Medicine and Health Sciences Commons^™

Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods. Adipocyte APN mRNA and protein expression and plasma APN and TNFα concentrations were determined. APN expression/production began to decline 3 h after reperfusion (reaching nadir 12 h after reperfusion), returning to control levels 7 days after reperfusion. Plasma TNFα levels began to increase 1 h after reperfusion, peaking at 3 h and returning to control levels 24 h after …

Effects Of Aging On Apoptosis Gene Expression In Oral Mucosal Tissues, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = …

Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo

Dartmouth Scholarship

During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, is robustly expressed in MaSCs and is required for preservation of self-renewing capacity in diverse epithelial structures. However, the mechanism(s) underlying subversion of this activity during forfeiture of self-renewing capacity are poorly understood. MicroRNAs (miRNAs) govern critical cellular functions including stem cell maintenance, development, cell cycle regulation and differentiation by disrupting translation of target mRNAs. Data presented here …

An Acacb Variant Implicated In Diabetic Nephropathy Associates With Body Mass Index And Gene Expression In Obese Subjects, Lijun Ma, Mariana Murea, James A. Snipes, Alejandra Marinelarena, Jacqueline Krüger, Pamela J. Hicks, Kurt A. Langberg, Meredith A. Bostrom, Jessica N. Cooke, Daisuke Suzuki, Tetsuya Babazono, Takashi Uzu, Sydney C. W. Tang, Ashis K. Mondal, Neeraj K. Sharma, Sayuko Kobes, Peter A. Antinozzi, Matthew Davis, Swapan K. Das, Neda Rasouli, Philip A. Kern, Nathan J. Shores, Lawrence L. Rudel, Matthias Blüher, Michael Stumvoll, Donald W. Bowden, Shiro Maeda, John S. Parks, Peter Kovacs, Robert L. Hanson, Leslie J. Baier, Steven C. Elbein, Barry I. Freedman

Internal Medicine Faculty Publications

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n …

Role Of An Iron-Dependent Transcriptional Regulator In The Pathogenesis And Host Response To Infection With Streptococcus Pneumoniae., Radha Gupta, Minny Bhatty, Edwin Swiatlo, Bindu Nanduri

CVM Publications

Iron is a critical cofactor for many enzymes and is known to regulate gene expression in many bacterial pathogens. Streptococcus pneumoniae normally inhabits the upper respiratory mucosa but can also invade and replicate in lungs and blood. These anatomic sites vary considerably in both the quantity and form of available iron. The genome of serotype 4 pneumococcal strain TIGR4 encodes a putative iron-dependent transcriptional regulator (IDTR). A mutant deleted at idtr (?idtr) exhibited growth kinetics similar to parent strain TIGR4 in vitro and in mouse blood for up to 48 hours following infection. However, ?idtr was significantly attenuated in a …

Stallion Sperm Transcriptome Comprises Functionally Coherent Coding And Regulatory Rnas As Revealed By Microarray Analysis And Rna-Seq., Pranab J. Das, Fiona M. Mccarthy, Monika Vishnoi, Nandina Paria, Cathy Gresham, Gang Li, Priyanka Kachroo, A. Kendrick Sudderth, Sheila Teague, Charles C. Love, Dickson D. Varner, Bhanu P. Chowdhary, Terje Raudsepp

CVM Publications

Mature mammalian sperm contain a complex population of RNAs some of which might regulate spermatogenesis while others probably play a role in fertilization and early development. Due to this limited knowledge, the biological functions of sperm RNAs remain enigmatic. Here we report the first characterization of the global transcriptome of the sperm of fertile stallions. The findings improved understanding of the biological significance of sperm RNAs which in turn will allow the discovery of sperm-based biomarkers for stallion fertility. The stallion sperm transcriptome was interrogated by analyzing sperm and testes RNA on a 21,000-element equine whole-genome oligoarray and by RNA-seq. …

