Animal Experimentation and Research Commons^™

Analyzing And Modeling The Dysfunction Of Inhibitory Neurons In Alzheimer’S Disease, Carlos Perez, Jokubas Ziburkus, Ghamim Ullah

Physics Faculty Publications

Alzheimer’s disease (AD) is characterized by the abnormal proteolytic processing of amyloid precursor protein, resulting in increased production of a self-aggregating form of beta amyloid (Aβ). Several lines of work on AD patients and transgenic mice with high Aβ levels exhibit altered rhythmicity, aberrant neuronal network activity and hyperexcitability reflected in clusters of hyperactive neurons, and spontaneous epileptic activity. Recent studies highlight that abnormal accumulation of Aβ changes intrinsic properties of inhibitory neurons, which is one of the main reasons underlying the impaired network activity. However, specific cellular mechanisms leading to interneuronal dysfunction are not completely …

Act On The Registration And Evaluation Of Chemicals (K-Reach) And Replacement, Reduction Or Refinement Best Practices, Soojin Ha, Troy Seidle, Kyung-Min Lim

Legal Regulation of Animal Research Collection

Objectives - Korea’s Act on the Registration and Evaluation of Chemicals (K-REACH) was enacted for the protection of human health and the environment in 2015. Considering that about 2000 new substances are introduced annually across the globe, the extent of animal testing requirement could be overwhelming unless regulators and companies work proactively to institute and enforce global best practices to replace, reduce or refine animal use. In this review, the way to reduce the animal use for K-REACH is discussed. Methods - Background of the enforcement of the K-REACH and its details was reviewed along with the papers and regulatory …

Animal-Friendly Affinity Reagents: Replacing The Needless In The Haystack, A. C. Gray, S. S. Sidhu, P. C. Chandrasekera, C. F.M. Hendriksen, C. A.K. Borrebaeck

Biomedicine and Animal Models in Research Collection

The multibillion-dollar global antibody industry produces an indispensable resource but that is generated using millions of animals. Despite the irrefutable maturation and availability of animal-friendly affinity reagents (AFAs) employing na€ive B lymphocyte or synthetic recombinant technologies expressed by phage display, animal immunisation is still authorised for antibody production. Remarkably, replacement opportunities have been overlooked, despite the enormous potential reduction in animal use. Directive 2010/63/EU requires that animals are not used where alternatives exist. To ensure its implementation, we have engaged in discussions with the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) and the Directorate General for Environment …

Arkansas Animal Science Department Report 2016, Paul Beck, Jason Apple, Shane Gadberry, Beth Kegley, Charles Rosenkrans Jr.

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Nemo-Like Kinase (Nlk) Is A Pathological Signaling Effector In The Mouse Heart, Ruijie Liu

Peer Reviewed Articles

Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice. NLK transgenic mice demonstrated baseline cardiac hypertrophy, dilation, interstitial fibrosis, apoptosis and progression towards heart failure in response to two surgery-induced …

A Murine Model Of Inflammation-Induced Cerebral Microbleeds, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Tatiana B. Krasieva, Miriam Scadeng, Alexandra K. Dvornikova, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to …

Inducing Application Of Interdisciplinary Frameworks: Experiences From The Domains Of Information Literacy And Responsible Conduct Of Research, Anne E. Leonard, Jean E. Hillstrom

Publications and Research

Constructivist frameworks for information literacy and research ethics can be developed and nurtured in the context of an interdisciplinary course. Using the frameworks of two disciplines, students went on an experiential journey in support of ethics foundations through guest lectures and active learning exercises. This study describes the development and content of the responsible conduct of research and information literacy modules and discusses the role of each in an interdisciplinary course. Learning goals for both modules were evaluated by examining student responses in a free-writing exercise at the end of the semester, concluding with a discussion of the structural and …

Telonicher Marine Laboratory, Hsu Telonicher Marine Laboratory

Newsletters

No abstract provided.

