Modeling utilization distributions in space and time

USGS Publications Warehouse

Keating, K.A.; Cherry, S.

2009-01-01

W. Van Winkle defined the utilization distribution (UD) as a probability density that gives an animal's relative frequency of occurrence in a two-dimensional (x, y) plane. We extend Van Winkle's work by redefining the UD as the relative frequency distribution of an animal's occurrence in all four dimensions of space and time. We then describe a product kernel model estimation method, devising a novel kernel from the wrapped Cauchy distribution to handle circularly distributed temporal covariates, such as day of year. Using Monte Carlo simulations of animal movements in space and time, we assess estimator performance. Although not unbiased, the product kernel method yields models highly correlated (Pearson's r - 0.975) with true probabilities of occurrence and successfully captures temporal variations in density of occurrence. In an empirical example, we estimate the expected UD in three dimensions (x, y, and t) for animals belonging to each of two distinct bighorn sheep {Ovis canadensis) social groups in Glacier National Park, Montana, USA. Results show the method can yield ecologically informative models that successfully depict temporal variations in density of occurrence for a seasonally migratory species. Some implications of this new approach to UD modeling are discussed. ?? 2009 by the Ecological Society of America.

A novel ex-vivo porcine renal xenotransplantation model using a pulsatile machine preservation system.

PubMed

Guarrera, James V; Stone, Jonathan; Tulipan, Jacob; Jhang, Jeffrey; Arrington, Ben; Boykin, Jason; Markowitz, Glen; Ratner, Lloyd E

2011-01-01

Animal models to investigate pathophysiology and xenotransplantation require complex techniques and significant animal utilization. The aim of the study was to develop a reliable ex-vivo technique to test xenotransplant interventions. Miniature Swine being utilized for a nonsurvival study acted as donor animals. Kidneys were flushed and rapidly explanted and chilled to 4°C. Kidneys were assigned to be the control (CK) (n=3) and the mate were used as a Xenograft Kidneys (XK) (n=3). Kidneys were perfused on separate Waters RM 3 perfusion devices. Perfusion temperature was 35-37°C and pressure was 100-110/60-70 mmHg at 60 pulses per minute. CKs were reperfused with autologous blood collected at the time of organ procurement. XKs were reperfused using freshly donated whole human blood. Physical characteristics, urine output were recorded. Core needle biopsies were obtained and examined by a blinded pathologist for evidence of antibody mediated rejection. XK kidneys demonstrated homogenous reperfusion which rapidly became patchy at 5-7 minutes. XK kidneys had become complete black and thrombosed by 60-70 minutes. XK biopsies demonstrated peritubular capillaritis. CK kidneys demonstrated homogenous reperfusion and urine production. H&E stain of CKs only demonstrated nonspecific inflammation. Our ex-vivo porcine xenotransplant model shows early promise as a tool for studying Xeno- associated hyperacute rejection. This technique saves resources and animal utilization.

Animal models of female pelvic organ prolapse: lessons learned

PubMed Central

Couri, Bruna M; Lenis, Andrew T; Borazjani, Ali; Paraiso, Marie Fidela R; Damaser, Margot S

2012-01-01

Pelvic organ prolapse is a vaginal protrusion of female pelvic organs. It has high prevalence worldwide and represents a great burden to the economy. The pathophysiology of pelvic organ prolapse is multifactorial and includes genetic predisposition, aberrant connective tissue, obesity, advancing age, vaginal delivery and other risk factors. Owing to the long course prior to patients becoming symptomatic and ethical questions surrounding human studies, animal models are necessary and useful. These models can mimic different human characteristics – histological, anatomical or hormonal, but none present all of the characteristics at the same time. Major animal models include knockout mice, rats, sheep, rabbits and nonhuman primates. In this article we discuss different animal models and their utility for investigating the natural progression of pelvic organ prolapse pathophysiology and novel treatment approaches. PMID:22707980

Properties of animal-manure based hydrochars and predictions using published models

USDA-ARS?s Scientific Manuscript database

In order to fully utilize hydrothermal carbonization (HTC) to produce value-added hydrochars from animal manures, it is important to understand how process conditions (e.g., temperature, reaction time, solids concentration) influence product characteristics. The effect of process conditions on the e...

A living model for obesity and aging research: Caenorhabditis elegans.

PubMed

Shen, Peiyi; Yue, Yiren; Park, Yeonhwa

2018-03-24

Caenorhabditis elegans (C. elegans) is a free-living nematode that has been extensively utilized as an animal model for research involving aging and neurodegenerative diseases, like Alzheimer's and Parkinson's, etc. Compared with traditional animal models, this small nematode possesses many benefits, such as small body size, short lifespan, completely sequenced genome, and more than 65% of the genes associated with human disease. All these characteristics make this organism an ideal living system for obesity and aging studies. This review gives a brief introduction of C. elegans as an animal model, highlights some advantages of research using this model and describes methods to evaluate the effect of treatments on obesity and aging of this organism.

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.

PubMed

Gordon, Sarah; Daneshian, Mardas; Bouwstra, Joke; Caloni, Francesca; Constant, Samuel; Davies, Donna E; Dandekar, Gudrun; Guzman, Carlos A; Fabian, Eric; Haltner, Eleonore; Hartung, Thomas; Hasiwa, Nina; Hayden, Patrick; Kandarova, Helena; Khare, Sangeeta; Krug, Harald F; Kneuer, Carsten; Leist, Marcel; Lian, Guoping; Marx, Uwe; Metzger, Marco; Ott, Katharina; Prieto, Pilar; Roberts, Michael S; Roggen, Erwin L; Tralau, Tewes; van den Braak, Claudia; Walles, Heike; Lehr, Claus-Michael

2015-01-01

Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

Traumatic Brain Injury – Modeling Neuropsychiatric Symptoms in Rodents

PubMed Central

Malkesman, Oz; Tucker, Laura B.; Ozl, Jessica; McCabe, Joseph T.

2013-01-01

Each year in the US, ∼1.5 million people sustain a traumatic brain injury (TBI). Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms – and why some patients experience differing assortments of persistent maladies – are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory, and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential. PMID:24109476

Animal models for microbicide safety and efficacy testing.

PubMed

Veazey, Ronald S

2013-07-01

Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

Animal models in burn research.

PubMed

Abdullahi, A; Amini-Nik, S; Jeschke, M G

2014-09-01

Burn injury is a severe form of trauma affecting more than 2 million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury, to elucidate the pathophysiology, and to explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research.

Animal Models in Burn Research

PubMed Central

Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G

2014-01-01

Burn injury is a severe form of trauma affecting more than two million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury; to elucidate the pathophysiology and explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review paper aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research. PMID:24714880

Technique Refinement and Validation of Variable Aortic Occlusion via Extracorporeal Flow Circuit in a Pig Model (Sus scrofa) of Uncontrolled Hemorrhage with Subsequent Resuscitation and Critical Care

DTIC Science & Technology

2016-07-24

60th Medical Group (AMC), Travis AFB, CA INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) FINAL REPORT SUMMARY (Please type all information. Use...TRIENNIAL REVISION DATE: N/A FUNDING SOURCE: HQ USAF SG 1. RECORD OF ANIMAL USAGE: Animal Species: Total # Approved # Used this FY Total # Used to...Restraint Training: non-Live Animal Health Promotion Research: Survival (chronic) Prevention x_ Research: non-Survival (acute) Utilization Mgt. Other

Opportunities for the replacement of animals in the study of nausea and vomiting

PubMed Central

Holmes, AM; Rudd, JA; Tattersall, FD; Aziz, Q; Andrews, PLR

2009-01-01

Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms. PMID:19371333

EXPERIMENTAL MODELS FOR THE STUDY OF ORAL CLEFTS

EPA Science Inventory

Toxicology and teratology studies routinely utilize animal models to determine the potential for chemical and physical agents to produce reproductive and developmental toxicity, including birth defects such as cleft palate. The standardized teratology screen typically tests co...

Utility of Small Animal Models of Developmental Programming.

PubMed

Reynolds, Clare M; Vickers, Mark H

2018-01-01

Any effective strategy to tackle the global obesity and rising noncommunicable disease epidemic requires an in-depth understanding of the mechanisms that underlie these conditions that manifest as a consequence of complex gene-environment interactions. In this context, it is now well established that alterations in the early life environment, including suboptimal nutrition, can result in an increased risk for a range of metabolic, cardiovascular, and behavioral disorders in later life, a process preferentially termed developmental programming. To date, most of the mechanistic knowledge around the processes underpinning development programming has been derived from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. This review will cover the utility of small animal models in developmental programming, the limitations of such models, and potential future directions that are required to fully maximize information derived from preclinical models in order to effectively translate to clinical use.

Engineering Large Animal Species to Model Human Diseases.

PubMed

Rogers, Christopher S

2016-07-01

Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk.

PubMed

Shi, Danni; Vine, Donna F

2012-07-01

To review rodent animal models of polycystic ovary syndrome (PCOS), with a focus on those associated with the metabolic syndrome and cardiovascular disease risk factors. Review. Rodent models of PCOS. Description and comparison of animal models. Comparison of animal models to clinical phenotypes of PCOS. Animals used to study PCOS include rodents, mice, rhesus monkeys, and ewes. Major methods to induce PCOS in these models include subcutaneous injection or implantation of androgens, estrogens, antiprogesterone, letrozole, prenatal exposure to excess androgens, and exposure to constant light. In addition, transgenic mice models and spontaneous PCOS-like rodent models have also been developed. Rodents are the most economical and widely used animals to study PCOS and ovarian dysfunction. The model chosen to study the development of PCOS and other metabolic parameters remains dependent on the specific etiologic hypotheses being investigated. Rodent models have been shown to demonstrate changes in insulin metabolism, with or without induction of hyperandrogenemia, and limited studies have investigated cardiometabolic risk factors for type 2 diabetes and cardiovascular disease. Given the clinical heterogeneity of PCOS, the utilization of different animal models may be the best approach to further our understanding of the pathophysiologic mechanisms associated with the early etiology of PCOS and cardiometabolic risk. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

GPR Imaging of Prehistoric Animal Bone-beds

NASA Astrophysics Data System (ADS)

Schneider, Blair Benson

This research investigates the detection capabilities of Ground-penetrating radar for imaging prehistoric animal bone-beds. The first step of this investigation was to determine the dielectric properties of modern animal bone as a proxy for applying non-invasive ground-penetrating radar (GPR) for detecting prehistoric animal remains. Over 90 thin section samples were cut from four different modern faunal skeleton remains: bison, cow, deer, and elk. One sample of prehistoric mammoth core was also analyzed. Sample dielectric properties (relative permittivity, loss factor, and loss-tangent values) were measured with an impedance analyzer over frequencies ranging from 10 MHz to 1 GHz. The results reveal statistically significant dielectric-property differences among different animal fauna, as well as variation as a function of frequency. The measured sample permittivity values were then compared to modeled sample permittivity values using common dielectric-mixing models. The dielectric mixing models were used to report out new reported values of dry bone mineral of 3-5 in the frequency range of 10 MHz to 1 GHz. The second half of this research collected controlled GPR experiments over a sandbox containing buried bison bone elements to evaluate GPR detection capabilities of buried animal bone. The results of the controlled GPR sandbox tests were then compared to numerical models in order to predict the ability of GPR to detect buried animal bone given a variety of different depositional factors, the size and orientation of the bone target and the degree of bone weathering. The radar profiles show that GPR is an effective method for imaging the horizontal and vertical extent of buried animal bone. However, increased bone weathering and increased bone dip were both found to affect GPR reflection signal strength. Finally, the controlled sandbox experiments were also utilized to investigate the impact of survey design for imaging buried animal bone. In particular, the effects of GPR antenna orientation relative to the survey line (broad-side mode versus end-fire mode) and polarization effects of the buried bone targets were investigated. The results reveal that animal bone does exhibit polarization effects. However, the polarization results are greatly affected by the irregular shape and size of the bone, which ultimately limits the potential usefulness of trying to utilize polarization data to determine the orientation of buried bone targets. In regard to antenna orientation, end-fire mode was found to have little difference in amplitude response as compared to the more commonly used broad-side mode and in fact sometimes outperformed the broad-side mode. Future GPR investigations should consider utilizing multiple antenna orientations during data collection.

Creating speech-synchronized animation.

PubMed

King, Scott A; Parent, Richard E

2005-01-01

We present a facial model designed primarily to support animated speech. Our facial model takes facial geometry as input and transforms it into a parametric deformable model. The facial model uses a muscle-based parameterization, allowing for easier integration between speech synchrony and facial expressions. Our facial model has a highly deformable lip model that is grafted onto the input facial geometry to provide the necessary geometric complexity needed for creating lip shapes and high-quality renderings. Our facial model also includes a highly deformable tongue model that can represent the shapes the tongue undergoes during speech. We add teeth, gums, and upper palate geometry to complete the inner mouth. To decrease the processing time, we hierarchically deform the facial surface. We also present a method to animate the facial model over time to create animated speech using a model of coarticulation that blends visemes together using dominance functions. We treat visemes as a dynamic shaping of the vocal tract by describing visemes as curves instead of keyframes. We show the utility of the techniques described in this paper by implementing them in a text-to-audiovisual-speech system that creates animation of speech from unrestricted text. The facial and coarticulation models must first be interactively initialized. The system then automatically creates accurate real-time animated speech from the input text. It is capable of cheaply producing tremendous amounts of animated speech with very low resource requirements.

The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data.

PubMed

Van Otterloo, Eric; Williams, Trevor; Artinger, Kristin Bruk

2016-07-15

The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis and Management of Animal Populations: Modeling, Estimation and Decision Making

USGS Publications Warehouse

Williams, B.K.; Nichols, J.D.; Conroy, M.J.

2002-01-01

This book deals with the processes involved in making informed decisions about the management of animal populations. It covers the modeling of population responses to management actions, the estimation of quantities needed in the modeling effort, and the application of these estimates and models to the development of sound management decisions. The book synthesizes and integrates in a single volume the methods associated with these themes, as they apply to ecological assessment and conservation of animal populations. KEY FEATURES * Integrates population modeling, parameter estimation and * decision-theoretic approaches to management in a single, cohesive framework * Provides authoritative, state-of-the-art descriptions of quantitative * approaches to modeling, estimation and decision-making * Emphasizes the role of mathematical modeling in the conduct of science * and management * Utilizes a unifying biological context, consistent mathematical notation, * and numerous biological examples

Individual differences in the behavioral effects of nicotine: A review of the preclinical animal literature

PubMed Central

Falco, Adriana M.; Bevins, Rick A.

2015-01-01

Not everyone who tries tobacco or other nicotine-containing products becomes a long-term user. Certain traits or factors that are differentially present in these individuals must be able to help health care providers and researchers determine who is more likely to become chronic users of nicotine-containing products. Some of these factors, particularly sensation-seeking/novelty, impulsivity, and anxiety, lend themselves to the creation of animal models of reactivity to nicotine. These models of reactivity to nicotine can improve the translational aspects of preclinical animal research on nicotine-induced behaviors and treatments in order to help reduce negative outcomes in human populations. The goal of this review is to evaluate the current status of animal models of individual differences that serve to predict the later behavioral effects of nicotine. The limited utility and inconsistency of existing novelty models is considered, as well as the promise of impulsivity and anxiety models in preclinical animal populations. Finally, other models that could be employed to extend the benefit of the current research are examined. PMID:26410616

Animal Models for HIV Cure Research.

PubMed

Policicchio, Benjamin B; Pandrea, Ivona; Apetrei, Cristian

2016-01-01

The HIV-1/AIDS pandemic continues to spread unabated worldwide, and no vaccine exists within our grasp. Effective antiretroviral therapy (ART) has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for human immunodeficiency virus (HIV) infection will require multiple tools, and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure) or eliminating the reservoir altogether (sterilizing cure). Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new non-human primate and mouse models, along with a certain interest in the feline model, has the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal.

Animal Models for HIV Cure Research

PubMed Central

Policicchio, Benjamin B.; Pandrea, Ivona; Apetrei, Cristian

2016-01-01

The HIV-1/AIDS pandemic continues to spread unabated worldwide, and no vaccine exists within our grasp. Effective antiretroviral therapy (ART) has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for human immunodeficiency virus (HIV) infection will require multiple tools, and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure) or eliminating the reservoir altogether (sterilizing cure). Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new non-human primate and mouse models, along with a certain interest in the feline model, has the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal. PMID:26858716

A bovine model for polycystic ovary syndrome

USDA-ARS?s Scientific Manuscript database

Polycystic ovary syndrome (PCOS) results in the greatest single cause of anovulatory infertility in reproductive age women (affecting 5-10%). Previously, research groups have created animal models utilizing non-human primates and sheep to better understand the mechanisms involved in PCOS. However, c...

Concepts in Cancer Modeling: A Brief History

PubMed Central

Thomas, Renee M.; Van Dyke, Terry; Merlino, Glenn; Day, Chi-Ping

2016-01-01

Modeling, an experimental approach to investigate complex biological systems, has significantly contributed to our understanding of cancer. While extensive cancer research has been conducted utilizing animal models for elucidating mechanisms and developing therapeutics, the concepts in a good model design and its application have not been well elaborated. In this review, we discuss the theory underlying biological modeling and the process of producing a valuable and relevant animal model. Several renowned examples in the history of cancer research will be used to illustrate how modeling can be translatable to clinical applications. Finally, we will also discuss how the advances in cancer genomics and cancer modeling will influence each other going forward. PMID:27694601

Genetically Engineered Pig Models for Human Diseases

PubMed Central

Prather, Randall S.; Lorson, Monique; Ross, Jason W.; Whyte, Jeffrey J.; Walters, Eric

2015-01-01

Although pigs are used widely as models of human disease, their utility as models has been enhanced by genetic engineering. Initially, transgenes were added randomly to the genome, but with the application of homologous recombination, zinc finger nucleases, and transcription activator-like effector nuclease (TALEN) technologies, now most any genetic change that can be envisioned can be completed. To date these genetic modifications have resulted in animals that have the potential to provide new insights into human diseases for which a good animal model did not exist previously. These new animal models should provide the preclinical data for treatments that are developed for diseases such as Alzheimer's disease, cystic fibrosis, retinitis pigmentosa, spinal muscular atrophy, diabetes, and organ failure. These new models will help to uncover aspects and treatments of these diseases that were otherwise unattainable. The focus of this review is to describe genetically engineered pigs that have resulted in models of human diseases. PMID:25387017

Challenges in the development of chronic pulmonary hypertension models in large animals

PubMed Central

Rothman, Abraham; Wiencek, Robert G.; Davidson, Stephanie; Evans, William N.; Restrepo, Humberto; Sarukhanov, Valeri; Mann, David

2017-01-01

Pulmonary hypertension (PH) results in significant morbidity and mortality. Chronic PH animal models may advance the study of PH’s mechanisms, evolution, and therapy. In this report, we describe the challenges and successes in developing three models of chronic PH in large animals: two models (one canine and one swine) utilized repeated infusions of ceramic microspheres into the pulmonary vascular bed, and the third model employed a surgical aorto-pulmonary shunt. In the canine model, seven dogs underwent microsphere infusions that resulted in progressive elevation of pulmonary arterial pressure over a few months. In this model, pulmonary endoarterial tissue was obtained for histology. In the aorto-pulmonary shunt swine model, 17 pigs developed systemic level pulmonary pressures after 2–3 months. In this model, pulmonary endoarterial tissue was sequentially obtained to assess for changes in gene and microRNA expression. In the swine microsphere infusion model, three pigs developed only a modest chronic increase in pulmonary arterial pressure, despite repeated infusions of microspheres (up to 40 in one animal). The main purpose of this model was for vasodilator testing, which was performed successfully immediately after acute microsphere infusions. Chronic PH in large animal models can be successfully created; however, a model’s characteristics need to match the investigational goals. PMID:28680575

From psychiatric disorders to animal models: a bidirectional and dimensional approach

PubMed Central

Donaldson, Zoe. R.; Hen, René

2014-01-01

Psychiatric genetics research is bidirectional in nature, with human and animal studies becoming more closely integrated as techniques for genetic manipulations allow for more subtle exploration of disease phenotypes. This synergy, however, highlights the importance of considering the way in which we approach the genotype-phenotype relationship. In particular, the nosological divide of psychiatric illness, while clinically relevant, is not directly translatable in animal models. For instance, mice will never fully re-capitulate the broad criteria for many psychiatric disorders; nor will they have guilty ruminations, suicidal thoughts, or rapid speech. Instead, animal models have been and continue to provide a means to explore dimensions of psychiatric disorders in order to identify neural circuits and mechanisms underlying disease-relevant phenotypes. Thus, the genetic investigation of psychiatric illness will yield the greatest insights if efforts continue to identify and utilize biologically valid phenotypes across species. In this review we discuss the progress to date and the future efforts that will enhance translation between human and animal studies, including the identification of intermediate phenotypes that can be studied across species, as well as the importance of refined modeling of human disease-associated genetic variation in mice and other animal models. PMID:24650688

A Theoretically Based Model of Rat Personality with Implications for Welfare

PubMed Central

Franks, Becca; Higgins, E. Tory; Champagne, Frances A.

2014-01-01

As animal personality research becomes more central to the study of animal behavior, there is increasing need for theoretical frameworks addressing its causes and consequences. We propose that regulatory focus theory (RFT) could serve as one such framework while also providing insights into how animal personality relates to welfare. RFT distinguishes between two types of approach motivation: promotion, the motivation to approach gains, and prevention, the motivation to approach or maintain safety. Decades of research have established the utility of RFT as a model of human behavior and recent evidence from zoo-housed primates and laboratory rats has suggested that it may be applicable to nonhuman animal behavior as well. Building on these initial studies, we collected data on 60 rats, Rattus norvegicus, navigating an automated maze that allowed individuals to maintain darkness (indicative of prevention/safety-approach motivation) and/or activate food rewards (indicative of promotion/gain-approach motivation). As predicted, both behaviors showed stable individual differences (Ps <0.01) and were inversely associated with physiological signs of chronic stress, possibly indicating poor welfare (Ps <0.05). Subsequently, half the rats were exposed to a manageable threat (noxious novel object) in the homecage. Re-testing in the maze revealed that threat exposure increased darkness time achieved (P<0.05), suggesting a mechanism by which prevention motivation may be enhanced. These results point toward the potential utility of RFT as a model for animal behavior and welfare. PMID:24755737

The Utility of Behavioral Economics in Expanding the Free-Feed Model of Obesity

PubMed Central

Rasmussen, Erin B.; Robertson, Stephen H.; Rodriguez, Luis R.

2016-01-01

Animal models of obesity are numerous and diverse in terms of identifying specific neural and peripheral mechanisms related to obesity; however, they are limited when it comes to behavior. The standard behavioral measure of food intake in most animal models occurs in a free-feeding environment. While easy and cost-effective for the researcher, the free-feeding environment omits some of the most important features of obesity-related food consumption—namely, properties of food availability, such as effort and delay to obtaining food. Behavior economics expands behavioral measures of obesity animal models by identifying such behavioral mechanisms. First, economic demand analysis allows researchers to understand the role of effort in food procurement, and how physiological and neural mechanisms are related. Second, studies on delay discounting contribute to a growing literature that shows that sensitivity to delayed food- and food-related outcomes is likely a fundamental process of obesity. Together, these data expand the animal model in a manner that better characterizes how environmental factors influence food consumption. PMID:26923097

Genetically engineered livestock for biomedical models.

PubMed

Rogers, Christopher S

2016-06-01

To commemorate Transgenic Animal Research Conference X, this review summarizes the recent progress in developing genetically engineered livestock species as biomedical models. The first of these conferences was held in 1997, which turned out to be a watershed year for the field, with two significant events occurring. One was the publication of the first transgenic livestock animal disease model, a pig with retinitis pigmentosa. Before that, the use of livestock species in biomedical research had been limited to wild-type animals or disease models that had been induced or were naturally occurring. The second event was the report of Dolly, a cloned sheep produced by somatic cell nuclear transfer. Cloning subsequently became an essential part of the process for most of the models developed in the last 18 years and is stilled used prominently today. This review is intended to highlight the biomedical modeling achievements that followed those key events, many of which were first reported at one of the previous nine Transgenic Animal Research Conferences. Also discussed are the practical challenges of utilizing livestock disease models now that the technical hurdles of model development have been largely overcome.

MARTI: man-machine animation real-time interface

NASA Astrophysics Data System (ADS)

Jones, Christian M.; Dlay, Satnam S.

1997-05-01

The research introduces MARTI (man-machine animation real-time interface) for the realization of natural human-machine interfacing. The system uses simple vocal sound-tracks of human speakers to provide lip synchronization of computer graphical facial models. We present novel research in a number of engineering disciplines, which include speech recognition, facial modeling, and computer animation. This interdisciplinary research utilizes the latest, hybrid connectionist/hidden Markov model, speech recognition system to provide very accurate phone recognition and timing for speaker independent continuous speech, and expands on knowledge from the animation industry in the development of accurate facial models and automated animation. The research has many real-world applications which include the provision of a highly accurate and 'natural' man-machine interface to assist user interactions with computer systems and communication with one other using human idiosyncrasies; a complete special effects and animation toolbox providing automatic lip synchronization without the normal constraints of head-sets, joysticks, and skilled animators; compression of video data to well below standard telecommunication channel bandwidth for video communications and multi-media systems; assisting speech training and aids for the handicapped; and facilitating player interaction for 'video gaming' and 'virtual worlds.' MARTI has introduced a new level of realism to man-machine interfacing and special effect animation which has been previously unseen.

A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis

PubMed Central

Mears, Emily Rose; Modabber, Farrokh; Don, Robert; Johnson, George E.

2015-01-01

The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host–parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major–C57BL/6 mice (or–vervet monkey, or–rhesus monkeys), L. tropica–CsS-16 mice, L. amazonensis–CBA mice, L. braziliensis–golden hamster (or–rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations. PMID:26334763

Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.

PubMed

Bezard, Erwan; Yue, Zhenyu; Kirik, Deniz; Spillantini, Maria Grazia

2013-01-01

Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials. Copyright © 2013 Movement Disorders Society.

Animal models of obsessive–compulsive disorder: utility and limitations

PubMed Central

Alonso, Pino; López-Solà, Clara; Real, Eva; Segalàs, Cinto; Menchón, José Manuel

2015-01-01

Obsessive–compulsive disorder (OCD) is a disabling and common neuropsychiatric condition of poorly known etiology. Many attempts have been made in the last few years to develop animal models of OCD with the aim of clarifying the genetic, neurochemical, and neuroanatomical basis of the disorder, as well as of developing novel pharmacological and neurosurgical treatments that may help to improve the prognosis of the illness. The latter goal is particularly important given that around 40% of patients with OCD do not respond to currently available therapies. This article summarizes strengths and limitations of the leading animal models of OCD including genetic, pharmacologically induced, behavioral manipulation-based, and neurodevelopmental models according to their face, construct, and predictive validity. On the basis of this evaluation, we discuss that currently labeled “animal models of OCD” should be regarded not as models of OCD but, rather, as animal models of different psychopathological processes, such as compulsivity, stereotypy, or perseverance, that are present not only in OCD but also in other psychiatric or neurological disorders. Animal models might constitute a challenging approach to study the neural and genetic mechanism of these phenomena from a trans-diagnostic perspective. Animal models are also of particular interest as tools for developing new therapeutic options for OCD, with the greatest convergence focusing on the glutamatergic system, the role of ovarian and related hormones, and the exploration of new potential targets for deep brain stimulation. Finally, future research on neurocognitive deficits associated with OCD through the use of analogous animal tasks could also provide a genuine opportunity to disentangle the complex etiology of the disorder. PMID:26346234

Predictive animal models of mania: hits, misses and future directions

PubMed Central

Young, Jared W; Henry, Brook L; Geyer, Mark A

2011-01-01

Mania has long been recognized as aberrant behaviour indicative of mental illness. Manic states include a variety of complex and multifaceted symptoms that challenge clear clinical distinctions. Symptoms include over-activity, hypersexuality, irritability and reduced need for sleep, with cognitive deficits recently linked to functional outcome. Current treatments have arisen through serendipity or from other disorders. Hence, treatments are not efficacious for all patients, and there is an urgent need to develop targeted therapeutics. Part of the drug discovery process is the assessment of therapeutics in animal models. Here we review pharmacological, environmental and genetic manipulations developed to test the efficacy of therapeutics in animal models of mania. The merits of these models are discussed in terms of the manipulation used and the facet of mania measured. Moreover, the predictive validity of these models is discussed in the context of differentiating drugs that succeed or fail to meet criteria as approved mania treatments. The multifaceted symptomatology of mania has not been reflected in the majority of animal models, where locomotor activity remains the primary measure. This approach has resulted in numerous false positives for putative treatments. Recent work highlights the need to utilize multivariate strategies to enable comprehensive assessment of affective and cognitive dysfunction. Advances in therapeutic treatment may depend on novel models developed with an integrated approach that includes: (i) a comprehensive battery of tests for different aspects of mania, (ii) utilization of genetic information to establish aetiological validity and (iii) objective quantification of patient behaviour with translational cross-species paradigms. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21410454

A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models.

PubMed

Asaad, Mazen; Lee, Jin Hyung

2018-05-18

Alzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models. © 2018. Published by The Company of Biologists Ltd.

A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models

PubMed Central

Asaad, Mazen

2018-01-01

ABSTRACT Alzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models. PMID:29784664

Rodent Models of Experimental Endometriosis: Identifying Mechanisms of Disease and Therapeutic Targets

PubMed Central

Bruner-Tran, Kaylon L.; Mokshagundam, Shilpa; Herington, Jennifer L.; Ding, Tianbing; Osteen, Kevin G.

2018-01-01

Background: Although it has been more than a century since endometriosis was initially described in the literature, understanding the etiology and natural history of the disease has been challenging. However, the broad utility of murine and rat models of experimental endometriosis has enabled the elucidation of a number of potentially targetable processes which may otherwise promote this disease. Objective: To review a variety of studies utilizing rodent models of endometriosis to illustrate their utility in examining mechanisms associated with development and progression of this disease. Results: Use of rodent models of endometriosis has provided a much broader understanding of the risk factors for the initial development of endometriosis, the cellular pathology of the disease and the identification of potential therapeutic targets. Conclusion: Although there are limitations with any animal model, the variety of experimental endometriosis models that have been developed has enabled investigation into numerous aspects of this disease. Thanks to these models, our under-standing of the early processes of disease development, the role of steroid responsiveness, inflammatory processes and the peritoneal environment has been advanced. More recent models have begun to shed light on how epigenetic alterations con-tribute to the molecular basis of this disease as well as the multiple comorbidities which plague many patients. Continued de-velopments of animal models which aid in unraveling the mechanisms of endometriosis development provide the best oppor-tunity to identify therapeutic strategies to prevent or regress this enigmatic disease.

Multi-tissue DNA methylation age: Molecular relationships and perspectives for advancing biomarker utility.

PubMed

Nwanaji-Enwerem, Jamaji C; Weisskopf, Marc G; Baccarelli, Andrea A

2018-04-23

The multi-tissue DNA methylation estimator of chronological age (DNAm-age) has been associated with a wide range of exposures and health outcomes. Still, it is unclear how DNAm-age can have such broad relationships and how it can be best utilized as a biomarker. Understanding DNAm-age's molecular relationships is a promising approach to address this critical knowledge gap. In this review, we discuss the existing literature regarding DNAm-age's molecular relationships in six major categories: animal model systems, cancer processes, cellular aging processes, immune system processes, metabolic processes, and nucleic acid processes. We also present perspectives regarding the future of DNAm-age research, including the need to translate a greater number of ongoing research efforts to experimental and animal model systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Visually guided tube thoracostomy insertion comparison to standard of care in a large animal model.

PubMed

Hernandez, Matthew C; Vogelsang, David; Anderson, Jeff R; Thiels, Cornelius A; Beilman, Gregory; Zielinski, Martin D; Aho, Johnathon M

2017-04-01

Tube thoracostomy (TT) is a lifesaving procedure for a variety of thoracic pathologies. The most commonly utilized method for placement involves open dissection and blind insertion. Image guided placement is commonly utilized but is limited by an inability to see distal placement location. Unfortunately, TT is not without complications. We aim to demonstrate the feasibility of a disposable device to allow for visually directed TT placement compared to the standard of care in a large animal model. Three swine were sequentially orotracheally intubated and anesthetized. TT was conducted utilizing a novel visualization device, tube thoracostomy visual trocar (TTVT) and standard of care (open technique). Position of the TT in the chest cavity were recorded using direct thoracoscopic inspection and radiographic imaging with the operator blinded to results. Complications were evaluated using a validated complication grading system. Standard descriptive statistical analyses were performed. Thirty TT were placed, 15 using TTVT technique, 15 using standard of care open technique. All of the TT placed using TTVT were without complication and in optimal position. Conversely, 27% of TT placed using standard of care open technique resulted in complications. Necropsy revealed no injury to intrathoracic organs. Visual directed TT placement using TTVT is feasible and non-inferior to the standard of care in a large animal model. This improvement in instrumentation has the potential to greatly improve the safety of TT. Further study in humans is required. Therapeutic Level II. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical utility and development of biomarkers in invasive aspergillosis.

PubMed

Patterson, Thomas F

2011-01-01

The diagnosis of invasive aspergillosis remains very difficult, and there are limited treatment options for the disease. Pre-clinical models have been used to evaluate the diagnosis and treatment of Aspergillus infection and to assess the pathogenicity and virulence of the organism. Extensive efforts in Aspergillus research have significantly expanded the genomic information about this microorganism. The standardization of animal models of invasive aspergillosis can be used to enhance the evaluation of genomic information about the organism to improve the diagnosis and treatment of invasive aspergillosis. One approach to this process has been the award of a contract by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to establish and standardize animal models of invasive aspergillosis for the development of new diagnostic technologies for both pulmonary and disseminated Aspergillus infection. This work utilizes molecular approaches for the genetic manipulation of Aspergillus strains that can be tested in animal-model systems to establish new diagnostic targets and tools. Studies have evaluated the performance characteristics of assays for cell-wall antigens of Aspergillus including galactomannan and beta-D-glucan, as well as for DNA targets in the organism, through PCR. New targets, such as proteomic and genomic approaches, and novel detection methods, such as point-of-care lateral-flow devices, have also been evaluated. The goal of this paper is to provide a framework for evaluating genomic targets in animal models to improve the diagnosis and treatment of invasive aspergillosis toward ultimately improving the outcomes for patients with this frequently fatal infection.

A cross-species analysis method to analyze animal models' similarity to human's disease state

PubMed Central

2012-01-01

Background Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism. Results We developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery. We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning. Conclusions We developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology. PMID:23282076

A cross-species analysis method to analyze animal models' similarity to human's disease state.

PubMed

Yu, Shuhao; Zheng, Lulu; Li, Yun; Li, Chunyan; Ma, Chenchen; Li, Yixue; Li, Xuan; Hao, Pei

2012-01-01

Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism. We developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery. We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning. We developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology.

Therapeutic Utility of Non-Peptidic CRF1 Receptor Antagonists in Anxiety, Depression, and Stress-Related Disorders: Evidence from Animal Models

PubMed Central

Kehne, John H.; Cain, Christopher K.

2012-01-01

Adaptive responding to threatening stressors is of fundamental importance for survival. Dysfunctional hyperactivation of corticotropin releasing factor type-1 (CRF1) receptors in stress response system pathways is linked to stress-related psychopathology and CRF1 receptor antagonists (CRAs) have been proposed as novel therapeutic agents. CRA effects in diverse animal models of stress that detect anxiolytics and/or antidepressants are reviewed, with the goal of evaluating their potential therapeutic utility in depression, anxiety, and other stress-related disorders. CRAs have a distinct phenotype in animals that has similarities to, and differences from, those of classic antidepressants and anxiolytics. CRAs are generally behaviorally silent, indicating that CRF1 receptors are normally in a state of low basal activation. CRAs reduce stressor-induced HPA axis activation by blocking pituitary and possibly brain CRF1 receptors which may ameliorate chronic stress-induced pathology. In animal models sensitive to anxiolytics and/or antidepressants, CRAs are generally more active in those with high stress levels, conditions which may maximize CRF1 receptor hyperactivation. Clinically, CRAs have demonstrated good tolerability and safety, but have thus far lacked compelling efficacy in major depressive disorder, generalized anxiety disorder, or irritable bowel syndrome. CRAs may be best suited for disorders in which stressors clearly contribute to the underlying pathology (e.g. posttraumatic stress disorder, early life trauma, withdrawal/abstinence from addictive substances), though much work is needed to explore these possibilities. An evolving literature exploring the genetic, developmental and environmental factors linking CRF1 receptor dysfunction to stress-related psychopathology is discussed in the context of improving the translational value of current animal models. PMID:20826181

Animal to human translational paradigms relevant for approach avoidance conflict decision making.

PubMed

Kirlic, Namik; Young, Jared; Aupperle, Robin L

2017-09-01

Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work. Copyright © 2017 Elsevier Ltd. All rights reserved.

9 CFR 315.2 - Carcasses and parts passed for cooking; utilization for food purposes after cooking.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Carcasses and parts passed for cooking; utilization for food purposes after cooking. 315.2 Section 315.2 Animals and Animal Products FOOD SAFETY AND... PARTS PASSED FOR COOKING § 315.2 Carcasses and parts passed for cooking; utilization for food purposes...

Mapping Thermal Habitat of Ectotherms Based on Behavioral Thermoregulation in a Controlled Thermal Environment

NASA Astrophysics Data System (ADS)

Fei, T.; Skidmore, A.; Liu, Y.

2012-07-01

Thermal environment is especially important to ectotherm because a lot of physiological functions rely on the body temperature such as thermoregulation. The so-called behavioural thermoregulation function made use of the heterogeneity of the thermal properties within an individual's habitat to sustain the animal's physiological processes. This function links the spatial utilization and distribution of individual ectotherm with the thermal properties of habitat (thermal habitat). In this study we modelled the relationship between the two by a spatial explicit model that simulates the movements of a lizard in a controlled environment. The model incorporates a lizard's transient body temperatures with a cellular automaton algorithm as a way to link the physiology knowledge of the animal with the spatial utilization of its microhabitat. On a larger spatial scale, 'thermal roughness' of the habitat was defined and used to predict the habitat occupancy of the target species. The results showed the habitat occupancy can be modelled by the cellular automaton based algorithm at a smaller scale, and can be modelled by the thermal roughness index at a larger scale.

[Thoughts on the complex relationship between medicine and animals: a death prayer for a loyal cat].

PubMed

Cabello C, Felipe

2013-11-01

From its basis in the writings of the philosopher Peter Singer and the bioethical shortcomings of animal experimentation and animal husbandry, the animal rights movement has evolved into an important societal movement critical of animal experimentation in biomedical research. A lack of dialogue and transparency, an absence of understanding and an unreasonable radicalization of different positions regarding animal experimentation has frequently resulted in an adversarial relationship between some members of the scientific community and societal groups aggressively protecting animal rights. In response to this problem, both the bioethical regulations pertaining to biomedical experimentation with animals and the powers of animal care committees (IACUCs) have been strengthened. Careful analysis of the relevance of animal models to human conditions, replacement of these models with non-animal models when possible, adequate re-examination of existing knowledge before undertaking new experimental projects involving animals, and the improvement of methods to avoid animal stress and pain have further strengthened the bioethical basis of animal experimentation. To improve the ethical integrity of research conducted with animals, it is also necessary to increase the editorial scrutiny of the bioethical standards of potentially publishable research utilizing animals. Of note is also the recent use of animals in alternative animal associated therapies (AAT) to ameliorate several medical conditions. Education of the biomedical community, including students and professionals, and of societal groups concerned about this issue as well as directness and continuous dialogue among all the stakeholders are essential to insure the wellbeing of animals and the ethical integrity of biomedical research.

A critical evaluation of validity and utility of translational imaging in pain and analgesia: Utilizing functional imaging to enhance the process.

PubMed

Upadhyay, Jaymin; Geber, Christian; Hargreaves, Richard; Birklein, Frank; Borsook, David

2018-01-01

Assessing clinical pain and metrics related to function or quality of life predominantly relies on patient reported subjective measures. These outcome measures are generally not applicable to the preclinical setting where early signs pointing to analgesic value of a therapy are sought, thus introducing difficulties in animal to human translation in pain research. Evaluating brain function in patients and respective animal model(s) has the potential to characterize mechanisms associated with pain or pain-related phenotypes and thereby provide a means of laboratory to clinic translation. This review summarizes the progress made towards understanding of brain function in clinical and preclinical pain states elucidated using an imaging approach as well as the current level of validity of translational pain imaging. We hypothesize that neuroimaging can describe the central representation of pain or pain phenotypes and yields a basis for the development and selection of clinically relevant animal assays. This approach may increase the probability of finding meaningful new analgesics that can help satisfy the significant unmet medical needs of patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

The relevance of non-human primate and rodent malaria models for humans

PubMed Central

2011-01-01

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material. PMID:21288352

Investigation of nutriactive phytochemical - gamma-oryzanol in experimental animal models.

PubMed

Szcześniak, K A; Ostaszewski, P; Ciecierska, A; Sadkowski, T

2016-08-01

Gamma-oryzanol (GO) is an abundant dietary antioxidant that is considered to have beneficial effects in cardiovascular disease, cancer and diabetes. Other potential properties of GO include inhibition of gastric acid secretion and decreased post-exercise muscle fatigue. GO is a unique mixture of triterpene alcohol and sterol ferulates present in rice bran oil, a byproduct of rice processing. GO has been studied by many researchers over the last three decades. In particular, the utility of GO supplementation has been documented in numerous animal models. A large variety of species was examined, and various experimental methodologies and targets were applied. The aim of this study was to summarize the body of research on GO supplementation in animals and to examine possible mechanisms of GO action. Furthermore, while the safety of GO supplementation in animals has been well documented, studies demonstrating pharmacokinetics, pharmacodynamics and efficiency are less clear. The observed differences in these findings are also discussed. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Preparation of swine for the laboratory.

PubMed

Smith, Alison C; Swindle, M Michael

2006-01-01

Swine are an important model in many areas of biomedical research. These animals have been used predominantly as preclinical models involving surgical and interventional protocols. The systems most commonly studied include cardiovascular, integumentary, digestive, and urological. Swine are intelligent social animals and require species-specific socialization and handling techniques. It is important to acclimate the animals to the facility and to personnel before they are placed on chronic protocols. Gentle handling techniques instead of forceful procedures are essential to their socialization. They require sturdy caging with specific construction standards, and toys for environmental enrichment. Because the species is covered by both the Animal Welfare Act and the US Department of Agriculture, interstate transport requires a health certificate with destination state-specific disease screening standards. This manuscript provides an overview of best practices that have been utilized in the authors' facility.

Animal models of asthma: utility and limitations.

PubMed

Aun, Marcelo Vivolo; Bonamichi-Santos, Rafael; Arantes-Costa, Fernanda Magalhães; Kalil, Jorge; Giavina-Bianchi, Pedro

2017-01-01

Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila , rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes of allergen administration.

Gonadal and Sex Differentiation Abnormalities of Dogs and Cats

PubMed Central

Meyers-Wallen, V.N.

2012-01-01

The molecular steps in normal sexual development were largely discovered by studying patients and animal models with disorders of sexual development (DSD). Although several types of DSD have been reported in the cat and dog, which are often strikingly similar to human DSD, these have been infrequently utilized to contribute to our knowledge of mammalian sexual development. Canine and feline cases of DSD with sufficient evidence to be considered as potential models are summarized in this report. The consensus DSD terminology, and reference to previous terminology, is used to foster adoption of a common nomenclature that will facilitate communication and collaboration between veterinarians, physicians, and researchers. To efficiently utilize these unique resources as molecular tools continue to improve, it will be helpful to deposit samples from valuable cases into repositories where they are available to contribute to our understanding of sexual development, and thus improve human and animal health. PMID:22005097

Insights revealed by rodent models of sugar binge eating.

PubMed

Murray, Susan M; Tulloch, Alastair J; Chen, Eunice Y; Avena, Nicole M

2015-12-01

Binge eating is seen across the spectrum of eating disorder diagnoses as well as among individuals who do not meet diagnostic criteria. Analyses of the specific types of foods that are frequently binged upon reveal that sugar-rich items feature prominently in binge-type meals, making the effects of binge consumption of sugar an important focus of study. One avenue to do this involves the use of animal models. Foundational and recent studies of animal models of sugar bingeing, both outlined here, lend insight into the various neurotransmitters and neuropeptides that may participate in or be altered by this behavior. Further, several preclinical studies incorporating sugar bingeing paradigms have explored the utility of pharmacological agents that target such neural systems for reducing sugar bingeing in an effort to enhance clinical treatment. Indeed, the translational implications of findings generated using animal models of sugar bingeing are considered here, along with potential avenues for further study.

The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies

PubMed Central

Modi, Meera E.; Young, Larry J.

2012-01-01

Animal models and behavioral paradigms are critical for elucidating the neural mechanism involved in complex behaviors, including social cognition. Both genotype and phenotype based models have implicated the neuropeptide oxytocin (OT) in the regulation of social behavior. Based on the findings in animal models, alteration of the OT system has been hypothesized to play a role in the social deficits associated with autism and other neuropsychiatric disorders. While the evidence linking the peptide to the etiology of the disorder is not yet conclusive, evidence from multiple animal models suggest modulation of the OT system may be a viable strategy for the pharmacological treatment of social deficits. In this review, we will discuss how animal models have been utilized to understand the role of OT in social cognition and how those findings can be applied to the conceptualization and treatment of the social impairments in ASD. Animal models with genetic alterations of the OT system, like the OT, OT receptor and CD38 knock-out mice, and those with phenotypic variation in social behavior, like BTBR inbred mice and prairie voles, coupled with behavioral paradigms with face and construct validity may prove to have predictive validity for identifying the most efficacious methods of stimulating the OT system to enhance social cognition in humans. The widespread use of strong animal models of social cognition has the potential yield pharmacological, interventions for the treatment social impairments psychiatric disorders. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. PMID:22206823

Self Motion Perception and Motion Sickness

NASA Technical Reports Server (NTRS)

Fox, Robert A. (Principal Investigator)

1991-01-01

The studies conducted in this research project examined several aspects of motion sickness in animal models. A principle objective of these studies was to investigate the neuroanatomy that is important in motion sickness with the objectives of examining both the utility of putative models and defining neural mechanisms that are important in motion sickness.

Use of a Guinea Pig-Specific Transcriptome Array for Evaluation of Protective Immunity against Genital Chlamydial Infection following Intranasal Vaccination in Guinea Pigs

PubMed Central

Veselenak, Ronald L.; Li, Yansong; Yu, Jieh-Juen; Murthy, Ashlesh K.; Cap, Andrew P.; Guentzel, M. Neal; Chambers, James P.; Zhong, Guangming; Rank, Roger G.; Pyles, Richard B.; Arulanandam, Bernard P.

2014-01-01

Guinea pigs have been used as a second animal model to validate putative anti-chlamydial vaccine candidates tested in mice. However, the lack of guinea pig-specific reagents has limited the utility of this animal model in Chlamydia sp. vaccine studies. Using a novel guinea pig-specific transcriptome array, we determined correlates of protection in guinea pigs vaccinated with Chlamydia caviae (C. caviae) via the intranasal route, previously reported by us and others to provide robust antigen specific immunity against subsequent intravaginal challenge. C. caviae vaccinated guinea pigs resolved genital infection by day 3 post challenge. In contrast, mock vaccinated animals continued to shed viable Chlamydia up to day 18 post challenge. Importantly, at day 80 post challenge, vaccinated guinea pigs experienced significantly reduced genital pathology - a sequelae of genital chlamydial infections, in comparison to mock vaccinated guinea pigs. Sera from vaccinated guinea pigs displayed antigen specific IgG responses and increased IgG1 and IgG2 titers capable of neutralizing GPIC in vitro. Th1-cellular/inflammatory immune genes and Th2-humoral associated genes were also found to be elevated in vaccinated guinea pigs at day 3 post-challenge and correlated with early clearance of the bacterium. Overall, this study provides the first evidence of guinea pig-specific genes involved in anti-chlamydial vaccination and illustrates the enhancement of the utility of this animal model in chlamydial pathogenesis. PMID:25502875

The virtual craniofacial patient: 3D jaw modeling and animation.

PubMed

Enciso, Reyes; Memon, Ahmed; Fidaleo, Douglas A; Neumann, Ulrich; Mah, James

2003-01-01

In this paper, we present new developments in the area of 3D human jaw modeling and animation. CT (Computed Tomography) scans have traditionally been used to evaluate patients with dental implants, assess tumors, cysts, fractures and surgical procedures. More recently this data has been utilized to generate models. Researchers have reported semi-automatic techniques to segment and model the human jaw from CT images and manually segment the jaw from MRI images. Recently opto-electronic and ultrasonic-based systems (JMA from Zebris) have been developed to record mandibular position and movement. In this research project we introduce: (1) automatic patient-specific three-dimensional jaw modeling from CT data and (2) three-dimensional jaw motion simulation using jaw tracking data from the JMA system (Zebris).

Emerging Technologies to Create Inducible and Genetically Defined Porcine Cancer Models.

PubMed

Schook, Lawrence B; Rund, Laurie; Begnini, Karine R; Remião, Mariana H; Seixas, Fabiana K; Collares, Tiago

2016-01-01

There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic, and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research.

Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis

PubMed Central

Tashiro, Jun; Rubio, Gustavo A.; Limper, Andrew H.; Williams, Kurt; Elliot, Sharon J.; Ninou, Ioanna; Aidinis, Vassilis; Tzouvelekis, Argyrios; Glassberg, Marilyn K.

2017-01-01

Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis—though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent. Additional studies that profile these examples of spontaneous fibroses in animals for similarities to human IPF should prove useful for both human and animal investigators. In the meantime, studies of BLM-induced fibrosis in aged male mice remain the most clinically relevant model for preclinical study for human IPF. Addressing issues such as time course of treatment, animal size and characteristics, clinically irrelevant treatment endpoints, and reproducibility of therapeutic outcomes will improve the current status of preclinical studies. Elucidating the mechanisms responsible for the development of fibrosis and disrepair associated with aging through a collaborative approach between researchers will promote the development of models that more accurately represent the realm of interstitial lung diseases in humans. PMID:28804709

Northern Great Basin Seasonal Lakes: Vulnerability to Climate Change.

NASA Astrophysics Data System (ADS)

Russell, M.; Eitel, J.

2017-12-01

Seasonal alkaline lakes in southeast Oregon, northeast California, and northwest Nevada serve as important habitat for migrating birds utilizing the Pacific Flyway, as well as local plant and animal communities. Despite their ecological importance, and anecdotal suggestions that these lakes are becoming less reliable, little is known about the vulnerability of these lakes to climate change. Our research seeks to understand the vulnerability of Northern Great Basin seasonal lakes to climate change. For this, we will be using historical information from the European Space Agency's Global Surface Water Explorer and the University of Idaho's gridMET climate product, to build a model that allows estimating surface water extent and timing based on climate variables. We will then utilize downscaled future climate projections to model surface water extent and timing in the coming decades. In addition, an unmanned aerial system (UAS) will be utilized at a subset of dried basins to obtain precise 3D bathymetry and calculate water volume hypsographs, a critical factor in understanding the likelihood of water persistence and biogeochemical habitat suitability. These results will be incorporated into decision support tools that land managers can utilize in water conservation, wildlife management, and climate mitigation actions. Future research may pair these forecasts with animal movement data to examine fragmentation of migratory corridors and species-specific impacts.

Dystrophin-deficient large animal models: translational research and exon skipping

PubMed Central

Yu, Xinran; Bao, Bo; Echigoya, Yusuke; Yokota, Toshifumi

2015-01-01

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder caused by mutations in the dystrophin gene. Affecting approximately 1 in 3,600-9337 boys, DMD patients exhibit progressive muscle degeneration leading to fatality as a result of heart or respiratory failure. Despite the severity and prevalence of the disease, there is no cure available. While murine models have been successfully used in illustrating the mechanisms of DMD, their utility in DMD research is limited due to their mild disease phenotypes such as lack of severe skeletal muscle and cardiac symptoms. To address the discrepancy between the severity of disease displayed by murine models and human DMD patients, dystrophin-deficient dog models with a splice site mutation in intron 6 were established. Examples of these are Golden Retriever muscular dystrophy and beagle-based Canine X-linked muscular dystrophy. These large animal models are widely employed in therapeutic DMD research due to their close resemblance to the severity of human patient symptoms. Recently, genetically tailored porcine models of DMD with deleted exon 52 were developed by our group and others, and can potentially act as a new large animal model. While therapeutic outcomes derived from these large animal models can be more reliably extrapolated to DMD patients, a comprehensive understanding of these models is still needed. This paper will discuss recent progress and future directions of DMD studies with large animal models such as canine and porcine models. PMID:26396664

Zebrafish: A Versatile Animal Model for Fertility Research.

PubMed

Hoo, Jing Ying; Kumari, Yatinesh; Shaikh, Mohd Farooq; Hue, Seow Mun; Goh, Bey Hing

2016-01-01

The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research.

Zebrafish: A Versatile Animal Model for Fertility Research

PubMed Central

Hoo, Jing Ying; Kumari, Yatinesh; Shaikh, Mohd Farooq; Hue, Seow Mun

2016-01-01

The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research. PMID:27556045

Epigenetic and gene expression changes in the adolescent brain: What have we learned from animal models?

PubMed

Mychasiuk, Richelle; Metz, Gerlinde A S

2016-11-01

Adolescence is defined as the gradual period of transition between childhood and adulthood that is characterized by significant brain maturation, growth spurts, sexual maturation, and heightened social interaction. Although originally believed to be a uniquely human aspect of development, rodent and non-human primates demonstrate maturational patterns that distinctly support an adolescent stage. As epigenetic processes are essential for development and differentiation, but also transpire in mature cells in response to environmental influences, they are an important aspect of adolescent brain maturation. The purpose of this review article was to examine epigenetic programming in animal models of brain maturation during adolescence. The discussion focuses on animal models to examine three main concepts; epigenetic processes involved in normal adolescent brain maturation, the influence of fetal programming on adolescent brain development and the epigenome, and finally, postnatal experiences such as exercise and drugs that modify epigenetic processes important for adolescent brain maturation. This corollary emphasizes the utility of animal models to further our understanding of complex processes such as epigenetic regulation and brain development. Copyright © 2016 Elsevier Ltd. All rights reserved.

The science and necessity of using animal models in the study of necrotizing enterocolitis.

PubMed

Ares, Guillermo J; McElroy, Steven J; Hunter, Catherine J

2018-02-01

Necrotizing enterocolitis (NEC) remains one of the highest causes of mortality and of acute and long-term morbidity in premature infants. Multiple factors are involved in the pathophysiology of NEC including the immaturity of the immune system and the complex changing composition of the intestinal microbiome. This is compounded by the fact that the premature infant should ideally still be a developing fetus and has an immature intestinal tract. Because these complexities are beyond the scope of studies in single-cell cultures, animal models are absolutely essential to understand the mechanisms involved in the pathophysiology of NEC and the effects of inflammation on the immature intestinal tract. To this end, investigators have utilized many different species (e.g., rats, mice, rabbits, quails, piglets, and non-human primates) and conditions to develop models of NEC. Each animal has distinct advantages and drawbacks related to its preterm viability, body size, genetic variability, and cost. The choice of animal model is strongly influenced by the scientific question being addressed. While no model perfectly mimics human NEC, each has greatly improved our understanding of disease. Examples of recent discoveries in NEC pathogenesis and prevention underscore the importance of continued animal research in NEC. Copyright © 2018 Elsevier Inc. All rights reserved.

SHEEP AS AN EXPERIMENTAL MODEL FOR BIOMATERIAL IMPLANT EVALUATION

PubMed Central

SARTORETTO, SUELEN CRISTINA; UZEDA, MARCELO JOSÉ; MIGUEL, FÚLVIO BORGES; NASCIMENTO, JHONATHAN RAPHAELL; ASCOLI, FABIO; CALASANS-MAIA, MÔNICA DIUANA

2016-01-01

ABSTRACT Objective: Based on a literature review and on our own experience, this study proposes sheep as an experimental model to evaluate the bioactive capacity of bone substitute biomaterials, dental implant systems and orthopedics devices. The literature review covered relevant databases available on the Internet from 1990 until to date, and was supplemented by our own experience. Methods: For its resemblance in size and weight to humans, sheep are quite suitable for use as an experimental model. However, information about their utility as an experimental model is limited. The different stages involving sheep experiments were discussed, including the care during breeding and maintenance of the animals obtaining specimens for laboratory processing, and highlighting the unnecessary euthanasia of animals at the end of study, in accordance to the guidelines of the 3Rs Program. Results: All experiments have been completed without any complications regarding the animals and allowed us to evaluate hypotheses and explain their mechanisms. Conclusion: The sheep is an excellent animal model for evaluation of biomaterial for bone regeneration and dental implant osseointegration. From an ethical point of view, one sheep allows for up to 12 implants per animal, permitting to keep them alive at the end of the experiments. Level of Evidence II, Retrospective Study. PMID:28149193

Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model

PubMed Central

Canal, Clint E.; Morgan, Drake

2013-01-01

Two primary animal models persist for assessing hallucinogenic potential of novel compounds and for examining the pharmacological and neurobiological substrates underlying the actions of classical hallucinogens, the two-lever drug discrimination procedure and the drug-induced head-twitch response (HTR) in rodents. The substituted amphetamine hallucinogen, serotonin 2 (5-HT2) receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI) has emerged as the most popular pharmacological tool used in HTR studies of hallucinogens. Synthesizing classic, recent, and relatively overlooked findings, addressing ostensibly conflicting observations, and considering contemporary theories in receptor and behavioural pharmacology, this review provides an up-to-date and comprehensive synopsis of DOI and the HTR model, from neural mechanisms to utility for understanding psychiatric diseases. Also presented is support for the argument that, although both the two-lever drug discrimination and the HTR models in rodents are useful for uncovering receptors, interacting proteins, intracellular signalling pathways, and neurochemical processes affected by DOI and related classical hallucinogens, results from both models suggest they are not reporting hallucinogenic experiences in animals. PMID:22517680

The interstitial stem cells in Hydractinia and their role in regeneration.

PubMed

Gahan, James M; Bradshaw, Brian; Flici, Hakima; Frank, Uri

2016-10-01

Hydractinia species have been animal models in developmental biology and comparative immunology for over a century, but are having a renaissance due to the establishment of modern genetic and genomic tools by the growing community of researchers utilizing them. Hydractinia has a predictable and accessible life cycle and its stem cell system, known as interstitial- or i-cells has been a paradigm for animal stem cells since the late 1800s. In adult Hydractinia, i-cells continuously provide progenitors to sustain clonal growth, tissue homeostasis, sexual reproduction and regeneration. We review recent developments in stem cell and regeneration research centered on this animal. Hydractinia joins an established team of cnidarian genetic models in times of rapid progress in these disciplines. While each animal is particularly suited to specific experimental settings, jointly they can provide an integrative insight into the diversity of animal stem cell systems, how they drive regeneration, and how they evolved. Copyright © 2016 Elsevier Ltd. All rights reserved.

Successful implementation of cooperative handling eliminates the need for restraint in a complex nonhuman primate disease model

PubMed Central

Graham, Melanie L; Rieke, Eric F; Mutch, Lucas A; Zolondek, Elizabeth K; Faig, Aaron W; DuFour, Theresa A; Munson, James W; Kittredge, Jessica A; Schuurman, Henk-Jan

2011-01-01

Introduction Streptozotocin-induced diabetic nonhuman primates are used to study efficacy and safety of innovative immunosuppression after islet transplantation. We implemented a training program for medical management of a chronic disease state. Methods Cooperation with hand feeding and drinking; shifting; and limb presentation were trained utilizing predominately positive but also negative reinforcement in 52 animals compared with 28 macaques subjected to conventional physical and/or chemical restraint. The success of and timing of behavior acquisition was evaluated in a representative subset of 14 animals. Results Over 90% of animals were successful in behavior acquisition. Programmatically this resulted in complete elimination of chair restraint and negligible requirement for sedation. About half of trained animals had no to moderate thymic involution, indicative of a substantial reduction in stress. Conclusion Cooperative handling enhances animal well-being. This contributes to validity of scientific results and eliminates model-induced confounding that can obstruct interpretation of safety and efficacy data. PMID:22150842

Propagation modeling for sperm whale acoustic clicks in the northern Gulf of Mexico

NASA Astrophysics Data System (ADS)

Sidorovskaia, Natalia A.; Udovydchenkov, Ilya A.; Rypina, Irina I.; Ioup, George E.; Ioup, Juliette W.; Caruthers, Jerald W.; Newcomb, Joal; Fisher, Robert

2004-05-01

Simulations of acoustic broadband (500-6000 Hz) pulse propagation in the northern Gulf of Mexico, based on environmental data collected as a part of the Littoral Acoustic Demonstration Center (LADC) experiments in the summers of 2001 and 2002, are presented. The results of the modeling support the hypothesis that consistent spectrogram interference patterns observed in the LADC marine mammal phonation data cannot be explained by the propagation effects for temporal analysis windows corresponding to the duration of an animal click, and may be due to a uniqueness of an individual animal phonation apparatus. The utilization of simulation data for the development of an animal tracking algorithm based on the acoustic recordings of a single bottom-moored hydrophone is discussed. The identification of the bottom and surface reflected clicks from the same animal is attempted. The critical ranges for listening to a deep-water forging animal by a surface receiving system are estimated. [Research supported by ONR.