Muc4 Overexpression Augments Cell Migration And Metastasis Through Egfr Family Proteins In Triple Negative Breast Cancer Cells., Partha Mukhopadhyay, Imayavaramban Lakshmanan, Moorthy P. Ponnusamy, Subhankar Chakraborty, Maneesh Jain, Priya Pai, Lynette M. Smith, Subodh M. Lele, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

INTRODUCTION: Current studies indicate that triple negative breast cancer (TNBC), an aggressive breast cancer subtype, is associated with poor prognosis and an early pattern of metastasis. Emerging evidence suggests that MUC4 mucin is associated with metastasis of various cancers, including breast cancer. However, the functional role of MUC4 remains unclear in breast cancers, especially in TNBCs.

METHOD: In the present study, we investigated the functional and mechanistic roles of MUC4 in potentiating pathogenic signals including EGFR family proteins to promote TNBC aggressiveness using in vitro and in vivo studies. Further, we studied the expression of MUC4 in invasive TNBC tissue …

Engineering A Bcr-Abl–Activated Caspase For The Selective Elimination Of Leukemic Cells, Manabu Kurokawa, Takahiro Ito, Chih-Sheng Yang, Chen Zhao

Dartmouth Scholarship

Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of …

Caveolin-1 Deficiency Induces Spontaneous Endothelial-To-Mesenchymal Transition In Murine Pulmonary Endothelial Cells In Vitro., Zhaodong Li, Peter J. Wermuth, Bryan S. Benn, Michael P. Lisanti, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

It was previously demonstrated that transforming growth factor β (TGF-β) induces endothelial-to-mesenchymal transition (EndoMT) in murine lung endothelial cells (ECs) in vitro. Owing to the important role of caveolin-1 (CAV1) in TGF-β receptor internalization and TGF-β signaling, the participation of CAV1 in the induction of EndoMT in murine lung ECs was investigated. Pulmonary ECs were isolated from wild-type and Cav1 knockout mice using immunomagnetic methods with sequential anti-CD31 and anti-CD102 antibody selection followed by in vitro culture and treatment with TGF-β1. EndoMT was assessed by semiquantitative RT-PCR for Acta2, Col1a1, Snai1, and Snai2; by immunofluorescence for α-smooth muscle actin; and …

Block Copolymer Cross-Linked Nanoassemblies Improve Particle Stability And Biocompatibility Of Superparamagnetic Iron Oxide Nanoparticles, Mo Dan, Daniel F. Scott, Peter A. Hardy, Robert J. Wydra, J. Zach Hilt, Robert A. Yokel, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

PURPOSE: To develop cross-linked nanoassemblies (CNAs) as carriers for superparamagnetic iron oxide nanoparticles (IONPs).

METHODS: Ferric and ferrous ions were co-precipitated inside core-shell type nanoparticles prepared by cross-linking poly(ethylene glycol)-poly(aspartate) block copolymers to prepare CNAs entrapping Fe(3)O(4) IONPs (CNA-IONPs). Particle stability and biocompatibility of CNA-IONPs were characterized in comparison to citrate-coated Fe(3)O(4) IONPs (Citrate-IONPs).

RESULTS: CNA-IONPs, approximately 30 nm in diameter, showed no precipitation in water, PBS, or a cell culture medium after 3 or 30 h, at 22, 37, and 43°C, and 1, 2.5, and 5 mg/mL, whereas Citrate-IONPs agglomerated rapidly (> 400 nm) in all …

Properties Of Ribbon And Non-Ribbon Release From Rod Photoreceptors Revealed By Visualizing Individual Synaptic Vesicles., Minghui Chen, Matthew J. Van Hook, David Zenisek, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

