Medical Anatomy Commons^™

The Mglur2/3 Agonist Ly397268 Improves Morphometric And Behavioral Outcomes In R6/2 Huntington's Disease Mice, Dennis Craig Lafferty

Theses and Dissertations (ETD)

A prominent theory for the pathology of Huntington's Disease (HD) is the excitotoxic injury to the striatum. Continual exposure of ionotropic NMDA receptors to glutamate from the cortex can be excitotoxic in HD and leave striatal neurons vulnerable to damage. Activation of presynaptic mGluR2/3 by an agonist dampens glutamate release from corticostriatal terminals. Treatments that target excitoxicity and oxidative stress thus may improve some of the symptoms in HD patients and it is therefore logical to pursue therapies aimed in this direction. LY379268 is an inviting mGluR2/3 agonist that has been shown to be neuroprotective in hypoxic and ischemic injuries …

S-Glutathionylation Activates Stim1 And Alters Mitochondrial Homeostasis., Brian J Hawkins, Krishna M Irrinki, Karthik Mallilankaraman, Yu-Chin Lien, Youjun Wang, Cunnigaiper D Bhanumathy, Ramasamy Subbiah, Michael F Ritchie, Jonathan Soboloff, Yoshihiro Baba, Tomohiro Kurosaki, Suresh K Joseph, Donald L Gill, Muniswamy Madesh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca(2+) signaling. However, precisely how oxidants influence Ca(2+) signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca(2+) mobilization from an oscillatory to a sustained elevated pattern via calcium release-activated calcium (CRAC)-mediated capacitive Ca(2+) entry, and stromal interaction molecule 1 (STIM1)- and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca(2+) entry alters mitochondrial Ca(2+) handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to …

Descending Branch Of The Lateral Circumflex Femoral Artery - Arterial Genicular Anastomoses, Maher Sabalbal

Maher Sabalbal

Genicular collateral arterial circulation is required for perfusion of the lower leg should the superficial femoral artery (SFA) become obstructed by trauma or disease. When describing the anatomy, textbooks only provide a schematic representation of the genicular collateral circulation and suggest that the descending branch of the lateral circumflex artery (DBLCFA) plays a critical role. The DBLCFA may be removed for bypass and reconstructive surgeries; therefore, a sound anatomical description of this artery is essential. This study combines dissection with 3D reconstruction to describe the anatomy of the DBLCFA and to provide a morphological description of its involvement in the …

Inference Of Cancer-Specific Gene Regulatory Networks Using Soft Computing Rules., Xiaosheng Wang, Osamu Gotoh

Journal Articles: Genetics, Cell Biology & Anatomy

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One …

Azi-Isoflurane, A Photolabel Analog Of The Commonly Used Inhaled General Anesthetic Isoflurane., Roderic G Eckenhoff, Jin Xi, Motomu Shimaoka, Aditya Bhattacharji, Manuel Covarrubias, William P Dailey

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Volatility and low-affinity hamper an ability to define molecular targets of the inhaled anesthetics. Photolabels have proven to be a useful approach in this regard, although none have closely mimicked contemporary drugs. We report here the synthesis and validation of azi-isoflurane, a compound constructed by adding a diazirinyl moiety to the methyl carbon of the commonly used general anesthetic isoflurane. Azi-isoflurane is slightly more hydrophobic than isoflurane, and more potent in tadpoles. This novel compound inhibits Shaw2 K(+) channel currents similarly to isoflurane and binds to apoferritin with enhanced affinity. Finally, when irradiated at 300 nm, azi-isoflurane adducts to residues …

A Robust Gene Selection Method For Microarray-Based Cancer Classification., Xiaosheng Wang, Osamu Gotoh

Journal Articles: Genetics, Cell Biology & Anatomy

Gene selection is of vital importance in molecular classification of cancer using high-dimensional gene expression data. Because of the distinct characteristics inherent to specific cancerous gene expression profiles, developing flexible and robust feature selection methods is extremely crucial. We investigated the properties of one feature selection approach proposed in our previous work, which was the generalization of the feature selection method based on the depended degree of attribute in rough sets. We compared the feature selection method with the established methods: the depended degree, chi-square, information gain, Relief-F and symmetric uncertainty, and analyzed its properties through a series of classification …

Large Scale Analysis Of Positional Effects Of Single-Base Mismatches On Microarray Gene Expression Data, Fenghai Duan, Mark A. Pauley, Eliot R. Spindel, Li Zhang, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Affymetrix GeneChips utilize 25-mer oligonucleotides probes linked to a silica surface to detect targets in solution. Mismatches due to single nucleotide polymorphisms (SNPs) can affect the hybridization between probes and targets. Previous research has indicated that binding between probes and targets strongly depends on the positions of these mismatches. However, there has been substantial variability in the effect of mismatch type across studies.

METHODS: By taking advantage of naturally occurring mismatches between rhesus macaque transcripts and human probes from the Affymetrix U133 Plus 2 GeneChip, we collected the largest 25-mer probes dataset with single-base mismatches at each of the …

Sustained Expression Of Tdp-43 And Fus In Motor Neurons In Rodent's Lifetime., Cao Huang, Pedro Yuxing Xia, Hongxia Zhou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS) are two highly conserved ribonucleoproteins. Pathogenic mutations of the TDP-43 or the FUS gene are all linked to amyotrophic lateral sclerosis (ALS) that is characterized by progressive degeneration of motor neurons. To better understand the correlation of ALS disease genes with the selectivity of chronic motor neuron degeneration, we examined the longitudinal expression of the TDP-43 and the FUS genes in C57BL6 mice and in Sprague-Dawley rats. TDP-43 and FUS were robustly and ubiquitously expressed in the postnatal mice and rats, but were markedly decreased in the adult rodents. In adulthood, …

Use Of Electronic Anatomy Practical Examinations For Remediating “At Risk” Students, Frank J. Daly

Biomedical Sciences Faculty Publications

Restrictive laboratory scheduling, an increasing number of human cadaver-based anatomy courses and a reduction in the curricular time allotted to anatomy courses have created problems with cadaver laboratory access at the University of New England. This article describes a combination of anatomy testing and grading strategies to allow “at risk” (borderline failing) students an opportunity to remediate their lowest set of examination scores and pass their anatomy course. An alternative electronic practical examination for these students provided flexibility in laboratory scheduling, thereby increasing laboratory access for other students taking concurrent courses. Specifically, the electronic examinations allowed for a reduction in …

Characterization And Optimization Of Microelectrode Arrays For Glutamate Measurements In The Rat Hippocampus, Pooja Mahendra Talauliker

University of Kentucky Doctoral Dissertations

An overarching goal of the Gerhardt laboratory is the development of an implantable neural device that allows for long-term glutamate recordings in the hippocampus. Proper L-glutamate regulation is essential for hippocampal function, while glutamate dysregulation is implicated in many neurodegenerative diseases. Direct evidence for subregional glutamate regulation is lacking in previous in vivo studies because of limitations in the spatio-temporal resolution of conventional experimental techniques. We used novel enzyme-coated microelectrode arrays (MEAs) for rapid measurements (2Hz) of extracellular glutamate in urethane-anesthetized rats. Potassium-evoked glutamate release was highest in the cornu ammonis 1 (CA1) subregion and lowest in the cornu ammonis …