Utility and translatability of mathematical modeling, cell culture and small and large animal models in magnetic nanoparticle hyperthermia cancer treatment research

NASA Astrophysics Data System (ADS)

Hoopes, P. J.; Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Pearce, John A.; Ryan, Thomas P.

2015-03-01

For more than 50 years, hyperthermia-based cancer researchers have utilized mathematical models, cell culture studies and animal models to better understand, develop and validate potential new treatments. It has been, and remains, unclear how and to what degree these research techniques depend on, complement and, ultimately, translate accurately to a successful clinical treatment. In the past, when mathematical models have not proven accurate in a clinical treatment situation, the initiating quantitative scientists (engineers, mathematicians and physicists) have tended to believe the biomedical parameters provided to them were inaccurately determined or reported. In a similar manner, experienced biomedical scientists often tend to question the value of mathematical models and cell culture results since those data typically lack the level of biologic and medical variability and complexity that are essential to accurately study and predict complex diseases and subsequent treatments. Such quantitative and biomedical interdependence, variability, diversity and promise have never been greater than they are within magnetic nanoparticle hyperthermia cancer treatment. The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and, recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. The goal of this paper is to use proven concepts and current research to address the potential pathobiology, modeling and quantification of the effects of treatment as pertaining to the similarities and differences in energy delivered by known external delivery techniques and iron oxide nanoparticles.

Transgenic Mice Expressing Yeast CUP1 Exhibit Increased Copper Utilization from Feeds

PubMed Central

Chen, Zhenliang; Liao, Rongrong; Zhang, Xiangzhe; Wang, Qishan; Pan, Yuchun

2014-01-01

Copper is required for structural and catalytic properties of a variety of enzymes participating in many vital biological processes for growth and development. Feeds provide most of the copper as an essential micronutrient consumed by animals, but inorganic copper could not be utilized effectively. In the present study, we aimed to develop transgenic mouse models to test if copper utilization will be increased by providing the animals with an exogenous gene for generation of copper chelatin in saliva. Considering that the S. cerevisiae CUP1 gene encodes a Cys-rich protein that can bind copper as specifically as copper chelatin in yeast, we therefore constructed a transgene plasmid containing the CUP1 gene regulated for specific expression in the salivary glands by a promoter of gene coding pig parotid secretory protein. Transgenic CUP1 was highly expressed in the parotid and submandibular salivary glands and secreted in saliva as a 9-kDa copper-chelating protein. Expression of salivary copper-chelating proteins reduced fecal copper contents by 21.61% and increased body-weight by 12.97%, suggesting that chelating proteins improve the utilization and absorbed efficacy of copper. No negative effects on the health of the transgenic mice were found by blood biochemistry and histology analysis. These results demonstrate that the introduction of the salivary CUP1 transgene into animals offers a possible approach to increase the utilization efficiency of copper and decrease the fecal copper contents. PMID:25265503

Genomics of coloration in natural animal populations.

PubMed

San-Jose, Luis M; Roulin, Alexandre

2017-07-05

Animal coloration has traditionally been the target of genetic and evolutionary studies. However, until very recently, the study of the genetic basis of animal coloration has been mainly restricted to model species, whereas research on non-model species has been either neglected or mainly based on candidate approaches, and thereby limited by the knowledge obtained in model species. Recent high-throughput sequencing technologies allow us to overcome previous limitations, and open new avenues to study the genetic basis of animal coloration in a broader number of species and colour traits, and to address the general relevance of different genetic structures and their implications for the evolution of colour. In this review, we highlight aspects where genome-wide studies could be of major utility to fill in the gaps in our understanding of the biology and evolution of animal coloration. The new genomic approaches have been promptly adopted to study animal coloration although substantial work is still needed to consider a larger range of species and colour traits, such as those exhibiting continuous variation or based on reflective structures. We argue that a robust advancement in the study of animal coloration will also require large efforts to validate the functional role of the genes and variants discovered using genome-wide tools.This article is part of the themed issue 'Animal coloration: production, perception, function and application'. © 2017 The Author(s).

Efficacy and safety of herbal medicines in treating gastric ulcer: a review.

PubMed

Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

2014-12-07

Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects.

Emerging Technologies to Create Inducible and Genetically Defined Porcine Cancer Models

PubMed Central

Schook, Lawrence B.; Rund, Laurie; Begnini, Karine R.; Remião, Mariana H.; Seixas, Fabiana K.; Collares, Tiago

2016-01-01

There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic, and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research. PMID:26973698

Blunted Hypothalamo-pituitary Adrenal Axis Response to Predator Odor Predicts High Stress Reactivity

PubMed Central

Whitaker, Annie M.; Gilpin, Nicholas W.

2015-01-01

Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as ‘Avoiders’ or Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24 hours and 11 days), anxiety-like behavior (48 hours and 5 days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24 hours that persisted 11 days post-stress. Both Avoiders and Non-Avoiders exhibited heightened anxiety-like behavior at 48 hours and 5 days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and builds on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. PMID:25824191

Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity.

PubMed

Whitaker, Annie M; Gilpin, Nicholas W

2015-08-01

Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as 'Avoiders' or 'Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24h and 11days), anxiety-like behavior (48h and 5days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24h that persisted 11days post-stress. Both Avoiders and Non-Avoiders exhibited a heightened anxiety-like behavior at 48h and 5days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and build on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. Copyright © 2015. Published by Elsevier Inc.

Experimental Model of Biofilm Implant-Related Osteomyelitis To Test Combination Biomaterials Using Biofilms as Initial Inocula

PubMed Central

Williams, Dustin L.; Haymond, Bryan S.; Woodbury, Kassie L.; Beck, J. Peter; Moore, David E.; Epperson, R. Tyler; Bloebaum, Roy D.

2012-01-01

Currently, the majority of animal models that are used to study biofilm-related infections utilize planktonic bacterial cells as initial inocula to produce positive signals of infection in biomaterials studies. However, the use of planktonic cells has potentially led to inconsistent results in infection outcomes. In this study, well-established biofilms of methicillin-resistant Staphylococcus aureus (MRSA) were grown and used as initial inocula in an animal model of a Type IIIB open fracture. The goal of the work was to establish, for the first time, a repeatable model of biofilm implant-related osteomyelitis wherein biofilms were used as initial inocula to test combination biomaterials. Results showed that 100% of animals that were treated with biofilms developed osteomyelitis, whereas 0% of animals not treated with biofilm developed infection. The development of this experimental model may lead to an important shift in biofilm and biomaterials research by showing that when biofilms are used as initial inocula, they may provide additional insights into how biofilm-related infections in the clinic develop and how they can be treated with combination biomaterials to eradicate and/or prevent biofilm formation. PMID:22492534

Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

PubMed

Hoffman, Andrew M; Dow, Steven W

2016-07-01

Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. © 2016 AlphaMed Press.

Asymmetry hidden in birds’ tracks reveals wind, heading, and orientation ability over the ocean

PubMed Central

Goto, Yusuke; Yoda, Ken; Sato, Katsufumi

2017-01-01

Numerous flying and swimming animals constantly need to control their heading (that is, their direction of orientation) in a flow to reach their distant destination. However, animal orientation in a flow has yet to be satisfactorily explained because it is difficult to directly measure animal heading and flow. We constructed a new animal movement model based on the asymmetric distribution of the GPS (Global Positioning System) track vector along its mean vector, which might be caused by wind flow. This statistical model enabled us to simultaneously estimate animal heading (navigational decision-making) and ocean wind information over the range traversed by free-ranging birds. We applied this method to the tracking data of homing seabirds. The wind flow estimated by the model was consistent with the spatiotemporally coarse wind information provided by an atmospheric simulation model. The estimated heading information revealed that homing seabirds could head in a direction different from that leading to the colony to offset wind effects and to enable them to eventually move in the direction they intended to take, even though they are over the open sea where visual cues are unavailable. Our results highlight the utility of combining large data sets of animal movements with the “inverse problem approach,” enabling unobservable causal factors to be estimated from the observed output data. This approach potentially initiates a new era of analyzing animal decision-making in the field. PMID:28959724

Using satellite and airborne LiDAR to model woodpecker habitat occupancy at the landscape scale

Treesearch

Lee A. Vierling; Kerri T. Vierling; Patrick Adam; Andrew T. Hudak

2013-01-01

Incorporating vertical vegetation structure into models of animal distributions can improve understanding of the patterns and processes governing habitat selection. LiDAR can provide such structural information, but these data are typically collected via aircraft and thus are limited in spatial extent. Our objective was to explore the utility of satellite-based LiDAR...

Insights from animal models of bladder cancer: recent advances, challenges, and opportunities

PubMed Central

John, Bincy Anu; Said, Neveen

2017-01-01

Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis. They allow for the investigation of premalignant phases of the disease that are not clinically encountered. They can be useful for identification of diagnostic and prognostic biomarkers for disease progression and for preclinical identification and validation of therapeutic targets/candidates, advancing translation of basic research to clinic. This review summarizes the latest advances in the currently available bladder cancer animal models, their translational potential, merits and demerits, and the prevalent tumor evaluation modalities. Thereby, findings from these model systems would provide valuable information that can help researchers and clinicians utilize the model that best answers their research questions. PMID:28915710

Animal models of Helicobacter-induced disease: methods to successfully infect the mouse.

PubMed

Taylor, Nancy S; Fox, James G

2012-01-01

Animal models of microbial diseases in humans are an essential component for determining fulfillment of Koch's postulates and determining how the organism causes disease, host response(s), disease prevention, and treatment. In the case of Helicobacter pylori, establishing an animal model to fulfill Koch's postulates initially proved so challenging that out of frustration a human volunteer undertook an experiment to become infected with H. pylori and to monitor disease progression in order to determine if it did cause gastritis. For the discovery of the organism and his fulfillment of Koch's postulates he and a colleague were awarded the Nobel Prize in Medicine. After H. pylori was established as a gastric pathogen, it took several years before a model was developed in mice, opening the study of the organism and its pathogenicity to the general scientific community. However, while the model is widely utilized, there are a number of difficulties that can arise and need to be overcome. The purpose of this chapter is to raise awareness regarding the problems, and to offer reliable protocols for successfully establishing the H. pylori mouse model.

Genomic Indicators in the blood predict drug-induced liver injury

EPA Science Inventory

Hepatotoxicity and other forms of liver injury stemming from exposure to toxicants and idiosyncratic drug reactions are major concerns during the drug discovery process. Animal model systems have been utilized in an attempt to extrapolate the risk of harmful agents to humans and...

Rodent models of diabetic nephropathy: their utility and limitations

PubMed Central

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-01-01

Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic nephropathy. PMID:27881924

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma-Past, Present, and Future.

PubMed

Kapoor, Harit; Lohani, Kush Raj; Lee, Tommy H; Agrawal, Devendra K; Mittal, Sumeet K

2015-12-01

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long-standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5-year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett's esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett's esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett's esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett's carcinogenesis. © 2015 Wiley Periodicals, Inc.

Animal models of the serotonin syndrome: a systematic review.

PubMed

Haberzettl, Robert; Bert, Bettina; Fink, Heidrun; Fox, Meredith A

2013-11-01

The serotonin syndrome (SS) is a potentially life-threatening disorder in humans which is induced by ingestion of an overdose or by combination of two or more serotonin (5-HT)-enhancing drugs. In animals, acute administration of direct and indirect 5-HT agonists also leads to a set of behavioral and autonomic responses. In the current review, we provide an overview of the existing versions of the animal model of the SS. With a focus on studies in rats and mice, we analyze the frequency of behavioral and autonomic responses following administration of 5-HT-enhancing drugs and direct 5-HT agonists administered alone or in combination, and we briefly discuss the receptor mediation of these responses. Considering species differences, we identify a distinct set of behavioral and autonomic responses that are consistently observed following administration of direct and indirect 5-HT agonists. Finally, we discuss the importance of a standardized assessment of SS responses in rodents and the utility of animal models of the SS in translational studies, and provide suggestions for future research. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Zebrafish tracking using convolutional neural networks.

PubMed

Xu, Zhiping; Cheng, Xi En

2017-02-17

Keeping identity for a long term after occlusion is still an open problem in the video tracking of zebrafish-like model animals, and accurate animal trajectories are the foundation of behaviour analysis. We utilize the highly accurate object recognition capability of a convolutional neural network (CNN) to distinguish fish of the same congener, even though these animals are indistinguishable to the human eye. We used data augmentation and an iterative CNN training method to optimize the accuracy for our classification task, achieving surprisingly accurate trajectories of zebrafish of different size and age zebrafish groups over different time spans. This work will make further behaviour analysis more reliable.

Zebrafish tracking using convolutional neural networks

NASA Astrophysics Data System (ADS)

Xu, Zhiping; Cheng, Xi En

2017-02-01

Keeping identity for a long term after occlusion is still an open problem in the video tracking of zebrafish-like model animals, and accurate animal trajectories are the foundation of behaviour analysis. We utilize the highly accurate object recognition capability of a convolutional neural network (CNN) to distinguish fish of the same congener, even though these animals are indistinguishable to the human eye. We used data augmentation and an iterative CNN training method to optimize the accuracy for our classification task, achieving surprisingly accurate trajectories of zebrafish of different size and age zebrafish groups over different time spans. This work will make further behaviour analysis more reliable.

Of mice and rats: key species variations in the sexual differentiation of brain and behavior.

PubMed

Bonthuis, P J; Cox, K H; Searcy, B T; Kumar, P; Tobet, S; Rissman, E F

2010-07-01

Mice and rats are important mammalian models in biomedical research. In contrast to other biomedical fields, work on sexual differentiation of brain and behavior has traditionally utilized comparative animal models. As mice are gaining in popularity, it is essential to acknowledge the differences between these two rodents. Here we review neural and behavioral sexual dimorphisms in rats and mice, which highlight species differences and experimental gaps in the literature, that are needed for direct species comparisons. Moving forward, investigators must answer fundamental questions about their chosen organism, and attend to both species and strain differences as they select the optimal animal models for their research questions. Copyright 2010 Elsevier Inc. All rights reserved.

Invited review: Experimental design, data reporting, and sharing in support of animal systems modeling research.

PubMed

McNamara, J P; Hanigan, M D; White, R R

2016-12-01

The National Animal Nutrition Program "National Research Support Project 9" supports efforts in livestock nutrition, including the National Research Council's committees on the nutrient requirements of animals. Our objective was to review the status of experimentation and data reporting in animal nutrition literature and to provide suggestions for the advancement of animal nutrition research and the ongoing improvement of field-applied nutrient requirement models. Improved data reporting consistency and completeness represent a substantial opportunity to improve nutrition-related mathematical models. We reviewed a body of nutrition research; recorded common phrases used to describe diets, animals, housing, and environmental conditions; and proposed equivalent numerical data that could be reported. With the increasing availability of online supplementary material sections in journals, we developed a comprehensive checklist of data that should be included in publications. To continue to improve our research effectiveness, studies utilizing multiple research methodologies to address complex systems and measure multiple variables will be necessary. From the current body of animal nutrition literature, we identified a series of opportunities to integrate research focuses (nutrition, reproduction and genetics) to advance the development of nutrient requirement models. From our survey of current experimentation and data reporting in animal nutrition, we identified 4 key opportunities to advance animal nutrition knowledge: (1) coordinated experiments should be designed to employ multiple research methodologies; (2) systems-oriented research approaches should be encouraged and supported; (3) publication guidelines should be updated to encourage and support sharing of more complete data sets; and (4) new experiments should be more rapidly integrated into our knowledge bases, research programs and practical applications. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development of a Multiroute Human PBPK Model for Bromodichloromethane (BDCM)

EPA Science Inventory

BDCM is an animal carcinogen and developmental toxicant. Due to its presence as a disinfection byproduct in finished drinking water, BDCM may pose a risk for exposure via ingestion, inhalation or dermal exposure. Utilizing a unique data set in which human subjects were exposed ...

Production of accurate skeletal models of domestic animals using three-dimensional scanning and printing technology.

PubMed

Li, Fangzheng; Liu, Chunying; Song, Xuexiong; Huan, Yanjun; Gao, Shansong; Jiang, Zhongling

2018-01-01

Access to adequate anatomical specimens can be an important aspect in learning the anatomy of domestic animals. In this study, the authors utilized a structured light scanner and fused deposition modeling (FDM) printer to produce highly accurate animal skeletal models. First, various components of the bovine skeleton, including the femur, the fifth rib, and the sixth cervical (C6) vertebra were used to produce digital models. These were then used to produce 1:1 scale physical models with the FDM printer. The anatomical features of the digital models and three-dimensional (3D) printed models were then compared with those of the original skeletal specimens. The results of this study demonstrated that both digital and physical scale models of animal skeletal components could be rapidly produced using 3D printing technology. In terms of accuracy between models and original specimens, the standard deviations of the femur and the fifth rib measurements were 0.0351 and 0.0572, respectively. All of the features except the nutrient foramina on the original bone specimens could be identified in the digital and 3D printed models. Moreover, the 3D printed models could serve as a viable alternative to original bone specimens when used in anatomy education, as determined from student surveys. This study demonstrated an important example of reproducing bone models to be used in anatomy education and veterinary clinical training. Anat Sci Educ 11: 73-80. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

MAP3K11/GDF15 axis is a critical driver of cancer cachexia

PubMed Central

Tao, Julie; Liu, Qing; Nicoletti, Richard; Feng, Bin; Krieger, Brian; Mazsa, Elizabeth; Siddiquee, Zakir; Wang, Ruoji; Huang, Lucia; Shen, Luhua; Lin, Jie; Vigano, Antonio; Chiu, M. Isabel; Weng, Zhigang; Winston, William; Weiler, Solly

2015-01-01

Abstract Background Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro‐inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome. Methods Genetically engineered and xenograft tumour models were used to dissect the molecular mechanisms driving cancer cachexia. Cytokine profiling from the plasma of cachectic and non‐cachectic cancer patients and mouse models was utilized to correlate circulating cytokine levels with the cachexia phenotype. Results Utilizing engineered tumour models we identified MAP3K11/GDF15 pathway activation as a potent inducer of cancer cachexia. Increased expression and high circulating levels of GDF15 acted as a key mediator of this process. In animal models, tumour‐produced GDF15 was sufficient to trigger the cachexia phenotype. Elevated GDF15 circulating levels correlated with the onset and progression of cachexia in animal models and in patients with cancer. Inhibition of GDF15 biological activity with a specific antibody reversed body weight loss and restored muscle and fat tissue mass in several cachectic animal models regardless of their complex secreted cytokine profile. Conclusions The combination of correlative observations, gain of function, and loss of function experiments validated GDF15 as a key driver of cancer cachexia and as a potential therapeutic target for the treatment and/or prevention of this syndrome. PMID:27239403

Exploring the Impact of an Animal Assisted Therapy Dog upon the Emotional, Educational, and Social Actualization of Middle School Students Receiving Counseling Services

ERIC Educational Resources Information Center

Jenkins, Christie D.

2009-01-01

The purpose of this study was to examine animal assisted therapy (AAT) in the school setting. This study reviewed the potential social, emotional, and educational benefits that children and adolescents may gain from utilizing an animal assisted therapy dog. This study utilized The Relationship Inventory and The AAT (Animal Assisted Therapy)…

Functional PET Evaluation of the Photosensitive Baboon

PubMed Central

Szabó, C. Ákos; Salinas, Felipe S; Narayana, Shalini

2011-01-01

The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes. PMID:22276085

Mouse Models of Gastric Cancer

PubMed Central

Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

2013-01-01

Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

Animal Models in Genomic Research: Techniques, Applications, and Roles for Nurses

PubMed Central

Osier, Nicole D.; Pham, Lan; Savarese, Amanda; Sayles, Kendra

2016-01-01

Animal research has been conducted by scientists for over two millennia resulting in a better understanding of human anatomy, physiology, and pathology, as well as testing of novel therapies. In the molecular genomic era, pre-clinical models represent a key tool for understanding the genomic underpinnings of health and disease and are relevant to precision medicine initiatives. Nurses contribute to improved health by collecting and translating evidence from clinically relevant pre-clinical models. Using animal models, nurses can ask questions that would not be feasible or ethical to address in humans, and establish the safety and efficacy of interventions before translating them to clinical trials. Two advantages of using pre-clinical models are reduced variability between test subjects and the opportunity for precisely controlled experimental exposures. Standardized care controls the effects of diet and environment, while the availability of inbred strains significantly reduces the confounding effects of genetic differences. Outside the laboratory, nurses can contribute to the approval and oversight of animal studies, as well as translation to clinical trials and, ultimately, patient care. This review is intended as a primer on the use of animal models to advance nursing science; specifically, the paper discusses the utility of preclinical models for studying the pathophysiologic and genomic contributors to health and disease, testing interventions, and evaluating effects of environmental exposures. Considerations specifically geared to nurse researchers are also introduced, including discussion of how to choose an appropriate model and controls, potential confounders, as well as legal and ethical concerns. Finally, roles for nurse clinicians in pre-clinical research are also highlighted. PMID:27969037

Animal models in genomic research: Techniques, applications, and roles for nurses.

PubMed

Osier, Nicole D; Pham, Lan; Savarese, Amanda; Sayles, Kendra; Alexander, Sheila A

2016-11-01

Animal research has been conducted by scientists for over two millennia resulting in a better understanding of human anatomy, physiology, and pathology, as well as testing of novel therapies. In the molecular genomic era, pre-clinical models represent a key tool for understanding the genomic underpinnings of health and disease and are relevant to precision medicine initiatives. Nurses contribute to improved health by collecting and translating evidence from clinically relevant pre-clinical models. Using animal models, nurses can ask questions that would not be feasible or ethical to address in humans, and establish the safety and efficacy of interventions before translating them to clinical trials. Two advantages of using pre-clinical models are reduced variability between test subjects and the opportunity for precisely controlled experimental exposures. Standardized care controls the effects of diet and environment, while the availability of inbred strains significantly reduces the confounding effects of genetic differences. Outside the laboratory, nurses can contribute to the approval and oversight of animal studies, as well as translation to clinical trials and, ultimately, patient care. This review is intended as a primer on the use of animal models to advance nursing science; specifically, the paper discusses the utility of preclinical models for studying the pathophysiologic and genomic contributors to health and disease, testing interventions, and evaluating effects of environmental exposures. Considerations specifically geared to nurse researchers are also introduced, including discussion of how to choose an appropriate model and controls, potential confounders, as well as legal and ethical concerns. Finally, roles for nurse clinicians in pre-clinical research are also highlighted. Copyright © 2016 Elsevier Inc. All rights reserved.

Recommendation for a non-animal alternative to rat caries testing.

PubMed

Featherstone, John D B; Stookey, George K; Kaminski, Michael A; Faller, Robert V

2011-10-01

As a requirement of the Food & Drug Administration's final monograph on "Anticaries drug products for over-the-counter human use", the toothpaste industry has been conducting animal caries tests on every fluoride-containing toothpaste introduced into the U.S. market since 1996. The practice of testing in animals, although required by law, is in stark conflict with the corporate policy of many U.S. and global toothpaste manufacturers, in which, if possible, alternatives to animal testing are utilized. A provision does exist within the regulation which allows the use of an alternative method to demonstrate efficacy. However, to take advantage of this provision, a petition must be submitted to the FDA and in this petition data demonstrating the alternative provides results of "equivalent accuracy" must be included. After many years of research, model development and model comparisons, we have identified one particular laboratory model that demonstrated excellent correlation with the currently accepted animal caries models. This model, known as the Featherstone pH cycling model, is discussed in this paper. The Featherstone pH cycling model has been shown to produce results of equivalent accuracy to the animal caries model by: (1) demonstrating a clinically relevant fluoride dose response similar to that shown in the animal caries model (including 1100 ppm F, 250 ppm F and placebo); (2) demonstrating similar results to the animal caries model for clinically proven dentifrice formulations relative to positive and negative controls; (3) demonstrating discriminating ability in strong agreement with the animal caries model for differentiating between a dentifrice formulation with attenuated fluoride activity and a USP standard; and (4) providing a clinically relevant representation of the caries process, as demonstrated by orthodontic banding studies. In addition, the model sufficiently addresses both salivary and abrasive/anticalculus agent interference concerns. For more than 50 years, fluoride has been the first defense in the fight against dental caries. The clinical effectiveness of fluoride is well accepted and documented extensively in the literature. The mechanism through which fluoride provides its benefit is very straightforward and well understood. The proposed laboratory model effectively simulates the effect of the caries process and has been shown to demonstrate equivalent accuracy to animal caries. This indicates that there are strong scientific grounds for the use of this model as an alternative to the animal caries test. Based on the strength of the data and the correlations noted between the two models, we recommend that the scientific community and the toothpaste industry broadly accept the Featherstone laboratory pH cycling model as an appropriate alternative to animal testing, particularly for ionic fluoride based dentifrices.

Animal models of yellow fever and their application in clinical research.

PubMed

Julander, Justin G

2016-06-01

Yellow fever virus (YFV) is an arbovirus that causes significant human morbidity and mortality. This virus has been studied intensively over the past century, although there are still no treatment options for those who become infected. Periodic and unpredictable yellow fever (YF) outbreaks in Africa and South America continue to occur and underscore the ongoing need to further understand this viral disease and to develop additional countermeasures to prevent or treat cases of illness. The use of animal models of YF is critical to accomplishing this goal. There are several animal models of YF that replicate various aspects of clinical disease and have provided insight into pathogenic mechanisms of the virus. These typically include mice, hamsters and non-human primates (NHP). The utilities and shortcomings of the available animal models of YF are discussed. Information on recent discoveries that have been made in the field of YFV research is also included as well as important future directions in further ameliorating the morbidity and mortality that occur as a result of YFV infection. It is anticipated that these model systems will help facilitate further improvements in the understanding of this virus and in furthering countermeasures to prevent or treat infections. Copyright © 2016 Elsevier B.V. All rights reserved.

Selenium-mercury relationships in Idaho lake fish versus Northeastern USA lake fish

EPA Science Inventory

Methyl-mercury (MeHg) exposure to wildlife and humans occurs primarily through the foodweb, notably fish consumption. Selenium moderates the toxicity of MeHg in all animal models that utilize selenoenzymatic protein synthesis, as do humans. A Se:Hg molar ratio of <1:1 appears to...

A brucellosis disease control strategy for the Kakheti region of the country of Georgia: an agent-based model.

PubMed

Havas, K A; Boone, R B; Hill, A E; Salman, M D

2014-06-01

Brucellosis has been reported in livestock and humans in the country of Georgia with Brucella melitensis as the most common species causing disease. Georgia lacked sufficient data to assess effectiveness of the various potential control measures utilizing a reliable population-based simulation model of animal-to-human transmission of this infection. Therefore, an agent-based model was built using data from previous studies to evaluate the effect of an animal-level infection control programme on human incidence and sheep flock and cattle herd prevalence of brucellosis in the Kakheti region of Georgia. This model simulated the patterns of interaction of human-animal workers, sheep flocks and cattle herds with various infection control measures and returned population-based data. The model simulates the use of control measures needed for herd and flock prevalence to fall below 2%. As per the model output, shepherds had the greatest disease reduction as a result of the infection control programme. Cattle had the greatest influence on the incidence of human disease. Control strategies should include all susceptible animal species, sheep and cattle, identify the species of brucellosis present in the cattle population and should be conducted at the municipality level. This approach can be considered as a model to other countries and regions when assessment of control strategies is needed but data are scattered. © 2013 Blackwell Verlag GmbH.

Targeting Cancer Protein Profiles with Split-Enzyme Reporter Fragments to Achieve Chemical Resolution for Molecular Imaging

DTIC Science & Technology

2013-08-01

We next tested the utility of the construct to accumulate in tumors expressing EGFR using an orthotopic mouse model for brain tumors. Glioma cells...filament tumor marker, identified implanted cells within the orthotopic mouse model which were of human origin, i.e. Gli36Δ5 cells, and demonstrated that...forward into in vivo animal tumor model studies. • In vivo imaging of EGFR targeted-complex in orthotopic mouse model of brain tumor. • Ex vivo validation

Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy.

PubMed

Goldstein, Lee E; McKee, Ann C; Stanton, Patric K

2014-01-01

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath.

Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy

PubMed Central

2014-01-01

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath. PMID:25478023

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

NASA Technical Reports Server (NTRS)

Griko, Yuri V.; Rask, Jon C.; Raychev, Raycho

2017-01-01

As the world's space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organism's self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as "pathfinders," which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes. In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed.

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

NASA Technical Reports Server (NTRS)

Griko, Yuri V.; Rask, Jon C.; Raychev, Raycho

2017-01-01

As the worlds space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organisms self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as pathfinders, which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes.In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed.

Use of animal models for space flight physiology studies, with special focus on the immune system

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

2005-01-01

Animal models have been used to study the effects of space flight on physiological systems. The animal models have been used because of the limited availability of human subjects for studies to be carried out in space as well as because of the need to carry out experiments requiring samples and experimental conditions that cannot be performed using humans. Experiments have been carried out in space using a variety of species, and included developmental biology studies. These species included rats, mice, non-human primates, fish, invertebrates, amphibians and insects. The species were chosen because they best fit the experimental conditions required for the experiments. Experiments with animals have also been carried out utilizing ground-based models that simulate some of the effects of exposure to space flight conditions. Most of the animal studies have generated results that parallel the effects of space flight on human physiological systems. Systems studied have included the neurovestibular system, the musculoskeletal system, the immune system, the neurological system, the hematological system, and the cardiovascular system. Hindlimb unloading, a ground-based model of some of the effects of space flight on the immune system, has been used to study the effects of space flight conditions on physiological parameters. For the immune system, exposure to hindlimb unloading has been shown to results in alterations of the immune system similar to those observed after space flight. This has permitted the development of experiments that demonstrated compromised resistance to infection in rodents maintained in the hindlimb unloading model as well as the beginning of studies to develop countermeasures to ameliorate or prevent such occurrences. Although there are limitations to the use of animal models for the effects of space flight on physiological systems, the animal models should prove very valuable in designing countermeasures for exploration class missions of the future.

Telos, conservation of welfare, and ethical issues in genetic engineering of animals.

PubMed

Rollin, Bernard E

2015-01-01

The most long-lived metaphysics or view of reality in the history of Western thought is Aristotle's teleology, which reigned for almost 2,000 years. Biology was expressed in terms of function or telos, and accorded perfectly with common sense. The rise of mechanistic, Newtonian science vanquished teleological explanations. Understanding and accommodating animal telos was essential to success in animal husbandry, which involved respect for telos, and was presuppositional to our "ancient contract" with domestic animals. Telos was further abandoned with the rise of industrial agriculture, which utilized "technological fixes" to force animal into environments they were unsuited for, while continuing to be productive. Loss of husbandry and respect for telos created major issues for farm animal welfare, and forced the creation of a new ethic demanding respect for telos. As genetic engineering developed, the notion arose of modifying animals to fit their environment in order to avoid animal suffering, rather than fitting them into congenial environments. Most people do not favor changing the animals, rather than changing the conditions under which they are reared. Aesthetic appreciation of husbandry and virtue ethics militate in favor of restoring husbandry, rather than radically changing animal teloi. One, however, does not morally wrong teloi by changing them-one can only wrong individuals. In biomedical research, we do indeed inflict major pain, suffering and disease on animals. And genetic engineering seems to augment our ability to create animals to model diseases, particularly more than 3,000 known human genetic diseases. The disease, known as Lesch-Nyhan's syndrome or HPRT deficiency, which causes self-mutilation and mental retardation, provides us with a real possibility for genetically creating "animal models" of this disease, animals doomed to a life of great and unalleviable suffering. This of course creates a major moral dilemma. Perhaps one can use the very genetic engineering which creates this dilemma to ablate consciousness in such animal models, thereby escaping a moral impasse.

Real-time physics-based 3D biped character animation using an inverted pendulum model.

PubMed

Tsai, Yao-Yang; Lin, Wen-Chieh; Cheng, Kuangyou B; Lee, Jehee; Lee, Tong-Yee

2010-01-01

We present a physics-based approach to generate 3D biped character animation that can react to dynamical environments in real time. Our approach utilizes an inverted pendulum model to online adjust the desired motion trajectory from the input motion capture data. This online adjustment produces a physically plausible motion trajectory adapted to dynamic environments, which is then used as the desired motion for the motion controllers to track in dynamics simulation. Rather than using Proportional-Derivative controllers whose parameters usually cannot be easily set, our motion tracking adopts a velocity-driven method which computes joint torques based on the desired joint angular velocities. Physically correct full-body motion of the 3D character is computed in dynamics simulation using the computed torques and dynamical model of the character. Our experiments demonstrate that tracking motion capture data with real-time response animation can be achieved easily. In addition, physically plausible motion style editing, automatic motion transition, and motion adaptation to different limb sizes can also be generated without difficulty.

Adulteration of Argentinean milk fats with animal fats: Detection by fatty acids analysis and multivariate regression techniques.

PubMed

Rebechi, S R; Vélez, M A; Vaira, S; Perotti, M C

2016-02-01

The aims of the present study were to test the accuracy of the fatty acid ratios established by the Argentinean Legislation to detect adulterations of milk fat with animal fats and to propose a regression model suitable to evaluate these adulterations. For this purpose, 70 milk fat, 10 tallow and 7 lard fat samples were collected and analyzed by gas chromatography. Data was utilized to simulate arithmetically adulterated milk fat samples at 0%, 2%, 5%, 10% and 15%, for both animal fats. The fatty acids ratios failed to distinguish adulterated milk fats containing less than 15% of tallow or lard. For each adulterant, Multiple Linear Regression (MLR) was applied, and a model was chosen and validated. For that, calibration and validation matrices were constructed employing genuine and adulterated milk fat samples. The models were able to detect adulterations of milk fat at levels greater than 10% for tallow and 5% for lard. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy and safety of herbal medicines in treating gastric ulcer: A review

PubMed Central

Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

2014-01-01

Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects. PMID:25493014

The Application of Humanized Mouse Models for the Study of Human Exclusive Viruses.

PubMed

Vahedi, Fatemeh; Giles, Elizabeth C; Ashkar, Ali A

2017-01-01

The symbiosis between humans and viruses has allowed human tropic pathogens to evolve intricate means of modulating the human immune response to ensure its survival among the human population. In doing so, these viruses have developed profound mechanisms that mesh closely with our human biology. The establishment of this intimate relationship has created a species-specific barrier to infection, restricting the virus-associated pathologies to humans. This specificity diminishes the utility of traditional animal models. Humanized mice offer a model unique to all other means of study, providing an in vivo platform for the careful examination of human tropic viruses and their interaction with human cells and tissues. These types of animal models have provided a reliable medium for the study of human-virus interactions, a relationship that could otherwise not be investigated without questionable relevance to humans.

The emperor's new wardrobe: Rebalancing diversity of animal models in neuroscience research.

PubMed

Yartsev, Michael M

2017-10-27

The neuroscience field is steaming ahead, fueled by a revolution in cutting-edge technologies. Concurrently, another revolution has been underway-the diversity of species utilized for neuroscience research is sharply declining, as the field converges on a few selected model organisms. Here, from the perspective of a young scientist, I naively ask: Is the great diversity of questions in neuroscience best studied in only a handful of animal models? I review some of the limitations the field is facing following this convergence and how these can be rectified by increasing the diversity of appropriate model species. I propose that at this exciting time of revolution in genetics and device technologies, neuroscience might be ready to diversify again, if provided the appropriate support. Copyright © 2017, American Association for the Advancement of Science.

Optimal behaviour can violate the principle of regularity.

PubMed

Trimmer, Pete C

2013-07-22

Understanding decisions is a fundamental aim of behavioural ecology, psychology and economics. The regularity axiom of utility theory holds that a preference between options should be maintained when other options are made available. Empirical studies have shown that animals violate regularity but this has not been understood from a theoretical perspective, such decisions have therefore been labelled as irrational. Here, I use models of state-dependent behaviour to demonstrate that choices can violate regularity even when behavioural strategies are optimal. I also show that the range of conditions over which regularity should be violated can be larger when options do not always persist into the future. Consequently, utility theory--based on axioms, including transitivity, regularity and the independence of irrelevant alternatives--is undermined, because even alternatives that are never chosen by an animal (in its current state) can be relevant to a decision.

The Syrian hamster model of hantavirus pulmonary syndrome

PubMed Central

Safronetz, David; Ebihara, Hideki; Feldmann, Heinz; Hooper, Jay W.

2012-01-01

Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS. PMID:22705798

Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero

PubMed Central

Banerjee, Anwesha; Engineer, Crystal T.; Sauls, Bethany L.; Morales, Anna A.; Kilgard, Michael P.; Ploski, Jonathan E.

2014-01-01

Autism Spectrum Disorders (ASD) are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA) during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg) or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg) exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning. PMID:25429264

Laser-enhanced high-intensity focused ultrasound heating in an in vivo small animal model

NASA Astrophysics Data System (ADS)

Jo, Janggun; Yang, Xinmai

2016-11-01

The enhanced heating effect during the combination of high-intensity focused ultrasound (HIFU) and low-optical-fluence laser illumination was investigated by using an in vivo murine animal model. The thighs of murine animals were synergistically irradiated by HIFU and pulsed nano-second laser light. The temperature increases in the target region were measured by a thermocouple under different HIFU pressures, which were 6.2, 7.9, and 9.8 MPa, in combination with 20 mJ/cm2 laser exposures at 532 nm wavelength. In comparison with conventional laser therapies, the laser fluence used here is at least one order of magnitude lower. The results showed that laser illumination could enhance temperature during HIFU applications. Additionally, cavitation activity was enhanced when laser and HIFU irradiation were concurrently used. Further, a theoretical simulation showed that the inertial cavitation threshold was indeed decreased when laser and HIFU irradiation were utilized concurrently.

Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine.

PubMed

Howard, Jeremy T; Ashwell, Melissa S; Baynes, Ronald E; Brooks, James D; Yeatts, James L; Maltecca, Christian

2018-01-01

In livestock, the regulation of drugs used to treat livestock has received increased attention and it is currently unknown how much of the phenotypic variation in drug metabolism is due to the genetics of an animal. Therefore, the objective of the study was to determine the amount of phenotypic variation in fenbendazole and flunixin meglumine drug metabolism due to genetics. The population consisted of crossbred female and castrated male nursery pigs ( n = 198) that were sired by boars represented by four breeds. The animals were spread across nine batches. Drugs were administered intravenously and blood collected a minimum of 10 times over a 48 h period. Genetic parameters for the parent drug and metabolite concentration within each drug were estimated based on pharmacokinetics (PK) parameters or concentrations across time utilizing a random regression model. The PK parameters were estimated using a non-compartmental analysis. The PK model included fixed effects of sex and breed of sire along with random sire and batch effects. The random regression model utilized Legendre polynomials and included a fixed population concentration curve, sex, and breed of sire effects along with a random sire deviation from the population curve and batch effect. The sire effect included the intercept for all models except for the fenbendazole metabolite (i.e., intercept and slope). The mean heritability across PK parameters for the fenbendazole and flunixin meglumine parent drug (metabolite) was 0.15 (0.18) and 0.31 (0.40), respectively. For the parent drug (metabolite), the mean heritability across time was 0.27 (0.60) and 0.14 (0.44) for fenbendazole and flunixin meglumine, respectively. The errors surrounding the heritability estimates for the random regression model were smaller compared to estimates obtained from PK parameters. Across both the PK and plasma drug concentration across model, a moderate heritability was estimated. The model that utilized the plasma drug concentration across time resulted in estimates with a smaller standard error compared to models that utilized PK parameters. The current study found a low to moderate proportion of the phenotypic variation in metabolizing fenbendazole and flunixin meglumine that was explained by genetics in the current study.

Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine

PubMed Central

Howard, Jeremy T.; Ashwell, Melissa S.; Baynes, Ronald E.; Brooks, James D.; Yeatts, James L.; Maltecca, Christian

2018-01-01

In livestock, the regulation of drugs used to treat livestock has received increased attention and it is currently unknown how much of the phenotypic variation in drug metabolism is due to the genetics of an animal. Therefore, the objective of the study was to determine the amount of phenotypic variation in fenbendazole and flunixin meglumine drug metabolism due to genetics. The population consisted of crossbred female and castrated male nursery pigs (n = 198) that were sired by boars represented by four breeds. The animals were spread across nine batches. Drugs were administered intravenously and blood collected a minimum of 10 times over a 48 h period. Genetic parameters for the parent drug and metabolite concentration within each drug were estimated based on pharmacokinetics (PK) parameters or concentrations across time utilizing a random regression model. The PK parameters were estimated using a non-compartmental analysis. The PK model included fixed effects of sex and breed of sire along with random sire and batch effects. The random regression model utilized Legendre polynomials and included a fixed population concentration curve, sex, and breed of sire effects along with a random sire deviation from the population curve and batch effect. The sire effect included the intercept for all models except for the fenbendazole metabolite (i.e., intercept and slope). The mean heritability across PK parameters for the fenbendazole and flunixin meglumine parent drug (metabolite) was 0.15 (0.18) and 0.31 (0.40), respectively. For the parent drug (metabolite), the mean heritability across time was 0.27 (0.60) and 0.14 (0.44) for fenbendazole and flunixin meglumine, respectively. The errors surrounding the heritability estimates for the random regression model were smaller compared to estimates obtained from PK parameters. Across both the PK and plasma drug concentration across model, a moderate heritability was estimated. The model that utilized the plasma drug concentration across time resulted in estimates with a smaller standard error compared to models that utilized PK parameters. The current study found a low to moderate proportion of the phenotypic variation in metabolizing fenbendazole and flunixin meglumine that was explained by genetics in the current study. PMID:29487615

A clinically authentic mouse model of enterovirus 71 (EV-A71)-induced neurogenic pulmonary oedema.

PubMed

Victorio, Carla Bianca Luena; Xu, Yishi; Ng, Qimei; Chua, Beng Hooi; Alonso, Sylvie; Chow, Vincent T K; Chua, Kaw Bing

2016-06-30

Enterovirus 71 (EV-A71) is a neurotropic virus that sporadically causes fatal neurologic illness among infected children. Animal models of EV-A71 infection exist, but they do not recapitulate in animals the spectrum of disease and pathology observed in fatal human cases. Specifically, neurogenic pulmonary oedema (NPE)-the main cause of EV-A71 infection-related mortality-is not observed in any of these models. This limits their utility in understanding viral pathogenesis of neurologic infections. We report the development of a mouse model of EV-A71 infection displaying NPE in severely affected animals. We inoculated one-week-old BALB/c mice with an adapted EV-A71 strain and identified clinical signs consistent with observations in human cases and other animal models. We also observed respiratory distress in some mice. At necropsy, we found their lungs to be heavier and incompletely collapsed compared to other mice. Serum levels of catecholamines and histopathology of lung and brain tissues of these mice strongly indicated onset of NPE. The localization of virally-induced brain lesions also suggested a potential pathogenic mechanism for EV-A71-induced NPE. This novel mouse model of virally-induced NPE represents a valuable resource for studying viral mechanisms of neuro-pathogenesis and pre-clinical testing of potential therapeutics and prophylactics against EV-A71-related neurologic complications.

Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

PubMed Central

Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T.; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young

2016-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance. PMID:27133257

Regulatory Forum Opinion Piece*: Use and Utility of Animal Models of Disease for Nonclinical Safety Assessment: A Pharmaceutical Industry Survey.

PubMed

Morgan, Sherry J; Couch, Jessica; Guzzie-Peck, Peggy; Keller, Douglas A; Kemper, Ray; Otieno, Monicah A; Schulingkamp, Robert J; Jones, Thomas W

2017-04-01

An Innovation and Quality (IQ) Consortium focus group conducted a cross-company survey to evaluate current practices and perceptions around the use of animal models of disease (AMDs) in nonclinical safety assessment of molecules in clinical development. The IQ Consortium group is an organization of pharmaceutical and biotechnology companies with the mission of advancing science and technology. The survey queried the utilization of AMDs during drug discovery in which drug candidates are evaluated in efficacy models and limited short-duration non-Good Laboratory Practices (GLP) toxicology testing and during drug development in which drug candidates are evaluated in GLP toxicology studies. The survey determined that the majority of companies used AMDs during drug discovery primarily as a means for proactively assessing potential nonclinical safety issues prior to the conduct of toxicology studies, followed closely by the use of AMDs to better understand toxicities associated with exaggerated pharmacology in traditional toxicology models or to derisk issues when the target is only expressed in the disease state. In contrast, the survey results indicated that the use of AMDs in development is infrequent, being used primarily to investigate nonclinical safety issues associated with targets expressed only in disease states and/or in response to requests from global regulatory authorities.

A freely-moving monkey treadmill model.

PubMed

Foster, Justin D; Nuyujukian, Paul; Freifeld, Oren; Gao, Hua; Walker, Ross; I Ryu, Stephen; H Meng, Teresa; Murmann, Boris; J Black, Michael; Shenoy, Krishna V

2014-08-01

Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the flexibility and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average firing rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic motor neuroscience and for the successful translation of BMIs to people with paralysis.

Validation of a multi-criteria evaluation model for animal welfare.

PubMed

Martín, P; Czycholl, I; Buxadé, C; Krieter, J

2017-04-01

The aim of this paper was to validate an alternative multi-criteria evaluation system to assess animal welfare on farms based on the Welfare Quality® (WQ) project, using an example of welfare assessment of growing pigs. This alternative methodology aimed to be more transparent for stakeholders and more flexible than the methodology proposed by WQ. The WQ assessment protocol for growing pigs was implemented to collect data in different farms in Schleswig-Holstein, Germany. In total, 44 observations were carried out. The aggregation system proposed in the WQ protocol follows a three-step aggregation process. Measures are aggregated into criteria, criteria into principles and principles into an overall assessment. This study focussed on the first two steps of the aggregation. Multi-attribute utility theory (MAUT) was used to produce a value of welfare for each criterion and principle. The utility functions and the aggregation function were constructed in two separated steps. The MACBETH (Measuring Attractiveness by a Categorical-Based Evaluation Technique) method was used for utility function determination and the Choquet integral (CI) was used as an aggregation operator. The WQ decision-makers' preferences were fitted in order to construct the utility functions and to determine the CI parameters. The validation of the MAUT model was divided into two steps, first, the results of the model were compared with the results of the WQ project at criteria and principle level, and second, a sensitivity analysis of our model was carried out to demonstrate the relative importance of welfare measures in the different steps of the multi-criteria aggregation process. Using the MAUT, similar results were obtained to those obtained when applying the WQ protocol aggregation methods, both at criteria and principle level. Thus, this model could be implemented to produce an overall assessment of animal welfare in the context of the WQ protocol for growing pigs. Furthermore, this methodology could also be used as a framework in order to produce an overall assessment of welfare for other livestock species. Two main findings are obtained from the sensitivity analysis, first, a limited number of measures had a strong influence on improving or worsening the level of welfare at criteria level and second, the MAUT model was not very sensitive to an improvement in or a worsening of single welfare measures at principle level. The use of weighted sums and the conversion of disease measures into ordinal scores should be reconsidered.

Behavioral toxicology of cognition: extrapolation from experimental animal models to humans: behavioral toxicology symposium overview.

PubMed

Paule, Merle G; Green, Leonard; Myerson, Joel; Alvarado, Maria; Bachevalier, Jocelyne; Schneider, Jay S; Schantz, Susan L

2012-03-01

A variety of behavioral instruments are available for assessing important aspects of cognition in both animals and humans and, in many cases, the same instruments can be used in both. While nonhuman primates are phylogenetically closest to humans, rodents, pigeons and other animals also offer behaviors worthy of note. Delay Discounting procedures are as useful as any in studies of impulsivity and may have utility in shedding light on processes associated with drug abuse. Specific memory tests such as Visual Paired Comparisons tasks (similar to the Fagan test of infant intelligence) can be modified to allow for assessment of different aspects of memory such as spatial memory. Use of these and other specific memory tasks can be used to directly monitor aspects of cognitive development in infant animals, particularly in nonhuman primates such as monkeys, and children and to draw inferences with respect to possible neuroanatomical substrates sub-serving their functions. Tasks for assessing working memory such as Variable Delayed Response (VDR), modified VDR and Spatial Working Memory tasks are now known to be affected in Parkinson's disease (PD). These and other cognitive function tasks are being used in a monkey model of PD to assess the ability of anti-Parkinson's disease therapies to ameliorate these cognitive deficits without diminishing their therapeutic effects on motor dysfunction. Similarly, in a rat model of the cognitive deficits associated with perinatal exposure to polychlorinated biphenyls (PCBs), clear parallels with children can be seen in at least two areas of executive function: cognitive flexibility and response inhibition. In the rat model, discrimination reversal tasks were utilized to assess cognitive flexibility, a function often assessed in humans using the Wisconsin Card Sorting Task. Response inhibition was assessed using performance in a Differential Reinforcement of Low Response Rates (DRL) task. As the data continue to accumulate, it becomes more clear that our attempts to adapt animal-appropriate tasks for the study of important aspects of human cognition have proven to be very fruitful. Published by Elsevier Inc.

A unique in vivo approach for investigating antimicrobial materials utilizing fistulated animals

NASA Astrophysics Data System (ADS)

Berean, Kyle J.; Adetutu, Eric M.; Zhen Ou, Jian; Nour, Majid; Nguyen, Emily P.; Paull, David; McLeod, Jess; Ramanathan, Rajesh; Bansal, Vipul; Latham, Kay; Bishop-Hurley, Greg J.; McSweeney, Chris; Ball, Andrew S.; Kalantar-Zadeh, Kourosh

2015-06-01

Unique in vivo tests were conducted through the use of a fistulated ruminant, providing an ideal environment with a diverse and vibrant microbial community. Utilizing such a procedure can be especially invaluable for investigating the performance of antimicrobial materials related to human and animal related infections. In this pilot study, it is shown that the rumen of a fistulated animal provides an excellent live laboratory for assessing the properties of antimicrobial materials. We investigate microbial colonization onto model nanocomposites based on silver (Ag) nanoparticles at different concentrations into polydimethylsiloxane (PDMS). With implantable devices posing a major risk for hospital-acquired infections, the present study provides a viable solution to understand microbial colonization with the potential to reduce the incidence of infection through the introduction of Ag nanoparticles at the optimum concentrations. In vitro measurements were also conducted to show the validity of the approach. An optimal loading of 0.25 wt% Ag is found to show the greatest antimicrobial activity and observed through the in vivo tests to reduce the microbial diversity colonizing the surface.

Designing Empathetic Animated Agents for a B-Learning Training Environment within the Electrical Domain

ERIC Educational Resources Information Center

Hernández, Yasmin; Pérez-Ramírez, Miguel; Zatarain-Cabada, Ramon; Barrón-Estrada, Lucia; Alor-Hernández, Giner

2016-01-01

Electrical tests involve high risk; therefore utility companies require highly qualified electricians and efficient training. Recently, training for electrical tests has been supported by virtual reality systems; nonetheless, these training systems are not yet adaptive. We propose a b-learning model to support adaptive and distance training. The…

Effects of exposure to HZE particles on the cognitive performance of ovariectomized and intact female rats

USDA-ARS?s Scientific Manuscript database

INTRODUCTION It is likely that both male and female astronauts will comprise the crew on exploratory class missions. Despite this, the majority of the research using animal models has utilized male subjects. However, the limited data currently available suggests that the cognitive effects of exposu...

Quantile regression reveals hidden bias and uncertainty in habitat models

Treesearch

Brian S. Cade; Barry R. Noon; Curtis H. Flather

2005-01-01

We simulated the effects of missing information on statistical distributions of animal response that covaried with measured predictors of habitat to evaluate the utility and performance of quantile regression for providing more useful intervals of uncertainty in habitat relationships. These procedures were evaulated for conditions in which heterogeneity and hidden bias...

USE OF HIGH CONTENT IMAGE ANALYSES TO DETECT CHEMICAL-MEDIATED EFFECTS ON NEURITE SUB-POPULATIONS IN PRIMARY RAT CORTICAL NEURONS

EPA Science Inventory

Traditional developmental neurotoxicity tests performed in vivo are costly, time-consuming and utilize a large number of animals. In order to address these inefficiencies, in vitro models of neuronal development have been used in a first tier screening approach for developmenta...

Application of molecular target homology-based approaches to predict species sensitivities to two pesticides, permethrin and propiconozole

EPA Science Inventory

In the U.S., registration of pesticide active ingredients requires a battery of intensive and costly in vivo toxicity tests which utilize large numbers of test animals. These tests use a limited array of model species from various aquatic and terrestrial taxa to represent all pla...

Emergence of a snake-like structure in mobile distributed agents: an exploratory agent-based modeling approach.

PubMed

Niazi, Muaz A

2014-01-01

The body structure of snakes is composed of numerous natural components thereby making it resilient, flexible, adaptive, and dynamic. In contrast, current computer animations as well as physical implementations of snake-like autonomous structures are typically designed to use either a single or a relatively smaller number of components. As a result, not only these artificial structures are constrained by the dimensions of the constituent components but often also require relatively more computationally intensive algorithms to model and animate. Still, these animations often lack life-like resilience and adaptation. This paper presents a solution to the problem of modeling snake-like structures by proposing an agent-based, self-organizing algorithm resulting in an emergent and surprisingly resilient dynamic structure involving a minimal of interagent communication. Extensive simulation experiments demonstrate the effectiveness as well as resilience of the proposed approach. The ideas originating from the proposed algorithm can not only be used for developing self-organizing animations but can also have practical applications such as in the form of complex, autonomous, evolvable robots with self-organizing, mobile components with minimal individual computational capabilities. The work also demonstrates the utility of exploratory agent-based modeling (EABM) in the engineering of artificial life-like complex adaptive systems.

Emergence of a Snake-Like Structure in Mobile Distributed Agents: An Exploratory Agent-Based Modeling Approach

PubMed Central

Niazi, Muaz A.

2014-01-01

The body structure of snakes is composed of numerous natural components thereby making it resilient, flexible, adaptive, and dynamic. In contrast, current computer animations as well as physical implementations of snake-like autonomous structures are typically designed to use either a single or a relatively smaller number of components. As a result, not only these artificial structures are constrained by the dimensions of the constituent components but often also require relatively more computationally intensive algorithms to model and animate. Still, these animations often lack life-like resilience and adaptation. This paper presents a solution to the problem of modeling snake-like structures by proposing an agent-based, self-organizing algorithm resulting in an emergent and surprisingly resilient dynamic structure involving a minimal of interagent communication. Extensive simulation experiments demonstrate the effectiveness as well as resilience of the proposed approach. The ideas originating from the proposed algorithm can not only be used for developing self-organizing animations but can also have practical applications such as in the form of complex, autonomous, evolvable robots with self-organizing, mobile components with minimal individual computational capabilities. The work also demonstrates the utility of exploratory agent-based modeling (EABM) in the engineering of artificial life-like complex adaptive systems. PMID:24701135

The Autism Diagnosis in Translation: Shared Affect in Children and Mouse Models of ASD

PubMed Central

Bishop, Somer L.; Lahvis, Garet P.

2013-01-01

In recent years, there have been significant improvements in assessment and diagnostic procedures for autism spectrum disorders (ASD). Standardized diagnostic instruments have been developed, promoting consistent diagnostic practices among clinicians. For clinical researchers, these instruments have facilitated collaborations across different sites by providing standardized metrics with which to evaluate ASD symptoms. Nevertheless, because ASD remains a diagnosis that is defined on the basis of behavior, there are significant challenges associated with modeling ASD social behaviors in laboratory animals. In order to more effectively study the causes of ASD symptoms and behaviors, there is a need to develop new ways of measuring social behaviors that can be applied to non-human species. Critically, while verbal dialogue between the clinician and patient is integral to clinical diagnoses, it cannot be employed for studies of animal models. However, observations of autistic-like social interactions can be modeled in animals. In this regard, communication between professionals in the clinical and basic sciences is necessary to break down the complex diagnosis into units of social impairment that can be more feasibly measured in different species. This paper presents a discussion between an animal researcher and a clinical psychologist. Using shared affect as an example, we explore potential avenues for increasing the utility of animal models to move us toward a better understanding of the mechanisms underlying social impairments in ASD. In the absence of molecular biomarkers that can be used to diagnose ASD, current diagnostic tools depend upon clinical assessments of behavior. Research efforts with human subjects have successfully utilized standardized diagnostic instruments, which include clinician interviews with parents and direct observation of the children themselves (Risi et al., 2006). However, because clinical instruments are semi-structured and rely heavily on dynamic social processes and clinical skill, scores from these measures do not necessarily lend themselves directly to experimental investigations into the causes of ASD. Studies of the neurobiology of autism require experimental animal models. Mice are particularly useful, in this regard, for elucidating genetic and toxicologjcal contributions to impairments in social function (Halladay et al., 2009). Behavioral tests have been developed that are relevant to autism (Crawley, 2004, 2007), including measures of repetitive behaviors (Lewis, Tanimura, Lee, & Bodfish, 2007; Moy et al., 2008), social behavior (Brodkin, 2007; Lijam et al., 1997; Moretti, Bouwknecht, Teague, Paylor, & Zoghbi, 2005), and vocal communication (Panksepp et al., 2007). Advances also include development of high-throughput measures of mouse sociability that can be used to reliably compare inbred mouse strains (Moy, et al., 2008; Nadler et al., 2004), as well as measures of social reward (Panksepp & Lahvis, 2007) and empathy (Chen, Panksepp, & Lahvis, 2009; Langford et al., 2006). With continued generation of mouse gene-targeted mice that are directly relevant to genetic linkages in ASD, there remains an urgent need to utilize a full suite of mouse behavioral tests that allows for a comprehensive assessment of the spectrum of social difficulties relevant to ASD. Using impairments in shared affect as an example, this paper explores potential avenues for collaboration between clinical and basic scientists, within an amply considered translational framework. PMID:21882361

Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standarizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

DTIC Science & Technology

2008-08-01

To better understand the cellular basis of a long bone defect, we have utilized the GFP reporters in the closed tibial fracture. The surprise finding...callus. In the coming year we will apply the information learned from the calvarial defect to a non-union extension of the tibial fracture model...initiated a comprehensive examination of the tibial fracture model in mice bearing GFP reporters of lineage progression. This project has been assumed

The Effect of Hypotensive Resuscitation and Fluid Type on Mortality, Bleeding, Coagulation and Dysfunctional Inflammation in a Swine Grade V Liver Injury Model

DTIC Science & Technology

2011-01-01

Specific Aim 6 Methods – Efficacy of Tranexamic Acid in a Model of Polytrauma Nineteen swine (12 study, 6 model development, 1 death) were utilized...Institutional Animal Care and Use Committee. Female Yorkshire Crossbred swine underwent the following polytrauma protocol to assess the efficacy of Tranexamic ... acid (TXA). This drug is commonly prescribed for control of excess bleeding. To date only a single trial in trauma (CRASH-2) has been conducted

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hrycushko, B; Medin, P

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 ofmore » 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work was funded by the Cancer Prevention Research Institute of Texas (CPRIT).« less

Monkeys choose as if maximizing utility compatible with basic principles of revealed preference theory.

PubMed

Pastor-Bernier, Alexandre; Plott, Charles R; Schultz, Wolfram

2017-03-07

Revealed preference theory provides axiomatic tools for assessing whether individuals make observable choices "as if" they are maximizing an underlying utility function. The theory evokes a tradeoff between goods whereby individuals improve themselves by trading one good for another good to obtain the best combination. Preferences revealed in these choices are modeled as curves of equal choice (indifference curves) and reflect an underlying process of optimization. These notions have far-reaching applications in consumer choice theory and impact the welfare of human and animal populations. However, they lack the empirical implementation in animals that would be required to establish a common biological basis. In a design using basic features of revealed preference theory, we measured in rhesus monkeys the frequency of repeated choices between bundles of two liquids. For various liquids, the animals' choices were compatible with the notion of giving up a quantity of one good to gain one unit of another good while maintaining choice indifference, thereby implementing the concept of marginal rate of substitution. The indifference maps consisted of nonoverlapping, linear, convex, and occasionally concave curves with typically negative, but also sometimes positive, slopes depending on bundle composition. Out-of-sample predictions using homothetic polynomials validated the indifference curves. The animals' preferences were internally consistent in satisfying transitivity. Change of option set size demonstrated choice optimality and satisfied the Weak Axiom of Revealed Preference (WARP). These data are consistent with a version of revealed preference theory in which preferences are stochastic; the monkeys behaved "as if" they had well-structured preferences and maximized utility.

Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo.

