Medicine and Health Sciences Commons^™

Increased Interactions And Engulfment Of Dendrites By Microglia Precede Purkinje Cell Degeneration In A Mouse Model Of Niemann Pick Type-C., Larisa Kavetsky, Kayla K Green, Bridget R Boyle, Fawad A K Yousufzai, Zachary M Padron, Sierra E Melli, Victoria L Kuhnel, Harriet M Jackson, Rosa E Blanco, Gareth R Howell, Ileana Soto Reyes

Ileana Soto Reyes

Niemann Pick Type-C disease (NPC) is an inherited lysosomal storage disease (LSD) caused by pathogenic variants in the Npc1 or Npc2 genes that lead to the accumulation of cholesterol and lipids in lysosomes. NPC1 deficiency causes neurodegeneration, dementia and early death. Cerebellar Purkinje cells (PCs) are particularly hypersensitive to NPC1 deficiency and degenerate earlier than other neurons in the brain. Activation of microglia is an important contributor to PCs degeneration in NPC. However, the mechanisms by which activated microglia promote PCs degeneration in NPC are not completely understood. Here, we are demonstrating that in the Npc1nmf164 mouse cerebellum, microglia …

Meox2 Haploinsufficiency Accelerates Axonal Degeneration In Dba/2j Glaucoma, Rebecca A Buchanan, Kate E Foley, Keating W Pepper, Alaina M Reagan, Kelly J Keezer, Amanda A Hewes, Cory A Diemler, Christoph Preuss, Ileana Soto Reyes, Simon W M John, Gareth R Howell

Ileana Soto Reyes

Purpose: Glaucoma is a complex disease with major risk factors including advancing age and increased intraocular pressure (IOP). Dissecting these earliest events will likely identify new avenues for therapeutics. Previously, we performed transcriptional profiling in DBA/2J (D2) mice, a widely used mouse model relevant to glaucoma. Here, we use these data to identify and test regulators of early gene expression changes in DBA/2J glaucoma.

Methods: Upstream regulator analysis (URA) in Ingenuity Pathway Analysis was performed to identify potential master regulators of differentially expressed genes. The function of one putative regulator, mesenchyme homeobox 2 (Meox2), was tested using a combination of …

Enhancing Face Validity Of Mouse Models Of Alzheimer's Disease With Natural Genetic Variation., Kristen D Onos, Asli Uyar, Kelly J Keezer, Harriet M Jackson, Christoph Preuss, Casey J Acklin, Rita O'Rourke, Rebecca Buchanan, Travis L Cossette, Stacey J Sukoff Rizzo, Ileana Soto Reyes, Gregory W Carter, Gareth R Howell

Ileana Soto Reyes

Classical laboratory strains show limited genetic diversity and do not harness natural genetic variation. Mouse models relevant to Alzheimer's disease (AD) have largely been developed using these classical laboratory strains, such as C57BL/6J (B6), and this has likely contributed to the failure of translation of findings from mice to the clinic. Therefore, here we test the potential for natural genetic variation to enhance the translatability of AD mouse models. Two widely used AD-relevant transgenes, APPswe and PS1de9 (APP/PS1), were backcrossed from B6 to three wild-derived strains CAST/EiJ, WSB/EiJ, PWK/PhJ, representative of three Mus musculus subspecies. These new AD strains were …

The Economic Impacts Of Blackbird (Icteridae) Damage To Sunflower In The Usa, Karina Ernst, Julie Elser, George Linz, Hans Kandel, Jason Holderieath, Samantha Degroot, Steven Shwiff, Stephanie Shwiff

Jason Holderieath

BACKGROUND: Blackbird (Icteridae) damage to ripening sunflower (Helianthus annuus L.) has been a persistent economic issue in the USA for the last five decades. To quantify losses, we surveyed blackbird damage from 2001 to 2013 (excluding 2004) to physiologically mature sunflower in eight states: North Dakota, South Dakota, Texas, Nebraska, Minnesota, Colorado, Kansas, and Vermont.

