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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 …

Molecular Diversity Of Bacteroidales In Fecal And Environmental Samples And Swine-Associated Subpopulations, Regina Lamendella, Kent C. Li, Daniel B. Oerther, Jorge W. Santo Domingo

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

Several swine-specific microbial source tracking methods are based on PCR assays targeting Bacteroidales 16S rRNA gene sequences. The limited application of these assays can be explained by the poor understanding of their molecular diversity in fecal sources and environmental waters. In order to address this, we studied the diversity of 9,340 partial (>600bp in length) Bacteroidales 16S rRNA gene sequences from 13 fecal sources and nine feces-contaminated watersheds. The compositions of major Bacteroidales populations were analyzed to determine which host and environmental sequences were contributing to each group. This information allowed us to identify populations which were both exclusive …

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 …

The Eagleville Times,Volume 11, Issue 2, Debbie Ryan

Eagleville Times

No abstract provided.

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 …

Tree Climbing And Human Evolution, Vivek V. Venkataraman, Thomas S. Kraft, Nathaniel J. Dominy

Dartmouth Scholarship

Paleoanthropologists have long argued—often contentiously—about the climbing abilities of early hominins and whether a foot adapted to terrestrial bipedalism constrained regular access to trees. However, some modern humans climb tall trees routinely in pursuit of honey, fruit, and game, often without the aid of tools or support systems. Mortality and morbidity associated with facultative arboreality is expected to favor behaviors and anatomies that facilitate safe and efficient climbing. Here we show that Twa hunter–gatherers use extraordinary ankle dorsiflexion (>45°) during climbing, similar to the degree observed in wild chimpanzees. Although we did not detect a skeletal signature of dorsiflexion …

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 …

If All Other Options Fail: The Plight Of Wild Horses And The Dubois Case For Horse Slaughtering, Brendan Vandor

University of Michigan Journal of Law Reform Caveat

Robert Redford recently joined forces with former presidential candidate Bill Richardson to stop the return of horse slaughtering to the United States. Few among us would bet against that duo in their fight for a cause that appears on its face to be unassailably just. Yet, horse slaughtering is a highly complex issue that boasts its fair share of credible supporters, and the activity is poised for a revival after a six-year ban if Redford, Richardson, and various animal rights groups do not win a recently-brought federal lawsuit. This Comment recommends a multi-pronged approach to solving the problem of wild …

Coordinated Dynamic Gene Expression Changes In The Central Nucleus Of The Amygdala During Alcohol Withdrawal., Kate Freeman, Mary M. Staehle, Rajanikanth Vadigepalli, Gregory E Gonye, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber

College of Science & Mathematics Departmental Research

BACKGROUND: Chronic alcohol use causes widespread changes in the cellular biology of the amygdala's central nucleus (CeA), a GABAergic center that integrates autonomic physiology with the emotional aspects of motivation and learning. While alcohol-induced neurochemical changes play a role in dependence and drinking behavior, little is known about the CeA's dynamic changes during withdrawal, a period of emotional and physiologic disturbance.

METHODS: We used a qRT-PCR platform to measure 139 transcripts in 92 rat CeA samples from control (N = 33), chronically alcohol exposed (N = 26), and withdrawn rats (t = 4, 8, 18, 32, and 48 hours; N …

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 …

Neutrophils Control The Magnitude And Spread Of The Immune Response In A Thromboxane A2-Mediated Process, Chiao-Wen Yang, Emil R. Unanue

Open Access Publications

Neutrophils are obligate cells entering lymph nodes shortly after immunization with protein antigens in adjuvants, starting during the first hour and continuing for several days in two distinct waves. Previously, we demonstrated the strong suppressive effects of neutrophils on CD4 T cell and B cell responses, using either neutrophil-depleting antibodies or genetically neutropenic mice. In this study, we find that neutrophils are the major cells controlling the spread of T cell responses to distal lymph nodes. Although in the presence of neutrophils, ∼75% of the response was restricted to the draining node, in their absence, most of the response was …