PubMed

Jiang, Lihong; Herzog, Raimund I; Mason, Graeme F; de Graaf, Robin A; Rothman, Douglas L; Sherwin, Robert S; Behar, Kevin L

2009-06-01

The objective of this study was to characterize the changes in brain metabolism caused by antecedent recurrent hypoglycemia under euglycemic and hypoglycemic conditions in a rat model and to test the hypothesis that recurrent hypoglycemia changes the brain's capacity to utilize different energy substrates. Rats exposed to recurrent insulin-induced hypoglycemia for 3 days (3dRH rats) and untreated controls were subject to the following protocols: [2-(13)C]acetate infusion under euglycemic conditions (n = 8), [1-(13)C]glucose and unlabeled acetate coinfusion under euglycemic conditions (n = 8), and [2-(13)C]acetate infusion during a hyperinsulinemic-hypoglycemic clamp (n = 8). In vivo nuclear magnetic resonance spectroscopy was used to monitor the rise of(13)C-labeling in brain metabolites for the calculation of brain metabolic fluxes using a neuron-astrocyte model. At euglycemia, antecedent recurrent hypoglycemia increased whole-brain glucose metabolism by 43 +/- 4% (P < 0.01 vs. controls), largely due to higher glucose utilization in neurons. Although acetate metabolism remained the same, control and 3dRH animals showed a distinctly different response to acute hypoglycemia: controls decreased pyruvate dehydrogenase (PDH) flux in astrocytes by 64 +/- 20% (P = 0.01), whereas it increased by 37 +/- 3% in neurons (P = 0.01). The 3dRH animals decreased PDH flux in both compartments (-75 +/- 20% in astrocytes, P < 0.001, and -36 +/- 4% in neurons, P = 0.005). Thus, acute hypoglycemia reduced total brain tricarboxylic acid cycle activity in 3dRH animals (-37 +/- 4%, P = 0.001), but not in controls. Our findings suggest that after antecedent hypoglycemia, glucose utilization is increased at euglycemia and decreased after acute hypoglycemia, which was not the case in controls. These findings may help to identify better methods of preserving brain function and reducing injury during acute hypoglycemia.

Porcine models of digestive disease: the future of large animal translational research

PubMed Central

Gonzalez, Liara M.; Moeser, Adam J.; Blikslager, Anthony T.

2015-01-01

There is increasing interest in non-rodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia/ reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine as well as to mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine. PMID:25655839

A Multi-Mode Shock Tube for Investigation of Blast-Induced Traumatic Brain Injury

PubMed Central

Reneer, Dexter V.; Hisel, Richard D.; Hoffman, Joshua M.; Kryscio, Richard J.; Lusk, Braden T.

2011-01-01

Abstract Blast-induced mild traumatic brain injury (bTBI) has become increasingly common in recent military conflicts. The mechanisms by which non-impact blast exposure results in bTBI are incompletely understood. Current small animal bTBI models predominantly utilize compressed air-driven membrane rupture as their blast wave source, while large animal models use chemical explosives. The pressure-time signature of each blast mode is unique, making it difficult to evaluate the contributions of the different components of the blast wave to bTBI when using a single blast source. We utilized a multi-mode shock tube, the McMillan blast device, capable of utilizing compressed air- and compressed helium-driven membrane rupture, and the explosives oxyhydrogen and cyclotrimethylenetrinitramine (RDX, the primary component of C-4 plastic explosives) as the driving source. At similar maximal blast overpressures, the positive pressure phase of compressed air-driven blasts was longer, and the positive impulse was greater, than those observed for shockwaves produced by other driving sources. Helium-driven shockwaves more closely resembled RDX blasts, but by displacing air created a hypoxic environment within the shock tube. Pressure-time traces from oxyhydrogen-driven shockwaves were very similar those produced by RDX, although they resulted in elevated carbon monoxide levels due to combustion of the polyethylene bag used to contain the gases within the shock tube prior to detonation. Rats exposed to compressed air-driven blasts had more pronounced vascular damage than those exposed to oxyhydrogen-driven blasts of the same peak overpressure, indicating that differences in blast wave characteristics other than peak overpressure may influence the extent of bTBI. Use of this multi-mode shock tube in small animal models will enable comparison of the extent of brain injury with the pressure-time signature produced using each blast mode, facilitating evaluation of the blast wave components contributing to bTBI. PMID:21083431

A multi-mode shock tube for investigation of blast-induced traumatic brain injury.

PubMed

Reneer, Dexter V; Hisel, Richard D; Hoffman, Joshua M; Kryscio, Richard J; Lusk, Braden T; Geddes, James W

2011-01-01

Blast-induced mild traumatic brain injury (bTBI) has become increasingly common in recent military conflicts. The mechanisms by which non-impact blast exposure results in bTBI are incompletely understood. Current small animal bTBI models predominantly utilize compressed air-driven membrane rupture as their blast wave source, while large animal models use chemical explosives. The pressure-time signature of each blast mode is unique, making it difficult to evaluate the contributions of the different components of the blast wave to bTBI when using a single blast source. We utilized a multi-mode shock tube, the McMillan blast device, capable of utilizing compressed air- and compressed helium-driven membrane rupture, and the explosives oxyhydrogen and cyclotrimethylenetrinitramine (RDX, the primary component of C-4 plastic explosives) as the driving source. At similar maximal blast overpressures, the positive pressure phase of compressed air-driven blasts was longer, and the positive impulse was greater, than those observed for shockwaves produced by other driving sources. Helium-driven shockwaves more closely resembled RDX blasts, but by displacing air created a hypoxic environment within the shock tube. Pressure-time traces from oxyhydrogen-driven shockwaves were very similar those produced by RDX, although they resulted in elevated carbon monoxide levels due to combustion of the polyethylene bag used to contain the gases within the shock tube prior to detonation. Rats exposed to compressed air-driven blasts had more pronounced vascular damage than those exposed to oxyhydrogen-driven blasts of the same peak overpressure, indicating that differences in blast wave characteristics other than peak overpressure may influence the extent of bTBI. Use of this multi-mode shock tube in small animal models will enable comparison of the extent of brain injury with the pressure-time signature produced using each blast mode, facilitating evaluation of the blast wave components contributing to bTBI.

Robotic and endoscopic transoral thyroidectomy: feasibility and description of the technique in the cadaveric model.

PubMed

Kahramangil, Bora; Mohsin, Khuzema; Alzahrani, Hassan; Bu Ali, Daniah; Tausif, Syed; Kang, Sang-Wook; Kandil, Emad; Berber, Eren

2017-12-01

Numerous new approaches have been described over the years to improve the cosmetic outcomes of thyroid surgery. Transoral approach is a new technique that aims to achieve superior cosmetic outcomes by concealing the incision in the oral cavity. Transoral thyroidectomy through vestibular approach was performed in two institutions on cadaveric models. Procedure was performed endoscopically in one institution, while the robotic technique was utilized at the other. Transoral thyroidectomy was successfully performed at both institutions with robotic and endoscopic techniques. All vital structures were identified and preserved. Transoral thyroidectomy has been performed in animal and cadaveric models, as well as in some clinical studies. Our initial experience indicates the feasibility of this approach. More clinical studies are required to elucidate its full utility.

The Neurological Ecology of Fear: Insights Neuroscientists and Ecologists Have to Offer one Another

PubMed Central

Clinchy, Michael; Schulkin, Jay; Zanette, Liana Y.; Sheriff, Michael J.; McGowan, Patrick O.; Boonstra, Rudy

2011-01-01

That the fear and stress of life-threatening experiences can leave an indelible trace on the brain is most clearly exemplified by post-traumatic stress disorder (PTSD). Many researchers studying the animal model of PTSD have adopted utilizing exposure to a predator as a life-threatening psychological stressor, to emulate the experience in humans, and the resulting body of literature has demonstrated numerous long-lasting neurological effects paralleling those in PTSD patients. Even though much more extreme, predator-induced fear and stress in animals in the wild was, until the 1990s, not thought to have any lasting effects, whereas recent experiments have demonstrated that the effects on free-living animals are sufficiently long-lasting to even affect reproduction, though the lasting neurological effects remain unexplored. We suggest neuroscientists and ecologists both have much to gain from collaborating in studying the neurological effects of predator-induced fear and stress in animals in the wild. We outline the approaches taken in the lab that appear most readily translatable to the field, and detail the advantages that studying animals in the wild can offer researchers investigating the “predator model of PTSD.” PMID:21629856

A Bayesian mixture model for missing data in marine mammal growth analysis

PubMed Central

Shotwell, Mary E.; McFee, Wayne E.; Slate, Elizabeth H.

2016-01-01

Much of what is known about bottle nose dolphin (Tursiops truncatus) anatomy and physiology is based on necropsies from stranding events. Measurements of total body length, total body mass, and age are used to estimate growth. It is more feasible to retrieve and transport smaller animals for total body mass measurement than larger animals, introducing a systematic bias in sampling. Adverse weather events, volunteer availability, and other unforeseen circumstances also contribute to incomplete measurement. We have developed a Bayesian mixture model to describe growth in detected stranded animals using data from both those that are fully measured and those not fully measured. Our approach uses a shared random effect to link the missingness mechanism (i.e. full/partial measurement) to distinct growth curves in the fully and partially measured populations, thereby enabling drawing of strength for estimation. We use simulation to compare our model to complete case analysis and two common multiple imputation methods according to model mean square error. Results indicate that our mixture model provides better fit both when the two populations are present and when they are not. The feasibility and utility of our new method is demonstrated by application to South Carolina strandings data. PMID:28503080

A One Health Approach to Hypertrophic Cardiomyopathy

PubMed Central

Ueda, Yu; Stern, Joshua A.

2017-01-01

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in humans and results in significant morbidity and mortality. Research over the past 25 years has contributed enormous insight into this inherited disease particularly in the areas of genetics, molecular mechanisms, and pathophysiology. Our understanding continues to be limited by the heterogeneity of clinical presentations with various genetic mutations associated with HCM. Transgenic mouse models have been utilized especially studying the genotypic and phenotypic interactions. However, mice possess intrinsic cardiac and hemodynamic differences compared to humans and have limitations preventing their direct translation. Other animal models of HCM have been studied or generated in part to overcome these limitations. HCM in cats shows strikingly similar molecular, histopathological, and genetic similarities to human HCM, and offers an important translational opportunity for the study of this disease. Recently, inherited left ventricular hypertrophy in rhesus macaques was identified and collaborative investigations have been conducted to begin to develop a non-human primate HCM model. These naturally-occurring large-animal models may aid in advancing our understanding of HCM and developing novel therapeutic approaches to this disease. This review will highlight the features of HCM in humans and the relevant available and developing animal models of this condition. PMID:28955182

Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system.

PubMed

Yong, Kylie Su Mei; Ng, Justin Han Jia; Her, Zhisheng; Hey, Ying Ying; Tan, Sue Yee; Tan, Wilson Wei Sheng; Irac, Sergio Erdal; Liu, Min; Chan, Xue Ying; Gunawan, Merry; Foo, Randy Jee Hiang; Low, Dolyce Hong Wen; Mendenhall, Ian Hewitt; Chionh, Yok Teng; Dutertre, Charles-Antoine; Chen, Qingfeng; Wang, Lin-Fa

2018-03-16

Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproduction rates. To overcome this, we transplanted bat cells from bone marrow (BM) and spleen into an immunodeficient mouse strain NOD-scid IL-2R -/- (NSG), and have successfully established stable, long-term reconstitution of bat immune cells in mice (bat-mice). Immune functionality of our bat-mouse model was demonstrated through generation of antigen-specific antibody response by bat cells following immunization. Post-engraftment of total bat BM cells and splenocytes, bat immune cells survived, expanded and repopulated the mouse without any observable clinical abnormalities. Utilizing bat's remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.

The Comparative Study of Metacognition: Sharper Paradigms, Safer Inferences

PubMed Central

Smith, J. David; Beran, Michael J.; Couchman, Justin J.; Coutinho, Mariana V. C.

2015-01-01

Results that point to animals’ metacognitive capacity bear a heavy burden given the potential for competing behavioral descriptions. This article uses formal models to evaluate the force of these descriptions. One example is that many existing studies have directly rewarded so-called “uncertainty” responses. Modeling confirms that this practice is an interpretative danger because it supports associative processes and encourages simpler interpretations. Another example is that existing studies raise the concern that animals avoid difficult stimuli not because of uncertainty monitored but because of aversion given error-causing or reinforcement-lean stimuli. Modeling also justifies this concern and shows that this problem is not addressed by the common practice of comparing performance on Chosen and Forced trials. The models and related discussion have utility for metacognition researchers and theorists broadly because they specify the experimental operations that will best indicate a metacognitive capacity in humans or animals by eliminating alternative behavioral accounts. PMID:18792496

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

PubMed Central

Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

Minipigs as an Animal Model for Dermal Vaccine Delivery

PubMed Central

Ploemen, Ivo HJ; Hirschberg, Hoang JHB; Kraan, Heleen; Zeltner, Adrian; van Kuijk, Sandra; Lankveld, Danielle PK; Royals, Michael; Kersten, Gideon FA; Amorij, Jean-Pierre

2014-01-01

Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery. Here we describe the immunization of Göttingen minipigs by using intradermal and intramuscular delivery of hepatitis B surface antigen (HBsAg). Intradermal vaccine delivery by needle and syringe and by needle-free jet injection induced humoral antiHBsAg responses. Priming immunization by using the disposable syringe jet injector (DSJI) resulted in a higher antibody titer than did conventional intradermal immunization and a titer comparable to that after intramuscular vaccination with HBsAg and Al(OH)3 adjuvant. This study highlights the utility of the minipig model in vaccine studies assessing the efficacy of conventional and novel methods of dermal delivery. Moreover, we include suggestions regarding working with minipigs during dermal vaccine delivery studies, thereby fostering future work in this area of vaccinology. PMID:24512961

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

PubMed

Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

Using Satellite and Airborne LiDAR to Model Woodpecker Habitat Occupancy at the Landscape Scale

PubMed Central

Vierling, Lee A.; Vierling, Kerri T.; Adam, Patrick; Hudak, Andrew T.

2013-01-01

Incorporating vertical vegetation structure into models of animal distributions can improve understanding of the patterns and processes governing habitat selection. LiDAR can provide such structural information, but these data are typically collected via aircraft and thus are limited in spatial extent. Our objective was to explore the utility of satellite-based LiDAR data from the Geoscience Laser Altimeter System (GLAS) relative to airborne-based LiDAR to model the north Idaho breeding distribution of a forest-dependent ecosystem engineer, the Red-naped sapsucker (Sphyrapicus nuchalis). GLAS data occurred within ca. 64 m diameter ellipses spaced a minimum of 172 m apart, and all occupancy analyses were confined to this grain scale. Using a hierarchical approach, we modeled Red-naped sapsucker occupancy as a function of LiDAR metrics derived from both platforms. Occupancy models based on satellite data were weak, possibly because the data within the GLAS ellipse did not fully represent habitat characteristics important for this species. The most important structural variables influencing Red-naped Sapsucker breeding site selection based on airborne LiDAR data included foliage height diversity, the distance between major strata in the canopy vertical profile, and the vegetation density near the ground. These characteristics are consistent with the diversity of foraging activities exhibited by this species. To our knowledge, this study represents the first to examine the utility of satellite-based LiDAR to model animal distributions. The large area of each GLAS ellipse and the non-contiguous nature of GLAS data may pose significant challenges for wildlife distribution modeling; nevertheless these data can provide useful information on ecosystem vertical structure, particularly in areas of gentle terrain. Additional work is thus warranted to utilize LiDAR datasets collected from both airborne and past and future satellite platforms (e.g. GLAS, and the planned IceSAT2 mission) with the goal of improving wildlife modeling for more locations across the globe. PMID:24324655

Optimal behaviour can violate the principle of regularity

PubMed Central

Trimmer, Pete C.

2013-01-01

Understanding decisions is a fundamental aim of behavioural ecology, psychology and economics. The regularity axiom of utility theory holds that a preference between options should be maintained when other options are made available. Empirical studies have shown that animals violate regularity but this has not been understood from a theoretical perspective, such decisions have therefore been labelled as irrational. Here, I use models of state-dependent behaviour to demonstrate that choices can violate regularity even when behavioural strategies are optimal. I also show that the range of conditions over which regularity should be violated can be larger when options do not always persist into the future. Consequently, utility theory—based on axioms, including transitivity, regularity and the independence of irrelevant alternatives—is undermined, because even alternatives that are never chosen by an animal (in its current state) can be relevant to a decision. PMID:23740781

Parameterized Facial Expression Synthesis Based on MPEG-4

NASA Astrophysics Data System (ADS)

Raouzaiou, Amaryllis; Tsapatsoulis, Nicolas; Karpouzis, Kostas; Kollias, Stefanos

2002-12-01

In the framework of MPEG-4, one can include applications where virtual agents, utilizing both textual and multisensory data, including facial expressions and nonverbal speech help systems become accustomed to the actual feelings of the user. Applications of this technology are expected in educational environments, virtual collaborative workplaces, communities, and interactive entertainment. Facial animation has gained much interest within the MPEG-4 framework; with implementation details being an open research area (Tekalp, 1999). In this paper, we describe a method for enriching human computer interaction, focusing on analysis and synthesis of primary and intermediate facial expressions (Ekman and Friesen (1978)). To achieve this goal, we utilize facial animation parameters (FAPs) to model primary expressions and describe a rule-based technique for handling intermediate ones. A relation between FAPs and the activation parameter proposed in classical psychological studies is established, leading to parameterized facial expression analysis and synthesis notions, compatible with the MPEG-4 standard.

Predicting mosaics and wildlife diversity resulting from fire disturbance to a forest ecosystem

NASA Astrophysics Data System (ADS)

Potter, Meredith W.; Kessell, Stephen R.

1980-05-01

A model for predicting community mosaics and wildlife diversity resulting from fire disturbance to a forest ecosystem is presented. It applies an algorithm that delineates the size and shape of each patch from grid-based input data and calculates standard diversity measures for the entire mosaic of community patches and their included animal species. The user can print these diversity calculations, maps of the current community-type-age-class mosaic, and maps of habitat utilization by each animal species. Furthermore, the user can print estimates of changes in each resulting from natural disturbance. Although data and resolution level independent, the model is demonstrated and tested with data from the Lewis and Clark National Forest in Montana.

Integrating animal welfare into veterinary education: using an online, interactive course.

PubMed

Siegford, Janice M; Bernardo, Theresa M; Malinowski, Robert P; Laughlin, Kirsty; Zanella, Adroaldo J

2005-01-01

Veterinarians in the United States and abroad are faced with growing public concern for the welfare of animals, particularly those in production. To prepare veterinarians to exert the leadership expected by the public and industry, steps should be taken to provide instruction in animal welfare at veterinary colleges. The ultimate goal is to offer courses in animal welfare in a consistent manner on a global scale, utilizing existing expertise in an efficient and cost-effective manner. Given the intense curricula of veterinary schools and the scarcity of instructors trained in animal welfare, a nontraditional approach is needed to educate veterinary students in the United States and abroad in animal welfare. Michigan State University (MSU) is developing a graduate-level, online interactive course in animal welfare assessment. The course will approach the topic of animal welfare education from a holistic, multidisciplinary standpoint (encompassing ethics, economics, and behavior) and address issues important to the general public and the international community. The MSU course will draw on renowned international animal welfare experts, allowing students to receive high-quality education that would be difficult in any other circumstance. The course will bridge an important gap in the veterinary curriculum and offer a complete and congruous education in animal welfare to veterinarians worldwide. The MSU course will also serve as a model for collaboration in content assembly and course delivery, by using technology to leverage global expertise in the interests of educational equity. In addition to innovative technology, such as the use of Web-collaboration software to create the course, a variety of media that enable students to interact with the material will also be incorporated throughout the course. Thus, the course will not only utilize the Internet to provide access to high-quality material, but will also require the active participation of the student, which is needed for effective learning.

Cyclooxygenase Inhibition in Sepsis: Is There Life after Death?

PubMed Central

Aronoff, David M.

2012-01-01

Prostaglandins are important mediators and modulators of the inflammatory response to infection. The prostaglandins participate in the pathogenesis of hemodynamic collapse, organ failure, and overwhelming inflammation that characterize severe sepsis and shock. In light of this, cyclooxygenase (COX) inhibiting pharmacological agents have been extensively studied for their capacity to ameliorate the aberrant physiological and immune responses during severe sepsis. Animal models of sepsis, using the systemic administration of pathogen-associated molecular patterns (PAMPs) or live pathogens, have been used to examine the effectiveness of COX inhibition as a treatment for severe sepsis. These studies have largely shown beneficial effects on mortality. However, human studies have failed to show clinical utility of COX inhibitor treatment in severely septic patients. Why this approach “worked” in animals but not in humans might reflect differences in the controlled nature of animal investigations compared to human studies. This paper contrasts the impact of COX inhibitors on mortality in animal models of sepsis and human studies of sepsis and examines potential reasons for differences between these two settings. PMID:22665954

Mathematics as a Conduit for Translational Research in Post-Traumatic Osteoarthritis

PubMed Central

Ayati, Bruce P.; Kapitanov, Georgi I.; Coleman, Mitchell C.; Anderson, Donald D.; Martin, James A.

2016-01-01

Biomathematical models offer a powerful method of clarifying complex temporal interactions and the relationships among multiple variables in a system. We present a coupled in silico biomathematical model of articular cartilage degeneration in response to impact and/or aberrant loading such as would be associated with injury to an articular joint. The model incorporates fundamental biological and mechanical information obtained from explant and small animal studies to predict post-traumatic osteoarthritis (PTOA) progression, with an eye toward eventual application in human patients. In this sense, we refer to the mathematics as a “conduit of translation”. The new in silico framework presented in this paper involves a biomathematical model for the cellular and biochemical response to strains computed using finite element analysis. The model predicts qualitative responses presently, utilizing system parameter values largely taken from the literature. To contribute to accurate predictions, models need to be accurately parameterized with values that are based on solid science. We discuss a parameter identification protocol that will enable us to make increasingly accurate predictions of PTOA progression using additional data from smaller scale explant and small animal assays as they become available. By distilling the data from the explant and animal assays into parameters for biomathematical models, mathematics can translate experimental data to clinically relevant knowledge. PMID:27653021

Identification and Characterization of Liver MicroRNAs of the Chinese Tree Shrew via Deep Sequencing.

PubMed

Feng, Yue; Feng, Yue-Mei; Feng, Yang; Lu, Caixia; Liu, Li; Sun, Xiaomei; Dai, Jiejie; Xia, Xueshan

2015-10-01

Chinese tree shrew (Tupaia belangeri chinensis) is a small animal that possess many features, which are valuable in biomedical research, as experimental models. Currently, there are numerous attempts to utilize tree shrews as models for hepatitis C virus (HCV) infection. This study aimed to construct a liver microRNA (miRNA) data of the tree shrew. Three second filial generation tree shrews were used in this study. Total RNA was extracted from each liver of the tree shrew and equal quality mixed, then reverse-transcribed to complementary DNA (cDNA). The cDNAs were amplified by polymerase chain reaction and subjected to high-throughput sequencing. A total of 2060 conserved miRNAs were identified through alignment with the mature miRNAs in miRBase 20.0 database. The gene ontology and Kyoto encyclopedia of genes and genomes analyses of the target genes of the miRNAs revealed several candidate miRNAs, genes and pathways that may involve in the process of HCV infection. The abundance of miR-122 and Let-7 families and their other characteristics provided us more evidences for the utilization of this animal, as a potential model for HCV infection and other related biomedical research. Moreover, 80 novel microRNAs were predicted using the software Mireap. The top 3 abundant miRNAs were validated in other tree samples, based on stem-loop quantitative reverse transcription-polymerase chain reaction. According to the liver microRNA data of Chinese tree shrew, characteristics of the miR-122 and Let-7 families further highlight the suitability of tree shrew as the animal model in HCV research.

The aquatic animals' transcriptome resource for comparative functional analysis.

PubMed

Chou, Chih-Hung; Huang, Hsi-Yuan; Huang, Wei-Chih; Hsu, Sheng-Da; Hsiao, Chung-Der; Liu, Chia-Yu; Chen, Yu-Hung; Liu, Yu-Chen; Huang, Wei-Yun; Lee, Meng-Lin; Chen, Yi-Chang; Huang, Hsien-Da

2018-05-09

Aquatic animals have great economic and ecological importance. Among them, non-model organisms have been studied regarding eco-toxicity, stress biology, and environmental adaptation. Due to recent advances in next-generation sequencing techniques, large amounts of RNA-seq data for aquatic animals are publicly available. However, currently there is no comprehensive resource exist for the analysis, unification, and integration of these datasets. This study utilizes computational approaches to build a new resource of transcriptomic maps for aquatic animals. This aquatic animal transcriptome map database dbATM provides de novo assembly of transcriptome, gene annotation and comparative analysis of more than twenty aquatic organisms without draft genome. To improve the assembly quality, three computational tools (Trinity, Oases and SOAPdenovo-Trans) were employed to enhance individual transcriptome assembly, and CAP3 and CD-HIT-EST software were then used to merge these three assembled transcriptomes. In addition, functional annotation analysis provides valuable clues to gene characteristics, including full-length transcript coding regions, conserved domains, gene ontology and KEGG pathways. Furthermore, all aquatic animal genes are essential for comparative genomics tasks such as constructing homologous gene groups and blast databases and phylogenetic analysis. In conclusion, we establish a resource for non model organism aquatic animals, which is great economic and ecological importance and provide transcriptomic information including functional annotation and comparative transcriptome analysis. The database is now publically accessible through the URL http://dbATM.mbc.nctu.edu.tw/ .

Three-dimensional modeling and animation of two carpal bones: a technique.

PubMed

Green, Jason K; Werner, Frederick W; Wang, Haoyu; Weiner, Marsha M; Sacks, Jonathan M; Short, Walter H

2004-05-01

The objectives of this study were to (a). create 3D reconstructions of two carpal bones from single CT data sets and animate these bones with experimental in vitro motion data collected during dynamic loading of the wrist joint, (b). develop a technique to calculate the minimum interbone distance between the two carpal bones, and (c). validate the interbone distance calculation process. This method utilized commercial software to create the animations and an in-house program to interface with three-dimensional CAD software to calculate the minimum distance between the irregular geometries of the bones. This interbone minimum distance provides quantitative information regarding the motion of the bones studied and may help to understand and quantify the effects of ligamentous injury.

The Syrian hamster model of hantavirus pulmonary syndrome.

PubMed

Safronetz, David; Ebihara, Hideki; Feldmann, Heinz; Hooper, Jay W

2012-09-01

Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS. Copyright © 2012 Elsevier B.V. All rights reserved.

Generation of germline ablated male pigs by CRISPR/Cas9 editing of the NANOS2 gene

USDA-ARS?s Scientific Manuscript database

Genome editing tools have revolutionized the generation of genetically modified animals including livestock. In particular, the domestic pig is a proven model of human physiology and an agriculturally important species. In this study, we utilized the CRISPR/Cas9 system to edit the NANOS2 gene in p...

Interkingdom cues by bacteria associated with conspecific and heterospecific eggs of Cochliomyia macellaria and Chrysomya rufifacies (Diptera: Calliphoridae) potentially govern succession on carrion

USDA-ARS?s Scientific Manuscript database

Deciphering the mechanisms that regulate animal behavior related to succession on ephemeral resources is critical for elucidating food web dynamics and nutrient recycling. Blow fly (Diptera: Calliphoridae) colonization and utilization of vertebrate carrion serve as a model for such studies, as the...

Operational Details of the Five Domains Model and Its Key Applications to the Assessment and Management of Animal Welfare

PubMed Central

Mellor, David J.

2017-01-01

Simple Summary The Five Domains Model is a focusing device to facilitate systematic, structured, comprehensive and coherent assessment of animal welfare; it is not a definition of animal welfare, nor is it intended to be an accurate representation of body structure and function. The purpose of each of the five domains is to draw attention to areas that are relevant to both animal welfare assessment and management. This paper begins by briefly describing the major features of the Model and the operational interactions between the five domains, and then it details seven interacting applications of the Model. These underlie its utility and increasing application to welfare assessment and management in diverse animal use sectors. Abstract In accord with contemporary animal welfare science understanding, the Five Domains Model has a significant focus on subjective experiences, known as affects, which collectively contribute to an animal’s overall welfare state. Operationally, the focus of the Model is on the presence or absence of various internal physical/functional states and external circumstances that give rise to welfare-relevant negative and/or positive mental experiences, i.e., affects. The internal states and external circumstances of animals are evaluated systematically by referring to each of the first four domains of the Model, designated “Nutrition”, “Environment”, “Health” and “Behaviour”. Then affects, considered carefully and cautiously to be generated by factors in these domains, are accumulated into the fifth domain, designated “Mental State”. The scientific foundations of this operational procedure, published in detail elsewhere, are described briefly here, and then seven key ways the Model may be applied to the assessment and management of animal welfare are considered. These applications have the following beneficial objectives—they (1) specify key general foci for animal welfare management; (2) highlight the foundations of specific welfare management objectives; (3) identify previously unrecognised features of poor and good welfare; (4) enable monitoring of responses to specific welfare-focused remedial interventions and/or maintenance activities; (5) facilitate qualitative grading of particular features of welfare compromise and/or enhancement; (6) enable both prospective and retrospective animal welfare assessments to be conducted; and, (7) provide adjunct information to support consideration of quality of life evaluations in the context of end-of-life decisions. However, also noted is the importance of not overstating what utilisation of the Model can achieve. PMID:28792485

Deriving movement properties and the effect of the environment from the Brownian bridge movement model in monkeys and birds.

PubMed

Buchin, Kevin; Sijben, Stef; van Loon, E Emiel; Sapir, Nir; Mercier, Stéphanie; Marie Arseneau, T Jean; Willems, Erik P

2015-01-01

The Brownian bridge movement model (BBMM) provides a biologically sound approximation of the movement path of an animal based on discrete location data, and is a powerful method to quantify utilization distributions. Computing the utilization distribution based on the BBMM while calculating movement parameters directly from the location data, may result in inconsistent and misleading results. We show how the BBMM can be extended to also calculate derived movement parameters. Furthermore we demonstrate how to integrate environmental context into a BBMM-based analysis. We develop a computational framework to analyze animal movement based on the BBMM. In particular, we demonstrate how a derived movement parameter (relative speed) and its spatial distribution can be calculated in the BBMM. We show how to integrate our framework with the conceptual framework of the movement ecology paradigm in two related but acutely different ways, focusing on the influence that the environment has on animal movement. First, we demonstrate an a posteriori approach, in which the spatial distribution of average relative movement speed as obtained from a "contextually naïve" model is related to the local vegetation structure within the monthly ranging area of a group of wild vervet monkeys. Without a model like the BBMM it would not be possible to estimate such a spatial distribution of a parameter in a sound way. Second, we introduce an a priori approach in which atmospheric information is used to calculate a crucial parameter of the BBMM to investigate flight properties of migrating bee-eaters. This analysis shows significant differences in the characteristics of flight modes, which would have not been detected without using the BBMM. Our algorithm is the first of its kind to allow BBMM-based computation of movement parameters beyond the utilization distribution, and we present two case studies that demonstrate two fundamentally different ways in which our algorithm can be applied to estimate the spatial distribution of average relative movement speed, while interpreting it in a biologically meaningful manner, across a wide range of environmental scenarios and ecological contexts. Therefore movement parameters derived from the BBMM can provide a powerful method for movement ecology research.

Making Progress and Gaining Momentum in Global 3Rs Efforts: How the European Pharmaceutical Industry Is Contributing

PubMed Central

Fleetwood, Gill; Chlebus, Magda; Coenen, Joachim; Dudoignon, Nicolas; Lecerf, Catherine; Maisonneuve, Catherine; Robinson, Sally

2015-01-01

Animal research together with other investigational methods (computer modeling, in vitro tests, etc) remains an indispensable part of the pharmaceutical research and development process. The European pharmaceutical industry recognizes the responsibilities inherent in animal research and is committed to applying and enhancing 3Rs principles. New nonsentient, ex vivo, and in vitro methods are developed every day and contribute to reducing and, in some instances, replacing in vivo studies. Their utility is however limited by the extent of our current knowledge and understanding of complex biological systems. Until validated alternative ways to model these complex interactions become available, animals remain indispensable in research and safety testing. In the interim, scientists continue to look for ways to reduce the number of animals needed to obtain valid results, refine experimental techniques to enhance animal welfare, and replace animals with other research methods whenever feasible. As research goals foster increasing cross-sector and international collaboration, momentum is growing to enhance and coordinate scientific innovation globally—beyond a single company, stakeholder group, sector, region, or country. The implementation of 3Rs strategies can be viewed as an integral part of this continuously evolving science, demonstrating the link between science and welfare, benefiting both the development of new medicines and animal welfare. This goal is one of the key objectives of the Research and Animal Welfare working group of the European Federation of Pharmaceutical Industries and Associations. PMID:25836966

Making progress and gaining momentum in global 3Rs efforts: how the European pharmaceutical industry is contributing.

PubMed

Fleetwood, Gill; Chlebus, Magda; Coenen, Joachim; Dudoignon, Nicolas; Lecerf, Catherine; Maisonneuve, Catherine; Robinson, Sally

2015-03-01

Animal research together with other investigational methods (computer modeling, in vitro tests, etc) remains an indispensable part of the pharmaceutical research and development process. The European pharmaceutical industry recognizes the responsibilities inherent in animal research and is committed to applying and enhancing 3Rs principles. New nonsentient, ex vivo, and in vitro methods are developed every day and contribute to reducing and, in some instances, replacing in vivo studies. Their utility is however limited by the extent of our current knowledge and understanding of complex biological systems. Until validated alternative ways to model these complex interactions become available, animals remain indispensable in research and safety testing. In the interim, scientists continue to look for ways to reduce the number of animals needed to obtain valid results, refine experimental techniques to enhance animal welfare, and replace animals with other research methods whenever feasible. As research goals foster increasing cross-sector and international collaboration, momentum is growing to enhance and coordinate scientific innovation globally-beyond a single company, stakeholder group, sector, region, or country. The implementation of 3Rs strategies can be viewed as an integral part of this continuously evolving science, demonstrating the link between science and welfare, benefiting both the development of new medicines and animal welfare. This goal is one of the key objectives of the Research and Animal Welfare working group of the European Federation of Pharmaceutical Industries and Associations.

Longitudinal Assessment of Lung Cancer Progression in Mice Using the Sodium Iodide Symporter Reporter Gene and SPECT/CT Imaging.

PubMed

Price, Dominique N; McBride, Amber A; Anton, Martina; Kusewitt, Donna F; Norenberg, Jeffrey P; MacKenzie, Debra A; Thompson, Todd A; Muttil, Pavan

2016-01-01

Lung cancer has the highest mortality rate of any tissue-specific cancer in both men and women. Research continues to investigate novel drugs and therapies to mitigate poor treatment efficacy, but the lack of a good descriptive lung cancer animal model for preclinical drug evaluation remains an obstacle. Here we describe the development of an orthotopic lung cancer animal model which utilizes the human sodium iodide symporter gene (hNIS; SLC5A5) as an imaging reporter gene for the purpose of non-invasive, longitudinal tumor quantification. hNIS is a glycoprotein that naturally transports iodide (I-) into thyroid cells and has the ability to symport the radiotracer 99mTc-pertechnetate (99mTcO4-). A549 lung adenocarcinoma cells were genetically modified with plasmid or lentiviral vectors to express hNIS. Modified cells were implanted into athymic nude mice to develop two tumor models: a subcutaneous and an orthotopic xenograft tumor model. Tumor progression was longitudinally imaged using SPECT/CT and quantified by SPECT voxel analysis. hNIS expression in lung tumors was analyzed by quantitative real-time PCR. Additionally, hematoxylin and eosin staining and visual inspection of pulmonary tumors was performed. We observed that lentiviral transduction provided enhanced and stable hNIS expression in A549 cells. Furthermore, 99mTcO4- uptake and accumulation was observed within lung tumors allowing for imaging and quantification of tumor mass at two-time points. This study illustrates the development of an orthotopic lung cancer model that can be longitudinally imaged throughout the experimental timeline thus avoiding inter-animal variability and leading to a reduction in total animal numbers. Furthermore, our orthotopic lung cancer animal model is clinically relevant and the genetic modification of cells for SPECT/CT imaging can be translated to other tissue-specific tumor animal models.

Longitudinal Assessment of Lung Cancer Progression in Mice Using the Sodium Iodide Symporter Reporter Gene and SPECT/CT Imaging

PubMed Central

Anton, Martina; Kusewitt, Donna F.; Norenberg, Jeffrey P.; MacKenzie, Debra A.; Thompson, Todd A.; Muttil, Pavan

2016-01-01

Lung cancer has the highest mortality rate of any tissue-specific cancer in both men and women. Research continues to investigate novel drugs and therapies to mitigate poor treatment efficacy, but the lack of a good descriptive lung cancer animal model for preclinical drug evaluation remains an obstacle. Here we describe the development of an orthotopic lung cancer animal model which utilizes the human sodium iodide symporter gene (hNIS; SLC5A5) as an imaging reporter gene for the purpose of non-invasive, longitudinal tumor quantification. hNIS is a glycoprotein that naturally transports iodide (I-) into thyroid cells and has the ability to symport the radiotracer 99mTc-pertechnetate (99mTcO4-). A549 lung adenocarcinoma cells were genetically modified with plasmid or lentiviral vectors to express hNIS. Modified cells were implanted into athymic nude mice to develop two tumor models: a subcutaneous and an orthotopic xenograft tumor model. Tumor progression was longitudinally imaged using SPECT/CT and quantified by SPECT voxel analysis. hNIS expression in lung tumors was analyzed by quantitative real-time PCR. Additionally, hematoxylin and eosin staining and visual inspection of pulmonary tumors was performed. We observed that lentiviral transduction provided enhanced and stable hNIS expression in A549 cells. Furthermore, 99mTcO4- uptake and accumulation was observed within lung tumors allowing for imaging and quantification of tumor mass at two-time points. This study illustrates the development of an orthotopic lung cancer model that can be longitudinally imaged throughout the experimental timeline thus avoiding inter-animal variability and leading to a reduction in total animal numbers. Furthermore, our orthotopic lung cancer animal model is clinically relevant and the genetic modification of cells for SPECT/CT imaging can be translated to other tissue-specific tumor animal models. PMID:28036366

A systematic review of current osteoporotic metaphyseal fracture animal models.

PubMed

Wong, R M Y; Choy, M H V; Li, M C M; Leung, K-S; K-H Chow, S; Cheung, W-H; Cheng, J C Y

2018-01-01

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article : R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6-11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2. © 2018 Wong et al.

Animal models of myasthenia gravis: utility and limitations

PubMed Central

Mantegazza, Renato; Cordiglieri, Chiara; Consonni, Alessandra; Baggi, Fulvio

2016-01-01

Myasthenia gravis (MG) is a chronic autoimmune disease caused by the immune attack of the neuromuscular junction. Antibodies directed against the acetylcholine receptor (AChR) induce receptor degradation, complement cascade activation, and postsynaptic membrane destruction, resulting in functional reduction in AChR availability. Besides anti-AChR antibodies, other autoantibodies are known to play pathogenic roles in MG. The experimental autoimmune MG (EAMG) models have been of great help over the years in understanding the pathophysiological role of specific autoantibodies and T helper lymphocytes and in suggesting new therapies for prevention and modulation of the ongoing disease. EAMG can be induced in mice and rats of susceptible strains that show clinical symptoms mimicking the human disease. EAMG models are helpful for studying both the muscle and the immune compartments to evaluate new treatment perspectives. In this review, we concentrate on recent findings on EAMG models, focusing on their utility and limitations. PMID:27019601

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

PubMed

Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

PubMed Central

Fulkerson, Christopher M.; Ratliff, Timothy L.; Hahn, Noah M.

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed. PMID:28487862

Endovascular ischemic stroke models of adult rhesus monkeys: a comparison of two endovascular methods.

PubMed

Wu, Di; Chen, Jian; Wang, Bincheng; Zhang, Mo; Shi, Jingfei; Ma, Yanhui; Zhu, Zixin; Yan, Feng; He, Xiaoduo; Li, Shengli; Dornbos Iii, David; Ding, Yuchuan; Ji, Xunming

2016-08-18

To further investigate and improve upon current stroke models in nonhuman primates, infarct size, neurologic function and survival were evaluated in two endovascular ischemic models in sixteen rhesus monkeys. The first method utilized a micro-catheter or an inflatable balloon to occlude the M1 segment in six monkeys. In the second model, an autologous clot was injected via a micro-catheter into the M1 segment in ten monkeys. MRI scanning was performed on all monkeys both at baseline and 3 hours after the onset of ischemia. Spetzler neurologic functions were assessed post-operatively, and selective perfusion deficits were confirmed by DSA and MRI in all monkeys. Animals undergoing micro-catheter or balloon occlusion demonstrated more profound hemiparesis, larger infarct sizes, lower Spetzler neurologic scores and increased mortality compared to the thrombus occlusion group. In animals injected with the clot, there was no evidence of dissolution, and the thrombus was either near the injection site (M1) or flushed into the superior division of the MCA (M2). All animals survived the M2 occlusion. M1 occlusion with thrombus generated 50% mortality. This study highlighted clinically important differences in these two models, providing a platform for further study of a translational thromboembolic model of acute ischemic stroke.

The contribution of animal models to the study of obesity.

PubMed

Speakman, John; Hambly, Catherine; Mitchell, Sharon; Król, Elzbieta

2008-10-01

Obesity results from prolonged imbalance of energy intake and energy expenditure. Animal models have provided a fundamental contribution to the historical development of understanding the basic parameters that regulate the components of our energy balance. Five different types of animal model have been employed in the study of the physiological and genetic basis of obesity. The first models reflect single gene mutations that have arisen spontaneously in rodent colonies and have subsequently been characterized. The second approach is to speed up the random mutation rate artificially by treating rodents with mutagens or exposing them to radiation. The third type of models are mice and rats where a specific gene has been disrupted or over-expressed as a deliberate act. Such genetically-engineered disruptions may be generated through the entire body for the entire life (global transgenic manipulations) or restricted in both time and to certain tissue or cell types. In all these genetically-engineered scenarios, there are two types of situation that lead to insights: where a specific gene hypothesized to play a role in the regulation of energy balance is targeted, and where a gene is disrupted for a different purpose, but the consequence is an unexpected obese or lean phenotype. A fourth group of animal models concern experiments where selective breeding has been utilized to derive strains of rodents that differ in their degree of fatness. Finally, studies have been made of other species including non-human primates and dogs. In addition to studies of the physiological and genetic basis of obesity, studies of animal models have also informed us about the environmental aspects of the condition. Studies in this context include exploring the responses of animals to high fat or high fat/high sugar (Cafeteria) diets, investigations of the effects of dietary restriction on body mass and fat loss, and studies of the impact of candidate pharmaceuticals on components of energy balance. Despite all this work, there are many gaps in our understanding of how body composition and energy storage are regulated, and a continuing need for the development of pharmaceuticals to treat obesity. Accordingly, reductions in the use of animal models, while ethically desirable, will not be feasible in the short to medium term, and indeed an expansion in activity using animal models is anticipated as the epidemic continues and spreads geographically.

A regional mass balance model based on total ammoniacal nitrogen for estimating ammonia emissions from beef cattle in Alberta Canada

NASA Astrophysics Data System (ADS)

Chai, Lilong; Kröbel, Roland; Janzen, H. Henry; Beauchemin, Karen A.; McGinn, Sean M.; Bittman, Shabtai; Atia, Atta; Edeogu, Ike; MacDonald, Douglas; Dong, Ruilan

2014-08-01

Animal feeding operations are primary contributors of anthropogenic ammonia (NH3) emissions in North America and Europe. Mathematical modeling of NH3 volatilization from each stage of livestock manure management allows comprehensive quantitative estimates of emission sources and nutrient losses. A regionally-specific mass balance model based on total ammoniacal nitrogen (TAN) content in animal manure was developed for estimating NH3 emissions from beef farming operations in western Canada. Total N excretion in urine and feces was estimated from animal diet composition, feed dry matter intake and N utilization for beef cattle categories and production stages. Mineralization of organic N, immobilization of TAN, nitrification, and denitrification of N compounds in manure, were incorporated into the model to account for quantities of TAN at each stage of manure handling. Ammonia emission factors were specified for different animal housing (feedlots, barns), grazing, manure storage (including composting and stockpiling) and land spreading (tilled and untilled land), and were modified for temperature. The model computed NH3 emissions from all beef cattle sub-classes including cows, calves, breeding bulls, steers for slaughter, and heifers for slaughter and replacement. Estimated NH3 emissions were about 1.11 × 105 Mg NH3 in Alberta in 2006, with a mean of 18.5 kg animal-1 yr-1 (15.2 kg NH3-N animal-1 yr-1) which is 23.5% of the annual N intake of beef cattle (64.7 kg animal-1 yr-1). The percentage of N intake volatilized as NH3-N was 50% for steers and heifers for slaughter, and between 11 and 14% for all other categories. Steers and heifers for slaughter were the two largest contributors (3.5 × 104 and 3.9 × 104 Mg, respectively) at 31.5 and 32.7% of total NH3 emissions because most growing animals were finished in feedlots. Animal housing and grazing contributed roughly 63% of the total NH3 emissions (feedlots, barns and pastures contributed 54.4, 0.2 and 8.1% of total emissions, respectively.). Manure storage (composting and stockpiling) and land spreading contributed 23 and 14% of the total emissions, respectively. Parameters from this TAN-based mass balance model will be incorporated into the HOLOS model - a farm-level greenhouse gas calculator.

Determination of Energy and Nutrient Utilization of Enzyme-treated Rump Round Meat and Lotus Root Designed for Senior People with Young and Age d Hens as an Animal Model

PubMed Central

Kim, Jong Woong; Kil, Dong Yong

2016-01-01

This study aimed to examine the nutrient utilization of rump round meat and lotus root using young (32 wk) and aged hens (108 wk) as an animal model. Rump round meat and lotus root were prepared with or without enzymatic treatment. For each age group of laying hens, a total of 24 Hy-Line Brown laying hens were randomly allotted to one of two dietary treatments with six replicates. For rump round meat, the true total tract retention rate (TTTR) of dry matter (DM) and nitrogen (N) were unaffected by either enzymatic treatment or hen age. However, aged hens had greater (p<0.01) TTTR of energy and crude fat than young hens. Enzymatic treatment did not influence the TTTR of energy or crude fat. In addition, we did not observe any significant interaction between the TTTR of DM, energy, N, or crude fat in rump round meat and hen age or enzymatic treatment. The TTTR of DM remained unchanged between controls and enzyme-treated lotus root for young hens. However, enzyme-treated lotus root exhibited greater (p<0.05) TTTR of DM than control lotus root for aged hens, resulting in a significant interaction (p<0.05). The TTTR of energy and N in lotus roots were greater (p<0.01) for aged hens than for young hens. In conclusion, enzymatic treatment exerted beneficial effects on energy and nutrient utilization in aged hens, suggesting the aged hen model is practical for simulation of metabolism of elderly individuals. PMID:27499671

Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.

PubMed

Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

2018-01-01

Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

PubMed Central

Ratajczak, Jessica; Gervois, Pascal; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

2018-01-01

Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair. PMID:29535784

Robotic and endoscopic transoral thyroidectomy: feasibility and description of the technique in the cadaveric model

PubMed Central

Kahramangil, Bora; Mohsin, Khuzema; Alzahrani, Hassan; Bu Ali, Daniah; Tausif, Syed; Kang, Sang-Wook; Kandil, Emad

2017-01-01

Background Numerous new approaches have been described over the years to improve the cosmetic outcomes of thyroid surgery. Transoral approach is a new technique that aims to achieve superior cosmetic outcomes by concealing the incision in the oral cavity. Methods Transoral thyroidectomy through vestibular approach was performed in two institutions on cadaveric models. Procedure was performed endoscopically in one institution, while the robotic technique was utilized at the other. Results Transoral thyroidectomy was successfully performed at both institutions with robotic and endoscopic techniques. All vital structures were identified and preserved. Conclusions Transoral thyroidectomy has been performed in animal and cadaveric models, as well as in some clinical studies. Our initial experience indicates the feasibility of this approach. More clinical studies are required to elucidate its full utility. PMID:29302476

Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals

PubMed Central

Lieu, Dustin; Asatryan, Liana; Davies, Daryl L.

2016-01-01

Prior to testing novel therapeutics in humans, short and long term preclinical (i.e., animal), repetitive pharmacological and toxicological testing is required. In most cases, the preferred route of administration is via oral delivery. At the present time, oral delivery is mostly accomplished using an oral gavage procedure, in part, because it can achieve consistent and precise dosing in the animal model. Although this method is well established it does have complications that can result in a high rate of animal attrition. To this end, the procedure introduced here describes an alternative to the oral gavage method in which the desired drug is incorporated into a tastant, orally dissolving strip (ODS) that can simply be presented to the test animal where it is then rapidly taken up with minimal manipulation of the test subject. Herein, we demonstrate that preclinical, oral drug delivery using the ODS method represents a safe, convenient, and humane alternative to oral gavage. PMID:27078261

Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity.

PubMed

Clippinger, Amy J; Allen, David; Behrsing, Holger; BéruBé, Kelly A; Bolger, Michael B; Casey, Warren; DeLorme, Michael; Gaça, Marianna; Gehen, Sean C; Glover, Kyle; Hayden, Patrick; Hinderliter, Paul; Hotchkiss, Jon A; Iskandar, Anita; Keyser, Brian; Luettich, Karsta; Ma-Hock, Lan; Maione, Anna G; Makena, Patrudu; Melbourne, Jodie; Milchak, Lawrence; Ng, Sheung P; Paini, Alicia; Page, Kathryn; Patlewicz, Grace; Prieto, Pilar; Raabe, Hans; Reinke, Emily N; Roper, Clive; Rose, Jane; Sharma, Monita; Spoo, Wayne; Thorne, Peter S; Wilson, Daniel M; Jarabek, Annie M

2018-06-20

New approaches are needed to assess the effects of inhaled substances on human health. These approaches will be based on mechanisms of toxicity, an understanding of dosimetry, and the use of in silico modeling and in vitro test methods. In order to accelerate wider implementation of such approaches, development of adverse outcome pathways (AOPs) can help identify and address gaps in our understanding of relevant parameters for model input and mechanisms, and optimize non-animal approaches that can be used to investigate key events of toxicity. This paper describes the AOPs and the toolbox of in vitro and in silico models that can be used to assess the key events leading to toxicity following inhalation exposure. Because the optimal testing strategy will vary depending on the substance of interest, here we present a decision tree approach to identify an appropriate non-animal integrated testing strategy that incorporates consideration of a substance's physicochemical properties, relevant mechanisms of toxicity, and available in silico models and in vitro test methods. This decision tree can facilitate standardization of the testing approaches. Case study examples are presented to provide a basis for proof-of-concept testing to illustrate the utility of non-animal approaches to inform hazard identification and risk assessment of humans exposed to inhaled substances. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment.

PubMed

Mouri, Akihiro; Noda, Yukihiro; Enomoto, Takeshi; Nabeshima, Toshitaka

2007-01-01

In humans, phencyclidine (PCP), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, reproduces a schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Thus, the glutamatergic neuronal dysfunction hypothesis is one of the main explanatory hypotheses and PCP-treated animals have been utilized as an animal model of schizophrenia. The adult rodents treated with PCP repeatedly exhibit hyperlocomotion as an index of positive symptoms, a social behavioral deficit in a social interaction test and enhanced immobility in a forced swimming test as indices of negative symptoms. They also show a sensorimotor gating deficits and cognitive dysfunctions in several learning and memory tests. Some of these behavioral changes endure after withdrawal from repeated PCP treatment. Furthermore, repeated PCP treatment induces some neurochemical and neuroanatomical changes. On the other hand, the exposure to viral or environmental insult in the second trimester of pregnancy increases the probability of subsequently developing schizophrenia as an adult. NMDA receptor has been implicated in controlling the structure and plasticity of developing brain circuitry. Based on neurodevelopment hypothesis of schizophrenia, schizophrenia model rats treated with PCP at the perinatal stage is developed. Perinatal PCP treatment impairs neuronal development and induces long-lasting schizophrenia-like behaviors in adult period. Many findings suggest that these PCP animal models would be useful for evaluating novel therapeutic candidates and for confirming pathological mechanisms of schizophrenia.

Presentation of Anatomical Variations Using the Aurasma Mobile App

PubMed Central

Bézard, Georg; Lozanoff, Beth K; Labrash, Steven; Lozanoff, Scott

2015-01-01

Knowledge of anatomical variations is critical to avoid clinical complications and it enables an understanding of morphogenetic mechanisms. Depictions are comprised of photographs or illustrations often limiting appreciation of three-dimensional (3D) spatial relationships. The purpose of this study is to describe an approach for presenting anatomical variations utilizing video clips emphasizing 3D anatomical relationships delivered on personal electronic devices. An aberrant right subclavian artery (ARSA) was an incidental finding in a routine dissection of an 89-year-old man cadaver during a medical student instructional laboratory. The specimen was photographed and physical measurements were recorded. Three-dimensional models were lofted and rendered with Maya software and converted as Quicktime animations. Photographs of the first frame of the animations were recorded and registered with Aurasma Mobile App software (www.aurasma.com). Resulting animations were viewed on mobile devices. The ARSA model can be manipulated on the mobile device enabling the student to view and appreciate spatial relationships. Model elements can be de-constructed to provide even greater spatial resolution of anatomical relationships. Animations provide a useful approach for visualizing anatomical variations. Future work will be directed at creating a library of variants and underlying mechanism of formation for presentation through the Aurasma application. PMID:26793410

Real-time animation software for customized training to use motor prosthetic systems.

PubMed

Davoodi, Rahman; Loeb, Gerald E

2012-03-01

Research on control of human movement and development of tools for restoration and rehabilitation of movement after spinal cord injury and amputation can benefit greatly from software tools for creating precisely timed animation sequences of human movement. Despite their ability to create sophisticated animation and high quality rendering, existing animation software are not adapted for application to neural prostheses and rehabilitation of human movement. We have developed a software tool known as MSMS (MusculoSkeletal Modeling Software) that can be used to develop models of human or prosthetic limbs and the objects with which they interact and to animate their movement using motion data from a variety of offline and online sources. The motion data can be read from a motion file containing synthesized motion data or recordings from a motion capture system. Alternatively, motion data can be streamed online from a real-time motion capture system, a physics-based simulation program, or any program that can produce real-time motion data. Further, animation sequences of daily life activities can be constructed using the intuitive user interface of Microsoft's PowerPoint software. The latter allows expert and nonexpert users alike to assemble primitive movements into a complex motion sequence with precise timing by simply arranging the order of the slides and editing their properties in PowerPoint. The resulting motion sequence can be played back in an open-loop manner for demonstration and training or in closed-loop virtual reality environments where the timing and speed of animation depends on user inputs. These versatile animation utilities can be used in any application that requires precisely timed animations but they are particularly suited for research and rehabilitation of movement disorders. MSMS's modeling and animation tools are routinely used in a number of research laboratories around the country to study the control of movement and to develop and test neural prostheses for patients with paralysis or amputations.

A lethal murine infection model for dengue virus 3 in AG129 mice deficient in type I and II interferon receptors leads to systemic disease.

PubMed

Sarathy, Vanessa V; White, Mellodee; Li, Li; Gorder, Summer R; Pyles, Richard B; Campbell, Gerald A; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

2015-01-15

The mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads to acute illness and results in lifelong homotypic immunity, but individuals remain susceptible to infection by the other three DENVs. The lack of a small-animal model that mimics systemic DEN disease without neurovirulence has been an obstacle, but DENV-2 models that resemble human disease have been recently developed in AG129 mice (deficient in interferon alpha/beta and interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4 models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human isolate to develop a lethal infection model in AG129 mice. Intraperitoneal inoculation of six to eight-week-old animals with strain C0360/94 led to rapid, fatal disease. Lethal C0360/94 infection resulted in physical signs of illness, high viral loads in the spleen, liver, and large intestine, histological changes in the liver and spleen tissues, and increased serum cytokine levels. Importantly, the animals developed vascular leakage, thrombocytopenia, and leukopenia. Overall, we have developed a lethal DENV-3 murine infection model, with no evidence of neurotropic disease based on a non-mouse-adapted human isolate, which can be used to investigate DEN pathogenesis and to evaluate candidate vaccines and antivirals. This suggests that murine models utilizing non-mouse-adapted isolates can be obtained for all four DENVs. Dengue (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3, and -4) that have no treatments or vaccines. Primary infection with one DENV usually leads to acute illness followed by lifelong homotypic immunity, but susceptibility to infection by the other three DENVs remains. Therefore, a vaccine needs to protect from all four DENVs simultaneously. To date a suitable animal model to mimic systemic human illness exists only for DENV-2 in immunocompromised mice using passaged viruses; however, models are still needed for the remaining serotypes. This study describes establishment of a lethal systemic DENV-3 infection model with a human isolate in immunocompromised mice and is the first report of lethal infection by a nonadapted clinical DENV isolate without evidence of neurological disease. Our DENV-3 model provides a relevant platform to test DEN vaccines and antivirals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Percutaneous Steerable Robotic Tool Delivery Platform and Metal MEMS Device for Tissue Manipulation and Approximation: Closure of Patent Foramen Ovale in an Animal Model

PubMed Central

Vasilyev, Nikolay V.; Gosline, Andrew H.; Butler, Evan; Lang, Nora; Codd, Patrick J.; Yamauchi, Haruo; Feins, Eric N.; Folk, Chris R.; Cohen, Adam L.; Chen, Richard; Zurakowski, David; del Nido, Pedro J.; Dupont, Pierre E

2013-01-01

Background Beating-heart image-guided intracardiac interventions have been evolving rapidly. To extend the domain of catheter-based and transcardiac interventions into reconstructive surgery, a new robotic tool delivery platform (TDP) and tissue approximation device have been developed. Initial results employing these tools to perform patent foramen ovale (PFO) closure are described. Methods and Results A robotic TDP comprised of superelastic metal tubes provides the capability of delivering and manipulating tools and devices inside the beating heart. A new device technology is also presented that utilizes a metal-based MicroElectroMechanical Systems (MEMS) manufacturing process to produce fully-assembled and fully-functional millimeter-scale tools. As a demonstration of both technologies, a PFO creation and closure was performed in a swine model. In the first group of animals (N=10), a preliminary study was performed. The procedural technique was validated with a transcardiac handheld delivery platform and epicardial echocardiography, video-assisted cardioscopy and fluoroscopy. In the second group (N=9), the procedure was performed percutaneously using the robotic TDP under epicardial echocardiography and fluoroscopy imaging. All PFO’s were completely closed in the first group. In the second group, the PFO was not successfully created in 1 animal, and the defects were completely closed in 6 of the 8 remaining animals. Conclusions In contrast to existing robotic catheter technologies, the robotic TDP utilizes a combination of stiffness and active steerability along its length to provide the positioning accuracy and force application capability necessary for tissue manipulation. In combination with a MEMS tool technology, it can enable reconstructive procedures inside the beating heart. PMID:23899870

Characterization of 7- and 19-month-old Tg2576 mice using multimodal in vivo imaging: limitations as a translatable model of Alzheimer's disease.

PubMed

Luo, Feng; Rustay, Nathan R; Ebert, Ulrich; Hradil, Vincent P; Cole, Todd B; Llano, Daniel A; Mudd, Sarah R; Zhang, Yumin; Fox, Gerard B; Day, Mark

2012-05-01

With 90% of neuroscience clinical trials failing to see efficacy, there is a clear need for the development of disease biomarkers that can improve the ability to predict human Alzheimer's disease (AD) trial outcomes from animal studies. Several lines of evidence, including genetic susceptibility and disease studies, suggest the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) as a potential biomarker with congruency between humans and animal models. For example, early in AD, patients present with decreased glucose metabolism in the entorhinal cortex and several regions of the brain associated with disease pathology and cognitive decline. While several of the commonly used AD mouse models fail to show all the hallmarks of the disease or the limbic to cortical trajectory, there has not been a systematic evaluation of imaging-derived biomarkers across animal models of AD, contrary to what has been achieved in recent years in the Alzheimer's Disease Neuroimaging Initiative (ADNI) (Miller, 2009). If animal AD models were found to mimic endpoints that correlate with the disease onset, progression, and relapse, then the identification of such markers in animal models could afford the field a translational tool to help bridge the preclinical-clinical gap. Using a combination of FDG-PET and functional magnetic resonance imaging (fMRI), we examined the Tg2576 mouse for global and regional measures of brain glucose metabolism at 7 and 19 months of age. In experiment 1 we observed that at younger ages, when some plaque burden and cognitive deficits have been reported, Tg2576 mice showed hypermetabolism as assessed with FDG-PET. This hypermetabolism decreased with age to levels similar to wild type (WT) counterparts such that the 19-month-old transgenic (Tg) mice did not differ from age matched WTs. In experiment 2, using cerebral blood volume (CBV) fMRI, we demonstrated that the hypermetabolism observed in Tg mice at 7 months could not be explained by changes in hemodynamic parameters as no differences were observed when compared with WTs. Taken together, these data identify brain hypermetabolism in Tg2576 mice which cannot be accounted for by changes in vascular compliance. Instead, the hypermetabolism may reflect a neuronal compensatory mechanism. Our data are discussed in the context of disease biomarker identification and target validation, suggesting little or no utility for translational based studies using Tg2576 mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat.

PubMed

Bentzley, Brandon S; Jhou, Thomas C; Aston-Jones, Gary

2014-08-12

Development of new treatments for drug addiction will depend on high-throughput screening in animal models. However, an addiction biomarker fit for rapid testing, and useful in both humans and animals, is not currently available. Economic models are promising candidates. They offer a structured quantitative approach to modeling behavior that is mathematically identical across species, and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity. However, economic demand has not yet been established as a biomarker of addiction-like behavior in animals, an essential final step in linking animal and human studies of addiction through economic models. We recently developed a mathematical approach for rapidly modeling economic demand in rats trained to self-administer cocaine. We show here that economic demand, as both a spontaneous trait and induced state, predicts addiction-like behavior, including relapse propensity, drug seeking in abstinence, and compulsive (punished) drug taking. These findings confirm economic demand as a biomarker of addiction-like behavior in rats. They also support the view that excessive motivation plays an important role in addiction while extending the idea that drug dependence represents a shift from initially recreational to compulsive drug use. Finally, we found that economic demand for cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in attenuating cocaine-seeking behaviors across individuals, demonstrating that economic measures may be used to rapidly identify the clinical utility of prospective addiction treatments.

Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat

PubMed Central

Bentzley, Brandon S.; Jhou, Thomas C.; Aston-Jones, Gary

2014-01-01

Development of new treatments for drug addiction will depend on high-throughput screening in animal models. However, an addiction biomarker fit for rapid testing, and useful in both humans and animals, is not currently available. Economic models are promising candidates. They offer a structured quantitative approach to modeling behavior that is mathematically identical across species, and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity. However, economic demand has not yet been established as a biomarker of addiction-like behavior in animals, an essential final step in linking animal and human studies of addiction through economic models. We recently developed a mathematical approach for rapidly modeling economic demand in rats trained to self-administer cocaine. We show here that economic demand, as both a spontaneous trait and induced state, predicts addiction-like behavior, including relapse propensity, drug seeking in abstinence, and compulsive (punished) drug taking. These findings confirm economic demand as a biomarker of addiction-like behavior in rats. They also support the view that excessive motivation plays an important role in addiction while extending the idea that drug dependence represents a shift from initially recreational to compulsive drug use. Finally, we found that economic demand for cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in attenuating cocaine-seeking behaviors across individuals, demonstrating that economic measures may be used to rapidly identify the clinical utility of prospective addiction treatments. PMID:25071176

Simultaneous estimation of diet composition and calibration coefficients with fatty acid signature data

USGS Publications Warehouse

Bromaghin, Jeffrey F.; Budge, Suzanne M.; Thiemann, Gregory W.; Rode, Karyn D.

2017-01-01

Knowledge of animal diets provides essential insights into their life history and ecology, although diet estimation is challenging and remains an active area of research. Quantitative fatty acid signature analysis (QFASA) has become a popular method of estimating diet composition, especially for marine species. A primary assumption of QFASA is that constants called calibration coefficients, which account for the differential metabolism of individual fatty acids, are known. In practice, however, calibration coefficients are not known, but rather have been estimated in feeding trials with captive animals of a limited number of model species. The impossibility of verifying the accuracy of feeding trial derived calibration coefficients to estimate the diets of wild animals is a foundational problem with QFASA that has generated considerable criticism. We present a new model that allows simultaneous estimation of diet composition and calibration coefficients based only on fatty acid signature samples from wild predators and potential prey. Our model performed almost flawlessly in four tests with constructed examples, estimating both diet proportions and calibration coefficients with essentially no error. We also applied the model to data from Chukchi Sea polar bears, obtaining diet estimates that were more diverse than estimates conditioned on feeding trial calibration coefficients. Our model avoids bias in diet estimates caused by conditioning on inaccurate calibration coefficients, invalidates the primary criticism of QFASA, eliminates the need to conduct feeding trials solely for diet estimation, and consequently expands the utility of fatty acid data to investigate aspects of ecology linked to animal diets.

Spinal Cord Injury Veterans: Disability Benefits, Outcomes, and Health Care Utilization Patterns

DTIC Science & Technology

2016-08-01

PRINCIPAL INVESTIGATOR: Denise Fyffe, PhD ORGANIZATION : Kessler Medical Rehabilitation Research & Education Corporation West Orange, NJ 07052 REPORT DATE... research material (e.g., Germplasm; cell lines, DNA probes, animal models); • clinical interventions; • new business creation; and • other...the research , exchanged personnel, or otherwise contributed. Provide the following information for each partnership: Organization Name

The Road to Reproducibility in Animal Research.

PubMed

Jilka, Robert L

2016-07-01

Reproducibility of research findings is the hallmark of scientific advance. However, the recently noted lack of reproducibility and transparency of published research using animal models of human biology and disease has alarmed funders, scientists, and the public. Improved reporting of methodology and better use of statistical tools are needed to enhance the quality and utility of published research. Reporting guidelines like Animal Research: Reporting In Vivo Experiments (ARRIVE) have been devised to achieve these goals, but most biomedical research journals, including the JBMR, have not been able to obtain high compliance. Cooperative efforts among authors, reviewers and editors-empowered by increased awareness of their responsibilities, and enabled by user-friendly guidelines-are needed to solve this problem. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 4. Medical Imaging Procedures.

PubMed

Byrum, Russell; Keith, Lauren; Bartos, Christopher; St Claire, Marisa; Lackemeyer, Matthew G; Holbrook, Michael R; Janosko, Krisztina; Barr, Jason; Pusl, Daniela; Bollinger, Laura; Wada, Jiro; Coe, Linda; Hensley, Lisa E; Jahrling, Peter B; Kuhn, Jens H; Lentz, Margaret R

2016-10-03

Medical imaging using animal models for human diseases has been utilized for decades; however, until recently, medical imaging of diseases induced by high-consequence pathogens has not been possible. In 2014, the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Integrated Research Facility at Fort Detrick opened an Animal Biosafety Level 4 (ABSL-4) facility to assess the clinical course and pathology of infectious diseases in experimentally infected animals. Multiple imaging modalities including computed tomography (CT), magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography are available to researchers for these evaluations. The focus of this article is to describe the workflow for safely obtaining a CT image of a live guinea pig in an ABSL-4 facility. These procedures include animal handling, anesthesia, and preparing and monitoring the animal until recovery from sedation. We will also discuss preparing the imaging equipment, performing quality checks, communication methods from "hot side" (containing pathogens) to "cold side," and moving the animal from the holding room to the imaging suite.

A freely-moving monkey treadmill model

NASA Astrophysics Data System (ADS)

Foster, Justin D.; Nuyujukian, Paul; Freifeld, Oren; Gao, Hua; Walker, Ross; Ryu, Stephen I.; Meng, Teresa H.; Murmann, Boris; Black, Michael J.; Shenoy, Krishna V.

2014-08-01

Objective. Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. Approach. We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the flexibility and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. Main results. Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average firing rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. Significance. Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic motor neuroscience and for the successful translation of BMIs to people with paralysis.

Frequency domain fluorescence diffuse tomography of small animals

NASA Astrophysics Data System (ADS)

Orlova, Anna G.; Turchin, Ilya V.; Kamensky, Vladislav A.; Plehanov, Vladimir I.; Balalaeva, Irina V.; Sergeeva, Ekaterina A.; Shirmanova, Marina V.; Kleshnin, Michail S.

2007-05-01

Fluorescent compounds for selective cancer cell marking are used for development of novel medical diagnostic methods, investigation of the influence of external factors on tumor growth, regress and metastasis. Only special tools for turbid media imaging, such as optical diffusion tomography permit noninvasive monitoring of fluorescent-labeled tumor alterations deep in animal tissue. In this work, the results of preliminary experiments utilizing frequency-domain fluorescent diffusion tomography (FD FDT) experimental setup in small animal are presented. Low-frequency modulated light (1 kHz) from Nd:YAG laser with second harmonic generation at the wavelength of 532 nm was used in the setup. The transilluminative planar configuration was used in the setup. A series of model experiments has been conducted and show good agreement between theoretical and experimental fluorescence intensity. Models of deep tumors were created by two methods: (1) glass capsules containing fluorophore solution were inserted into esophagus of small animals to simulate marked tumors; (2) a suspension of transfected HEΚ293-Turbo-RFP cells was subcutaneously injected to small animal. The conducted experiments have shown that FD FDT allows one to detect the presence of labeled tumor cells in small animals, to determine the volume of an experimental tumor, to perform 3D tumor reconstruction, as well as to conduct monitoring investigations. The obtained results demonstrate the potential capability of the FD FDT method for noninvasive whole-body imaging in cancer studies, diagnostics and therapy.

Novel diagnostics of metabolic dysfunction detected in breath and plasma by selective isotope-assisted labeling.

PubMed

Haviland, Julia A; Tonelli, Marco; Haughey, Dermot T; Porter, Warren P; Assadi-Porter, Fariba M

2012-08-01

Metabolomics is the study of a unique fingerprint of small molecules present in biological systems under healthy and disease conditions. One of the major challenges in metabolomics is validation of fingerprint molecules to identify specifically perturbed pathways in metabolic aberrations. This step is crucial to the understanding of budding metabolic pathologies and the ability to identify early indicators of common diseases such as obesity, type 2 diabetes mellitus, metabolic syndrome, polycystic ovary syndrome, and cancer. We present a novel approach to diagnosing aberrations in glucose utilization including metabolic pathway switching in a disease state. We used a well-defined prenatally exposed glucocorticoid mouse model that results in adult females with metabolic dysfunction. We applied the complementary technologies of nuclear magnetic resonance spectroscopy and cavity ring-down spectroscopy to analyze serial plasma samples and real-time breath measurements following selective (13)C-isotope-assisted labeling. These platforms allowed us to trace metabolic markers in whole animals and identify key metabolic pathway switching in prenatally glucocorticoid-treated animals. Total glucose flux is significantly proportionally increased through the major oxidative pathways of glycolysis and the pentose phosphate pathway in the prenatally glucocorticoid-treated animals relative to the control animals. This novel diagnostics approach is fast, noninvasive, and sensitive for determining specific pathway utilization, and provides a direct translational application in the health care field. Copyright © 2012 Elsevier Inc. All rights reserved.

From Lévy to Brownian: a computational model based on biological fluctuation.

PubMed

Nurzaman, Surya G; Matsumoto, Yoshio; Nakamura, Yutaka; Shirai, Kazumichi; Koizumi, Satoshi; Ishiguro, Hiroshi

2011-02-03

Theoretical studies predict that Lévy walks maximizes the chance of encountering randomly distributed targets with a low density, but Brownian walks is favorable inside a patch of targets with high density. Recently, experimental data reports that some animals indeed show a Lévy and Brownian walk movement patterns when forage for foods in areas with low and high density. This paper presents a simple, Gaussian-noise utilizing computational model that can realize such behavior. We extend Lévy walks model of one of the simplest creature, Escherichia coli, based on biological fluctuation framework. We build a simulation of a simple, generic animal to observe whether Lévy or Brownian walks will be performed properly depends on the target density, and investigate the emergent behavior in a commonly faced patchy environment where the density alternates. Based on the model, animal behavior of choosing Lévy or Brownian walk movement patterns based on the target density is able to be generated, without changing the essence of the stochastic property in Escherichia coli physiological mechanism as explained by related researches. The emergent behavior and its benefits in a patchy environment are also discussed. The model provides a framework for further investigation on the role of internal noise in realizing adaptive and efficient foraging behavior.

Let there be bioluminescence – Development of a biophotonic imaging platform for in situ analyses of oral biofilms in animal models

PubMed Central

Merritt, Justin; Senpuku, Hidenobu; Kreth, Jens

2016-01-01

Summary In the current study, we describe a novel biophotonic imaging-based reporter system that is particularly useful for the study of virulence in polymicrobial infections and interspecies interactions within animal models. A suite of luciferase enzymes was compared using three early colonizing species of the human oral flora (Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis) to determine the utility of the different reporters for multiplexed imaging studies in vivo. Using the multiplex approach, we were able to track individual species within a dual species oral infection model in mice with both temporal and spatial resolution. We also demonstrate how biophotonic imaging of multiplexed luciferase reporters could be adapted for real-time quantification of bacterial gene expression in situ. By creating an inducible dual-luciferase expressing reporter strain of S. mutans, we were able to exogenously control and measure expression of nlmAB (encoding the bacteriocin mutacin IV) within mice to assess its importance for the persistence ability of S. mutans in the oral cavity. The imaging system described in the current study circumvents many of the inherent limitations of current animal model systems, which should now make it feasible to test hypotheses that were previously impractical to model. PMID:26119252

Utility of the Hebb-Williams Maze Paradigm for Translational Research in Fragile X Syndrome: A Direct Comparison of Mice and Humans.

PubMed

Boutet, Isabelle; Collin, Charles A; MacLeod, Lindsey S; Messier, Claude; Holahan, Matthew R; Berry-Kravis, Elizabeth; Gandhi, Reno M; Kogan, Cary S

2018-01-01

To generate meaningful information, translational research must employ paradigms that allow extrapolation from animal models to humans. However, few studies have evaluated translational paradigms on the basis of defined validation criteria. We outline three criteria for validating translational paradigms. We then evaluate the Hebb-Williams maze paradigm (Hebb and Williams, 1946; Rabinovitch and Rosvold, 1951) on the basis of these criteria using Fragile X syndrome (FXS) as model disease. We focused on this paradigm because it allows direct comparison of humans and animals on tasks that are behaviorally equivalent (criterion #1) and because it measures spatial information processing, a cognitive domain for which FXS individuals and mice show impairments as compared to controls (criterion #2). We directly compared the performance of affected humans and mice across different experimental conditions and measures of behavior to identify which conditions produce comparable patterns of results in both species. Species differences were negligible for Mazes 2, 4, and 5 irrespective of the presence of visual cues, suggesting that these mazes could be used to measure spatial learning in both species. With regards to performance on the first trial, which reflects visuo-spatial problem solving, Mazes 5 and 9 without visual cues produced the most consistent results. We conclude that the Hebb-Williams mazes paradigm has the potential to be utilized in translational research to measure comparable cognitive functions in FXS humans and animals (criterion #3).

3D geospatial visualizations: Animation and motion effects on spatial objects

NASA Astrophysics Data System (ADS)

Evangelidis, Konstantinos; Papadopoulos, Theofilos; Papatheodorou, Konstantinos; Mastorokostas, Paris; Hilas, Constantinos

2018-02-01

Digital Elevation Models (DEMs), in combination with high quality raster graphics provide realistic three-dimensional (3D) representations of the globe (virtual globe) and amazing navigation experience over the terrain through earth browsers. In addition, the adoption of interoperable geospatial mark-up languages (e.g. KML) and open programming libraries (Javascript) makes it also possible to create 3D spatial objects and convey on them the sensation of any type of texture by utilizing open 3D representation models (e.g. Collada). One step beyond, by employing WebGL frameworks (e.g. Cesium.js, three.js) animation and motion effects are attributed on 3D models. However, major GIS-based functionalities in combination with all the above mentioned visualization capabilities such as for example animation effects on selected areas of the terrain texture (e.g. sea waves) as well as motion effects on 3D objects moving in dynamically defined georeferenced terrain paths (e.g. the motion of an animal over a hill, or of a big fish in an ocean etc.) are not widely supported at least by open geospatial applications or development frameworks. Towards this we developed and made available to the research community, an open geospatial software application prototype that provides high level capabilities for dynamically creating user defined virtual geospatial worlds populated by selected animated and moving 3D models on user specified locations, paths and areas. At the same time, the generated code may enhance existing open visualization frameworks and programming libraries dealing with 3D simulations, with the geospatial aspect of a virtual world.

Exploring Autophagy in Drosophila

PubMed Central

Juhász, Gábor

2017-01-01

Autophagy is a catabolic process in eukaryotic cells promoting bulk or selective degradation of cellular components within lysosomes. In recent decades, several model systems were utilized to dissect the molecular machinery of autophagy and to identify the impact of this cellular “self-eating” process on various physiological and pathological processes. Here we briefly discuss the advantages and limitations of using the fruit fly Drosophila melanogaster, a popular model in cell and developmental biology, to apprehend the main pathway of autophagy in a complete animal. PMID:28704946

Animal exploitation in northeast Tibetan Plateau during Neolithic-Bronze Age

NASA Astrophysics Data System (ADS)

Dong, Guanghui; Ren, Lele; Li, Zhipeng; Zhang, Dongju; Chen, Fahu

2017-04-01

The history and driving force for prehistoric human occupation of the Tibetan Plateau has been intensively concerned in recent years. Multidisciplinary studies reveal that human extensively and year-roundly settled below 2500 m asl in northeast Tibetan Plateau (NETP) since 5200BP mainly with the utilization of millet crops, and above 3000 m asl post 3600BP primarily with cold-tolerant barley. However, the strategy for human animal utilization during Neolithic and Bronze periods in NETP still remains enigmatic. We collected and identified hundreds of animal bones from 14 Neolithic and Bronze sites in NETP, with the application of radiocarbon dating, carbon and nitrogen isotopes analysis, and ancient DNA analysis, we explore the changing patterns of animal utilization, and potential human behaviours for taming wild animals in this area throughout late prehistoric times. These works shed lights for understanding when and how husbandry and pastoral economies emerged, and how prehistoric human adapted to the high-cold environment of the Tibetan Plateau..

Environmental chemistry of animal manure

USDA-ARS?s Scientific Manuscript database

Animal manure is traditionally regarded as a valuable resource of plant nutrients. However, there is an increasing environmental concern associated with animal manure utilization due to high and locally concentrated volumes of manure produced in modern intensified animal production. Although conside...

CO-FIRING COAL: FEEDLOT AND LITTER BIOMASS FUELS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalyan Annamalai; John Sweeten; Saqib Mukhtar

2003-06-01

Reburn with animal waste yield NO{sub x} reduction of the order of 70-80%, which is much higher than those previously reported in the literature for natural gas, coal and agricultural biomass as reburn fuels. Further, the NO{sub x} reduction is almost independent of stoichiometry from stoichiometric to upto 10% deficient air in reburn zone. As a first step towards understanding the reburn process in a boiler burner, a simplified zero-dimensional model has been developed for estimating the NO{sub x} reduction in the reburn process using simulated animal waste based biomass volatiles. However the first model does not include the gradualmore » heat up of reburn fuel particle, pyrolysis and char combustion. Hence there is a need for more rigorous treatment of the model with animal waste as reburn fuel. To address this issue, an improved zero-dimensional model is being developed which can handle any solid reburn fuel, along with more detailed heterogeneous char reactions and homogeneous global reactions. The model on ''NO{sub x} Reduction for Reburn Process using Feedlot Biomass,'' incorporates; (a) mixing between reburn fuel and main-burner gases, (b) gradual heat-up of reburn fuel accompanied by pyrolysis, oxidation of volatiles and char oxidation, (c) fuel-bound nitrogen (FBN) pyrolysis, and FBN including both forward and backward reactions, (d) prediction of NO{sub x} as a function of time in the reburn zone, and (e) gas phase and solid phase temperature as a function of time. The fuel bound nitrogen is assumed to be released to the gas phase by two processes, (a) FBN evolution to N{sub 2}, HCN, and NH{sub 3}, and (b) FBN oxidation to NO at the char surface. The formulation has been completed, code has been developed, and preliminary runs have been made to test the code. Note that, the current model does not incorporate the overfire air. The results of the simulation will be compared with the experimental results. During this quarter, three journal and four conference publications dealing with utilization of animal waste as fuel have been published. In addition a presentation was made to a utility company interested in the new reburn technology for NO{sub x} reduction.« less

Application of PBPK modelling in drug discovery and development at Pfizer.

PubMed

Jones, Hannah M; Dickins, Maurice; Youdim, Kuresh; Gosset, James R; Attkins, Neil J; Hay, Tanya L; Gurrell, Ian K; Logan, Y Raj; Bungay, Peter J; Jones, Barry C; Gardner, Iain B

2012-01-01

Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however, some limitations need to be addressed to realize its application and utility more broadly.

Advances in the Study of Heart Development and Disease Using Zebrafish

PubMed Central

Brown, Daniel R.; Samsa, Leigh Ann; Qian, Li; Liu, Jiandong

2016-01-01

Animal models of cardiovascular disease are key players in the translational medicine pipeline used to define the conserved genetic and molecular basis of disease. Congenital heart diseases (CHDs) are the most common type of human birth defect and feature structural abnormalities that arise during cardiac development and maturation. The zebrafish, Danio rerio, is a valuable vertebrate model organism, offering advantages over traditional mammalian models. These advantages include the rapid, stereotyped and external development of transparent embryos produced in large numbers from inexpensively housed adults, vast capacity for genetic manipulation, and amenability to high-throughput screening. With the help of modern genetics and a sequenced genome, zebrafish have led to insights in cardiovascular diseases ranging from CHDs to arrhythmia and cardiomyopathy. Here, we discuss the utility of zebrafish as a model system and summarize zebrafish cardiac morphogenesis with emphasis on parallels to human heart diseases. Additionally, we discuss the specific tools and experimental platforms utilized in the zebrafish model including forward screens, functional characterization of candidate genes, and high throughput applications. PMID:27335817

Design and assessment of a novel SPECT system for desktop open-gantry imaging of small animals: A simulation study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeraatkar, Navid; Farahani, Mohammad Hossein; Rahmim, Arman

Purpose: Given increasing efforts in biomedical research utilizing molecular imaging methods, development of dedicated high-performance small-animal SPECT systems has been growing rapidly in the last decade. In the present work, we propose and assess an alternative concept for SPECT imaging enabling desktop open-gantry imaging of small animals. Methods: The system, PERSPECT, consists of an imaging desk, with a set of tilted detector and pinhole collimator placed beneath it. The object to be imaged is simply placed on the desk. Monte Carlo (MC) and analytical simulations were utilized to accurately model and evaluate the proposed concept and design. Furthermore, a dedicatedmore » image reconstruction algorithm, finite-aperture-based circular projections (FABCP), was developed and validated for the system, enabling more accurate modeling of the system and higher quality reconstructed images. Image quality was quantified as a function of different tilt angles in the acquisition and number of iterations in the reconstruction algorithm. Furthermore, more complex phantoms including Derenzo, Defrise, and mouse whole body were simulated and studied. Results: The sensitivity of the PERSPECT was 207 cps/MBq. It was quantitatively demonstrated that for a tilt angle of 30°, comparable image qualities were obtained in terms of normalized squared error, contrast, uniformity, noise, and spatial resolution measurements, the latter at ∼0.6 mm. Furthermore, quantitative analyses demonstrated that 3 iterations of FABCP image reconstruction (16 subsets/iteration) led to optimally reconstructed images. Conclusions: The PERSPECT, using a novel imaging protocol, can achieve comparable image quality performance in comparison with a conventional pinhole SPECT with the same configuration. The dedicated FABCP algorithm, which was developed for reconstruction of data from the PERSPECT system, can produce high quality images for small-animal imaging via accurate modeling of the system as incorporated in the forward- and back-projection steps. Meanwhile, the developed MC model and the analytical simulator of the system can be applied for further studies on development and evaluation of the system.« less

Visualizing Astronomical Data with Blender

NASA Astrophysics Data System (ADS)

Kent, Brian R.

2014-01-01

We present methods for using the 3D graphics program Blender in the visualization of astronomical data. The software's forte for animating 3D data lends itself well to use in astronomy. The Blender graphical user interface and Python scripting capabilities can be utilized in the generation of models for data cubes, catalogs, simulations, and surface maps. We review methods for data import, 2D and 3D voxel texture applications, animations, camera movement, and composite renders. Rendering times can be improved by using graphic processing units (GPUs). A number of examples are shown using the software features most applicable to various kinds of data paradigms in astronomy.

Animal models for ebolavirus countermeasures discovery: what defines a useful model?

PubMed

Shurtleff, Amy C; Bavari, Sina

2015-07-01

Ebolaviruses are highly pathogenic filoviruses, which cause disease in humans and nonhuman primates (NHP) in Africa. The Zaire ebolavirus outbreak in 2014, which continues to greatly affect Western Africa and other countries to which the hemorrhagic fever was exported due to travel of unsymptomatic yet infected individuals, was complicated by the lack of available licensed vaccines or therapeutics to combat infection. After almost a year of research at an increased pace to find and test vaccines and therapeutics, there is now a deeper understanding of the available disease models for ebolavirus infection. Demonstration of vaccine or therapeutic efficacy in NHP models of ebolavirus infection is crucial to the development and eventual licensure of ebolavirus medical countermeasures, so that safe and effective countermeasures can be accelerated into human clinical trials. The authors describe ebolavirus hemorrhagic fever (EHF) disease in various animal species: mice, guinea pigs, hamsters, pigs and NHP, to include baboons, marmosets, rhesus and cynomolgus macaques, as well as African green monkeys. Because the NHP models are supremely useful for therapeutics and vaccine testing, emphasis is placed on comparison of these models, and their use as gold-standard models of EHF. Animal models of EHF varying from rodents to NHP species are currently under evaluation for their reproducibility and utility for modeling infection in humans. Complete development and licensure of therapeutic agents and vaccines will require demonstration that mechanisms conferring protection in NHP models of infection are predictive of protective responses in humans, for a given countermeasure.

The Argos-CLS Kalman Filter: Error Structures and State-Space Modelling Relative to Fastloc GPS Data.

PubMed

Lowther, Andrew D; Lydersen, Christian; Fedak, Mike A; Lovell, Phil; Kovacs, Kit M

2015-01-01

Understanding how an animal utilises its surroundings requires its movements through space to be described accurately. Satellite telemetry is the only means of acquiring movement data for many species however data are prone to varying amounts of spatial error; the recent application of state-space models (SSMs) to the location estimation problem have provided a means to incorporate spatial errors when characterising animal movements. The predominant platform for collecting satellite telemetry data on free-ranging animals, Service Argos, recently provided an alternative Doppler location estimation algorithm that is purported to be more accurate and generate a greater number of locations that its predecessor. We provide a comprehensive assessment of this new estimation process performance on data from free-ranging animals relative to concurrently collected Fastloc GPS data. Additionally, we test the efficacy of three readily-available SSM in predicting the movement of two focal animals. Raw Argos location estimates generated by the new algorithm were greatly improved compared to the old system. Approximately twice as many Argos locations were derived compared to GPS on the devices used. Root Mean Square Errors (RMSE) for each optimal SSM were less than 4.25 km with some producing RMSE of less than 2.50 km. Differences in the biological plausibility of the tracks between the two focal animals used to investigate the utility of SSM highlights the importance of considering animal behaviour in movement studies. The ability to reprocess Argos data collected since 2008 with the new algorithm should permit questions of animal movement to be revisited at a finer resolution.

Voluntary Co-Consumption of Alcohol and Nicotine: Effects of Abstinence, Intermittency, and Withdrawal in Mice

PubMed Central

O’Rourke, Kyu Y.; Touchette, Jillienne C.; Hartell, Elizabeth C.; Bade, Elizabeth J.; Lee, Anna M.

2018-01-01

Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. PMID:27342124

Cell Science and Cell Biology Research at MSFC: Summary

NASA Technical Reports Server (NTRS)

2003-01-01

The common theme of these research programs is that they investigate regulation of gene expression in cells, and ultimately gene expression is controlled by the macromolecular interactions between regulatory proteins and DNA. The NASA Critical Path Roadmap identifies Muscle Alterations and Atrophy and Radiation Effects as Very Serious Risks and Severe Risks, respectively, in long term space flights. The specific problem addressed by Dr. Young's research ("Skeletal Muscle Atrophy and Muscle Cell Signaling") is that skeletal muscle loss in space cannot be prevented by vigorous exercise. Aerobic skeletal muscles (i.e., red muscles) undergo the most extensive atrophy during long-term space flight. Of the many different potential avenues for preventing muscle atrophy, Dr. Young has chosen to study the beta-adrenergic receptor (betaAR) pathway. The reason for this choice is that a family of compounds called betaAR agonists will preferentially cause an increase in muscle mass of aerobic muscles (i.e., red muscle) in animals, potentially providing a specific pharmacological solution to muscle loss in microgravity. In addition, muscle atrophy is a widespread medical problem in neuromuscular diseases, spinal cord injury, lack of exercise, aging, and any disease requiring prolonged bedridden status. Skeletal muscle cells in cell culture are utilized as a model system to study this problem. Dr. Richmond's research ("Radiation & Cancer Biology of Mammary Cells in Culture") is directed toward developing a laboratory model for use in risk assessment of cancer caused by space radiation. This research is unique because a human model will be developed utilizing human mammary cells that are highly susceptible to tumor development. This approach is preferential over using animal cells because of problems in comparing radiation-induced cancers between humans and animals.

Increased cortical extracellular adenosine correlates with seizure termination.

PubMed

Van Gompel, Jamie J; Bower, Mark R; Worrell, Gregory A; Stead, Matt; Chang, Su-Youne; Goerss, Stephan J; Kim, Inyong; Bennet, Kevin E; Meyer, Fredric B; Marsh, W Richard; Blaha, Charles D; Lee, Kendall H

2014-02-01

Seizures are currently defined by their electrographic features. However, neuronal networks are intrinsically dependent on neurotransmitters of which little is known regarding their periictal dynamics. Evidence supports adenosine as having a prominent role in seizure termination, as its administration can terminate and reduce seizures in animal models. Furthermore, microdialysis studies in humans suggest that adenosine is elevated periictally, but the relationship to the seizure is obscured by its temporal measurement limitations. Because electrochemical techniques can provide vastly superior temporal resolution, we test the hypothesis that extracellular adenosine concentrations rise during seizure termination in an animal model and humans using electrochemistry. White farm swine (n = 45) were used in an acute cortical model of epilepsy, and 10 human epilepsy patients were studied during intraoperative electrocorticography (ECoG). Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS)-based fast scan cyclic voltammetry (FSCV) and fixed potential amperometry were obtained utilizing an adenosine-specific triangular waveform or biosensors, respectively. Simultaneous ECoG and electrochemistry demonstrated an average adenosine increase of 260% compared to baseline, at 7.5 ± 16.9 s with amperometry (n = 75 events) and 2.6 ± 11.2 s with FSCV (n = 15 events) prior to electrographic seizure termination. In agreement with these animal data, adenosine elevation prior to seizure termination in a human patient utilizing FSCV was also seen. Simultaneous ECoG and electrochemical recording supports the hypothesis that adenosine rises prior to seizure termination, suggesting that adenosine itself may be responsible for seizure termination. Future work using intraoperative WINCS-based FSCV recording may help to elucidate the precise relationship between adenosine and seizure termination. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Ineffectiveness of saxagliptin as a neuroprotective drug in 6-OHDA-lesioned rats.

PubMed

Turnes, Joelle de Melo; Bassani, Taysa Bervian; Souza, Leonardo C; Vital, Maria A B F

2018-05-16

To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats. Male Wistar rats (weighing 280-300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days. The motor function was evaluated using the open field and rotarod (RT) tests. In addition, cognition was assessed with the novel object recognition test (ORT). After the evaluation of the behavioural tests, the animals were transcardially perfused to perform immunohistochemistry staining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc). Saxagliptin impaired the memory of animals in the sham group. Saxagliptin treatment did not exhibit neuroprotection and it did not improve the cognitive and motor deficits in the 6-OHDA model of PD. Interestingly, when saxagliptin was administered to the sham animals, a cognitive decline was observed. Therefore, this drug should be investigated as a possible treatment for PTSD. © 2018 Royal Pharmaceutical Society.

Individual Pause-and-Go Motion Is Instrumental to the Formation and Maintenance of Swarms of Marching Locust Nymphs

PubMed Central

Ariel, Gil; Ophir, Yotam; Levi, Sagi; Ben-Jacob, Eshel; Ayali, Amir

2014-01-01

The principal interactions leading to the emergence of order in swarms of marching locust nymphs was studied both experimentally, using small groups of marching locusts in the lab, and using computer simulations. We utilized a custom tracking algorithm to reveal fundamental animal-animal interactions leading to collective motion. Uncovering this behavior introduced a new agent-based modeling approach in which pause-and-go motion is pivotal. The behavioral and modeling findings are largely based on motion-related visual sensory inputs obtained by the individual locust. Results suggest a generic principle, in which intermittent animal motion can be considered as a sequence of individual decisions as animals repeatedly reassess their situation and decide whether or not to swarm. This interpretation implies, among other things, some generic characteristics regarding the build-up and emergence of collective order in swarms: in particular, that order and disorder are generic meta-stable states of the system, suggesting that the emergence of order is kinetic and does not necessarily require external environmental changes. This work calls for further experimental as well as theoretical investigation of the neural mechanisms underlying locust coordinative behavior. PMID:24988464

An improved cost-effective, reproducible method for evaluation of bone loss in a rodent model.

PubMed

Fine, Daniel H; Schreiner, Helen; Nasri-Heir, Cibele; Greenberg, Barbara; Jiang, Shuying; Markowitz, Kenneth; Furgang, David

2009-02-01

This study was designed to investigate the utility of two "new" definitions for assessment of bone loss in a rodent model of periodontitis. Eighteen rats were divided into three groups. Group 1 was infected by Aggregatibacter actinomycetemcomitans (Aa), group 2 was infected with an Aa leukotoxin knock-out, and group 3 received no Aa (controls). Microbial sampling and antibody titres were determined. Initially, two examiners measured the distance from the cemento-enamel-junction to alveolar bone crest using the three following methods; (1) total area of bone loss by radiograph, (2) linear bone loss by radiograph, (3) a direct visual measurement (DVM) of horizontal bone loss. Two "new" definitions were adopted; (1) any site in infected animals showing bone loss >2 standard deviations above the mean seen at that site in control animals was recorded as bone loss, (2) any animal with two or more sites in any quadrant affected by bone loss was considered as diseased. Using the "new" definitions both evaluators independently found that infected animals had significantly more disease than controls (DVM system; p<0.05). The DVM method provides a simple, cost effective, and reproducible method for studying periodontal disease in rodents.

Biochemical, metabolic, and behavioral characteristics of immature chronic hyperphenylalanemic rats

PubMed Central

Dienel, Gerald A.; Cruz, Nancy F.

2015-01-01

Phenylketonuria and hyperphenylalanemia are inborn errors in metabolism of phenylalanine arising from defects in steps to convert phenylalanine to tyrosine. Phe accumulation causes severe mental retardation that can be prevented by timely identification of affected individuals and their placement on a Phe-restricted diet. In spite of many studies in patients and animal models, the basis for acquisition of mental retardation during the critical period of brain development is not adequately understood. All animal models for human disease have advantages and limitations, and characteristics common to different models are most likely to correspond to the disorder. This study established similar levels of Phe exposure in developing rats between 3 and 16 days of age using three models to produce chronic hyperphenylalanemia, and identified changes in brain amino acid levels common to all models that persist for ~16h of each day. In a representative model, local rates of glucose utilization (CMRglc) were determined at 25–27 days of age, and only selective changes that appeared to depend on Phe exposure were observed. CMRglc was reduced in frontal cortex and thalamus and increased in hippocampus and globus pallidus. Behavioral testing to evaluate neuromuscular competence revealed poor performance in chronically-hyperphenylalanemic rats that persisted for at least three weeks after cessation of Phe injections and did not occur with mild or acute hyperphenylalanemia. Thus, the abnormal amino acid environment, including hyperglycinemia, in developing rat brain is associated with selective regional changes in glucose utilization and behavioral abnormalities that are not readily reversed after they are acquired. PMID:26224289

Design and implementation of optical imaging and sensor systems for characterization of deep-sea biological camouflage

NASA Astrophysics Data System (ADS)

Haag, Justin Mathew

The visual ecology of deep-sea animals has long been of scientific interest. In the open ocean, where there is no physical structure to hide within or behind, diverse strategies have evolved to solve the problem of camouflage from a potential predator. Simulations of specific predator-prey scenarios have yielded estimates of the range of possible appearances that an animal may exhibit. However, there is a limited amount of quantitative information available related to both animal appearance and the light field at mesopelagic depths (200 m to 1000 m). To mitigate this problem, novel optical instrumentation, taking advantage of recent technological advances, was developed and is described in this dissertation. In the first half of this dissertation, the appearance of mirrored marine animals is quantitatively evaluated. A portable optical imaging scatterometer was developed to measure angular reflectance, described by the bidirectional reflectance distribution function (BRDF), of biological specimens. The instrument allows for BRDF capture from samples of arbitrary size, over a significant fraction of the reflectance hemisphere. Multiple specimens representing two species of marine animals, collected at mesopelagic depths, were characterized using the scatterometer. Low-dimensional parametric models were developed to simplify use of the data sets, and to validate the BRDF method. Results from principal component analysis confirm that BRDF measurements can be used to study intra- and interspecific variability of mirrored marine animal appearance. Collaborative efforts utilizing the BRDF data sets to develop physically-based scattering models are underway. In the second half of this dissertation, another key part of the deep-sea biological camouflage problem is examined. Two underwater radiometers, capable of low-light measurements, were developed to address the lack of available information related to the deep-sea light field. Quantitative comparison of spectral downward irradiance profiles at blue (~470~nm) and green (~560~nm) wavelengths, collected at Pacific and Atlantic field stations, provide insight into the presence of Raman (inelastic) scattering effects at mesopelagic depths. The radiometers were also used to collect in situ flashes of bioluminescence. Collaborations utilizing both the downward irradiance and bioluminescence data sets are planned.

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor.

PubMed

Zheng, X; Goodwin, A F; Tian, H; Jheon, A H; Klein, O D

2017-11-01

The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration. Utilizing models of Ras dysregulation as well as inhibitors of the MAPK and PI3K pathways, we found that MAPK and PI3K regulate dental epithelial stem cell activity, transit-amplifying cell proliferation, and enamel formation in the mouse incisor.

Optimal estimation of recurrence structures from time series

NASA Astrophysics Data System (ADS)

beim Graben, Peter; Sellers, Kristin K.; Fröhlich, Flavio; Hutt, Axel

2016-05-01

Recurrent temporal dynamics is a phenomenon observed frequently in high-dimensional complex systems and its detection is a challenging task. Recurrence quantification analysis utilizing recurrence plots may extract such dynamics, however it still encounters an unsolved pertinent problem: the optimal selection of distance thresholds for estimating the recurrence structure of dynamical systems. The present work proposes a stochastic Markov model for the recurrent dynamics that allows for the analytical derivation of a criterion for the optimal distance threshold. The goodness of fit is assessed by a utility function which assumes a local maximum for that threshold reflecting the optimal estimate of the system's recurrence structure. We validate our approach by means of the nonlinear Lorenz system and its linearized stochastic surrogates. The final application to neurophysiological time series obtained from anesthetized animals illustrates the method and reveals novel dynamic features of the underlying system. We propose the number of optimal recurrence domains as a statistic for classifying an animals' state of consciousness.

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.

PubMed

Del Prete, Gregory Q; Ailers, Braiden; Moldt, Brian; Keele, Brandon F; Estes, Jacob D; Rodriguez, Anthony; Sampias, Marissa; Oswald, Kelli; Fast, Randy; Trubey, Charles M; Chertova, Elena; Smedley, Jeremy; LaBranche, Celia C; Montefiori, David C; Burton, Dennis R; Shaw, George M; Markowitz, Marty; Piatak, Michael; KewalRamani, Vineet N; Bieniasz, Paul D; Lifson, Jeffrey D; Hatziioannou, Theodora

2014-09-10

Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

Behavioral assays to model cognitive and affective dimensions of depression and anxiety in rats

PubMed Central

Lapiz-Bluhm, M. Danet S.; Bondi, Corina O.; Doyen, Julianne; Rodriguez, Gustavo; Bédard-Arana, Tania; Morilak, David A.

2008-01-01

Animal models have been used extensively to investigate neuropsychiatric disorders, such as depression, and their treatment. However, the etiology and pathophysiology of many such disorders are largely unknown, which makes validation of animal models particularly challenging. Further, many diagnostic symptoms are difficult to define, operationalize and quantify, especially in experimental animals such as rats. Thus, rather than attempting to model such complex human syndromes as depression in their entirety, it can be more productive instead to define and model components of the illness that may account for clusters of co-varying symptoms, and that may share common underlying neurobiological mechanisms. In our preclinical investigations of the neural regulatory mechanisms linking stress to depression and anxiety disorders, as well as the mechanisms by which chronic treatment with antidepressant drugs may exert their beneficial effects in these conditions, we have employed a number of behavioral tests in rats to model specific cognitive and anxiety-like components of depression and anxiety disorders. In this paper, we review the procedures for conducting four such behavioral assays: the attentional set-shifting test, the elevated-plus maze, the social interaction test and the shock-probe defensive burying test. The purpose is to serve as a guide to the utility and limitations of these tools, and as an aid in optimizing their use and productivity. PMID:18673411

Model Organisms and Traditional Chinese Medicine Syndrome Models

PubMed Central

Xu, Jin-Wen

2013-01-01

Traditional Chinese medicine (TCM) is an ancient medical system with a unique cultural background. Nowadays, more and more Western countries due to its therapeutic efficacy are accepting it. However, safety and clear pharmacological action mechanisms of TCM are still uncertain. Due to the potential application of TCM in healthcare, it is necessary to construct a scientific evaluation system with TCM characteristics and benchmark the difference from the standard of Western medicine. Model organisms have played an important role in the understanding of basic biological processes. It is easier to be studied in certain research aspects and to obtain the information of other species. Despite the controversy over suitable syndrome animal model under TCM theoretical guide, it is unquestionable that many model organisms should be used in the studies of TCM modernization, which will bring modern scientific standards into mysterious ancient Chinese medicine. In this review, we aim to summarize the utilization of model organisms in the construction of TCM syndrome model and highlight the relevance of modern medicine with TCM syndrome animal model. It will serve as the foundation for further research of model organisms and for its application in TCM syndrome model. PMID:24381636

Sensory feedback in a bump attractor model of path integration.

PubMed

Poll, Daniel B; Nguyen, Khanh; Kilpatrick, Zachary P

2016-04-01

Mammalian spatial navigation systems utilize several different sensory information channels. This information is converted into a neural code that represents the animal's current position in space by engaging place cell, grid cell, and head direction cell networks. In particular, sensory landmark (allothetic) cues can be utilized in concert with an animal's knowledge of its own velocity (idiothetic) cues to generate a more accurate representation of position than path integration provides on its own (Battaglia et al. The Journal of Neuroscience 24(19):4541-4550 (2004)). We develop a computational model that merges path integration with feedback from external sensory cues that provide a reliable representation of spatial position along an annular track. Starting with a continuous bump attractor model, we explore the impact of synaptic spatial asymmetry and heterogeneity, which disrupt the position code of the path integration process. We use asymptotic analysis to reduce the bump attractor model to a single scalar equation whose potential represents the impact of asymmetry and heterogeneity. Such imperfections cause errors to build up when the network performs path integration, but these errors can be corrected by an external control signal representing the effects of sensory cues. We demonstrate that there is an optimal strength and decay rate of the control signal when cues appear either periodically or randomly. A similar analysis is performed when errors in path integration arise from dynamic noise fluctuations. Again, there is an optimal strength and decay of discrete control that minimizes the path integration error.

Mesenchymal stem cells protective effect in adriamycin model of nephropathy.

PubMed

Magnasco, Alberto; Corselli, Mirko; Bertelli, Roberta; Ibatici, Adalberto; Peresi, Monica; Gaggero, Gabriele; Cappiello, Valentina; Chiavarina, Barbara; Mattioli, Girolamo; Gusmano, Rosanna; Ravetti, Jean Louis; Frassoni, Francesco; Ghiggeri, Gian Marco

2008-01-01

Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue after damage; however, lack of biological knowledge and variability of results in animal models limit their utilization. We studied the effects of MSCs on podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal toxicity. The in vivo experimental approach was carried out in male Sprague-Dawley rats (overall 60 animals) treated with different ADR schemes to induce acute and chronic nephrosis. MSCs were given a) concomitantly to ADR in tail vein or b) in aorta and c) in tail vein 60 days after ADR. Homing was assessed with PKH26-MSCs. MSCs rescued podocytes from apoptosis induced by ADR in vitro. The maximal effect (80% rescue) was obtained with MSCs/podocytes coculture ratio of 1:1 for 72 h. All rats treated with ADR developed nephrosis. MSCs did not modify the clinical parameters (i.e., proteinuria, serum creatinine, lipids) but protected the kidney from severe glomerulosclerosis when given concomitantly to ADR. Rats given MSCs 60 days after ADR developed the same severe renal damage. Only a few MSCs were found in renal tubule-interstitial areas 1-24 h after injection and no MSCs were detected in glomeruli. MSCs reduced apoptosis of podocytes treated with ADR in vitro. Early and repeated MSCs infusion blunted glomerular damage in chronic ADR-induced nephropathy. MSCs did not modify proteinuria and progression to renal failure, which implies lack of regenerative potential in this model.

Habitat Use and Selection by Giant Pandas.

PubMed

Hull, Vanessa; Zhang, Jindong; Huang, Jinyan; Zhou, Shiqiang; Viña, Andrés; Shortridge, Ashton; Li, Rengui; Liu, Dian; Xu, Weihua; Ouyang, Zhiyun; Zhang, Hemin; Liu, Jianguo

2016-01-01

Animals make choices about where to spend their time in complex and dynamic landscapes, choices that reveal information about their biology that in turn can be used to guide their conservation. Using GPS collars, we conducted a novel individual-based analysis of habitat use and selection by the elusive and endangered giant pandas (Ailuropoda melanoleuca). We constructed spatial autoregressive resource utilization functions (RUF) to model the relationship between the pandas' utilization distributions and various habitat characteristics over a continuous space across seasons. Results reveal several new insights, including use of a broader range of habitat characteristics than previously understood for the species, particularly steep slopes and non-forest areas. We also used compositional analysis to analyze habitat selection (use with respect to availability of habitat types) at two selection levels. Pandas selected against low terrain position and against the highest clumped forest at the at-home range level, but no significant factors were identified at the within-home range level. Our results have implications for modeling and managing the habitat of this endangered species by illustrating how individual pandas relate to habitat and make choices that differ from assumptions made in broad scale models. Our study also highlights the value of using a spatial autoregressive RUF approach on animal species for which a complete picture of individual-level habitat use and selection across space is otherwise lacking.

Habitat Use and Selection by Giant Pandas

PubMed Central

Hull, Vanessa; Zhang, Jindong; Huang, Jinyan; Zhou, Shiqiang; Viña, Andrés; Shortridge, Ashton; Li, Rengui; Liu, Dian; Xu, Weihua; Ouyang, Zhiyun; Zhang, Hemin; Liu, Jianguo

2016-01-01

Animals make choices about where to spend their time in complex and dynamic landscapes, choices that reveal information about their biology that in turn can be used to guide their conservation. Using GPS collars, we conducted a novel individual-based analysis of habitat use and selection by the elusive and endangered giant pandas (Ailuropoda melanoleuca). We constructed spatial autoregressive resource utilization functions (RUF) to model the relationship between the pandas' utilization distributions and various habitat characteristics over a continuous space across seasons. Results reveal several new insights, including use of a broader range of habitat characteristics than previously understood for the species, particularly steep slopes and non-forest areas. We also used compositional analysis to analyze habitat selection (use with respect to availability of habitat types) at two selection levels. Pandas selected against low terrain position and against the highest clumped forest at the at-home range level, but no significant factors were identified at the within-home range level. Our results have implications for modeling and managing the habitat of this endangered species by illustrating how individual pandas relate to habitat and make choices that differ from assumptions made in broad scale models. Our study also highlights the value of using a spatial autoregressive RUF approach on animal species for which a complete picture of individual-level habitat use and selection across space is otherwise lacking. PMID:27627805

Preclinical Performance Evaluation of Percutaneous Glucose Biosensors: Experimental Considerations and Recommendations.

PubMed

Soto, Robert J; Schoenfisch, Mark H

2015-06-17

The utility of continuous glucose monitoring devices remains limited by an obstinate foreign body response (FBR) that degrades the analytical performance of the in vivo sensor. A number of novel materials that resist or delay the FBR have been proposed as outer, tissue-contacting glucose sensor membranes as a strategy to improve sensor accuracy. Traditionally, researchers have examined the ability of a material to minimize the host response by assessing adsorbed cell morphology and tissue histology. However, these techniques do not adequately predict in vivo glucose sensor function, necessitating sensor performance evaluation in a relevant animal model prior to human testing. Herein, the effects of critical experimental parameters, including the animal model and data processing methods, on the reliability and usefulness of preclinical sensor performance data are considered. © 2015 Diabetes Technology Society.

Comparing immunocompetent and immunodeficient mice as animal models for bone tissue engineering.

PubMed

Zhang, Y; Li, X; Chihara, T; Mizoguchi, T; Hori, A; Udagawa, N; Nakamura, H; Hasegawa, H; Taguchi, A; Shinohara, A; Kagami, H

2015-07-01

To understand the differences and similarities between immunocompetent and immunodeficient mice as ectopic transplantation animal models for bone tissue engineering. Osteogenic cells from mouse leg bones were cultured, seeded on β-TCP granules, and transplanted onto the backs of either immunocompetent or immunodeficient nude mice. At 1, 2, 4, and 8 weeks postoperatively, samples were harvested and evaluated by hematoxylin-eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemical staining and quantitative PCR. In immunocompetent mice, inflammatory cell infiltration was evident at 1 week postoperatively and relatively higher expression of TNF-α and IL-4 was observed. In immunodeficient mice, new bone area and the number of TRAP-positive cells were larger at 4 weeks than in immunocompetent mice. The volume of new bone area in immunodeficient mice was reduced by 8 weeks. Bone regeneration was feasible in immunocompetent mice. However, some differences were observed between immunocompetent and immunodeficient mice in the bone regeneration process possibly due to different cytokine expression, which should be considered when utilizing in vivo animal models. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The development of an instrument to match individuals with disabilities and service animals.

PubMed

Zapf, S A; Rough, R B

There has been an increase in the use of service animals assisting persons with disabilities in the past decade. However many of the service dog agencies do not utilize an assessment that is designed to match the person to the animal in the rehabilitation and psycho-social domains. The purpose of this study was to develop the Service Animal Adaptive Intervention Assessment (SAAIA) and to measure the content validity, inter-rater reliability and clinical utility of the assessment. Two subject groups were used. Subject group one had 43 subjects who measured the content validity and clinical utility of the SAAIA Survey. Subject group two had 12 subjects who measured the inter-rater reliability by completing the SAAIA using information obtained through a video-taped client case scenario. Content validity results indicated a good to high percentage of agreement and a fair percentage of agreement for clinical utility. Inter-rater reliability results indicate good to high agreement on six of the eight variables of the SAAIA. However, the Kappa score indicates low inter-rater reliability. Results indicate the SAAIA has good content validity and inter-rater reliability and fair clinical utility based on percent agreement. However, further research is needed on the reliability of the SAAIA.

Voluntary exercise enhances activity rhythms and ameliorates anxiety- and depression-like behaviors in the sand rat model of circadian rhythm-related mood changes.

PubMed

Tal-Krivisky, Katy; Kronfeld-Schor, Noga; Einat, Haim

2015-11-01

Physical exercise is a non-pharmacological treatment for affective disorders. The mechanisms of its effects are unknown although some suggest a relationship to synchronization of circadian rhythms. One way to explore mechanisms is to utilize animal models. We previously demonstrated that the diurnal fat sand rat is an advantageous model for studying the interactions between photoperiods and mood. The current study was designed to evaluate the effects of voluntary exercise on activity rhythms and anxiety and depression-like behaviors in sand rats as a step towards better understanding of the underlying mechanisms. Male sand rats were housed in short photoperiod (SP; 5h light/19 h dark) or neutral light (NP; 12h light/12h dark) regimens for 3 weeks and divided into subgroups with or without running wheels. Activity was monitored for 3 additional weeks and then animals were tested in the elevated plus-maze, the forced swim test and the social interaction test. Activity rhythms were enhanced by the running wheels. As hypothesized, voluntary exercise had significant effects on SP animals' anxiety- and depression-like behaviors but not on NP animals. Results are discussed in the context of interactions between physical exercise, circadian rhythms and mood. We suggest that the sand rat model can be used to explore the underlying mechanism of the effects of physical exercise for mood disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics.

PubMed

Marmarou, A; Foda, M A; van den Brink, W; Campbell, J; Kita, H; Demetriadou, K

1994-02-01

This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.

Evaluating the Efficacy of an Animation to Enhance Understanding of First Motion Diagrams

NASA Astrophysics Data System (ADS)

Farmer, E. C.

2011-12-01

Having taught the interpretation of first motion diagrams (sometimes referred to as "beach ball diagrams" due to their appearance) in an Introduction to Physical Geology class over many semesters, I was frustrated with the hand-waving this effort entailed when describing static diagrams. I searched for a computer animation that would show how the initial ground motions in an earthquake correspond to the various shaded regions in each first motion diagram, but was not able to find such a pedagogical tool in existence. I decided to work with the staff of my University's Faculty Computing Services to create something that would serve this need. We designed and constructed an animation of strike-slip motions, which can be seen at http://people.hofstra.edu/alex_smiros/earthquake/grid_22march2011.swf. A still image of the animation appears in Figure 1. In order to see if utilizing this visualization enhanced student understanding of the difficult concepts involved in interpreting first motion diagrams, I compared scores on test questions involving first motion diagrams from two different semester iterations of the course: one was taught without utilizing the animation, and one was taught with utilization of the animation.

Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis.

PubMed

Zhang, Chenyu; Lowery, Frank J; Yu, Dihua

2017-02-08

Metastasis, the spread and growth of malignant cells at secondary sites within a patient's body, accounts for > 90% of cancer-related mortality. Recently, impressive advances in novel therapies have dramatically prolonged survival and improved quality of life for many cancer patients. Sadly, incidence of brain metastatic recurrences is fast rising, and all current therapies are merely palliative. Hence, good experimental animal models are urgently needed to facilitate in-depth studies of the disease biology and to assess novel therapeutic regimens for preclinical evaluation. However, the standard in vivo metastasis assay via tail vein injection of cancer cells produces predominantly lung metastatic lesions; animals usually succumb to the lung tumor burden before any meaningful outgrowth of brain metastasis. Intracardiac injection of tumor cells produces metastatic lesions to multiple organ sites including the brain; however, the variability of tumor growth produced with this model is large, dampening its utility in evaluating therapeutic efficacy. To generate reliable and consistent animal models for brain metastasis study, here we describe a procedure for producing experimental brain metastasis in the house mouse (Mus musculus) via intracarotid injection of tumor cells. This approach allows one to produce large number of brain metastasis-bearing mice with similar growth and mortality characteristics, thus facilitating research efforts to study basic biological mechanisms and to assess novel therapeutic agents.

Gut Microbiome Standardization in Control and Experimental Mice.

PubMed

McCoy, Kathy D; Geuking, Markus B; Ronchi, Francesca

2017-04-03

Mouse models are used extensively to study human health and to investigate the mechanisms underlying human disease. In the past, most animal studies were performed without taking into consideration the impact of the microbiota. However, the microbiota that colonizes all body surfaces, including the gastrointestinal tract, respiratory tract, genitourinary tract, and skin, heavily impacts nearly every aspect of host physiology. When performing studies utilizing mouse models it is critical to understand that the microbiome is heavily impacted by environmental factors, including (but not limited to) food, bedding, caging, and temperature. In addition, stochastic changes in the microbiota can occur over time that also play a role in shaping microbial composition. These factors lead to massive variability in the composition of the microbiota between animal facilities and research institutions, and even within a single facility. Lack of experimental reproducibility between research groups has highlighted the necessity for rigorously controlled experimental designs in order to standardize the microbiota between control and experimental animals. Well controlled experiments are mandatory in order to reduce variability and allow correct interpretation of experimental results, not just of host-microbiome studies but of all mouse models of human disease. The protocols presented are aimed to design experiments that control the microbiota composition between different genetic strains of experimental mice within an animal unit. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Biomedical Research and the Animal Rights Movement: A Contrast in Values.

ERIC Educational Resources Information Center

Morrison, Adrian R.

1993-01-01

This article explains how animals are used in research in an effort to counteract animal rights literature. Reveals how medical professionals and others trained in scholarship have misquoted the scientific literature to bolster their claims against the utility of animal research. (PR)

Modeling menopause: The utility of rodents in translational behavioral endocrinology research.

PubMed

Koebele, Stephanie V; Bimonte-Nelson, Heather A

2016-05-01

The human menopause transition and aging are each associated with an increase in a variety of health risk factors including, but not limited to, cardiovascular disease, osteoporosis, cancer, diabetes, stroke, sexual dysfunction, affective disorders, sleep disturbances, and cognitive decline. It is challenging to systematically evaluate the biological underpinnings associated with the menopause transition in the human population. For this reason, rodent models have been invaluable tools for studying the impact of gonadal hormone fluctuations and eventual decline on a variety of body systems. While it is essential to keep in mind that some of the mechanisms associated with aging and the transition into a reproductively senescent state can differ when translating from one species to another, animal models provide researchers with opportunities to gain a fundamental understanding of the key elements underlying reproduction and aging processes, paving the way to explore novel pathways for intervention associated with known health risks. Here, we discuss the utility of several rodent models used in the laboratory for translational menopause research, examining the benefits and drawbacks in helping us to better understand aging and the menopause transition in women. The rodent models discussed are ovary-intact, ovariectomy, and 4-vinylcylohexene diepoxide for the menopause transition. We then describe how these models may be implemented in the laboratory, particularly in the context of cognition. Ultimately, we aim to use these animal models to elucidate novel perspectives and interventions for maintaining a high quality of life in women, and to potentially prevent or postpone the onset of negative health consequences associated with these significant life changes during aging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Constant-parameter capture-recapture models

USGS Publications Warehouse

Brownie, C.; Hines, J.E.; Nichols, J.D.

1986-01-01

Jolly (1982, Biometrics 38, 301-321) presented modifications of the Jolly-Seber model for capture-recapture data, which assume constant survival and/or capture rates. Where appropriate, because of the reduced number of parameters, these models lead to more efficient estimators than the Jolly-Seber model. The tests to compare models given by Jolly do not make complete use of the data, and we present here the appropriate modifications, and also indicate how to carry out goodness-of-fit tests which utilize individual capture history information. We also describe analogous models for the case where young and adult animals are tagged. The availability of computer programs to perform the analysis is noted, and examples are given using output from these programs.

The Pregnant Sheep as a Model for Human Pregnancy

PubMed Central

Barry, James S.; Anthony, Russell V.

2008-01-01

Successful outcome of human pregnancy not only impacts the quality of infant life and well-being, but considerable evidence now suggests that what happens during fetal development may well impact health and well-being into adulthood. Consequently, a thorough understanding of the developmental events that occur between conception and delivery is needed. For obvious ethical reasons, many of the questions remaining about the progression of human pregnancy can not be answered directly, necessitating the use of appropriate animal models. A variety of animal models exist for the study of both normal and compromised pregnancies, including laboratory rodents, non-human primates and domestic ruminants. While all of these animal models have merit, most suffer from the inability to repetitively sample from both the maternal and fetal side of the placenta, limiting their usefulness in the study of placental or fetal physiology under non-stressed in vivo conditions. No animal model truly recapitulates human pregnancy, yet the pregnant sheep has been used extensively to investigate maternal-fetal interactions. This is due in part to the ability to surgically place and maintain catheters in both the maternal and fetal vasculature, allowing repeated sampling from non-anesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep. These findings were often confirmed in human pregnancies once appropriate technologies became available. The purpose of this review is to provide an overview of human and sheep pregnancy, with emphasis placed on placental development and function as an organ of nutrient transfer. PMID:17976713

Influence of indigenous microbiota on experimental toxoplasmosis in conventional and germ-free mice.

PubMed

Nascimento, Bruna B; Cartelle, Christiane T; Noviello, Maria de L; Pinheiro, Breno V; de Almeida Vitor, Ricardo W; Souza, Danielle da G; de Vasconcelos Generoso, Simone; Cardoso, Valbert N; Martins, Flaviano Dos S; Nicoli, Jacques R; Arantes, Rosa M E

2017-08-01

Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii, causes a severe innate pro-inflammatory response. The indigenous intestinal microbiota promotes host animal homoeostasis and may protect the host against pathogens. Germ-free (GF) animals provide an important tool for the study of interactions between host and microbiota. In this study, we assessed the role of indigenous microorganisms in disease development utilizing a murine toxoplasmosis model, which includes conventional (CV) and GF NIH Swiss mice. CV and GF mice orally inoculated with T. gondii had similar survival curves. However, disease developed differently in the two animal groups. In CV mice, intestinal permeability increased and levels of intestinal pro-inflammatory cytokines were altered. In GF animals, there were discrete epithelial degenerative changes and mucosal oedema, but the liver and lungs displayed significant lesions. We conclude that, despite similar survival curves, CV animals succumb to an exaggerated inflammatory response, whereas GF mice fail to produce an adequate systemic response. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

PubMed

Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

2018-02-01

This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

Guinea pig adenovirus infection does not inhibit cochlear transfection with human adenoviral vectors in a model of hearing loss.

PubMed

Hankenson, F Claire; Wathen, Asheley B; Eaton, Kathryn A; Miyazawa, Toru; Swiderski, Donald L; Raphael, Yehoash

2010-04-01

Routine surveillance of guinea pigs maintained within a barrier facility detected guinea pig adenovirus (GPAdV) in sentinel animals. These guinea pigs served as models of induced hearing loss followed by regeneration of cochlear sensory (hair) cells through transdifferentiation of nonsensory cells by using human adenoviral (hAV) gene therapy. To determine whether natural GPAdV infection affected the ability of hAV vectors to transfect inner ear cells, adult male pigmented guinea pigs (n = 7) were enrolled in this study because of their prolonged exposure to GPAdV-seropositive conspecifics. Animals were deafened chemically (n = 2), received an hAV vector carrying the gene for green fluorescent protein (hAV-GFP) surgically without prior deafening (n = 2), or were deafened chemically with subsequent surgical inoculation of hAV-GFP (n = 3). Cochleae were evaluated by using fluorescence microscopy, and GFP expression in supporting cells indicated that the hAV-GFP vector was able to transfect inner ears in GPAdV-seropositive guinea pigs that had been chemically deafened. Animals had histologic evidence of interstitial pneumonia, attributable to prior infection with GPAdV. These findings confirmed that the described guinea pigs were less robust animal models with diminished utility for the overall studies. Serology tests confirmed that 5 of 7 animals (71%) were positive for antibodies against GPAdV at necropsy, approximately 7 mo after initial detection of sentinel infection. Control animals (n = 5) were confirmed to be seronegative for GPAdV with clinically normal pulmonary tissue. This study is the first to demonstrate that natural GPAdV infection does not negatively affect transfection with hAV vectors into guinea pig inner ear cells, despite the presence of other health complications attributed to the viral infection.