RESULTS:We pooled data gathered during the most recent 5 years (2009 to 2013) of the survey and found losses averaged $US2.5 million and $US11.3 million for confectionery and oilseed hybrids, respectively. Three states, North Dakota, South Dakota, and Nebraska, had sufficient acreage and bird damage …

A Belmont Report For Animals?, Hope Ferdowsian, L. Syd M. Johnson, Jane Johnson, Andrew Fenton, Adam Shriver, John Gluck

John P. Gluck, PhD

Human and animal research both operate within established standards. In the United States, criticism of the human research environment and recorded abuses of human research subjects served as the impetus for the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and the resulting Belmont Report. The Belmont Report established key ethical principles to which human research should adhere: respect for autonomy, obligations to beneficence and justice, and special protections for vulnerable individuals and populations. While current guidelines appropriately aim to protect the individual interests of human participants in research, no similar, comprehensive, …

Incorporating New Technologies Into Toxicity Testing And Risk Assessment: Moving From 21st Century Vision To A Data-Driven Framework, Russell S. Thomas, Martin A. Philbert, Scott Auerbach, Barbara A. Wetmore, Michael J. Devito, Ila Cote, J. Craig Rowlands, Maurice Whelan, Sean M. Hays, Melvin E. Andersen, M.E. (Bette) Meek, Lawrence W. Reiter, Jason C. Lambert, Harvey J. Clewell Iii, Martin L. Stephens, Q. Jay Zhao, Scott C. Wesselkamper, Lynn Flowers, Edward W. Carney, Tim P. Pastoor, Dan D. Petersen, Carole L. Yauk, Andy Nong

Martin Stephens, PhD

Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions …

Evidence-Based Toxicology For The 21st Century: Opportunities And Challenges, Martin L. Stephens, Melvin E. Andersen, Richard A. Becker, Kellyn Betts, Kim Boekelheide, Ed Carney, Robert Chapin, Dennis Devlin, Suzanne C. Fitzpatrick, John R. Fowle Iii, Patricia Harlow, Thomas Hartung, Sebastian Hoffman, Michael P. Holsapple, Abigail Jacobs, Richard Judson, Olga Naidenko, Tim Pastoor, Grace Patlewicz, Andrew Rowan, Roberta Scherer, Rashid Shaikh, Ted Simon, Douglas Wolf, Joanne Zurlo

Martin Stephens, PhD

The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that …

Beyond The 3rs: Expanding The Use Of Human-Relevant Replacement Methods In Biomedical Research, Kathrin Herrmann, Francesca Pistollato, Martin L. Stephens

Martin Stephens, PhD

This year marks the 60th anniversary of Russell and Burch’s pioneering book, The Principles of Humane Experimental Technique. Their 3Rs framework has helped to inspire humane and scientific progress in experimental technique. However, it is time to update its strategic application. The 21st century has already seen the development of promising, high-tech non-animal models, such as organs-on-a-chip and computational approaches that, in our view, will replace animals as the default option in biomedical experimentation. How fast this transition will take place will depend on the pace at which these new models are optimized to reflect the biology of humans, rather …

Adaptation Of The Systematic Review Framework To The Assessment Of Toxicological Test Methods: Challenges And Lessons Learned With The Zebrafish Embryotoxicity Test, Martin L. Stephens, Sevcan Gül Akgün-Ölmez, Sebastian Hoffman, Rob De Vries, Burkhard Flick, Thomas Hartung, Manoj Lalu, Alexandra Maertens, Hilda Witters, Robert Wright, Katya Tsaioun

Martin Stephens, PhD

Systematic review methodology is a means of addressing specific questions through structured, consistent, and transparent examinations of the relevant scientific evidence. This methodology has been used to advantage in clinical medicine, and is being adapted for use in other disciplines. Although some applications to toxicology have been explored, especially for hazard identification, the present preparatory study is, to our knowledge, the first attempt to adapt it to the assessment of toxicological test methods. As our test case, we chose the zebrafish embryotoxicity test (ZET) for developmental toxicity and its mammalian counterpart, the standard mammalian prenatal development toxicity study, focusing the …