Vesicle release from rod photoreceptors is regulated by Ca(2+) entry through L-type channels located near synaptic ribbons. We characterized sites and kinetics of vesicle release in salamander rods by using total internal reflection fluorescence microscopy to visualize fusion of individual synaptic vesicles. A small number of vesicles were loaded by brief incubation with FM1-43 or a dextran-conjugated, pH-sensitive form of rhodamine, pHrodo. Labeled organelles matched the diffraction-limited size of fluorescent microspheres and disappeared rapidly during stimulation. Consistent with fusion, depolarization-evoked vesicle disappearance paralleled electrophysiological release kinetics and was blocked by inhibiting Ca(2+) influx. Rods maintained tonic release at resting membrane …

Genetic Diversity In The Modern Horse Illustrated From Genome-Wide Snp Data, Jessica L. Petersen, James R. Mickelson, E. Gus Cothran, Lisa S. Andersson, Jeanette Axelsson, Ernie Bailey, Danika Bannasch, Matthew M. Binns, Alexandre S. Borges, Pieter Brama, Artur Da Câmara Machado, Ottmar Distl, Michela Felicetti, Laura Fox-Clipsham, Kathryn T. Graves, Gérard Guérin, Bianca Haase, Telhisa Hasegawa, Karin Hemmann, Emmeline W. Hill, Tosso Leeb, Gabriella Lindgren, Hannes Lohi, Maria Susana Lopes, Beatrice A. Mcgivney, Sofia Mikko, Nicholas Orr, M. Cecilia T. Penedo, Richard J. Piercy, Marja Raekallio, Stefan Rieder, Knut H. Røed, Maurizio Silvestrelli, June Swinburne, Teruaki Tozaki, Mark Vaudin, Claire M. Wade, Molly E. Mccue

Veterinary Science Faculty Publications

Horses were domesticated from the Eurasian steppes 5,000-6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. F(ST) calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect …

Genome-Wide Analysis Reveals Selection For Important Traits In Domestic Horse Breeds, Jessica L. Petersen, James R. Mickelson, Aaron K. Rendahl, Stephanie J. Valberg, Lisa S. Andersson, Jeanette Axelsson, Ernie Bailey, Danika Bannasch, Matthew M. Binns, Alexandre S. Borges, Pieter Brama, Artur Da Câmara Machado, Stefano Capomaccio, Katia Cappelli, E. Gus Cothran, Ottmar Distl, Laura Fox-Clipsham, Kathryn T. Graves, Gérard Guérin, Bianca Haase, Telhisa Hasegawa, Karin Hemmann, Emmeline W. Hill, Tosso Leeb, Gabriella Lindgren, Hannes Lohi, Maria Susana Lopes, Beatrice A. Mcgivney, Sofia Mikko, Nicholas Orr, M. Cecilia T. Penedo, Richard J. Piercy, Marja Raekallio, Stefan Rieder, Knut H Røed, June Swinburne, Teruaki Tozaki, Mark Vaudin, Claire M. Wade, Molly E. Mccue

Veterinary Science Faculty Publications

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F(ST)-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with …

Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F. Bjeldanes, Keith Rayburn

Natural Sciences and Mathematics | Faculty Scholarship

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …

Lateral Mobility Of L-Type Calcium Channels In Synaptic Terminals Of Retinal Bipolar Cells., Wallace B. Thoreson, Aaron J. Mercer, Karlene M. Cork, Robert J. Szalewski

Journal Articles: Ophthalmology

PURPOSE: Efficient and precise release of glutamate from retinal bipolar cells is ensured by the positioning of L-type Ca(2+) channels close to release sites at the base of the synaptic ribbon. We investigated whether Ca(2+) channels at bipolar cell ribbon synapses are fixed in position or capable of moving in the membrane.

METHODS: We tracked the movements of individual L-type Ca(2+) channels in bipolar cell terminals after labeling channels with quantum dots (QDs) attached to α(2)δ(4) accessory Ca(2+) channel subunits via intermediary antibodies.