A novel open-source drug-delivery system that allows for first-of-kind simulation of nonadherence to pharmacological interventions in animal disease models.

PubMed

Thomson, Kyle E; White, H Steve

2014-12-30

Nonadherence to a physician-prescribed therapeutic intervention is a costly, dangerous, and sometimes fatal concern in healthcare. To date, the study of nonadherence has been constrained to clinical studies. The novel approach described herein allows for the preclinical study of nonadherence in etiologically relevant disease animal model systems. The method herein describes a novel computer-automated pellet delivery system which allows for the study of nonadherence in animals. This system described herein allows for tight experimenter control of treatment using a drug-in-food protocol. Food-restricted animals receive either medicated or unmedicated pellets, designed to mimic either "taking" or "missing" a drug. The system described permits the distribution of medicated or unmedicated food pellets on an experimenter-defined feeding schedule. The flexibility of this system permits the delivery of drug according to the known pharmacokinetics of investigational drugs. Current clinical adherence research relies on medication-event monitoring system (MEMS) tracking caps, which allows clinicians to directly monitor patient adherence. However, correlating the effects of nonadherence to efficacy still relies on the accuracy of patient journals. This system allows for the design of studies to address the impact of nonadherence in an etiologically relevant animal model. Given methodological and ethical concerns of designing clinical studies of nonadherence, animal studies are critical to better understand medication adherence. While the system described was designed to measure the impact of nonadherence on seizure control, it is clear that the utility of this system extends beyond epilepsy to include other disease states. Copyright © 2014 Elsevier B.V. All rights reserved.

Culture-independent Profiling of the Fecal Microbiome to Identify Microbial Species Associated with a Diarrheal Outbreak in Immunocompromised Mice.

PubMed

Misic, Ana M; Miedel, Emily L; Brice, Angela K; Cole, Stephen; Zhang, Grace F; Dyer, Cecilia D; Secreto, Anthony; Smith, Abigail L; Danet-Desnoyers, Gwenn; Beiting, Daniel P

2018-06-13

Immunocompromised mice are used frequently in biomedical research, in part because they accommodate the engraftmentandstudy of primary human cells within a mouse model; however, these animals are susceptible to opportunistic infectionsand require special husbandry considerations. In 2015, an outbreak marked by high morbidity but low mortality swept througha colony of immunocompromised mice; this outbreak rapidly affected 75% of the colony and ultimately required completedepopulation of the barrier suite. Conventional microbiologic and molecular diagnostics were unsuccessful in determiningthe cause; therefore, we explored culture-independent methods to broadly profile the microbial community in the feces of affected animals. This approach identified 4 bacterial taxa-Candidatus Arthromitus, Clostridium celatum, Clostridiales bacterium VE202-01, and Bifidobacterium pseudolongum strain PV8-2- that were significantly enriched in the affected mice. Based on these results, specific changes were made to the animal husbandry procedures for immunocompromised mice. This case report highlights the utility of culture-independent methods in laboratory animal diagnostics.

Stem cells and regenerative medicine in domestic and companion animals: a multispecies perspective.

PubMed

Gonçalves, N N; Ambrósio, C E; Piedrahita, J A

2014-10-01

Since their original isolation, the majority of the work on embryonic stem cells (ESC) has been carried out in mice. While the mouse is an outstanding model for basic research, it also has considerable limitations for translational work, especially in the area of regenerative medicine. This is due to a combination of factors that include physiological and size differences when compared to humans. In contrast, domestic animal species, such as swine, and companion animal species, such as dogs, provide unique opportunities to develop regenerative medicine protocols that can then be utilized in humans. Unfortunately, at present, the state of knowledge related to, and availability of, ESC from domestic animals vary among species such as pig, horse, dog and cat, and without exception lags significantly behind the mouse and human. It is clear that much still needs to be discovered. The 'stem cell-like' cell lines being reported are still not satisfactorily used in regenerative medicine, due to reasons such as heterogeneity and chromosomal instability. As a result, investigators have searched for alternate source of cells that can be used for regenerative medicine. This approach has uncovered a range of adult stem cells and adult progenitor cells that have utility in both human and veterinary medicine. Here, we review a range of stem cells, from ESC to induced pluripotent stem cells, and discuss their potential application in the field of regenerative medicine. © 2014 Blackwell Verlag GmbH.

Right Ventricular Longitudinal Strain Is Depressed in a Bovine Model of Pulmonary Hypertension.

PubMed

Bartels, Karsten; Brown, R Dale; Fox, Daniel L; Bull, Todd M; Neary, Joseph M; Dorosz, Jennifer L; Fonseca, Brian M; Stenmark, Kurt R

2016-05-01

Pulmonary hypertension and resulting right ventricular (RV) dysfunction are associated with significant perioperative morbidity and mortality. Although echocardiography permits real-time, noninvasive assessment of RV function, objective and comparative measures are underdeveloped, and appropriate animal models to study their utility are lacking. Longitudinal strain analysis is a novel echocardiographic method to quantify RV performance. Herein, we hypothesized that peak RV longitudinal strain would worsen in a bovine model of pulmonary hypertension compared with control animals. Newborn Holstein calves were randomly chosen for induction of pulmonary hypertension versus control conditions. Pulmonary hypertension was induced by exposing animals to 14 days of hypoxia (equivalent to 4570 m above sea level or 430 mm Hg barometric pressure). Control animals were kept at ambient pressure/normoxia. At the end of the intervention, transthoracic echocardiography was performed in awake calves. Longitudinal wall strain was analyzed from modified apical 4-chamber views focused on the RV. Comparisons between measurements in hypoxic versus nonhypoxic conditions were performed using Student t test for independent samples and unequal variances. After 14 days at normoxic versus hypoxic conditions, 15 calves were examined with echocardiography. Pulmonary hypertension was confirmed by right heart catheterization and associated with reduced RV systolic function. Mean systolic strain measurements were compared in normoxia-exposed animals (n = 8) and hypoxia-exposed animals (n = 7). Peak global systolic longitudinal RV strain after hypoxia worsened compared to normoxia (-10.5% vs -16.1%, P = 0.0031). Peak RV free wall strain also worsened after hypoxia compared to normoxia (-9.6% vs -17.3%, P = 0.0031). Findings from strain analysis were confirmed by measurement of tricuspid annular peak systolic excursion. Peak longitudinal RV strain detected worsened RV function in animals with hypoxia-induced pulmonary hypertension compared with control animals. This relationship was demonstrated in the transthoracic echocardiographic 4-chamber view independently for the RV free wall and for the combination of the free and septal walls. This innovative model of bovine pulmonary hypertension may prove useful to compare different monitoring technologies for the assessment of early events of RV dysfunction. Further studies linking novel RV imaging applications with mechanistic and therapeutic approaches are needed.

Effects of HIV-1 on Cognition in Humanized NSG Mice

NASA Astrophysics Data System (ADS)

Akhter, Sidra Pervez

Host species specificity of human immunodeficiency virus (HIV) creates a challenge to study the pathology, diagnostic tools, and therapeutic agents. The closely related simian immunodeficiency virus and studies of neurocognitive impairments on transgenic animals expressing partial viral genome have significant limitations. The humanized mice model provides a small animal system in which a human immune system can be engrafted and immunopathobiology of HIV-1 infection can be studied. However, features of HIV-associated neurocognitive disorders (HAND) were not evaluated in this model. Open field activity test was selected to characterize behavior of original strain NOD/scid-IL-2Rgammac null (NSG) mice, effects of engraftment of human CD34+ hematopoietic stem cells (HSCs) and functional human immune system (huNSG), and finally, investigate the behavior changes induced by chronic HIV-1 infection. Long-term infected HuNSG mice showed the loss of working memory and increased anxiety in the open field. Additionally, these animals were utilized for evaluation of central nervous system metabolic and structural changes. Detected behavioral abnormalities are correlated with obtained neuroimaging and histological abnormalities published.

Measurement of nasal patency in anesthetized and conscious dogs.

PubMed

Koss, Michael C; Yu, Yongxin; Hey, John A; McLeod, Robbie L

2002-02-01

Experiments were undertaken to characterize a noninvasive chronic, model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Compound 48/80 was administered intranasally to elicit nasal congestion in five beagle dogs either by syringe (0.5 ml) in thiopental sodium-anesthetized animals or as a mist (0.25 ml) in the same animals in the conscious state. Effects of mast cell degranulation on nasal cavity volume as well as on minimal cross-sectional area (A(min)) and intranasal distance to A(min) (D(min)) were studied. Compound 48/80 caused a dose-related decrease in nasal cavity volume and A(min) together with a variable increase in D(min). Maximal responses were seen at 90-120 min. Compound 48/80 was less effective in producing nasal congestion in conscious animals, which also had significantly larger basal nasal cavity volumes. These results demonstrate the utility of using acoustic rhinometry to measure parameters of nasal patency in dogs and suggest that this model may prove useful in studies of the actions of decongestant drugs.

From Lévy to Brownian: A Computational Model Based on Biological Fluctuation

PubMed Central

Nurzaman, Surya G.; Matsumoto, Yoshio; Nakamura, Yutaka; Shirai, Kazumichi; Koizumi, Satoshi; Ishiguro, Hiroshi

2011-01-01

Background Theoretical studies predict that Lévy walks maximizes the chance of encountering randomly distributed targets with a low density, but Brownian walks is favorable inside a patch of targets with high density. Recently, experimental data reports that some animals indeed show a Lévy and Brownian walk movement patterns when forage for foods in areas with low and high density. This paper presents a simple, Gaussian-noise utilizing computational model that can realize such behavior. Methodology/Principal Findings We extend Lévy walks model of one of the simplest creature, Escherichia coli, based on biological fluctuation framework. We build a simulation of a simple, generic animal to observe whether Lévy or Brownian walks will be performed properly depends on the target density, and investigate the emergent behavior in a commonly faced patchy environment where the density alternates. Conclusions/Significance Based on the model, animal behavior of choosing Lévy or Brownian walk movement patterns based on the target density is able to be generated, without changing the essence of the stochastic property in Escherichia coli physiological mechanism as explained by related researches. The emergent behavior and its benefits in a patchy environment are also discussed. The model provides a framework for further investigation on the role of internal noise in realizing adaptive and efficient foraging behavior. PMID:21304911

Gene-environment interactions and construct validity in preclinical models of psychiatric disorders.

PubMed

Burrows, Emma L; McOmish, Caitlin E; Hannan, Anthony J

2011-08-01

The contributions of genetic risk factors to susceptibility for brain disorders are often so closely intertwined with environmental factors that studying genes in isolation cannot provide the full picture of pathogenesis. With recent advances in our understanding of psychiatric genetics and environmental modifiers we are now in a position to develop more accurate animal models of psychiatric disorders which exemplify the complex interaction of genes and environment. Here, we consider some of the insights that have emerged from studying the relationship between defined genetic alterations and environmental factors in rodent models. A key issue in such animal models is the optimization of construct validity, at both genetic and environmental levels. Standard housing of laboratory mice and rats generally includes ad libitum food access and limited opportunity for physical exercise, leading to metabolic dysfunction under control conditions, and thus reducing validity of animal models with respect to clinical populations. A related issue, of specific relevance to neuroscientists, is that most standard-housed rodents have limited opportunity for sensory and cognitive stimulation, which in turn provides reduced incentive for complex motor activity. Decades of research using environmental enrichment has demonstrated beneficial effects on brain and behavior in both wild-type and genetically modified rodent models, relative to standard-housed littermate controls. One interpretation of such studies is that environmentally enriched animals more closely approximate average human levels of cognitive and sensorimotor stimulation, whereas the standard housing currently used in most laboratories models a more sedentary state of reduced mental and physical activity and abnormal stress levels. The use of such standard housing as a single environmental variable may limit the capacity for preclinical models to translate into successful clinical trials. Therefore, there is a need to optimize 'environmental construct validity' in animal models, while maintaining comparability between laboratories, so as to ensure optimal scientific and medical outcomes. Utilizing more sophisticated models to elucidate the relative contributions of genetic and environmental factors will allow for improved construct, face and predictive validity, thus facilitating the identification of novel therapeutic targets. Copyright © 2010 Elsevier Inc. All rights reserved.

Mathematics as a conduit for translational research in post-traumatic osteoarthritis.

PubMed

Ayati, Bruce P; Kapitanov, Georgi I; Coleman, Mitchell C; Anderson, Donald D; Martin, James A

2017-03-01

Biomathematical models offer a powerful method of clarifying complex temporal interactions and the relationships among multiple variables in a system. We present a coupled in silico biomathematical model of articular cartilage degeneration in response to impact and/or aberrant loading such as would be associated with injury to an articular joint. The model incorporates fundamental biological and mechanical information obtained from explant and small animal studies to predict post-traumatic osteoarthritis (PTOA) progression, with an eye toward eventual application in human patients. In this sense, we refer to the mathematics as a "conduit of translation." The new in silico framework presented in this paper involves a biomathematical model for the cellular and biochemical response to strains computed using finite element analysis. The model predicts qualitative responses presently, utilizing system parameter values largely taken from the literature. To contribute to accurate predictions, models need to be accurately parameterized with values that are based on solid science. We discuss a parameter identification protocol that will enable us to make increasingly accurate predictions of PTOA progression using additional data from smaller scale explant and small animal assays as they become available. By distilling the data from the explant and animal assays into parameters for biomathematical models, mathematics can translate experimental data to clinically relevant knowledge. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:566-572, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Sex Steroid Modulation of Fatty Acid Utilization and Fatty Acid Binding Protein Concentration in Rat Liver

PubMed Central

Ockner, Robert K.; Lysenko, Nina; Manning, Joan A.; Monroe, Scott E.; Burnett, David A.

1980-01-01

The mechanism by which sex steroids influence very low density hepatic lipoprotein triglyceride production has not been fully elucidated. In previous studies we showed that [14C]oleate utilization and incorporation into triglycerides were greater in hepatocyte suspensions from adult female rats than from males. The sex differences were not related to activities of the enzymes of triglyceride biosynthesis, whereas fatty acid binding protein (FABP) concentration in liver cytosol was greater in females. These findings suggested that sex differences in lipoprotein could reflect a sex steroid influence on the availability of fatty acids for hepatocellular triglyceride biosynthesis. In the present studies, sex steroid effects on hepatocyte [14C]oleate utilization and FABP concentration were investigated directly. Hepatocytes from immature (30-d-old) rats exhibited no sex differences in [14C]oleate utilization. With maturation, total [14C]oleate utilization and triglyceride biosynthesis increased moderately in female cells and decreased markedly in male cells; the profound sex differences in adults were maximal by age 60 d. Fatty acid oxidation was little affected. Rats were castrated at age 30 d, and received estradiol, testosterone, or no hormone until age 60 d, when hepatocyte [14C]oleate utilization was studied. Castration virtually eliminated maturational changes and blunted the sex differences in adults. Estradiol or testosterone largely reproduced the appropriate adult pattern of [14C]oleate utilization regardless of the genotypic sex of the treated animal. In immature females and males, total cytosolic FABP concentrations were similar. In 60-d-old animals, there was a striking correlation among all groups (females, males, castrates, and hormone-treated) between mean cytosolic FABP concentration on the one hand, and mean total [14C]oleate utilization (r = 0.91) and incorporation into triglycerides (r = 0.94) on the other. In 30-d-old animals rates of [14C]oleate utilization were greater, relative to FABP concentrations, than in 60-d-old animals. The sex differences that characterize fatty acid utilization in adult rat hepatocytes are not present in cells from immature animals, and reflect in part the influence of sex steroids. It remains to be determined whether the observed relationship of hepatic FABP concentration to [14C]oleate utilization in adult cells is causal or secondary to changes in cellular fatty acid uptake effected through another mechanism. In either case, modulation of triglyceride-rich lipoprotein production by six steroids appears to be mediated to a significant extent by their effects on hepatic fatty acid utilization. PMID:7364935

Utilization of solar radiation by polar animals: an optical model for pelts.

PubMed

Grojean, R E; Sousa, J A; Henry, M C

1980-02-01

A summary of existing passive solar-heat conversion panels provides the basis for a definition of an ideal passive solar-heat converter. Evidence for the existence of a biological greenhouse effect in certain homopolar homeothermic species is reviewed. The thermal and optical properties of homeothermic pelts, in particular those of the polar bear, are described, and a qualitative optical model of the polar bear pelt is proposed. The effectiveness of polar bear and seal pelts as solar-heat converters is discussed, and comparison is made with the ideal converter.

Microscopic Optical Projection Tomography In Vivo

PubMed Central

Meyer, Heiko; Ripoll, Jorge; Tavernarakis, Nektarios

2011-01-01

We describe a versatile optical projection tomography system for rapid three-dimensional imaging of microscopic specimens in vivo. Our tomographic setup eliminates the in xy and z strongly asymmetric resolution, resulting from optical sectioning in conventional confocal microscopy. It allows for robust, high resolution fluorescence as well as absorption imaging of live transparent invertebrate animals such as C. elegans. This system offers considerable advantages over currently available methods when imaging dynamic developmental processes and animal ageing; it permits monitoring of spatio-temporal gene expression and anatomical alterations with single-cell resolution, it utilizes both fluorescence and absorption as a source of contrast, and is easily adaptable for a range of small model organisms. PMID:21559481

Brain Inositol Is a Novel Stimulator for Promoting Cryptococcus Penetration of the Blood-Brain Barrier

PubMed Central

Wang, Yina; Toffaletti, Dena L.; Eugenin, Eliseo; Perfect, John R.; Kim, Kee Jun; Xue, Chaoyang

2013-01-01

Cryptococcus neoformans is the most common cause of fungal meningitis, with high mortality and morbidity. The reason for the frequent occurrence of Cryptococcus infection in the central nervous system (CNS) is poorly understood. The facts that human and animal brains contain abundant inositol and that Cryptococcus has a sophisticated system for the acquisition of inositol from the environment suggests that host inositol utilization may contribute to the development of cryptococcal meningitis. In this study, we found that inositol plays an important role in Cryptococcus traversal across the blood-brain barrier (BBB) both in an in vitro human BBB model and in in vivo animal models. The capacity of inositol to stimulate BBB crossing was dependent upon fungal inositol transporters, indicated by a 70% reduction in transmigration efficiency in mutant strains lacking two major inositol transporters, Itr1a and Itr3c. Upregulation of genes involved in the inositol catabolic pathway was evident in a microarray analysis following inositol treatment. In addition, inositol increased the production of hyaluronic acid in Cryptococcus cells, which is a ligand known to binding host CD44 receptor for their invasion. These studies suggest an inositol-dependent Cryptococcus traversal of the BBB, and support our hypothesis that utilization of host-derived inositol by Cryptococcus contributes to CNS infection. PMID:23592982

Sex differences in mechanical allodynia: how can it be preclinically quantified and analyzed?

PubMed Central

Nicotra, Lauren; Tuke, Jonathan; Grace, Peter M.; Rolan, Paul E.; Hutchinson, Mark R.

2014-01-01

Translating promising preclinical drug discoveries to successful clinical trials remains a significant hurdle in pain research. Although animal models have significantly contributed to understanding chronic pain pathophysiology, the majority of research has focused on male rodents using testing procedures that produce sex difference data that do not align well with comparable clinical experiences. Additionally, the use of animal pain models presents ongoing ethical challenges demanding continuing refinement of preclinical methods. To this end, this study sought to test a quantitative allodynia assessment technique and associated statistical analysis in a modified graded nerve injury pain model with the aim to further examine sex differences in allodynia. Graded allodynia was established in male and female Sprague Dawley rats by altering the number of sutures placed around the sciatic nerve and quantified by the von Frey test. Linear mixed effects modeling regressed response on each fixed effect (sex, oestrus cycle, pain treatment). On comparison with other common von Frey assessment techniques, utilizing lower threshold filaments than those ordinarily tested, at 1 s intervals, appropriately and successfully investigated female mechanical allodynia, revealing significant sex and oestrus cycle difference across the graded allodynia that other common behavioral methods were unable to detect. Utilizing this different von Frey approach and graded allodynia model, a single suture inflicting less allodynia was sufficient to demonstrate exaggerated female mechanical allodynia throughout the phases of dioestrus and pro-oestrus. Refining the von Frey testing method, statistical analysis technique and the use of a graded model of chronic pain, allowed for examination of the influences on female mechanical nociception that other von Frey methods cannot provide. PMID:24592221

Scattered Dose Calculations and Measurements in a Life-Like Mouse Phantom

PubMed Central

Welch, David; Turner, Leah; Speiser, Michael; Randers-Pehrson, Gerhard; Brenner, David J.

2017-01-01

Anatomically accurate phantoms are useful tools for radiation dosimetry studies. In this work, we demonstrate the construction of a new generation of life-like mouse phantoms in which the methods have been generalized to be applicable to the fabrication of any small animal. The mouse phantoms, with built-in density inhomogeneity, exhibit different scattering behavior dependent on where the radiation is delivered. Computer models of the mouse phantoms and a small animal irradiation platform were devised in Monte Carlo N-Particle code (MCNP). A baseline test replicating the irradiation system in a computational model shows minimal differences from experimental results from 50 Gy down to 0.1 Gy. We observe excellent agreement between scattered dose measurements and simulation results from X-ray irradiations focused at either the lung or the abdomen within our phantoms. This study demonstrates the utility of our mouse phantoms as measurement tools with the goal of using our phantoms to verify complex computational models. PMID:28140787

Micro-tattoo guided OCT imaging of site specific inflammation

NASA Astrophysics Data System (ADS)

Phillips, Kevin G.; Choudhury, Niloy; Samatham, Ravikant V.; Singh, Harvinder; Jacques, Steven L.

2010-02-01

Epithelial biologists studying human skin diseases such as cancer formation and psoriasis commonly utilize mouse models to characterize the interplay among cells and intracellular signal transduction pathways that result in programmed changes in gene expression and cellular behaviors. The information obtained from animal models is useful only when phenotypic presentations of disease recapitulate those observed in humans. Excision of tissues followed by histochemical analysis is currently the primary means of establishing the morphological presentation. Non invasive imaging of animal models provides an alternate means to characterize tissue morphology associated with the disease of interest in vivo. While useful, the ability to perform in vivo imaging at different time points in the same tissue location has been a challenge. This information is key to understanding site specific changes as the imaged tissue can now be extracted and analyzed for mRNA expression. We present a method employing a micro-tattoo to guide optical coherence tomography (OCT) imaging of ultraviolet induced inflammation over time in the same tissue locations.

An ethnobiological study in Kala Chitta hills of Pothwar region, Pakistan: multinomial logit specification

PubMed Central

2014-01-01

Background This paper constitutes an important ethnobiological survey in the context of utilizing biological resources by residents of Kala Chitta hills of Pothwar region, Pakistan. The fundamental aim of this research endeavour was to catalogue and analyse the indigenous knowledge of native community about plants and animals. The study is distinctive in the sense to explore both ethnobotanical and ethnozoological aspects of indigenous culture, and exhibits novelty, being based on empirical approach of Multinomial Logit Specifications (MLS) for examining ethnobotanical and ethnozoological uses of specific plants and animals. Methods To document the ethnobiological knowledge, the survey was conducted during 2011–12 by employing a semi-structured questionnaire and thus 54 informants were interviewed. Plant and animal specimens were collected, photographed and properly identified. Distribution of plants and animals were explored by descriptive and graphical examination. MLS were further incorporated to identify the probability of occurrence of diversified utilization of plants and animals in multipurpose domains. Results Traditional uses of 91 plant and 65 animal species were reported. Data analysis revealed more medicinal use of plants and animals than all other use categories. MLS findings are also in line with these proportional configurations. They reveal that medicinal and food consumption of underground and perennial plants was more as compared to aerial and annual categories of plants. Likewise, medicinal utilization of wild animals and domestic animals were more commonly observed as food items. However, invertebrates are more in the domain of medicinal and food utilization. Also carnivores are fairly common in the use of medicine while herbivores are in the category of food consumption. Conclusion This study empirically scans a good chunk of ethnobiological knowledge and depicts its strong connection with indigenous traditions. It is important to make local residents beware of conservation status of species and authentication of this knowledge needs to be done in near future. Moreover, Statistically significant findings impart novelty in the existing literature in the field of ethnobiology. Future conservation, phytochemical and pharmacological studies are recommended on these identified plants and animals in order to use them in a more sustainable and effective way. PMID:24467739

Changes seen in gut bacteria content and distribution with obesity: causation or association?

PubMed

Bell, David S H

2015-01-01

In the microbiota of both obese animals and humans there is an increased ratio of the gram positive Firmicutes to the gram negative Bacteroidetes (the obesity pattern). To assess if altering this ratio in animals and humans would prevent obesity or reduce body weight in the obese subject this review was preformed. A survey of all the available English language literature utilizing Medline on this topic was obtained and critically reviewed. The key words that were utilized were gut microbiota, diet and obesity. In both humans and animals changes in diet, particularly the utilization of the high fat, high calorie Western diet, utilization of artificial sweeteners and disruption of the diurnal rhythm will quickly change the microbiota from a thin to an obese pattern. In animals, the transfer of an obese microbiota to germ free animals and thin animals results in obesity and the introduction of a lean microbiota will result in weight loss in obese animals. However, in humans similar changes in the gut microbiota induced with probiotics and prebiotics have not been shown to result in weight loss. In both animals and humans the most dramatic changes in the gut microbiota occur following weight loss resulting from a gastric bypass where there is a restoration to a normal Firmicutes to Bacteroidetes ratio. These changes could either be due to the dramatic change in the composition of the diet which occurs following this surgery or due to down-regulation of the Farnesoid X Receptor which causes a decrease in bile acid production and an elevation of the gut pH which in turn allows the regrowth of bacteria associated with weight loss which were previously unable to grow in the acidic intestinal environment caused by excess production of bile acids. In both humans and animals there are characteristic changes in the gut microbiota associated with obesity. In animals but not in humans altering the microbiota can result in weight loss and weight gain which does not occur in humans. This suggests that in humans the changes in gut microbiota are an association with rather than the cause of obesity.

Effects of Bisphenol A and its Analogs on Reproductive Health: A Mini Review.

PubMed

Siracusa, Jacob Steven; Yin, Lei; Measel, Emily; Liang, Shenuxan; Yu, Xiaozhong

2018-06-17

Known endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. Its structural analogs: bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) are increasingly being used in consumer products. However, these analogs may exert similar adverse effects on the reproductive system, and their toxicological data are still limited. This mini-review examined studies on both BPA and BPA analog exposure and reproductive toxicity. It outlines the current state of knowledge on human exposure, toxicokinetics, endocrine activities, and reproductive toxicities of BPA and its analogs. BPA analogs showed similar endocrine potencies when compared to BPA, and emerging data suggest they may pose threats as reproductive hazards in animal models. While evidence based on epidemiological studies is still weak, we have utilized current studies to highlight knowledge gaps and research needs for future risk assessments. Copyright © 2018. Published by Elsevier Inc.

On the Utilization of Social Animals as a Model for Social Robotics

PubMed Central

Miklósi, Ádám; Gácsi, Márta

2012-01-01

Social robotics is a thriving field in building artificial agents. The possibility to construct agents that can engage in meaningful social interaction with humans presents new challenges for engineers. In general, social robotics has been inspired primarily by psychologists with the aim of building human-like robots. Only a small subcategory of “companion robots” (also referred to as robotic pets) was built to mimic animals. In this opinion essay we argue that all social robots should be seen as companions and more conceptual emphasis should be put on the inter-specific interaction between humans and social robots. This view is underlined by the means of an ethological analysis and critical evaluation of present day companion robots. We suggest that human–animal interaction provides a rich source of knowledge for designing social robots that are able to interact with humans under a wide range of conditions. PMID:22457658

Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction.

PubMed

Yamasue, Hidenori; Yee, Jason R; Hurlemann, René; Rilling, James K; Chen, Frances S; Meyer-Lindenberg, Andreas; Tost, Heike

2012-10-10

The prevalence of autism spectrum disorder (ASD) is as high as 1 in 100 individuals and is a heavy burden to society. Thus, identifying causes and treatments is imperative. Here, we briefly review the topics covered in our 2012 Society for Neuroscience Mini-Symposium entitled "Integrative Approaches Using Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to ASD's Social Dysfunction." This work is not meant to be a comprehensive review of oxytocin and prosocial behavior. Instead, we wish to share the newest findings on the effects of oxytocin on social behavior, the brain, and the social dysfunction of ASD at the molecular, genetic, systemic, and behavior levels, in varied subjects ranging from animal models to humans suffering from autism for the purpose of promoting further study for developing the clinical use of oxytocin in treating ASD.

Nonhuman Primate Models in the Genomic Era: A Paradigm Shift

PubMed Central

Vallender, Eric J.; Miller, Gregory M.

2013-01-01

Because of their strong similarities to humans across physiologic, developmental, behavioral, immunologic, and genetic levels, nonhuman primates are essential models for a wide spectrum of biomedical research. But unlike other animal models, nonhuman primates possess substantial outbred genetic variation, reducing statistical power and potentially confounding interpretation of results in research studies. Although unknown genetic variation is a hindrance in studies that allocate animals randomly, taking genetic variation into account in study design affords an opportunity to transform the way that nonhuman primates are used in biomedical research. New understandings of how the function of individual genes in rhesus macaques mimics that seen in humans are greatly advancing the rhesus macaques utility as research models, but epistatic interaction, epigenetic regulatory mechanisms, and the intricacies of gene networks limit model development. We are now entering a new era of nonhuman primate research, brought on by the proliferation and rapid expansion of genomic data. Already the cost of a rhesus macaque genome is dwarfed by its purchase and husbandry costs, and complete genomic datasets will inevitably encompass each rhesus macaque used in biomedical research. Advancing this outcome is paramount. It represents an opportunity to transform the way animals are assigned and used in biomedical research and to develop new models of human disease. The genetic and genomic revolution brings with it a paradigm shift for nonhuman primates and new mandates on how nonhuman primates are used in biomedical research. PMID:24174439

Decreased CB receptor binding and cannabinoid signaling in three brain regions of a rat model of schizophrenia.

PubMed

Szűcs, Edina; Dvorácskó, Szabolcs; Tömböly, Csaba; Büki, Alexandra; Kékesi, Gabriella; Horváth, Gyöngyi; Benyhe, Sándor

2016-10-28

Schizophrenia is a serious mental health disorder characterized by several behavioral and biochemicel abnormalities. In a previous study we have shown that mu-opioid (MOP) receptor signaling is impaired in specific brain regions of our three-hit animal model of schizophrenia. Since the cannabinoid system is significantly influenced in schizophrenic patients, in the present work we investigated cannabinoid (CB) receptor binding and G-protein activation in cortical, subcortical and cerebellar regions of control and 'schizophrenic' rats. Cannabinoid agonist (WIN-55,212-2 mesylate) mediated G-protein activation was consistently decreased in all areas tested, and the difference was extremely significant in membranes prepared from the cerebellum. Interestingly, the cerebellar activity of WIN-55,212-2 stimulated G-proteins was substantially higher than those of cerebral cortex and subcortical region in control animals, indicating a primordial role of the cannabinoid system in the cerebellum. At the level of radioligand binding, the affinities of the CB receptors were also markedly decreased in the model animals. Capacity of the [ 3 H]WIN-55,212-2 binding was only higher in the cerebellum of 'schizophrenic' model rats. Taken together, in all three brain areas of model rats both cannabinoid receptor binding and cannabinoid agonist-mediated G-protein activation were regularly decreased. Our results revealed that besides the opioids, the endocannabinoid - cannabis receptor system also shows impairment in our rat model, increasing its face validity and translational utility. Copyright © 2016. Published by Elsevier Ireland Ltd.

Mass Spectrometric Monitoring of Animal Feed for BSE Spread

ERIC Educational Resources Information Center

King, Angela G.

2004-01-01

The researchers in London have developed an emerging technology that utilizes mass spectrometry to detect processed animal protein (PAP) in animal feed. The amount of animal protein in the feed can be determined by the ratio of the hydrolyzed gelatine signal at m/z 1044 to an internal standard signal at m/z 556.

Association of the Environmental Attitudes "Preservation" and "Utilization" with Pro-Animal Attitudes

ERIC Educational Resources Information Center

Binngießer, Janine; Randler, Christoph

2015-01-01

The relevance of environmental attitudes is obvious and attitudes towards farm and companion animals and animal welfare in medical research are an important aspect of education. However, both have rarely been linked with each other, and animal attitudes are only sparsely represented within environmental education assessment instruments. Linking…

Automation in Animal Housing and Production

USDA-ARS?s Scientific Manuscript database

Intensive, controlled environment animal production began modestly in the mid-20th century as poultry were brought indoors. While mankind had utilized structures to provide shelter for their animals for centuries, the availability of relatively inexpensive energy and the electrification of rural are...

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

PubMed Central

Soontornniyomkij, Virawudh; Kesby, James P.; Morgan, Erin E.; Bischoff-Grethe, Amanda; Minassian, Arpi; Brown, Gregory G.; Grant, Igor

2016-01-01

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value. PMID:27484318

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models.

PubMed

Soontornniyomkij, Virawudh; Kesby, James P; Morgan, Erin E; Bischoff-Grethe, Amanda; Minassian, Arpi; Brown, Gregory G; Grant, Igor

2016-09-01

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value.

Agro-economic impact of cattle cloning.

PubMed

Faber, D C; Ferre, L B; Metzger, J; Robl, J M; Kasinathan, P

2004-01-01

The purpose of this paper is to review the economic and social implications of cloned cattle, their products, and their offspring as related to production agriculture. Cloning technology in cattle has several applications outside of traditional production agriculture. These applications can include bio-medical applications, such as the production of pharmaceuticals in the blood or milk of transgenic cattle. Cloning may also be useful in the production of research models. These models may or may not include genetic modifications. Uses in agriculture include many applications of the technology. These include making genetic copies of elite seed stock and prize winning show cattle. Other purposes may range from "insurance" to making copies of cattle that have sentimental value, similar to cloning of pets. Increased selection opportunities available with cloning may provide for improvement in genetic gain. The ultimate goal of cloning has often been envisioned as a system for producing quantity and uniformity of the perfect dairy cow. However, only if heritability were 100%, would clone mates have complete uniformity. Changes in the environment may have significant impact on the productivity and longevity of the resulting clones. Changes in consumer preferences and economic input costs may all change the definition of the perfect cow. The cost of producing such animals via cloning must be economically feasible to meet the intended applications. Present inefficiencies limit cloning opportunities to highly valued animals. Improvements are necessary to move the applications toward commercial application. Cloning has additional obstacles to conquer. Social and regulatory acceptance of cloning is paramount to its utilization in production agriculture. Regulatory acceptance will need to address the animal, its products, and its offspring. In summary, cloning is another tool in the animal biotechnology toolbox, which includes artificial insemination, sexing of semen, embryo sexing and in vitro fertilization. While it will not replace any of the above mentioned, its degree of utilization will depend on both improvement in efficiency as well as social and regulatory acceptance.

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds.

PubMed

Voorhees, Jaymie R; Rohlman, Diane S; Lein, Pamela J; Pieper, Andrew A

2016-01-01

Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.

Dopamine Reward Prediction Error Responses Reflect Marginal Utility

PubMed Central

Stauffer, William R.; Lak, Armin; Schultz, Wolfram

2014-01-01

Summary Background Optimal choices require an accurate neuronal representation of economic value. In economics, utility functions are mathematical representations of subjective value that can be constructed from choices under risk. Utility usually exhibits a nonlinear relationship to physical reward value that corresponds to risk attitudes and reflects the increasing or decreasing marginal utility obtained with each additional unit of reward. Accordingly, neuronal reward responses coding utility should robustly reflect this nonlinearity. Results In two monkeys, we measured utility as a function of physical reward value from meaningful choices under risk (that adhered to first- and second-order stochastic dominance). The resulting nonlinear utility functions predicted the certainty equivalents for new gambles, indicating that the functions’ shapes were meaningful. The monkeys were risk seeking (convex utility function) for low reward and risk avoiding (concave utility function) with higher amounts. Critically, the dopamine prediction error responses at the time of reward itself reflected the nonlinear utility functions measured at the time of choices. In particular, the reward response magnitude depended on the first derivative of the utility function and thus reflected the marginal utility. Furthermore, dopamine responses recorded outside of the task reflected the marginal utility of unpredicted reward. Accordingly, these responses were sufficient to train reinforcement learning models to predict the behaviorally defined expected utility of gambles. Conclusions These data suggest a neuronal manifestation of marginal utility in dopamine neurons and indicate a common neuronal basis for fundamental explanatory constructs in animal learning theory (prediction error) and economic decision theory (marginal utility). PMID:25283778

Generation of improved humanized mouse models for human infectious diseases

PubMed Central

Brehm, Michael A.; Wiles, Michael V.; Greiner, Dale L.; Shultz, Leonard D.

2014-01-01

The study of human-specific infectious agents has been hindered by the lack of optimal small animal models. More recently development of novel strains of immunodeficient mice has begun to provide the opportunity to utilize small animal models for the study of many human-specific infectious agents. The introduction of a targeted mutation in the IL2 receptor common gamma chain gene (IL2rgnull) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues, effectively creating human immune systems in immunodeficient mice. These humanized mice are becoming increasingly important as pre-clinical models for the study of human immunodeficiency virus-1 (HIV-1) and other human-specific infectious agents. However, there remain a number of opportunities to further improve humanized mouse models for the study of human-specific infectious agents. This is being done by the implementation of innovative technologies, which collectively will accelerate the development of new models of genetically modified mice, including; i) modifications of the host to reduce innate immunity, which impedes human cell engraftment; ii) genetic modification to provide human-specific growth factors and cytokines required for optimal human cell growth and function; iii) and new cell and tissue engraftment protocols. The development of “next generation” humanized mouse models continues to provide exciting opportunities for the establishment of robust small animal models to study the pathogenesis of human-specific infectious agents, as well as for testing the efficacy of therapeutic agents and experimental vaccines. PMID:24607601

[Animal feeding and feed legislation after the detection of the first indigenous BSE cases in Germany].

PubMed

Kamphues, J

2002-08-01

In Great Britain, even the earliest tangible signs indicating the epidemiologic significance of meat and bone meal in the spreading of BSE soon gave rise to increasingly rigorous legislative measures regulating animal feedstuffs. In 1994 a ban on the feeding of animal proteins to ruminants was implemented throughout the entire EU. But until the first BSE cases were actually confirmed in locally raised cattle (November 2000), feeding practice and legislation more or less in Germany remained unaffected by the efforts undertaken in Great Britain. This situation was suddenly changed on 1 December, 2000, when the so-called "Verfütterungsverbot" was put into effect, a law which drastically extended bans regarding the feedstuffs (including fishmeal and animal fats) as well as the species concerned (all animals used in food production). In 2001 the "contamination" phenomenon (ingredients of animal origin were detected in mixed feeds) became a vital issue for the feed industry; through the media, the subject "feedstuff safety" gained a previously unseen level of public awareness. Those circles concerned with mixed feed production and animal husbandry were increasingly confronted with the consequences of the "Verfütterungsverbot" (availability and pricing of substitute ingredients; the demand for amino acids and inorganic sources of phosphorus; problems finding adequate substitutes for animal fats; poor digestibility of alternative components such as indigenous legumes or vegetable fats in calf diets; lower utilization rate of original phosphorus in mixed feeds with negative consequences for skeletal development). With the conditional approval of fishmeal (except in feeds for ruminants) the situation has eased again to a certain degree; on the EU level there are increasing signals pointing toward a political intention to reinstate the utilization of by-products of slaughtered animals qualified for human consumption (with the exception of fallen/dead animals and specific risk material) in poultry and swine feeding. In Germany, at least, the question of animal fat utilization for food-producing animals is still unsolved.

Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here?

PubMed Central

Marklund, Niklas; Hillered, Lars

2011-01-01

Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Survivors of TBI frequently suffer from long-term personality changes and deficits in cognitive and motor performance, urgently calling for novel pharmacological treatment options. To date, all clinical trials evaluating neuroprotective compounds have failed in demonstrating clinical efficacy in cohorts of severely injured TBI patients. The purpose of the present review is to describe the utility of animal models of TBI for preclinical evaluation of pharmacological compounds. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI. To successfully develop compounds for clinical TBI, a thorough evaluation in several TBI models and injury severities is crucial. Additionally, brain pharmacokinetics and the time window must be carefully evaluated. Although the search for a single-compound, ‘silver bullet’ therapy is ongoing, a combination of drugs targeting various aspects of neuroprotection, neuroinflammation and regeneration may be needed. In summary, finding drugs and prove clinical efficacy in TBI is a major challenge ahead for the research community and the drug industry. For a successful translation of basic science knowledge to the clinic to occur we believe that a further refinement of animal models and functional outcome methods is important. In the clinical setting, improved patient classification, more homogenous patient cohorts in clinical trials, standardized treatment strategies, improved central nervous system drug delivery systems and monitoring of target drug levels and drug effects is warranted. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21175576

The rise of the starlet sea anemone Nematostella vectensis as a model system to investigate development and regeneration

PubMed Central

Rentzsch, Fabian; Röttinger, Eric

2016-01-01

Reverse genetics and next‐generation sequencing unlocked a new era in biology. It is now possible to identify an animal(s) with the unique biology most relevant to a particular question and rapidly generate tools to functionally dissect that biology. This review highlights the rise of one such novel model system, the starlet sea anemone Nematostella vectensis. Nematostella is a cnidarian (corals, jellyfish, hydras, sea anemones, etc.) animal that was originally targeted by EvoDevo researchers looking to identify a cnidarian animal to which the development of bilaterians (insects, worms, echinoderms, vertebrates, mollusks, etc.) could be compared. Studies in Nematostella have accomplished this goal and informed our understanding of the evolution of key bilaterian features. However, Nematostella is now going beyond its intended utility with potential as a model to better understand other areas such as regenerative biology, EcoDevo, or stress response. This review intends to highlight key EvoDevo insights from Nematostella that guide our understanding about the evolution of axial patterning mechanisms, mesoderm, and nervous systems in bilaterians, as well as to discuss briefly the potential of Nematostella as a model to better understand the relationship between development and regeneration. Lastly, the sum of research to date in Nematostella has generated a variety of tools that aided the rise of Nematostella to a viable model system. We provide a catalogue of current resources and techniques available to facilitate investigators interested in incorporating Nematostella into their research. WIREs Dev Biol 2016, 5:408–428. doi: 10.1002/wdev.222 For further resources related to this article, please visit the WIREs website. PMID:26894563

Development of a new auxiliary heterotopic partial liver transplantation technique using a liver cirrhosis model in minipigs: Preliminary report of eight transplants

PubMed Central

ZHANG, JUN-JING; NIU, JIAN-XIANG; YUE, GEN-QUAN; ZHONG, HAI-YAN; MENG, XING-KAI

2012-01-01

This study aimed to develop a new auxiliary heterotopic partial liver transplantation (AHPLT) technique in minipigs using a model of liver cirrhosis. Based on our previous study, 14 minipigs were induced to cirrhosis by administration of carbon tetrachloride (CCl4) through intraperitoneal injection. All of the cirrhotic animals were utilized as recipients. The donor’s liver was placed on the recipient’s splenic bed, and the anastomosis was performed as follows: end-to-end anastomosis between the donor’s portal vein and the recipient’s splenic vein, end-to-side anastomosis between the donor’s suprahepatic vena cava and the recipient’s suprahepatic vena cava, and end-to-end anastomosis between the donor’s hepatic artery and the recipient’s splenic artery. The common bile duct of the donor was intubated and bile was collected with an extracorporeal bag. Vital signs, portal vein pressure (PVP), hepatic venous pressure (HVP) and portal vein pressure gradient (PVPG) were monitored throughout the transplantation. All 8 minipigs that developed liver cirrhosis were utilized to establish the new AHPLT; 7 cases survived. Following the surgical intervention, the PVP and PVPG of the recipients were lower than those prior to the operation (P<0.05), whereas the PVP and PVPG of the donors increased significantly compared to those of the normal animals (P<0.05). A new operative technique for AHPLT has been successfully described herein using a model of liver cirrhosis. PMID:22969983

Zebrafish models in neuropsychopharmacology and CNS drug discovery.

PubMed

Khan, Kanza M; Collier, Adam D; Meshalkina, Darya A; Kysil, Elana V; Khatsko, Sergey L; Kolesnikova, Tatyana; Morzherin, Yury Yu; Warnick, Jason E; Kalueff, Allan V; Echevarria, David J

2017-07-01

Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets. © 2017 The British Pharmacological Society.

Inversion of left-right asymmetry alters performance of Xenopus tadpoles in nonlateralized cognitive tasks.

PubMed

Blackiston, Douglas J; Levin, Michael

2013-08-01

Left-right behavioural biases are well documented across the animal kingdom, and handedness has long been associated with cognitive performance. However, the relationship between body laterality and cognitive ability is poorly understood. The embryonic pathways dictating normal left-right patterning have been molecularly dissected in model vertebrates, and numerous genetic and pharmacological treatments now facilitate experimental randomization or reversal of the left-right axis in these animals. Several recent studies showed a link between brain asymmetry and strongly lateralized behaviours such as eye use preference. However, links between laterality of the body and performance on cognitive tasks utilizing nonlateralized cues remain unknown. Xenopus tadpoles are an established model for the study of early left-right patterning, and protocols were recently developed to quantitatively evaluate learning and memory in these animals. Using an automated testing and training platform, we tested wild-type, left-right-randomized and left-right-reversed tadpoles for their ability to learn colour cues in an automated assay. Our results indicate that animals with either randomization or reversal of somatic left-right patterning learned more slowly than wild-type siblings, although all groups were able to reach the same performance optimum given enough training sessions. These results are the first analysis of the link between body laterality and learning of nonlateralized cues, and they position the Xenopus tadpole as an attractive and tractable model for future studies of the links between asymmetry of the body, lateralization of the brain and behaviour.

Biota Modeling in EPA's Preliminary Remediation Goal and Dose Compliance Concentration Calculators for Use in EPA Superfund Risk Assessment: Explanation of Intake Rate Derivation, Transfer Factor Compilation, and Mass Loading Factor Sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manning, Karessa L.; Dolislager, Fredrick G.; Bellamy, Michael B.

The Preliminary Remediation Goal (PRG) and Dose Compliance Concentration (DCC) calculators are screening level tools that set forth Environmental Protection Agency's (EPA) recommended approaches, based upon currently available information with respect to risk assessment, for response actions at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) sites, commonly known as Superfund. The screening levels derived by the PRG and DCC calculators are used to identify isotopes contributing the highest risk and dose as well as establish preliminary remediation goals. Each calculator has a residential gardening scenario and subsistence farmer exposure scenarios that require modeling of the transfer of contaminants frommore » soil and water into various types of biota (crops and animal products). New publications of human intake rates of biota; farm animal intakes of water, soil, and fodder; and soil to plant interactions require updates be implemented into the PRG and DCC exposure scenarios. Recent improvements have been made in the biota modeling for these calculators, including newly derived biota intake rates, more comprehensive soil mass loading factors (MLFs), and more comprehensive soil to tissue transfer factors (TFs) for animals and soil to plant transfer factors (BV's). New biota have been added in both the produce and animal products categories that greatly improve the accuracy and utility of the PRG and DCC calculators and encompass greater geographic diversity on a national and international scale.« less

Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a Murine Model of Gastrointestinal Anthrax

PubMed Central

Huang, Bruce; Xie, Tao; Rotstein, David; Fang, Hui; Frucht, David M.

2015-01-01

The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay. PMID:26426050

Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a Murine Model of Gastrointestinal Anthrax.

PubMed

Huang, Bruce; Xie, Tao; Rotstein, David; Fang, Hui; Frucht, David M

2015-09-29

The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography.

PubMed

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M D; Rotenberg, Alexander; Daskalakis, Zafiris J; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography

PubMed Central

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M. D.; Rotenberg, Alexander; Daskalakis, Zafiris J.; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research. PMID:27713691

Pharmacokinetics of meso-(tetrahydroxyphenyl)chlorin (m-THPC) studied by fluorescence spectroscopy on early cancer of the cheek pouch mucosa of Golden Syrian hamsters

NASA Astrophysics Data System (ADS)

Glanzmann, Thomas M.; Theumann, Jean-Francois; Braichotte, Daniel; Forrer, Martin; Wagnieres, Georges A.; van den Bergh, Hubert; Andrejevic-Blant, Snezana; Savary, Jean-Francois; Monnier, Philippe

1995-01-01

Golden Syrian hamsters are evaluated as an animal model for phototherapy of early squamous cell carcinomas of the mucosa of the upper aerodigestive tract, the esophagus and the tracheobronchial tree. Carcinomas of this type are induced on the hamster cheek pouch mucosa by the application of the carcinogen 7,12 DMBA. For phototherapeutic experiments on the animals we utilized meso- (tetrahydoxyphenyl)chlorin (mTHPC). The same drug is currently in phase I, II clinical trials for ENT patients with superficial squamous cell carcinomas. By means of light induced fluorescence (LIF) we measured in vivo the kinetics of the uptake and removal of mTHPC in the normal and tumoral cheek mucosa and in the skin. The photodynamic therapy (PDT) reaction of the tissue after excitation of the photosensitizer by laser light at 652 nm was studied. Both pharmacokinetics and PDT efficacy are compared between animal model and clinical results with special emphasis on selectivity between normal and tumoral mucosa. These first experiments show that this tumor model in the hamster cheek pouch seems to be suitable for tests of a number of PDT variables of new photosensitizers preceding their clinical application as well as for optimization of the multiple parameters of clinical phototherapy.

Computational Prediction of Alzheimer’s and Parkinson’s Disease MicroRNAs in Domestic Animals

PubMed Central

Wang, Hai Yang; Lin, Zi Li; Yu, Xian Feng; Bao, Yuan; Cui, Xiang-Shun; Kim, Nam-Hyung

2016-01-01

As the most common neurodegenerative diseases, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two of the main health concerns for the elderly population. Recently, microRNAs (miRNAs) have been used as biomarkers of infectious, genetic, and metabolic diseases in humans but they have not been well studied in domestic animals. Here we describe a computational biology study in which human AD- and PD-associated miRNAs (ADM and PDM) were utilized to predict orthologous miRNAs in the following domestic animal species: dog, cow, pig, horse, and chicken. In this study, a total of 121 and 70 published human ADM and PDM were identified, respectively. Thirty-seven miRNAs were co-regulated in AD and PD. We identified a total of 105 unrepeated human ADM and PDM that had at least one 100% identical animal homolog, among which 81 and 54 showed 100% sequence identity with 241 and 161 domestic animal miRNAs, respectively. Over 20% of the total mature horse miRNAs (92) showed perfect matches to AD/PD-associated miRNAs. Pigs, dogs, and cows have similar numbers of AD/PD-associated miRNAs (63, 62, and 59). Chickens had the least number of perfect matches (34). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that humans and dogs are relatively similar in the functional pathways of the five selected highly conserved miRNAs. Taken together, our study provides the first evidence for better understanding the miRNA-AD/PD associations in domestic animals, and provides guidance to generate domestic animal models of AD/PD to replace the current rodent models. PMID:26954182

Temporal segmentation of animal trajectories informed by habitat use

USGS Publications Warehouse

van Toor, Marielle L.; Newman, Scott H.; Takekawa, John Y.; Wegmann, Martin; Safi, Kamran

2016-01-01

Most animals live in seasonal environments and experience very different conditions throughout the year. Behavioral strategies like migration, hibernation, and a life cycle adapted to the local seasonality help to cope with fluctuations in environmental conditions. Thus, how an individual utilizes the environment depends both on the current availability of habitat and the behavioral prerequisites of the individual at that time. While the increasing availability and richness of animal movement data has facilitated the development of algorithms that classify behavior by movement geometry, changes in the environmental correlates of animal movement have so far not been exploited for a behavioral annotation. Here, we suggest a method that uses these changes in individual–environment associations to divide animal location data into segments of higher ecological coherence, which we term niche segmentation. We use time series of random forest models to evaluate the transferability of habitat use over time to cluster observational data accordingly. We show that our method is able to identify relevant changes in habitat use corresponding to both changes in the availability of habitat and how it was used using simulated data, and apply our method to a tracking data set of common teal (Anas crecca). The niche segmentation proved to be robust, and segmented habitat suitability outperformed models neglecting the temporal dynamics of habitat use. Overall, we show that it is possible to classify animal trajectories based on changes of habitat use similar to geometric segmentation algorithms. We conclude that such an environmentally informed classification of animal trajectories can provide new insights into an individuals' behavior and enables us to make sensible predictions of how suitable areas might be connected by movement in space and time.

Evaluation with mTHPC of early squamous cell carcinomas of the cheek pouch mucosa of Golden Syrian hamsters as a model for clinical PDT of early cancers in the upper aerodigestive tract, the esophag

NASA Astrophysics Data System (ADS)

Glanzmann, Thomas M.; Theumann, Jean-Francois; Forrer, Martin; Braichotte, Daniel; Wagnieres, Georges A.; van den Bergh, Hubert; Andrejevic-Blant, Snezana; Savary, Jean-Francois; Monnier, Philippe

1995-03-01

Golden Syrian hamsters are evaluated as an animal model for light induced fluorescence (LIF) photodetection and phototherapy of early squamous cell carcinomas of the upper aerodigestive tract, the esophagus, and the traecheo-bronchial tree. Carcinomas of this type are induced on the hamster cheek pouch mucosa by the application of the carcinogen 7,12-DMBA. For phototherapeutic experiments on the animals we utilized meso-(tetrahydoxyphenyl) chlorin (mTHPC). This drug is currently in phase I and II clinical trials for ENT patients presenting superficial `early' squamous cell carcinomas. By means of LIF we measured in vivo the kinetics of the uptake and removal of mTHPC in the normal and tumoral cheek mucosa and in the skin. The photodynamic therapy (PDT) reaction of the tissue after excitation of the photosensitizer with laser light at 652 nm was studied. Both pharmacokinetics and PDT efficacy are compared between animal model and clinical results with special emphasis on selectivity between normal and tumoral mucosa. These first experiments show that this tumor model in the hamster cheek pouch seems to be suitable for testing new photosensitizers preceding their clinical application as well as for optimization of the multiple parameters of clinical PDT.

Average dispersal success: linking home range, dispersal, and metapopulation dynamics to reserve design.

PubMed

Fagan, William F; Lutscher, Frithjof

2006-04-01

Spatially explicit models for populations are often difficult to tackle mathematically and, in addition, require detailed data on individual movement behavior that are not easily obtained. An approximation known as the "average dispersal success" provides a tool for converting complex models, which may include stage structure and a mechanistic description of dispersal, into a simple matrix model. This simpler matrix model has two key advantages. First, it is easier to parameterize from the types of empirical data typically available to conservation biologists, such as survivorship, fecundity, and the fraction of juveniles produced in a study area that also recruit within the study area. Second, it is more amenable to theoretical investigation. Here, we use the average dispersal success approximation to develop estimates of the critical reserve size for systems comprising single patches or simple metapopulations. The quantitative approach can be used for both plants and animals; however, to provide a concrete example of the technique's utility, we focus on a special case pertinent to animals. Specifically, for territorial animals, we can characterize such an estimate of minimum viable habitat area in terms of the number of home ranges that the reserve contains. Consequently, the average dispersal success framework provides a framework through which home range size, natal dispersal distances, and metapopulation dynamics can be linked to reserve design. We briefly illustrate the approach using empirical data for the swift fox (Vulpes velox).

Engineered cell and tissue models of pulmonary fibrosis.

PubMed

Sundarakrishnan, Aswin; Chen, Ying; Black, Lauren D; Aldridge, Bree B; Kaplan, David L

2018-04-01

Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3years' post-diagnosis. Treatments for IPF are limited to two FDA approved drugs, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis. Copyright © 2017. Published by Elsevier B.V.

Utilization and cost of log production from animal loging operations

Treesearch

Suraj P. Shrestha; Bobby L. Lanford; Robert B. Rummer; Mark Dubois

2006-01-01

Forest harvesting with animals is a labor-intensive operation. It is expensive to use machines on smaller woodlots, which require frequent moves if mechanically logged. So, small logging systems using animals may be more cost effective. In this study, work sampling was used for five animal logging operations in Alabama to measure productive and non-productive time...

Utility functions predict variance and skewness risk preferences in monkeys.

PubMed

Genest, Wilfried; Stauffer, William R; Schultz, Wolfram

2016-07-26

Utility is the fundamental variable thought to underlie economic choices. In particular, utility functions are believed to reflect preferences toward risk, a key decision variable in many real-life situations. To assess the validity of utility representations, it is therefore important to examine risk preferences. In turn, this approach requires formal definitions of risk. A standard approach is to focus on the variance of reward distributions (variance-risk). In this study, we also examined a form of risk related to the skewness of reward distributions (skewness-risk). Thus, we tested the extent to which empirically derived utility functions predicted preferences for variance-risk and skewness-risk in macaques. The expected utilities calculated for various symmetrical and skewed gambles served to define formally the direction of stochastic dominance between gambles. In direct choices, the animals' preferences followed both second-order (variance) and third-order (skewness) stochastic dominance. Specifically, for gambles with different variance but identical expected values (EVs), the monkeys preferred high-variance gambles at low EVs and low-variance gambles at high EVs; in gambles with different skewness but identical EVs and variances, the animals preferred positively over symmetrical and negatively skewed gambles in a strongly transitive fashion. Thus, the utility functions predicted the animals' preferences for variance-risk and skewness-risk. Using these well-defined forms of risk, this study shows that monkeys' choices conform to the internal reward valuations suggested by their utility functions. This result implies a representation of utility in monkeys that accounts for both variance-risk and skewness-risk preferences.

Use of Medaka in Toxicity Testing

PubMed Central

Cowden, John; Hinton, David E.; Johnson, Rodney; Flynn, Kevin; Hardman, Ronald C.; Yuen, Bonny; Law, Sheran; Kullman, Seth W.; Au, Doris W.T.

2015-01-01

Small aquarium fishes are increasingly used as animal models, and one of these, Japanese Medaka (Oryzias latipes), is frequently utilized for toxicity testing. While these vertebrates have many similarities with their terrestrial counterparts, there are differences that must be considered if these organisms are to be used to their highest potential. Testing commonly may employ either the developing embryo or adults; both are easy to use and to work with. We present here three main protocols to illustrate the utility and breadth of toxicity testing possible using medaka fish. The first protocol assesses neurotoxicity in developing embryos. The second protocol describes the sexual genotyping of medaka to evaluate toxicant effects on sexual phenotype after treatment with endocrine disrupting chemicals. The third protocol assesses hepatotoxicity in adult fish after treatment with a model hepatotoxicant. The methods run the gamut from immunohistology through PCR to basic histological techniques. PMID:20922755

TASI: A software tool for spatial-temporal quantification of tumor spheroid dynamics.

PubMed

Hou, Yue; Konen, Jessica; Brat, Daniel J; Marcus, Adam I; Cooper, Lee A D

2018-05-08

Spheroid cultures derived from explanted cancer specimens are an increasingly utilized resource for studying complex biological processes like tumor cell invasion and metastasis, representing an important bridge between the simplicity and practicality of 2-dimensional monolayer cultures and the complexity and realism of in vivo animal models. Temporal imaging of spheroids can capture the dynamics of cell behaviors and microenvironments, and when combined with quantitative image analysis methods, enables deep interrogation of biological mechanisms. This paper presents a comprehensive open-source software framework for Temporal Analysis of Spheroid Imaging (TASI) that allows investigators to objectively characterize spheroid growth and invasion dynamics. TASI performs spatiotemporal segmentation of spheroid cultures, extraction of features describing spheroid morpho-phenotypes, mathematical modeling of spheroid dynamics, and statistical comparisons of experimental conditions. We demonstrate the utility of this tool in an analysis of non-small cell lung cancer spheroids that exhibit variability in metastatic and proliferative behaviors.

Application of a model of instrumental conditioning to mobile robot control

NASA Astrophysics Data System (ADS)

Saksida, Lisa M.; Touretzky, D. S.

1997-09-01

Instrumental conditioning is a psychological process whereby an animal learns to associate its actions with their consequences. This type of learning is exploited in animal training techniques such as 'shaping by successive approximations,' which enables trainers to gradually adjust the animal's behavior by giving strategically timed reinforcements. While this is similar in principle to reinforcement learning, the real phenomenon includes many subtle effects not considered in the machine learning literature. In addition, a good deal of domain information is utilized by an animal learning a new task; it does not start from scratch every time it learns a new behavior. For these reasons, it is not surprising that mobile robot learning algorithms have yet to approach the sophistication and robustness of animal learning. A serious attempt to model instrumental learning could prove fruitful for improving machine learning techniques. In the present paper, we develop a computational theory of shaping at a level appropriate for controlling mobile robots. The theory is based on a series of mechanisms for 'behavior editing,' in which pre-existing behaviors, either innate or previously learned, can be dramatically changed in magnitude, shifted in direction, or otherwise manipulated so as to produce new behavioral routines. We have implemented our theory on Amelia, an RWI B21 mobile robot equipped with a gripper and color video camera. We provide results from training Amelia on several tasks, all of which were constructed as variations of one innate behavior, object-pursuit.

A lethal model of disseminated dengue virus type 1 infection in AG129 mice.