Accelerating The Development Of 21st-Century Toxicology: Outcome Of A Human Toxicology Project Consortium Workshop, Martin L. Stephens, Craig Barrow, Melvin E. Andersen, Kim Boekelheide, Paul L. Carmichael, Michael P. Holsapple, Mark Lafranconi

Martin Stephens, PhD

The U.S. National Research Council (NRC) report on “Toxicity Testing in the 21st century” calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to “toxicity pathways,” i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report’s implementation, the Human Toxicology Project Consortium hosted a workshop on 9–10 November 2010 in Washington, …

Welfare Challenges Influence The Complexity Of Movement: Fractal Analysis Of Behaviour In Zebrafish, Anthony G. Deakin, Joseph W. Spencer, Andrew R. Cossins, Iain S. Young, Lynne U. Sneddon

Lynne Sneddon, PhD

The ability to assess welfare is an important refinement that will ensure the good condition of animals used in experimentation. The present study investigated the impact of invasive procedures on the patterns of movement of zebrafish (Danio rerio). Recordings were made before and after fin clipping, PIT tagging and a standard pain test and these were compared with control and sham handled zebrafish. The fractal dimension (FD) from the 3D trajectories was calculated to determine the effect of these treatments on the complexity of movement patterns. While the FD of zebrafish trajectories did not differ over time in either the …

Report Of A Meeting On Contemporary Topics In Zebrafish Husbandry And Care, Nikki Osborne, Gregory Paull, Adam Grierson, Karen Dunford, Elisabeth M. Busch-Nentwich, Lynne U. Sneddon, Natalie Wren, Joe Higgins, Penny Hawkins

Lynne Sneddon, PhD

A meeting on Contemporary Topics in Zebrafish Husbandry and Care was held in the United Kingdom in 2014, with the aim of providing a discussion forum for researchers, animal technologists, and veterinarians from academia and industry to share good practice and exchange ideas. Presentation topics included protocols for optimal larval rearing, implementing the 3Rs (replacement, reduction, and refinement) in large-scale colony management, and environmental enrichment. The audience also participated in a survey of current practice relating to practical husbandry, cryopreservation, and the provision of enrichment.

Physiological And Behavioural Evaluation Of Common Anaesthesia Practices In The Rainbow Trout, Kieran C. Pounder, Jennifer L. Mitchell, Jack S. Thomson, Tom G. Pottinger, Lynne U. Sneddon

Lynne Sneddon, PhD

Anaesthetic drugs are commonly administered to fish in aquaculture, research and veterinary contexts. Anaesthesia causes temporary absence of consciousness and may reduce the stress and/or pain associated with handling and certain invasive procedures. The rainbow trout (Oncorhynchus mykiss) is a widely-used model species with relevance to both aquaculture and natural ecosystems. This study sought to establish the relative acute impact of commonly used anaesthetics on rainbow trout when used for anaesthesia or euthanasia by exploring their effects on aversion behaviour and stress physiology. Five widely used anaesthetics were investigated at two concentrations reflective of common laboratory practises: MS-222, benzocaine, 2-phenoxyethanol, …

Reduction In Activity By Noxious Chemical Stimulation Is Ameliorated By Immersion In Analgesic Drugs In Zebrafish, Javier Lopez-Luna, Qussay Al-Jubouri, Waleed Al-Nuaimy, Lynne U. Sneddon

Lynne Sneddon, PhD

Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a range of analgesic drugs to determine their efficacy to reduce these responses. This approach aimed to validate larval zebrafish as a reliable replacement for adults as well as providing a high-throughput means of analysing behavioural responses. Zebrafish at 5 days postfertilization were exposed to known noxious stimuli: acetic acid (0.01%, 0.1% and 0.25%) and citric acid (0.1%, 1% and 5%). The behavioural response of each …

Considering Aspects Of The 3rs Principles Within Experimental Animal Biology, Lynne U. Sneddon, Lewis G. Halsey, Nic R. Bury