RESULTS: We found that individual Ca(2+) channels moved within a confined domain of 0.13-0.15 μm(2) in bipolar …

Dual-Tracer Background Subtraction Approach For Fluorescent Molecular Tomography, Kenneth M. Tichauer, Robert W. Holt, Fadi El-Ghussein, Scott C. Davis, Kimberly S. Samkoe, Jason R. Gunn, Frederic Leblond, Brian W. Pogue

Dartmouth Scholarship

Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction …

Long-Term Upregulation Of Inflammation And Suppression Of Cell Proliferation In The Brain Of Adult Rats Exposed To Traumatic Brain Injury Using The Controlled Cortical Impact Model, Sandra A. Acosta, Naoki Tajiri, Kazutaka Shinozuka, Hiroto Ishikawa, Bethany Grimmig, David M. Diamond, Paul R. Sanberg, Paula C. Bickford, Yuji Kaneko, Cesario V. Borlongan

Psychology Faculty Publications

The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal …

Gleevec, An Abl Family Inhibitor, Produces A Profound Change In Cell Shape And Migration, Zaozao Chen, Elizabeth Lessey, Matthew E. Berginski, Li Cao, Jonathan Li, Xavier Trepat, Michelle Itano, Shawn M. Gomez, Maryna Kapustina, Cai Huang, Keith Burridge, George Truskey, Ken Jacobson

Markey Cancer Center Faculty Publications

The issue of how contractility and adhesion are related to cell shape and migration pattern remains largely unresolved. In this paper we report that Gleevec (Imatinib), an Abl family kinase inhibitor, produces a profound change in the shape and migration of rat bladder tumor cells (NBTII) plated on collagen-coated substrates. Cells treated with Gleevec adopt a highly spread D-shape and migrate more rapidly with greater persistence. Accompanying this more spread state is an increase in integrin-mediated adhesion coupled with increases in the size and number of discrete adhesions. In addition, both total internal reflection fluorescence microscopy (TIRFM) and interference reflection …

P38 Mapk Regulates Cavitation And Tight Junction Function In The Mouse Blastocyst., Christine E Bell, Andrew J Watson

Obstetrics & Gynaecology Publications

UNLABELLED: Blastocyst formation is essential for implantation and maintenance of pregnancy and is dependent on the expression and coordinated function of a series of proteins involved in establishing and maintaining the trans-trophectoderm ion gradient that enables blastocyst expansion. These consist of Na/K-ATPase, adherens junctions, tight junctions (TJ) and aquaporins (AQP). While their role in supporting blastocyst formation is established, the intracellular signaling pathways that coordinate their function is unclear. The p38 MAPK pathway plays a role in regulating these proteins in other cell types and is required for embryo development at the 8-16 cell stage, but its role has not …

Loss Of Dendritic Inhibition In The Hippocampus After Repeated Early-Life Hyperthermic Seizures In Rats., Richard Boyce, L Stan Leung

Physiology and Pharmacology Publications

Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but …

Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory., Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this …

Characterization Of Induced Neural Progenitors From Skin Fibroblasts By A Novel Combination Of Defined Factors., Changhai Tian, Qiang Liu, Kangmu Ma, Yongxiang Wang, Qiang Chen, Randall Ambroz, David L. Klinkebiel, Yuju Li, Yunlong Huang, Jianqing Ding, Jie Wu, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

Recent reports have demonstrated that somatic cells can be directly converted to other differentiated cell types through ectopic expression of sets of transcription factors, directly avoiding the transition through a pluripotent state. Our previous experiments generated induced neural progenitor-like cells (iNPCs) by a novel combination of five transcription factors (Sox2, Brn2, TLX, Bmi1 and c-Myc). Here we demonstrated that the iNPCs not only possess NPC-specific marker genes, but also have qualities of primary brain-derived NPCs (WT-NPCs), including tripotent differentiation potential, mature neuron differentiation capability and synapse formation. Importantly, the mature neurons derived from iNPCs exhibit significant physiological properties, such as …