PubMed

Milligan, Gregg N; Sarathy, Vanessa V; White, Mellodee M; Greenberg, M Banks; Campbell, Gerald A; Pyles, Richard B; Barrett, Alan D T; Bourne, Nigel

2017-10-01

The mosquito-borne disease dengue is caused by four serologically and genetically related flaviviruses termed DENV-1 to DENV-4. Dengue is a global public health concern, with both the geographical range and burden of disease increasing rapidly. Clinically, dengue ranges from a relatively mild self-limiting illness to a severe life-threatening and sometimes fatal disease. Infection with one DENV serotype produces life-long homotypic immunity, but incomplete and short-term heterotypic protection. The development of small-animal models that recapitulate the characteristics of the disseminated disease seen clinically has been difficult, slowing the development of vaccines and therapeutics. The AG129 mouse (deficient in interferon alpha/beta and gamma receptor signalling) has proven to be valuable for this purpose, with the development of models of disseminated DENV-2,-3 and -4 disease. Recently, a DENV-1 AG129 model was described, but it requires antibody-dependent enhancement (ADE) to produce lethality. Here we describe a new AG129 model utilizing a non-mouse-adapted DENV-1 strain, West Pacific 74, that does not require ADE to induce lethal disease. Following high-titre intraperitoneal challenge, animals experience a virus infection with dissemination to multiple visceral tissues, including the liver, spleen and intestine. The animals also become thrombocytopenic, but vascular leakage is less prominent than in AG129 models with other DENV serotypes. Taken together, our studies demonstrate that this model is an important addition to dengue research, particularly for understanding the pathological basis of the disease between DENV serotypes and allowing the full spectrum of activity to test comparisons for putative vaccines and antivirals.

Permeability Evaluation Through Chitosan Membranes Using Taguchi Design

PubMed Central

Sharma, Vipin; Marwaha, Rakesh Kumar; Dureja, Harish

2010-01-01

In the present study, chitosan membranes capable of imitating permeation characteristics of diclofenac diethylamine across animal skin were prepared using cast drying method. The effect of concentration of chitosan, concentration of cross-linking agent (NaTPP), crosslinking time was studied using Taguchi design. Taguchi design ranked concentration of chitosan as the most important factor influencing the permeation parameters of diclofenac diethylamine. The flux of the diclofenac diethylamine solution through optimized chitosan membrane (T9) was found to be comparable to that obtained across rat skin. The mathematical model developed using multilinear regression analysis can be used to formulate chitosan membranes that can mimic the desired permeation characteristics. The developed chitosan membranes can be utilized as a substitute to animal skin for in vitro permeation studies. PMID:21179329

Permeability evaluation through chitosan membranes using taguchi design.

PubMed

Sharma, Vipin; Marwaha, Rakesh Kumar; Dureja, Harish

2010-01-01

In the present study, chitosan membranes capable of imitating permeation characteristics of diclofenac diethylamine across animal skin were prepared using cast drying method. The effect of concentration of chitosan, concentration of cross-linking agent (NaTPP), crosslinking time was studied using Taguchi design. Taguchi design ranked concentration of chitosan as the most important factor influencing the permeation parameters of diclofenac diethylamine. The flux of the diclofenac diethylamine solution through optimized chitosan membrane (T9) was found to be comparable to that obtained across rat skin. The mathematical model developed using multilinear regression analysis can be used to formulate chitosan membranes that can mimic the desired permeation characteristics. The developed chitosan membranes can be utilized as a substitute to animal skin for in vitro permeation studies.

Development of a broad-spectrum antiviral with activity against Ebola virus.

PubMed

Aman, M Javad; Kinch, Michael S; Warfield, Kelly; Warren, Travis; Yunus, Abdul; Enterlein, Sven; Stavale, Eric; Wang, Peifang; Chang, Shaojing; Tang, Qingsong; Porter, Kevin; Goldblatt, Michael; Bavari, Sina

2009-09-01

We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.

Design and testing of a controlled electromagnetic spinal cord impactor for use in large animal models of acute traumatic spinal cord injury.

PubMed

Petteys, Rory J; Spitz, Steven M; Syed, Hasan; Rice, R Andrew; Sarabia-Estrada, Rachel; Goodwin, C Rory; Sciubba, Daniel M; Freedman, Brett A

2017-09-01

Spinal cord injury (SCI) causes debilitating neurological dysfunction and has been observed in warfighters injured in IED blasts. Clinical benefit of SCI treatment remains elusive and better large animal models are needed to assess treatment options. Here, we describe a controlled electromagnetic spinal cord impactor for use in large animal models of SCI. A custom spinal cord impactor and platform were fabricated for large animals (e.g., pig, sheep, dog, etc.). Impacts were generated by a voice coil actuator; force and displacement were measured with a load cell and potentiometer respectively. Labview (National Instruments, Austin, TX) software was used to control the impact cycle and import force and displacement data. Software finite impulse response (FIR) filtering was employed for all input data. Silicon tubing was used a surrogate for spinal cord in order to test the device; repeated impacts were performed at 15, 25, and 40 Newtons. Repeated impacts demonstrated predictable results at each target force. The average duration of impact was 71.2 ±6.1ms. At a target force of 40N, the output force was 41.5 ±0.7N. With a target of 25N, the output force was 23.5 ±0.6N; a target of 15Newtons revealed an output force of 15.2 ±1.4N. The calculated acceleration range was 12.5-21.2m/s 2 . This custom spinal cord impactor reliably delivers precise impacts to the spinal cord and will be utilized in future research to study acute traumatic SCI in a large animal. Published by Elsevier Ltd.

Differential susceptibility of C57BL/6NCr and B6.Cg-Ptprca mice to commensal bacteria after whole body irradiation in translational bone marrow transplant studies

PubMed Central

Duran-Struuck, Raimon; Hartigan, Adam; Clouthier, Shawn G; Dyson, Melissa C; Lowler, Kathi; Gatza, Erin; Tawara, Isao; Toubai, Tomomi; Weisiger, Elisabeth; Hugunin, Kelly; Reddy, Pavan; Wilkinson, John E

2008-01-01

Background The mouse is an important and widely utilized animal model for bone marrow transplant (BMT) translational studies. Here, we document the course of an unexpected increase in mortality of congenic mice that underwent BMT. Methods Thirty five BMTs were analyzed for survival differences utilizing the Log Rank test. Affected animals were evaluated by physical examination, necropsy, histopathology, serology for antibodies to infectious disease, and bacterial cultures. Results Severe bacteremia was identified as the main cause of death. Gastrointestinal (GI) damage was observed in histopathology. The bacteremia was most likely caused by the translocation of bacteria from the GI tract and immunosuppression caused by the myeloablative irradiation. Variability in groups of animals affected was caused by increased levels of gamma and X-ray radiation and the differing sensitivity of the two nearly genetically identical mouse strains used in the studies. Conclusion Our retrospective analysis of thirty five murine BMTs performed in three different laboratories, identified C57BL/6NCr (Ly5.1) as being more radiation sensitive than B6.Cg-Ptprca/NCr (Ly5.2). This is the first report documenting a measurable difference in radiation sensitivity and its effects between an inbred strain of mice and its congenic counterpart eventually succumbing to sepsis after BMT. PMID:18307812

Polylysine-modified polyethylenimine (PEI-PLL) mediated VEGF gene delivery protects dopaminergic neurons in cell culture and in rat models of Parkinson's Disease (PD).

PubMed

Sheikh, Muhammad Abid; Malik, Yousra Saeed; Xing, Zhenkai; Guo, Zhaopei; Tian, Huayu; Zhu, Xiaojuan; Chen, Xuesi

2017-05-01

Parkinson's Disease (PD) is a chronic neurodegenerative disorder characterized by motor deficits which result from the progressive loss of dopaminergic neurons. Gene therapy using growth factors such as VEGF seems to be a viable approach for potential therapeutic treatment of PD. In this study, we utilized a novel non-viral gene carrier designated as PEI-PLL synthesized by our laboratory to deliver VEGF gene to study its effect by using both cell culture as well as animal models of PD. For cell culture experiments, we utilized 6-hydroxydopamine (6-OHDA) mediated cell death model of MN9D cells following transfection with either a control plasmid or VEGF expressing plasmid. As compared to control transfected cells, PEI-PLL mediated VEGF gene delivery to MN9D cells resulted in increased cell viability, increase in the number of Tyrosine hydroxylase (TH) positive cells and decreased apoptosis following 6-OHDA insult. Next, we studied the therapeutic potential of PEI-PLL mediated VEGF gene delivery in SNPc by using unilateral 6-OHDA Medial forebrain bundle (MFB) lesion model of PD in rats. VEGF administration prevented the loss of motor functions induced by 6-OHDA as determined by behavior analysis. Similarly, VEGF inhibited the 6-OHDA mediated loss of DA neurons in Substantia Nigra Pars Compacta (SNPc) as well as DA nerve fibers in striatum as determined by TH immunostaining. In addition, PEI-PLL mediated VEGF gene delivery also prevented apoptosis and microglial activation in PD rat models. Together, these results clearly demonstrated the beneficial effects of PEI-PLL mediated VEGF gene delivery on dopaminergic system in both cell culture and animal models of PD. In this report, we exploited the potential of PEI-PLL to deliver VEGF gene for the potential therapeutic treatment of PD by using both cell culture and animal models of PD. To the best of our knowledge, this is the first report describing the use of novel polymeric gene carriers for the delivery of VEGF gene to DA neurons with improved transfection efficiency. Finally, the study will lead to a significant advancement in the field of non-viral PD gene therapy treatment. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Non-animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin.

PubMed

Ud-Din, Sara; Bayat, Ardeshir

2017-04-01

Tissue repair models are essential to explore the pathogenesis of wound healing and scar formation, identify new drug targets/biomarkers and to test new therapeutics. However, no animal model is an exact replicate of the clinical situation in man as in addition to differences in the healing of animal skin; the response to novel therapeutics can be variable when compared to human skin. The aim of this review is to evaluate currently available non-animal wound repair models in human skin, including: in silico, in vitro, ex vivo, and in vivo. The appropriate use of these models is extremely relevant to wound-healing research as it enables improved understanding of the basic mechanisms present in the wound healing cascade and aid in discovering better means to regulate them for enhanced healing or prevention of abnormal scarring. The advantage of in silico models is that they can be used as a first in virtue screening tool to predict the effect of a drug/stimulus on cells/tissues and help plan experimental research/clinical trial studies but remain theoretical until validated. In vitro models allow direct quantitative examination of an effect on specific cell types alone without incorporating other tissue-matrix components, which limits their utility. Ex vivo models enable immediate and short-term evaluation of a particular effect on cells and its surrounding tissue components compared with in vivo models that provide direct analysis of a stimulus in the living human subject before/during/after exposure to a stimulus. Despite clear advantages, there remains a lack of standardisation in design, evaluation and follow-up, for acute/chronic wounds and scars in all models. In conclusion, ideal models of wound healing research are desirable and should mimic not only the structure but also the cellular and molecular interactions, of wound types in human skin. Future models may also include organ/skin-on-a-chip with potential application in wound healing research. © 2017 by the Wound Healing Society.

Development of a Model of Chronic Kidney Disease in the C57BL/6 Mouse with Properties of Progressive Human CKD

PubMed Central

Cruz, Gaile L.; Lu, Chao; Carlisle, Rachel E.; Werner, Kaitlyn E.; Ask, Kjetil; Dickhout, Jeffrey G.

2015-01-01

Chronic kidney disease (CKD) is a major healthcare problem with increasing prevalence in the population. CKD leads to end stage renal disease and increases the risk of cardiovascular disease. As such, it is important to study the mechanisms underlying CKD progression. To this end, an animal model was developed to allow the testing of new treatment strategies or molecular targets for CKD prevention. Many underlying risk factors result in CKD but the disease itself has common features, including renal interstitial fibrosis, tubular epithelial cell loss through apoptosis, glomerular damage, and renal inflammation. Further, CKD shows differences in prevalence between the genders with premenopausal women being relatively resistant to CKD. We sought to develop and characterize an animal model with these common features of human CKD in the C57BL/6 mouse. Mice of this genetic background have been used to produce transgenic strains that are commercially available. Thus, a CKD model in this strain would allow the testing of the effects of numerous genes on the severity or progression of CKD with minimal cost. This paper describes such a mouse model of CKD utilizing angiotensin II and deoxycorticosterone acetate as inducers. PMID:26064882

Investigating the underlying mechanisms of aberrant behaviors in bipolar disorder from patients to models

PubMed Central

van Enkhuizen, Jordy; Geyer, Mark A.; Minassian, Arpi; Perry, William; Henry, Brook L.; Young, Jared W.

2015-01-01

Psychiatric patients with bipolar disorder suffer from states of depression and mania, during which a variety of symptoms are present. Current treatments are limited and neurocognitive deficits in particular often remain untreated. Targeted therapies based on the biological mechanisms of bipolar disorder could fill this gap and benefit patients and their families. Developing targeted therapies would benefit from appropriate animal models which are challenging to establish, but remain a vital tool. In this review, we summarize approaches to create a valid model relevant to bipolar disorder. We focus on studies that use translational tests of multivariate exploratory behavior, sensorimotor gating, decision-making under risk, and attentional functioning to discover profiles that are consistent between patients and rodent models. Using this battery of translational tests, similar behavior profiles in bipolar mania patients and mice with reduced dopamine transporter activity have been identified. Future investigations should combine other animal models that are biologically relevant to the neuropsychiatric disorder with translational behavioral assessment as outlined here. This methodology can be utilized to develop novel targeted therapies that relieve symptoms for more patients without common side effects caused by current treatments. PMID:26297513

Animal-based folk remedies sold in public markets in Crato and Juazeiro do Norte, Ceará, Brazil.

PubMed

Ferreira, Felipe S; Brito, Samuel V; Ribeiro, Samuel C; Saraiva, Antônio A F; Almeida, Waltécio O; Alves, Rômulo R N

2009-06-03

Human communities consistently develop a detailed knowledge of the therapeutical and medicinal properties of the local flora and fauna, and these folk remedies often substitute medicines produced by the pharmaceutical industry. Animals (and their derived products) are essential ingredients in the preparation of many traditional remedies. The present work prepared an inventory of the animals sold in public markets in the cities of Crato and Juazeiro do Norte, Ceará State, Brazil. Information was obtained through the use of semi-structured questionnaires in interviews held with 27 merchants of medicinal animals (18 in the municipality of Juazeiro do Norte [11 men and 7 women] and 9 people in the municipality of Crato [6 men and 3 women]). We calculated the Informant Consensus Factor (ICF) to determine the consensus over which species are effective for particular ailments, as well as the species Use Value (UV) to determine the extent of utilization of each species. A total of 31 animal species, distributed among 21 families were identified as being used medicinally. The taxa most represented were: insects (8 species), mammals (7), fish (5), reptiles (5) and birds (4). The animals sold in these markets are used to treat a total of 24 ailments, with rheumatism, asthma, and inflammations having the largest numbers of citations. Three species not previously reported as having medicinal use were encountered: Leporinus steindachneri (utilized for treating cholesterol problems), Gryllus assimilis (utilized in treating urinary infections), and Phrynops tuberosus (used to treat asthma, rheumatism and bruises). The composition of the local fauna, the popular culture, and commercial considerations are factors that maintain and drive the market for therapeutic animal products - and the lack of monitoring and regulation of this commerce is worrisome from a conservationist perspective. A detailed knowledge of the fauna utilized in alternative medicine is fundamental to the conservation and rational use of the Brazilian fauna.

Animal-based folk remedies sold in public markets in Crato and Juazeiro do Norte, Ceará, Brazil

PubMed Central

Ferreira, Felipe S; Brito, amuel V; Ribeiro, Samuel C; Saraiva, Antônio AF; Almeida, Waltécio O; Alves, Rômulo RN

2009-01-01

Background Human communities consistently develop a detailed knowledge of the therapeutical and medicinal properties of the local flora and fauna, and these folk remedies often substitute medicines produced by the pharmaceutical industry. Animals (and their derived products) are essential ingredients in the preparation of many traditional remedies. The present work prepared an inventory of the animals sold in public markets in the cities of Crato and Juazeiro do Norte, Ceará State, Brazil. Methods Information was obtained through the use of semi-structured questionnaires in interviews held with 27 merchants of medicinal animals (18 in the municipality of Juazeiro do Norte [11 men and 7 women] and 9 people in the municipality of Crato [6 men and 3 women]). We calculated the Informant Consensus Factor (ICF) to determine the consensus over which species are effective for particular ailments, as well as the species Use Value (UV) to determine the extent of utilization of each species. Results A total of 31 animal species, distributed among 21 families were identified as being used medicinally. The taxa most represented were: insects (8 species), mammals (7), fish (5), reptiles (5) and birds (4). The animals sold in these markets are used to treat a total of 24 ailments, with rheumatism, asthma, and inflammations having the largest numbers of citations. Three species not previously reported as having medicinal use were encountered: Leporinus steindachneri (utilized for treating cholesterol problems), Gryllus assimilis (utilized in treating urinary infections), and Phrynops tuberosus (used to treat asthma, rheumatism and bruises). Conclusion The composition of the local fauna, the popular culture, and commercial considerations are factors that maintain and drive the market for therapeutic animal products – and the lack of monitoring and regulation of this commerce is worrisome from a conservationist perspective. A detailed knowledge of the fauna utilized in alternative medicine is fundamental to the conservation and rational use of the Brazilian fauna. PMID:19493345

The Utility, Limitations, and Promise of Proteomics in Animal Science

USDA-ARS?s Scientific Manuscript database

Proteomics experiments have the ability to simultaneously identify and quantify potentially thousands of proteins in one experiment. The use of this technology in animal science is still in its infancy, yet it holds significant promise as a method for advancing animal science research. Examples of...

Utility, Limitations, and Promise of Proteomics in Animal Science

USDA-ARS?s Scientific Manuscript database

Proteomics experiments have the ability to simultaneously identify and quantify thousands of proteins in one experiment. The use of this technology in veterinary/animal science is still in its infancy, yet it holds significant promise as a method for advancing veterinary/animal science research. E...

A Unimodal Model for Double Observer Distance Sampling Surveys.

PubMed

Becker, Earl F; Christ, Aaron M

2015-01-01

Distance sampling is a widely used method to estimate animal population size. Most distance sampling models utilize a monotonically decreasing detection function such as a half-normal. Recent advances in distance sampling modeling allow for the incorporation of covariates into the distance model, and the elimination of the assumption of perfect detection at some fixed distance (usually the transect line) with the use of double-observer models. The assumption of full observer independence in the double-observer model is problematic, but can be addressed by using the point independence assumption which assumes there is one distance, the apex of the detection function, where the 2 observers are assumed independent. Aerially collected distance sampling data can have a unimodal shape and have been successfully modeled with a gamma detection function. Covariates in gamma detection models cause the apex of detection to shift depending upon covariate levels, making this model incompatible with the point independence assumption when using double-observer data. This paper reports a unimodal detection model based on a two-piece normal distribution that allows covariates, has only one apex, and is consistent with the point independence assumption when double-observer data are utilized. An aerial line-transect survey of black bears in Alaska illustrate how this method can be applied.

Final Report 2007: DOE-FG02-87ER60561

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kilbourn, Michael R

2007-04-26

This project involved a multi-faceted approach to the improvement of techniques used in Positron Emission Tomography (PET), from radiochemistry to image processing and data analysis. New methods for radiochemical syntheses were examined, new radiochemicals prepared for evaluation and eventual use in human PET studies, and new pre-clinical methods examined for validation of biochemical parameters in animal studies. The value of small animal PET imaging in measuring small changes of in vivo biochemistry was examined and directly compared to traditional tissue sampling techniques. In human imaging studies, the ability to perform single experimental sessions utilizing two overlapping injections of radiopharmaceuticals wasmore » tested, and it was shown that valid biochemical measures for both radiotracers can be obtained through careful pharmacokinetic modeling of the PET emission data. Finally, improvements in reconstruction algorithms for PET data from small animal PET scanners was realized and these have been implemented in commercial releases. Together, the project represented an integrated effort to improve and extend all basic science aspects of PET imaging at both the animal and human level.« less

Recent advances in the analysis of behavioural organization and interpretation as indicators of animal welfare

PubMed Central

Asher, Lucy; Collins, Lisa M.; Ortiz-Pelaez, Angel; Drewe, Julian A.; Nicol, Christine J.; Pfeiffer, Dirk U.

2009-01-01

While the incorporation of mathematical and engineering methods has greatly advanced in other areas of the life sciences, they have been under-utilized in the field of animal welfare. Exceptions are beginning to emerge and share a common motivation to quantify ‘hidden’ aspects in the structure of the behaviour of an individual, or group of animals. Such analyses have the potential to quantify behavioural markers of pain and stress and quantify abnormal behaviour objectively. This review seeks to explore the scope of such analytical methods as behavioural indicators of welfare. We outline four classes of analyses that can be used to quantify aspects of behavioural organization. The underlying principles, possible applications and limitations are described for: fractal analysis, temporal methods, social network analysis, and agent-based modelling and simulation. We hope to encourage further application of analyses of behavioural organization by highlighting potential applications in the assessment of animal welfare, and increasing awareness of the scope for the development of new mathematical methods in this area. PMID:19740922

Biodiesel production from waste frying oil using waste animal bone and solar heat.

PubMed

Corro, Grisel; Sánchez, Nallely; Pal, Umapada; Bañuelos, Fortino

2016-01-01

A two-step catalytic process for the production of biodiesel from waste frying oil (WFO) at low cost, utilizing waste animal-bone as catalyst and solar radiation as heat source is reported in this work. In the first step, the free fatty acids (FFA) in WFO were esterified with methanol by a catalytic process using calcined waste animal-bone as catalyst, which remains active even after 10 esterification runs. The trans-esterification step was catalyzed by NaOH through thermal activation process. Produced biodiesel fulfills all the international requirements for its utilization as a fuel. A probable reaction mechanism for the esterification process is proposed considering the presence of hydroxyapatite at the surface of calcined animal bones. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of a Salmonella sugar kinase essential for the utilization of fructose-asparagine.

PubMed

Biswas, Pradip K; Behrman, Edward J; Gopalan, Venkat

2017-04-01

Salmonella can utilize fructose-asparagine (F-Asn), a naturally occurring Amadori product, as its sole carbon and nitrogen source. Conversion of F-Asn to the common intermediates glucose-6-phosphate, aspartate, and ammonia was predicted to involve the sequential action of an asparaginase, a kinase, and a deglycase. Mutants lacking the deglycase are highly attenuated in mouse models of intestinal inflammation owing to the toxic build-up of the deglycase substrate. The limited distribution of this metabolic pathway in the animal gut microbiome raises the prospects for antibacterial discovery. We report the biochemical characterization of the kinase that was expected to transform fructose-aspartate to 6-phosphofructose-aspartate during F-Asn utilization. In addition to confirming its anticipated function, we determined through studies of fructose-aspartate analogues that this kinase exhibits a substrate-specificity with greater tolerance to changes to the amino acid (including the d-isomer of aspartate) than to the sugar.

Mammalian models of chemically induced primary malignancies exploitable for imaging-based preclinical theragnostic research

PubMed Central

Liu, Yewei; Yin, Ting; Feng, Yuanbo; Cona, Marlein Miranda; Huang, Gang; Liu, Jianjun; Song, Shaoli; Jiang, Yansheng; Xia, Qian; Swinnen, Johannes V.; Bormans, Guy; Himmelreich, Uwe; Oyen, Raymond

2015-01-01

Compared with transplanted tumor models or genetically engineered cancer models, chemically induced primary malignancies in experimental animals can mimic the clinical cancer progress from the early stage on. Cancer caused by chemical carcinogens generally develops through three phases namely initiation, promotion and progression. Based on different mechanisms, chemical carcinogens can be divided into genotoxic and non-genotoxic ones, or complete and incomplete ones, usually with an organ-specific property. Chemical carcinogens can be classified upon their origins such as environmental pollutants, cooked meat derived carcinogens, N-nitroso compounds, food additives, antineoplastic agents, naturally occurring substances and synthetic carcinogens, etc. Carcinogen-induced models of primary cancers can be used to evaluate the diagnostic/therapeutic effects of candidate drugs, investigate the biological influential factors, explore preventive measures for carcinogenicity, and better understand molecular mechanisms involved in tumor initiation, promotion and progression. Among commonly adopted cancer models, chemically induced primary malignancies in mammals have several advantages including the easy procedures, fruitful tumor generation and high analogy to clinical human primary cancers. However, in addition to the time-consuming process, the major drawback of chemical carcinogenesis for translational research is the difficulty in noninvasive tumor burden assessment in small animals. Like human cancers, tumors occur unpredictably also among animals in terms of timing, location and the number of lesions. Thanks to the availability of magnetic resonance imaging (MRI) with various advantages such as ionizing-free scanning, superb soft tissue contrast, multi-parametric information, and utility of diverse contrast agents, now a workable solution to this bottleneck problem is to apply MRI for noninvasive detection, diagnosis and therapeutic monitoring on those otherwise uncontrollable animal models with primary cancers. Moreover, it is foreseeable that the combined use of chemically induced primary cancer models and molecular imaging techniques may help to develop new anticancer diagnostics and therapeutics. PMID:26682141

9 CFR 54.8 - Requirements for flock plans and post-exposure management and monitoring plans.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Requirements for flock plans and post... and post-exposure management and monitoring plans. (a) The owner of the flock or his or her agent must...: Utilization of a live-animal screening test; restrictions on the animals that may be moved from the flock...

9 CFR 54.8 - Requirements for flock plans and post-exposure management and monitoring plans.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Requirements for flock plans and post... and post-exposure management and monitoring plans. (a) The owner of the flock or his or her agent must...: Utilization of a live-animal screening test; restrictions on the animals that may be moved from the flock...

9 CFR 54.8 - Requirements for flock plans and post-exposure management and monitoring plans.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Requirements for flock plans and post... and post-exposure management and monitoring plans. (a) The owner of the flock or his or her agent must...: Utilization of a live-animal screening test; restrictions on the animals that may be moved from the flock...

9 CFR 54.8 - Requirements for flock plans and post-exposure management and monitoring plans.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Requirements for flock plans and post... and post-exposure management and monitoring plans. (a) The owner of the flock or his or her agent must...: Utilization of a live-animal screening test; restrictions on the animals that may be moved from the flock...

9 CFR 54.8 - Requirements for flock plans and post-exposure management and monitoring plans.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Requirements for flock plans and post... and post-exposure management and monitoring plans. (a) The owner of the flock or his or her agent must...: Utilization of a live-animal screening test; restrictions on the animals that may be moved from the flock...

Tourists' Attitudes toward the Use of Animals in Tourist Attractions: An Empirical Investigation

ERIC Educational Resources Information Center

Shani, Amir

2009-01-01

From time immemorial human beings have utilized animals for various needs and purposes, which led societies to debate the justification for using animals and to reflect on the way in which animals are treated. These concerns have also resulted in various contemporary studies aimed to reveal interest groups'--as well as the general publics'--views…

[Abdominal wall reconstruction with collagen membrane in an animal model of abdominal hernia. A preliminary report].

PubMed

Łukasiewicz, Aleksander; Drewa, Tomasz; Skopińska-Wiśniewska, Joanna; Molski, Stanisław

2008-01-01

Abdominal hernia repair is one of the most common surgical procedures. Current data indicate that the best treatment results are achieved with use of synthetic material to reinforce weakened abdominal wall. Prosthetic materials utilized for hernia repair induce adhesions with underlying viscera. They should be therefore separated from them by a layer of peritoneum otherwise adhesions may cause to serious complications such as bowel-skin fistulas. The aim of our work was to determine if implantation of our collagen membrane into abdominal wall defect induce adhesions in rat model of ventral hernia. The collagen film was obtained by acetic acid extraction of rat tail tendons and than casting the soluble fraction onto polyethylene shits. Abdominal wall defect was created in 10 Wistar male rats. Collagen membranes were implanted into the defect using interrupted polypropylene stitches. After 3 months of observation all animals were sacrificed. No adhesions between path structure and bowel developed. In one often rats (10%) adhesion between fixating stitch and omentum was observed. Complete mesothelium lining and vascular ingrowth were microscopically observed within implanted structure. Promising result requires further confirmation in a larger series of animals.

Prevention of intra-abdominal adhesion by bi-layer electrospun membrane.

PubMed

Jiang, Shichao; Wang, Wei; Yan, Hede; Fan, Cunyi

2013-06-04

The aim of this study was to compare the anti-adhesion efficacy of a bi-layer electrospun fibrous membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer with a single-layer PCL electrospun fibrous membrane in a rat cecum abrasion model. The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The bi-layer and PCL membranes were applied between the cecum and the abdominal wall, respectively. Control animals did not receive any treatment. After postoperative day 14, a visual semiquantitative grading scale was used to grade the extent of adhesion. Histological analysis was performed to reveal the features of adhesion tissues. Bi-layer membrane treated animals showed significantly lower adhesion scores than control animals (p < 0.05) and a lower adhesion score compared with the PCL membrane. Histological analysis of the bi-layer membrane treated rat rarely demonstrated tissue adhesion while that of the PCL membrane treated rat and control rat showed loose and dense adhesion tissues, respectively. Bi-layer membrane can efficiently prevent adhesion formation in abdominal cavity and showed a significantly decreased adhesion tissue formation compared with the control.

Density estimation in tiger populations: combining information for strong inference

USGS Publications Warehouse

Gopalaswamy, Arjun M.; Royle, J. Andrew; Delampady, Mohan; Nichols, James D.; Karanth, K. Ullas; Macdonald, David W.

2012-01-01

A productive way forward in studies of animal populations is to efficiently make use of all the information available, either as raw data or as published sources, on critical parameters of interest. In this study, we demonstrate two approaches to the use of multiple sources of information on a parameter of fundamental interest to ecologists: animal density. The first approach produces estimates simultaneously from two different sources of data. The second approach was developed for situations in which initial data collection and analysis are followed up by subsequent data collection and prior knowledge is updated with new data using a stepwise process. Both approaches are used to estimate density of a rare and elusive predator, the tiger, by combining photographic and fecal DNA spatial capture–recapture data. The model, which combined information, provided the most precise estimate of density (8.5 ± 1.95 tigers/100 km2 [posterior mean ± SD]) relative to a model that utilized only one data source (photographic, 12.02 ± 3.02 tigers/100 km2 and fecal DNA, 6.65 ± 2.37 tigers/100 km2). Our study demonstrates that, by accounting for multiple sources of available information, estimates of animal density can be significantly improved.

Density estimation in tiger populations: combining information for strong inference.

PubMed

Gopalaswamy, Arjun M; Royle, J Andrew; Delampady, Mohan; Nichols, James D; Karanth, K Ullas; Macdonald, David W

2012-07-01

A productive way forward in studies of animal populations is to efficiently make use of all the information available, either as raw data or as published sources, on critical parameters of interest. In this study, we demonstrate two approaches to the use of multiple sources of information on a parameter of fundamental interest to ecologists: animal density. The first approach produces estimates simultaneously from two different sources of data. The second approach was developed for situations in which initial data collection and analysis are followed up by subsequent data collection and prior knowledge is updated with new data using a stepwise process. Both approaches are used to estimate density of a rare and elusive predator, the tiger, by combining photographic and fecal DNA spatial capture-recapture data. The model, which combined information, provided the most precise estimate of density (8.5 +/- 1.95 tigers/100 km2 [posterior mean +/- SD]) relative to a model that utilized only one data source (photographic, 12.02 +/- 3.02 tigers/100 km2 and fecal DNA, 6.65 +/- 2.37 tigers/100 km2). Our study demonstrates that, by accounting for multiple sources of available information, estimates of animal density can be significantly improved.

Germline Transgenic Pigs by Sleeping Beauty Transposition in Porcine Zygotes and Targeted Integration in the Pig Genome

PubMed Central

Garrels, Wiebke; Mátés, Lajos; Holler, Stephanie; Dalda, Anna; Taylor, Ulrike; Petersen, Björn; Niemann, Heiner; Izsvák, Zsuzsanna; Ivics, Zoltán; Kues, Wilfried A.

2011-01-01

Genetic engineering can expand the utility of pigs for modeling human diseases, and for developing advanced therapeutic approaches. However, the inefficient production of transgenic pigs represents a technological bottleneck. Here, we assessed the hyperactive Sleeping Beauty (SB100X) transposon system for enzyme-catalyzed transgene integration into the embryonic porcine genome. The components of the transposon vector system were microinjected as circular plasmids into the cytoplasm of porcine zygotes, resulting in high frequencies of transgenic fetuses and piglets. The transgenic animals showed normal development and persistent reporter gene expression for >12 months. Molecular hallmarks of transposition were confirmed by analysis of 25 genomic insertion sites. We demonstrate germ-line transmission, segregation of individual transposons, and continued, copy number-dependent transgene expression in F1-offspring. In addition, we demonstrate target-selected gene insertion into transposon-tagged genomic loci by Cre-loxP-based cassette exchange in somatic cells followed by nuclear transfer. Transposase-catalyzed transgenesis in a large mammalian species expands the arsenal of transgenic technologies for use in domestic animals and will facilitate the development of large animal models for human diseases. PMID:21897845

Molecular Imaging of Experimental Abdominal Aortic Aneurysms

PubMed Central

Ramaswamy, Aneesh K.; Hamilton, Mark; Joshi, Rucha V.; Kline, Benjamin P.; Li, Rui; Wang, Pu; Goergen, Craig J.

2013-01-01

Current laboratory research in the field of abdominal aortic aneurysm (AAA) disease often utilizes small animal experimental models induced by genetic manipulation or chemical application. This has led to the use and development of multiple high-resolution molecular imaging modalities capable of tracking disease progression, quantifying the role of inflammation, and evaluating the effects of potential therapeutics. In vivo imaging reduces the number of research animals used, provides molecular and cellular information, and allows for longitudinal studies, a necessity when tracking vessel expansion in a single animal. This review outlines developments of both established and emerging molecular imaging techniques used to study AAA disease. Beyond the typical modalities used for anatomical imaging, which include ultrasound (US) and computed tomography (CT), previous molecular imaging efforts have used magnetic resonance (MR), near-infrared fluorescence (NIRF), bioluminescence, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). Mouse and rat AAA models will hopefully provide insight into potential disease mechanisms, and the development of advanced molecular imaging techniques, if clinically useful, may have translational potential. These efforts could help improve the management of aneurysms and better evaluate the therapeutic potential of new treatments for human AAA disease. PMID:23737735

Separability of drag and thrust in undulatory animals and machines

NASA Astrophysics Data System (ADS)

Bale, Rahul; Shirgaonkar, Anup A.; Neveln, Izaak D.; Bhalla, Amneet Pal Singh; Maciver, Malcolm A.; Patankar, Neelesh A.

2014-12-01

For nearly a century, researchers have tried to understand the swimming of aquatic animals in terms of a balance between the forward thrust from swimming movements and drag on the body. Prior approaches have failed to provide a separation of these two forces for undulatory swimmers such as lamprey and eels, where most parts of the body are simultaneously generating drag and thrust. We nonetheless show that this separation is possible, and delineate its fundamental basis in undulatory swimmers. Our approach unifies a vast diversity of undulatory aquatic animals (anguilliform, sub-carangiform, gymnotiform, bal-istiform, rajiform) and provides design principles for highly agile bioinspired underwater vehicles. This approach has practical utility within biology as well as engineering. It is a predictive tool for use in understanding the role of the mechanics of movement in the evolutionary emergence of morphological features relating to locomotion. For example, we demonstrate that the drag-thrust separation framework helps to predict the observed height of the ribbon fin of electric knifefish, a diverse group of neotropical fish which are an important model system in sensory neurobiology. We also show how drag-thrust separation leads to models that can predict the swimming velocity of an organism or a robotic vehicle.

Utilization of MRI for Cerebral White Matter Injury in a Hypobaric Swine Model-Validation of Technique

DTIC Science & Technology

2017-05-23

study demonstrates high reproducibility of quantitative noninvasive MRI, suggesting MRI is an appropriate assessment tool for TBI and hypobaric-induced...propofol/ketamine adjusted to maintain stable physiological parameters and anesthesia. On study day 1, baseline imaging was performed. Exposure episodes...began on study day 3 with three subject animals exposed six times to 9,144 meters (ascent/descent time 15 minutes) over 12 days, one exposed five times

An individual-based model of skipjack tuna (Katsuwonus pelamis) movement in the tropical Pacific ocean

NASA Astrophysics Data System (ADS)

Scutt Phillips, Joe; Sen Gupta, Alex; Senina, Inna; van Sebille, Erik; Lange, Michael; Lehodey, Patrick; Hampton, John; Nicol, Simon

2018-05-01

The distribution of marine species is often modeled using Eulerian approaches, in which changes to population density or abundance are calculated at fixed locations in space. Conversely, Lagrangian, or individual-based, models simulate the movement of individual particles moving in continuous space, with broader-scale patterns such as distribution being an emergent property of many, potentially adaptive, individuals. These models offer advantages in examining dynamics across spatiotemporal scales and making comparisons with observations from individual-scale data. Here, we introduce and describe such a model, the Individual-based Kinesis, Advection and Movement of Ocean ANimAls model (Ikamoana), which we use to replicate the movement processes of an existing Eulerian model for marine predators (the Spatial Ecosystem and Population Dynamics Model, SEAPODYM). Ikamoana simulates the movement of either individual or groups of animals by physical ocean currents, habitat-dependent stochastic movements (kinesis), and taxis movements representing active searching behaviours. Applying our model to Pacific skipjack tuna (Katsuwonus pelamis), we show that it accurately replicates the evolution of density distribution simulated by SEAPODYM with low time-mean error and a spatial correlation of density that exceeds 0.96 at all times. We demonstrate how the Lagrangian approach permits easy tracking of individuals' trajectories for examining connectivity between different regions, and show how the model can provide independent estimates of transfer rates between commonly used assessment regions. In particular, we find that retention rates in most assessment regions are considerably smaller (up to a factor of 2) than those estimated by this population of skipjack's primary assessment model. Moreover, these rates are sensitive to ocean state (e.g. El Nino vs La Nina) and so assuming fixed transfer rates between regions may lead to spurious stock estimates. A novel feature of the Lagrangian approach is that individual schools can be tracked through time, and we demonstrate that movement between two assessment regions at broad temporal scales includes extended transits through other regions at finer-scales. Finally, we discuss the utility of this modeling framework for the management of marine reserves, designing effective monitoring programmes, and exploring hypotheses regarding the behaviour of hard-to-observe oceanic animals.

Compartmental analysis of the disposition of benzo[a]pyrene in rats.

PubMed

Bevan, D R; Weyand, E H

1988-11-01

We have previously reported the disposition of benzo[a]pyrene (B[a]P) and its metabolites in male Sprague-Dawley rats following intratracheal instillation of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1986) Cancer Res., 46, 5655-5661]. In some experiments, cannulas were implanted in the bile duct of the animals prior to administration of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1987) Drug Metab. Disposition, 15, 442-448]. Based on these data, we have developed a compartmental model of the distribution of radioactivity to provide a quantitative description of the fate of B[a]P and its metabolites in rats. Modeling of the distribution of radioactivity was performed using the Simulation, Analysis and Modeling (SAAM) and conversational SAAM (CONSAM) computer programs. Compartments in the model included organs into which the largest amounts of radioactivity were distributed as well as pathways for excretion of radioactivity from the animals. Data from animals with and without cannulas implanted in the bile duct were considered simultaneously during modeling. Radioactivity was so rapidly absorbed from the lungs that an absorption phase into blood was not apparent at the earliest sampling times. Using the model of extrapolate to shorter times, it was predicted that the maximum amount of radioactivity was present in blood within 2 min after administration. In addition, considerable recycling of radioactivity back to lungs from blood was predicted by the model. Transfer of radioactivity from blood to liver and carcass (skin, muscle, bones, fat and associated blood) also was extensive. Carcass was modeled as the sum of two compartments to obtain agreement between the model and experimental data. The model accounted for enterohepatic circulation of B[a]P metabolites; data also required that intestinal secretion be included in the model. Quantitative data obtained from compartmental analysis included rate constants for transfer of radioactivity among compartments as well as statistical parameters indicating the identifiability of the rate constants. That the model is consistent with two sets of data, those obtained in animals with and without a biliary cannula, indicates its potential utility in predicting the disposition of B[a]P and its metabolites in vivo.

Immune Recognition of Gene Transfer Vectors: Focus on Adenovirus as a Paradigm

PubMed Central

Aldhamen, Yasser Ali; Seregin, Sergey S.; Amalfitano, Andrea

2011-01-01

Recombinant Adenovirus (Ad) based vectors have been utilized extensively as a gene transfer platform in multiple pre-clinical and clinical applications. These applications are numerous, and inclusive of both gene therapy and vaccine based approaches to human or animal diseases. The widespread utilization of these vectors in both animal models, as well as numerous human clinical trials (Ad-based vectors surpass all other gene transfer vectors relative to numbers of patients treated, as well as number of clinical trials overall), has shed light on how this virus vector interacts with both the innate and adaptive immune systems. The ability to generate and administer large amounts of this vector likely contributes not only to their ability to allow for highly efficient gene transfer, but also their elicitation of host immune responses to the vector and/or the transgene the vector expresses in vivo. These facts, coupled with utilization of several models that allow for full detection of these responses has predicted several observations made in human trials, an important point as lack of similar capabilities by other vector systems may prevent detection of such responses until only after human trials are initiated. Finally, induction of innate or adaptive immune responses by Ad vectors may be detrimental in one setting (i.e., gene therapy) and be entirely beneficial in another (i.e., prophylactic or therapeutic vaccine based applications). Herein, we review the current understanding of innate and adaptive immune responses to Ad vectors, as well some recent advances that attempt to capitalize on this understanding so as to further broaden the safe and efficient use of Ad-based gene transfer therapies in general. PMID:22566830

COMPARATIVE DIVERSITY OF FECAL BACTERIA IN AGRICULTURALLY SIGNIFICANT ANIMALS TO IDENTIFY ALTERNATIVE TARGETS FOR MICROBIAL SOURCE TRACKING

EPA Science Inventory

Animals of agricultural significance contribute a large percentage of fecal pollution to waterways via runoff contamination. The premise of microbial source tracking is to utilize fecal bacteria to identify target populations which are directly correlated to specific animal feces...

The utility of animal behavior studies in natural resource management

USDA-ARS?s Scientific Manuscript database

Although research on the behavior of individual animals has been growing in recent years in parts of the scientific community, the role that individual variation among animals may play in the outcome of species interactions in nature may be somewhat overlooked in natural resource management. Recogni...

Current biotechnologies and future possibilities in preservation of animal germplasm

USDA-ARS?s Scientific Manuscript database

Animal germplasm (semen, eggs, embryos, DNA, tissue) can be preserved from all agricultural species and result in the regeneration of animal lines or breeds. However, there are limitations to successful utilization of the material that are attributed to the type, post-thaw quality, and available as...

Deployment and evaluation of an active RFID tracking system for finishing pigs

USDA-ARS?s Scientific Manuscript database

Modern swine facilities were developed mainly based on logistics of feeding and moving animals. In recent years, the public has become increasingly concerned about animal care and well-being. A better understanding of the animal space utilization in current facilities could lead to improved facilit...

14 CFR 1232.102 - Policy.

Code of Federal Regulations, 2012 CFR

2012-01-01

... animal subjects held or used for research, testing, teaching, or other activities supported by the... Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training” on pp. 81-83 of the Guide... Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CARE AND USE OF ANIMALS IN THE CONDUCT OF...

14 CFR 1232.102 - Policy.

Code of Federal Regulations, 2011 CFR

2011-01-01

... animal subjects held or used for research, testing, teaching, or other activities supported by the... Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training” on pp. 81-83 of the Guide... Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CARE AND USE OF ANIMALS IN THE CONDUCT OF...

14 CFR 1232.102 - Policy.

Code of Federal Regulations, 2010 CFR

2010-01-01

... animal subjects held or used for research, testing, teaching, or other activities supported by the... Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training” on pp. 81-83 of the Guide... Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CARE AND USE OF ANIMALS IN THE CONDUCT OF...

14 CFR § 1232.102 - Policy.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., handling, and treatment of animal subjects held or used for research, testing, teaching, or other... “Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training” on pp... Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CARE AND USE OF ANIMALS IN THE CONDUCT OF...

14 CFR 1232.102 - Policy.

Code of Federal Regulations, 2013 CFR

2013-01-01

... animal subjects held or used for research, testing, teaching, or other activities supported by the... Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training” on pp. 81-83 of the Guide... Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CARE AND USE OF ANIMALS IN THE CONDUCT OF...

COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

EPA Science Inventory

The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

GEOTHERMAL ENVIRONMENTAL IMPACT ASSESSMENT: PROCEDURES FOR USING FAUNA AS BIOLOGICAL MONITORS OF POTENTIAL GEOTHERMAL POLLUTANTS

EPA Science Inventory

This is the first in a series of reports that covers the feasibility of utilizing wildlife and domestic animals to design a monitoring strategy for assessing the environmental impact of geothermal resource development. Animal tissues and animal products were collected in the vici...

Testing the consistency of wildlife data types before combining them: the case of camera traps and telemetry.

PubMed

Popescu, Viorel D; Valpine, Perry; Sweitzer, Rick A

2014-04-01

Wildlife data gathered by different monitoring techniques are often combined to estimate animal density. However, methods to check whether different types of data provide consistent information (i.e., can information from one data type be used to predict responses in the other?) before combining them are lacking. We used generalized linear models and generalized linear mixed-effects models to relate camera trap probabilities for marked animals to independent space use from telemetry relocations using 2 years of data for fishers (Pekania pennanti) as a case study. We evaluated (1) camera trap efficacy by estimating how camera detection probabilities are related to nearby telemetry relocations and (2) whether home range utilization density estimated from telemetry data adequately predicts camera detection probabilities, which would indicate consistency of the two data types. The number of telemetry relocations within 250 and 500 m from camera traps predicted detection probability well. For the same number of relocations, females were more likely to be detected during the first year. During the second year, all fishers were more likely to be detected during the fall/winter season. Models predicting camera detection probability and photo counts solely from telemetry utilization density had the best or nearly best Akaike Information Criterion (AIC), suggesting that telemetry and camera traps provide consistent information on space use. Given the same utilization density, males were more likely to be photo-captured due to larger home ranges and higher movement rates. Although methods that combine data types (spatially explicit capture-recapture) make simple assumptions about home range shapes, it is reasonable to conclude that in our case, camera trap data do reflect space use in a manner consistent with telemetry data. However, differences between the 2 years of data suggest that camera efficacy is not fully consistent across ecological conditions and make the case for integrating other sources of space-use data.

Dopamine reward prediction error responses reflect marginal utility.

PubMed

Stauffer, William R; Lak, Armin; Schultz, Wolfram

2014-11-03

Optimal choices require an accurate neuronal representation of economic value. In economics, utility functions are mathematical representations of subjective value that can be constructed from choices under risk. Utility usually exhibits a nonlinear relationship to physical reward value that corresponds to risk attitudes and reflects the increasing or decreasing marginal utility obtained with each additional unit of reward. Accordingly, neuronal reward responses coding utility should robustly reflect this nonlinearity. In two monkeys, we measured utility as a function of physical reward value from meaningful choices under risk (that adhered to first- and second-order stochastic dominance). The resulting nonlinear utility functions predicted the certainty equivalents for new gambles, indicating that the functions' shapes were meaningful. The monkeys were risk seeking (convex utility function) for low reward and risk avoiding (concave utility function) with higher amounts. Critically, the dopamine prediction error responses at the time of reward itself reflected the nonlinear utility functions measured at the time of choices. In particular, the reward response magnitude depended on the first derivative of the utility function and thus reflected the marginal utility. Furthermore, dopamine responses recorded outside of the task reflected the marginal utility of unpredicted reward. Accordingly, these responses were sufficient to train reinforcement learning models to predict the behaviorally defined expected utility of gambles. These data suggest a neuronal manifestation of marginal utility in dopamine neurons and indicate a common neuronal basis for fundamental explanatory constructs in animal learning theory (prediction error) and economic decision theory (marginal utility). Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The National Research Initiative Competitive Grants Program in animal reproduction: changes in priorities and scope relevant to United States animal agriculture.

PubMed

Mirando, M A

2007-03-01

The National Research Initiative (NRI) Competitive Grants Program is the USDA's major competitive grants program and is administered by the Cooperative State Research, Education, and Extension Service. The NRI was authorized by the US Congress in the 1990 Farm Bill at a funding level of $500 million; however, the maximal NRI appropriation was $181.17 million in fiscal year (FY) 2006. Across all programs, the NRI is mandated to use 40% of its funding to support mission-linked research. Since its inception in 1991, the NRI has funded competitive grants in the discipline of animal reproduction. Before 2004, the Animal Reproduction Program funded a broad range of projects encompassing almost every subdiscipline in reproductive biology of farm animals, including aquatic species important to the aquaculture industry and laboratory animals. During FY 2004, the NRI Animal Reproduction Program narrowed the focus of its funding priorities to 5 issue-based topics in an effort to make greater measurable improvements in a few high-impact areas over the next 10 years. Funding priorities were narrowed further in FY 2006 to 3 subdisciplines based, in part, on recommendations that emerged from a stakeholder workshop conducted by Cooperative State Research, Education, and Extension Service in August 2004. In FY 2003, Congress authorized expenditure of up to 20% of the funds appropriated to the NRI to support projects that integrate at least 2 of the 3 functions of research, education, and extension. In FY 2004, the Animal Reproduction Program included a funding priority for integrated projects focused primarily on infertility in dairy cattle. The program funded its first integrated project in FY 2005. During FY 2002, increased emphasis on justification for the use of model systems (e.g., laboratory animals and in vitro systems) was included in the NRI request for applications. In FY 2006, applications proposing to primarily utilize nonagricultural animal models were excluded from the program. Currently, all proposed studies must be thoroughly justified in terms of their relevance to US animal agriculture and to program priorities identified within the request for applications.

Evaluation of the GARD assay in a blind Cosmetics Europe study.

PubMed

Johansson, Henrik; Gradin, Robin; Forreryd, Andy; Agemark, Maria; Zeller, Kathrin; Johansson, Angelica; Larne, Olivia; van Vliet, Erwin; Borrebaeck, Carl; Lindstedt, Malin

2017-01-01

Chemical hypersensitivity is an immunological response towards foreign substances, commonly referred to as sensitizers, which gives rise primarily to the clinical symptoms known as allergic contact dermatitis. For the purpose of mitigating risks associated with consumer products, chemicals are screened for sensitizing effects. Historically, such predictive screenings have been performed using animal models. However, due to industrial and regulatory demand, animal models for the purpose of sensitization assessment are being replaced by non-animal testing methods, a global trend that is spreading across industries and market segments. To meet this demand, the Genomic Allergen Rapid Detection (GARD) assay was developed. GARD is a novel, cell-based assay that utilizes the innate recognition of xenobiotic substances by dendritic cells, as measured by a multivariate readout of genomic biomarkers. Following cellular stimulation, chemicals are classified as sensitizers or non-sensitizers based on induced transcriptional profiles. Recently, a number of non-animal methods were comparatively evaluated by Cosmetics Europe, using a coherent and blinded test panel of reference chemicals with human and local lymph node assay data, comprising a wide range of sensitizers and non-sensitizers. The outcome of the GARD assay is presented in this paper. It was demonstrated that GARD is a highly functional assay with a predictive performance of 83% in this Cosmetics Europe dataset. The average accumulated predictive accuracy of GARD across independent datasets was 86% for skin sensitization hazard.

Neuroplasticity to a single-episode traumatic stress revealed by resting-state fMRI in awake rats.

PubMed

Liang, Zhifeng; King, Jean; Zhang, Nanyin

2014-12-01

Substantial evidence has suggested that the brain structures of the medial prefrontal cortex (mPFC) and amygdala (AMYG) are implicated in the pathophysiology of stress-related disorders. However, little is known with respect to the system-level adaptation of their neural circuitries to the perturbations of traumatic stressors. By utilizing behavioral tests and an awake animal imaging approach, in the present study we non-invasively investigated the impact of single-episode predator odor exposure in an inescapable environment on behaviors and neural circuits in rodents. We found that predator odor exposure significantly increased the freezing behavior. In addition, animals exhibited heightened anxiety levels seven days after the exposure. Intriguingly, we also found that the intrinsic functional connectivity within the AMYG-mPFC circuit was considerably compromised seven days after the traumatic event. Our data provide neuroimaging evidence suggesting that prolonged neuroadaptation induced by a single episode of traumatic stress can be non-invasively detected in rodents. These results also support the face validity and construction validity of using the paradigm of single trauma exposure in an inescapable environment as an animal model for post-traumatic stress disorder. Taken together, the present study has opened a new avenue to investigating animal models of stress-related mental disorders by going beyond static neuroanatomy, and ultimately bridging the gap between basic biomedical and human imaging research. Copyright © 2014 Elsevier Inc. All rights reserved.

Altered CB receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine.

PubMed

Rodríguez-Gaztelumendi, Antonio; Rojo, M Luisa; Pazos, Angel; Díaz, Alvaro

2009-03-01

Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB(1) receptor density ([(3)H]CP55490 binding) and functionality (stimulation of [(35)S]GTPgammaS binding by the cannabinoid (CB) agonist WIN 55212-2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity in the open-field test was fully abolished. Interestingly, chronic fluoxetine fully reversed the enhanced CB(1)-receptor signaling in PFC observed following OBX. The CB agonist Delta(9)-tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any behavioral effect in sham-operated animals but returned locomotor activity to control values in OBX rats. As both acute administration of Delta(9)-tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect in the OBX rat, it is not unlikely that the regionally selective enhancement of CB(1) receptor-signaling in the PFC could be related with the altered OBX behavior. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants.

Effects of organophosphorus anticholinesterase compounds on brain glucose and energy metabolism. Annual summary report, 1 October 1982-29 February 1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medina, M.A.; Miller, A.L.

1984-09-01

The effects of paraoxon and Soman on glucose utilization and of Soman on the levels of intermediary metabolites were investigated in rat brain. The rate of glucose utilization and the levels of intermediary metabolites were determined in six brain areas at varying time periods after administration of 0.5 or 0.8 of the paraoxon or Soman LD50. Behavioral changes were observed only with the 0.8 LD50 dose of both compounds and some of the animals exhibited convulsive activity with this dose of Soman. Brain glucose utilization tended to be decreased by 0.8 LD50 paraoxon and 0.5 LD50 Soman. Some alterations inmore » metabolite levels were observed but these were not consistent and could not be correlated with the rate of glucose utilization. In animals with Soman-induced convulsions, glucose utilization and lactate levels were elevated only in the cortex and thalamus/basal ganglia. ATP, creatine phosphate and glucose levels were decreased in the cortex but not in other brain areas, suggesting the possibility of uncoupling of oxidative phosphorylation. Pretreatment with atropine prevented the behavioral responses and the changes in glucose utilization previously observed with 0.8 Soman LD50. Our results in convulsing animals are similar to those which have been observed with the excitatorytoxins kainic acid and bicuculline.« less

Behavioral profiling as a translational approach in an animal model of posttraumatic stress disorder.

PubMed

Ardi, Ziv; Albrecht, Anne; Richter-Levin, Alon; Saha, Rinki; Richter-Levin, Gal

2016-04-01

Diagnosis of psychiatric disorders in humans is based on comparing individuals to the normal population. However, many animal models analyze averaged group effects, thus compromising their translational power. This discrepancy is particularly relevant in posttraumatic stress disorder (PTSD), where only a minority develop the disorder following a traumatic experience. In our PTSD rat model, we utilize a novel behavioral profiling approach that allows the classification of affected and unaffected individuals in a trauma-exposed population. Rats were exposed to underwater trauma (UWT) and four weeks later their individual performances in the open field and elevated plus maze were compared to those of the control group, allowing the identification of affected and resilient UWT-exposed rats. Behavioral profiling revealed that only a subset of the UWT-exposed rats developed long-lasting behavioral symptoms. The proportion of affected rats was further enhanced by pre-exposure to juvenile stress, a well-described risk factor of PTSD. For a biochemical proof of concept we analyzed the expression levels of the GABAA receptor subunits α1 and α2 in the ventral, dorsal hippocampus and basolateral amygdala. Increased expression, mainly of α1, was observed in ventral but not dorsal hippocampus of exposed animals, which would traditionally be interpreted as being associated with the exposure-resultant psychopathology. However, behavioral profiling revealed that this increased expression was confined to exposed-unaffected individuals, suggesting a resilience-associated expression regulation. The results provide evidence for the importance of employing behavioral profiling in animal models of PTSD, in order to better understand the neural basis of stress vulnerability and resilience. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet-Kidney Transplantation.

PubMed

Vallabhajosyula, Prashanth; Hirakata, Atsushi; Weiss, Matthew; Griesemer, Adam; Shimizu, Akira; Hong, Hanzhou; Habertheuer, Andreas; Tchipashvili, Vaja; Yamada, Kazuhiko; Sachs, David H

2017-11-01

In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized. Three experimental donor animals underwent total pancreatectomy and autologous islet transplantation underneath the renal capsule to prepare an IK at a load of ≤1,000 islet equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the engraftment period (fasting blood glucose >250 mg/dL). Three control donor animals underwent partial pancreatectomy (sufficient to maintain normoglycemia during islet engraftment period) and IK preparation. As in vivo functional readout for islet engraftment, the IKs were transplanted across an immunologic minor or class I mismatch barrier into diabetic, nephrectomized recipients at an islet load of ∼4,500 IE/kg recipient weight. A 12-d course of cyclosporine was administered for tolerance induction. All experimental donors became diabetic and showed signs of end organ injury, while control donors maintained normoglycemia. All recipients of IK from both experimental and control donors achieved glycemic control over long-term follow-up, with reversal of diabetic nephropathy and with similar glucose tolerance tests. In this preclinical, large animal model, neither islet engraftment nor subsequent long-term islet function after transplantation appear to be affected by the diabetic state.

Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation

PubMed Central

Hirakata, Atsushi; Weiss, Matthew; Griesemer, Adam; Shimizu, Akira; Hong, Hanzhou; Habertheuer, Andreas; Tchipashvili, Vaja; Yamada, Kazuhiko; Sachs, David H.

2018-01-01

In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet–kidney (IK) model previously described by our laboratory was utilized. Three experimental donor animals underwent total pancreatectomy and autologous islet transplantation underneath the renal capsule to prepare an IK at a load of ≤1,000 islet equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the engraftment period (fasting blood glucose >250 mg/dL). Three control donor animals underwent partial pancreatectomy (sufficient to maintain normoglycemia during islet engraftment period) and IK preparation. As in vivo functional readout for islet engraftment, the IKs were transplanted across an immunologic minor or class I mismatch barrier into diabetic, nephrectomized recipients at an islet load of ∼4,500 IE/kg recipient weight. A 12-d course of cyclosporine was administered for tolerance induction. All experimental donors became diabetic and showed signs of end organ injury, while control donors maintained normoglycemia. All recipients of IK from both experimental and control donors achieved glycemic control over long-term follow-up, with reversal of diabetic nephropathy and with similar glucose tolerance tests. In this preclinical, large animal model, neither islet engraftment nor subsequent long-term islet function after transplantation appear to be affected by the diabetic state. PMID:29338381

AN ANIMAL MODEL OF SCHIZOPHRENIA BASED ON CHRONIC LSD ADMINISTRATION: OLD IDEA, NEW RESULTS

PubMed Central

Marona-Lewicka, Danuta; Nichols, Charles D.; Nichols, David E.

2011-01-01

Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as “clearly a paranoid state.” We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT2A receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP. PMID:21352832

Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

PubMed

Whittaker, Alexandra L; Lymn, Kerry A; Wallace, Georgia L; Howarth, Gordon S

2016-01-01

Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

Adult carrion arthropod community in a tropical rainforest of Malaysia: analysis on three common forensic entomology animal models.

PubMed

Azwandi, A; Nina Keterina, H; Owen, L C; Nurizzati, M D; Omar, B

2013-09-01

Decomposing carrion provides a temporary microhabitat and food source for a distinct community of organisms. Arthropods constitute a major part of this community and can be utilized to estimate the postmortem interval (PMI) of cadavers during criminal investigations. However, in Malaysia, knowledge of carrion arthropod assemblages and their succession is superficial. Therefore, a study on three types of forensic entomology animal model was conducted from 27 September 2010 to 28 October 2010 in a tropical rainforest at National University of Malaysia, Bangi, Selangor, Malaysia. Over one month collections of arthropods were made on nine animal carcasses: three laboratory rats (Rattus norvegicus, mean weight: 0.508 ± 0.027 kg), three rabbits (Oryctolagus cuniculus, mean weight: 2.538 ± 0.109 kg) and three long tailed macaque (Macaca fascicularis, mean weight: 5.750 ± 0.551 kg). A total of 31,433 arthropods belonging to eight orders and twenty-eight families were collected from all carcasses. Among 2924 of adults flies collected, approximately 19% were calliphorids with Chrysomya megacephala (Fabricius, 1794) being the most abundant. Arthropod taxon richness was lower on rat carcasses compared to that of rabbit and monkey carcasses, and this was more apparent during the first week of decomposition. However, there were no significant differences in Shannon-Weiner index (H'), Simpson dominance index (C) and Pielou's Evenness index (J) between different animal model. The arthropod assemblages associated to animal model were different significantly (p<0.05) while decomposition stage was a significant factor influencing insect assemblages (p<0.05). Analysis on the arthropods succession indicated that some taxa have a clear visitation period while the others, particularly Coleoptera, did not show a clear successional pattern thus require futher insect succession study. Although human bodies were not possible for the succession study, most of the arthropods collected are necrophagous, and will also possibly colonize human cadaver, and potentially be useful in assisting in estimates of PMI in future forensic cases in Malaysia.

Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa

PubMed Central

Ross, Rachel A.; Mandelblat-Cerf, Yael; Verstegen, Anne M.J.

2017-01-01

Anorexia nervosa (AN) is a psychiatric illness with minimal effective treatments and a very high rate of mortality. Understanding the neurobiological underpinnings of the disease is imperative for improving outcomes and can be aided by the study of animal models. The activity-based anorexia rodent model (ABA) is the current best parallel for the study of AN. This review describes the basic neurobiology of feeding and hyperactivity seen in both ABA and AN, and compiles the research on the role that stress-response and reward pathways play in modulating the homeostatic drive to eat and to expend energy, which become dysfunctional in ABA and AN. PMID:27824637

Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa.

PubMed

Ross, Rachel A; Mandelblat-Cerf, Yael; Verstegen, Anne M J

Anorexia nervosa (AN) is a psychiatric illness with minimal effective treatments and a very high rate of mortality. Understanding the neurobiological underpinnings of the disease is imperative for improving outcomes and can be aided by the study of animal models. The activity-based anorexia rodent model (ABA) is the current best parallel for the study of AN. This review describes the basic neurobiology of feeding and hyperactivity seen in both ABA and AN, and compiles the research on the role that stress-response and reward pathways play in modulating the homeostatic drive to eat and to expend energy, which become dysfunctional in ABA and AN.

To pair or not to pair: Sources of social variability with white-faced saki monkeys (Pithecia pithecia) as a case study.

PubMed

Thompson, Cynthia L

2016-05-01

Intraspecific variability in social systems is gaining increased recognition in primatology. Many primate species display variability in pair-living social organizations through incorporating extra adults into the group. While numerous models exist to explain primate pair-living, our tools to assess how and why variation in this trait occurs are currently limited. Here I outline an approach which: (i) utilizes conceptual models to identify the selective forces driving pair-living; (ii) outlines novel possible causes for variability in social organization; and (iii) conducts a holistic species-level analysis of social behavior to determine the factors contributing to variation in pair-living. A case study on white-faced sakis (Pithecia pithecia) is used to exemplify this approach. This species lives in either male-female pairs or groups incorporating "extra" adult males and/or females. Various conceptual models of pair-living suggest that high same-sex aggression toward extra-group individuals is a key component of the white-faced saki social system. Variable pair-living in white-faced sakis likely represents alternative strategies to achieve competency in this competition, in which animals experience conflicting selection pressures between achieving successful group defense and maintaining sole reproductive access to mates. Additionally, independent decisions by individuals may generate social variation by preventing other animals from adopting a social organization that maximizes fitness. White-faced saki inter-individual relationships and demographic patterns also lend conciliatory support to this conclusion. By utilizing both model-level and species-level approaches, with a consideration for potential sources of variation, researchers can gain insight into the factors generating variation in pair-living social organizations. © 2014 The Authors. American Journal of Primatology published by Wiley Periodicals, Inc.

Experimental model of traumatic ulcer in the cheek mucosa of rats.

PubMed

Cavalcante, Galyléia Meneses; Sousa de Paula, Renata Janaína; Souza, Leonardo Peres de; Sousa, Fabrício Bitu; Mota, Mário Rogério Lima; Alves, Ana Paula Negreiros Nunes

2011-06-01

To establish an experimental model of traumatic ulcer in rat cheek mucosa for utilization in future alternative therapy studies. A total of 60 adult male rats (250 - 300g) were used. Ulceration of the left cheek mucosa was provoked by abrasion using a nº 15 scalpel blade. The animals were observed for 10 days, during which they were weighed and their ulcers were measured. The histological characteristics were analyzed and scored according to the ulcer phase. In the statistical analysis, a value of p<0.01 was considered a statistically significant response in all cases. During the five first days, the animals lost weight (Student t test, p<0.01). The ulcerated area receded linearly over time and was almost completely cicatrized after 10 days (ANOVA, Tendency posttest, p<0.0001). Groups on days 1, 2 and 3 days displayed similar results, but a decrease in scores were observed after the 4th day. The proposed cheek mucosa ulcer model in rats can be considered an efficient, low-cost, reliable, and reproducible method.

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque’s and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines

PubMed Central

Kalkeri, Raj; Goebel, Scott; Cai, Zhaohui; Green, Brian; Lin, Shuling; Snyder, Beth; Hagelin, Kimberly; Walters, Kevin B.; Koide, Fusataka

2018-01-01

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains, obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasure development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge. PMID:29723973

Implications of genetic research on the role of the serotonin in depression: emphasis on the serotonin type 1A receptor and the serotonin transporter.

PubMed

Neumeister, Alexander; Young, Theresa; Stastny, Juergen

2004-08-01

Serotonin systems appear to play a key role in the pathophysiology of major depressive disorder. Consequently, ongoing research determines whether serotonin related genes account for the very robust differential behavioral and neural mechanisms that discriminate patients with depression from healthy controls. Serotonin type 1(A) receptors and the serotonin transporters are reduced in depression, and recent genetic research in animals and humans has implicated both in depression. Preclinical studies have utilized a variety of animal models that have been used to explain pathophysiological mechanisms in humans, although it is not clear at all whether these models constitute relevant models for depression in humans. However, data from preclinical studies can generate hypotheses that are tested in humans by combining genetic data with behavioral and physiological challenge paradigms and neuroimaging. These studies will enhance our understanding about combined influences from multiple interacting genes, as well as from environmental factors on brain circuits and their function, and about how these mechanisms may contribute to the pathophysiology of neuropsychiatric disorders.

Catalytic Properties and Biomedical Applications of Cerium Oxide Nanoparticles

PubMed Central

Walkey, Carl; Das, Soumen; Seal, Sudipta; Erlichman, Joseph; Heckman, Karin; Ghibelli, Lina; Traversa, Enrico; McGinnis, James F.; Self, William T.

2014-01-01

Cerium oxide nanoparticles (Nanoceria) have shown promise as catalytic antioxidants in the test tube, cell culture models and animal models of disease. However given the reactivity that is well established at the surface of these nanoparticles, the biological utilization of Nanoceria as a therapeutic still poses many challenges. Moreover the form that these particles take in a biological environment, such as the changes that can occur due to a protein corona, are not well established. This review aims to summarize the existing literature on biological use of Nanoceria, and to raise questions about what further study is needed to apply this interesting catalytic material to biomedical applications. These questions include: 1) How does preparation, exposure dose, route and experimental model influence the reported effects of Nanoceria in animal studies? 2) What are the considerations to develop Nanoceria as a therapeutic agent in regards to these parameters? 3) What biological targets of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are relevant to this targeting, and how do these properties also influence the safety of these nanomaterials? PMID:26207185

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque's and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines.

PubMed

Rayner, Jonathan O; Kalkeri, Raj; Goebel, Scott; Cai, Zhaohui; Green, Brian; Lin, Shuling; Snyder, Beth; Hagelin, Kimberly; Walters, Kevin B; Koide, Fusataka

2018-05-01

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains, obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasure development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

UTILIZING SPECTRAL TRANSCRANIAL DOPPLER TO CHARACTERIZE CEREBRAL HEMODYNAMICS IN A NON-HUMAN PRIMATE (RHESUS MACAQUE)

DTIC Science & Technology

2017-05-16

Animal Care and Use Committee (IACUC) in compliance with all applicable Federal regulations governing the protection of animals in research. Mr. G...13 Page | 4 Abbreviations AALAC Association for Assessment and Accreditation for Laboratory Animal Care...ETCO2 End-Tidal Carbon Dioxide IACUC Institutional Animal Care and Use Committee ICA Internal Carotid Siphon MAP Mean Arterial Pressure MCA Middle

Rhesus macaque model of chronic opiate dependence and neuro-AIDS: longitudinal assessment of auditory brainstem responses and visual evoked potentials

PubMed Central

Riazi, Mariam; Marcario, Joanne K; Samson, Frank K.; Kenjale, Himanshu; Adany, Istvan; Staggs, Vincent; Ledford, Emily; Marquis, Janet; Narayan, Opendra; Cheney, Paul D.

2013-01-01

Our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a rhesus macaque model of neuro-AIDS utilizing a chronic continuous drug delivery paradigm. The goal of this study was to clarify whether morphine is protective, or if it exacerbates simian immunodeficiency virus (SIV) related systemic and neurological disease. Our model employs a macrophage tropic CD4/CCR5 co-receptor virus, SIVmac239 (R71/E17), which crosses the blood brain barrier shortly after inoculation and closely mimics the natural disease course of human immunodeficiency virus (HIV) infection. The cohort was divided into 3 groups: morphine only, SIV only, and SIV + morphine. Evoked potential (EP) abnormalities in sub-clinically infected macaques were evident as early as eight weeks post-inoculation. Prolongations in EP latencies were observed in SIV-infected macaques across all modalities. Animals with the highest CSF viral loads and clinical disease showed more abnormalities than those with sub-clinical disease, confirming our previous work (Raymond et al, 1998, 1999, 2000). Although some differences were observed in auditory and visual evoked potentials in morphine treated compared to untreated SIV-infected animals, the effects were relatively small and not consistent across evoked potential type. However, morphine treated animals with subclinical disease had a clear tendency toward higher virus loads in peripheral and CNS tissues (Marcario et al., 2008) suggesting that if had been possible to follow all animals to end-stage disease, a clearer pattern of evoked potential abnormality might have emerged. PMID:19283490

Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model.

PubMed

Kaluzhny, Yulia; Kandárová, Helena; d'Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

2015-08-23

To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492.

Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

PubMed Central

Kaluzhny, Yulia; Kandárová, Helena; d’Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

2015-01-01

To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492. PMID:26325674

Maternal Nutrient Restriction in Guinea Pigs as an Animal Model for Inducing Fetal Growth Restriction.

PubMed

Elias, Alexander A; Ghaly, Andrew; Matushewski, Brad; Regnault, Timothy R H; Richardson, Bryan S

2016-02-01

We determined the impact of moderate maternal nutrient restriction (MNR) in guinea pigs on pregnancy outcomes, maternal/fetal growth parameters, and blood analytes to further characterize the utility of this model for inducing fetal growth restriction (FGR). Thirty guinea pig sows were fed ad libitum (Control) or 70% of the control diet prepregnant switching to 90% at midpregnancy (MNR). Animals were necropsied near term with weights obtained on all sows, fetuses, and placenta. Fetal blood sampling and organ dissection were undertaken in appropriate for gestational age (AGA) fetuses from Control litters and FGR fetuses from MNR litters using > or < 80 g which approximated the 10th percentile for the population weight distribution of the Control fetuses. MNR fetal demise rates (1/43) were extremely low in contrast to that seen with uterine artery ligation/ablation models, albeit with increased preterm delivery in MNR sows (3 of 15). We confirm that MNR fetuses are smaller and have increased placental/fetal weight ratios as often seen in human FGR infants. We provide justification for using a fetal weight threshold for categorizing AGA Control and FGR-MNR cohorts reducing population variance, and show that FGR-MNR fetuses have asymmetrical organ growth, and are polycythemic and hypoglycemic which are also well associated with moderate FGR in humans. These findings further support the utility of moderate MNR in guinea pigs for inducing FGR with many similarities to that in humans with moderate growth restriction whether resulting from maternal undernourishment or placental insufficiency. © The Author(s) 2015.

A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

PubMed

Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

2016-11-01

The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue response near the implant surface in a bone marrow microenvironment, and it also shows great potential in making transgenic animal resource applicable to biomaterial studies, so that the design of novel biomaterials could be better guided.

Chronic Histopathological and Behavioral Outcomes of Experimental Traumatic Brain Injury in Adult Male Animals

PubMed Central

Osier, Nicole D.; Carlson, Shaun W.; DeSana, Anthony

2015-01-01

Abstract The purpose of this review is to survey the use of experimental animal models for studying the chronic histopathological and behavioral consequences of traumatic brain injury (TBI). The strategies employed to study the long-term consequences of TBI are described, along with a summary of the evidence available to date from common experimental TBI models: fluid percussion injury; controlled cortical impact; blast TBI; and closed-head injury. For each model, evidence is organized according to outcome. Histopathological outcomes included are gross changes in morphology/histology, ventricular enlargement, gray/white matter shrinkage, axonal injury, cerebrovascular histopathology, inflammation, and neurogenesis. Behavioral outcomes included are overall neurological function, motor function, cognitive function, frontal lobe function, and stress-related outcomes. A brief discussion is provided comparing the most common experimental models of TBI and highlighting the utility of each model in understanding specific aspects of TBI pathology. The majority of experimental TBI studies collect data in the acute postinjury period, but few continue into the chronic period. Available evidence from long-term studies suggests that many of the experimental TBI models can lead to progressive changes in histopathology and behavior. The studies described in this review contribute to our understanding of chronic TBI pathology. PMID:25490251

An Exploratory Study of Animal-Assisted Interventions Utilized by Mental Health Professionals

ERIC Educational Resources Information Center

O'Callaghan, Dana M.; Chandler, Cynthia K.

2011-01-01

This study implemented an exploratory analysis to examine how a sample of mental health professionals incorporates specific animal-assisted techniques into the therapeutic process. An extensive review of literature related to animal-assisted therapy (AAT) resulted in the identification of 18 techniques and 10 intentions for the practice of AAT in…

Utility of arterial blood gas, CBC, biochemistry and cardiac hormones as evaluation parameters of cardiovascular disease in nonhuman primates.

PubMed

Nakayama, Shunya; Koie, Hiroshi; Kanayama, Kiichi; Katakai, Yuko; Ito-Fujishiro, Yasuyo; Sankai, Tadashi; Yasutomi, Yasuhiro; Ageyama, Naohide

2018-06-11

Cardiovascular disease (CVD) has a tremendous impact on the quality of life of humans. While experimental animals are valuable to medical research as models of human diseases, cardiac systems differ widely across various animal species. Thus, we examined a CVD model in cynomolgus monkeys. Laboratory primates are precious resources, making it imperative that symptoms of diseases and disorders are detected as early as possible. Thus, in this study we comprehensively examined important indicators of CVD in cynomolgus monkeys, including arterial blood gas, complete blood count (CBC), biochemistry, and cardiac hormones. The control group included 20 healthy macaques showing non-abnormal findings in screening tests, whereas the CVD group included 20 macaques with valvular disease and cardiomyopathy. An increase of red blood cell distribution width was observed in the CBC, indicating chronic inflammation related to CVD. An increase of HCO 3 was attributed to the correction of acidosis. Furthermore, development of the CVD model was supported by significant increases in natriuretic peptides. It is suggested that these results indicated a correlation between human CVD and the model in monkeys. Moreover, blood tests including arterial blood gas are non-invasive and can be performed more easily than other technical tests. CVD affected animals easily change their condition by anesthesia and surgical invasion. Pay attention to arterial blood gas and proper respond to their condition are important for research. This data may facilitate human research and aid in the management and veterinary care of nonhuman primates.

Convergent functional genomic studies of ω-3 fatty acids in stress reactivity, bipolar disorder and alcoholism.

PubMed

Le-Niculescu, H; Case, N J; Hulvershorn, L; Patel, S D; Bowker, D; Gupta, J; Bell, R; Edenberg, H J; Tsuang, M T; Kuczenski, R; Geyer, M A; Rodd, Z A; Niculescu, A B

2011-04-26

Omega-3 fatty acids have been proposed as an adjuvant treatment option in psychiatric disorders. Given their other health benefits and their relative lack of toxicity, teratogenicity and side effects, they may be particularly useful in children and in females of child-bearing age, especially during pregnancy and postpartum. A comprehensive mechanistic understanding of their effects is needed. Here we report translational studies demonstrating the phenotypic normalization and gene expression effects of dietary omega-3 fatty acids, specifically docosahexaenoic acid (DHA), in a stress-reactive knockout mouse model of bipolar disorder and co-morbid alcoholism, using a bioinformatic convergent functional genomics approach integrating animal model and human data to prioritize disease-relevant genes. Additionally, to validate at a behavioral level the novel observed effects on decreasing alcohol consumption, we also tested the effects of DHA in an independent animal model, alcohol-preferring (P) rats, a well-established animal model of alcoholism. Our studies uncover sex differences, brain region-specific effects and blood biomarkers that may underpin the effects of DHA. Of note, DHA modulates some of the same genes targeted by current psychotropic medications, as well as increases myelin-related gene expression. Myelin-related gene expression decrease is a common, if nonspecific, denominator of neuropsychiatric disorders. In conclusion, our work supports the potential utility of omega-3 fatty acids, specifically DHA, for a spectrum of psychiatric disorders such as stress disorders, bipolar disorder, alcoholism and beyond.

Disruption of visual circuit formation and refinement in a mouse model of autism

PubMed Central

Khanbabaei, Maryam; Murari, Kartikeya; Rho, Jong M.

2016-01-01

Aberrant connectivity is believed to contribute to the pathophysiology of autism spectrum disorder (ASD). Recent neuroimaging studies have increasingly identified such impairments in patients with ASD, including alterations in sensory systems. However, the cellular substrates and molecular underpinnings of disrupted connectivity remain poorly understood. Utilizing eye‐specific segregation in the dorsal lateral geniculate nucleus (dLGN) as a model system, we investigated the formation and refinement of precise patterning of synaptic connections in the BTBR T + tf/J (BTBR) mouse model of ASD. We found that at the neonatal stage, the shape of the dLGN occupied by retinal afferents was altered in the BTBR group compared to C57BL/6J (B6) animals. Notably, the degree of overlap between the ipsi‐ and contralateral afferents was significantly greater in the BTBR mice. Moreover, these abnormalities continued into mature stage in the BTBR animals, suggesting persistent deficits rather than delayed maturation of axonal refinement. Together, these results indicate disrupted connectivity at the synaptic patterning level in the BTBR mice, suggesting that in general, altered neural circuitry may contribute to autistic behaviours seen in this animal model. In addition, these data are consistent with the notion that lower‐level, primary processing mechanisms contribute to altered visual perception in ASD. Autism Res 2017, 10: 212–223. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. PMID:27529416

Complete depletion of primordial germ cells in an All-female fish leads to Sex-biased gene expression alteration and sterile All-male occurrence.

PubMed

Liu, Wei; Li, Shi-Zhu; Li, Zhi; Wang, Yang; Li, Xi-Yin; Zhong, Jian-Xiang; Zhang, Xiao-Juan; Zhang, Jun; Zhou, Li; Gui, Jian-Fang

2015-11-18

Gynogenesis is one of unisexual reproduction modes in vertebrates, and produces all-female individuals with identical genetic background. In sexual reproduction vertebrates, the roles of primordial germ cells on sexual dimorphism and gonadal differentiation have been largely studied, and two distinct functional models have been proposed. However, the role of primordial germ cells remains unknown in unisexual animals, and it is also unclear whether the functional models in sexual reproduction animals are common in unisexual animals. To solve these puzzles, we attempt to utilize the gynogenetic superiority of polyploid Carassius gibelio to create a complete germ cell-depleted gonad model by a similar morpholino-mediated knockdown approach used in other examined sexual reproduction fishes. Through the germ cell-depleted gonad model, we have performed comprehensive and comparative transcriptome analysis, and revealed a complete alteration of sex-biased gene expression. Moreover, the expression alteration leads to up-regulation of testis-biased genes and down-regulation of ovary-biased genes, and results in the occurrence of sterile all-males with testis-like gonads and secondary sex characteristics in the germ cell-depleted gynogenetic Carassius gibelio. Our current results have demonstrated that unisexual gynogenetic embryos remain keeping male sex determination information in the genome, and the complete depletion of primordial germ cells in the all-female fish leads to sex-biased gene expression alteration and sterile all-male occurrence.

Effect of different carotenoid-containing diets on the vitamin A levels and colour parameters in Iberian pigs' tissues: utility as biomarkers of traceability.

PubMed

Álvarez, R; Vicario, I M; Meléndez-Martínez, A J; Alcalde, M J

2014-10-01

Retinol and fat colour parameters in Iberian pigs fed on different carotenoid-containing diets were assessed. Thirty animals in two groups were considered: Iberian breed pigs fed on acorns and grass (Montanera) and on concentrate (Cebo). Carotenoids and retinoids were analysed in the diets and in plasma, liver and perirenal fat of the animals by HPLC and HPLC-MS. Retinol levels in plasma and fat were similar in Montanera and Cebo animals. The utility of retonids and colour parameters as traceability index was also explored. Retinoids in liver classified correctly 93% of the animals according to their diet L* and hab. CIELAB parameters of the perirenal fat discriminated correctly 78.6% of the animals according to their diet. L* values for the Montanera animals were significantly different (P<0.01) from those fed on concentrate. It can be claimed that the liver retinol profile and fat colour parameters can be useful for feeding traceability purposes in Iberian pigs breed in Montanera and Cebo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ocean Heat Content Reveals Secrets of Fish Migrations

PubMed Central

Luo, Jiangang; Ault, Jerald S.; Shay, Lynn K.; Hoolihan, John P.; Prince, Eric D.; Brown, Craig A.; Rooker, Jay R.

2015-01-01

For centuries, the mechanisms surrounding spatially complex animal migrations have intrigued scientists and the public. We present a new methodology using ocean heat content (OHC), a habitat metric that is normally a fundamental part of hurricane intensity forecasting, to estimate movements and migration of satellite-tagged marine fishes. Previous satellite-tagging research of fishes using archival depth, temperature and light data for geolocations have been too coarse to resolve detailed ocean habitat utilization. We combined tag data with OHC estimated from ocean circulation and transport models in an optimization framework that substantially improved geolocation accuracy over SST-based tracks. The OHC-based movement track provided the first quantitative evidence that many of the tagged highly migratory fishes displayed affinities for ocean fronts and eddies. The OHC method provides a new quantitative tool for studying dynamic use of ocean habitats, migration processes and responses to environmental changes by fishes, and further, improves ocean animal tracking and extends satellite-based animal tracking data for other potential physical, ecological, and fisheries applications. PMID:26484541

Authentication of animal origin of heparin and low molecular weight heparin including ovine, porcine and bovine species using 1D NMR spectroscopy and chemometric tools.

PubMed

Monakhova, Yulia B; Diehl, Bernd W K; Fareed, Jawed

2018-02-05

High resolution (600MHz) nuclear magnetic resonance (NMR) spectroscopy is used to distinguish heparin and low-molecular weight heparins (LMWHs) produced from porcine, bovine and ovine mucosal tissues as well as their blends. For multivariate analysis several statistical methods such as principal component analysis (PCA), factor discriminant analysis (FDA), partial least squares - discriminant analysis (PLS-DA), linear discriminant analysis (LDA) were utilized for the modeling of NMR data of more than 100 authentic samples. Heparin and LMWH samples from the independent test set (n=15) were 100% correctly classified according to its animal origin. Moreover, by using 1 H NMR coupled with chemometrics and several batches of bovine heparins from two producers were differentiated. Thus, NMR spectroscopy combined with chemometrics is an efficient tool for simultaneous identification of animal origin and process based manufacturing difference in heparin products. Copyright © 2017 Elsevier B.V. All rights reserved.

Advancing Behavior Analysis in Zoos and Aquariums.

PubMed

Maple, Terry L; Segura, Valerie D

2015-05-01

Zoos, aquariums, and other captive animal facilities offer promising opportunities to advance the science and practice of behavior analysis. Zoos and aquariums are necessarily concerned with the health and well-being of their charges and are held to a high standard by their supporters (visitors, members, and donors), organized critics, and the media. Zoos and aquariums offer unique venues for teaching and research and a locus for expanding the footprint of behavior analysis. In North America, Europe, and the UK, formal agreements between zoos, aquariums, and university graduate departments have been operating successfully for decades. To expand on this model, it will be necessary to help zoo and aquarium managers throughout the world to recognize the value of behavior analysis in the delivery of essential animal health and welfare services. Academic institutions, administrators, and invested faculty should consider the utility of training students to meet the growing needs of applied behavior analysis in zoos and aquariums and other animal facilities such as primate research centers, sanctuaries, and rescue centers.

Anatomical and metabolic small-animal whole-body imaging using ring-shaped confocal photoacoustic computed tomography

NASA Astrophysics Data System (ADS)

Xia, Jun; Chatni, Muhammad; Maslov, Konstantin; Wang, Lihong V.

2013-03-01

Due to the wide use of animals for human disease studies, small animal whole-body imaging plays an increasingly important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose metabolic information, leading to higher costs of building dual-modality systems. Even with image coregistration, the spatial resolution of the metabolic imaging modality is not improved. We present a ring-shaped confocal photoacoustic computed tomography (RC-PACT) system that can provide both assessments in a single modality. Utilizing the novel design of confocal full-ring light delivery and ultrasound transducer array detection, RC-PACT provides full-view cross-sectional imaging with high spatial resolution. Scanning along the orthogonal direction provides three-dimensional imaging. While the mouse anatomy was imaged with endogenous hemoglobin contrast, the glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose. Through mouse tumor models, we demonstrate that RC-PACT may be a paradigm shifting imaging method for preclinical research.

A framework for optimizing micro-CT in dual-modality micro-CT/XFCT small-animal imaging system

NASA Astrophysics Data System (ADS)

Vedantham, Srinivasan; Shrestha, Suman; Karellas, Andrew; Cho, Sang Hyun

2017-09-01

Dual-modality Computed Tomography (CT)/X-ray Fluorescence Computed Tomography (XFCT) can be a valuable tool for imaging and quantifying the organ and tissue distribution of small concentrations of high atomic number materials in small-animal system. In this work, the framework for optimizing the micro-CT imaging system component of the dual-modality system is described, either when the micro-CT images are concurrently acquired with XFCT and using the x-ray spectral conditions for XFCT, or when the micro-CT images are acquired sequentially and independently of XFCT. This framework utilizes the cascaded systems analysis for task-specific determination of the detectability index using numerical observer models at a given radiation dose, where the radiation dose is determined using Monte Carlo simulations.

Venus in motion: An animated video catalog of Pioneer Venus Orbiter Cloud Photopolarimeter images

NASA Technical Reports Server (NTRS)

Limaye, Sanjay S.

1992-01-01

Images of Venus acquired by the Pioneer Venus Orbiter Cloud Photopolarimeter (OCPP) during the 1982 opportunity have been utilized to create a short video summary of the data. The raw roll by roll images were first navigated using the spacecraft attitude and orbit information along with the CPP instrument pointing information. The limb darkening introduced by the variation of solar illumination geometry and the viewing angle was then modelled and removed. The images were then projected to simulate a view obtained from a fixed perspective with the observer at 10 Venus radii away and located above a Venus latitude of 30 degrees south and a longitude 60 degrees west. A total of 156 images from the 1982 opportunity have been animated at different dwell rates.

Can microbes compete with cows for sustainable protein production - A feasibility study on high quality protein

NASA Astrophysics Data System (ADS)

Vestergaard, Mike; Chan, Siu Hung Joshua; Jensen, Peter Ruhdal

2016-11-01

An increasing population and their increased demand for high-protein diets will require dramatic changes in the food industry, as limited resources and environmental issues will make animal derived foods and proteins, gradually more unsustainable to produce. To explore alternatives to animal derived proteins, an economic model was built around the genome-scale metabolic network of E. coli to study the feasibility of recombinant protein production as a food source. Using a novel model, we predicted which microbial production strategies are optimal for economic return, by capturing the tradeoff between the market prices of substrates, product output and the efficiency of microbial production. A case study with the food protein, Bovine Alpha Lactalbumin was made to evaluate the upstream economic feasibilities. Simulations with different substrate profiles at maximum productivity were used to explore the feasibility of recombinant Bovine Alpha Lactalbumin production coupled with market prices of utilized materials. We found that recombinant protein production could be a feasible food source and an alternative to traditional sources.

Automatic creation of three-dimensional avatars

NASA Astrophysics Data System (ADS)

Villa-Uriol, Maria-Cruz; Sainz, Miguel; Kuester, Falko; Bagherzadeh, Nader

2003-01-01

Highly accurate avatars of humans promise a new level of realism in engineering and entertainment applications, including areas such as computer animated movies, computer game development interactive virtual environments and tele-presence. In order to provide high-quality avatars, new techniques for the automatic acquisition and creation are required. A framework for the capture and construction of arbitrary avatars from image data is presented in this paper. Avatars are automatically reconstructed from multiple static images of a human subject by utilizing image information to reshape a synthetic three-dimensional articulated reference model. A pipeline is presented that combines a set of hardware-accelerated stages into one seamless system. Primary stages in this pipeline include pose estimation, skeleton fitting, body part segmentation, geometry construction and coloring, leading to avatars that can be animated and included into interactive environments. The presented system removes traditional constraints in the initial pose of the captured subject by using silhouette-based modification techniques in combination with a reference model. Results can be obtained in near-real time with very limited user intervention.

Noninvasive in vivo glucose sensing using an iris based technique

NASA Astrophysics Data System (ADS)

Webb, Anthony J.; Cameron, Brent D.

2011-03-01

Physiological glucose monitoring is important aspect in the treatment of individuals afflicted with diabetes mellitus. Although invasive techniques for glucose monitoring are widely available, it would be very beneficial to make such measurements in a noninvasive manner. In this study, a New Zealand White (NZW) rabbit animal model was utilized to evaluate a developed iris-based imaging technique for the in vivo measurement of physiological glucose concentration. The animals were anesthetized with isoflurane and an insulin/dextrose protocol was used to control blood glucose concentration. To further help restrict eye movement, a developed ocular fixation device was used. During the experimental time frame, near infrared illuminated iris images were acquired along with corresponding discrete blood glucose measurements taken with a handheld glucometer. Calibration was performed using an image based Partial Least Squares (PLS) technique. Independent validation was also performed to assess model performance along with Clarke Error Grid Analysis (CEGA). Initial validation results were promising and show that a high percentage of the predicted glucose concentrations are within 20% of the reference values.

Applications of population genetics to animal breeding, from wright, fisher and lush to genomic prediction.

PubMed

Hill, William G

2014-01-01

Although animal breeding was practiced long before the science of genetics and the relevant disciplines of population and quantitative genetics were known, breeding programs have mainly relied on simply selecting and mating the best individuals on their own or relatives' performance. This is based on sound quantitative genetic principles, developed and expounded by Lush, who attributed much of his understanding to Wright, and formalized in Fisher's infinitesimal model. Analysis at the level of individual loci and gene frequency distributions has had relatively little impact. Now with access to genomic data, a revolution in which molecular information is being used to enhance response with "genomic selection" is occurring. The predictions of breeding value still utilize multiple loci throughout the genome and, indeed, are largely compatible with additive and specifically infinitesimal model assumptions. I discuss some of the history and genetic issues as applied to the science of livestock improvement, which has had and continues to have major spin-offs into ideas and applications in other areas.

Prokaryotic expression and in vitro functional analysis of IL-1β and MCP-1 from guinea pig.

PubMed

Dirisala, Vijaya R; Jeevan, Amminikutty; Ly, Lan H; McMurray, David N

2013-06-01

The Guinea pig (Cavia porcellus) is an excellent animal model for studying human tuberculosis (TB) and also for a number of other infectious and non-infectious diseases. One of the major roadblocks in effective utilization of this animal model is the lack of readily available immunological reagents. In order to address this issue, guinea pig interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were efficiently cloned and expressed in a prokaryotic expression vector, and the expressed proteins in soluble form from both the genes were confirmed by N-terminal sequencing. The biological activity of recombinant guinea pig IL-1β was demonstrated by its ability to drive proliferation in thymocytes, and the recombinant guinea pig MCP-1 exhibited chemotactic activity for guinea pig resident peritoneal macrophages. These biologically active recombinant guinea pig proteins will facilitate an in-depth understanding of the role they play in the immune responses of the guinea pig to TB and other diseases.

Lit appearance modeling of illumination systems

NASA Astrophysics Data System (ADS)

Koshel, R. John

2002-09-01

In illumination systems the look and feel are often more important than objective criterion, such as uniformity and efficiency. The reason for this is two fold: the lit appearance often sells an item and substantial variation in the illumination distribution (up to 50%) over a broad region is not noticeable to an observer. Therefore, subjective criterion, such as the lit appearance, typically plays a crucial role in the development of an illumination system. Additionally, by using computer models to ascertain the lit appearance before manufacture of the system, it allows the designer to modify the system while not demanding investment to produce prototypes. I discuss methods of determining the lit appearance for illumination systems. This modeling includes the inclusion of material and surface properties, such as surface finish, spectral transmission, and internal scattering; the response of the human eye; and the amount of rays that must be traced. By archiving the ray data, animations as a function of position and angle can be developed. Examples are developed to highlight the utility of this technique. These examples include taillights for the automotive industry and a backlit LCD screen for a laptop. Animations of these models demonstrate their luminance.

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

PubMed Central

Voorhees, Jaymie R.; Rohlman, Diane S.; Lein, Pamela J.; Pieper, Andrew A.

2017-01-01

Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally. PMID:28149268

Evaluating Trauma Sonography for Operational Use in the Microgravity Environment

NASA Technical Reports Server (NTRS)

Kirkpatrick, Andrew W.; Jones, Jeffrey A.; Sargsyan, Ashot; Hamilton, Douglas; Melton, Shannon; Beck, George; Nicolaou, Savvas; Campbell, Mark; Dulchavsky, Scott

2007-01-01

Sonography is the only medical imaging modality aboard the ISS, and is likely to remain the leading imaging modality in future human space flight programs. While trauma sonography (TS) has been well recognized for terrestrial trauma settings, the technique had to be evaluated for suitability in space flight prior to adopting it as an operational capability. The authors found the following four-phased evaluative approach applicable to this task: 1) identifying standard or novel terrestrial techniques for potential use in space medicine; 2) developing and testing these techniques with suggested modifications on the ground (1g) either in clinical settings or in animal models, as appropriate; 3) evaluating and refining the techniques in parabolic flight (0g); and 4) validating and implementing for clinical use in space. In Phase I of the TS project, expert opinion and literature review suggested TS to be a potential screening tool for trauma in space. In Phase II, animal models were developed and tested in ground studies, and clinical studies were carried out in collaborating trauma centers. In Phase III, animal models were flight-tested in the NASA KC-135 Reduced Gravity Laboratory. Preliminary results of the first three phases demonstrated potential clinical utility of TS in microgravity. Phase IV studies have begun to address crew training issues, on-board imaging protocols, and data transfer procedures necessary to offer the modified TS technique for space use.

Longitudinal Analysis of Mouse SDOCT Volumes

PubMed Central

Antony, Bhavna J.; Carass, Aaron; Lang, Andrew; Kim, Byung-Jin; Zack, Donald J.; Prince, Jerry L.

2017-01-01

Spectral-domain optical coherence tomography (SDOCT), in addition to its routine clinical use in the diagnosis of ocular diseases, has begun to find increasing use in animal studies. Animal models are frequently used to study disease mechanisms as well as to test drug efficacy. In particular, SDOCT provides the ability to study animals longitudinally and non-invasively over long periods of time. However, the lack of anatomical landmarks makes the longitudinal scan acquisition prone to inconsistencies in orientation. Here, we propose a method for the automated registration of mouse SDOCT volumes. The method begins by accurately segmenting the blood vessels and the optic nerve head region in the scans using a pixel classification approach. The segmented vessel maps from follow-up scans were registered using an iterative closest point (ICP) algorithm to the baseline scan to allow for the accurate longitudinal tracking of thickness changes. Eighteen SDOCT volumes from a light damage model study were used to train a random forest utilized in the pixel classification step. The area under the curve (AUC) in a leave-one-out study for the retinal blood vessels and the optic nerve head (ONH) was found to be 0.93 and 0.98, respectively. The complete proposed framework, the retinal vasculature segmentation and the ICP registration, was applied to a secondary set of scans obtained from a light damage model. A qualitative assessment of the registration showed no registration failures. PMID:29138527

A human pathogenic bacterial infection model using the two-spotted cricket, Gryllus bimaculatus.

PubMed

Kochi, Yuto; Miyashita, Atsushi; Tsuchiya, Kohsuke; Mitsuyama, Masao; Sekimizu, Kazuhisa; Kaito, Chikara

2016-08-01

Invertebrate animal species that can withstand temperatures as high as 37°C, the human body temperature, are limited. In the present study, we utilized the two-spotted cricket, Gryllus bimaculatus, which lives in tropical and subtropical regions, as an animal model of human pathogenic bacterial infection. Injection of Pseudomonas aeruginosa or Staphylococcus aureus into the hemolymph killed crickets. Injected P. aeruginosa or S. aureus proliferated in the hemolymph until the cricket died. The ability of these pathogenic bacteria to kill the crickets was blocked by the administration of antibiotics. S. aureus gene-knockout mutants of virulence factors, including cvfA, agr and srtA, exhibited decreased killing ability compared with the parent strain. The dose at which 50% of crickets were killed by P. aeruginosa or S. aureus was not decreased at 37°C compared with that at 27°C. Injection of Listeria monocytogenes, which upregulates toxin expression at 37°C, killed crickets, and the dose at which 50% of crickets were killed was decreased at 37°C compared with that at 27°C. These findings suggest that the two-spotted cricket is a useful model animal for evaluating the virulence properties of various human pathogenic bacteria at variable temperature including 37°C. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Optical coherence tomography for assessment of microbicide safety in a small animal model

NASA Astrophysics Data System (ADS)

Bell, Brent A.; Vincent, Kathleen L.; Bourne, Nigel; Vargas, Gracie; Motamedi, Massoud

2013-04-01

Sensitive imaging techniques for small animals are needed to assess drug toxicity in preclinical studies. Optical coherence tomography (OCT) provides a noninvasive tool for high-resolution, depth-resolved visualization of drug-induced changes in tissue morphology. In a mouse model, we utilize OCT to assess vaginal tissue integrity following the application of topical microbicides (drugs used to prevent infection). Mice are challenged with herpes simplex virus-2 (HSV-2) to determine the correlation of tissue damage as quantified by OCT to increased susceptibility. The microbicide benzalkonium chloride (BZK) (0.02, 0.2, or 2%) or phosphate buffered saline control is administered intravaginally. In vivo OCT imaging and collection of tissue samples are performed after treatment. A quantitative OCT scoring system is applied to assess epithelial damage, and the results are compared with those of histology. A separate group of mice are treated similarly then challenged with HSV-2. Epithelial morphology quantified noninvasively by OCT and histology are dose-dependent (p<0.0001). The OCT scoring system detected a significant increase in epithelial damage with increasing BZK concentration (p<0.0001). These results paralleled an increase in HSV-2 susceptibility (p<0.005). OCT can be used as a noninvasive tool to assess topical drug toxicity in a small animal model with potential to predict increased susceptibility to vaginal infection.

Longitudinal analysis of mouse SDOCT volumes

NASA Astrophysics Data System (ADS)

Antony, Bhavna J.; Carass, Aaron; Lang, Andrew; Kim, Byung-Jin; Zack, Donald J.; Prince, Jerry L.

2017-03-01

Spectral-domain optical coherence tomography (SDOCT), in addition to its routine clinical use in the diagnosis of ocular diseases, has begun to fund increasing use in animal studies. Animal models are frequently used to study disease mechanisms as well as to test drug efficacy. In particular, SDOCT provides the ability to study animals longitudinally and non-invasively over long periods of time. However, the lack of anatomical landmarks makes the longitudinal scan acquisition prone to inconsistencies in orientation. Here, we propose a method for the automated registration of mouse SDOCT volumes. The method begins by accurately segmenting the blood vessels and the optic nerve head region in the scans using a pixel classification approach. The segmented vessel maps from follow-up scans were registered using an iterative closest point (ICP) algorithm to the baseline scan to allow for the accurate longitudinal tracking of thickness changes. Eighteen SDOCT volumes from a light damage model study were used to train a random forest utilized in the pixel classification step. The area under the curve (AUC) in a leave-one-out study for the retinal blood vessels and the optic nerve head (ONH) was found to be 0.93 and 0.98, respectively. The complete proposed framework, the retinal vasculature segmentation and the ICP registration, was applied to a secondary set of scans obtained from a light damage model. A qualitative assessment of the registration showed no registration failures.

Latent variables affecting behavioral response to the human intruder test in infant rhesus macaques (Macaca mulatta).

PubMed

Gottlieb, Daniel H; Capitanio, John P

2013-04-01

The human intruder test is a testing paradigm designed to measure rhesus macaques' behavioral responses to a stressful and threatening situation. In the test, an unfamiliar human positions him/herself in various threatening positions relative to a caged macaque. This paradigm has been utilized for over 20 years to measure a variety of behavioral constructs, including fear and anxiety, behavioral inhibition, emotionality, and aggression. To date, there have been no attempts to evaluate comprehensively the structure of the behavioral responses to the test. Our first goal was to identify the underlying latent factors affecting the different responses among subjects, and our second goal was to determine if rhesus reared in different environments respond differently in this testing paradigm. To accomplish this, we first performed exploratory and confirmatory factor analyses on the behavioral responses of 3- to 4-month-old rhesus macaques, utilizing data from over 2,000 separate tests conducted between 2001-2007. Using the resulting model, we then tested to see whether early rearing experience affected responses in the test. Our first analyses suggested that most of the variation in infant behavioral responses to the human intruder test could be explained by four latent factors: "activity," "emotionality," "aggression," and "displacement." Our second analyses revealed a significant effect of rearing condition for each factor score (P < 0.001); most notable socially reared animals had the lowest activity score (P < 0.001), indoor mother-reared animals had the highest displacement score (P < 0.001), and nursery-reared animals had the highest emotionality (P < 0.001) and lowest aggression scores (P < 0.001). These results demonstrate that this standardized testing paradigm reveals multiple patterns of response, which are influenced by an animal's rearing history. © 2012 Wiley Periodicals, Inc.

Step selection techniques uncover the environmental predictors of space use patterns in flocks of Amazonian birds.

PubMed

Potts, Jonathan R; Mokross, Karl; Stouffer, Philip C; Lewis, Mark A

2014-12-01

Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal-habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities.

Rapid, non-invasive imaging of alphaviral brain infection: reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals.

PubMed

Patterson, Michael; Poussard, Allison; Taylor, Katherine; Seregin, Alexey; Smith, Jeanon; Peng, Bi-Hung; Walker, Aida; Linde, Jenna; Smith, Jennifer; Salazar, Milagros; Paessler, Slobodan

2011-11-21

Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume's 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion. Copyright © 2011 Elsevier Ltd. All rights reserved.

Potential value of the common vetch (Vicia sativa L.) as an animal feedstuff: a review.

PubMed

Huang, Y F; Gao, X L; Nan, Z B; Zhang, Z X

2017-10-01

The objective of this review was to systematically evaluate common vetch seeds as a potential feedstuff for animals, by summarizing and discussing the available published literature covering their nutritional composition as well as their content of antinutritional factors and potential techniques for their reduction. In addition, animal feeding studies that have investigated the effect of inclusion of common vetch seeds on animal growth and performance were identified and evaluated to stimulate interest in their use as a good source of nutrients for inclusion in animal diets. The collective literature shows that common vetch seeds are a less costly (in comparison with alternatives) and rich source of protein and minerals for farmed animals, are of high digestibility and have a high energy content, and can be used to partially or totally replace soya bean meal and/or to replace a large proportion of cereals in the diet. Furthermore, the literature shows that common vetch seeds contain a range of antinutritional factors which, if they are to be utilized in non-ruminant diets and to increase their utilizing efficiency, need to be removed or inactivated. This can be achieved via certain pre-processing methods, the combination of which may deliver better results. Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.

Animating the Discussion about Climate Change

NASA Astrophysics Data System (ADS)

Ratner, A.

2016-12-01

Abstract concepts such as climate change are extremely difficult for both students and adults to grasp. Given that many of these concepts involve issues at global scales or at a microscopic level, photos and video are simply insufficient much of the time. Through an innovative partnership between The Marine Mammal Center, a marine mammal hospital and education facility, and the California College of the Arts Animation Department, we have been able to provide animation students real-world experience in producing scientific animations, and the Center has been able to create an animated video highlighting the science of climate change and effects on marine mammals. Using the science direct from our veterinary and research teams, along with scientifically tested communication strategies related to climate change from the National Network of Ocean and Climate Change Interpretation and Frameworks Institute, this video enables us to teach students and adults of all ages these complex scientific concepts in a fun, engaging, and easily understandable way. Utilizing the skill set and expertise of the College professor as director (currently a lead animator at Pixar Animation), this video provided animation students critical experience in the animation field, exposure and engagement in a critical environmental issue, and an understanding of the opportunities available within the field of animation for educational and scientific purposes. This presentation will highlight the opportunities to utilize animation for educational purposes and provide resources surrounding climate change that could be beneficial to educators at their own organizations.

Feeding and reward: Perspectives from Three Rat Models of Binge Eating

PubMed Central

Cowin, Rebecca L; Avena, Nicole M.; Boggiano, Mary M.

2011-01-01

Research has focused on understanding how overeating can affect brain reward mechanisms and subsequent behaviors, both preclinically and in clinical research settings. This work is partly driven by the need to uncover the etiology and possible treatments for the ongoing obesity epidemic. However, overeating, or non-homeostatic feeding behavior, can occur independent of obesity. Isolating the variable of overeating from the consequence of increased body weight is of great utility, as it is well known that increased body weight or obesity can impart its own deleterious effects on physiology, neural processes, and behavior. In this review, we present data from three selected animal models of normal-weight non-homeostatic feeding behavior that have been significantly influenced by Bart Hoebel’s 40+-yr career studying motivation, feeding, reinforcement, and the neural mechanisms that participate in the regulation of these processes. First, a model of sugar bingeing is described (Avena/Hoebel), in which animals with repeated, intermittent access to a sugar solution develop behaviors and brain changes that are similar to the effects of some drugs of abuse, serving as the first animal model of food addiction. Second, another model is described (Boggiano) in which a history of dieting and stress can perpetuate further binge eating of palatable and non-palatable food. In addition, a model (Boggiano) is described that allows animals to be classified as having a binge-prone vs. binge-resistant phenotype. Lastly, a limited access model is described (Corwin) in which non-food deprived rats with sporadic limited access to a high-fat food develop binge-type behaviors. These models are considered within the context of their effects on brain reward systems, including dopamine, the opioids, cholinergic systems, serotonin, and GABA. Collectively, the data derived from the use of these models clearly show that behavioral and neuronal consequences of bingeing on a palatable food, even when at a normal body weight, are different from those that result from simply consuming the palatable food in a non-binge manner. These findings may be important in understanding how overeating can influence behavior and brain chemistry. PMID:21549136

NOTES: Issues and Technical Details With Introduction of NOTES Into a Small General Surgery Residency Program

PubMed Central

Mirza, Brian; Horne, Walter; Moskowitz, Jesse B.

2008-01-01

Background and Objectives: Natural orifice translumenal endoscopic surgery (NOTES) is a development of recent origin. In 2004, Kalloo et al first described NOTES investigation in an animal model. Since then, several investigators have pursued NOTES study in animal survival and nonsurvival models. Our objectives for this project included studying NOTES intervention in a laboratory environment using large animal (swine) models and learning to do so in a safe, controlled manner. Ultimately, we intend to introduce NOTES methodology into our surgical residency training program. The expertise of an experienced laparoscopic surgeon, fellowship-trained laparoendoscopic surgeon, and veterinarian along with a senior surgical resident was utilized to bring the input of several disciplines to this study. The Institutional Animal Care and Use Committee (IACUC) of Northeastern Ohio Universities College of Medicine and Pharmacy (NEOUCOM/COP) approved this study. Methods: A series of 5 laboratory sessions using mixed breed farm swine varying in weight from 37 kg to 43.1 kg was planned for the initial phase of NOTES introduction into our residency program. Animals were not kept alive in this investigation. All animals were anesthetized using a standard swine protocol and euthanized following guidelines issued by the American Veterinary Medical Association Panel on Euthanasia. Equipment included a Fujinon EVE endoscope 0.8 cm in diameter with a suction/irrigation channel and one working channel. Initially, a US Endoscopy gastric overtube, 19.5 mm OD and 50 cm in length, was used to facilitate passage of the endoscope. However, this device was found to have insufficient length. Subsequently, commercially available 5/8” diameter clear plastic tubing, 70 cm to 80 cm in length, was adapted for use as an overtube. Standard endoscopic instruments included Boston Scientific biopsy forceps, needle-knife, papillotome, endoscopic clip applier, and Valley Lab electrosurgical unit. A Karl Storz laparoscope and tower were used for laparoscopic observation of NOTES maneuvers. Necropsy was performed to determine specific details of surgical intervention. Results: NOTES intervention is feasible in an animal model. Insight into the potential of NOTES was obtained in this investigation. Conclusions: NOTES investigation in a controlled, laboratory setting using an animal model proved to have value for our program. A steep learning curve was encountered despite the availability of an investigator familiar with elementary NOTES procedures. The authors strongly suggest investigators adopt the ASGE/SAGES working group recommendations for a multidisciplinary team possessing advanced therapeutic endoscopic and advanced laparoscopic skills to study NOTES before human investigation. Animal laboratory facilities to perform research and training should be available to the multidisciplinary team for exploration of NOTES techniques and procedures. Institutional Review Board (IRB) approval must be obtained before introduction of NOTES procedures in human patients. PMID:18402737

Rheumatoid arthritis exacerbates the severity of osteonecrosis of the jaws (ONJ) in mice. A randomized, prospective, controlled animal study

PubMed Central

de Molon, Rafael Scaf; Hsu, Chingyun; Bezouglaia, Olga; Dry, Sarah M.; Pirih, Flavia Q.; Soundia, Akrivoula; Cunha, Fernando Queiroz; Cirelli, Joni Augusto; Aghaloo, Tara L.; Tetradis, Sotirios

2016-01-01

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J-mice were divided in 4 groups: control, zoledronic acid (ZA), collagen induced arthritis (CIA), and CIA-ZA. Animals were pre-treated with vehicle or ZA. Bovine collagen II emulsified in Freund’s adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8-weeks. ONJ indices were measured by micro-CT and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by micro-CT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, PDL space widening, lamina dura loss and cortex thinning. ZA prevented theses changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development. PMID:26950411

Targeting IL-2: an unexpected effect in treating immunological diseases.

PubMed

Ye, Congxiu; Brand, David; Zheng, Song G

2018-01-01

Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.

Novel transcranial magnetic stimulation coil for mice

NASA Astrophysics Data System (ADS)

March, Stephen; Stark, Spencer; Crowther, Lawrence; Hadimani, Ravi; Jiles, David

2014-03-01

Transcranial magnetic stimulation (TMS) shows potential for non-invasive treatment of various neurological disorders. Significant work has been performed on the design of coils used for TMS on human subjects but few reports have been made on the design of coils for use on the brains of animals such as mice. This work is needed as TMS studies utilizing mice can allow rapid preclinical development of TMS for human disorders but the coil designs developed for use on humans are inadequate for optimal stimulation of the much smaller mouse brain. A novel TMS coil has been developed with the goal of inducing strong and focused electric fields for the stimulation of small animals such as mice. Calculations of induced electric fields were performed utilizing an MRI derived inhomogeneous model of an adult male mouse. Mechanical and thermal analysis of this new TMS helmet-coil design have also been performed at anticipated TMS operating conditions to ensure mechanical stability of the new coil and establish expected linear attraction and rotational force values. Calculated temperature increases for typical stimulation periods indicate the helmet-coil system is capable of operating within established medical standards. A prototype of the coil has been fabricated and characterization results are presented.

Green Care: A Review of the Benefits and Potential of Animal-Assisted Care Farming Globally and in Rural America

PubMed Central

Artz, Brianna; Bitler Davis, Doris

2017-01-01

Simple Summary The term Green Care encompasses a number of therapeutic strategies that can include farm-animal-assisted therapy, horticultural therapy, and general, farm-based therapy. This review article provides an overview of how Green Care has been used as part of the therapeutic plan for a variety of psychological disorders and related physical disabilities in children, adolescents and adults. While many countries have embraced Green Care, and research-based evidence supports its efficacy in a variety of therapeutic models, it has not yet gained widespread popularity in the United States. We suggest that Green Care could prove to be an effective approach to providing mental health care in the U.S., particularly in rural areas that are typically underserved by more traditional mental health facilities, but have an abundance of farms, livestock, and green spaces where care might be effectively provided. Abstract The term Green Care includes therapeutic, social or educational interventions involving farming; farm animals; gardening or general contact with nature. Although Green Care can occur in any setting in which there is interaction with plants or animals, this review focuses on therapeutic practices occurring on farms. The efficacy of care farming is discussed and the broad utilization of care farming and farm care communities in Europe is reviewed. Though evidence from care farms in the United States is included in this review, the empirical evidence which could determine its efficacy is lacking. For example, the empirical evidence supporting or refuting the efficacy of therapeutic horseback riding in adults is minimal, while there is little non-equine care farming literature with children. The health care systems in Europe are also much different than those in the United States. In order for insurance companies to cover Green Care techniques in the United States, extensive research is necessary. This paper proposes community-based ways that Green Care methods can be utilized without insurance in the United States. Though Green Care can certainly be provided in urban areas, this paper focuses on ways rural areas can utilize existing farms to benefit the mental and physical health of their communities. PMID:28406428

The use of fish models to study human neurological disorders.

PubMed

Matsui, Hideaki

2017-07-01

Small teleost fish including zebrafish and medaka have been used as animal models in basic science research due to the relative ease of handling and transparency during embryogenesis. Current advances in genetic engineering and progress in disease genetics allowed utilization of these fish to study neurological diseases and psychiatric disorders. This review summarizes the advantages and disadvantages of using fish for neuropsychiatric research using primarily our own studies as examples. We discuss how fish belong to a class of vertebrates, are feasible for imaging, and include diverse species with multiple research possibilities yet to be discovered. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Self-Motion Perception and Motion Sickness

NASA Technical Reports Server (NTRS)

Fox, Robert A.

1991-01-01

Motion sickness typically is considered a bothersome artifact of exposure to passive motion in vehicles of conveyance. This condition seldom has significant impact on the health of individuals because it is of brief duration, it usually can be prevented by simply avoiding the eliciting condition and, when the conditions that produce it are unavoidable, sickness dissipates with continued exposure. The studies conducted examined several aspects of motion sickness in animal models. A principle objective of these studies was to investigate the neuroanatomy that is important in motion sickness with the objectives of examining both the utility of putative models and defining neural mechanisms that are important in motion sickness.

Genome-wide association study on legendre random regression coefficients for the growth and feed intake trajectory on Duroc Boars.

PubMed

Howard, Jeremy T; Jiao, Shihui; Tiezzi, Francesco; Huang, Yijian; Gray, Kent A; Maltecca, Christian

2015-05-30

Feed intake and growth are economically important traits in swine production. Previous genome wide association studies (GWAS) have utilized average daily gain or daily feed intake to identify regions that impact growth and feed intake across time. The use of longitudinal models in GWAS studies, such as random regression, allows for SNPs having a heterogeneous effect across the trajectory to be characterized. The objective of this study is therefore to conduct a single step GWAS (ssGWAS) on the animal polynomial coefficients for feed intake and growth. Corrected daily feed intake (DFI Adj) and average daily weight measurements (DBW Avg) on 8981 (n=525,240 observations) and 5643 (n=283,607 observations) animals were utilized in a random regression model using Legendre polynomials (order=2) and a relationship matrix that included genotyped and un-genotyped animals. A ssGWAS was conducted on the animal polynomials coefficients (intercept, linear and quadratic) for animals with genotypes (DFIAdj: n=855; DBWAvg: n=590). Regions were characterized based on the variance of 10-SNP sliding windows GEBV (WGEBV). A bootstrap analysis (n=1000) was conducted to declare significance. Heritability estimates for the traits trajectory ranged from 0.34-0.52 to 0.07-0.23 for DBWAvg and DFIAdj, respectively. Genetic correlations across age classes were large and positive for both DBWAvg and DFIAdj, albeit age classes at the beginning had a small to moderate genetic correlation with age classes towards the end of the trajectory for both traits. The WGEBV variance explained by significant regions (P<0.001) for each polynomial coefficient ranged from 0.2-0.9 to 0.3-1.01% for DBWAvg and DFIAdj, respectively. The WGEBV variance explained by significant regions for the trajectory was 1.54 and 1.95% for DBWAvg and DFIAdj. Both traits identified candidate genes with functions related to metabolite and energy homeostasis, glucose and insulin signaling and behavior. We have identified regions of the genome that have an impact on the intercept, linear and quadratic terms for DBWAvg and DFIAdj. These results provide preliminary evidence that individual growth and feed intake trajectories are impacted by different regions of the genome at different times.

Quantitative determination of H2-utilizing acetogenic and sulfate-reducing bacteria and methanogenic archaea from digestive tract of different mammals.

PubMed

Morvan, B; Bonnemoy, F; Fonty, G; Gouet, P

1996-03-01

Total number of bacteria, cellulolytic bacteria, and H2-utilizing microbial populations (methanogenic archaea, acetogenic and sulfate-reducing bacteria) were enumerated in fresh rumen samples from sheep, cattle, buffaloes, deer, llamas, and caecal samples from horses. Methanogens and sulfate reducers were found in all samples, whereas acetogenes were not detected in some samples of each animal. Archaea methanogens were the largest H2-utilizing populations in all animals, and a correlation was observed between the numbers of methanogens and those of cellulolytic microorganisms. Higher counts of acetogens were found in horses and llamas (1 x 10(4) and 4 x 10(4) cells ml-1 respectively).

Predicting caregiver burden in general veterinary clients: Contribution of companion animal clinical signs and problem behaviors.

PubMed

Spitznagel, M B; Jacobson, D M; Cox, M D; Carlson, M D

2018-06-01

Caregiver burden, found in many clients with a chronically or terminally ill companion animal, has been linked to poorer psychosocial function in the client and greater utilization of non-billable veterinary services. To reduce client caregiver burden, its determinants must first be identified. This study examined if companion animal clinical signs and problem behaviors predict veterinary client burden within broader client- and patient-based risk factor models. Data were collected in two phases. Phase 1 included 238 companion animal owners, including those with a sick companion animal (n=119) and matched healthy controls (n=119) recruited online. Phase 2 was comprised of 602 small animal general veterinary hospital clients (n=95 with a sick dog or cat). Participants completed cross-sectional online assessments of caregiver burden, psychosocial resources (social support, active coping, self-mastery), and an item pool of companion animal clinical signs and problem behaviors. Several signs/behaviors correlated with burden, most prominently: weakness, appearing sad/depressed or anxious, appearing to have pain/discomfort, change in personality, frequent urination, and excessive sleeping/lethargy. Within patient-based risk factors, caregiver burden was predicted by frequency of the companion animal's signs/behaviors (P<.01). Within client-based factors, potentially modifiable factors of client reaction to the animal's signs/behaviors (P=.01), and client sense of control (P<.04) predicted burden. Understanding burden may enhance veterinarian-client communication, and is important due to potential downstream effects of client burden, such as higher workload for the veterinarian. Supporting the client's sense of control may help alleviate burden when amelioration of the companion animal's presentation is not feasible. Copyright © 2018 Elsevier Ltd. All rights reserved.

Population modeling for furbearer management

USGS Publications Warehouse

Johnson, D.H.; Sanderson, G.C.

1982-01-01

The management of furbearers has become increasingly complex as greater demands are placed on their populations. Correspondingly, needs for information to use in management have increased. Inadequate information leads the manager to err on the conservative side; unless the size of the 'harvestable surplus' is known, the population cannot be fully exploited. Conversely, information beyond what is needed becomes an unaffordable luxury. Population modeling has proven useful for organizing information on numerous game animals. Modeling serves to determine if information of the right kind and proper amount is being gathered; systematizes data collection, data interpretation, and decision making; and permits more effective management and better utilization of game populations. This report briefly reviews the principles of population modeling, describes what has been learned from previous modeling efforts on furbearers, and outlines the potential role of population modeling in furbearer management.

Doggone Good? Potential Benefits of Assistance Animals for Students on College Campuses

ERIC Educational Resources Information Center

Polking, Amanda K.; Cornelius-White, Jeffrey H. D.; Stout, Tracy L.

2017-01-01

The presence of and request for assistance, service, and support animals has skyrocketed on college campuses in recent years. The purpose of this literature review is to explore potential benefits in the utilization of assistance animals within higher education, especially as it concerns disability service offices. It begins with an overview of…

The Occurrence, Biosynthesis, and Molecular Structure of Proanthocyanidins and Their Effects on Legume Forage Protein Precipitation, Digestion and Absorption in the Ruminant Digestive Tract

PubMed Central

Jonker, Arjan; Yu, Peiqiang

2017-01-01

Forages grown in temperate regions, such as alfalfa (Medicago sativa L.) and white clover (Trefolium repens L.), typically have a high nutritional value when fed to ruminants. Their high protein content and degradation rate result, however, in poor utilization of protein from the forage resulting in excessive excretion of nitrogen into the environment by the animal. Proanthocyanindins (also known as condensed tannins) found in some forage legumes such as birdsfoot trefoil (Lotus corniculatus L.), bind to dietary protein and can improve protein utilization in the animal. This review will focus on (1) the occurrence of proanthocyanidins; (2) biosynthesis and structure of proanthocyanidins; (3) effects of proanthocyanidins on protein metabolism; (4) protein precipitating capacity of proanthocyanidins and their effects on true intestinal protein adsorption by ruminants; and (5) effect on animal health, animal performance and environmental emissions. PMID:28531145

Bacterial exopolymer utilization by a harpacticoid copepod: A methodology and results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Decho, A.W.; Moriarty, D.J.W.

1990-07-01

Exopolymer mucus secretions of bacteria and diatoms are potential foods for benthic animals. These secretions are coincidently ingested by animals during consumption of microbial cells and sediments. The utilization of microbial secretions was investigated with exopolymer derived from a marine bacterium (pseudomonas sp.) from seagrass beds and a harpacticoid copepod Laophonte sp. from the same habitat. A new technique was developed to examine ingestion, absorption, and absorption efficiencies of these bacterial secretions by consumers. Exopolymer mucus (from the bacterium in stationary phase) was labeled with {sup 14}C, collected, purified, and bound onto bacterium-sized beads. The exopolymer slime coating mimicked themore » coatings associated with many marine bacteria. Results from feeding experiments where the coated beads were mixed with sediment demonstrated that the mucus-exopolymer secretions of bacteria were ingested and utilized by Laophonte sp. Absorption efficiencies, determined directly, were > 80% in the presence of other food resources, indicating that exopolymer is potentially a highly labile C resource for this animal.« less

Efficacy and safety of damage control in experimental animal models of injury: protocol for a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Although abbreviated surgery with planned reoperation (damage control surgery) is now widely used to manage major trauma patients, the procedure and its component interventions have not been evaluated in randomized controlled trials (RCTs). While some have suggested the need for such trials, they are unlikely to be conducted because of patient safety concerns. As animal studies may overcome several of the limitations of existing observational damage control studies, the primary objective of this study is to evaluate the efficacy and safety of damage control versus definitive surgery in experimental animal models of injury. Methods/design We will search electronic databases (Medline, Embase, PubMed, Web of Science, Scopus, and the Cochrane Library), conference abstracts, personal files, and bibliographies of included articles. We will include RCTs and prospective cohort studies that utilized an animal model of injury and compared damage control surgery (or specific damage control interventions or adjuncts) to definitive surgery (or specific definitive surgical interventions). Two investigators will independently evaluate the internal and external/construct validity of individual studies. The primary outcome will be all-cause mortality. Secondary outcomes will include blood loss amounts; blood pressures and heart rates; urinary outputs; core body temperatures; arterial lactate, pH, and base deficit/excess values; prothrombin and partial thromboplastin times; international normalized ratios; and thromboelastography (TEG) results/activated clotting times. We will calculate summary relative risks (RRs) of mortality and mean differences (for continuous outcomes) using DerSimonian and Laird random effects models. Heterogeneity will be explored using subgroup meta-analysis and meta-regression. We will assess for publication bias using funnel plots and Begg’s and Egger’s tests. When evidence of publication bias exists, we will use the Duval and Tweedie trim and fill method to estimate the potential influence of this bias on pooled summary estimates. Discussion This study will evaluate the efficacy and safety of damage control in experimental animal models of injury. Study results will be used to guide future clinical evaluations of damage control surgery, determine which animal study outcomes may potentially be generalizable to the clinical setting, and to provide guidelines to strengthen the conduct and relevance of future pre-clinical studies. PMID:25416175

High-fat high-sugar diet induces polycystic ovary syndrome in a rodent model.

PubMed

Roberts, Jacob S; Perets, Ron A; Sarfert, Kathryn S; Bowman, John J; Ozark, Patrick A; Whitworth, Gregg B; Blythe, Sarah N; Toporikova, Natalia

2017-01-27

Obesity has been linked with a host of metabolic and reproductive disorders including polycystic ovary syndrome (PCOS). While a clear association exists between obesity and PCOS, the exact nature of this relationship remains unexplained. The primary symptoms of PCOS include hyperandrogenism, anovulation, and polycystic ovaries. Most animal models utilize androgen treatments to induce PCOS. However, these models often fail to address the underlying causes of the disease and do not effectively reproduce key metabolic features such as hyperinsulinemia. Here, we present a novel rodent model of diet-induced obesity that recapitulates both the metabolic and reproductive phenotypes of human PCOS. Rats on a high-fat high-sugar (HFHS) diet not only demonstrated signs of metabolic impairment, but they also developed polycystic ovaries and experienced irregular estrous cycling. Though hyperandrogenism was not characteristic of HFHS animals as a group, elevated testosterone levels were predictive of high numbers of ovarian cysts. Alterations in steroidogenesis and folliculogenesis gene expression were also found via RNA sequencing of ovarian tissue. Importantly, the PCOS-like symptoms induced in these rats may share a similar etiology to PCOS in humans. Therefore, this model offers a unique opportunity to study PCOS at its genesis rather than following the development of disease symptoms.

Target specific delivery of anticancer drug in silk fibroin based 3D distribution model of bone-breast cancer cells.

PubMed

Subia, Bano; Dey, Tuli; Sharma, Shaily; Kundu, Subhas C

2015-02-04

To avoid the indiscriminating action of anticancer drugs, the cancer cell specific targeting of drug molecule becomes a preferred choice for the treatment. The successful screening of the drug molecules in 2D culture system requires further validation. The failure of target specific drug in animal model raises the issue of creating a platform in between the in vitro (2D) and in vivo animal testing. The metastatic breast cancer cells migrate and settle at different sites such as bone tissue. This work evaluates the in vitro 3D model of the breast cancer and bone cells to understand the cellular interactions in the presence of a targeted anticancer drug delivery system. The silk fibroin based cytocompatible 3D scaffold is used as in vitro 3D distribution model. Human breast adenocarcinoma and osteoblast like cells are cocultured to evaluate the efficiency of doxorubicin loaded folic acid conjugated silk fibroin nanoparticle as drug delivery system. Decreasing population of the cancer cells, which lower the levels of vascular endothelial growth factors, glucose consumption, and lactate production are observed in the drug treated coculture constructs. The drug treated constructs do not show any major impact on bone mineralization. The diminished expression of osteogenic markers such as osteocalcein and alkaline phosphatase are recorded. The result indicates that this type of silk based 3D in vitro coculture model may be utilized as a bridge between the traditional 2D and animal model system to evaluate the new drug molecule (s) or to reassay the known drug molecules or to develop target specific drug in cancer research.

Understanding the Hows and Whys of Decision-Making: From Expected Utility to Divisive Normalization.

PubMed

Glimcher, Paul

2014-01-01

Over the course of the last century, economists and ethologists have built detailed models from first principles of how humans and animals should make decisions. Over the course of the last few decades, psychologists and behavioral economists have gathered a wealth of data at variance with the predictions of these economic models. This has led to the development of highly descriptive models that can often predict what choices people or animals will make but without offering any insight into why people make the choices that they do--especially when those choices reduce a decision-maker's well-being. Over the course of the last two decades, neurobiologists working with economists and psychologists have begun to use our growing understanding of how the nervous system works to develop new models of how the nervous system makes decisions. The result, a growing revolution at the interdisciplinary border of neuroscience, psychology, and economics, is a new field called Neuroeconomics. Emerging neuroeconomic models stand to revolutionize our understanding of human and animal choice behavior by combining fundamental properties of neurobiological representation with decision-theoretic analyses. In this overview, one class of these models, based on the widely observed neural computation known as divisive normalization, is presented in detail. The work demonstrates not only that a discrete class of computation widely observed in the nervous system is fundamentally ubiquitous, but how that computation shapes behaviors ranging from visual perception to financial decision-making. It also offers the hope of reconciling economic analysis of what choices we should make with psychological observations of the choices we actually do make. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Expanding veterinary biosurveillance in Washington, DC: The creation and utilization of an electronic-based online veterinary surveillance system.

PubMed

Hennenfent, Andrew; DelVento, Vito; Davies-Cole, John; Johnson-Clarke, Fern

2017-03-01

To enhance the early detection of emerging infectious diseases and bioterrorism events using companion animal-based surveillance. Washington, DC, small animal veterinary facilities (n=17) were surveyed to determine interest in conducting infectious disease surveillance. Using these results, an electronic-based online reporting system was developed and launched in August 2015 to monitor rates of canine influenza, canine leptospirosis, antibiotic resistant infections, canine parvovirus, and syndromic disease trends. Nine of the 10 facilities that responded expressed interest conducting surveillance. In September 2015, 17 canine parvovirus cases were reported. In response, a campaign encouraging regular veterinary preventative care was launched and featured on local media platforms. Additionally, during the system's first year of operation it detected 5 canine leptospirosis cases and 2 antibiotic resistant infections. No canine influenza cases were reported and syndromic surveillance compliance varied, peaking during National Special Security Events. Small animal veterinarians and the general public are interested in companion animal disease surveillance. The system described can serve as a model for establishing similar systems to monitor disease trends of public health importance in pet populations and enhance biosurveillance capabilities. Copyright © 2017 Elsevier B.V. All rights reserved.

Learning to Select Actions with Spiking Neurons in the Basal Ganglia

PubMed Central

Stewart, Terrence C.; Bekolay, Trevor; Eliasmith, Chris

2012-01-01

We expand our existing spiking neuron model of decision making in the cortex and basal ganglia to include local learning on the synaptic connections between the cortex and striatum, modulated by a dopaminergic reward signal. We then compare this model to animal data in the bandit task, which is used to test rodent learning in conditions involving forced choice under rewards. Our results indicate a good match in terms of both behavioral learning results and spike patterns in the ventral striatum. The model successfully generalizes to learning the utilities of multiple actions, and can learn to choose different actions in different states. The purpose of our model is to provide both high-level behavioral predictions and low-level spike timing predictions while respecting known neurophysiology and neuroanatomy. PMID:22319465

Breeding goals for the Kenya dual purpose goat. I. Model development and application to smallholder production systems.

PubMed

Bett, R C; Kosgey, I S; Bebe, B O; Kahi, A K

2007-10-01

A deterministic model was developed and applied to evaluate biological and economic variables that characterize smallholder production systems utilizing the Kenya Dual Purpose goat (KDPG) in Kenya. The systems were defined as: smallholder low-potential (SLP), smallholder medium-potential (SMP) and smallholder high-potential (SHP). The model was able to predict revenues and costs to the system. Revenues were from sale of milk, surplus yearlings and cull-forage animals, while costs included those incurred for feeds, husbandry, marketing and fixed asset (fixed costs). Of the total outputs, revenue from meat and milk accounted for about 55% and 45%, respectively, in SMP and 39% and 61% in SHP. Total costs comprised mainly variable costs (98%), with husbandry costs being the highest in both SMP and SLP. The total profit per doe per year was KSh 315.48 in SMP, KSh -1352.75 in SLP and KSh -80.22 in SHP. Results suggest that the utilization of the KDPG goat in Kenya is more profitable in the smallholder medium-potential production system. The implication for the application of the model to smallholder production systems in Kenya is discussed.

ANIMAL WASTE COMPOSTING WITH CARBONACEOUS MATERIAL

EPA Science Inventory

High rate thermophilic composting of animal wastes with added carbonaceous waste materials followed by land application has considerable potential as a means of treatment and useful final disposal of these wastes. The process described in this report utilizes a mechanically mixed...

Dietary antioxidant synergy in chemical and biological systems.

PubMed

Wang, Sunan; Zhu, Fan

2017-07-24

Antioxidant (AOX) synergies have been much reported in chemical ("test-tube" based assays focusing on pure chemicals), biological (tissue culture, animal and clinical models), and food systems during the past decade. Tentative synergies differ from each other due to the composition of AOX and the quantification methods. Regeneration mechanism responsible for synergy in chemical systems has been discussed. Solvent effects could contribute to the artifacts of synergy observed in the chemical models. Synergy in chemical models may hardly be relevant to biological systems that have been much less studied. Apparent discrepancies exist in understanding the molecular mechanisms in both chemical and biological systems. This review discusses diverse variables associated with AOX synergy and molecular scenarios for explanation. Future research to better utilize the synergy is suggested.

Control of movement initiation underlies the development of balance

PubMed Central

Ehrlich, David E.; Schoppik, David

2017-01-01

Summary Balance arises from the interplay of external forces acting on the body and internally generated movements. Many animal bodies are inherently unstable, necessitating corrective locomotion to maintain stability. Understanding how developing animals come to balance remains a challenge. Here we study the interplay between environment, sensation, and action as balance develops in larval zebrafish. We first model the physical forces that challenge underwater balance and experimentally confirm that larvae are subject to constant destabilization. Larvae propel in swim bouts that, we find, tend to stabilize the body. We confirm the relationship between locomotion and balance by changing larval body composition, exacerbating instability and eliciting more frequent swimming. Intriguingly, developing zebrafish come to control the initiation of locomotion, swimming preferentially when unstable, thus restoring preferred postures. To test the sufficiency of locomotor-driven stabilization and the developing control of movement timing, we incorporate both into a generative model of swimming. Simulated larvae recapitulate observed postures and movement timing across early development, but only when locomotor-driven stabilization and control of movement initiation are both utilized. We conclude the ability to move when unstable is the key developmental improvement to balance in larval zebrafish. Our work informs how emerging sensorimotor ability comes to impact how and why animals move when they do. PMID:28111151

Dissociable contributions of anterior cingulate cortex and basolateral amygdala on a rodent cost/benefit decision-making task of cognitive effort.

PubMed

Hosking, Jay G; Cocker, Paul J; Winstanley, Catharine A

2014-06-01

Personal success often requires the choice to expend greater effort for larger rewards, and deficits in such effortful decision making accompany a number of illnesses including depression, schizophrenia, and attention-deficit/hyperactivity disorder. Animal models have implicated brain regions such as the basolateral amygdala (BLA) and anterior cingulate cortex (ACC) in physical effort-based choice, but disentangling the unique contributions of these two regions has proven difficult, and effort demands in industrialized society are predominantly cognitive in nature. Here we utilize the rodent cognitive effort task (rCET), a modification of the five-choice serial reaction-time task, wherein animals can choose to expend greater visuospatial attention to obtain larger sucrose rewards. Temporary inactivation (via baclofen-muscimol) of BLA and ACC showed dissociable effects: BLA inactivation caused hard-working rats to 'slack off' and 'slacker' rats to work harder, whereas ACC inactivation caused all animals to reduce willingness to expend mental effort. Furthermore, BLA inactivation increased the time needed to make choices, whereas ACC inactivation increased motor impulsivity. These data illuminate unique contributions of BLA and ACC to effort-based decision making, and imply overlapping yet distinct circuitry for cognitive vs physical effort. Our understanding of effortful decision making may therefore require expanding our models beyond purely physical costs.

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy.

PubMed

Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-06-01

Animal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases. Allergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment. In atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles.

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

PubMed Central

Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-01-01

Purpose of review Animal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases. Recent findings Allergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment. Summary In atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles. PMID:28375932

Separability of drag and thrust in undulatory animals and machines

PubMed Central

Bale, Rahul; Shirgaonkar, Anup A.; Neveln, Izaak D.; Bhalla, Amneet Pal Singh; MacIver, Malcolm A.; Patankar, Neelesh A.

2014-01-01

For nearly a century, researchers have tried to understand the swimming of aquatic animals in terms of a balance between the forward thrust from swimming movements and drag on the body. Prior approaches have failed to provide a separation of these two forces for undulatory swimmers such as lamprey and eels, where most parts of the body are simultaneously generating drag and thrust. We nonetheless show that this separation is possible, and delineate its fundamental basis in undulatory swimmers. Our approach unifies a vast diversity of undulatory aquatic animals (anguilliform, sub-carangiform, gymnotiform, bal-istiform, rajiform) and provides design principles for highly agile bioinspired underwater vehicles. This approach has practical utility within biology as well as engineering. It is a predictive tool for use in understanding the role of the mechanics of movement in the evolutionary emergence of morphological features relating to locomotion. For example, we demonstrate that the drag-thrust separation framework helps to predict the observed height of the ribbon fin of electric knifefish, a diverse group of neotropical fish which are an important model system in sensory neurobiology. We also show how drag-thrust separation leads to models that can predict the swimming velocity of an organism or a robotic vehicle. PMID:25491270

Alterations of local cerebral glucose utilization in lean and obese fa/fa rats after acute adrenalectomy.

PubMed

Doyle, P; Rohner-Jeanrenaud, F; Jeanrenaud, B

1994-08-29

An animal model often used to investigate the aetiology of obesity is the genetically obese fa/fa rat. It has many abnormalities, including hyperphagia, hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an overactive hypothalamo-pituitary adrenal (HPA) axis with resulting hypercorticism. Due to the latter consideration, the aim of this work was to study the impact of acute adrenalectomy (ADX) on the local cerebral glucose utilization (LCGU) of lean and obese fa/fa rats. ADX resulted in discrete increases in LCGU of regions common to both lean and obese rats. These common regions were found to belong to be related to the limbic system. Within this system, the LCGU of the brain of obese rats was either normalized to lean sham operated values or increased by ADX to a similar degree in both groups on a percentage basis. It was concluded that the LCGU of both lean and obese animals appears to be negatively regulated, albeit to different extents, by glucocorticoids. Such negative regulation is particularly salient within the limbic system of the lean rat and even more so in the fa/fa rat. It is suggested that the long-term hypercorticism of obese fa/fa rats due to abnormal regulation of the HPA axis may result in a decreased LCGU in limbic and related regions of the brain of fa/fa rats and contribute to the expression of the obese phenotype.

Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review.

PubMed

Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F; Huo, Li-Jun

2017-01-01

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

PubMed Central

Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F.; Huo, Li-Jun

2017-01-01

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations. PMID:28928662

Dissociation of metabolic and hemodynamic levodopa responses in the 6-hydroxydopamine rat model.

PubMed

Lerner, Renata P; Bimpisidis, Zisis; Agorastos, Stergiani; Scherrer, Sandra; Dewey, Stephen L; Cenci, M Angela; Eidelberg, David

2016-12-01

Dissociation of vasomotor and metabolic responses to levodopa has been observed in human subjects with Parkinson's disease (PD) studied with PET and in autoradiograms from 6-hydroxydopamine (6-OHDA) rat. In both species, acute levodopa administration was associated with increases in basal ganglia cerebral blood flow (CBF) with concurrent reductions in cerebral metabolic rate (CMR) for glucose in the same brain regions. In this study, we used a novel dual-tracer microPET technique to measure CBF and CMR levodopa responses in the same animal. Rats with unilateral 6-OHDA or sham lesion underwent sequential 15 O-water (H 2 15 O) and 18 F-fluorodeoxyglucose (FDG) microPET to map CBF and CMR following the injection of levodopa or saline. A subset of animals was separately scanned under ketamine/xylazine and isoflurane to compare the effects of these anesthetics. Regardless of anesthetic agent, 6-OHDA animals exhibited significant dissociation of vasomotor (ΔCBF) and metabolic (ΔCMR) responses to levodopa, with stereotyped increases in CBF and reductions in CMR in the basal ganglia ipsilateral to the dopamine lesion. No significant changes were seen in sham-lesioned animals. These data faithfully recapitulate analogous dissociation effects observed previously in human PD subjects scanned sequentially during levodopa infusion. This approach may have utility in the assessment of new drugs targeting the exaggerated regional vasomotor responses seen in human PD and in experimental models of levodopa-induced dyskinesia. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of a multi-criteria evaluation system to assess growing pig welfare.

PubMed

Martín, P; Traulsen, I; Buxadé, C; Krieter, J

2017-03-01

The aim of this paper was to present an alternative multi-criteria evaluation model to assess animal welfare on farms based on the Welfare Quality® (WQ) project, using an example of welfare assessment of growing pigs. The WQ assessment protocol follows a three-step aggregation process. Measures are aggregated into criteria, criteria into principles and principles into an overall assessment. This study focussed on the first step of the aggregation. Multi-attribute utility theory (MAUT) was used to produce a value of welfare for each criterion. The utility functions and the aggregation function were constructed in two separated steps. The Measuring Attractiveness by a Categorical Based Evaluation Technique (MACBETH) method was used for utility function determination and the Choquet Integral (CI) was used as an aggregation operator. The WQ decision-makers' preferences were fitted in order to construct the utility functions and to determine the CI parameters. The methods were tested with generated data sets for farms of growing pigs. Using the MAUT, similar results were obtained to the ones obtained applying the WQ protocol aggregation methods. It can be concluded that due to the use of an interactive approach such as MACBETH, this alternative methodology is more transparent and more flexible than the methodology proposed by WQ, which allows the possibility to modify the model according, for instance, to new scientific knowledge.

Economic Effects of Fascioliasis on Animal Traction Technology in Adamawa State, Nigeria

NASA Astrophysics Data System (ADS)

Jaafar-Furo, M. R.; Mshelia, S. I.; Suleiman, A.

This study reports the results of a survey conducted in 2001 to investigate the economic effects of Fascioliasis (Liverflukes) on drought animals in Adamawa State, Nigeria. Data were collected from 60 and 74 farmers` owners of 148 non-infested and 204 infested drought animals, respectively, through a cost-route method using structured questionnaires and supplemented with interviews. Analysis using descriptive statistics and animal traction efficiency measure showed that the non-infested drought animals were efficiently utilized than the infested drought animals. It was concluded that the non-infested drought animals were more productive. The study therefore, recommend among others, the regular deworming of drought animals in order to improve their efficiency.

Direct versus Indirect Questioning: An Application to the Well-Being of Farm Animals

ERIC Educational Resources Information Center

Lusk, Jayson L.; Norwood, F. Bailey

2010-01-01

Recent events suggest people are increasingly concerned not just with their own well-being but that of animals as well. However, there is little systematic evidence on people's willingness-to-trade their own well-being and quality of life for improvements in the well-being of farm animals. In this paper, we utilize a straightforward and…

Computer-aided pulmonary image analysis in small animal models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J.

Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next.more » The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.« less

Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies

PubMed Central

Hooijmans, Carlijn R.; de Vries, Rob B. M.; Ritskes-Hoitinga, Merel; Rovers, Maroeska M.; Leeflang, Mariska M.; IntHout, Joanna; Wever, Kimberley E.; Hooft, Lotty; de Beer, Hans; Kuijpers, Ton; Macleod, Malcolm R.; Sena, Emily S.; ter Riet, Gerben; Morgan, Rebecca L.; Thayer, Kristina A.; Rooney, Andrew A.; Guyatt, Gordon H.; Schünemann, Holger J.

2018-01-01

Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only relevant or controlled data and directly inform clinical management decisions. Systematic reviews and meta-analyses are important tools to provide robust and informative evidence summaries of these animal studies. Rating how certain we are about the evidence could provide important information about the translational probability of findings in experimental animal studies to clinical practice and probably improve it. Evidence summaries and certainty in the evidence ratings could also be used (1) to support selection of interventions with best therapeutic potential to be tested in clinical trials, (2) to justify a regulatory decision limiting human exposure (to drug or toxin), or to (3) support decisions on the utility of further animal experiments. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is the most widely used framework to rate the certainty in the evidence and strength of health care recommendations. Here we present how the GRADE approach could be used to rate the certainty in the evidence of preclinical animal studies in the context of therapeutic interventions. We also discuss the methodological challenges that we identified, and for which further work is needed. Examples are defining the importance of consistency within and across animal species and using GRADE’s indirectness domain as a tool to predict translation from animal models to humans. PMID:29324741

Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies.

PubMed

Hooijmans, Carlijn R; de Vries, Rob B M; Ritskes-Hoitinga, Merel; Rovers, Maroeska M; Leeflang, Mariska M; IntHout, Joanna; Wever, Kimberley E; Hooft, Lotty; de Beer, Hans; Kuijpers, Ton; Macleod, Malcolm R; Sena, Emily S; Ter Riet, Gerben; Morgan, Rebecca L; Thayer, Kristina A; Rooney, Andrew A; Guyatt, Gordon H; Schünemann, Holger J; Langendam, Miranda W

2018-01-01

Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only relevant or controlled data and directly inform clinical management decisions. Systematic reviews and meta-analyses are important tools to provide robust and informative evidence summaries of these animal studies. Rating how certain we are about the evidence could provide important information about the translational probability of findings in experimental animal studies to clinical practice and probably improve it. Evidence summaries and certainty in the evidence ratings could also be used (1) to support selection of interventions with best therapeutic potential to be tested in clinical trials, (2) to justify a regulatory decision limiting human exposure (to drug or toxin), or to (3) support decisions on the utility of further animal experiments. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is the most widely used framework to rate the certainty in the evidence and strength of health care recommendations. Here we present how the GRADE approach could be used to rate the certainty in the evidence of preclinical animal studies in the context of therapeutic interventions. We also discuss the methodological challenges that we identified, and for which further work is needed. Examples are defining the importance of consistency within and across animal species and using GRADE's indirectness domain as a tool to predict translation from animal models to humans.

Sex differences underlying orofacial varicella zoster associated pain in rats.

PubMed

Stinson, Crystal; Deng, Mohong; Yee, Michael B; Bellinger, Larry L; Kinchington, Paul R; Kramer, Phillip R

2017-05-17

Most people are initially infected with varicella zoster virus (VZV) at a young age and this infection results in chickenpox. VZV then becomes latent and reactivates later in life resulting in herpes zoster (HZ) or "shingles". Often VZV infects neurons of the trigeminal ganglia to cause ocular problems, orofacial disease and occasionally a chronic pain condition termed post-herpetic neuralgia (PHN). To date, no model has been developed to study orofacial pain related to varicella zoster. Importantly, the incidence of zoster associated pain and PHN is known to be higher in women, although reasons for this sex difference remain unclear. Prior to this work, no animal model was available to study these sex-differences. Our goal was to develop an orofacial animal model for zoster associated pain which could be utilized to study the mechanisms contributing to this sex difference. To develop this model VZV was injected into the whisker pad of rats resulting in IE62 protein expression in the trigeminal ganglia; IE62 is an immediate early gene in the VZV replication program. Similar to PHN patients, rats showed retraction of neurites after VZV infection. Treatment of rats with gabapentin, an agent often used to combat PHN, ameliorated the pain response after whisker pad injection. Aversive behavior was significantly greater for up to 7 weeks in VZV injected rats over control inoculated rats. Sex differences were also seen such that ovariectomized and intact female rats given the lower dose of VZV showed a longer affective response than male rats. The phase of the estrous cycle also affected the aversive response suggesting a role for sex steroids in modulating VZV pain. These results suggest that this rat model can be utilized to study the mechanisms of 1) orofacial zoster associated pain and 2) the sex differences underlying zoster associated pain.

Utility of CRISPR/Cas9 systems in hematology research.

PubMed

Lucas, Daniel; O'Leary, Heather A; Ebert, Benjamin L; Cowan, Chad A; Tremblay, Cedric S

2017-10-01

Since the end of the 20th century, novel approaches have emerged to manipulate experimental models of hematological disorders so that they more accurately mirror what is observed in the clinical setting. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, given the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome-editing technologies have been developed to manipulate the genome specifically via deletion, insertion, or modification of targeted loci. These technologies have progressed swiftly, allowing their common use to investigate genetic function in experimental hematology. Among them, homologous-recombination-mediated targeting technologies have facilitated the manipulation of specific loci by generating knock-out and knock-in models. Despite promoting significant advances in our understanding of the molecular mechanisms involved in hematology, these inefficient, time-consuming, and labor-intensive approaches did not permit the development of cellular or animal models, recapitulating the complexity of hematological disorders. On October 26, 2016, Drs. Ben Ebert and Chad Cowan shared their knowledge of and experience with the utilization of CRISPR for models of myeloid malignancy, disease, and novel therapeutics in an International Society for Experimental Hematology webinar titled "Utility of CRISPR/Cas9 Systems in Hematology Research." Here, we provide an overview of the topics they covered, including their insights into the novel applications of the technique and its strengths and limitations. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Reactivation of Latent Tuberculosis: Variations on the Cornell Murine Model

PubMed Central

Scanga, Charles A.; Mohan, V. P.; Joseph, Heather; Yu, Keming; Chan, John; Flynn, JoAnne L.

1999-01-01

Mycobacterium tuberculosis causes active tuberculosis in only a small percentage of infected persons. In most cases, the infection is clinically latent, although immunosuppression can cause reactivation of a latent M. tuberculosis infection. Surprisingly little is known about the biology of the bacterium or the host during latency, and experimental studies on latent tuberculosis suffer from a lack of appropriate animal models. The Cornell model is a historical murine model of latent tuberculosis, in which mice infected with M. tuberculosis are treated with antibiotics (isoniazid and pyrazinamide), resulting in no detectable bacilli by organ culture. Reactivation of infection during this culture-negative state occurred spontaneously and following immunosuppression. In the present study, three variants of the Cornell model were evaluated for their utility in studies of latent and reactivated tuberculosis. The antibiotic regimen, inoculating dose, and antibiotic-free rest period prior to immunosuppression were varied. A variety of immunosuppressive agents, based on immunologic factors known to be important to control of acute infection, were used in attempts to reactivate the infection. Although reactivation of latent infection was observed in all three variants, these models were associated with characteristics that limit their experimental utility, including spontaneous reactivation, difficulties in inducing reactivation, and the generation of altered bacilli. The results from these studies demonstrate that the outcome of Cornell model-based studies depends critically upon the parameters used to establish the model. PMID:10456896

Neurocognitive dysfunction and pharmacological intervention using guanfacine in a rhesus macaque model of self-injurious behavior

PubMed Central

Freeman, Z T; Rice, K A; Soto, P L; Pate, K A M; Weed, M R; Ator, N A; DeLeon, I G; Wong, D F; Zhou, Y; Mankowski, J L; Zink, M C; Adams, R J; Hutchinson, E K

2015-01-01

Self-injurious behavior (SIB) is a common comorbidity of psychiatric disorders but there is a dearth of information about neurological mechanisms underlying the behavior, and few animal models exist. SIB in humans is characterized by any intentional self-directed behavior that leads to wounds, whereas in macaques it is not always accompanied by wounds. We describe a cohort of rhesus macaques displaying SIB as adults, in which changes within the central nervous system were associated with the SIB. In these macaques, increases in central nervous system striatal dopamine (DA) receptor binding (BPND) measured by positron emission tomography (PET) [11C]raclopride imaging correlated with severity of wounding (rs=0.662, P=0.014). Furthermore, utilizing standardized cognitive function tests, we showed that impulsivity (stop signal reaction time, SSRT) and deficits in attentional set shifting (intra-/extradimensional shift) were correlated with increased severity of SIB (rs=0.563, P=0.045 and rs=0.692, P=0.009, respectively). We also tested the efficacy of guanfacine, an α2A adrenergic agonist that acts to improve postsynaptic transmission of neuronal impulses, in reducing SIB. A subset of these animals were enrolled in a randomized experimenter-blinded study that demonstrated guanfacine decreased the severity of wounding in treated animals compared with vehicle-only-treated controls (P=0.043), with residual beneficial effects seen for several weeks after cessation of therapy. Animals with the highest severity of SIB that received guanfacine also showed the most significant improvement (rs=−0.761, P=0.009). The elevated PET BPND was likely due to low intrasynaptic DA, which in turn may have been improved by guanfacine. With underlying physiology potentially representative of the human condition and the ability to affect outcome measures of disease using pharmacotherapy, this model represents a unique opportunity to further our understanding of the biology and treatment of SIB in both animals and humans. PMID:25989141

Neurocognitive dysfunction and pharmacological intervention using guanfacine in a rhesus macaque model of self-injurious behavior.

PubMed

Freeman, Z T; Rice, K A; Soto, P L; Pate, K A M; Weed, M R; Ator, N A; DeLeon, I G; Wong, D F; Zhou, Y; Mankowski, J L; Zink, M C; Adams, R J; Hutchinson, E K

2015-05-19

Self-injurious behavior (SIB) is a common comorbidity of psychiatric disorders but there is a dearth of information about neurological mechanisms underlying the behavior, and few animal models exist. SIB in humans is characterized by any intentional self-directed behavior that leads to wounds, whereas in macaques it is not always accompanied by wounds. We describe a cohort of rhesus macaques displaying SIB as adults, in which changes within the central nervous system were associated with the SIB. In these macaques, increases in central nervous system striatal dopamine (DA) receptor binding (BPND) measured by positron emission tomography (PET) [11C]raclopride imaging correlated with severity of wounding (rs=0.662, P=0.014). Furthermore, utilizing standardized cognitive function tests, we showed that impulsivity (stop signal reaction time, SSRT) and deficits in attentional set shifting (intra-/extradimensional shift) were correlated with increased severity of SIB (rs=0.563, P=0.045 and rs=0.692, P=0.009, respectively). We also tested the efficacy of guanfacine, an α2A adrenergic agonist that acts to improve postsynaptic transmission of neuronal impulses, in reducing SIB. A subset of these animals were enrolled in a randomized experimenter-blinded study that demonstrated guanfacine decreased the severity of wounding in treated animals compared with vehicle-only-treated controls (P=0.043), with residual beneficial effects seen for several weeks after cessation of therapy. Animals with the highest severity of SIB that received guanfacine also showed the most significant improvement (rs=-0.761, P=0.009). The elevated PET BPND was likely due to low intrasynaptic DA, which in turn may have been improved by guanfacine. With underlying physiology potentially representative of the human condition and the ability to affect outcome measures of disease using pharmacotherapy, this model represents a unique opportunity to further our understanding of the biology and treatment of SIB in both animals and humans.

Identifying viscoelastic parameters of tissue specimens using Hertz contact mechanics

NASA Astrophysics Data System (ADS)

Namiri, Nikan K.; Maccabi, Ashkan; Bajwa, Neha; Badran, Karam W.; St. John, Maie A.; Taylor, Zachary D.; Grundfest, Warren S.; Saddik, George N.

2018-02-01

The unique viscoelastic properties of tissues throughout the human body can be utilized in a variety of clinical applications. Palpation techniques, for instance, enable surgeons to distinguish malignancies in tissue composition during surgical procedures. Additionally, imaging devices have begun utilizing the viscoelastic properties of tissue to delineate tumor margins. Vibroacoustography (VA), a non-invasive, high resolution imaging modality, has the ability to detect sub-millimeter differences in tissue composition. VA images tissue using a low frequency acoustic radiation force, which perturbs the target and causes an acoustic response that is dependent on the target's viscoelastic properties. Given the unique properties specific to human and animal tissues, there are far-reaching clinical applications of VA. To date, however, a comprehensive model that relates viscoelasticity to VA tissue response has yet to be developed. Utilizing tissue-mimicking phantoms (TMPs) and fresh ex vivo tissues, a mechanical stress relaxation model was developed to compare the viscoelastic properties of known and unknown specimens. This approach was conducted using the Hertz theory of contact mechanics. Fresh hepatic tissue was obtained from porcine subjects (n=10), while gelatin and agar TMPs (n=12) were fabricated from organic extracts. Each specimen's elastic modulus (E), long term shear modulus (η), and time constant (τ) were found to be unique. Additionally, each specimen's stress relaxation profiles were analyzed using Weichert-Maxwell viscoelastic modeling, and retained high precision (R2>0.9) among all samples.

MIDG-Emerging grid technologies for multi-site preclinical molecular imaging research communities.

PubMed

Lee, Jasper; Documet, Jorge; Liu, Brent; Park, Ryan; Tank, Archana; Huang, H K

2011-03-01

Molecular imaging is the visualization and identification of specific molecules in anatomy for insight into metabolic pathways, tissue consistency, and tracing of solute transport mechanisms. This paper presents the Molecular Imaging Data Grid (MIDG) which utilizes emerging grid technologies in preclinical molecular imaging to facilitate data sharing and discovery between preclinical molecular imaging facilities and their collaborating investigator institutions to expedite translational sciences research. Grid-enabled archiving, management, and distribution of animal-model imaging datasets help preclinical investigators to monitor, access and share their imaging data remotely, and promote preclinical imaging facilities to share published imaging datasets as resources for new investigators. The system architecture of the Molecular Imaging Data Grid is described in a four layer diagram. A data model for preclinical molecular imaging datasets is also presented based on imaging modalities currently used in a molecular imaging center. The MIDG system components and connectivity are presented. And finally, the workflow steps for grid-based archiving, management, and retrieval of preclincial molecular imaging data are described. Initial performance tests of the Molecular Imaging Data Grid system have been conducted at the USC IPILab using dedicated VMware servers. System connectivity, evaluated datasets, and preliminary results are presented. The results show the system's feasibility, limitations, direction of future research. Translational and interdisciplinary research in medicine is increasingly interested in cellular and molecular biology activity at the preclinical levels, utilizing molecular imaging methods on animal models. The task of integrated archiving, management, and distribution of these preclinical molecular imaging datasets at preclinical molecular imaging facilities is challenging due to disparate imaging systems and multiple off-site investigators. A Molecular Imaging Data Grid design, implementation, and initial evaluation is presented to demonstrate the secure and novel data grid solution for sharing preclinical molecular imaging data across the wide-area-network (WAN).

Utility of texture analysis for quantifying hepatic fibrosis on proton density MRI.

PubMed

Yu, HeiShun; Buch, Karen; Li, Baojun; O'Brien, Michael; Soto, Jorge; Jara, Hernan; Anderson, Stephan W

2015-11-01

To evaluate the potential utility of texture analysis of proton density maps for quantifying hepatic fibrosis in a murine model of hepatic fibrosis. Following Institutional Animal Care and Use Committee (IACUC) approval, a dietary model of hepatic fibrosis was used and 15 ex vivo murine liver tissues were examined. All images were acquired using a 30 mm bore 11.7T magnetic resonance imaging (MRI) scanner with a multiecho spin-echo sequence. A texture analysis was employed extracting multiple texture features including histogram-based, gray-level co-occurrence matrix-based (GLCM), gray-level run-length-based features (GLRL), gray level gradient matrix (GLGM), and Laws' features. Texture features were correlated with histopathologic and digital image analysis of hepatic fibrosis. Histogram features demonstrated very weak to moderate correlations (r = -0.29 to 0.51) with hepatic fibrosis. GLCM features correlation and contrast demonstrated moderate-to-strong correlations (r = -0.71 and 0.59, respectively) with hepatic fibrosis. Moderate correlations were seen between hepatic fibrosis and the GLRL feature short run low gray-level emphasis (SRLGE) (r = -0. 51). GLGM features demonstrate very weak to weak correlations with hepatic fibrosis (r = -0.27 to 0.09). Moderate correlations were seen between hepatic fibrosis and Laws' features L6 and L7 (r = 0.58). This study demonstrates the utility of texture analysis applied to proton density MRI in a murine liver fibrosis model and validates the potential utility of texture-based features for the noninvasive, quantitative assessment of hepatic fibrosis. © 2015 Wiley Periodicals, Inc.

Identification of sero-reactive antigens for the early diagnosis of Johne’s disease in cattle

PubMed Central

Randall, Arlo; Grohn, Yrjo T.; Katani, Robab; Schilling, Megan; Radzio-Basu, Jessica

2017-01-01

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), a chronic intestinal inflammatory disease of cattle and other ruminants. JD has a high herd prevalence and causes serious animal health problems and significant economic loss in domesticated ruminants throughout the world. Since serological detection of MAP infected animals during the early stages of infection remains challenging due to the low sensitivity of extant assays, we screened 180 well-characterized serum samples using a whole proteome microarray from Mycobacterium tuberculosis (MTB), a close relative of MAP. Based on extensive testing of serum and milk samples, fecal culture and qPCR for direct detection of MAP, the samples were previously assigned to one of 4 groups: negative low exposure (n = 30, NL); negative high exposure (n = 30, NH); fecal positive, ELISA negative (n = 60, F+E-); and fecal positive, ELISA positive (n = 60, F+E+). Of the 740 reactive proteins, several antigens were serologically recognized early but not late in infection, suggesting a complex and dynamic evolution of the MAP humoral immune response during disease progression. Ordinal logistic regression models identified a subset of 47 candidate proteins with significantly different normalized intensity values (p<0.05), including 12 in the NH and 23 in F+E- groups, suggesting potential utility for the early detection of MAP infected animals. Next, the diagnostic utility of four MAP orthologs (MAP1569, MAP2942c, MAP2609, and MAP1272c) was assessed and reveal moderate to high diagnostic sensitivities (range 48.3% to 76.7%) and specificity (range 96.7% to 100%), with a combined 88.3% sensitivity and 96.7% specificity. Taken together, the results of our analyses have identified several candidate MAP proteins of potential utility for the early detection of MAP infection, as well individual MAP proteins that may serve as the foundation for the next generation of well-defined serological diagnosis of JD in cattle. PMID:28863177

A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

PubMed

Ono, Yosuke; Fujita, Masanori; Ono, Sachiko; Ogata, Sho; Tachibana, Shoichi; Tanaka, Yuji

2016-06-30

Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 μg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.

Harmaline Tremor: Underlying Mechanisms in a Potential Animal Model of Essential Tremor

PubMed Central

Handforth, Adrian

2012-01-01

Background Harmaline and harmine are tremorigenic β-carbolines that, on administration to experimental animals, induce an acute postural and kinetic tremor of axial and truncal musculature. This drug-induced action tremor has been proposed as a model of essential tremor. Here we review what is known about harmaline tremor. Methods Using the terms harmaline and harmine on PubMed, we searched for papers describing the effects of these β-carbolines on mammalian tissue, animals, or humans. Results Investigations over four decades have shown that harmaline induces rhythmic burst-firing activity in the medial and dorsal accessory inferior olivary nuclei that is transmitted via climbing fibers to Purkinje cells and to the deep cerebellar nuclei, then to brainstem and spinal cord motoneurons. The critical structures required for tremor expression are the inferior olive, climbing fibers, and the deep cerebellar nuclei; Purkinje cells are not required. Enhanced synaptic norepinephrine or blockade of ionic glutamate receptors suppresses tremor, whereas enhanced synaptic serotonin exacerbates tremor. Benzodiazepines and muscimol suppress tremor. Alcohol suppresses harmaline tremor but exacerbates harmaline-associated neural damage. Recent investigations on the mechanism of harmaline tremor have focused on the T-type calcium channel. Discussion Like essential tremor, harmaline tremor involves the cerebellum, and classic medications for essential tremor have been found to suppress harmaline tremor, leading to utilization of the harmaline model for preclinical testing of antitremor drugs. Limitations are that the model is acute, unlike essential tremor, and only approximately half of the drugs reported to suppress harmaline tremor are subsequently found to suppress tremor in clinical trials. PMID:23440018

Towards the development of improved tests for negative symptoms of schizophrenia in a validated animal model.

PubMed

Sahin, Ceren; Doostdar, Nazanin; Neill, Joanna C

2016-10-01

Negative symptoms in schizophrenia remain an unmet clinical need. There is no licensed treatment specifically for this debilitating aspect of the disorder and effect sizes of new therapies are too small to make an impact on quality of life and function. Negative symptoms are multifactorial but often considered in terms of two domains, expressive deficit incorporating blunted affect and poverty of speech and avolition incorporating asociality and lack of drive. There is a clear need for improved understanding of the neurobiology of negative symptoms which can be enabled through the use of carefully validated animal models. While there are several tests for assessing sociability in animals, tests for blunted affect in schizophrenia are currently lacking. Two paradigms have recently been developed for assessing negative affect of relevance to depression in rats. Here we assess their utility for studying negative symptoms in schizophrenia using our well validated model for schizophrenia of sub-chronic (sc) treatment with Phencyclidine (PCP) in adult female rats. Results demonstrate that sc PCP treatment produces a significant negative affect bias in response to a high value reward in the optimistic and affective bias tests. Our results are not easily explained by the known cognitive deficits induced by sc PCP and support the hypothesis of a negative affective bias in this model. We suggest that further refinement of these two tests will provide a means to investigate the neurobiological basis of negative affect in schizophrenia, thus supporting the assessment of efficacy of new targets for this currently untreated symptom domain. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid enrichment of (homo)acetogenic consortia from animal feces using a high mass-transfer gas-lift reactor fed with syngas.

PubMed

Park, Shinyoung; Yasin, Muhammad; Kim, Daehee; Park, Hee-Deung; Kang, Chang Min; Kim, Duk Jin; Chang, In Seop

2013-09-01

A gas-lift reactor having a high mass transfer coefficient (k(L)a = 80.28 h(-1)) for a relatively insoluble gas (carbon monoxide; CO) was used to enrich (homo)acetogens from animal feces. Samples of fecal matter from cow, rabbit, chicken, and goat were used as sources of inoculum for the enrichment of CO and H(2) utilizing microbial consortia. To confirm the successful enrichment, the Hungate roll tube technique was employed to count and then isolate putative CO utilizers. The results of this work showed that CO and H(2) utilizing consortia were established for each inoculum source after 8 days. The number of colony-forming units in cow, rabbit, chicken, and goat fecal samples were 3.83 × 10(9), 1.03 × 10(9), 8.3 × 10(8), and 3.25 × 10(8) cells/ml, respectively. Forty-two colonies from the animal fecal samples were screened for the ability to utilize CO/H(2). Ten of these 42 colonies were capable of utilizing CO/H(2). Five isolates from cow feces (samples 5, 6, 8, 16, and 22) were highly similar to previously unknown (homo)acetogen, while cow-7 has shown 99 % similarity with Acetobacterium sp. as acetogens. On the other hand, four isolates from chicken feces (samples 3, 8, 10, and 11) have also shown high CO/H(2) utilizing activity. Hence, it is expected that this research could be used as the basis for the rapid enrichment of (homo)acetogenic consortia from various environmental sources.

Modeling of threonine requirement in fast-growing chickens, depending on age, sex, protein deposition, and dietary threonine efficiency.

PubMed

Samadi; Liebert, F

2006-11-01

In addition to dose-response studies, modeling of N utilization, depending on intake of the first limiting amino acid in the diet, is one of the tools for assessing amino acid requirements in growing animals. Based on a verified nonlinear N-utilization model and following the principles of the diet dilution technique, N-balance experiments were conducted to estimate the Thr requirement of fast-growing chickens (genotype Cobb), depending on age, sex, CP deposition. and efficiency of dietary Thr utilization. Different predictions were made for the feed intake to conclude the optimal Thr concentration in the feed. The results are based on N-balance experiments with a total of 144 male and 144 female growing chickens within 4 age periods (I: 10 to 25 d; II: 30 to 45 d; III: 50 to 65 d; IV: 70 to 85 d), using diets with graded protein supply (6.6, 13, 19.6, 25.1, 31.8, and 37.6% CP in DM) from high-protein soybean meal with a constant amino acid ratio and Thr as the first limiting amino acid (3.87 g of Thr/100 g of CP; dietary Lys:Thr = 1:0.54). The observed optimal Thr concentration (% of feed) was influenced by age, sex, level of CP deposition, dietary efficiency of Thr utilization, and predicted feed intake. For male chickens, assuming an average CP deposition (60% of the potential) and average efficiency of Thr utilization, 0.78% (10 to 25 d), 0.73% (30 to 45 d), 0.65% (50 to 65 d), and 0.55% (70 to 85 d) total dietary Thr were observed as optimal total Thr concentration in the diet (corresponding to 60, 135, 160, and 180 g of daily feed intake, respectively). Data are discussed in context with the main factors of influence like age, sex, level of daily CP deposition, efficiency of dietary Thr utilization, and predicted feed intake.

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

PubMed Central

Gardner, Jameson K.; Herbst-Kralovetz, Melissa M.

2016-01-01

The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies. PMID:27834891

Assessing Animal Welfare Impacts in the Management of European Rabbits (Oryctolagus cuniculus), European Moles (Talpa europaea) and Carrion Crows (Corvus corone)

PubMed Central

Baker, Sandra E.; Sharp, Trudy M.; Macdonald, David W.

2016-01-01

Human-wildlife conflict is a global issue. Attempts to manage this conflict impact upon wild animal welfare, an issue receiving little attention until relatively recently. Where human activities harm animal welfare these effects should be minimised where possible. However, little is known about the welfare impacts of different wildlife management interventions, and opinions on impacts vary widely. Welfare impacts therefore need to be assessed objectively. Our objectives were to: 1) establish whether an existing welfare assessment model could differentiate and rank the impacts of different wildlife management interventions (for decision-making purposes); 2) identify and evaluate any additional benefits of making formal welfare assessments; and 3) illustrate issues raised by application of the model. We applied the welfare assessment model to interventions commonly used with rabbits (Oryctolagus cuniculus), moles (Talpa europaea) and crows (Corvus corone) in the UK. The model ranked interventions for rabbits (least impact first: fencing, head shot, chest shot) and crows (shooting, scaring, live trapping with cervical dislocation). For moles, managing molehills and tunnels scored least impact. Both spring trapping, and live trapping followed by translocation, scored greater impacts, but these could not be compared directly as they scored on different axes of the model. Some rankings appeared counter-intuitive, highlighting the need for objective formal welfare assessments. As well as ranking the humaneness of interventions, the model highlighted future research needs and how Standard Operating Procedures might be improved. The model is a milestone in assessing wildlife management welfare impacts, but our research revealed some limitations of the model and we discuss likely challenges in resolving these. In future, the model might be developed to improve its utility, e.g. by refining the time-scales. It might also be used to reach consensus among stakeholders about relative welfare impacts or to identify ways of improving wildlife management practice in the field. PMID:26726808

Assessing Animal Welfare Impacts in the Management of European Rabbits (Oryctolagus cuniculus), European Moles (Talpa europaea) and Carrion Crows (Corvus corone).

PubMed

Baker, Sandra E; Sharp, Trudy M; Macdonald, David W

2016-01-01

Human-wildlife conflict is a global issue. Attempts to manage this conflict impact upon wild animal welfare, an issue receiving little attention until relatively recently. Where human activities harm animal welfare these effects should be minimised where possible. However, little is known about the welfare impacts of different wildlife management interventions, and opinions on impacts vary widely. Welfare impacts therefore need to be assessed objectively. Our objectives were to: 1) establish whether an existing welfare assessment model could differentiate and rank the impacts of different wildlife management interventions (for decision-making purposes); 2) identify and evaluate any additional benefits of making formal welfare assessments; and 3) illustrate issues raised by application of the model. We applied the welfare assessment model to interventions commonly used with rabbits (Oryctolagus cuniculus), moles (Talpa europaea) and crows (Corvus corone) in the UK. The model ranked interventions for rabbits (least impact first: fencing, head shot, chest shot) and crows (shooting, scaring, live trapping with cervical dislocation). For moles, managing molehills and tunnels scored least impact. Both spring trapping, and live trapping followed by translocation, scored greater impacts, but these could not be compared directly as they scored on different axes of the model. Some rankings appeared counter-intuitive, highlighting the need for objective formal welfare assessments. As well as ranking the humaneness of interventions, the model highlighted future research needs and how Standard Operating Procedures might be improved. The model is a milestone in assessing wildlife management welfare impacts, but our research revealed some limitations of the model and we discuss likely challenges in resolving these. In future, the model might be developed to improve its utility, e.g. by refining the time-scales. It might also be used to reach consensus among stakeholders about relative welfare impacts or to identify ways of improving wildlife management practice in the field.

A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: development and validation.

PubMed

Smith, Jordan Ned; Hinderliter, Paul M; Timchalk, Charles; Bartels, Michael J; Poet, Torka S

2014-08-01

Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages. Copyright © 2013 Elsevier Inc. All rights reserved.

Modeling the utility of binaural cues for underwater sound localization.

PubMed

Schneider, Jennifer N; Lloyd, David R; Banks, Patchouly N; Mercado, Eduardo

2014-06-01

The binaural cues used by terrestrial animals for sound localization in azimuth may not always suffice for accurate sound localization underwater. The purpose of this research was to examine the theoretical limits of interaural timing and level differences available underwater using computational and physical models. A paired-hydrophone system was used to record sounds transmitted underwater and recordings were analyzed using neural networks calibrated to reflect the auditory capabilities of terrestrial mammals. Estimates of source direction based on temporal differences were most accurate for frequencies between 0.5 and 1.75 kHz, with greater resolution toward the midline (2°), and lower resolution toward the periphery (9°). Level cues also changed systematically with source azimuth, even at lower frequencies than expected from theoretical calculations, suggesting that binaural mechanical coupling (e.g., through bone conduction) might, in principle, facilitate underwater sound localization. Overall, the relatively limited ability of the model to estimate source position using temporal and level difference cues underwater suggests that animals such as whales may use additional cues to accurately localize conspecifics and predators at long distances. Copyright © 2014 Elsevier B.V. All rights reserved.

Intra-Accumbens Injection of a Dopamine Aptamer Abates MK-801-Induced Cognitive Dysfunction in a Model of Schizophrenia

PubMed Central

Holahan, Matthew R.; Madularu, Dan; McConnell, Erin M.; Walsh, Ryan; DeRosa, Maria C.

2011-01-01

Systemic administration of the noncompetitive NMDA-receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. The present work investigated the ability of a dopamine-binding DNA aptamer to regulate these MK-801-induced cognitive deficits when injected into the nucleus accumbens. Rats were trained to bar press for chocolate pellet rewards then randomly assigned to receive an intra-accumbens injection of a DNA aptamer (200 nM; n = 7), tris buffer (n = 6) or a randomized DNA oligonucleotide (n = 7). Animals were then treated systemically with MK-801 (0.1 mg/kg) and tested for their ability to extinguish their bar pressing response. Two control groups were also included that did not receive MK-801. Data revealed that injection of Tris buffer or the random oligonucleotide sequence into the nucleus accumbens prior to treatment with MK-801 did not reduce the MK-801-induced extinction deficit. Animals continued to press at a high rate over the entire course of the extinction session. Injection of the dopamine aptamer reversed this MK-801-induced elevation in lever pressing to levels as seen in rats not treated with MK-801. Tests for activity showed that the aptamer did not impair locomotor activity. Results demonstrate the in vivo utility of DNA aptamers as tools to investigate neurobiological processes in preclinical animal models of mental health disease. PMID:21779401

N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease.

PubMed

Polyak, Erzsebet; Ostrovsky, Julian; Peng, Min; Dingley, Stephen D; Tsukikawa, Mai; Kwon, Young Joon; McCormack, Shana E; Bennett, Michael; Xiao, Rui; Seiler, Christoph; Zhang, Zhe; Falk, Marni J

2018-04-01

Oxidative stress is a known contributing factor in mitochondrial respiratory chain (RC) disease pathogenesis. Yet, no efficient means exists to objectively evaluate the comparative therapeutic efficacy or toxicity of different antioxidant compounds empirically used in human RC disease. We postulated that pre-clinical comparative analysis of diverse antioxidant drugs having suggested utility in primary RC disease using animal and cellular models of RC dysfunction may improve understanding of their integrated effects and physiologic mechanisms, and enable prioritization of lead antioxidant molecules to pursue in human clinical trials. Here, lifespan effects of N-acetylcysteine (NAC), vitamin E, vitamin C, coenzyme Q10 (CoQ10), mitochondrial-targeted CoQ10 (MS010), lipoate, and orotate were evaluated as the primary outcome in a well-established, short-lived C. elegans gas-1(fc21) animal model of RC complex I disease. Healthspan effects were interrogated to assess potential reversal of their globally disrupted in vivo mitochondrial physiology, transcriptome profiles, and intermediary metabolic flux. NAC or vitamin E fully rescued, and coenzyme Q, lipoic acid, orotic acid, and vitamin C partially rescued gas-1(fc21) lifespan toward that of wild-type N2 Bristol worms. MS010 and CoQ10 largely reversed biochemical pathway expression changes in gas-1(fc21) worms. While nearly all drugs normalized the upregulated expression of the "cellular antioxidant pathway", they failed to rescue the mutant worms' increased in vivo mitochondrial oxidant burden. NAC and vitamin E therapeutic efficacy were validated in human fibroblast and/or zebrafish complex I disease models. Remarkably, rotenone-induced zebrafish brain death was preventable partially with NAC and fully with vitamin E. Overall, these pre-clinical model animal data demonstrate that several classical antioxidant drugs do yield significant benefit on viability and survival in primary mitochondrial disease, where their major therapeutic benefit appears to result from targeting global cellular, rather than intramitochondria-specific, oxidative stress. Clinical trials are needed to evaluate whether the two antioxidants, NAC and vitamin E, that show greatest efficacy in translational model animals significantly improve the survival, function, and feeling of human subjects with primary mitochondrial RC disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Utilization and environmental management of residues from intensive animal production

USDA-ARS?s Scientific Manuscript database

Animal manures are traditional sources of nutrients in agriculture. Under proper management, manures provide nutrients to soil, reducing or eliminating the use of commercial fertilizers, as well as organic carbon that improves soil physical properties and soil health. However, excessive application ...

Development of the Digital Arthritis Index, a Novel Metric to Measure Disease Parameters in a Rat Model of Rheumatoid Arthritis.

PubMed

Lim, Maria A; Louie, Brenton; Ford, Daniel; Heath, Kyle; Cha, Paulyn; Betts-Lacroix, Joe; Lum, Pek Yee; Robertson, Timothy L; Schaevitz, Laura

2017-01-01

Despite a broad spectrum of anti-arthritic drugs currently on the market, there is a constant demand to develop improved therapeutic agents. Efficient compound screening and rapid evaluation of treatment efficacy in animal models of rheumatoid arthritis (RA) can accelerate the development of clinical candidates. Compound screening by evaluation of disease phenotypes in animal models facilitates preclinical research by enhancing understanding of human pathophysiology; however, there is still a continuous need to improve methods for evaluating disease. Current clinical assessment methods are challenged by the subjective nature of scoring-based methods, time-consuming longitudinal experiments, and the requirement for better functional readouts with relevance to human disease. To address these needs, we developed a low-touch, digital platform for phenotyping preclinical rodent models of disease. As a proof-of-concept, we utilized the rat collagen-induced arthritis (CIA) model of RA and developed the Digital Arthritis Index (DAI), an objective and automated behavioral metric that does not require human-animal interaction during the measurement and calculation of disease parameters. The DAI detected the development of arthritis similar to standard in vivo methods, including ankle joint measurements and arthritis scores, as well as demonstrated a positive correlation to ankle joint histopathology. The DAI also determined responses to multiple standard-of-care (SOC) treatments and nine repurposed compounds predicted by the SMarTR TM Engine to have varying degrees of impact on RA. The disease profiles generated by the DAI complemented those generated by standard methods. The DAI is a highly reproducible and automated approach that can be used in-conjunction with standard methods for detecting RA disease progression and conducting phenotypic drug screens.

Presence of multiple lesion types with vastly different microenvironments in C3HeB/FeJ mice following aerosol infection with Mycobacterium tuberculosis

PubMed Central

Irwin, Scott M.; Driver, Emily; Lyon, Edward; Schrupp, Christopher; Ryan, Gavin; Gonzalez-Juarrero, Mercedes; Basaraba, Randall J.; Nuermberger, Eric L.; Lenaerts, Anne J.

2015-01-01

ABSTRACT Cost-effective animal models that accurately reflect the pathological progression of pulmonary tuberculosis are needed to screen and evaluate novel tuberculosis drugs and drug regimens. Pulmonary disease in humans is characterized by a number of heterogeneous lesion types that reflect differences in cellular composition and organization, extent of encapsulation, and degree of caseous necrosis. C3HeB/FeJ mice have been increasingly used to model tuberculosis infection because they produce hypoxic, well-defined granulomas exhibiting caseous necrosis following aerosol infection with Mycobacterium tuberculosis. A comprehensive histopathological analysis revealed that C3HeB/FeJ mice develop three morphologically distinct lesion types in the lung that differ with respect to cellular composition, degree of immunopathology and control of bacterial replication. Mice displaying predominantly the fulminant necrotizing alveolitis lesion type had significantly higher pulmonary bacterial loads and displayed rapid and severe immunopathology characterized by increased mortality, highlighting the pathological role of an uncontrolled granulocytic response in the lung. Using a highly sensitive novel fluorescent acid-fast stain, we were able to visualize the spatial distribution and location of bacteria within each lesion type. Animal models that better reflect the heterogeneity of lesion types found in humans will permit more realistic modeling of drug penetration into solid caseous necrotic lesions and drug efficacy testing against metabolically distinct bacterial subpopulations. A more thorough understanding of the pathological progression of disease in C3HeB/FeJ mice could facilitate modulation of the immune response to produce the desired pathology, increasing the utility of this animal model. PMID:26035867

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model

PubMed Central

Jackson, George R.; Maione, Anna G.; Klausner, Mitchell

2018-01-01

Abstract Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal (in vitro) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1–2 and EPA Acute Inhalation Toxicity Category I–II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity. PMID:29904643

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model.

PubMed

Jackson, George R; Maione, Anna G; Klausner, Mitchell; Hayden, Patrick J

2018-06-01

Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal ( in vitro ) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1-2 and EPA Acute Inhalation Toxicity Category I-II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity.

Genetics of Aggression in Voles

PubMed Central

Gobrogge, Kyle L.; Wang, Zuoxin

2016-01-01

Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form pair bonds—a behavior composed of several social interactions including attachment with a familiar mate and aggression toward conspecific strangers. Therefore, this species has provided an excellent opportunity for the study of pair bonding behavior and its underlying neural mechanisms. In this chapter, we discuss the utility of this unique animal model in the study of aggression and review recent findings illustrating the neurochemical mechanisms underlying pair bonding-induced aggression. Implications of this research for our understanding of the neurobiology of human violence are also discussed. PMID:22078479

The recovery and utilization of space suit range-of-motion data

NASA Technical Reports Server (NTRS)

Reinhardt, AL; Walton, James S.

1988-01-01

A technique for recovering data for the range of motion of a subject wearing a space suit is described along with the validation of this technique on an EVA space suit. Digitized data are automatically acquired from video images of the subject; three-dimensional trajectories are recovered from these data, and can be displayed using three-dimensional computer graphics. Target locations are recovered using a unique video processor and close-range photogrammetry. It is concluded that such data can be used in such applications as the animation of anthropometric computer models.