Lynne Sneddon, PhD

The 3Rs – Replacement, Reduction and Refinement – are embedded into the legislation and guidelines governing the ethics of animal use in experiments. Here, we consider the advantages of adopting key aspects of the 3Rs into experimental biology, represented mainly by the fields of animal behaviour, neurobiology, physiology, toxicology and biomechanics. Replacing protected animals with less sentient forms or species, cells, tissues or computer modelling approaches has been broadly successful. However, many studies investigate specific models that exhibit a particular adaptation, or a species that is a target for conservation, such that their replacement is inappropriate. Regardless of the species …

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

Lynne Sneddon, PhD

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 …

Practical Considerations In Regenerative Medicine Research: Iacucs, Ethics, And The Use Of Animals In Stem Cell Studies, Susan Vandewoude, Bernard E. Rollin

Bernard Rollin, PhD

The intent of US federal laws mandating IACUC review of animal-related activities was to satisfy contemporary socioethical concerns by introducing deliberations about ethics and animal welfare into the research process when animals are used. These laws and the system they chartered have worked well for the most part in providing opportunities for consideration of animal welfare as a vital part of animal research. As a result, investigators today are far less naïve about the ethical issues raised by research on animals and typically more sympathetic about the need for such consideration. As evidence of this growing awareness, the literature on …

Beyond Pain—Controlling Suffering In Laboratory Animals, Bernard E. Rollin

Bernard Rollin, PhD

No abstract provided.

The True Meaning Of Keto Blast Reviews, Alesia O Pantoja

Alesia O Pantoja

The Animal Research Controversy: Protest, Process & Public Policy, Andrew N. Rowan, Franklin M. Loew, Joan C. Weer

Andrew N. Rowan, DPhil

The controversy today regarding the use of animals in research appears on the surface to be a strongly polarized struggle between the scientific community and the animal protection movement. However, there is a wide range of opinions and philosophies on both sides. Mistrust between the factions has blossomed while communication has withered. Through the 1960s, 1970s and early 1980s, the animal movement grew in numbers and financial resources, and developed much greater public recognition and political clout. The research community paid relatively little attention to the animal movement for much of this period but, alarmed by several public relations coups …

International Consensus Principles For Ethical Wildlife Control, Sara Dubois, Nicole Fenwick, Erin A. Ryan, Liv Baker, Sandra E. Baker, Ngaio J. Beausoleil, Scott Carter, Barbara Cartwright, Federico Costa, Chris Draper, John Griffin, Adam Grogan, Gregg Howald, Bidda Jones, Kate E. Littin, Amanda T. Lombard, David J. Mellor, Daniel Ramp, Catherine A. Schuppli, David Fraser

David Fraser, PhD

Human–wildlife conflicts are commonly addressed by excluding, relocating, or lethally controlling animals with the goal of preserving public health and safety, protecting property, or conserving other valued wildlife. However, declining wildlife populations, a lack of efficacy of control methods in achieving desired outcomes, and changes in how people value animals have triggered widespread acknowledgment of the need for ethical and evidence-based approaches to managing such conflicts. We explored international perspectives on and experiences with human–wildlife conflicts to develop principles for ethical wildlife control. A diverse panel of 20 experts convened at a 2-day workshop and developed the principles through a …

Distributions Of Hypothalamic Neuron Populations Co-Expressing Tyrosine Hydroxylase And The Vesicular Gaba Transporter In The Mouse., Kenichiro Negishi, Mikayla A. Payant, Kayla S. Schumacker, Gabor Wittman, Rebecca M. Butler, Ronald M. Lechan, Harry W. M. Steinbusch M, Arshad M. Khan, Melissa J. Chee

Arshad M. Khan, Ph.D.

No abstract provided.