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 …

Evaluation Of Copper Concentration In Subclinical Cases Of White Muscle Disease And Its Relationship With Cardiac Troponin I, F. Ataollahi, M. Mohri, H.A. Seifi, Belinda Pingguan-Murphy, Wan Abu Bakar Wan Abas, Noor Azuan Abu Osman

Research Publications (2011 to 2015)

The present study aims to evaluate the serum level of copper (Cu) in lambs suffering from subclinical forms of white muscle disease (WMD) and its relationship with cardiac troponin I (cTn-I) as a novel biomarker of cardiovascular disorders. Ten milliliters of jugular blood were taken from 200 lambs less than one year old to measure serum concentrations of Cu, selenium (Se), and cTn-I. The subjects were divided into 2 groups, namely, the deficient group which included 36 lambs, and the control group which included 164 lambs according to the reference serum Se concentration (50 ng/mL). Serum Se levels in the …

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 …

Force Generation By Kinesin And Myosin Cytoskeletal Motor Proteins, F. Jon Kull, Sharyn A. Endow

Dartmouth Scholarship

Kinesins and myosins hydrolyze ATP, producing force that drives spindle assembly, vesicle transport and muscle contraction. How do motors do this? Here we discuss mechanisms of motor force transduction, based on their mechanochemical cycles and conformational changes observed in crystal structures. Distortion or twisting of the central β-sheet - proposed to trigger actin-induced Pi and ADP release by myosin, and microtubule-induced ADP release by kinesins - is shown in a movie depicting the transition between myosin ATP-like and nucleotide-free states. Structural changes in the switch I region form a tube that governs ATP hydrolysis and Pi release by the motors, …

Ruminating On Ruminants: Goats And The People Who Raise Them In South Carolina, Brianna Dyan Farber

Theses and Dissertations

In South Carolina, many farmers and homesteaders have utilized goats as an adaptive and versatile resource and component of their diversified farming operations. This thesis addresses the experiences, motivations, difficulties, and successes of people raising goats in South Carolina, in the context of sustainable agricultural practice and landscapes. Goats cohabit insecure but promising ecological, political, economic, and sociocultural landscapes with humans and other nonhuman species. These relationships can undermine and support goats as belonging in South Carolina. My participants cannot simply raise goats as a purely economic choice because they create meaningful emotional relationships with their animals. Goats can become …

Tolerance Of Sponge Assemblages To Temperature Anomalies: Resilience And Proliferation Of Sponges Following The 1997-8 El-Niño Southern Oscillation., Francisco Kelmo, James J. Bell, Martin J. Attrill

School of Biological and Marine Sciences

Coral reefs across the world are under threat from a range of stressors, and while there has been considerable focus on the impacts of these stressors on corals, far less is known about their effect on other reef organisms. The 1997-8 El-Niño Southern Oscillation (ENSO) had notable and severe impacts on coral reefs worldwide, but not all reef organisms were negatively impacted by this large-scale event. Here we describe how the sponge fauna at Bahia, Brazil was influenced by the 1997-8 ENSO event. Sponge assemblages from three contrasting reef habitats (reef tops, walls and shallow banks) at four sites were …

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 …

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 …

The Evaluation Of Az66, An Optimized Sigma Receptor Antagonist, Against Methamphetamine-Induced Dopaminergic Neurotoxicity And Memory Impairment In Mice, Michael J. Seminerio, Rolf Hansen, Nidhi Kaushal, Han-Ting Zhang, Christopher R. Mccurdy, Rae R. Matsumoto

Faculty & Staff Scholarship

Sigma (σ) receptors have recently been identified as potential targets for the development of novel therapeutics aimed at mitigating the effects of methamphetamine. Particularly, σ receptors are believed to mitigate some of the neurotoxic effects of methamphetamine through modulation of dopamine, dopamine transporters and body temperature. Furthermore, recent evidence suggests that targeting σ receptors may prevent cognitive impairments produced by methamphetamine. In the present study, an optimized σ receptor antagonist, AZ66, was evaluated against methamphetamine-induced neurotoxicity and cognitive dysfunction. AZ66 was found to be highly selective for σ receptors compared to 64 other sites tested. Pretreatment of male, Swiss Webster …