Therapies For Neovascular Age-Related Macular Degeneration: Current Approaches And Pharmacologic Agents In Development., Mostafa Hanout, Daniel Ferraz, Mehreen Ansari, Natasha Maqsood, Saleema Kherani, Yasir J. Sepah, Nithya Rajagopalan, Mohamed Ibrahim, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is …

A Penile Spine/Vibrissa Enhancer Sequence Is Missing In Modern And Extinct Humans But Is Retained In Multiple Primates With Penile Spines And Sensory Vibrissae, Philip L. Reno, Cory Y Mclean, Jasmine E Hines, Terence D Capellini, Gill Bejerano, David M Kingsley

PCOM Scholarly Works

Previous studies show that humans have a large genomic deletion downstream of the Androgen Receptor gene that eliminates an ancestral mammalian regulatory enhancer that drives expression in developing penile spines and sensory vibrissae. Here we use a combination of large-scale sequence analysis and PCR amplification to demonstrate that the penile spine/vibrissa enhancer is missing in all humans surveyed and in the Neandertal and Denisovan genomes, but is present in DNA samples of chimpanzees and bonobos, as well as in multiple other great apes and primates that maintain some form of penile integumentary appendage and facial vibrissae. These results further strengthen …

Is The Reporting Timeliness Gap For Avian Flu And H1n1 Outbreaks In Global Health Surveillance Systems Associated With Country Transparency?, Feng-Jen Tsai, Eva Tseng, Chang-Chuan Chan, Hiko Tamashiro, Sandrine Motamed, André C Rougemont

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap.

METHODS: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging …

Combination Therapy For Inflammation And Neurodegeneration In Multiple Sclerosis Rodent Model, Nicole Neva Marie Trager

MUSC Theses and Dissertations

Multiple sclerosis (MS) is a complex demyelinating CNS disease that involves both immunologic and neurodegenerative mechanisms of pathophysiology. MS is characterized by lymphocyte infiltration in the CNS resulting in extensive axonal neurodegenerative processes. The current therapies for MS act through either immunomodulatory or immunosuppressive mechanisms; none address both the immune and degenerative arms of the disease. The immunomodulatory agents are generally broad spectrum and non-specific immunosuppression and are associated with significant toxicities. Thus, novel therapies or therapeutic strategies are needed to fully combat both inflammatory and neurodegenerative events that define MS. The animal model experimental autoimmune encephalomyelitis (EAE) is used …

Cattle-Related Injuries And Farm Management Practices On Kentucky Beef Cattle Farms, Steven R. Browning, Susan C. Westneat, Wayne T. Sanderson, Deborah B. Reed

Epidemiology and Environmental Health Faculty Publications

While working on farms with livestock increases the risk of injury among farm workers in comparison to other commodity farms, few studies have examined the role offarm management practices in association with the risk of cattle-related injury. We examined the farm management practices of Kentucky beef cattle farms in association with self-reported rates of cattle-related injuries among workers. We conducted a mail survey of a random sample of 2,500 members of the Kentucky Cattlemen's Association. Results from 1,149 farm operators who were currently raising beef cattle and provided complete survey response are reported. During the busy season, the principal operator …

Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib

Dartmouth Scholarship

Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the …

Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, Daniel W. Buster, Scott G. Daniel, Huy Q. Nguyen, Sarah L. Windler, Lara C. Skwarek, Maureen Peterson

Dartmouth Scholarship

Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCF(Slimb) ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCF(Slimb) function reorganized interphase chromosomes into dense, compact domains and disrupted …

Mitochondrial Cardiomyopathy: Pathophysiology, Diagnosis, And Management, Deborah E Meyers, Haseeb Ilias Basha, Mary Kay Koenig

The Texas Heart Institute Journal

Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy can be described as a myocardial condition characterized by abnormal heart-muscle structure, function, or both, secondary to genetic defects involving the mitochondrial respiratory …