Mental Stress From Animal Experiments: A Survey With Korean Researchers, Minji Kang, Ahram Han, Da-Eun Kim, Troy Seidle, Kyung-Min Lim, Seungjin Bae

Troy Seidle, PhD

Animal experiments have been widely conducted in the life sciences for more than a century, and have long been a subject of ethical and societal controversy due to the deliberate infliction of harm upon sentient animals. However, the harmful use of animals may also negatively impact the mental health of researchers themselves. We sought to evaluate the anxiety level of researchers engaged in animal use to analyse the mental stress from animal testing. The State Anxiety Scale of the State-Trait Anxiety Inventory (STAI) was used to evaluate how researchers feel when they conduct animal, as opposed to non-animal, based experiments …

Non-Invasive Methods Of Identifying And Tracking Wild Squid, Ruth A. Byrne, James B. Wood, Roland C. Anderson, Ulrike Griebel, Jennifer A. Mather

Jennifer Mather, PhD

The ability to identify individual free-living animals in the field is an important method for studying their behavior. Apart from invasive external or internal tags, which may cause injury or abnormal behavior, most cephalopods cannot be tagged, as their skin is too soft and delicate for tag retention. Additionally, cephalopods remove many types of tags. However, body markings have been successfully used as a non invasive method to identify individuals of many different species of animals, including whale sharks, grey whales, seals, and zebras. We developed methods to sex and individually identify Caribbean reef squid, Sepiotheuthis sepioidea. Males showed distinct …

Animal Organs In Humans: Uncalculated Risks And Unanswered Questions, Gillian R. Langley, Joyce D'Silva

Gill Langley, PhD

This report, produced jointly by the British Union for the Abolition of Vivisection and Compassion in World Farming, fills a number of significant gaps in the current debate about xenotransplantation.

In this report we also summarise the ethical and welfare issues concerning experiments on animals for xenotransplant research and their possible use as source animals for organs. Both these aspects are responsible for much pain and distress caused to many animals. We prefer the term “source animals” to “donor animals”, because animals do not choose to donate their organs for xenotransplantation.

Acute Toxicity Testing Without Animals: More Scientific And Less Of A Gamble, Gillian R. Langley

Gill Langley, PhD

In this report, we argue specifically that acute toxicity data should not be sought from animal tests. The underlying principle of such tests on rats and mice is that the results can be effectively extrapolated to humans. In fact, after nearly 80 years of use of these tests, the predictivity of rodent data for human acute toxic effects has been disputed but never proven.

Publication Reform To Safeguard Wildlife From Researcher Harm, Kate A. Field, Paul C. Paquet, Kyle A. Artelle, Gilbert Proulx, Ryan K. Brook, Chris T. Darimont

Chris Darimont, PhD

Despite abundant focus on responsible care of laboratory animals, we argue that inattention to the maltreatment of wildlife constitutes an ethical blind spot in contemporary animal research. We begin by reviewing significant shortcomings in legal and institutional oversight, arguing for the relatively rapid and transformational potential of editorial oversight at journals in preventing harm to vertebrates studied in the field and outside the direct supervision of institutions. Straightforward changes to animal care policies in journals, which our analysis of 206 journals suggests are either absent (34%), weak, incoherent, or neglected by researchers, could provide a practical, effective, and rapidly imposed …

Malanda Gold: The Tale Of A Unique Rainbowfish From The Atherton Table-Lands, Now On The Verge Of Extinction., Peter J. Unmack, Keith Martin, Michael P. Hammer, Brendan Ebner, Karl Moy, Culum Brown

Culum Brown, PhD

No abstract provided.

"Being Mindful" And Becoming A "Harmony Worker" During Unsettling Times.Docx

Carroy U "Cuf" Ferguson, Ph.D.

H-Index Is Important For Postural Control For People With Impaired Foot Sole Sensation, Shuqi Zhang, Brad Manor, Li Li

Shuqi Zhang

Introduction: People with Peripheral Neuropathy (PN), especially those with impaired sensory inputs through the small-afferent fiber (type II afferent fibers) reflex loop (SAF), might depend more on the large-afferent fiber (type I afferent fibers) reflex loop (LAF) for postural control.

Purpose: To examine whether the function of the LAF reflex loop, reflected by the H-reflex and ankle joint proprioception, influences postural control when the SAF reflex loop is impaired, as indicated by reduced foot sole cutaneous sensation.

Methods: Thirteen participants (8 women, 5 men) diagnosed with PN and 12 age-matched controls (7 women, 5 men) completed the testing protocol. Measures …