity, and alignment of the electrospun nanofibers. The methods include control of the nanoscale morphology and microscale alignment for the nanofibers, as well as the fabrication of macroscale, three-dimensional tubular structures. We then highlight recent studies that utilize electrospun nanofibers to manipulate biological processes relevant to nervous tissue regeneration, including stem cell differentiation, guidance of neurite extension, and peripheral nerve injury treatments. The main objective of this feature …

Laterality, Perception, And Action During The Size-Weight Illusion, Gavin Buckingham, Nathalie S. Ranger, Melvyn A. Goodale

Psychology Presentations

In the classic size-weight illusion (SWI), a small object will feel heavier than an larger object of equal weight (Charpentier, 1891). Individuals continue to perceive this illusory difference in weight long after their gripping and lifting forces have scaled to the actual, identical, mass of the illusion-inducing stimuli (Flanagan & Beltzner, 2000).

The independence of our weight perception and fingertip force application has only been quantified in the right hand of right-handers. The immunity to this perceptual illusion may be affected by manual asymmetries (e.g., Gonzalez, Ganel & Goodale, 2006).

We examined perception of heaviness and fingertip force scaling in …

Individualized Cognitive Modeling For Close-Loop Task Mitigation, Guangfan Zhang, Roger Xu, Wei Wang, Jiang Li, Tom Schnell, Mike Keller, Thomas E. Pinelli (Ed.)

Electrical & Computer Engineering Faculty Publications

An accurate real-time operator functional state assessment makes it possible to perform task management, minimize risks, and improve mission performance. In this paper, we discuss the development of an individualized operator functional state assessment model that identifies states likely leading to operational errors. To address large individual variations, we use two different approaches to build a model for each individual using its data as well as data from subjects with similar responses. If a subject's response is similar to that of the individual of interest in a specific functional state, all the training data from this subject will be used …

The Role Of The L-Type Calcium Channel And Its Carboxyl-Terminus, Miranda Jean Byse

University of Kentucky Doctoral Dissertations

In the heart, the primary role of the L-type calcium channel (LTCC) Ca_V1.2 is to conduct calcium into cardiomyocytes and initiate contraction. However, part of the Ca_V1.2 channel itself, the cleaved carboxyl-terminus (CCt) can also localize to the nucleus and regulate gene transcription. Therefore, the goal of this dissertation project was to determine the role and regulation of CCt in the embryonic and adult heart. The global hypothesis of my dissertation project is that CCt localizes to the nucleus in embryonic and adult cardiomyocytes via a calcium-mediated mechanism and regulates transcription. A model of pharmacological LTCC …

Local Synaptic Network Interactions In The Dentate Gyrus Of A Cortical Contusion Model Of Posttraumatic Epilepsy, Robert F. Hunt Iii

University of Kentucky Doctoral Dissertations

Posttraumatic epilepsy is a common consequence of brain trauma. However, little is known about how long-term changes in local excitatory and inhibitory synaptic networks contribute to epilepsy after closed-head brain injury. This study adapted a widely used model of experimental brain injury as a mouse model of posttraumatic epilepsy. Behavioral seizure activity and alterations in synaptic circuitry in the dentate gyrus were examined in mice after experimental cortical contusion brain injury. Spontaneous behavioral seizures were observed in 20% of mice after moderate injury and 36-40% of mice weeks after severe injury. In the dentate gyrus, most mice displayed regionally localized …