Pain And Laboratory Animals: Publication Practices For Better Data Reproducibility And Better Animal Welfare, Larry Carbone, Jamie Austin

Laboratory Research and Animal Welfare Collection

Scientists who perform major survival surgery on laboratory animals face a dual welfare and methodological challenge: how to choose surgical anesthetics and post-operative analgesics that will best control animal suffering, knowing that both pain and the drugs that manage pain can all affect research outcomes. Scientists who publish full descriptions of animal procedures allow critical and systematic reviews of data, demonstrate their adherence to animal welfare norms, and guide other scientists on how to conduct their own studies in the field. We investigated what information on animal pain management a reasonably diligent scientist might find in planning for a successful …

Single-Cell Transcriptional Analysis Of Normal, Aberrant, And Malignant Hematopoiesis In Zebrafish, Finola E. Moore, Elaine G. Garcia, Riadh Lobbardi, Esha Jain, Qin Tang, John C. Moore, Mauricio Cortes, Aleksey Molodtsov, Melissa Kasheta, Christina C. Luo, Amaris J. Garcia, Ravi Mylvaganam, Jeffrey A. Yoder, Jessica S. Blackburn, Ruslan I. Sadreyev, Craig J. Ceol, Trista E. North, David M. Langenau

Molecular and Cellular Biochemistry Faculty Publications

Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4⁺ cell type, representing a putative cytotoxic T/NK cell. Our platform …

Annotated Bibliography: Attitudes Toward Animal Research (2014-2015), Erich Yahner

BIBLIOGRAPHIES

No abstract provided.

The Ethics Of Animal Research: A Survey Of The Public And Scientists In North America, Ari R. Joffe, Meredith Bara, Natalie Anton, Nathan Nobis

Morality and Ethics of Animal Experimentation Collection

Background: To determine whether the public and scientists consider common arguments (and counterarguments) in support (or not) of animal research (AR) convincing.

Methods: After validation, the survey was sent to samples of public (Sampling Survey International (SSI; Canadian), Amazon Mechanical Turk (AMT; US), a Canadian city festival and children’s hospital), medical students (two second-year classes), and scientists (corresponding authors, and academic pediatricians). We presented questions about common arguments (with their counterarguments) to justify the moral permissibility (or not) of AR. Responses were compared using Chi-square with Bonferonni correction.

Results: There were 1220 public [SSI, n = 586; AMT, n = …

Mitigation Of Ergot Vasoconstriction By Clover Isoflavones In Goats (Capra Hircus), Glen E. Aiken, Michael D. Flythe, Isabelle A. Kagan, Huihua Ji, Lowell P. Bush

Kentucky Tobacco Research and Development Center Faculty Publications

Ergot alkaloids produced by a fungal endophyte (Epichloë coenophiala; formerly Neotyphodium coenophialum) that infects tall fescue (Lolium arundinaceum) can induce persistent constriction of the vasculature in ruminants, hindering their capability to thermo-regulate core body temperature. There is evidence that isoflavones produced by legumes can relax the vasculature, which suggests that they could relieve ergot alkaloid-induced vasoconstriction and mitigate the vulnerability to severe heat stress in ruminants that graze tall fescue. To test if isoflavones can relieve alkaloid-induced vasoconstriction, two pen experiments were conducted with rumen-fistulated goats (Capra hircus) to determine with ultrasonograpy if …

Non-Human Primates In Neuroscience Research: The Case Against Its Scientific Necessity, Jarrod Bailey, Katy Taylor

Experimentation Collection

Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP …

Does Environmental Enrichment Promote Recovery From Stress In Rainbow Trout?, Kieran C. Pounder, Jennifer L. Mitchell, Jack S. Thomson, Tom G. Pottinger, Jonathan Buckley, Lynne U. Sneddon

Experimental Research and Animal Welfare Collection

The EU Directive on animal experimentation suggests that all protected animals should have enrichment to improve welfare yet relatively little research has been conducted on the impact of enrichment in fish. Studies employing enrichment in zebrafish have been contradictory and all fish species should be provided with species-specific enrichments relevant to their ecology. Salmonids are important experimental models in studies within aquaculture, toxicology and natural ecosystems. This study therefore sought to establish whether an enriched environment in an experimental aquarium may promote improved welfare in rainbow trout (Oncorhynchus mykiss) by enhancing their recovery from invasive procedures. Trout were …

Use Of Non-Human Primates In Cocaine Research, Raija H. Bettauer

Experimentation Collection

No abstract provided.

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …

Assessment Of Celecoxib Poly(Lactic-Co-Glycolic) Acid Nanoformulation On Drug Pharmacodynamics And Pharmacokinetics In Rats, Sam Harirforoosh, Kelsi O. West, Derek E. Murrell, James W. Denham, Peter C. Panus, Greg A. Hanley

Pharmacy Faculty Articles and Research

OBJECTIVE: Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP).

MATERIALS AND METHODS: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma …