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Sample records for animal diseases host-pathogen

  1. MODELING HOST-PATHOGEN INTERACTIONS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS FOR INFECTIOUS DISEASE RESEARCH (Session introduction)

    SciTech Connect

    McDermott, Jason E.; Braun, Pascal; Bonneau, Richard A.; Hyduke, Daniel R.

    2011-12-01

    Pathogenic infections are a major cause of both human disease and loss of crop yields and animal stocks and thus cause immense damage to the worldwide economy. The significance of infectious diseases is expected to increase in an ever more connected warming world, in which new viral, bacterial and fungal pathogens can find novel hosts and ecologic niches. At the same time, the complex and sophisticated mechanisms by which diverse pathogenic agents evade defense mechanisms and subvert their hosts networks to suit their lifestyle needs is still very incompletely understood especially from a systems perspective [1]. Thus, understanding host-pathogen interactions is both an important and a scientifically fascinating topic. Recently, technology has offered the opportunity to investigate host-pathogen interactions on a level of detail and scope that offers immense computational and analytical possibilities. Genome sequencing was pioneered on some of these pathogens, and the number of strains and variants of pathogens sequenced to date vastly outnumbers the number of host genomes available. At the same time, for both plant and human hosts more and more data on population level genomic variation becomes available and offers a rich field for analysis into the genetic interactions between host and pathogen.

  2. Infectious Bursal Disease: a complex host-pathogen interaction.

    PubMed

    Ingrao, Fiona; Rauw, Fabienne; Lambrecht, Bénédicte; van den Berg, Thierry

    2013-11-01

    Infectious Bursal Disease (IBD) is caused by a small, non-enveloped virus, highly resistant in the outside environment. Infectious Bursal Disease Virus (IBDV) targets the chicken's immune system in a very comprehensive and complex manner by destroying B lymphocytes, attracting T cells and activating macrophages. As an RNA virus, IBDV has a high mutation rate and may thus give rise to viruses with a modified antigenicity or increased virulence, as emphasized during the last decades. The molecular basis of pathogenicity and the exact cause of clinical disease and death are still poorly understood, as it is not clearly related to the severity of the lesions and the extent of the bursal damage. Recent works however, pointed out the role of an exacerbated innate immune response during the early stage of the infection with upregulated production of promediators that will induce a cytokine storm. In the case of IBDV, immunosuppression is both a direct consequence of the infection of specific target immune cells and an indirect consequence of the interactions occurring in the immune network of the host. Recovery from disease or subclinical infection will be followed by immunosuppression with more serious consequences if the strain is very virulent and infection occurs early in life. Although the immunosuppression caused by IBDV is principally directed towards B-lymphocytes, an effect on cell-mediated immunity (CMI) has also been demonstrated therefore increasing the impact of IBDV on the immunocompetence of the chicken. In addition to its zootechnical impact and its role in the development of secondary infections, it may affect the immune response of the chicken to subsequent vaccinations, essential in all types of intensive farming. Recent progress in the field of avian immunology has allowed a better knowledge of the immunological mechanisms involved in the disease but also should give improved tools for the measurement of immunosuppression in the field situation

  3. Studying Host-Pathogen Interactions In 3-D: Organotypic Models For Infectious Disease And Drug Development

    NASA Technical Reports Server (NTRS)

    Nickerson, Cheryl A.; Richter, Emily G.; Ott, C. Mark

    2006-01-01

    Representative, reproducible and high-throughput models of human cells and tissues are critical for a meaningful evaluation of host-pathogen interactions and are an essential component of the research developmental pipeline. The most informative infection models - animals, organ explants and human trials - are not suited for extensive evaluation of pathogenesis mechanisms and screening of candidate drugs. At the other extreme, more cost effective and accessible infection models such as conventional cell culture and static co-culture may not capture physiological and three-dimensional aspects of tissue biology that are important in assessing pathogenesis, and effectiveness and cytotoxicity of therapeutics. Our lab has used innovative bioengineering technology to establish biologically meaningful 3-D models of human tissues that recapitulate many aspects of the differentiated structure and function of the parental tissue in vivo, and we have applied these models to study infectious disease. We have established a variety of different 3-D models that are currently being used in infection studies - including small intestine, colon, lung, placenta, bladder, periodontal ligament, and neuronal models. Published work from our lab has shown that our 3-D models respond to infection with bacterial and viral pathogens in ways that reflect the infection process in vivo. By virtue of their physiological relevance, 3-D cell cultures may also hold significant potential as models to provide insight into the neuropathogenesis of HIV infection. Furthermore, the experimental flexibility, reproducibility, cost-efficiency, and high throughput platform afforded by these 3-D models may have important implications for the design and development of drugs with which to effectively treat neurological complications of HIV infection.

  4. Update on host-pathogen interactions in cystic fibrosis lung disease.

    PubMed

    Hector, Andreas; Frey, Nina; Hartl, Dominik

    2016-12-01

    Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease. PMID:26905568

  5. Mechanisms of Disease: Host-Pathogen Interactions between Burkholderia Species and Lung Epithelial Cells

    PubMed Central

    David, Jonathan; Bell, Rachel E.; Clark, Graeme C.

    2015-01-01

    Members of the Burkholderia species can cause a range of severe, often fatal, respiratory diseases. A variety of in vitro models of infection have been developed in an attempt to elucidate the mechanism by which Burkholderia spp. gain entry to and interact with the body. The majority of studies have tended to focus on the interaction of bacteria with phagocytic cells with a paucity of information available with regard to the lung epithelium. However, the lung epithelium is becoming more widely recognized as an important player in innate immunity and the early response to infections. Here we review the complex relationship between Burkholderia species and epithelial cells with an emphasis on the most pathogenic species, Burkholderia pseudomallei and Burkholderia mallei. The current gaps in knowledge in our understanding are highlighted along with the epithelial host-pathogen interactions that offer potential opportunities for therapeutic intervention. PMID:26636042

  6. Warmer temperatures increase disease transmission and outbreak intensity in a host-pathogen system.

    PubMed

    Elderd, Bret D; Reilly, James R

    2014-07-01

    While rising global temperatures are increasingly affecting both species and their biotic interactions, the debate about whether global warming will increase or decrease disease transmission between individuals remains far from resolved. This may stem from the lack of empirical data. Using a tractable and easily manipulated insect host-pathogen system, we conducted a series of field and laboratory experiments to examine how increased temperatures affect disease transmission using the crop-defoliating pest, the fall armyworm (Spodoptera frugiperda) and its species-specific baculovirus, which causes a fatal infection. To examine the effects of temperature on disease transmission in the field, we manipulated baculovirus density and temperature. As infection occurs when a host consumes leaf tissue on which the pathogen resides, baculovirus density was controlled by placing varying numbers of infected neonate larvae on experimental plants. Temperature was manipulated by using open-top chambers (OTCs). The laboratory experiments examined how increased temperatures affect fall armyworm feeding and development rates, which provide insight into how host feeding behaviour and physiology may affect transmission. Disease transmission and outbreak intensity, measured as the cumulative fraction infected during an epizootic, increased at higher temperatures. However, there was no appreciable change in the mean transmission rate of the disease, which is often the focus of empirical and theoretical research. Instead, the coefficient of variation (CV) associated with the transmission rate shrunk. As the CV decreased, heterogeneity in disease risk across individuals declined, which resulted in an increase in outbreak intensity. In the laboratory, increased temperatures increased feeding rates and decreased developmental times. As the host consumes the virus along with the leaf tissue on which it resides, increased feeding rate is likely to increase the probability of an individual

  7. The Use of High Pressure Freezing and Freeze Substitution to Study Host-Pathogen Interactions in Fungal Diseases of Plants

    NASA Astrophysics Data System (ADS)

    Mims, C. W.; Celio, Gail J.; Richardson, Elizabeth A.

    2003-12-01

    This article reports on the use of high pressure freezing followed by freeze substitution (HPF/FS) to study ultrastructural details of host pathogen interactions in fungal diseases of plants. The specific host pathogen systems discussed here include a powdery mildew infection of poinsettia and rust infections of daylily and Indian strawberry. The three pathogens considered here all attack the leaves of their hosts and produce specialized hyphal branches known as haustoria that invade individual host cells without killing them. We found that HPF/FS provided excellent preservation of both haustoria and host cells for all three host pathogen systems. Preservation of fungal and host cell membranes was particularly good and greatly facilitated the detailed study of host pathogen interfaces. In some instances, HPF/FS provided information that was not available in samples prepared for study using conventional chemical fixation. On the other hand, we did encounter various problems associated with the use of HPF/FS. Examples included freeze damage of samples, inconsistency of fixation in different samples, separation of plant cell cytoplasm from cell walls, breakage of cell walls and membranes, and splitting of thin sections. However, we believe that the outstanding preservation of ultrastructural details afforded by HPF/FS significantly outweighs these problems and we highly recommend the use of this fixation protocol for future studies of fungal host-plant interactions.

  8. Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

    PubMed Central

    Carter, C. J.

    2013-01-01

    Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (P  from  8.01E − 05  (ADHD)  to  1.22E − 71) (multiple sclerosis), and autism (P = 0.013), but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD) to 33% (MS) of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively) to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity) and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as) to the disease itself. PMID:23533776

  9. Physiology of host-pathogen interaction in wilt diseases of cotton in relation to pathogen management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Verticillium and Fusarium wilts are important vascular wilt diseases of cotton that significantly reduce cotton yields and negatively impact fiber quality. In spite of intense efforts to control these diseases, yield losses persist and in the US alone were estimated to be about 133 and 28 thousand b...

  10. Examining host-pathogen interactions at mucosal surfaces reveals novel molecular targets for columnaris disease intervention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Columnaris disease, caused by the bacterial pathogen Flavobacterium columnare, is a major problem globally and leads to tremendous losses of freshwater fish, particularly in intensively farmed aquaculture species. Despite its widespread importance, our understanding of F. columnare infectious proce...

  11. Toll-like receptor cascade and gene polymorphism in host-pathogen interaction in Lyme disease.

    PubMed

    Rahman, Shusmita; Shering, Maria; Ogden, Nicholas H; Lindsay, Robbin; Badawi, Alaa

    2016-01-01

    Lyme disease (LD) risk occurs in North America and Europe where the tick vectors of the causal agent Borrelia burgdorferi sensu lato are found. It is associated with local and systemic manifestations, and has persistent posttreatment health complications in some individuals. The innate immune system likely plays a critical role in both host defense against B. burgdorferi and disease severity. Recognition of B. burgdorferi, activation of the innate immune system, production of proinflammatory cytokines, and modulation of the host adaptive responses are all initiated by Toll-like receptors (TLRs). A number of Borrelia outer-surface proteins (eg, OspA and OspB) are recognized by TLRs. Specifically, TLR1 and TLR2 were identified as the receptors most relevant to LD. Several functional single-nucleotide polymorphisms have been identified in TLR genes, and are associated with varying cytokines types and synthesis levels, altered pathogen recognition, and disruption of the downstream signaling cascade. These single-nucleotide polymorphism-related functional alterations are postulated to be linked to disease development and posttreatment persistent illness. Elucidating the role of TLRs in LD may facilitate a better understanding of disease pathogenesis and can provide an insight into novel therapeutic targets during active disease or postinfection and posttreatment stages. PMID:27330321

  12. Progress in computational studies of host-pathogen interactions.

    PubMed

    Zhou, Hufeng; Jin, Jingjing; Wong, Limsoon

    2013-04-01

    Host-pathogen interactions are important for understanding infection mechanism and developing better treatment and prevention of infectious diseases. Many computational studies on host-pathogen interactions have been published. Here, we review recent progress and results in this field and provide a systematic summary, comparison and discussion of computational studies on host-pathogen interactions, including prediction and analysis of host-pathogen protein-protein interactions; basic principles revealed from host-pathogen interactions; and database and software tools for host-pathogen interaction data collection, integration and analysis. PMID:23600809

  13. Variation in Inflammatory Response during Pneumococcal Infection Is Influenced by Host-Pathogen Interactions but Associated with Animal Survival

    PubMed Central

    Escudero, Laura; Sylvius, Nicolas; Norman, Martin; Henriques-Normark, Birgitta

    2016-01-01

    Inflammation is a crucial part of innate immune responses but, if imbalanced, can lead to serious clinical conditions or even death. Cytokines regulate inflammation, and studies report their impact on clinical outcome. However, host and pathogen genetic backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profiles (if any) relate to improved prognosis. Streptococcus pneumoniae is a common human pathogen associated with asymptomatic nasopharyngeal carriage. Infrequently, it can lead to a wide range of diseases with high morbidity and mortality rates. Studies show that both pneumococcal serotype and host genetic background affect the development of disease and contribute to variation in inflammatory responses. In this study, we investigated the impact of the host and pneumococcal genetic backgrounds on pulmonary cytokine responses and their relationship to animal survival. Two inbred mouse strains, BALB/c and CBA/Ca, were infected with 10 pneumococcal strains, and the concentrations of six pulmonary cytokines were measured at 6 h and 24 h postinfection. Collected data were analyzed by principal-component analysis to identify whether there is any pattern in the observed cytokine variation. Our results show that host-pneumococcus combination was at the core of observed variation in cytokine responses, yet the resulting cytokine profile discriminated only between survivors and fatalities but not mouse or pneumococcal strains used during infection. Therefore, our results indicate that although alternative inflammatory profiles are generated during pneumococcal infection, a common pattern emerged, which determined the clinical outcome of pneumococcal infections. PMID:26787718

  14. Variation in Inflammatory Response during Pneumococcal Infection Is Influenced by Host-Pathogen Interactions but Associated with Animal Survival.

    PubMed

    Jonczyk, Magda S; Escudero, Laura; Sylvius, Nicolas; Norman, Martin; Henriques-Normark, Birgitta; Andrew, Peter W

    2016-04-01

    Inflammation is a crucial part of innate immune responses but, if imbalanced, can lead to serious clinical conditions or even death. Cytokines regulate inflammation, and studies report their impact on clinical outcome. However, host and pathogen genetic backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profiles (if any) relate to improved prognosis.Streptococcus pneumonia is a common human pathogen associated with asymptomatic nasopharyngeal carriage. Infrequently, it can lead to a wide range of diseases with high morbidity and mortality rates. Studies show that both pneumococcal serotype and host genetic background affect the development of disease and contribute to variation in inflammatory responses. In this study, we investigated the impact of the host and pneumococcal genetic backgrounds on pulmonary cytokine responses and their relationship to animal survival. Two inbred mouse strains, BALB/c and CBA/Ca, were infected with 10 pneumococcal strains, and the concentrations of six pulmonary cytokines were measured at 6 h and 24 h postinfection. Collected data were analyzed by principal-component analysis to identify whether there is any pattern in the observed cytokine variation. Our results show that host-pneumococcus combination was at the core of observed variation in cytokine responses, yet the resulting cytokine profile discriminated only between survivors and fatalities but not mouse or pneumococcal strains used during infection. Therefore, our results indicate that although alternative inflammatory profiles are generated during pneumococcal infection, a common pattern emerged, which determined the clinical outcome of pneumococcal infections. PMID:26787718

  15. Sensitivity of Borrelia genospecies to serum complement from different animals and human: a host-pathogen relationship.

    PubMed

    Bhide, Mangesh R; Travnicek, Milan; Levkutova, Maria; Curlik, Jan; Revajova, Viera; Levkut, Mikulas

    2005-02-01

    Different Borrelia species and serotypes were tested for their sensitivity to serum complement from various animals and human. Complement-mediated Borrelia killing in cattle, European bison and deer was higher irrespective of the Borrelia species whereas in other animals and human it was intermediate and Borrelia species-dependent. Activation of the alternative complement pathway by particular Borrelia strain was in correlation with its sensitivity or resistance. These results support the incompetent reservoir nature of cattle, European bison, red, roe and fallow deer, at the same time present the probable reservoir nature of mouflon, dog, wolf, cat and lynx. In short, this study reviews Borrelia-host relationship and its relevance in reservoir competence nature of animals. PMID:15681146

  16. Multi-event capture-recapture modeling of host-pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns.

    PubMed

    Santoro, Simone; Pacios, Isa; Moreno, Sacramento; Bertó-Moran, Alejandro; Rouco, Carlos

    2014-01-01

    Host-pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture-recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host-pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

  17. Scaling up complexity in host-pathogens interaction models. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Z. Wang et al.

    NASA Astrophysics Data System (ADS)

    Aguiar, Maíra

    2015-12-01

    Caused by micro-organisms that are pathogenic to the host, infectious diseases have caused debilitation and premature death to large portions of the human population, leading to serious social-economic concerns. The persistence and increase in the occurrence of infectious diseases as well the emergence or resurgence of vector-borne diseases are closely related with demographic factors such as the uncontrolled urbanization and remarkable population growth, political, social and economical changes, deforestation, development of resistance to insecticides and drugs and increased human travel. In recent years, mathematical modeling became an important tool for the understanding of infectious disease epidemiology and dynamics, addressing ideas about the components of host-pathogen interactions. Acting as a possible tool to understand, predict the spread of infectious diseases these models are also used to evaluate the introduction of intervention strategies like vector control and vaccination. Many scientific papers have been published recently on these topics, and most of the models developed try to incorporate factors focusing on several different aspects of the disease (and eventually biological aspects of the vector), which can imply rich dynamic behavior even in the most basic dynamical models. As one example to be cited, there is a minimalistic dengue model that has shown rich dynamic structures, with bifurcations (Hopf, pitchfork, torus and tangent bifurcations) up to chaotic attractors in unexpected parameter regions [1,2], which was able to describe the large fluctuations observed in empirical outbreak data [3,4].

  18. Host-pathogen interactions in bacterial meningitis.

    PubMed

    Doran, Kelly S; Fulde, Marcus; Gratz, Nina; Kim, Brandon J; Nau, Roland; Prasadarao, Nemani; Schubert-Unkmeir, Alexandra; Tuomanen, Elaine I; Valentin-Weigand, Peter

    2016-02-01

    Bacterial meningitis is a devastating disease occurring worldwide with up to half of the survivors left with permanent neurological sequelae. Due to intrinsic properties of the meningeal pathogens and the host responses they induce, infection can cause relatively specific lesions and clinical syndromes that result from interference with the function of the affected nervous system tissue. Pathogenesis is based on complex host-pathogen interactions, some of which are specific for certain bacteria, whereas others are shared among different pathogens. In this review, we summarize the recent progress made in understanding the molecular and cellular events involved in these interactions. We focus on selected major pathogens, Streptococcus pneumonia, S. agalactiae (Group B Streptococcus), Neisseria meningitidis, and Escherichia coli K1, and also include a neglected zoonotic pathogen, Streptococcus suis. These neuroinvasive pathogens represent common themes of host-pathogen interactions, such as colonization and invasion of mucosal barriers, survival in the blood stream, entry into the central nervous system by translocation of the blood-brain and blood-cerebrospinal fluid barrier, and induction of meningeal inflammation, affecting pia mater, the arachnoid and subarachnoid spaces. PMID:26744349

  19. Exploring NAD+ metabolism in host-pathogen interactions.

    PubMed

    Mesquita, Inês; Varela, Patrícia; Belinha, Ana; Gaifem, Joana; Laforge, Mireille; Vergnes, Baptiste; Estaquier, Jérôme; Silvestre, Ricardo

    2016-03-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a vital molecule found in all living cells. NAD(+) intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD(+) metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD(+) metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD(+) homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD(+) or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD(+) metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases. PMID:26718485

  20. Host/pathogen interactions and immune effector mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An understanding of the host/pathogen interactions for mycobacterial infections underpins many of the outcomes required for improving disease control, including better diagnostic tests, vaccines and breeding for disease resistance. Upon infection these mycobacteria come in contact with cells of the ...

  1. Disentangling host, pathogen, and environmental determinants of a recently emerged wildlife disease: lessons from the first 15 years of amphibian chytridiomycosis research.

    PubMed

    James, Timothy Y; Toledo, L Felipe; Rödder, Dennis; da Silva Leite, Domingos; Belasen, Anat M; Betancourt-Román, Clarisse M; Jenkinson, Thomas S; Soto-Azat, Claudio; Lambertini, Carolina; Longo, Ana V; Ruggeri, Joice; Collins, James P; Burrowes, Patricia A; Lips, Karen R; Zamudio, Kelly R; Longcore, Joyce E

    2015-09-01

    The amphibian fungal disease chytridiomycosis, which affects species across all continents, recently emerged as one of the greatest threats to biodiversity. Yet, many aspects of the basic biology and epidemiology of the pathogen, Batrachochytrium dendrobatidis (Bd), are still unknown, such as when and from where did Bd emerge and what is its true ecological niche? Here, we review the ecology and evolution of Bd in the Americas and highlight controversies that make this disease so enigmatic. We explore factors associated with variance in severity of epizootics focusing on the disease triangle of host susceptibility, pathogen virulence, and environment. Reevaluating the causes of the panzootic is timely given the wealth of data on Bd prevalence across hosts and communities and the recent discoveries suggesting co-evolutionary potential of hosts and Bd. We generate a new species distribution model for Bd in the Americas based on over 30,000 records and suggest a novel future research agenda. Instead of focusing on pathogen "hot spots," we need to identify pathogen "cold spots" so that we can better understand what limits the pathogen's distribution. Finally, we introduce the concept of "the Ghost of Epizootics Past" to discuss expected patterns in postepizootic host communities. PMID:26445660

  2. Transcriptional Profiles of Host-Pathogen Responses to Necrotic Enteritis and Differential Regulation of Immune Genes in Two Inbreed Chicken Lines Showing Disparate Disease Susceptibility

    PubMed Central

    Kim, Duk Kyung; Lillehoj, Hyun S.; Jang, Seung I.; Lee, Sung Hyen; Hong, Yeong Ho; Cheng, Hans H.

    2014-01-01

    Necrotic enteritis (NE) is an important intestinal infectious disease of commercial poultry flocks caused by Clostridium perfringens. Using an experimental model of NE involving co-infection with C. perfringens and Eimeria maxima, transcriptome profiling and functional genomics approaches were applied to identify the genetic mechanisms that might regulate the host response to this disease. Microarray hybridization identified 1,049 transcripts whose levels were altered (601 increased, 448 decreased) in intestinal lymphocytes from C. perfringens/E. maxima co-infected Ross chickens compared with uninfected controls. Five biological functions, all related to host immunity and inflammation, and 11 pathways were identified from this dataset. To further elucidate the role of host genetics in NE susceptibility, two inbred chicken lines, ADOL line 6 and line 7 which share an identical B2 major histocompatibility complex haplotype but differ in their susceptibility to virus infection, were compared for clinical symptoms and the expression levels of a panel of immune-related genes during experimental NE. Line 6 chickens were more susceptible to development of experimental NE compared with line 7, as revealed by decreased body weight gain and increased E. maxima oocyst shedding. Of 21 immune-related genes examined, 15 were increased in C. perfringens/E. maxima co-infected line 6 vs. line 7 chickens. These results suggest that immune pathways are activated in response to experimental NE infection and that genetic determinants outside of the chicken B complex influence resistance to this disease. PMID:25504150

  3. Mining Host-Pathogen Protein Interactions to Characterize Burkholderia mallei Infectivity Mechanisms

    PubMed Central

    Memišević, Vesna; Zavaljevski, Nela; Rajagopala, Seesandra V.; Kwon, Keehwan; Pieper, Rembert; DeShazer, David; Reifman, Jaques; Wallqvist, Anders

    2015-01-01

    Burkholderia pathogenicity relies on protein virulence factors to control and promote bacterial internalization, survival, and replication within eukaryotic host cells. We recently used yeast two-hybrid (Y2H) screening to identify a small set of novel Burkholderia proteins that were shown to attenuate disease progression in an aerosol infection animal model using the virulent Burkholderia mallei ATCC 23344 strain. Here, we performed an extended analysis of primarily nine B. mallei virulence factors and their interactions with human proteins to map out how the bacteria can influence and alter host processes and pathways. Specifically, we employed topological analyses to assess the connectivity patterns of targeted host proteins, identify modules of pathogen-interacting host proteins linked to processes promoting infectivity, and evaluate the effect of crosstalk among the identified host protein modules. Overall, our analysis showed that the targeted host proteins generally had a large number of interacting partners and interacted with other host proteins that were also targeted by B. mallei proteins. We also introduced a novel Host-Pathogen Interaction Alignment (HPIA) algorithm and used it to explore similarities between host-pathogen interactions of B. mallei, Yersinia pestis, and Salmonella enterica. We inferred putative roles of B. mallei proteins based on the roles of their aligned Y. pestis and S. enterica partners and showed that up to 73% of the predicted roles matched existing annotations. A key insight into Burkholderia pathogenicity derived from these analyses of Y2H host-pathogen interactions is the identification of eukaryotic-specific targeted cellular mechanisms, including the ubiquitination degradation system and the use of the focal adhesion pathway as a fulcrum for transmitting mechanical forces and regulatory signals. This provides the mechanisms to modulate and adapt the host-cell environment for the successful establishment of host infections

  4. Simultaneous Host-Pathogen Transcriptome Analysis during Granulibacter bethesdensis Infection of Neutrophils from Healthy Subjects and Patients with Chronic Granulomatous Disease

    PubMed Central

    Greenberg, David E.; Sturdevant, Daniel E.; Marshall-Batty, Kimberly R.; Chu, Jessica; Pettinato, Anthony M.; Virtaneva, Kimmo; Lane, John; Geller, Bruce L.; Porcella, Stephen F.; Gallin, John I.; Holland, Steven M.

    2015-01-01

    Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species (ROS) due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by PMN of CGD patients (CGD PMN) and inhibits PMN apoptosis through unknown mechanisms. Microarray analysis was used to study mRNA expression in PMN from healthy subjects (normal PMN) and CGD PMN during incubation with G. bethesdensis and, simultaneously, in G. bethesdensis with normal and CGD PMN. We detected upregulation of antiapoptotic genes (e.g., XIAP and GADD45B) and downregulation of proapoptotic genes (e.g., CASP8 and APAF1) in infected PMN. Transcript and protein levels of inflammation- and immunity-related genes were also altered. Upon interaction with PMN, G. bethesdensis altered the expression of ROS resistance genes in the presence of normal but not CGD PMN. Levels of bacterial stress response genes, including the ClpB gene, increased during phagocytosis by both normal and CGD PMN demonstrating responses to oxygen-independent PMN antimicrobial systems. Antisense knockdown demonstrated that ClpB is dispensable for extracellular growth but is essential for bacterial resistance to both normal and CGD PMN. Metabolic adaptation of Granulibacter growth in PMN included the upregulation of pyruvate dehydrogenase. Pharmacological inhibition of pyruvate dehydrogenase by triphenylbismuthdichloride was lethal to Granulibacter. This study expands knowledge of microbial pathogenesis of Granulibacter in cells from permissive (CGD) and nonpermissive (normal) hosts and identifies potentially druggable microbial factors, such as pyruvate dehydrogenase and ClpB, to help combat this antibiotic-resistant pathogen. PMID:26283340

  5. Simultaneous Host-Pathogen Transcriptome Analysis during Granulibacter bethesdensis Infection of Neutrophils from Healthy Subjects and Patients with Chronic Granulomatous Disease.

    PubMed

    Greenberg, David E; Sturdevant, Daniel E; Marshall-Batty, Kimberly R; Chu, Jessica; Pettinato, Anthony M; Virtaneva, Kimmo; Lane, John; Geller, Bruce L; Porcella, Stephen F; Gallin, John I; Holland, Steven M; Zarember, Kol A

    2015-11-01

    Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species (ROS) due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by PMN of CGD patients (CGD PMN) and inhibits PMN apoptosis through unknown mechanisms. Microarray analysis was used to study mRNA expression in PMN from healthy subjects (normal PMN) and CGD PMN during incubation with G. bethesdensis and, simultaneously, in G. bethesdensis with normal and CGD PMN. We detected upregulation of antiapoptotic genes (e.g., XIAP and GADD45B) and downregulation of proapoptotic genes (e.g., CASP8 and APAF1) in infected PMN. Transcript and protein levels of inflammation- and immunity-related genes were also altered. Upon interaction with PMN, G. bethesdensis altered the expression of ROS resistance genes in the presence of normal but not CGD PMN. Levels of bacterial stress response genes, including the ClpB gene, increased during phagocytosis by both normal and CGD PMN demonstrating responses to oxygen-independent PMN antimicrobial systems. Antisense knockdown demonstrated that ClpB is dispensable for extracellular growth but is essential for bacterial resistance to both normal and CGD PMN. Metabolic adaptation of Granulibacter growth in PMN included the upregulation of pyruvate dehydrogenase. Pharmacological inhibition of pyruvate dehydrogenase by triphenylbismuthdichloride was lethal to Granulibacter. This study expands knowledge of microbial pathogenesis of Granulibacter in cells from permissive (CGD) and nonpermissive (normal) hosts and identifies potentially druggable microbial factors, such as pyruvate dehydrogenase and ClpB, to help combat this antibiotic-resistant pathogen. PMID:26283340

  6. Animal Diseases and Your Health

    MedlinePlus

    Animal diseases that people can catch are called zoonoses. Many diseases affecting humans can be traced to animals or animal products. You can get a disease directly from an animal, or indirectly, through the ...

  7. Small animal disease surveillance.

    PubMed

    Sánchez-Vizcaíno, Fernando; Jones, Philip H; Menacere, Tarek; Heayns, Bethaney; Wardeh, Maya; Newman, Jenny; Radford, Alan D; Dawson, Susan; Gaskell, Rosalind; Noble, Peter J M; Everitt, Sally; Day, Michael J; McConnell, Katie

    2015-12-12

    This is the first UK small animal disease surveillance report from SAVSNET. Future reports will expand to other syndromes and diseases. As data are collected for longer, the estimates of changes in disease burden will become more refined, allowing more targeted local and perhaps national interventions. Anonymised data can be accessed for research purposes by contacting the authors. SAVSNET welcomes feedback on this report. PMID:26667432

  8. Helicobacter pylori: Genomic Insight into the Host-Pathogen Interaction

    PubMed Central

    Haley, Kathryn P.; Gaddy, Jennifer A.

    2015-01-01

    The advent of genomic analyses has revolutionized the study of human health. Infectious disease research in particular has experienced an explosion of bacterial genomic, transcriptomic, and proteomic data complementing the phenotypic methods employed in traditional bacteriology. Together, these techniques have revealed novel virulence determinants in numerous pathogens and have provided information for potential chemotherapeutics. The bacterial pathogen, Helicobacter pylori, has been recognized as a class 1 carcinogen and contributes to chronic inflammation within the gastric niche. Genomic analyses have uncovered remarkable coevolution between the human host and H. pylori. Perturbation of this coevolution results in dysregulation of the host-pathogen interaction, leading to oncogenic effects. This review discusses the relationship of H. pylori with the human host and environment and the contribution of each of these factors to disease progression, with an emphasis on features that have been illuminated by genomic tools. PMID:25722969

  9. Myocardial diseases of animals.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1986-01-01

    In this review we have attempted a comprehensive compilation of the cardiac morphologic changes that occur in spontaneous and experimental myocardial diseases of animals. Our coverage addresses diseases of mammals and birds and includes these diseases found in both domesticated and wild animals. A similar review of the myocardial diseases in this broad range of animal species has not been attempted previously. We have summarized and illustrated the gross, microscopic, and ultrastructural alterations for these myocardial diseases; and, whenever possible, we have reviewed their biochemical pathogenesis. We have arranged the myocardial diseases for presentation and discussion according to an etiologic classification with seven categories. These include a group of idiopathic or primary cardiomyopathies recognized in man (hypertrophic, dilated, and restrictive types) and a large group of secondary cardiomyopathies with known causes, such as inherited tendency; nutritional deficiency; toxicity; physical injury and shock; endocrine disorders, and myocarditides of viral, bacterial, and protozoal causation. Considerable overlap exists between each of the etiologic groups in the spectrum of pathologic alterations seen in the myocardium. These include various degenerative changes, myocyte necrosis, and inflammatory lesions. However, some diseases show rather characteristic myocardial alterations such as vacuolar degeneration in anthracycline cardiotoxicity, myofibrillar lysis in furazolidone cardiotoxicity, calcification in calcinosis of mice, glycogen accumulation in the glycogenoses, lipofuscinosis in cattle, fatty degeneration in erucic acid cardiotoxicity, myofiber disarray in hypertrophic cardiomyopathy, and lymphocytic inflammation with inclusion bodies in canine parvoviral myocarditis. The myocardial diseases represent the largest group in the spectrum of spontaneous cardiac diseases of animals. Pericardial and endocardial diseases and congential cardiac diseases are

  10. Host-pathogen coevolution in human tuberculosis.

    PubMed

    Gagneux, Sebastien

    2012-03-19

    Tuberculosis (TB) is a disease of antiquity. Yet TB today still causes more adult deaths than any other single infectious disease. Recent studies show that contrary to the common view postulating an animal origin for TB, Mycobacterium tuberculosis complex (MTBC), the causative agent of TB, emerged as a human pathogen in Africa and colonized the world accompanying the Out-of-Africa migrations of modern humans. More recently, evolutionarily 'modern' lineages of MTBC expanded as a consequence of the global human population increase, and spread throughout the world following waves of exploration, trade and conquest. While epidemiological data suggest that the different phylogenetic lineages of MTBC might have adapted to different human populations, overall, the phylogenetically 'modern' MTBC lineages are more successful in terms of their geographical spread compared with the 'ancient' lineages. Interestingly, the global success of 'modern' MTBC correlates with a hypo-inflammatory phenotype in macrophages, possibly reflecting higher virulence, and a shorter latency in humans. Finally, various human genetic variants have been associated with different MTBC lineages, suggesting an interaction between human genetic diversity and MTBC variation. In summary, the biology and the epidemiology of human TB have been shaped by the long-standing association between MTBC and its human host. PMID:22312052

  11. Characterization of Pathogenicity, Virulence and Host-Pathogen Interractions

    SciTech Connect

    Krishnan, A; Folta, P

    2006-07-27

    The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improving our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the

  12. Host-Pathogen Interactions Made Transparent with the Zebrafish Model

    PubMed Central

    Meijer, Annemarie H; Spaink, Herman P

    2011-01-01

    The zebrafish holds much promise as a high-throughput drug screening model for immune-related diseases, including inflammatory and infectious diseases and cancer. This is due to the excellent possibilities for in vivo imaging in combination with advanced tools for genomic and large scale mutant analysis. The context of the embryo’s developing immune system makes it possible to study the contribution of different immune cell types to disease progression. Furthermore, due to the temporal separation of innate immunity from adaptive responses, zebrafish embryos and larvae are particularly useful for dissecting the innate host factors involved in pathology. Recent studies have underscored the remarkable similarity of the zebrafish and human immune systems, which is important for biomedical applications. This review is focused on the use of zebrafish as a model for infectious diseases, with emphasis on bacterial pathogens. Following a brief overview of the zebrafish immune system and the tools and methods used to study host-pathogen interactions in zebrafish, we discuss the current knowledge on receptors and downstream signaling components that are involved in the zebrafish embryo’s innate immune response. We summarize recent insights gained from the use of bacterial infection models, particularly the Mycobacterium marinum model, that illustrate the potential of the zebrafish model for high-throughput antimicrobial drug screening. PMID:21366518

  13. Competition for Manganese at the Host-Pathogen Interface.

    PubMed

    Kelliher, J L; Kehl-Fie, T E

    2016-01-01

    Transition metals such as manganese are essential nutrients for both pathogen and host. Vertebrates exploit this necessity to combat invading microbes by restricting access to these critical nutrients, a defense known as nutritional immunity. During infection, the host uses several mechanisms to impose manganese limitation. These include removal of manganese from the phagolysosome, sequestration of extracellular manganese, and utilization of other metals to prevent bacterial acquisition of manganese. In order to cause disease, pathogens employ a variety of mechanisms that enable them to adapt to and counter nutritional immunity. These adaptations include, but are likely not limited to, manganese-sensing regulators and high-affinity manganese transporters. Even though successful pathogens can overcome host-imposed manganese starvation, this defense inhibits manganese-dependent processes, reducing the ability of these microbes to cause disease. While the full impact of host-imposed manganese starvation on bacteria is unknown, critical bacterial virulence factors such as superoxide dismutases are inhibited. This chapter will review the factors involved in the competition for manganese at the host-pathogen interface and discuss the impact that limiting the availability of this metal has on invading bacteria. PMID:27571690

  14. The prion diseases of animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that affect several species of animals and include bovine spongiform encephalopathy (BSE), scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, and transmissible mink encephalopat...

  15. Association and Host Selectivity in Multi-Host Pathogens

    PubMed Central

    Malpica, José M.; Sacristán, Soledad; Fraile, Aurora; García-Arenal, Fernando

    2006-01-01

    The distribution of multi-host pathogens over their host range conditions their population dynamics and structure. Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution. Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host. To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations. Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively. Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens. Analyses also showed that viruses tended to associate positively in co-infected hosts. The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens. PMID:17183670

  16. Animal models for human diseases.

    PubMed

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  17. Animal Diseases and Your Health

    MedlinePlus

    ... cause Lyme disease. Some wild animals may carry rabies. Enjoy wildlife from a distance. Pets can also make you sick. Reptiles pose a particular risk. Turtles, snakes and iguanas can transmit Salmonella bacteria to their owners. You can get rabies from an infected dog or toxoplasmosis from handling ...

  18. Population extinction in an inhomogeneous host-pathogen model

    NASA Astrophysics Data System (ADS)

    Bagarti, Trilochan

    2016-01-01

    We study inhomogeneous host-pathogen dynamics to model the global amphibian population extinction in a lake basin system. The lake basin system is modeled as quenched disorder. In this model we show that once the pathogen arrives at the lake basin it spreads from one lake to another, eventually spreading to the entire lake basin system in a wave like pattern. The extinction time has been found to depend on the steady state host population and pathogen growth rate. Linear estimate of the extinction time is computed. The steady state host population shows a threshold behavior in the interaction strength for a given growth rate.

  19. Parathyroid diseases and animal models.

    PubMed

    Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

    2012-01-01

    CIRCULATING CALCIUM AND PHOSPHATE ARE TIGHTLY REGULATED BY THREE HORMONES: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies. PMID:22754549

  20. Determinants of the Sympatric Host-Pathogen Relationship in Tuberculosis

    PubMed Central

    David, Susana; Mateus, A. R. A.; Duarte, Elsa L.; Albuquerque, José; Portugal, Clara; Sancho, Luísa; Lavinha, João; Gonçalves, Guilherme

    2015-01-01

    Major contributions from pathogen genome analysis and host genetics have equated the possibility of Mycobacterium tuberculosis co-evolution with its human host leading to more stable sympatric host–pathogen relationships. However, the attribution to either sympatric or allopatric categories depends on the resolution or grain of genotypic characterization. We explored the influence on the sympatric host-pathogen relationship of clinical (HIV infection and multidrug-resistant tuberculosis [MDRTB]) and demographic (gender and age) factors in regards to the genotypic grain by using spacer oligonucleotide typing (spoligotyping) for classification of M. tuberculosis strains within the Euro-American lineage. We analyzed a total of 547 tuberculosis (TB) cases, from six year consecutive sampling in a setting with high TB-HIV coinfection (32.0%). Of these, 62.0% were caused by major circulating pathogen genotypes. The sympatric relationship was defined according to spoligotype in comparison to the international spoligotype database SpolDB4. While no significant association with Euro-American lineage was observed with any of the factors analyzed, increasing the resolution with spoligotyping evidenced a significant association of MDRTB with sympatric strains, regardless of the HIV status. Furthermore, distribution curves of the prevalence of sympatric and allopatric TB in relation to patients’ age showed an accentuation of the relevance of the age of onset in the allopatric relationship, as reflected in the trimodal distribution. On the contrary, sympatric TB was characterized by the tendency towards a typical (standard) distribution curve. Our results suggest that within the Euro-American lineage a greater degree of genotyping fine-tuning is necessary in modeling the biological processes behind the host-pathogen interplay. Furthermore, prevalence distribution of sympatric TB to age was suggestive of host genetic determinisms driven by more common variants. PMID:26529092

  1. The Impact of Fusarium Mycotoxins on Human and Animal Host Susceptibility to Infectious Diseases

    PubMed Central

    Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

    2014-01-01

    Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well. PMID:24476707

  2. The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases.

    PubMed

    Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

    2014-02-01

    Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well. PMID:24476707

  3. The evolution of sexual dimorphism and its potential impact on host-pathogen coevolution.

    PubMed

    Gipson, Stephen A Y; Hall, Matthew D

    2016-05-01

    Sex and infection are intimately linked. Many diseases are spread by sexual contact, males are thought to evolve exaggerated sexual signals to demonstrate their immune robustness, and pathogens have been shown to direct the evolution of recombination. In all of these examples, infection is influencing the evolution of male and female fitness, but less is known about how sex differences influence pathogen fitness. A defining characteristic of sexual dimorphism is not only divergent phenotypes, but also a complex genetic architecture involving changes in genetic correlations among shared fitness traits, and differences in the accumulation of mutations-all of which may affect selection on an invading pathogen. Here, we outline the implications that the genetics of sexual dimorphism can have for host-pathogen coevolution and argue that male-female differences influence more than just the environment that a pathogen experiences. PMID:27076194

  4. Entomopathogenic Fungi: New Insights into Host-Pathogen Interactions.

    PubMed

    Butt, T M; Coates, C J; Dubovskiy, I M; Ratcliffe, N A

    2016-01-01

    Although many insects successfully live in dangerous environments exposed to diverse communities of microbes, they are often exploited and killed by specialist pathogens. Studies of host-pathogen interactions (HPI) provide valuable insights into the dynamics of the highly aggressive coevolutionary arms race between entomopathogenic fungi (EPF) and their arthropod hosts. The host defenses are designed to exclude the pathogen or mitigate the damage inflicted while the pathogen responds with immune evasion and utilization of host resources. EPF neutralize their immediate surroundings on the insect integument and benefit from the physiochemical properties of the cuticle and its compounds that exclude competing microbes. EPF also exhibit adaptations aimed at minimizing trauma that can be deleterious to both host and pathogen (eg, melanization of hemolymph), form narrow penetration pegs that alleviate host dehydration and produce blastospores that lack immunogenic sugars/enzymes but facilitate rapid assimilation of hemolymph nutrients. In response, insects deploy an extensive armory of hemocytes and macromolecules, such as lectins and phenoloxidase, that repel, immobilize, and kill EPF. New evidence suggests that immune bioactives work synergistically (eg, lysozyme with antimicrobial peptides) to combat infections. Some proteins, including transferrin and apolipophorin III, also demonstrate multifunctional properties, participating in metabolism, homeostasis, and pathogen recognition. This review discusses the molecular intricacies of these HPI, highlighting the interplay between immunity, stress management, and metabolism. Increased knowledge in this area could enhance the efficacy of EPF, ensuring their future in integrated pest management programs. PMID:27131329

  5. Manganese acquisition and homeostasis at the host-pathogen interface

    PubMed Central

    Lisher, John P.; Giedroc, David P.

    2013-01-01

    Pathogenic bacteria acquire transition metals for cell viability and persistence of infection in competition with host nutritional defenses. The human host employs a variety of mechanisms to stress the invading pathogen with both cytotoxic metal ions and oxidative and nitrosative insults while withholding essential transition metals from the bacterium. For example, the S100 family protein calprotectin (CP) found in neutrophils is a calcium-activated chelator of extracellular Mn and Zn and is found in tissue abscesses at sites of infection by Staphylococcus aureus. In an adaptive response, bacteria have evolved systems to acquire the metals in the face of this competition while effluxing excess or toxic metals to maintain a bioavailability of transition metals that is consistent with a particular inorganic “fingerprint” under the prevailing conditions. This review highlights recent biological, chemical and structural studies focused on manganese (Mn) acquisition and homeostasis and connects this process to oxidative stress resistance and iron (Fe) availability that operates at the human host-pathogen interface. PMID:24367765

  6. HPIDB 2.0: a curated database for host-pathogen interactions.

    PubMed

    Ammari, Mais G; Gresham, Cathy R; McCarthy, Fiona M; Nanduri, Bindu

    2016-01-01

    Identification and analysis of host-pathogen interactions (HPI) is essential to study infectious diseases. However, HPI data are sparse in existing molecular interaction databases, especially for agricultural host-pathogen systems. Therefore, resources that annotate, predict and display the HPI that underpin infectious diseases are critical for developing novel intervention strategies. HPIDB 2.0 (http://www.agbase.msstate.edu/hpi/main.html) is a resource for HPI data, and contains 45, 238 manually curated entries in the current release. Since the first description of the database in 2010, multiple enhancements to HPIDB data and interface services were made that are described here. Notably, HPIDB 2.0 now provides targeted biocuration of molecular interaction data. As a member of the International Molecular Exchange consortium, annotations provided by HPIDB 2.0 curators meet community standards to provide detailed contextual experimental information and facilitate data sharing. Moreover, HPIDB 2.0 provides access to rapidly available community annotations that capture minimum molecular interaction information to address immediate researcher needs for HPI network analysis. In addition to curation, HPIDB 2.0 integrates HPI from existing external sources and contains tools to infer additional HPI where annotated data are scarce. Compared to other interaction databases, our data collection approach ensures HPIDB 2.0 users access the most comprehensive HPI data from a wide range of pathogens and their hosts (594 pathogen and 70 host species, as of February 2016). Improvements also include enhanced search capacity, addition of Gene Ontology functional information, and implementation of network visualization. The changes made to HPIDB 2.0 content and interface ensure that users, especially agricultural researchers, are able to easily access and analyse high quality, comprehensive HPI data. All HPIDB 2.0 data are updated regularly, are publically available for direct

  7. Diseases of Dairy Animals: Infectious Diseases: Johne's Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne's disease is a chronic, debilitating intestinal disorder in cattle, sheep and wild ruminants, characterized by diarrhea, weight loss and death. Animals usually become infected when they are young by ingesting feces or milk containing the causative bacteria. However, clinical signs of disease...

  8. An overview of animal prion diseases

    PubMed Central

    2011-01-01

    Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases. PMID:22044871

  9. An overview of animal prion diseases.

    PubMed

    Imran, Muhammad; Mahmood, Saqib

    2011-01-01

    Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases. PMID:22044871

  10. Leptospira spp.: Novel insights into host-pathogen interactions.

    PubMed

    Fernandes, Luis G; Siqueira, Gabriela H; Teixeira, Aline R F; Silva, Lucas P; Figueredo, Jupciana M; Cosate, Maria R; Vieira, Monica L; Nascimento, Ana L T O

    2016-08-01

    Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is an important infectious disease that affects humans and animals. The disease causes economic losses as it affects livestock, with decreased milk production and death. Our group is investigating the genome sequences of L. interrogans targeting surface-exposed proteins because, due to their location, these proteins are capable to interact with several host components that could allow establishment of the infection. These interactions may involve adhesion of the bacteria to extracellular matrix (ECM) components and, hence, help bacterial colonization. The bacteria could also react with the host fibrinolytic system and/or with the coagulation cascade components, such as, plasminogen (PLG) and fibrinogen (Fg), respectively. The binding with the first system generates plasmin (PLA), increasing the proteolytic power of the bacteria, while the second interferes with clotting in a thrombin-catalyzed reaction, which may promote hemorrhage foci and increase bacterial dissemination. Interaction with the complement system negative regulators may help bacteria to evade the host immune system, facilitating the invasion. This work compiles the main described leptospiral proteins that could act as adhesins, as PLG and fibrinogen receptors and as complement regulator binding proteins. We present models in which we suggest possible mechanisms of how leptospires might colonize and invade host tissues, causing the disease. Understanding leptospiral pathogenesis will help to identify antigen candidates that would contribute to the development of more effective vaccines and diagnostic tests. PMID:26727033

  11. Lawrence Livermore National Laboratory Workshop Characterization of Pathogenicity, Virulence and Host-Pathogen Interactions

    SciTech Connect

    Krishnan, A

    2006-08-30

    The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improving our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the

  12. Animal health: foot-and-mouth disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is one of the most contagious viral diseases that can affect cloven-hoofed livestock and wild animals. Outbreaks of FMD have caused devastating economic losses and the slaughter of millions of animals in many regions of the world affecting the food chain and global devel...

  13. Probing the protective mechanism of poly-ß-hydroxybutyrate against vibriosis by using gnotobiotic Artemia franciscana and Vibrio campbellii as host-pathogen model.

    PubMed

    Baruah, Kartik; Huy, Tran T; Norouzitallab, Parisa; Niu, Yufeng; Gupta, Sanjay K; De Schryver, Peter; Bossier, Peter

    2015-01-01

    The compound poly-ß-hydroxybutyrate (PHB), a polymer of the short chain fatty acid ß-hydroxybutyrate, was shown to protect experimental animals against a variety of bacterial diseases, (including vibriosis in farmed aquatic animals), albeit through undefined mechanisms. Here we aimed at unraveling the underlying mechanism behind the protective effect of PHB against bacterial disease using gnotobiotically-cultured brine shrimp Artemia franciscana and pathogenic Vibrio campbellii as host-pathogen model. The gnotobiotic model system is crucial for such studies because it eliminates any possible microbial interference (naturally present in any type of aquatic environment) in these mechanistic studies and furthermore facilitates the interpretation of the results in terms of a cause effect relationship. We showed clear evidences indicating that PHB conferred protection to Artemia host against V. campbellii by a mechanism of inducing heat shock protein (Hsp) 70. Additionally, our results also showed that this salutary effect of PHB was associated with the generation of protective innate immune responses, especially the prophenoloxidase and transglutaminase immune systems - phenomena possibly mediated by PHB-induced Hsp70. From overall results, we conclude that PHB induces Hsp70 and this induced Hsp70 might contribute in part to the protection of Artemia against pathogenic V. campbellii. PMID:25822312

  14. Probing the protective mechanism of poly-ß-hydroxybutyrate against vibriosis by using gnotobiotic Artemia franciscana and Vibrio campbellii as host-pathogen model

    PubMed Central

    Baruah, Kartik; Huy, Tran T.; Norouzitallab, Parisa; Niu, Yufeng; Gupta, Sanjay K.; De Schryver, Peter; Bossier, Peter

    2015-01-01

    The compound poly-ß-hydroxybutyrate (PHB), a polymer of the short chain fatty acid ß-hydroxybutyrate, was shown to protect experimental animals against a variety of bacterial diseases, (including vibriosis in farmed aquatic animals), albeit through undefined mechanisms. Here we aimed at unraveling the underlying mechanism behind the protective effect of PHB against bacterial disease using gnotobiotically-cultured brine shrimp Artemia franciscana and pathogenic Vibrio campbellii as host-pathogen model. The gnotobiotic model system is crucial for such studies because it eliminates any possible microbial interference (naturally present in any type of aquatic environment) in these mechanistic studies and furthermore facilitates the interpretation of the results in terms of a cause effect relationship. We showed clear evidences indicating that PHB conferred protection to Artemia host against V. campbellii by a mechanism of inducing heat shock protein (Hsp) 70. Additionally, our results also showed that this salutary effect of PHB was associated with the generation of protective innate immune responses, especially the prophenoloxidase and transglutaminase immune systems – phenomena possibly mediated by PHB-induced Hsp70. From overall results, we conclude that PHB induces Hsp70 and this induced Hsp70 might contribute in part to the protection of Artemia against pathogenic V. campbellii. PMID:25822312

  15. Visualization of coral host-pathogen interactions using a stable GFP-labeled Vibrio coralliilyticus strain

    NASA Astrophysics Data System (ADS)

    Pollock, F. Joseph; Krediet, Cory J.; Garren, Melissa; Stocker, Roman; Winn, Karina; Wilson, Bryan; Huete-Stauffer, Carla; Willis, Bette L.; Bourne, David G.

    2015-06-01

    The bacterium Vibrio coralliilyticus has been implicated as the causative agent of coral tissue loss diseases (collectively known as white syndromes) at sites across the Indo-Pacific and represents an emerging model pathogen for understanding the mechanisms linking bacterial infection and coral disease. In this study, we used a mini-Tn7 transposon delivery system to chromosomally label a strain of V. coralliilyticus isolated from a white syndrome disease lesion with a green fluorescent protein gene (GFP). We then tested the utility of this modified strain as a research tool for studies of coral host-pathogen interactions. A suite of biochemical assays and experimental infection trials in a range of model organisms confirmed that insertion of the GFP gene did not interfere with the labeled strain's virulence. Using epifluorescence video microscopy, the GFP-labeled strain could be reliably distinguished from non-labeled bacteria present in the coral holobiont, and the pathogen's interactions with the coral host could be visualized in real time. This study demonstrates that chromosomal GFP labeling is a useful technique for visualization and tracking of coral pathogens and provides a novel tool to investigate the role of V. coralliilyticus in coral disease pathogenesis.

  16. Engineering large animal models of human disease.

    PubMed

    Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P

    2016-01-01

    The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies. PMID:26414877

  17. Congenital and Genetic Disease in Domestic Animals

    ERIC Educational Resources Information Center

    Mulvihill, John J.

    1972-01-01

    Reviews observations on domestic animals that have led to the identification of environmental teratogens, and have provided insight into the pathogenesis of congenital defects and genetic diseases in man." (Author/AL)

  18. Animal models for motor neuron disease.

    PubMed

    Green, S L; Tolwani, R J

    1999-10-01

    Motor neuron disease is a general term applied to a broad class of neurodegenerative diseases that are characterized by fatally progressive muscular weakness, atrophy, and paralysis attributable to loss of motor neurons. At present, there is no cure for most motor neuron diseases, including amyotrophic lateral sclerosis (ALS), the most common human motor neuron disease--the cause of which remains largely unknown. Animal models of motor neuron disease (MND) have significantly contributed to the remarkable recent progress in understanding the cause, genetic factors, and pathologic mechanisms proposed for this class of human neurodegenerative disorders. Largely driven by ALS research, animal models of MND have proven their usefulness in elucidating potential causes and specific pathogenic mechanisms, and have helped to advance promising new treatments from "benchside to bedside." This review summarizes important features of selected established animal models of MND: genetically engineered mice and inherited or spontaneously occurring MND in the murine, canine, and equine species. PMID:10551448

  19. Cell scale host-pathogen modeling: another branch in the evolution of constraint-based methods

    PubMed Central

    Jamshidi, Neema; Raghunathan, Anu

    2015-01-01

    Constraint-based models have become popular methods for systems biology as they enable the integration of complex, disparate datasets in a biologically cohesive framework that also supports the description of biological processes in terms of basic physicochemical constraints and relationships. The scope, scale, and application of genome scale models have grown from single cell bacteria to multi-cellular interaction modeling; host-pathogen modeling represents one of these examples at the current horizon of constraint-based methods. There are now a small number of examples of host-pathogen constraint-based models in the literature, however there has not yet been a definitive description of the methodology required for the functional integration of genome scale models in order to generate simulation capable host-pathogen models. Herein we outline a systematic procedure to produce functional host-pathogen models, highlighting steps which require debugging and iterative revisions in order to successfully build a functional model. The construction of such models will enable the exploration of host-pathogen interactions by leveraging the growing wealth of omic data in order to better understand mechanism of infection and identify novel therapeutic strategies. PMID:26500611

  20. Small animal disease surveillance: respiratory disease.

    PubMed

    Sánchez-Vizcaíno, Fernando; Daly, Janet M; Jones, Philip H; Dawson, Susan; Gaskell, Rosalind; Menacere, Tarek; Heayns, Bethaney; Wardeh, Maya; Newman, Jenny; Everitt, Sally; Day, Michael J; McConnell, Katie; Noble, Peter J M; Radford, Alan D

    2016-04-01

    Presentation for respiratory disease comprised 1.7 per cent, 2.3 per cent and 2.5 per cent of canine, feline and rabbit consultations, respectively, between January 2014 and December 2015. Coughing was the most frequent respiratory sign reported in dogs (71.1 per cent of consultations); in cats it was sneezing (42.6 per cent). Mean percentage of samples testing positive for feline calicivirus (FCV) was 30.1 per cent in 2014 and 27.9 per cent in 2015. January was the month with the highest percentage of FCV-positive samples in both 2014 and 2015. PMID:27056810

  1. Infection and transmission heterogeneity of a multi-host pathogen (Batrachochytrium dendrobatidis) within an amphibian community.

    PubMed

    Fernández-Beaskoetxea, S; Bosch, J; Bielby, J

    2016-02-11

    The majority of parasites infect multiple hosts. As the outcome of the infection is different in each of them, most studies of wildlife disease focus on the few species that suffer the most severe consequences. However, the role that each host plays in the persistence and transmission of infection can be crucial to understanding the spread of a parasite and the risk it poses to the community. Current theory predicts that certain host species can modulate the infection in other species by amplifying or diluting both infection prevalence and infection intensity, both of which have implications for disease risk within those communities. The fungus Batrachochytrium dendrobatidis (Bd), the causal agent of the disease chytridiomycosis, has caused global amphibian population declines and extinctions. However, not all infected species are affected equally, and thus Bd is a good example of a multi-host pathogen that must ultimately be studied with a community approach. To test whether the common midwife toad Alytes obstetricans is a reservoir and possible amplifier of infection of other species, we used experimental approaches in captive and wild populations to determine the effect of common midwife toad larvae on infection of other amphibian species found in the Peñalara Massif, Spain. We observed that the most widely and heavily infected species, the common midwife toad, may be amplifying the infection loads in other species, all of which have different degrees of susceptibility to Bd infection. Our results have important implications for performing mitigation actions focused on potential 'amplifier' hosts and for better understanding the mechanisms of Bd transmission. PMID:26865231

  2. Animal models of chronic obstructive pulmonary disease.

    PubMed

    Pérez-Rial, Sandra; Girón-Martínez, Álvaro; Peces-Barba, Germán

    2015-03-01

    Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses. PMID:25201221

  3. Verticillium Wilt in Potato: Host-Pathogen Interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Verticillium wilt (VW) is a widespread disease that causes consistent yield losses in many potato growing regions worldwide. In the U.S., it is mainly caused by the soil-borne fungal pathogen Verticillium dahliae. Microsclerotia can survive in the soil for many years. When they germinate and infec...

  4. 9 CFR 95.3 - Byproducts from diseased animals prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Byproducts from diseased animals prohibited. 95.3 Section 95.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL...

  5. 9 CFR 95.3 - Byproducts from diseased animals prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Byproducts from diseased animals prohibited. 95.3 Section 95.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL...

  6. 9 CFR 95.3 - Byproducts from diseased animals prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Byproducts from diseased animals prohibited. 95.3 Section 95.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL...

  7. 9 CFR 95.3 - Byproducts from diseased animals prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Byproducts from diseased animals prohibited. 95.3 Section 95.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL...

  8. Protozoa lectins and their role in host-pathogen interactions.

    PubMed

    Singh, Ram Sarup; Walia, Amandeep Kaur; Kanwar, Jagat Rakesh

    2016-01-01

    Lectins are proteins/glycoproteins of non-immune origin that agglutinate red blood cells, lymphocytes, fibroblasts, etc., and bind reversibly to carbohydrates present on the apposing cells. They have at least two carbohydrate binding sites and their binding can be inhibited by one or more carbohydrates. Owing to carbohydrate binding specificity of lectins, they mediate cell-cell interactions and play role in protozoan adhesion and host cell cytotoxicity, thus are central to the pathogenic property of the parasite. Several parasitic protozoa possess lectins which mediate parasite adherence to host cells based on their carbohydrate specificities. These interactions could be exploited for development of novel therapeutics, targeting the adherence and thus helpful in eradicating wide spread of protozoan diseases. The current review highlights the present state knowledge with regard to protozoal lectins with an emphasis on their haemagglutination activity, carbohydrate specificity, characteristics and also their role in pathogenesis notably as adhesion molecules, thereby aiding the pathogen in disease establishment. PMID:27268207

  9. Genetics of Infectious Disease Resistance in Animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This presentation will summarize genomic resources available for studies of genetic control of infectious disease resistance in animals. It will then review data collected in our and collaborators’ labs of genetic control of swine resistance to viral infections, e.g., Porcine reproductive and respir...

  10. Animal models of chronic liver diseases.

    PubMed

    Liu, Yan; Meyer, Christoph; Xu, Chengfu; Weng, Honglei; Hellerbrand, Claus; ten Dijke, Peter; Dooley, Steven

    2013-03-01

    Chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, and intoxications (including alcohol abuse) to imbalanced diets. Although at early stages of disease the liver regenerates in the absence of the insult, advanced stages cannot be healed and may require organ transplantation. A better understanding of underlying mechanisms is mandatory for the design of new drugs to be used in clinic. Therefore, rodent models are being developed to mimic human liver disease. However, no model to date can completely recapitulate the "corresponding" human disorder. Limiting factors are the time frame required in humans to establish a certain liver disease and the fact that rodents possess a distinct immune system compared with humans and have different metabolic rates affecting liver homeostasis. These features account for the difficulties in developing adequate rodent models for studying disease progression and for testing new pharmaceuticals to be translated into the clinic. Nevertheless, traditional and new promising animal models that mimic certain attributes of chronic liver diseases are established and being used to deepen our understanding in the underlying mechanisms of distinct liver diseases. This review aims at providing a comprehensive overview of recent advances in animal models recapitulating different features and etiologies of human liver diseases. PMID:23275613

  11. An Enriched European Eel Transcriptome Sheds Light upon Host-Pathogen Interactions with Vibrio vulnificus

    PubMed Central

    Callol, Agnès; Reyes-López, Felipe E.; Roig, Francisco J.; Goetz, Giles; Goetz, Frederick W.; Amaro, Carmen; MacKenzie, Simon A.

    2015-01-01

    Infectious diseases are one of the principal bottlenecks for the European eel recovery. The aim of this study was to develop a new molecular tool to be used in host-pathogen interaction experiments in the eel. To this end, we first stimulated adult eels with different pathogen-associated molecular patterns (PAMPs), extracted RNA from the immune-related tissues and sequenced the transcriptome. We obtained more than 2x106 reads that were assembled and annotated into 45,067 new descriptions with a notable representation of novel transcripts related with pathogen recognition, signal transduction and the immune response. Then, we designed a DNA-microarray that was used to analyze the early immune response against Vibrio vulnificus, a septicemic pathogen that uses the gills as the portal of entry into the blood, as well as the role of the main toxin of this species (RtxA13) on this early interaction. The gill transcriptomic profiles obtained after bath infecting eels with the wild type strain or with a mutant deficient in rtxA13 were analyzed and compared. Results demonstrate that eels react rapidly and locally against the pathogen and that this immune-response is rtxA13-dependent as transcripts related with cell destruction were highly up-regulated only in the gills from eels infected with the wild-type strain. Furthermore, significant differences in the immune response against the wild type and the mutant strain also suggest that host survival after V. vulnificus infection could depend on an efficient local phagocytic activity. Finally, we also found evidence of the presence of an interbranchial lymphoid tissue in European eel gills although further experiments will be necessary to identify such tissue. PMID:26207370

  12. Host-pathogen interactions in urinary tract infection.

    PubMed

    Nielubowicz, Greta R; Mobley, Harry L T

    2010-08-01

    The urinary tract is a common site of bacterial infections; nearly half of all women experience at least one urinary tract infection (UTI) during their lifetime. These infections are classified based on the condition of the host. Uncomplicated infections affect otherwise healthy individuals and are most commonly caused by uropathogenic Escherichia coli, whereas complicated infections affect patients with underlying difficulties, such as a urinary tract abnormality or catheterization, and are commonly caused by species such as Proteus mirabilis. Virulence and fitness factors produced by both pathogens include fimbriae, toxins, flagella, iron acquisition systems, and proteins that function in immune evasion. Additional factors that contribute to infection include the formation of intracellular bacterial communities by E. coli and the production of urease by P. mirabilis, which can result in urinary stone formation. Innate immune responses are induced or mediated by pattern recognition receptors, antimicrobial peptides, and neutrophils. The adaptive immune response to UTI is less well understood. Host factors TLR4 and CXCR1 are implicated in disease outcome and susceptibility, respectively. Low levels of TLR4 are associated with asymptomatic bacteriuria while low levels of CXCR1 are associated with increased incidence of acute pyelonephritis. Current research is focused on the identification of additional virulence factors and therapeutic or prophylactic targets that might be used in the generation of vaccines against both uropathogens. PMID:20647992

  13. Jenner-predict server: prediction of protein vaccine candidates (PVCs) in bacteria based on host-pathogen interactions

    PubMed Central

    2013-01-01

    Background Subunit vaccines based on recombinant proteins have been effective in preventing infectious diseases and are expected to meet the demands of future vaccine development. Computational approach, especially reverse vaccinology (RV) method has enormous potential for identification of protein vaccine candidates (PVCs) from a proteome. The existing protective antigen prediction software and web servers have low prediction accuracy leading to limited applications for vaccine development. Besides machine learning techniques, those software and web servers have considered only protein’s adhesin-likeliness as criterion for identification of PVCs. Several non-adhesin functional classes of proteins involved in host-pathogen interactions and pathogenesis are known to provide protection against bacterial infections. Therefore, knowledge of bacterial pathogenesis has potential to identify PVCs. Results A web server, Jenner-Predict, has been developed for prediction of PVCs from proteomes of bacterial pathogens. The web server targets host-pathogen interactions and pathogenesis by considering known functional domains from protein classes such as adhesin, virulence, invasin, porin, flagellin, colonization, toxin, choline-binding, penicillin-binding, transferring-binding, fibronectin-binding and solute-binding. It predicts non-cytosolic proteins containing above domains as PVCs. It also provides vaccine potential of PVCs in terms of their possible immunogenicity by comparing with experimentally known IEDB epitopes, absence of autoimmunity and conservation in different strains. Predicted PVCs are prioritized so that only few prospective PVCs could be validated experimentally. The performance of web server was evaluated against known protective antigens from diverse classes of bacteria reported in Protegen database and datasets used for VaxiJen server development. The web server efficiently predicted known vaccine candidates reported from Streptococcus pneumoniae and

  14. Foreign animal disease outbreaks, the animal welfare implications for Canada: Risks apparent from international experience

    PubMed Central

    Whiting, Terry L.

    2003-01-01

    Any outbreak of an Office International des Épizooties List A disease, such as classical swine fever or foot and mouth disease, has severe consequences for animal welfare, livestock production, exports of animals and animal products, and the environment. The public concern with the animal welfare effects of methods of disease eradication that result in the destruction of large numbers of uninfected animals has initiated a reconsideration of disease eradication policy in Europe. In many recent List A disease epizootics, the financial cost of addressing animal welfare concerns in healthy animals has greatly exceeded the cost of stamping out disease in infected herds. In the event of a similar incursion in Canada, the number of animals subject to welfare slaughter will be far greater than the number of infected animals killed. Current national disease eradication plans in Canada do not address the animal welfare component of disease control methods. PMID:14601676

  15. Phaeohyphomycoses, Emerging Opportunistic Diseases in Animals

    PubMed Central

    Seyedmousavi, S.; Guillot, J.

    2013-01-01

    Emerging fungal diseases due to black yeasts and relatives in domestic or wild animals and in invertebrates or cold- and warm-blooded vertebrates are continually being reported, either as novel pathogens or as familiar pathogens affecting new species of hosts. Different epidemiological situations can be distinguished, i.e., occurrence as single infections or as zoonoses, and infection may occur sporadically in otherwise healthy hosts. Such infections are found mostly in mammals but also in cold-blooded animals, are frequently subcutaneous or cerebral, and bear much similarity to human primary disorders. Infections of the nervous system are mostly fatal, and the source and route of infection are currently unknown. A third epidemiological situation corresponds to pseudoepidemics, i.e., infection of a large host population due to a common source. It is often observed and generally hypothesized that the susceptible animals are under stress, e.g., due to poor housing conditions of mammals or to a change of basins in the case of fishes. The descriptions in this article represent an overview of the more commonly reported and recurring black fungi and the corresponding diseases in different types of animals. PMID:23297257

  16. Phaeohyphomycoses, emerging opportunistic diseases in animals.

    PubMed

    Seyedmousavi, S; Guillot, J; de Hoog, G S

    2013-01-01

    Emerging fungal diseases due to black yeasts and relatives in domestic or wild animals and in invertebrates or cold- and warm-blooded vertebrates are continually being reported, either as novel pathogens or as familiar pathogens affecting new species of hosts. Different epidemiological situations can be distinguished, i.e., occurrence as single infections or as zoonoses, and infection may occur sporadically in otherwise healthy hosts. Such infections are found mostly in mammals but also in cold-blooded animals, are frequently subcutaneous or cerebral, and bear much similarity to human primary disorders. Infections of the nervous system are mostly fatal, and the source and route of infection are currently unknown. A third epidemiological situation corresponds to pseudoepidemics, i.e., infection of a large host population due to a common source. It is often observed and generally hypothesized that the susceptible animals are under stress, e.g., due to poor housing conditions of mammals or to a change of basins in the case of fishes. The descriptions in this article represent an overview of the more commonly reported and recurring black fungi and the corresponding diseases in different types of animals. PMID:23297257

  17. Environmental protection during animal disease eradication programmes.

    PubMed

    McDaniel, H A

    1991-09-01

    This paper identifies animal disease eradication (ADE) programme activities which may have a negative impact on the environment. It suggests ways to lessen the impact of such activities without compromising the programme objectives. Reducing losses from livestock and poultry diseases with prevention, control and eradication programmes produces a net positive impact on the environment. An Environmental Impact Statement (EIS) should be integrated into the planning of any ADE programme. Decision-makers should give due consideration to the environmental effects of ADE programme activities, together with cost, personnel needs and other, more traditional, management concerns. A better environment will be a supplemental benefit from ADE programmes. PMID:1782433

  18. Atypical prion diseases in humans and animals.

    PubMed

    Tranulis, Michael A; Benestad, Sylvie L; Baron, Thierry; Kretzschmar, Hans

    2011-01-01

    Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrP(Sc)), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans. PMID:21598097

  19. Techniques for transferring host-pathogen protein interactions knowledge to new tasks.

    PubMed

    Kshirsagar, Meghana; Schleker, Sylvia; Carbonell, Jaime; Klein-Seetharaman, Judith

    2015-01-01

    We consider the problem of building a model to predict protein-protein interactions (PPIs) between the bacterial species Salmonella Typhimurium and the plant host Arabidopsis thaliana which is a host-pathogen pair for which no known PPIs are available. To achieve this, we present approaches, which use homology and statistical learning methods called "transfer learning." In the transfer learning setting, the task of predicting PPIs between Arabidopsis and its pathogen S. Typhimurium is called the "target task." The presented approaches utilize labeled data i.e., known PPIs of other host-pathogen pairs (we call these PPIs the "source tasks"). The homology based approaches use heuristics based on biological intuition to predict PPIs. The transfer learning methods use the similarity of the PPIs from the source tasks to the target task to build a model. For a quantitative evaluation we consider Salmonella-mouse PPI prediction and some other host-pathogen tasks where known PPIs exist. We use metrics such as precision and recall and our results show that our methods perform well on the target task in various transfer settings. We present a brief qualitative analysis of the Arabidopsis-Salmonella predicted interactions. We filter the predictions from all approaches using Gene Ontology term enrichment and only those interactions involving Salmonella effectors. Thereby we observe that Arabidopsis proteins involved e.g., in transcriptional regulation, hormone mediated signaling and defense response may be affected by Salmonella. PMID:25699028

  20. Successful aquatic animal disease emergency programmes.

    PubMed

    Håstein, T; Hill, B J; Winton, J R

    1999-04-01

    The authors provide examples of emergency programmes which have been successful in eradicating or controlling certain diseases of aquatic animals. The paper is divided into four parts. The first part describes the initial isolation of viral haemorrhagic septicaemia (VHS) virus in North America in the autumn of 1988 from feral adult chinook (Oncorhynchus tshawytscha) and coho salmon (O. kisutch) returning for spawning. The fish disease control policies at both State and Federal levels in the United States of America required quarantine and emergency eradication measures upon the finding of certain exotic fish pathogens, including VHS virus. The procedures for emergency plans, destruction of stocks and disinfection of facilities are described, as well as challenge experiments with the North American strains of VHS virus and the detection of the virus in marine fish species (cod [Gadus macrocephalus] and herring [Clupea harengus pallasi]) in the Pacific Ocean. The second part of the paper outlines the aquatic animal legislation in Great Britain and within the European Union, in regard to contingency plans, initial investigations, action on the suspicion of notifiable disease and action on confirmation of infection. The legal description is followed by an account of an outbreak of viral haemorrhagic septicaemia in turbot (Scophthalmus maximus) in Great Britain, including the stamping-out process at the affected farm and investigations conducted to screen other farms in the vicinity for possible infection. The third part provides a historical review of the build-up of infectious salmon anaemia (ISA) in Norway and the attempts to control the disease using legal measures in the absence of detailed knowledge of the aetiology, epizootiology, pathogenesis, etc. of the disease. The measures taken show that the spread of ISA can be controlled using restrictions on the movement of fish, disinfection procedures, etc. However, acceptance and understanding of the chosen strategy

  1. Successful aquatic animal disease emergency programmes

    USGS Publications Warehouse

    Hastein, T.; Hill, B.J.; Winton, J.R.

    1999-01-01

    The authors provide examples of emergency programmes which have been successful in eradicating or controlling certain diseases of aquatic animals. The paper is divided into four parts. The first part describes the initial isolation of viral haemorrhagic septicaemia (VHS) virus in North America in the autumn of 1988 from feral adult chinook (Oncorhynchus tshawytscha) and coho salmon (O.kisutch) returning for spawning. The fish disease control policies at both State and Federal levels in the United States of America required quarantine and emergency eradication measures upon the finding of certain exotic fish pathogens, including VHS virus. The procedures for emergency plans, destruction of stocks and disinfection of facilities are described, as well as challenge experiments with the North American strains of VHS virus and the detection of the virus in marine fish species (cod [Gadus macrocephalus] and herring [Clupea harengus pallasi]) in the Pacific Ocean. The second part of the paper outlines the aquatic animal legislation in Great Britain and within the European Union, in regard to contingency plans, initial investigations, action on the suspicion of notifiable disease and action on confirmation of infection. The legal description is followed by an account of an outbreak of viral haemorrhagic septicaemia in turbot (Scophthalmus maximus) in Great Britain, including the stamping-out process at the affected farm and investigations conducted to screen other farms in the vicinity for possible infection. The third part provides a historical review of the build-up of infectious salmon anaemia (ISA) in Norway and the attempts to control the disease using legal measures in the absence of detailed knowledge of the aetiology, epizootiology, pathogenesis, etc. of the disease. The measures taken show that the spread of ISA can be controlled using restrictions on the movement of fish, disinfection procedures, etc. However, acceptance and understanding of the chosen strategy by

  2. Animal models for genetic neuromuscular diseases.

    PubMed

    Vainzof, Mariz; Ayub-Guerrieri, Danielle; Onofre, Paula C G; Martins, Poliana C M; Lopes, Vanessa F; Zilberztajn, Dinorah; Maia, Lucas S; Sell, Karen; Yamamoto, Lydia U

    2008-03-01

    The neuromuscular disorders are a heterogeneous group of genetic diseases, caused by mutations in genes coding sarcolemmal, sarcomeric, and citosolic muscle proteins. Deficiencies or loss of function of these proteins leads to variable degree of progressive loss of motor ability. Several animal models, manifesting phenotypes observed in neuromuscular diseases, have been identified in nature or generated in laboratory. These models generally present physiological alterations observed in human patients and can be used as important tools for genetic, clinic, and histopathological studies. The mdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD). Although it is a good genetic and biochemical model, presenting total deficiency of the protein dystrophin in the muscle, this mouse is not useful for clinical trials because of its very mild phenotype. The canine golden retriever MD model represents a more clinically similar model of DMD due to its larger size and significant muscle weakness. Autosomal recessive limb-girdle MD forms models include the SJL/J mice, which develop a spontaneous myopathy resulting from a mutation in the Dysferlin gene, being a model for LGMD2B. For the human sarcoglycanopahties (SG), the BIO14.6 hamster is the spontaneous animal model for delta-SG deficiency, whereas some canine models with deficiency of SG proteins have also been identified. More recently, using the homologous recombination technique in embryonic stem cell, several mouse models have been developed with null mutations in each one of the four SG genes. All sarcoglycan-null animals display a progressive muscular dystrophy of variable severity and share the property of a significant secondary reduction in the expression of the other members of the sarcoglycan subcomplex and other components of the Dystrophin-glycoprotein complex. Mouse models for congenital MD include the dy/dy (dystrophia-muscularis) mouse and the allelic mutant dy(2J)/dy(2J) mouse

  3. Large animal models of cardiovascular disease.

    PubMed

    Tsang, H G; Rashdan, N A; Whitelaw, C B A; Corcoran, B M; Summers, K M; MacRae, V E

    2016-04-01

    The human cardiovascular system is a complex arrangement of specialized structures with distinct functions. The molecular landscape, including the genome, transcriptome and proteome, is pivotal to the biological complexity of both normal and abnormal mammalian processes. Despite our advancing knowledge and understanding of cardiovascular disease (CVD) through the principal use of rodent models, this continues to be an increasing issue in today's world. For instance, as the ageing population increases, so does the incidence of heart valve dysfunction. This may be because of changes in molecular composition and structure of the extracellular matrix, or from the pathological process of vascular calcification in which bone-formation related factors cause ectopic mineralization. However, significant differences between mice and men exist in terms of cardiovascular anatomy, physiology and pathology. In contrast, large animal models can show considerably greater similarity to humans. Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research. These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo. In turn, this will help bridge the gap between basic science and clinical applications by facilitating the refinement of therapies for cardiovascular disease. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26914991

  4. Imaging of Small-Animal Models of Infectious Diseases

    PubMed Central

    Jelicks, Linda A.; Lisanti, Michael P.; Machado, Fabiana S.; Weiss, Louis M.; Tanowitz, Herbert B.; Desruisseaux, Mahalia S.

    2014-01-01

    Infectious diseases are the second leading cause of death worldwide. Noninvasive small-animal imaging has become an important research tool for preclinical studies of infectious diseases. Imaging studies permit enhanced information through longitudinal studies of the same animal during the infection. Herein, we briefly review recent studies of animal models of infectious disease that have used imaging modalities. PMID:23201133

  5. Animal Models of Parkinson's Disease: Vertebrate Genetics

    PubMed Central

    Lee, Yunjong; Dawson, Valina L.; Dawson, Ted M.

    2012-01-01

    Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially mice, have aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of showing a broad range of phenotypes and, coupled with their conserved genetic and anatomical structures, provide unparalleled molecular and pathological tools to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. Here, we provide an overview of the generation and characterization of transgenic and knockout mice used to study PD followed by a review of the molecular insights that have been gleaned from current PD mouse models. Finally, potential approaches to refine and improve current models are discussed. PMID:22960626

  6. A Malaysian Experience with Animal Disease

    PubMed Central

    Little, P. B.

    1979-01-01

    The report summarizes a one year period of investigation of death losses in West Malaysian livestock. Lesions and etiological agents are mentioned for cattle, sheep, goats, swine, poultry and companion animals as well as some miscellaneous species. Special observations related to a common paramphistome induced hepatic biliary infestation in cattle, a serious malignant head catarrh outbreak in which possible cattle to cow aerosol transmission occurred. Trismus observed in some cattle with malignant head catarrh was associated with arteriolitis and ganglioneuritis of the V cranial nerve. Parasitic, bacterial, viral toxic and neoplastic diseases are recorded in the various species. The occurrence of fatal chronic fluorosis in laboratory guinea pigs and cerebral nematodiasis in a Thoroughbred racehorse are documented. ImagesFigure 1.FIGURE 2.FIGURE 3.FIGURE 4.FIGURE 5.FIGURE 6.FIGURE 7.FIGURE 8.FIGURE 9.FIGURE 10.FIGURE 11. PMID:761153

  7. Animal Models of Cardiac Disease and Stem Cell Therapy

    PubMed Central

    Ou, Lailiang; Li, Wenzhong; Liu, Yi; Zhang, Yue; Jie, Shen; Kong, Deling; Steinhoff, Gustav; Ma, Nan

    2010-01-01

    Animal models that mimic cardiovascular diseases are indispensable tools for understanding the mechanisms underlying the diseases at the cellular and molecular level. This review focuses on various methods in preclinical research to create small animal models of cardiac diseases, such as myocardial infarction, dilated cardiomyopathy, heart failure, myocarditis and cardiac hypertrophy, and the related stem cell treatment for these diseases. PMID:21258568

  8. Functional genomics approaches to study host pathogen interactions to mucosal pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coccidiosis is the major parasitic disease of poultry affecting the intestinal mucosa and is caused by the apicomplexan protozoa Eimeria. Coccidiosis seriously impairs the growth and feed utilization of infected animals resulting in loss of productivity. Conventional disease control strategies rel...

  9. Stability Switches in a Host-Pathogen Model as the Length of a Time Delay Increases

    NASA Astrophysics Data System (ADS)

    Reynolds, Jennifer J. H.; Sherratt, Jonathan A.; White, Andrew

    2013-12-01

    The destabilising effects of a time delay in mathematical models are well known. However, delays are not necessarily destabilising. In this paper, we explore an example of a biological system where a time delay can be both stabilising and destabilising. This example is a host-pathogen model, incorporating density-dependent prophylaxis (DDP). DDP describes when individual hosts invest more in immunity when population densities are high, due to the increased risk of infection in crowded conditions. In this system, as the delay length increases, there are a finite number of switches between stable and unstable behaviour. These stability switches are demonstrated and characterised using a combination of numerical methods and analysis.

  10. Animal models of cavitation in pulmonary tuberculosis.

    PubMed

    Helke, Kris L; Mankowski, Joseph L; Manabe, Yukari C

    2006-09-01

    Transmission of tuberculosis occurs with the highest frequency from patients with extensive, cavitary, pulmonary disease and positive sputum smear microscopy. In animal models of tuberculosis, the development of caseous necrosis is an important prerequisite for the formation of cavities although the immunological triggers for liquefaction are unknown. We review the relative merits and the information gleaned from the available animal models of pulmonary cavitation. Understanding the host-pathogen interaction important to the formation of cavities may lead to new strategies to prevent cavitation and thereby, block transmission. PMID:16359922

  11. Variation in infectivity and aggressiveness in space and time in wild host-pathogen systems – causes and consequences

    PubMed Central

    Tack, Ayco JM; Thrall, Peter H; Barrett, Luke G; Burdon, Jeremy J; Laine, Anna-Liisa

    2012-01-01

    Variation in host resistance and in the ability of pathogens to infect and grow (i.e. pathogenicity) is important as it provides the raw material for antagonistic (co)evolution, and therefore underlies risks of disease spread, disease evolution, and host shifts. Moreover, the distribution of this variation in space and time may inform us about the mode of coevolutionary selection (arms race vs. fluctuating selection dynamics) and the relative roles of GxG interactions, gene flow, selection and genetic drift in shaping coevolutionary processes. While variation in host resistance has recently been reviewed, little is known about overall patterns in the frequency and scale of variation in pathogenicity, particularly in natural systems. Using 48 studies from 30 distinct host-pathogen systems, this review demonstrates that variation in pathogenicity is ubiquitous across multiple spatial and temporal scales. Quantitative analysis of a subset of extensively studied plant-pathogen systemsshows that the magnitude of within-population variation in pathogenicity is large relative to among-population variation, and that the distribution of pathogenicity partly mirrors the distribution of host resistance. At least part of the variation in pathogenicity found at a given spatial scale is adaptive, as evidenced by studies that have examined local adaptation at scales ranging from single hosts through metapopulations to entire continents, and – to a lesser extent - by comparisons of pathogenicity with neutral genetic variation. Together these results support coevolutionary selection through fluctuating selection dynamics. We end by outlining several promising directions for future research. PMID:22905782

  12. Orchestration of host-pathogen interaction: relevance of iron in generation of potent anti-M. tuberculosis immunity.

    PubMed

    Rai, Ambak K; Sharma, Shivesh; Punj, Vasu

    2014-01-01

    Pathogenesis of tuberculosis is marked with infection of macrophages followed by expansion of M. tuberculosis. Every step of this host-pathogen interaction is determined by the battle between the pathogen and host immune factors. It starts with phagocytosis of bacilli by mononuclear cells including alveolar macrophages and Dendritic Cells (DCs), both of which are Antigen Presenting Cells (APCs). Phagocytosed M. tuberculosis is subject to degradation by various means inside the phagolysosome. This very specific anti-M. tuberculosis mechanism within the phagocytes is well orchestrated. Upon activation, macrophages exhibit elevated levels of various intermediates via the oxidative burst, which effectively kills the pathogen and inhibits its dissemination. Generation of these intermediates and then their neutralization is intricately linked with the balance of divalent and trivalent iron metals in and outside of the cell. This review will bring the insight of host-M. tuberculosis interaction and its effectiveness in containment of the disease. Furthermore, the physiological balance of iron, its pathogen driven perturbance as well as its effect on the disease will also be discussed. PMID:25429656

  13. Gene-for-gene relationship in the host-pathogen system Malus × robusta 5-Erwinia amylovora.

    PubMed

    Vogt, Isabelle; Wöhner, Thomas; Richter, Klaus; Flachowsky, Henryk; Sundin, George W; Wensing, Annette; Savory, Elizabeth A; Geider, Klaus; Day, Brad; Hanke, Magda-Viola; Peil, Andreas

    2013-03-01

    Fire blight is a destructive bacterial disease caused by Erwinia amylovora affecting plants in the family Rosaceae, including apple. Host resistance to fire blight is present mainly in accessions of Malus spp. and is thought to be quantitative in this pathosystem. In this study we analyzed the importance of the E. amylovora effector avrRpt2(EA) , a homolog of Pseudomonas syringae avrRpt2, for resistance of Malus × robusta 5 (Mr5). The deletion mutant E. amylovora Ea1189ΔavrRpt2(EA) was able to overcome the fire blight resistance of Mr5. One single nucleotide polymorphism (SNP), resulting in an exchange of cysteine to serine in the encoded protein, was detected in avrRpt2(EA) of several Erwinia strains differing in virulence to Mr5. E. amylovora strains encoding serine (S-allele) were able to overcome resistance of Mr5, whereas strains encoding cysteine (C-allele) were not. Allele specificity was also observed in a coexpression assay with Arabidopsis thaliana RIN4 in Nicotiana benthamiana. A homolog of RIN4 has been detected and isolated in Mr5. These results suggest a system similar to the interaction of RPS2 from A. thaliana and AvrRpt2 from P. syringae with RIN4 as guard. Our data are suggestive of a gene-for-gene relationship for the host-pathogen system Mr5 and E. amylovora. PMID:23301854

  14. Bacterial-induced cell reprogramming to stem cell-like cells: new premise in host-pathogen interactions

    PubMed Central

    Hess, Samuel; Rambukkana, Anura

    2015-01-01

    Bacterial pathogens employ a myriad of strategies to alter host tissue cell functions for bacterial advantage during infection. Recent advances revealed a fusion of infection biology with stem cell biology by demonstrating developmental reprogramming of lineage committed host glial cells to progenitor/stem cell-like cells by an intracellular bacterial pathogen Mycobacterium leprae. Acquisition of migratory and immunomodulatory properties of such reprogrammed cells provides an added advantage for promoting bacterial spread. This presents a previously unseen sophistication of cell manipulation by hijacking the genomic plasticity of host cells by a human bacterial pathogen. The rationale for such extreme fate conversion of host cells may be directly linked to the exceedingly passive obligate life style of M. leprae with a degraded genome and host cell dependence for both bacterial survival and dissemination, particularly the use of host-derived stem cell-like cells as a vehicle for spreading infection without being detected by immune cells. Thus, this unexpected link between cell reprogramming and infection opens up a new premise in host-pathogen interactions. Furthermore, such bacterial ingenuity could also be harnessed for developing natural ways of reprogramming host cells for repairing damaged tissues from infection, injury and diseases. PMID:25541240

  15. Establishment and Validation of Whole-Cell Based Fluorescence Assays to Identify Anti-Mycobacterial Compounds Using the Acanthamoeba castellanii - Mycobacterium marinum Host-Pathogen System

    PubMed Central

    Kicka, Sébastien; Trofimov, Valentin; Harrison, Christopher; Ouertatani-Sakouhi, Hajer; McKinney, John; Scapozza, Leonardo; Hilbi, Hubert; Cosson, Pierre; Soldati, Thierry

    2014-01-01

    Tuberculosis is considered to be one of the world’s deadliest disease with 2 million deaths each year. The need for new antitubercular drugs is further exacerbated by the emergence of drug-resistance strains. Despite multiple recent efforts, the majority of the hits discovered by traditional target-based screening showed low efficiency in vivo. Therefore, there is heightened demand for whole-cell based approaches directly using host-pathogen systems. The phenotypic host-pathogen assay described here is based on the monitoring of GFP-expressing Mycobacterium marinum during infection of the amoeba Acanthamoeba castellanii. The assay showed straight-forward medium-throughput scalability, robustness and ease of manipulation, demonstrating its qualities as an efficient compound screening system. Validation with a series of known antitubercular compounds highlighted the advantages of the assay in comparison to previously published macrophage-Mycobacterium tuberculosis-based screening systems. Combination with secondary growth assays based on either GFP-expressing D. discoideum or M. marinum allowed us to further fine-tune compound characterization by distinguishing and quantifying growth inhibition, cytotoxic properties and antibiotic activities of the compounds. The simple and relatively low cost system described here is most suitable to detect anti-infective compounds, whether they present antibiotic activities or not, in which case they might exert anti-virulence or host defense boosting activities, both of which are largely overlooked by classical screening approaches. PMID:24498207

  16. Understanding the host-pathogen interaction saves lives: lessons from vaccines and vaccinations.

    PubMed

    Garon, Julie R; Orenstein, Walter A

    2015-10-01

    Vaccines are one of the most successful and cost-effective public health tools employed to date, yet these benefits are only realized when the life-saving intervention reaches each and every targeted individual. Vaccine development is prioritized based on a number of factors such as health burden, feasibility, and determination of potential target populations. But only through an arduous process of pre-clinical development and progressive clinical trials does a vaccine become licensed and recommended for use. Once used in a wider and more diverse population safety issues, long-term impact and other unintended outcomes may become apparent, influencing policy modification. This commentary explores the role host-pathogen interaction plays in vaccine development and the operational and policy considerations that may impact vaccine success post-licensure. PMID:25974089

  17. The role of pathogen shedding in linking within- and between-host pathogen dynamics.

    PubMed

    Barfield, Michael; Orive, Maria E; Holt, Robert D

    2015-12-01

    A model linking within- and between-host pathogen dynamics via pathogen shedding (emission of pathogens throughout the course of infection) is developed, and several aspects of host availability and co-infection are considered. In this model, the rate of pathogen shedding affects both the pathogen population size within a host (also affecting host mortality) and the rate of infection of new hosts. Our goal is to ascertain how the rate of shedding is likely to evolve, and what factors permit coexistence of alternative shedding rates in a pathogen population. For a constant host population size (where an increase in infected hosts necessarily decreases susceptible hosts), important differences arise depending on whether pathogens compete only for susceptible (uninfected) hosts, or whether co-infection allows for competition for infected hosts. With no co-infection, the pathogen type that can persist with the lowest number of susceptible hosts will outcompete any other, which under the assumptions of the model is the pathogen with the highest basic reproduction number. This is often a pathogen with a relatively high shedding rate (s). If within-host competition is allowed, a trade-off develops due to the conflicting effects of shedding on within- and between-host pathogen dynamics, with within-host competition favoring clones with low shedding rates while between-host competition benefits clones with higher shedding rates. With within-host competition for the same host cells, low shedding rate clones should eliminate high-s clones in a co-infected host, if equilibrium is reached. With co-infection, but no within-host competition, pathogen clones still interact by affecting the mortality of co-infected hosts; here, coexistence is more likely. With co-infection, two clones can coexist if one is the superior competitor for uninfected hosts and the other for co-infected hosts. PMID:25958811

  18. Animal Models of Human Granulocyte Diseases

    PubMed Central

    Schäffer, Alejandro A.; Klein, Christoph

    2012-01-01

    In vivo animal models have proven very useful to understand basic biological pathways of the immune system, a prerequisite for the development of innovate therapies. This manuscript addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve diagnosis and therapy by use of the appropriate animal model system. PMID:23351993

  19. Clostridium difficile-mediated effects on human intestinal epithelia: Modelling host-pathogen interactions in a vertical diffusion chamber.

    PubMed

    Jafari, Nazila V; Kuehne, Sarah A; Minton, Nigel P; Allan, Elaine; Bajaj-Elliott, Mona

    2016-02-01

    Clostridium difficile infection is one of the leading causes of healthcare associated diarrhoea in the developed world. Although the contribution of C. difficile toxins to disease pathogenesis is now well understood, many facets of host-pathogen interactions between the human intestinal epithelia and the C. difficile bacterium that may contribute to asymptomatic carriage and/or clinical disease remain less clear. Herein, we tested the hypothesis that C. difficile strains mediate intestinal epithelial cell (IEC) antimicrobial immunity via toxin dependent and independent means and that the 'anaerobic' environment has a significant impact on bacterial-IEC interactions. Crosstalk between three C. difficile PCR ribotypes (RT) [RT027 (strain R20291), RT012 (strain 630) and RT017 (strains M68 and CF5)] and IEC cell-lines were investigated. All RTs showed significant engagement with human Toll-like receptors (TLR)-5, TLR2-CD14 and TLR2/6 as measured by IL-8 release from TLR-transfected HEK cells. Co-culture studies indicated minimal impact of R20291 and 630 TcdA and TcdB on bacterial adherence to Caco-2 cells. An apical anaerobic environment had a major effect on C. difficile-T84 crosstalk as significantly greater cytokine immunity and trans-epithelial electrical resistance (TEER) dysfunction was recorded when co-cultures were performed in an Ussing chamber system compared to standard 5% CO2 conditions. Overall, this study suggests that anaerobic C. difficile engagement with human IECs is a complex interplay that involves bacterial and toxin-mediated cellular events. PMID:26708704

  20. Animal models for prion-like diseases.

    PubMed

    Fernández-Borges, Natalia; Eraña, Hasier; Venegas, Vanesa; Elezgarai, Saioa R; Harrathi, Chafik; Castilla, Joaquín

    2015-09-01

    Prion diseases or Transmissible Spongiform Encephalopathies (TSEs) are a group of fatal neurodegenerative disorders affecting several mammalian species being Creutzfeldt-Jacob Disease (CJD) the most representative in human beings, scrapie in ovine, Bovine Spongiform Encephalopathy (BSE) in bovine and Chronic Wasting Disease (CWD) in cervids. As stated by the "protein-only hypothesis", the causal agent of TSEs is a self-propagating aberrant form of the prion protein (PrP) that through a misfolding event acquires a β-sheet rich conformation known as PrP(Sc) (from scrapie). This isoform is neurotoxic, aggregation prone and induces misfolding of native cellular PrP. Compelling evidence indicates that disease-specific protein misfolding in amyloid deposits could be shared by other disorders showing aberrant protein aggregates such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic lateral sclerosis (ALS) and systemic Amyloid A amyloidosis (AA amyloidosis). Evidences of shared mechanisms of the proteins related to each disease with prions will be reviewed through the available in vivo models. Taking prion research as reference, typical prion-like features such as seeding and propagation ability, neurotoxic species causing disease, infectivity, transmission barrier and strain evidences will be analyzed for other protein-related diseases. Thus, prion-like features of amyloid β peptide and tau present in AD, α-synuclein in PD, SOD-1, TDP-43 and others in ALS and serum α-amyloid (SAA) in systemic AA amyloidosis will be reviewed through models available for each disease. PMID:25907990

  1. Animal models of human granulocyte diseases.

    PubMed

    Schäffer, Alejandro A; Klein, Christoph

    2013-02-01

    In vivo animal models have proven very useful to the understanding of basic biologic pathways of the immune system, a prerequisite for the development of innovate therapies. This article addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish, and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve diagnosis and therapy by use of the appropriate animal model system. PMID:23351993

  2. Animal Diseases Caused by Orbiviruses, Algeria

    PubMed Central

    Madani, Hafsa; Casal, Jordi; Alba, Anna; Allepuz, Alberto; Cêtre-Sossah, Catherine; Hafsi, Leila; Kount-Chareb, Houria; Bouayed-Chaouach, Nadera; Saadaoui, Hassiba

    2011-01-01

    Antibodies against bluetongue virus were detected in cattle, sheep, goats, and camels in Algeria in 2008. Antibodies against epizootic hemorrhagic disease virus were detected in cattle, but antibodies against African horse sickness virus were not detected in horses and mules. Epizootic hemorrhagic disease in northern Africa poses a major risk for the European Union. PMID:22172371

  3. Improving Animal Disease Detection Through an Enhanced Passive Surveillance Platform.

    PubMed

    Thompson, Chelsea Wright; Holmstrom, Lindsey; Biggers, Keith; Wall, James; Beckham, Tammy; Coats, Matthew; Korslund, John; Colby, Michelle M

    2016-01-01

    The ability to rapidly detect and report infectious diseases of domestic animals and wildlife is paramount to reducing the size and duration of an outbreak. There is currently a need in the United States livestock industry for a centralized animal disease surveillance platform, capable of collecting, integrating, and analyzing multiple data streams with dissemination to end-users. Such a system would be disease agnostic and establish baseline information on animal health and disease prevalence; it would alert health officials to anomalies potentially indicative of emerging and/or transboundary disease outbreaks, changes in the status of endemic disease, or detection of other causative agents (eg, toxins). As a part of its mission to accelerate and develop countermeasures against the introduction of emerging and/or transboundary animal diseases into the United States, the Department of Homeland Security is leading and investing in the development of an enhanced passive surveillance platform capable of establishing animal health baselines over time and alerting health officials to potential infectious disease outbreaks or other health anomalies earlier, allowing for more rapid response, improved animal health, and increased economic security. PMID:27419928

  4. The Fuzzy Model for Diagnosis of Animal Disease

    NASA Astrophysics Data System (ADS)

    Jianhua, Xiao; Luyi, Shi; Yu, Zhang; Li, Gao; Honggang, Fan; Haikun, Ma; Hongbin, Wang

    The knowledge of animal disease diagnosis was fuzzy; the fuzzy model can imitate the character of clinical diagnosis for veterinary. The fuzzy model of disease, the methods for class the disease group of differential diagnosis and the fuzzy diagnosis model were discussed in this paper.

  5. Disease protection vs animal protection--synergisms and contradictions.

    PubMed

    Dimander, S O

    Health is an important part of animal welfare. This implies that measures for the protection against disease will also affect animal protection. In most instances, efforts to improve disease protection act synergistically with efforts to promote animal protection, and vice versa. In the context of farm animal transport, however, infectious disease protection and animal protection may not always be mutually beneficial. Examples of contradictions are: Logistic perturbations; Current farm animal production is increasingly sensitive to logistic perturbations. Control and prevention of epizootic diseases involve extraordinary transport precautions that rapidly result in overcrowded stables. Transhumance; The practise of transhumance is compromised when control measures are taken to prevent spread of epizootic diseases. Travel sickness; Travel sickness is a problem particularly in pigs. Starvation before transport prevents vomiting but result in hungry animals. Lack of experience; Animals that are kept under conditions estranged from situations associated with transport alike are more prone to transport induced stress. Flooring; A non-slip flooring is a prerequisite for firm footing but demand more careful cleaning and disinfection to prevent spread of infectious agents. PMID:16429802

  6. Animal models of human respiratory syncytial virus disease

    PubMed Central

    Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for novel therapies and preventative strategies. Present animal models include several target species for hRSV, including chimpanzees, cattle, sheep, cotton rats, and mice, as well as alternative animal pneumovirus models, such as bovine RSV and pneumonia virus of mice. These diverse animal models reproduce different features of hRSV disease, and their utilization should therefore be based on the scientific hypothesis under investigation. The purpose of this review is to summarize the strengths and limitations of each of these animal models. Our intent is to provide a resource for investigators and an impetus for future research. PMID:21571908

  7. Integrating genomics to understand the Marek's disease virus-chicken host-pathogen interaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poultry is the third largest agricultural commodity and the primary meat consumed in the U.S. According to the USDA Agricultural Statistics (www.nass.usda.gov), in 2004 (latest year with complete information), the U.S. produced 45.8 billion pounds of chicken meat, 7.3 billion pounds of turkey meat,...

  8. Humane killing of animals for disease control purposes.

    PubMed

    Thornber, P M; Rubira, R J; Styles, D K

    2014-04-01

    Killing for disease control purposes is an emotional issue for everyone concerned. Large-scale euthanasia or depopulation of animals may be necessary for the emergency control or eradication of animal diseases, to remove animals from a compromised situation (e.g. following flood, storm, fire, drought or a feed contamination event), to effect welfare depopulation when there is an oversupply due to a dysfunctional or closed marketing channel, or to depopulate and dispose of animals with minimal handling to decrease the risk of a zoonotic disease infecting humans. The World Organisation for Animal Health (OIE) developed international standards to provide advice on humane killing for various species and situations. Some fundamental issues are defined, such as competency of animal handling and implementation of humane killing techniques. Some of these methods have been used for many years, but novel approaches for the mass killing of particular species are being explored. Novel vaccines and new diagnostic techniques that differentiate between vaccinated and infected animals will save many animals from being killed as part of biosecurity response measures. Unfortunately, the destruction of affected livestock will still be required to control diseases whilst vaccination programmes are activated or where effective vaccines are not available. This paper reviews the principles of humane destruction and depopulation and explores available techniques with their associated advantages and disadvantages. It also identifies some current issues that merit consideration, such as legislative conflicts (emergency disease legislation versus animal welfare legislation, occupational health and safety), media issues, opinions on the future approaches to killing for disease control, and animal welfare. PMID:25000803

  9. Disease-protective symbiosis among fishes and other aquatic animals

    USGS Publications Warehouse

    Snieszko, S.F.

    1962-01-01

    There have been numerous observations of one species of animal removing parasites from another. These are, however, generally regarded as biological curiosities rather than as significant factors in the control of parasites or disease.

  10. Database of host-pathogen and related species interactions, and their global distribution

    PubMed Central

    Wardeh, Maya; Risley, Claire; McIntyre, Marie Kirsty; Setzkorn, Christian; Baylis, Matthew

    2015-01-01

    Interactions between species, particularly where one is likely to be a pathogen of the other, as well as the geographical distribution of species, have been systematically extracted from various web-based, free-access sources, and assembled with the accompanying evidence into a single database. The database attempts to answer questions such as what are all the pathogens of a host, and what are all the hosts of a pathogen, what are all the countries where a pathogen was found, and what are all the pathogens found in a country. Two datasets were extracted from the database, focussing on species interactions and species distribution, based on evidence published between 1950–2012. The quality of their evidence was checked and verified against well-known, alternative, datasets of pathogens infecting humans, domestic animals and wild mammals. The presented datasets provide a valuable resource for researchers of infectious diseases of humans and animals, including zoonoses. PMID:26401317

  11. Database of host-pathogen and related species interactions, and their global distribution.

    PubMed

    Wardeh, Maya; Risley, Claire; McIntyre, Marie Kirsty; Setzkorn, Christian; Baylis, Matthew

    2015-01-01

    Interactions between species, particularly where one is likely to be a pathogen of the other, as well as the geographical distribution of species, have been systematically extracted from various web-based, free-access sources, and assembled with the accompanying evidence into a single database. The database attempts to answer questions such as what are all the pathogens of a host, and what are all the hosts of a pathogen, what are all the countries where a pathogen was found, and what are all the pathogens found in a country. Two datasets were extracted from the database, focussing on species interactions and species distribution, based on evidence published between 1950-2012. The quality of their evidence was checked and verified against well-known, alternative, datasets of pathogens infecting humans, domestic animals and wild mammals. The presented datasets provide a valuable resource for researchers of infectious diseases of humans and animals, including zoonoses. PMID:26401317

  12. Systems approach to characterizing cell signaling in host-pathogen response to staphylococcus toxin.

    SciTech Connect

    Ambrosiano, J. J.; Gupta, G.; Gray, P. C.; Hush, D. R.; Fugate, M. L.; Cleland, T. J.; Roberts, R. M.; Hlavacek, W. S.; Smith, J. L.

    2002-01-01

    The mammalian immune system is capable of highly sensitive and specific responses when challenged by pathogens. It is believed that the human immune repertoire - the total number of distinct antigens that can be recognized - is between 10{sup 9} and 10{sup 11}. The most specific responses are cell mediated and involve complex and subtle communications among the immune cells via small proteins known as cytokines. The details of host-pathogen response are exceedingly complex, involving both intracellular and extracellular mechanisms. These include the presentation of antigen by B cells to helper T cells and subsequent stimulation of signal transduction pathways and gene expression within both B and T-cell populations. These in turn lead to the secretion of cytokines and receptor expression. Intercellular cytokine signaling can trigger a host of immune responses including the proliferation and specialization of naive immune cells and the marshaling of effector cells to combat infection. In the ever-evolving game of threat and countermeasure played out by pathogens and their intended hosts, there are direct assaults aimed at subverting the immune system's ability to recognize antigens and respond effectively to challenge by pathogens. Staphylococcus is one of these. Staph bacteria secrete a variety of toxins known generically as superantigens. Superantigen molecules bind simultaneously to the MHC receptors of antigen presenting cells and the TCR receptors of helper T cells, locking them in place and leading to overstimulation. This strategy can effectively burn out the immune system in a matter of days.

  13. Low host-pathogen specificity in the leaf-cutting ant-microbe symbiosis.

    PubMed

    Taerum, Stephen J; Cafaro, Matías J; Little, Ainslie E F; Schultz, Ted R; Currie, Cameron R

    2007-08-22

    Host-parasite associations are shaped by coevolutionary dynamics. One example is the complex fungus-growing ant-microbe symbiosis, which includes ancient host-parasite coevolution. Fungus-growing ants and the fungi they cultivate for food have an antagonistic symbiosis with Escovopsis, a specialized microfungus that infects the ants' fungus gardens. The evolutionary histories of the ant, cultivar and Escovopsis are highly congruent at the deepest phylogenetic levels, with specific parasite lineages exclusively associating with corresponding groups of ants and cultivar. Here, we examine host-parasite specificity at finer phylogenetic levels, within the most derived clade of fungus-growing ants, the leaf-cutters (Atta spp. and Acromyrmex spp.). Our molecular phylogeny of Escovopsis isolates from the leaf-cutter ant-microbe symbiosis confirms specificity at the broad phylogenetic level, but reveals frequent host-switching events between species and genera of leaf-cutter ants. Escovopsis strains isolated from Acromyrmex and Atta gardens occur together in the same clades, and very closely related strains can even infect the gardens of both ant genera. Experimental evidence supports low host-parasite specificity, with phylogenetically diverse strains of Escovopsis being capable of overgrowing all leaf-cutter cultivars examined. Thus, our findings indicate that this host-pathogen association is shaped by the farming ants having to protect their cultivated fungus from phylogenetically diverse Escovopsis garden pathogens. PMID:17550881

  14. Exploring host-pathogen interactions through genome wide protein microarray analysis.

    PubMed

    Scietti, Luigi; Sampieri, Katia; Pinzuti, Irene; Bartolini, Erika; Benucci, Barbara; Liguori, Alessia; Haag, Andreas F; Lo Surdo, Paola; Pansegrau, Werner; Nardi-Dei, Vincenzo; Santini, Laura; Arora, Seguinde; Leber, Xavier; Rindi, Simonetta; Savino, Silvana; Costantino, Paolo; Maione, Domenico; Merola, Marcello; Speziale, Pietro; Bottomley, Matthew J; Bagnoli, Fabio; Masignani, Vega; Pizza, Mariagrazia; Scharenberg, Meike; Schlaeppi, Jean-Marc; Nissum, Mikkel; Liberatori, Sabrina

    2016-01-01

    During bacterial pathogenesis extensive contacts between the human and the bacterial extracellular proteomes take place. The identification of novel host-pathogen interactions by standard methods using a case-by-case approach is laborious and time consuming. To overcome this limitation, we took advantage of large libraries of human and bacterial recombinant proteins. We applied a large-scale protein microarray-based screening on two important human pathogens using two different approaches: (I) 75 human extracellular proteins were tested on 159 spotted Staphylococcus aureus recombinant proteins and (II) Neisseria meningitidis adhesin (NadA), an important vaccine component against serogroup B meningococcus, was screened against ≈2300 spotted human recombinant proteins. The approach presented here allowed the identification of the interaction between the S. aureus immune evasion protein FLIPr (formyl-peptide receptor like-1 inhibitory protein) and the human complement component C1q, key players of the offense-defense fighting; and of the interaction between meningococcal NadA and human LOX-1 (low-density oxidized lipoprotein receptor), an endothelial receptor. The novel interactions between bacterial and human extracellular proteins here presented might provide a better understanding of the molecular events underlying S. aureus and N. meningitidis pathogenesis. PMID:27302108

  15. Adaptation of mammalian host-pathogen interactions in a changing arctic environment

    PubMed Central

    2011-01-01

    Many arctic mammals are adapted to live year-round in extreme environments with low winter temperatures and great seasonal variations in key variables (e.g. sunlight, food, temperature, moisture). The interaction between hosts and pathogens in high northern latitudes is not very well understood with respect to intra-annual cycles (seasons). The annual cycles of interacting pathogen and host biology is regulated in part by highly synchronized temperature and photoperiod changes during seasonal transitions (e.g., freezeup and breakup). With a warming climate, only one of these key biological cues will undergo drastic changes, while the other will remain fixed. This uncoupling can theoretically have drastic consequences on host-pathogen interactions. These poorly understood cues together with a changing climate by itself will challenge host populations that are adapted to pathogens under the historic and current climate regime. We will review adaptations of both host and pathogens to the extreme conditions at high latitudes and explore some potential consequences of rapid changes in the Arctic. PMID:21392401

  16. Investigating host-pathogen behavior and their interaction using genome-scale metabolic network models.

    PubMed

    Sadhukhan, Priyanka P; Raghunathan, Anu

    2014-01-01

    Genome Scale Metabolic Modeling methods represent one way to compute whole cell function starting from the genome sequence of an organism and contribute towards understanding and predicting the genotype-phenotype relationship. About 80 models spanning all the kingdoms of life from archaea to eukaryotes have been built till date and used to interrogate cell phenotype under varying conditions. These models have been used to not only understand the flux distribution in evolutionary conserved pathways like glycolysis and the Krebs cycle but also in applications ranging from value added product formation in Escherichia coli to predicting inborn errors of Homo sapiens metabolism. This chapter describes a protocol that delineates the process of genome scale metabolic modeling for analysing host-pathogen behavior and interaction using flux balance analysis (FBA). The steps discussed in the process include (1) reconstruction of a metabolic network from the genome sequence, (2) its representation in a precise mathematical framework, (3) its translation to a model, and (4) the analysis using linear algebra and optimization. The methods for biological interpretations of computed cell phenotypes in the context of individual host and pathogen models and their integration are also discussed. PMID:25048144

  17. Genome Scale Evolution of Myxoma Virus Reveals Host-Pathogen Adaptation and Rapid Geographic Spread

    PubMed Central

    Kerr, Peter J.; Rogers, Matthew B.; Fitch, Adam; DePasse, Jay V.; Cattadori, Isabella M.; Twaddle, Alan C.; Hudson, Peter J.; Tscharke, David C.; Read, Andrew F.; Holmes, Edward C.

    2013-01-01

    The evolutionary interplay between myxoma virus (MYXV) and the European rabbit (Oryctolagus cuniculus) following release of the virus in Australia in 1950 as a biological control is a classic example of host-pathogen coevolution. We present a detailed genomic and phylogeographic analysis of 30 strains of MYXV, including the Australian progenitor strain Standard Laboratory Strain (SLS), 24 Australian viruses isolated from 1951 to 1999, and three isolates from the early radiation in Britain from 1954 and 1955. We show that in Australia MYXV has spread rapidly on a spatial scale, with multiple lineages cocirculating within individual localities, and that both highly virulent and attenuated viruses were still present in the field through the 1990s. In addition, the detection of closely related virus lineages at sites 1,000 km apart suggests that MYXV moves freely in geographic space, with mosquitoes, fleas, and rabbit migration all providing means of transport. Strikingly, despite multiple introductions, all modern viruses appear to be ultimately derived from the original introductions of SLS. The rapidity of MYXV evolution was also apparent at the genomic scale, with gene duplications documented in a number of viruses. Duplication of potential virulence genes may be important in increasing the expression of virulence proteins and provides the basis for the evolution of novel functions. Mutations leading to loss of open reading frames were surprisingly frequent and in some cases may explain attenuation, but no common mutations that correlated with virulence or attenuation were identified. PMID:24067966

  18. Host-Pathogen Checkpoints and Population Bottlenecks in Persistent and Intracellular Uropathogenic E. coli Bladder Infection

    PubMed Central

    Hannan, Thomas J.; Totsika, Makrina; Mansfield, Kylie J.; Moore, Kate H.; Schembri, Mark A.; Hultgren, Scott J.

    2013-01-01

    Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multi-drug resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic E. coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the Quiescent Intracellular Reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection: QIR, ASB, or chronic cystitis, is determined within the first 24 hours of infection and constitutes a putative host-pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies. PMID:22404313

  19. Use of high-throughput mass spectrometry to elucidate host-pathogen interactions in Salmonella

    SciTech Connect

    Rodland, Karin D.; Adkins, Joshua N.; Ansong, Charles; Chowdhury, Saiful M.; Manes, Nathan P.; Shi, Liang; Yoon, Hyunjin; Smith, Richard D.; Heffron, Fred

    2008-12-01

    New improvements to mass spectrometry include increased sensitivity, improvements in analyzing the collected data, and most important, from the standpoint of this review, a much higher throughput allowing analysis of many samples in a single day. This short review describes how host-pathogen interactions can be dissected by mass spectrometry using Salmonella as a model system. The approach allowed direct identification of the majority of annotate Salmonella proteins, how expression changed under various in vitro growth conditions, and how this relates to virulence and expression within host cell cells. One of the most significant findings is that a very high percentage of the all annotated genes (>20%) are regulated post-transcriptionally. In addition, new and unexpected interactions have been identified for several Salmonella virulence regulators that involve protein-protein interactions suggesting additional functions of the regulator in coordinating virulence expression. Overall high throughput mass spectrometer provides a new view of pathogen-host interaction emphasizing the protein products and defining how protein interactions determine the outcome of infection.

  20. Use of high-throughput mass spectrometry to elucidate host pathogen interactions in Salmonella

    SciTech Connect

    Rodland, Karin D.; Adkins, Joshua N.; Ansong, Charles; Chowdhury, Saiful M.; Manes, Nathan P.; Shi, Liang; Yoon, Hyunjin; Smith, Richard D.; Heffron, Fred

    2008-12-01

    Capabilities in mass spectrometry are evolving rapidly, with recent improvements in sensitivity, data analysis, and most important, from the standpoint of this review, much higher throughput allowing analysis of many samples in a single day. This short review describes how these improvements in mass spectrometry can be used to dissect host-pathogen interactions using Salmonella as a model system. This approach enabled direct identification of the majority of annotated Salmonella proteins, quantitation of expression changes under various in vitro growth conditions, and new insights into virulence and expression of Salmonella proteins within host cell cells. One of the most significant findings is that a very high percentage of the all annotated genes (>20%) in Salmonella are regulated post-transcriptionally. In addition, new and unexpected interactions have been identified for several Salmonella virulence regulators that involve protein-protein interactions, suggesting additional functions of these regulators in coordinating virulence expression. Overall high throughput mass spectrometry provides a new view of pathogen-host interactions emphasizing the protein products and defining how protein interactions determine the outcome of infection.

  1. Assessing Student Understanding of Host Pathogen Interactions Using a Concept Inventory

    PubMed Central

    Marbach-Ad, Gili; Briken, Volker; El-Sayed, Najib M.; Frauwirth, Kenneth; Fredericksen, Brenda; Hutcheson, Steven; Gao, Lian-Yong; Joseph, Sam; Lee, Vincent T.; McIver, Kevin S.; Mosser, David; Quimby, B. Booth; Shields, Patricia; Song, Wenxia; Stein, Daniel C.; Yuan, Robert T.; Smith, Ann C.

    2009-01-01

    As a group of faculty with expertise and research programs in the area of host-pathogen interactions (HPI), we are concentrating on students’ learning of HPI concepts. As such we developed a concept inventory to measure level of understanding relative to HPI after the completion of a set of microbiology courses (presently eight courses). Concept inventories have been useful tools for assessing student learning, and our interest was to develop such a tool to measure student learning progression in our microbiology courses. Our teaching goal was to create bridges between our courses which would eliminate excessive overlap in our offerings and support a model where concepts and ideas introduced in one course would become the foundation for concept development in successive courses. We developed our HPI concept inventory in several phases. The final product was an 18-question, multiple-choice concept inventory. In fall 2006 and spring 2007 we administered the 18-question concept inventory in six of our courses. We collected pre- and postcourse surveys from 477 students. We found that students taking pretests in the advanced courses retained the level of understanding gained in the general microbiology prerequisite course. Also, in two of our courses there was significant improvement on the scores from pretest to posttest. As we move forward, we will concentrate on exploring the range of HPI concepts addressed in each course and determine and/or create effective methods for meaningful student learning of HPI aspects of microbiology. PMID:23653689

  2. Host-Pathogen Interaction Profiling Using Self-Assembling Human Protein Arrays

    PubMed Central

    Yu, Xiaobo; Decker, Kimberly B.; Barker, Kristi; Neunuebel, M. Ramona; Saul, Justin; Graves, Morgan; Westcott, Nathan; Hang, Howard; LaBaer, Joshua; Qiu, Ji; Machner, Matthias P.

    2015-01-01

    Host-pathogen protein interactions are fundamental to every microbial infection, yet their identification has remained challenging due to the lack of simple detection tools that avoid abundance biases while providing an open format for experimental modifications. Here, we applied the Nucleic Acid-Programmable Protein Array and a HaloTag-Halo ligand detection system to determine the interaction network of Legionella pneumophila effectors (SidM and LidA) with 10,000 unique human proteins. We identified known targets of these L. pneumophila proteins and potentially novel interaction candidates. In addition, we applied our Click chemistry-based NAPPA platform to identify the substrates for SidM, an effector with an adenylyl transferase domain that catalyzes AMPylation (adenylylation), the covalent addition of adenosine monophosphate (AMP). We confirmed a subset of the novel SidM and LidA targets in independent in vitro pull-down and in vivo cell-based assays, and provided further insight into how these effectors may discriminate between different host Rab GTPases. Our method circumvents the purification of thousands of human and pathogen proteins, and does not require antibodies against or pre-labeling of query proteins. This system is amenable to high-throughput analysis of effectors from a wide variety of human pathogens that may bind to and/or post-translationally modify targets within the human proteome. PMID:25739981

  3. Exploring host-pathogen interactions through genome wide protein microarray analysis

    PubMed Central

    Scietti, Luigi; Sampieri, Katia; Pinzuti, Irene; Bartolini, Erika; Benucci, Barbara; Liguori, Alessia; Haag, Andreas F.; Lo Surdo, Paola; Pansegrau, Werner; Nardi-Dei, Vincenzo; Santini, Laura; Arora, Seguinde; Leber, Xavier; Rindi, Simonetta; Savino, Silvana; Costantino, Paolo; Maione, Domenico; Merola, Marcello; Speziale, Pietro; Bottomley, Matthew J.; Bagnoli, Fabio; Masignani, Vega; Pizza, Mariagrazia; Scharenberg, Meike; Schlaeppi, Jean-Marc; Nissum, Mikkel; Liberatori, Sabrina

    2016-01-01

    During bacterial pathogenesis extensive contacts between the human and the bacterial extracellular proteomes take place. The identification of novel host-pathogen interactions by standard methods using a case-by-case approach is laborious and time consuming. To overcome this limitation, we took advantage of large libraries of human and bacterial recombinant proteins. We applied a large-scale protein microarray-based screening on two important human pathogens using two different approaches: (I) 75 human extracellular proteins were tested on 159 spotted Staphylococcus aureus recombinant proteins and (II) Neisseria meningitidis adhesin (NadA), an important vaccine component against serogroup B meningococcus, was screened against ≈2300 spotted human recombinant proteins. The approach presented here allowed the identification of the interaction between the S. aureus immune evasion protein FLIPr (formyl-peptide receptor like-1 inhibitory protein) and the human complement component C1q, key players of the offense-defense fighting; and of the interaction between meningococcal NadA and human LOX-1 (low-density oxidized lipoprotein receptor), an endothelial receptor. The novel interactions between bacterial and human extracellular proteins here presented might provide a better understanding of the molecular events underlying S. aureus and N. meningitidis pathogenesis. PMID:27302108

  4. Evolutionary diversification through hybridization in a wild host-pathogen interaction.

    PubMed

    Barrett, Luke G; Thrall, Peter H; Burdon, Jeremy J

    2007-07-01

    Coevolutionary outcomes between interacting species are predicted to vary across landscapes, as environmental conditions, gene flow, and the strength of selection vary among populations. Using a combination of molecular, experimental, and field approaches, we describe how broad-scale patterns of environmental heterogeneity, genetic divergence, and regional adaptation have the potential to influence coevolutionary processes in the Linum marginale-Melampsora lini plant-pathogen interaction. We show that two genetically and geographically divergent pathogen lineages dominate interactions with the host across Australia, and demonstrate a hybrid origin for one of the lineages. We further demonstrate that the geographic divergence of the two lineages of M. lini in Australia is related to variation among lineages in virulence, life-history characteristics, and response to environmental conditions. When correlated with data describing regional patterns of variation in host resistance diversity and mating system these observations highlight the potential for gene flow and geographic selection mosaics to generate and maintain coevolutionary diversification in long-standing host-pathogen interactions. PMID:17598744

  5. Animal disease regionalization and its impact on tropical countries.

    PubMed

    Bokma, B H

    1998-06-29

    This paper reviews progress that has been made around the world in animal disease regionalization. Signatory countries of the Uruguay Round of the General Agreement on Tariffs and Trade (GATT) and other free-trade associations are currently implementing regionalization, one of the cornerstone provisions of the Uruguay Round of the GATT and the World Trade Organization's (WTO) Sanitary and Phytosanitary Agreement. Regionalization allows countries to protect the health status of their animal herds and at the same time promote their animal and animal product export markets. The implementation of regionalization by importing countries affects export markets of tropical nations. Veterinary officials of tropical countries must give regionalization due priority such that import and export trade in animals and animal products is not hindered, and the public and animal herd health are protected. PMID:9668483

  6. Computational prediction of disease microRNAs in domestic animals

    PubMed Central

    2014-01-01

    Background The most important means of identifying diseases before symptoms appear is through the discovery of disease-associated biomarkers. Recently, microRNAs (miRNAs) have become highly useful biomarkers of infectious, genetic and metabolic diseases in human but they have not been well studied in domestic animals. It is probable that many of the animal homologs of human disease-associated miRNAs may be involved in domestic animal diseases. Here we describe a computational biology study in which human disease miRNAs were utilized to predict orthologous miRNAs in cow, chicken, pig, horse, and dog. Results We identified 287 human disease-associated miRNAs which had at least one 100% identical animal homolog. The 287 miRNAs were associated with 359 human diseases referenced in 2,863 Pubmed articles. Multiple sequence analysis indicated that over 60% of known horse mature miRNAs found perfect matches in human disease-associated miRNAs, followed by dog (50%). As expected, chicken had the least number of perfect matches (5%). Phylogenetic analysis of miRNA precursors indicated that 85% of human disease pre-miRNAs were highly conserved in animals, showing less than 5% nucleotide substitution rates over evolutionary time. As an example we demonstrated conservation of human hsa-miR-143-3p which is associated with type 2 diabetes and targets AKT1 gene which is highly conserved in pig, horse and dog. Functional analysis of AKT1 gene using Gene Ontology (GO) showed that it is involved in glucose homeostasis, positive regulation of glucose import, positive regulation of glycogen biosynthetic process, glucose transport and response to food. Conclusions This data provides the animal and veterinary research community with a resource to assist in generating hypothesis-driven research for discovering animal disease-related miRNA from their datasets and expedite development of prophylactic and disease-treatment strategies and also influence research efforts to identify novel

  7. Infectious diseases of animals and plants: an interdisciplinary approach.

    PubMed

    Wilkinson, Katy; Grant, Wyn P; Green, Laura E; Hunter, Stephen; Jeger, Michael J; Lowe, Philip; Medley, Graham F; Mills, Peter; Phillipson, Jeremy; Poppy, Guy M; Waage, Jeff

    2011-07-12

    Animal and plant diseases pose a serious and continuing threat to food security, food safety, national economies, biodiversity and the rural environment. New challenges, including climate change, regulatory developments, changes in the geographical concentration and size of livestock holdings, and increasing trade make this an appropriate time to assess the state of knowledge about the impact that diseases have and the ways in which they are managed and controlled. In this paper, the case is explored for an interdisciplinary approach to studying the management of infectious animal and plant diseases. Reframing the key issues through incorporating both social and natural science research can provide a holistic understanding of disease and increase the policy relevance and impact of research. Finally, in setting out the papers in this Theme Issue, a picture of current and future animal and plant disease threats is presented. PMID:21624914

  8. Engineering Large Animal Species to Model Human Diseases.

    PubMed

    Rogers, Christopher S

    2016-01-01

    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. PMID:27367161

  9. Infectious diseases of animals and plants: an interdisciplinary approach

    PubMed Central

    Wilkinson, Katy; Grant, Wyn P.; Green, Laura E.; Hunter, Stephen; Jeger, Michael J.; Lowe, Philip; Medley, Graham F.; Mills, Peter; Phillipson, Jeremy; Poppy, Guy M.; Waage, Jeff

    2011-01-01

    Animal and plant diseases pose a serious and continuing threat to food security, food safety, national economies, biodiversity and the rural environment. New challenges, including climate change, regulatory developments, changes in the geographical concentration and size of livestock holdings, and increasing trade make this an appropriate time to assess the state of knowledge about the impact that diseases have and the ways in which they are managed and controlled. In this paper, the case is explored for an interdisciplinary approach to studying the management of infectious animal and plant diseases. Reframing the key issues through incorporating both social and natural science research can provide a holistic understanding of disease and increase the policy relevance and impact of research. Finally, in setting out the papers in this Theme Issue, a picture of current and future animal and plant disease threats is presented. PMID:21624914

  10. Disease Tolerance as a Defense Strategy

    PubMed Central

    Medzhitov, Ruslan; Schneider, David S.; Soares, Miguel P.

    2013-01-01

    The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogen’s presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of “disease tolerance” into the conceptual toolkit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases. PMID:22363001

  11. Foreign Body Infection Models to Study Host-Pathogen Response and Antimicrobial Tolerance of Bacterial Biofilm

    PubMed Central

    Nowakowska, Justyna; Landmann, Regine; Khanna, Nina

    2014-01-01

    The number of implanted medical devices is steadily increasing and has become an effective intervention improving life quality, but still carries the risk of infection. These infections are mainly caused by biofilm-forming staphylococci that are difficult to treat due to the decreased susceptibility to both antibiotics and host defense mechanisms. To understand the particular pathogenesis and treatment tolerance of implant-associated infection (IAI) animal models that closely resemble human disease are needed. Applications of the tissue cage and catheter abscess foreign body infection models in the mouse will be discussed herein. Both models allow the investigation of biofilm and virulence of various bacterial species and a comprehensive insight into the host response at the same time. They have also been proven to serve as very suitable tools to study the anti-adhesive and anti-infective efficacy of different biomaterial coatings. The tissue cage model can additionally be used to determine pharmacokinetics, efficacy and cytotoxicity of antimicrobial compounds as the tissue cage fluid can be aspirated repeatedly without the need to sacrifice the animal. Moreover, with the advance in innovative imaging systems in rodents, these models may offer new diagnostic measures of infection. In summary, animal foreign body infection models are important tools in the development of new antimicrobials against IAI and can help to elucidate the complex interactions between bacteria, the host immune system, and prosthetic materials. PMID:27025752

  12. Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals

    PubMed Central

    Esch, Kevin J.

    2013-01-01

    Over 77 million dogs and 93 million cats share our households in the United States. Multiple studies have demonstrated the importance of pets in their owners' physical and mental health. Given the large number of companion animals in the United States and the proximity and bond of these animals with their owners, understanding and preventing the diseases that these companions bring with them are of paramount importance. Zoonotic protozoal parasites, including toxoplasmosis, Chagas' disease, babesiosis, giardiasis, and leishmaniasis, can cause insidious infections, with asymptomatic animals being capable of transmitting disease. Giardia and Toxoplasma gondii, endemic to the United States, have high prevalences in companion animals. Leishmania and Trypanosoma cruzi are found regionally within the United States. These diseases have lower prevalences but are significant sources of human disease globally and are expanding their companion animal distribution. Thankfully, healthy individuals in the United States are protected by intact immune systems and bolstered by good nutrition, sanitation, and hygiene. Immunocompromised individuals, including the growing number of obese and/or diabetic people, are at a much higher risk of developing zoonoses. Awareness of these often neglected diseases in all health communities is important for protecting pets and owners. To provide this awareness, this review is focused on zoonotic protozoal mechanisms of virulence, epidemiology, and the transmission of pathogens of consequence to pet owners in the United States. PMID:23297259

  13. Transmission and epidemiology of zoonotic protozoal diseases of companion animals.

    PubMed

    Esch, Kevin J; Petersen, Christine A

    2013-01-01

    Over 77 million dogs and 93 million cats share our households in the United States. Multiple studies have demonstrated the importance of pets in their owners' physical and mental health. Given the large number of companion animals in the United States and the proximity and bond of these animals with their owners, understanding and preventing the diseases that these companions bring with them are of paramount importance. Zoonotic protozoal parasites, including toxoplasmosis, Chagas' disease, babesiosis, giardiasis, and leishmaniasis, can cause insidious infections, with asymptomatic animals being capable of transmitting disease. Giardia and Toxoplasma gondii, endemic to the United States, have high prevalences in companion animals. Leishmania and Trypanosoma cruzi are found regionally within the United States. These diseases have lower prevalences but are significant sources of human disease globally and are expanding their companion animal distribution. Thankfully, healthy individuals in the United States are protected by intact immune systems and bolstered by good nutrition, sanitation, and hygiene. Immunocompromised individuals, including the growing number of obese and/or diabetic people, are at a much higher risk of developing zoonoses. Awareness of these often neglected diseases in all health communities is important for protecting pets and owners. To provide this awareness, this review is focused on zoonotic protozoal mechanisms of virulence, epidemiology, and the transmission of pathogens of consequence to pet owners in the United States. PMID:23297259

  14. The social and political impact of animal diseases.

    PubMed

    Evans, B

    2006-01-01

    The twenty-first century is characterised by 'epidemiological globalisation' on an unprecedented scale with resulting impacts at the interface of economic, scientific, social and political forces arising from the emergence and re-emergence of animal diseases. Throughout history, animals have served as a source to humankind of food, transportation, medicines, entertainment, clothing, fuel, military advantage and financial security. It is therefore not at all surprising that animal diseases have resulted in significant social and political impacts that have shaped and continue to shape the course of national and international events. The social impacts can be expressed as indirect health consequences or behavioural changes, changes in societal values and changes in social standing and can be felt at the individual, family or community level. The political impact of major disease outbreaks can include loss of public and consumer confidence, resistance to investments in disease surveillance, reluctance to report disease detections in a timely or transparent manner, failure to implement science-based international standards for safe trade (which protect animal, human and ecosystem health) and the removal of government officials. The magnitude of these impacts would support that social and political impacts warrant their inclusion in the consequence assessment of a robust animal disease risk analysis framework. PMID:20429074

  15. Surveillance of Zoonotic Infectious Disease Transmitted by Small Companion Animals

    PubMed Central

    Breitschwerdt, Edward; Cleaveland, Sarah; Karkare, Umesh; Khanna, Chand; Kirpensteijn, Jolle; Kuiken, Thijs; Lappin, Michael R.; McQuiston, Jennifer; Mumford, Elizabeth; Myers, Tanya; Palatnik-de-Sousa, Clarisa B.; Rubin, Carol; Takashima, Gregg; Thiermann, Alex

    2012-01-01

    The One Health paradigm for global health recognizes that most new human infectious diseases will emerge from animal reservoirs. Little consideration has been given to the known and potential zoonotic infectious diseases of small companion animals. Cats and dogs closely share the domestic environment with humans and have the potential to act as sources and sentinels of a wide spectrum of zoonotic infections. This report highlights the lack of a coordinated global surveillance scheme that monitors disease in these species and makes a case for the necessity of developing a strategy to implement such surveillance.

  16. Clinicopathologic aspects of animal and zoonotic diseases of bioterrorism.

    PubMed

    Mattix, Marc E; Zeman, David H; Moeller, Robert; Jackson, Carney; Larsen, Thomas

    2006-06-01

    We live in an era of emerging infectious diseases and the threat of bioterrorism. Most of the infectious agents of modern concern, from plague to avian influenza H5N1, are zoonotic diseases: infectious agents that reside in quiet animal reservoir cycles that are transmitted occasionally to humans. The public health, health care, and veterinary communities have an enormous challenge in the early recognition, reporting, treatment, and prevention of zoonotic diseases. An intimate understanding of the natural ecology, geographic distribution, clinical signs, lesions, and diagnosis of these diseases is essential for the early recognition and control of these diseases. PMID:16815461

  17. Climate change and animal diseases in South America.

    PubMed

    Pinto, J; Bonacic, C; Hamilton-West, C; Romero, J; Lubroth, J

    2008-08-01

    Climate strongly affects agriculture and livestock production and influences animal diseases, vectors and pathogens, and their habitat. Global warming trends predicted in the 2007 Intergovernmental Panel on Climatic Change (IPCC) report for South America are likely to change the temporal and geographical distribution of infectious diseases, including those that are vector-borne such as bluetongue, West Nile fever, vesicular stomatitis and New World screwworm. Changes in distribution will be partially modulated by El Niño Southern Oscillation events, which will become more frequent and lead to a greater frequency of droughts and floods. Active disease surveillance for animal diseases in South America, particularly for vector-borne diseases, is very poor. Disease reporting is often lacking, which affects knowledge of disease distribution and impact, and preparedness for early response. Improved reporting for animal diseases that may be affected by climate change is needed for better prevention and intervention measures in susceptible livestock, wildlife and vectors in South America. This requires contributions from multidisciplinary experts, including meteorologists, epidemiologists, biologists and ecologists, and from local communities. PMID:18819680

  18. Anaplasma phagocytophilum—a widespread multi-host pathogen with highly adaptive strategies

    PubMed Central

    Stuen, Snorre; Granquist, Erik G.; Silaghi, Cornelia

    2013-01-01

    The bacterium Anaplasma phagocytophilum has for decades been known to cause the disease tick-borne fever (TBF) in domestic ruminants in Ixodes ricinus-infested areas in northern Europe. In recent years, the bacterium has been found associated with Ixodes-tick species more or less worldwide on the northern hemisphere. A. phagocytophilum has a broad host range and may cause severe disease in several mammalian species, including humans. However, the clinical symptoms vary from subclinical to fatal conditions, and considerable underreporting of clinical incidents is suspected in both human and veterinary medicine. Several variants of A. phagocytophilum have been genetically characterized. Identification and stratification into phylogenetic subfamilies has been based on cell culturing, experimental infections, PCR, and sequencing techniques. However, few genome sequences have been completed so far, thus observations on biological, ecological, and pathological differences between genotypes of the bacterium, have yet to be elucidated by molecular and experimental infection studies. The natural transmission cycles of various A. phagocytophilum variants, the involvement of their respective hosts and vectors involved, in particular the zoonotic potential, have to be unraveled. A. phagocytophilum is able to persist between seasons of tick activity in several mammalian species and movement of hosts and infected ticks on migrating animals or birds may spread the bacterium. In the present review, we focus on the ecology and epidemiology of A. phagocytophilum, especially the role of wildlife in contribution to the spread and sustainability of the infection in domestic livestock and humans. PMID:23885337

  19. 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. PMID:27066769

  20. Control and eradication of animal diseases in New Zealand.

    PubMed

    Davidson, R M

    2002-01-01

    New Zealand is free from all the major epidemic (Office International des Epizooties List A) diseases of animals and other important diseases, such as rabies and the transmissible spongiform encephalopathies. The once endemic conditions of sheep scab (Psoroptes ovis), bovine brucellosis (Brucella abortus), hydatids (Echinococcus granulosus) and Aujeszky's disease have been eradicated. Anthrax (Bacillus anthracis) is no longer considered endemic and Pullorum disease (Salmonella Pullorum) has effectively been eradicated from commercial poultry flocks. There are current control programmes for bovine tuberculosis (Mycobacterium bovis), enzootic bovine leucosis in dairy cattle, infectious bursal disease, ovine epididymitis (Brucella ovis), and caprine arthritis encephalitis. Historically, incursions by three important non-endemic diseases, contagious bovine pleuropneumonia, classical swine fever and scrapie, have been successfully eliminated. Any new occurrence of a serious exotic disease would be dealt with swiftly using powerful legislative authorities available for the purpose. PMID:16032229

  1. Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology

    PubMed Central

    Olivier, Alicia K.; Gibson-Corley, Katherine N.

    2015-01-01

    Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF. PMID:25591863

  2. Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology.

    PubMed

    Olivier, Alicia K; Gibson-Corley, Katherine N; Meyerholz, David K

    2015-03-15

    Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF. PMID:25591863

  3. Critical Behavior in Cellular Automata Animal Disease Transmission Model

    NASA Astrophysics Data System (ADS)

    Morley, P. D.; Chang, Julius

    Using cellular automata model, we simulate the British Government Policy (BGP) in the 2001 foot and mouth epidemic in Great Britain. When clinical symptoms of the disease appeared in a farm, there is mandatory slaughter (culling) of all livestock in an infected premise (IP). Those farms in the neighboring of an IP (contiguous premise, CP), are also culled, aka nearest neighbor interaction. Farms where the disease may be prevalent from animal, human, vehicle or airborne transmission (dangerous contact, DC), are additionally culled, aka next-to-nearest neighbor interactions and lightning factor. The resulting mathematical model possesses a phase transition, whereupon if the physical disease transmission kernel exceeds a critical value, catastrophic loss of animals ensues. The nonlocal disease transport probability can be as low as 0.01% per day and the disease can still be in the high mortality phase. We show that the fundamental equation for sustainable disease transport is the criticality equation for neutron fission cascade. Finally, we calculate that the percentage of culled animals that are actually healthy is ≈30%.

  4. Regulatory T Cells and Their Role in Animal Disease.

    PubMed

    Veiga-Parga, T

    2016-07-01

    In humans and mouse models, Foxp3(+) regulatory T cells are known to control all aspects of immune responses. However, only limited information exists on these cells' role in diseases of other animals. In this review, we cover the most important features and different types of regulatory T cells, which include those that are thymus-derived and peripherally induced, the mechanisms by which they control immune responses by targeting effector T cells and antigen-presenting cells, and most important, their role in animal health and diseases including cancer, infections, and other conditions such as hypersensitivities and autoimmunity. Although the literature regarding regulatory T cells in domestic animal species is still limited, multiple articles have recently emerged and are discussed. Moreover, we also discuss the evidence suggesting that regulatory T cells might limit the magnitude of effector responses, which can have either a positive or negative result, depending on the context of animal and human disease. In addition, the issue of plasticity is discussed because plasticity in regulatory T cells can result in the loss of their protective function in some microenvironments during disease. Lastly, the manipulation of regulatory T cells is discussed in assessing the possibility of their use as a treatment in the future. PMID:26945003

  5. Animal Models Used to Study Superantigen-Mediated Diseases.

    PubMed

    Brosnahan, Amanda J

    2016-01-01

    Superantigens secreted by Staphylococcus aureus and Streptococcus pyogenes interact with the T-cell receptor and major histocompatibility class II molecules on antigen-presenting cells to elicit a massive cytokine release and activation of T cells in higher numbers than that seen with ordinary antigens. Because of this unique ability, superantigens have been implicated as etiological agents for many different types of diseases, including toxic shock syndrome, infective endocarditis, pneumonia, and inflammatory skin diseases. This review covers the main animal models that have been developed in order to identify the roles of superantigens in human disease. PMID:26676033

  6. Climate change and animal diseases: making the case for adaptation.

    PubMed

    Cáceres, Sigfrido Burgos

    2012-12-01

    The exponential expansion of the human population has led to overexploitation of resources and overproduction of items that have caused a series of potentially devastating effects, including ocean acidification, ozone depletion, biodiversity loss, the spread of invasive flora and fauna and climatic changes - along with the emergence of new diseases in animals and humans. Climate change occurs as a result of imbalances between incoming and outgoing radiation in the atmosphere. This process generates heat. As concentrations of atmospheric gases reach record levels, global temperatures are expected to increase significantly. The hydrologic cycle will be altered, since warmer air can retain more moisture than cooler air. This means that some geographic areas will have more rainfall, whereas others have more drought and severe weather. The potential consequences of significant and permanent climatic changes are altered patterns of diseases in animal and human populations, including the emergence of new disease syndromes and changes in the prevalence of existing diseases. A wider geographic distribution of known vectors and the recruitment of new strains to the vector pool could result in infections spreading to more and potentially new species of hosts. If these predictions turn out to be accurate, there will be a need for policymakers to consider alternatives, such as adaptation. This review explores the linkages between climate change and animal diseases, and examines interrelated issues that arise from altered biological dynamics. Its aim is to consider various risks and vulnerabilities and to make the case for policies favoring adaptation. PMID:23253166

  7. Prion and prion-like diseases in animals.

    PubMed

    Aguilar-Calvo, Patricia; García, Consolación; Espinosa, Juan Carlos; Andreoletti, Olivier; Torres, Juan María

    2015-09-01

    Transmissible spongiform encephalopaties (TSEs) are fatal neurodegenerative diseases characterized by the aggregation and accumulation of the misfolded prion protein in the brain. Other proteins such as β-amyloid, tau or Serum Amyloid-A (SAA) seem to share with prions some aspects of their pathogenic mechanism; causing a variety of so called prion-like diseases in humans and/or animals such as Alzheimer's, Parkinson's, Huntington's, Type II diabetes mellitus or amyloidosis. The question remains whether these misfolding proteins have the ability to self-propagate and transmit in a similar manner to prions. In this review, we describe the prion and prion-like diseases affecting animals as well as the recent findings suggesting the prion-like transmissibility of certain non-prion proteins. PMID:25444937

  8. Impact of foreign animal diseases at the industry level.

    PubMed

    Sundberg, P

    2006-01-01

    Industry-level impacts of highly contagious foreign animal diseases can be extensive and disruptive. These impacts are the sum of disease effects on the separate economic units that comprise the input supply, production, processing and marketing system of that industry. These industry-level effects would not include government costs or costs associated with disrupted travel or tourism or general economic activity. Direct impacts are those that are related to production and result in direct economic consequences for animal protein producers. Indirect impacts are consequences that include loss of trade, market and consumer confidence, among others. While it is prudent for governments to identify the costs of effective surveillance and prevention, these costs are often very small compared to the total cost of response and recovery associated with a disease outbreak. It is important that the effectiveness of those prevention programmes not be compromised because of other short-term priorities perceived to be more urgent. PMID:20429073

  9. Impairments of Synaptic Plasticity in Aged Animals and in Animal Models of Alzheimer's Disease

    PubMed Central

    Balietti, Marta; Tamagnini, Francesco; Fattoretti, Patrizia; Burattini, Costanza; Casoli, Tiziana; Platano, Daniela; Lattanzio, Fabrizia

    2012-01-01

    Abstract Aging is associated with a gradual decline in cognitive functions, and more dramatic cognitive impairments occur in patients affected by Alzheimer's disease (AD). Electrophysiological and molecular studies performed in aged animals and in animal models of AD have shown that cognitive decline is associated with significant modifications in synaptic plasticity (i.e., activity-dependent changes in synaptic strength) and have elucidated some of the cellular mechanisms underlying this process. Morphological studies have revealed a correlation between the quality of memory performance and the extent of structural changes of synaptic contacts occurring during memory consolidation. We briefly review recent experimental evidence here. PMID:22533439

  10. Animal models of skin disease for drug discovery

    PubMed Central

    Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; De Melo, Wanessa CMA; Huang, Ying-Ying; Yin, Rui; Rakkiyappan, Chandran; Kumar, Raj; Otufowora, Ayodeji; Nyame, Theodore; Hamblin, Michael R

    2013-01-01

    Introduction Discovery of novel drugs, treatments, and testing of consumer products in the field of dermatology is a multi-billion dollar business. Due to the distressing nature of many dermatological diseases, and the enormous consumer demand for products to reverse the effects of skin photodamage, aging, and hair loss, this is a very active field. Areas covered In this paper, we will cover the use of animal models that have been reported to recapitulate to a greater or lesser extent the features of human dermatological disease. There has been a remarkable increase in the number and variety of transgenic mouse models in recent years, and the basic strategy for constructing them is outlined. Expert opinion Inflammatory and autoimmune skin diseases are all represented by a range of mouse models both transgenic and normal. Skin cancer is mainly studied in mice and fish. Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia. PMID:23293893

  11. High-impact animal health research conducted at the USDA's National Animal Disease Center.

    PubMed

    Bannantine, John P; Olsen, Steven C; Kehrli, Marcus E; Stanton, Thad B; Casas, Eduardo; Whipple, Diana L; Zuelke, Kurt A

    2013-08-30

    Commissioned by President Dwight Eisenhower in 1958 and opened with a dedication ceremony in December 1961, the USDA, Agricultural Research Service (ARS), National Animal Disease Center (NADC) celebrated its 50-year anniversary in November 2011. Over these 50 years, the NADC established itself among the world's premier animal health research centers. Its historic mission has been to conduct basic and applied research on selected endemic diseases of economic importance to the U.S. livestock and poultry industries. Research from NADC has impacted control or management efforts on nearly every major animal disease in the United States since 1961. For example, diagnostic tests and vaccines developed by NADC scientists to detect and prevent hog cholera were integral in the ultimate eradication of this costly swine disease from the U.S. Most major veterinary vaccines for critical diseases such as brucellosis and leptospirosis in cattle, porcine respiratory and reproductive syndrome (PRRS), porcine parvovirus and influenza in swine had their research origins or were developed and tested at the NADC. Additional discoveries made by NADC scientists have also resulted in the development of a nutritional approach and feed additives to prevent milk fever in transition dairy cattle. More recently, NADC's archive of historic swine influenza viruses combined with an established critical mass of influenza research expertise enabled NADC researchers to lead an effective national research response to the pandemic associated with the novel 2009 H1N1 influenza virus. This review commemorates some of the key animal health contributions in NADC's first 50 years, recaps the newly completed modernization of the center into new facilities, and offers highlights of the ongoing research that will define NADC's mission going forward. PMID:23642415

  12. The Cambridge MRI database for animal models of Huntington disease.

    PubMed

    Sawiak, Stephen J; Morton, A Jennifer

    2016-01-01

    We describe the Cambridge animal brain magnetic resonance imaging repository comprising 400 datasets to date from mouse models of Huntington disease. The data include raw images as well as segmented grey and white matter images with maps of cortical thickness. All images and phenotypic data for each subject are freely-available without restriction from (http://www.dspace.cam.ac.uk/handle/1810/243361/). Software and anatomical population templates optimised for animal brain analysis with MRI are also available from this site. PMID:25941090

  13. High-Throughput Microfluidic Method To Study Biofilm Formation and Host-Pathogen Interactions in Pathogenic Escherichia coli

    PubMed Central

    Tremblay, Yannick D. N.; Vogeleer, Philippe; Jacques, Mario

    2015-01-01

    Biofilm formation and host-pathogen interactions are frequently studied using multiwell plates; however, these closed systems lack shear force, which is present at several sites in the host, such as the intestinal and urinary tracts. Recently, microfluidic systems that incorporate shear force and very small volumes have been developed to provide cell biology models that resemble in vivo conditions. Therefore, the objective of this study was to determine if the BioFlux 200 microfluidic system could be used to study host-pathogen interactions and biofilm formation by pathogenic Escherichia coli. Strains of various pathotypes were selected to establish the growth conditions for the formation of biofilms in the BioFlux 200 system on abiotic (glass) or biotic (eukaryotic-cell) surfaces. Biofilm formation on glass was observed for the majority of strains when they were grown in M9 medium at 30°C but not in RPMI medium at 37°C. In contrast, HRT-18 cell monolayers enhanced binding and, in most cases, biofilm formation by pathogenic E. coli in RPMI medium at 37°C. As a proof of principle, the biofilm-forming ability of a diffusely adherent E. coli mutant strain lacking AIDA-I, a known mediator of attachment, was assessed in our models. In contrast to the parental strain, which formed a strong biofilm, the mutant formed a thin biofilm on glass or isolated clusters on HRT-18 monolayers. In conclusion, we describe a microfluidic method for high-throughput screening that could be used to identify novel factors involved in E. coli biofilm formation and host-pathogen interactions under shear force. PMID:25681176

  14. Phenotypic Variation Is Almost Entirely Independent of the Host-Pathogen Relationship in Clinical Isolates of S. aureus

    PubMed Central

    Land, Adrian D.; Hogan, Patrick; Fritz, Stephanie; Levin, Petra Anne

    2015-01-01

    Background A key feature of Staphylococcus aureus biology is its ability to switch from an apparently benign colonizer of ~30% of the population to a cutaneous pathogen, to a deadly invasive pathogen. Little is known about the mechanisms driving this transition or the propensity of different S. aureus strains to engender different types of host-pathogen interactions. At the same time, significant weight has been given to the role of specific in vitro phenotypes in S. aureus virulence. Biofilm formation, hemolysis and pigment formation have all been associated with virulence in mice. Design To determine if there is a correlation between in vitro phenotype and the three types of host-pathogen relationships commonly exhibited by S. aureus in the context of its natural human host, we assayed 300 clinical isolates for phenotypes implicated in virulence including hemolysis, sensitivity to autolysis, and biofilm formation. For comparative purposes, we also assayed phenotype in 9 domesticated S. aureus strains routinely used for analysis of virulence determinants in laboratory settings. Results Strikingly, the clinical strains exhibited significant phenotypic uniformity in each of the assays evaluated in this study. One exception was a small, but significant, correlation between an increased propensity for biofilm formation and isolation from skin and soft tissue infections (SSTIs). In contrast, we observed a high degree of phenotypic variation between common laboratory strains that exhibit virulence in mouse models. These data suggest the existence of significant evolutionary pressure on the S. aureus genome and highlight a role for host factors as a strong determinant of the host-pathogen relationship. In addition, the high degree of variation between laboratory strains emphasizes the need for caution when applying data obtained in one lab strain to the analysis of another. PMID:26098551

  15. Animal models in the drug discovery pipeline for Alzheimer's disease

    PubMed Central

    Van Dam, Debby; De Deyn, Peter Paul

    2011-01-01

    With increasing feasibility of predicting conversion of mild cognitive impairment to dementia based on biomarker profiling, the urgent need for efficacious disease-modifying compounds has become even more critical. Despite intensive research, underlying pathophysiological mechanisms remain insufficiently documented for purposeful target discovery. Translational research based on valid animal models may aid in alleviating some of the unmet needs in the current Alzheimer's disease pharmaceutical market, which includes disease-modification, increased efficacy and safety, reduction of the number of treatment unresponsive patients and patient compliance. The development and phenotyping of animal models is indeed essential in Alzheimer's disease-related research as valid models enable the appraisal of early pathological processes – which are often not accessible in patients, and subsequent target discovery and evaluation. This review paper summarizes and critically evaluates currently available animal models, and discusses their value to the Alzheimer drug discovery pipeline. Models dealt with include spontaneous models in various species, including senescence-accelerated mice, chemical and lesion-induced rodent models, and genetically modified models developed in Drosophila melanogaster, Caenorhabditis elegans, Danio rerio and rodents. Although highly valid animal models exist, none of the currently available models recapitulates all aspects of human Alzheimer's disease, and one should always be aware of the potential dangers of uncritical extrapolating from model organisms to a human condition that takes decades to develop and mainly involves higher cognitive functions. 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:21371009

  16. Effects of Pesticide Mixtures on Host-Pathogen Dynamics of the Amphibian Chytrid Fungus

    PubMed Central

    Buck, Julia C.; Hua, Jessica; Brogan, William R.; Dang, Trang D.; Urbina, Jenny; Bendis, Randall J.; Stoler, Aaron B.; Blaustein, Andrew R.; Relyea, Rick A.

    2015-01-01

    Anthropogenic and natural stressors often interact to affect organisms. Amphibian populations are undergoing unprecedented declines and extinctions with pesticides and emerging infectious diseases implicated as causal factors. Although these factors often co-occur, their effects on amphibians are usually examined in isolation. We hypothesized that exposure of larval and metamorphic amphibians to ecologically relevant concentrations of pesticide mixtures would increase their post-metamorphic susceptibility to the fungus Batrachochytrium dendrobatidis (Bd), a pathogen that has contributed to amphibian population declines worldwide. We exposed five anuran species (Pacific treefrog, Pseudacris regilla; spring peeper, Pseudacris crucifer; Cascades frog, Rana cascadae; northern leopard frog, Lithobates pipiens; and western toad, Anaxyrus boreas) from three families to mixtures of four common insecticides (chlorpyrifos, carbaryl, permethrin, and endosulfan) or herbicides (glyphosate, acetochlor, atrazine, and 2,4-D) or a control treatment, either as tadpoles or as newly metamorphic individuals (metamorphs). Subsequently, we exposed animals to Bd or a control inoculate after metamorphosis and compared survival and Bd load. Bd exposure significantly increased mortality in Pacific treefrogs, spring peepers, and western toads, but not in Cascades frogs or northern leopard frogs. However, the effects of pesticide exposure on mortality were negligible, regardless of the timing of exposure. Bd load varied considerably across species; Pacific treefrogs, spring peepers, and western toads had the highest loads, whereas Cascades frogs and northern leopard frogs had the lowest loads. The influence of pesticide exposure on Bd load depended on the amphibian species, timing of pesticide exposure, and the particular pesticide treatment. Our results suggest that exposure to realistic pesticide concentrations has minimal effects on Bd-induced mortality, but can alter Bd load. This result

  17. Common and emerging infectious diseases in the animal shelter.

    PubMed

    Pesavento, P A; Murphy, B G

    2014-03-01

    The beneficial role that animal shelters play is unquestionable. An estimated 3 to 4 million animals are cared for or placed in homes each year, and most shelters promote public health and support responsible pet ownership. It is, nonetheless, inevitable that shelters are prime examples of anthropogenic biological instability: even well-run shelters often house transient, displaced, and mixed populations of animals. Many of these animals have received minimal to no prior health care, and some have a history of scavenging or predation to survive. Overcrowding and poor shelter conditions further magnify these inherent risks to create individual, intraspecies, and interspecies stress and provide an environment conducive to exposure to numerous potentially collaborative pathogens. All of these factors can contribute to the evolution and emergence of new pathogens or to alterations in virulence of endemic pathogens. While it is not possible to effectively anticipate the timing or the pathogen type in emergence events, their sites of origin are less enigmatic, and pathologists and diagnosticians who work with sheltered animal populations have recognized several such events in the past decade. This article first considers the contribution of the shelter environment to canine and feline disease. This is followed by summaries of recent research on the pathogenesis of common shelter pathogens, as well as research that has led to the discovery of novel or emerging diseases and the methods that are used for their diagnosis and discovery. For the infectious agents that commonly affect sheltered dogs and cats, including canine distemper virus, canine influenza virus, Streptococcus spp, parvoviruses, feline herpesvirus, feline caliciviruses, and feline infectious peritonitis virus, we present familiar as well as newly recognized lesions associated with infection. Preliminary studies on recently discovered viruses like canine circovirus, canine bocavirus, and feline norovirus

  18. Proteomics in Animal Models of Alzheimer's and Parkinson's Diseases

    PubMed Central

    Sowell, Renã A.; Owen, Joshua B.; Butterfield, D. Allan

    2009-01-01

    The risk of developing neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD) diseases increases with age. AD and PD are the two most common neurodegenerative diseases that currently affect millions of persons within the United States population. While many clues about the mechanisms of these disorders have been uncovered, to date, the molecular mechanisms associated with the cause of these diseases are not completely understood. Furthermore, there are no available cures or preventative treatments for either disorder. Animal models of AD and PD, though not perfect, offer a means to gain knowledge of the basic biochemistry associated with these disorders and with drug efficacy. The field of proteomics which focuses on identifying the dynamic nature of the protein content expressed within a particular cell, tissue, or organism, has provided many insights into these disturbing disorders. Proteomic studies have revealed many pathways that are associated with disease pathogenesis and that may lead to the development of potential therapeutic targets. This review provides a discussion of key findings from AD and PD proteomics-based studies in various animal models of disease. PMID:18703168

  19. Mobile technologies for disease surveillance in humans and animals.

    PubMed

    Mwabukusi, Mpoki; Karimuribo, Esron D; Rweyemamu, Mark M; Beda, Eric

    2014-01-01

    A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara), Burundi (Muyinga) and Zambia (Kazungula and Sesheke). Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server-client model. Smart phones running the Android operating system (minimum required version: Android 1.6), and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing timely response in rural remote areas of

  20. Infectious disease in animal metapopulations: the importance of environmental transmission.

    PubMed

    Park, Andrew W

    2012-07-01

    Motivated by an array of infectious diseases that threaten wildlife populations, a simple metapopulation model (subpopulations connected by animal movement) is developed, which allows for both movement-based and environmental transmission. The model demonstrates that for a range of plausible parameterizations of environmental transmission, increased movement rate of animals between discrete habitats can lead to a decrease in the overall proportion of sites that are occupied. This can limit the ability of the rescue effect to ensure locally extinct populations become recolonized and can drive metapopulations down in size so that extinction by mechanisms other than disease may become more likely. It further highlights that, in the context of environmental transmission, the environmental persistence time of pathogens and the probability of acquiring infection by environmental transmission can affect host metapopulations both qualitatively and quantitatively. Additional spillover sources of infection from alternate reservoir hosts are also included in the model and a synthesis of all three types of transmission, acting alone or in combination, is performed revealing that movement-based transmission is the only necessary condition for a decline in the proportion of occupied sites with increasing movement rate, but that the presence of other types of transmission can reverse this qualitative result. By including the previously neglected role of environmental transmission, this work contributes to the general discussion of when dispersal by wild animals is beneficial or detrimental to populations experiencing infectious disease. PMID:22957148

  1. Infectious disease in animal metapopulations: the importance of environmental transmission

    PubMed Central

    Park, Andrew W

    2012-01-01

    Motivated by an array of infectious diseases that threaten wildlife populations, a simple metapopulation model (subpopulations connected by animal movement) is developed, which allows for both movement-based and environmental transmission. The model demonstrates that for a range of plausible parameterizations of environmental transmission, increased movement rate of animals between discrete habitats can lead to a decrease in the overall proportion of sites that are occupied. This can limit the ability of the rescue effect to ensure locally extinct populations become recolonized and can drive metapopulations down in size so that extinction by mechanisms other than disease may become more likely. It further highlights that, in the context of environmental transmission, the environmental persistence time of pathogens and the probability of acquiring infection by environmental transmission can affect host metapopulations both qualitatively and quantitatively. Additional spillover sources of infection from alternate reservoir hosts are also included in the model and a synthesis of all three types of transmission, acting alone or in combination, is performed revealing that movement-based transmission is the only necessary condition for a decline in the proportion of occupied sites with increasing movement rate, but that the presence of other types of transmission can reverse this qualitative result. By including the previously neglected role of environmental transmission, this work contributes to the general discussion of when dispersal by wild animals is beneficial or detrimental to populations experiencing infectious disease. PMID:22957148

  2. The enduring importance of animal modelsin understanding periodontal disease

    PubMed Central

    Hajishengallis, George; Lamont, Richard J; Graves, Dana T

    2015-01-01

    Whereas no single animal model can reproduce the complexity of periodontitis, different aspects of the disease can be addressed by distinct models. Despite their limitations, animal models are essential for testing the biological significance of in vitro findings and for establishing cause-and-effect relationships relevant to clinical observations, which are typically correlative. We provide evidence that animal-based studies have generated a durable framework for dissecting the mechanistic basis of periodontitis. These studies have solidified the etiologic role of bacteria in initiating the inflammatory response that leads to periodontal bone loss and have identified key mediators (IL-1, TNF, prostaglandins, complement, RANKL) that induce inflammatory breakdown. Moreover, animal studies suggest that dysbiosis, rather than individual bacterial species, are important in initiating periodontal bone loss and have introduced the concept that organisms previously considered commensals can play important roles as accessory pathogens or pathobionts. These studies have also provided insight as to how systemic conditions, such as diabetes or leukocyte adhesion deficiency, contribute to tissue destruction. In addition, animal studies have identified and been useful in testing therapeutic targets. PMID:25574929

  3. Animal behavioral assessments in current research of Parkinson's disease.

    PubMed

    Asakawa, Tetsuya; Fang, Huan; Sugiyama, Kenji; Nozaki, Takao; Hong, Zhen; Yang, Yilin; Hua, Fei; Ding, Guanghong; Chao, Dongman; Fenoy, Albert J; Villarreal, Sebastian J; Onoe, Hirotaka; Suzuki, Katsuaki; Mori, Norio; Namba, Hiroki; Xia, Ying

    2016-06-01

    Parkinson's disease (PD), a neurodegenerative disorder, is traditionally classified as a movement disorder. Patients typically suffer from many motor dysfunctions. Presently, clinicians and scientists recognize that many non-motor symptoms are associated with PD. There is an increasing interest in both motor and non-motor symptoms in clinical studies on PD patients and laboratory research on animal models that imitate the pathophysiologic features and symptoms of PD patients. Therefore, appropriate behavioral assessments are extremely crucial for correctly understanding the mechanisms of PD and accurately evaluating the efficacy and safety of novel therapies. This article systematically reviews the behavioral assessments, for both motor and non-motor symptoms, in various animal models involved in current PD research. We addressed the strengths and weaknesses of these behavioral tests and their appropriate applications. Moreover, we discussed potential mechanisms behind these behavioral tests and cautioned readers against potential experimental bias. Since most of the behavioral assessments currently used for non-motor symptoms are not particularly designed for animals with PD, it is of the utmost importance to greatly improve experimental design and evaluation in PD research with animal models. Indeed, it is essential to develop specific assessments for non-motor symptoms in PD animals based on their characteristics. We concluded with a prospective view for behavioral assessments with real-time assessment with mobile internet and wearable device in future PD research. PMID:27026638

  4. A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection

    SciTech Connect

    Kaiser, Brooke LD; Li, Jie; Sanford, James A.; Kim, Young-Mo; Kronewitter, Scott R.; Jones, Marcus B.; Peterson, Christine; Peterson, Scott N.; Frank, Bryan C.; Purvine, Samuel O.; Brown, Joseph N.; Metz, Thomas O.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2013-06-26

    The potential for commensal microorganisms indigenous to a host (the ‘microbiome’ or ‘microbiota’) to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics “systems” approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e.g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alteration of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimurium’s lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.

  5. A Novel Mechanism of Host-Pathogen Interaction through sRNA in Bacterial Outer Membrane Vesicles

    PubMed Central

    Koeppen, Katja; Hampton, Thomas H.; Jarek, Michael; Scharfe, Maren; Gerber, Scott A.; Mielcarz, Daniel W.; Demers, Elora G.; Dolben, Emily L.; Hammond, John H.; Hogan, Deborah A.; Stanton, Bruce A.

    2016-01-01

    Bacterial outer membrane vesicle (OMV)-mediated delivery of proteins to host cells is an important mechanism of host-pathogen communication. Emerging evidence suggests that OMVs contain differentially packaged short RNAs (sRNAs) with the potential to target host mRNA function and/or stability. In this study, we used RNA-Seq to characterize differentially packaged sRNAs in Pseudomonas aeruginosa OMVs, and to show transfer of OMV sRNAs to human airway cells. We selected one sRNA for further study based on its stable secondary structure and predicted mRNA targets. Our candidate sRNA (sRNA52320), a fragment of a P. aeruginosa methionine tRNA, was abundant in OMVs and reduced LPS-induced as well as OMV-induced IL-8 secretion by cultured primary human airway epithelial cells. We also showed that sRNA52320 attenuated OMV-induced KC cytokine secretion and neutrophil infiltration in mouse lung. Collectively, these findings are consistent with the hypothesis that sRNA52320 in OMVs is a novel mechanism of host-pathogen interaction whereby P. aeruginosa reduces the host immune response. PMID:27295279

  6. Ovarian autoimmune disease: clinical concepts and animal models

    PubMed Central

    Warren, Bryce D; Kinsey, William K; McGinnis, Lynda K; Christenson, Lane K; Jasti, Susmita; Stevens, Anne M; Petroff, Brian K; Petroff, Margaret G

    2014-01-01

    The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models. PMID:25327908

  7. 9 CFR 71.3 - Interstate movement of diseased animals and poultry generally prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and at... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Interstate movement of diseased animals and poultry generally prohibited. 71.3 Section 71.3 Animals and Animal Products ANIMAL AND...

  8. 9 CFR 71.3 - Interstate movement of diseased animals and poultry generally prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and on... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Interstate movement of diseased animals and poultry generally prohibited. 71.3 Section 71.3 Animals and Animal Products ANIMAL AND...

  9. Animal models for the evolution of thrombotic disease.

    PubMed

    Dodds, W J

    1987-01-01

    Naturally occurring hemorrhagic and thrombotic diseases of animals closely parallel their human counterparts. While such models may be particularly useful in studying the pathogenesis of human disease, it is usually more realistic to depend upon experimentally induced disease models. The species selected for use is therefore of major importance in providing meaningful extrapolation to humans, as are the experimental design and type of procedure (in vitro, ex vivo, in vivo). Regardless of the test system used when in vitro procedures are employed, these must be translated eventually to the in vivo situation. Information about the normal aging process of different species is important here and should influence selection of the species and test system. The ideal situation may not be feasible or pertain because of cost, availability, size, and investigator familiarity, or lack thereof, with the most suitable species or model. PMID:3326489

  10. Identifying the Achilles heel of multi-host pathogens: the concept of keystone ‘host’ species illustrated by Mycobacterium ulcerans transmission

    NASA Astrophysics Data System (ADS)

    Roche, Benjamin; Benbow, M. Eric; Merritt, Richard; Kimbirauskas, Ryan; McIntosh, Mollie; Small, Pamela L. C.; Williamson, Heather; Guégan, Jean-François

    2013-12-01

    Pathogens that use multiple host species are an increasing public health issue due to their complex transmission, which makes them difficult to mitigate. Here, we explore the possibility of using networks of ecological interactions among potential host species to identify the particular disease-source species to target to break down transmission of such pathogens. We fit a mathematical model on prevalence data of Mycobacterium ulcerans in western Africa and we show that removing the most abundant taxa for this category of pathogen is not an optimal strategy to decrease the transmission of the mycobacterium within aquatic ecosystems. On the contrary, we reveal that the removal of some taxa, especially Oligochaeta worms, can clearly reduce rates of pathogen transmission, and these should be considered as keystone organisms for its transmission because they lead to a substantial reduction in pathogen prevalence regardless of the network topology. Besides their potential application for the understanding of M. ulcerans ecology, we discuss how networks of species interactions can modulate transmission of multi-host pathogens.

  11. Congenital ureteropelvic junction obstruction: human disease and animal models

    PubMed Central

    Klein, Julie; Gonzalez, Julien; Miravete, Mathieu; Caubet, Cécile; Chaaya, Rana; Decramer, Stéphane; Bandin, Flavio; Bascands, Jean-Loup; Buffin-Meyer, Bénédicte; Schanstra, Joost P

    2011-01-01

    Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology and function and describe the molecular mechanisms involved in the progression of the lesions, including inflammation, proliferation/apoptosis, renin–angiotensin system activation and fibrosis, based on both human and animal data. Also we propose that during obstructive nephropathy, hydrodynamic modifications are early inducers of the tubular lesions, which are potentially at the origin of the pathology. Finally, an important observation in animal models is that relief of obstruction during kidney development has important effects on renal function later in adult life. A major short-coming is the absence of data on the impact of UPJ obstruction on long-term adult renal function to elucidate whether these animal data are also valid in humans. PMID:20681980

  12. Genetic Animal Models of Parkinson’s Disease

    PubMed Central

    Dawson, Ted M.; Ko, Han Seok; Dawson, Valina L.

    2010-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by the degeneration of dopamine (DA) and non-DA neurons, the almost uniform presence of Lewy bodies, and motor deficits. Although the majority of PD is sporadic, specific genetic defects in rare familial cases have provided unique insights into the pathogenesis of PD. Through the creation of animal and cellular models of mutations in LRRK2 and α-synuclein, which are linked to autosomal dominant PD, and mutations in parkin, DJ-1, and PINK1, which are responsible for autosomal recessive PD, insight into the molecular mechanisms of this disorder are leading to new ideas about the pathogenesis of PD. In this review, we discuss the animal models for these genetic causes of PD, their limitations and value. Moreover, we discuss future directions and potential strategies for optimization of the genetic models. PMID:20547124

  13. Circadian Disruption and Metabolic Disease: Findings from Animal Models

    PubMed Central

    Arble, Deanna Marie; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-01-01

    Social opportunities and work demands have caused humans to become increasingly active during the late evening hours, leading to a shift from the predominantly diurnal lifestyle of our ancestors to a more nocturnal one. This voluntarily decision to stay awake long into the evening hours leads to circadian disruption at the system, tissue, and cellular levels. These derangements are in turn associated with clinical impairments in metabolic processes and physiology. The use of animal models for circadian disruption provides an important opportunity to determine mechanisms by which disorganization in the circadian system can lead to metabolic dysfunction in response to genetic, environmental, and behavioral perturbations. Here we review recent key animal studies involving circadian disruption and discuss the possible translational implications of these studies for human health and particularly for the development of metabolic disease. PMID:21112026

  14. Genetics of host-pathogen interactions in the wheat-Stagonospora nodorum pathosystem

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stagonospora nodorum causes the disease Stagonospora nodorum blotch (SNB) in wheat. S. nodorum produces numerous host-selective toxins (HSTs), all of which interact with dominant host sensitivity genes to cause disease. These host-toxin interactions are mirror images of classical gene-for-gene inter...

  15. Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

    PubMed Central

    Muller, Jean; Laporte, Jocelyn

    2012-01-01

    Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1) a common molecular pathway underlying these different neuromuscular diseases, and (2) tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches. PMID:22496665

  16. Animal genomics and infectious disease resistance in poultry.

    PubMed

    Smith, J; Gheyas, A; Burt, D W

    2016-04-01

    Avian pathogens are responsible for major costs to society, both in terms of huge economic losses to the poultry industry and their implications for human health. The health and welfare of millions of birds is under continued threat from many infectious diseases, some of which are increasing in virulence and thus becoming harder to control, such as Marek's disease virus and avian influenza viruses. The current era in animal genomics has seen huge developments in both technologies and resources, which means that researchers have never been in a better position to investigate the genetics of disease resistance and determine the underlying genes/mutations which make birds susceptible or resistant to infection. Avian genomics has reached a point where the biological mechanisms of infectious diseases can be investigated and understood in poultry and other avian species. Knowledge of genes conferring disease resistance can be used in selective breeding programmes or to develop vaccines which help to control the effects of these pathogens, which have such a major impact on birds and humans alike. PMID:27217172

  17. Back to the metal age: battle for metals at the host-pathogen interface during urinary tract infection.

    PubMed

    Subashchandrabose, Sargurunathan; Mobley, Harry L T

    2015-06-01

    Urinary tract infection (UTI) represents one of the most common bacterial infections in humans and uropathogenic E. coli (UPEC) is the major causative agent of UTI in people. Research on UPEC and other bacterial pathogens causing UTI has now identified the critical role of metal transport systems in the pathogenesis of UTI. Here we review the major effectors of metal transport in bacteria and host proteins that impair metal acquisition by bacterial pathogens. In particular, we describe the studies that identified iron, zinc and nickel import and copper export as key virulence and fitness determinants during UTI. Various metal transport systems and mechanisms that govern the expression of metal transport systems are also presented here. Specific examples from UPEC and other uropathogens, when available, are presented to depict the battle for metals at the host-pathogen interface during UTI. PMID:25677827

  18. 9 CFR 80.3 - Movement of domestic animals that are positive to an official Johne's disease test.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... positive to an official Johne's disease test. 80.3 Section 80.3 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.3 Movement of domestic animals that are positive to an official Johne's disease test. (a) Movement of domestic animals...

  19. 9 CFR 80.3 - Movement of domestic animals that are positive to an official Johne's disease test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... positive to an official Johne's disease test. 80.3 Section 80.3 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.3 Movement of domestic animals that are positive to an official Johne's disease test. (a) Movement of domestic animals...

  20. 9 CFR 80.4 - Segregation of animals positive to an official Johne's disease test during interstate movement.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... official Johne's disease test during interstate movement. 80.4 Section 80.4 Animals and Animal Products... ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.4 Segregation of animals positive to an official Johne's disease test during interstate movement. Animals that are...

  1. 9 CFR 80.3 - Movement of domestic animals that are positive to an official Johne's disease test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... positive to an official Johne's disease test. 80.3 Section 80.3 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.3 Movement of domestic animals that are positive to an official Johne's disease test. (a) Movement of domestic animals...

  2. 9 CFR 80.4 - Segregation of animals positive to an official Johne's disease test during interstate movement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... official Johne's disease test during interstate movement. 80.4 Section 80.4 Animals and Animal Products... ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.4 Segregation of animals positive to an official Johne's disease test during interstate movement. Animals that are...

  3. 9 CFR 80.3 - Movement of domestic animals that are positive to an official Johne's disease test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... positive to an official Johne's disease test. 80.3 Section 80.3 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.3 Movement of domestic animals that are positive to an official Johne's disease test. (a) Movement of domestic animals...

  4. 9 CFR 80.4 - Segregation of animals positive to an official Johne's disease test during interstate movement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... official Johne's disease test during interstate movement. 80.4 Section 80.4 Animals and Animal Products... ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.4 Segregation of animals positive to an official Johne's disease test during interstate movement. Animals that are...

  5. 9 CFR 80.3 - Movement of domestic animals that are positive to an official Johne's disease test.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... positive to an official Johne's disease test. 80.3 Section 80.3 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.3 Movement of domestic animals that are positive to an official Johne's disease test. (a) Movement of domestic animals...

  6. 9 CFR 80.4 - Segregation of animals positive to an official Johne's disease test during interstate movement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... official Johne's disease test during interstate movement. 80.4 Section 80.4 Animals and Animal Products... ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.4 Segregation of animals positive to an official Johne's disease test during interstate movement. Animals that are...

  7. 9 CFR 80.4 - Segregation of animals positive to an official Johne's disease test during interstate movement.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... official Johne's disease test during interstate movement. 80.4 Section 80.4 Animals and Animal Products... ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS JOHNE'S DISEASE IN DOMESTIC ANIMALS § 80.4 Segregation of animals positive to an official Johne's disease test during interstate movement. Animals that are...

  8. Animal Models of Pulmonary Hypertension: Matching Disease Mechanisms to Etiology of the Human Disease

    PubMed Central

    Colvin, Kelley L.; Yeager, Michael E.

    2015-01-01

    Recently a great deal of progress has been made in our understanding of pulmonary hypertension (PH). Research from the past 30 years has resulted in newer treatments that provide symptomatic improvements and delayed disease progression. Unfortunately, the cure for patients with this lethal syndrome remains stubbornly elusive. With the relative explosion of scientific literature regarding PH, confusion has arisen regarding animal models of the disease and their correlation to the human condition. This short review uniquely focuses on the clear and present need to better correlate mechanistic insights from existing and emerging animal models of PH to specific etiologies and histopathologies of human PH. A better understanding of the pathologic processes in various animal models and how they relate to the human disease should accelerate the development of newer and more efficacious therapies. PMID:25705569

  9. Verticillium Wilt in Potato: Host-Pathogen Interactions and Breeding for Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Verticillium wilt (VW) is a widespread disease that causes consistent yield losses in many potato growing regions worldwide. In the U.S., it is mainly caused by the soil-borne fungal pathogen Verticillium dahliae. Microsclerotia can survive in the soil for many years. When they germinate and infe...

  10. Genetic mechanisms of host-pathogen interactions for charcoal rot in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean is a leading agronomic crop and it is contributing to food and agricultural security with expanding production in diverse regions around the world. Although soybean is attacked by several diseases and pests, and progress has been made in understanding and managing some of these pathogens and...

  11. New evidence that Deformed Wing Virus and Black Queen Cell Virus are Multi-host pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The host-range breadth of pathogens can have important consequences for pathogens’ long term evolution and virulence, and play critical roles in the emergence and spread of the new diseases. Black queen cell virus (BQCV) and Deformed wing virus (DWV) are the two most common and prevalent viruses in...

  12. Economic analysis of animal disease outbreaks--BSE and Bluetongue disease as examples.

    PubMed

    Gethmann, Jörn; Probst, Carolina; Sauter-Louis, Carola; Conraths, Franz Josef

    2015-01-01

    Although there is a long tradition of research on animal disease control, economic evaluation of control measures is rather limited in veterinary medicine. This may, on the one hand, be due to the different types of costs and refunds and the different people and organizations bearing them, such as animal holders, county, region, state or European Union, but it may also be due to the fact that economic analyses are both complex and time consuming. Only recently attention has turned towards economic analysis in animal disease control. Examples include situations, when decisions between different control measures must be taken, especially if alternatives to culling or compulsory vaccination are under discussion. To determine an optimal combination of control measures (strategy), a cost-benefit analysis should be performed. It is not necessary to take decisions only based on the financial impact, but it becomes possible to take economic aspects into account. To this end, the costs caused by the animal disease and the adopted control measures must be assessed. This article presents a brief overview of the methodological approaches used to retrospectively analyse the economic impact of two particular relevant diseases in Germany in the last few years: Blue-tongue disease (BT) and Bovine Spongiform Encephalopathy (BSE). PMID:26697715

  13. Role of import and export regulatory animal health officials in international control and surveillance for animal diseases.

    PubMed

    Bokma, Bob H

    2006-10-01

    The challenges to those who regulate the import and export of animals and animal products are escalating, due to the evolving nature of animal and human disease agents. The diseases and agents of interest may include low pathogenic avian influenza, bluetongue, bovine spongiform encephalopathy, and foot-and-mouth disease. Fear of an incursion of an unknown or incompletely understood threat can significantly limit risk tolerance. The fear may be that an incursion will affect export trade or tourism. An incomplete knowledge of the animal health situation in the exporting country, due to insufficient surveillance for the disease agent of concern, may limit the application of science in import decisions. In addition, the disease agent may be inappropriately considered exotic if it has not been described. As a result, excessive safeguards for disease agents that do not present any new threat may be employed. To confront these challenges, we are striving toward transparency in international reporting. Moreover, regulatory import decisions exceeding the recommendations of the Terrestrial Animal Health Code and the Aquatic Animal Health Code of the World Organization for Animal Health must be fair and science-based. PMID:17135497

  14. Host-pathogen interplay in the respiratory environment of Cystic Fibrosis

    PubMed Central

    Hurley, Bryan P.; Bragonzi, Alessandra

    2015-01-01

    Significant advances have been made in the understanding of disease progression in cystic fibrosis (CF), revealing a complex interplay between host and pathogenic organisms. The diverse CF microbiota within the airway activates an aberrant immune response that is ineffective in clearing infection. An appreciation of how the CF host immune system interacts with these organisms is crucial to understanding the pathogenesis of CF pulmonary disease. Here we discuss the microbial complexity present in the lungs of individuals with CF, review emerging concepts of innate and adaptive immune responses to pathogens that chronically inhabit the CF lung, and discuss therapies that target the aberrant inflammatory response that characterizes CF. A greater understanding of the underlying mechanisms will shed light on pathogenesis and guide more targeted therapies in the future that serve to reduce infection, minimize lung pathology, and improve the quality of life for patients with CF. PMID:25800687

  15. Vestibular animal models: contributions to understanding physiology and disease.

    PubMed

    Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E

    2016-04-01

    Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more "exotic" species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies. PMID:27083880

  16. Transgenic animals modelling polyamine metabolism-related diseases.

    PubMed

    Alhonen, Leena; Uimari, Anne; Pietilä, Marko; Hyvönen, Mervi T; Pirinen, Eija; Keinänen, Tuomo A

    2009-01-01

    Cloning of genes related to polyamine metabolism has enabled the generation of genetically modified mice and rats overproducing or devoid of proteins encoded by these genes. Our first transgenic mice overexpressing ODC (ornithine decarboxylase) were generated in 1991 and, thereafter, most genes involved in polyamine metabolism have been used for overproduction of the respective proteins, either ubiquitously or in a tissue-specific fashion in transgenic animals. Phenotypic characterization of these animals has revealed a multitude of changes, many of which could not have been predicted based on the previous knowledge of the polyamine requirements and functions. Animals that overexpress the genes encoding the inducible key enzymes of biosynthesis and catabolism, ODC and SSAT (spermidine/spermine N1-acetyltransferase) respectively, appear to possess the most pleiotropic phenotypes. Mice overexpressing ODC have particularly been used as cancer research models. Transgenic mice and rats with enhanced polyamine catabolism have revealed an association of rapidly depleted polyamine pools and accelerated metabolic cycle with development of acute pancreatitis and a fatless phenotype respectively. The latter phenotype with improved glucose tolerance and insulin sensitivity is useful in uncovering the mechanisms that lead to the opposite phenotype in humans, Type 2 diabetes. Disruption of the ODC or AdoMetDC [AdoMet (S-adenosylmethionine) decarboxylase] gene is not compatible with mouse embryogenesis, whereas mice with a disrupted SSAT gene are viable and show no harmful phenotypic changes, except insulin resistance at a late age. Ultimately, the mice with genetically altered polyamine metabolism can be used to develop targeted means to treat human disease conditions that they relevantly model. PMID:20095974

  17. Large Animal Models and New Therapies for Glycogen Storage Disease

    PubMed Central

    Brooks, Elizabeth D.

    2015-01-01

    Glycogen storage diseases (GSD), a unique category of inherited metabolic disorders, were first described early in the 20th century. Since then, the biochemical and genetic bases of these disorders have been determined, and an increasing number of animal models for GSD have become available. At least 7 large mammalian models have been developed for laboratory research on GSDs. These models have facilitated the development of new therapies, including gene therapy, which are undergoing clinical translation. For example, gene therapy prolonged survival and prevented hypoglycemia during fasting for greater than one year in dogs with GSD type Ia, and the need for periodic re-administration to maintain efficacy was demonstrated in that dog model. The further development of gene therapy could provide curative therapy for patients with GSD and other inherited metabolic disorders. PMID:25224826

  18. Large animal models and new therapies for glycogen storage disease.

    PubMed

    Brooks, Elizabeth D; Koeberl, Dwight D

    2015-05-01

    Glycogen storage diseases (GSD), a unique category of inherited metabolic disorders, were first described early in the twentieth century. Since then, the biochemical and genetic bases of these disorders have been determined, and an increasing number of animal models for GSD have become available. At least seven large mammalian models have been developed for laboratory research on GSDs. These models have facilitated the development of new therapies, including gene therapy, which are undergoing clinical translation. For example, gene therapy prolonged survival and prevented hypoglycemia during fasting for greater than one year in dogs with GSD type Ia, and the need for periodic re-administration to maintain efficacy was demonstrated in that dog model. The further development of gene therapy could provide curative therapy for patients with GSD and other inherited metabolic disorders. PMID:25224826

  19. Neuroprotective Transcription Factors in Animal Models of Parkinson Disease

    PubMed Central

    Blaudin de Thé, François-Xavier; Rekaik, Hocine; Prochiantz, Alain; Fuchs, Julia; Joshi, Rajiv L.

    2016-01-01

    A number of transcription factors, including En1/2, Foxa1/2, Lmx1a/b, Nurr1, Otx2, and Pitx3, with key roles in midbrain dopaminergic (mDA) neuron development, also regulate adult mDA neuron survival and physiology. Mouse models with targeted disruption of some of these genes display several features reminiscent of Parkinson disease (PD), in particular the selective and progressive loss of mDA neurons in the substantia nigra pars compacta (SNpc). The characterization of these animal models has provided valuable insights into various mechanisms of PD pathogenesis. Therefore, the dissection of the mechanisms and survival signalling pathways engaged by these transcription factors to protect mDA neuron from degeneration can suggest novel therapeutic strategies. The work on En1/2-mediated neuroprotection also highlights the potential of protein transduction technology for neuroprotective approaches in PD. PMID:26881122

  20. Recombinant Ranaviruses for Studying Evolution of Host-Pathogen Interactions in Ectothermic Vertebrates.

    PubMed

    Robert, Jacques; Jancovich, James K

    2016-01-01

    Ranaviruses (Iridoviridae) are large DNA viruses that are causing emerging infectious diseases at an alarming rate in both wild and captive cold blood vertebrate species all over the world. Although the general biology of these viruses that presents some similarities with poxvirus is characterized, many aspects of their replication cycles, host cell interactions and evolution still remain largely unclear, especially in vivo. Over several years, strategies to generate site-specific ranavirus recombinant, either expressing fluorescent reporter genes or deficient for particular viral genes, have been developed. We review here these strategies, the main ranavirus recombinants characterized and their usefulness for in vitro and in vivo studies. PMID:27399758

  1. Imaging of cerebrovascular pathology in animal models of Alzheimer's disease

    PubMed Central

    Klohs, Jan; Rudin, Markus; Shimshek, Derya R.; Beckmann, Nicolau

    2014-01-01

    In Alzheimer's disease (AD), vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ) deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature. PMID:24659966

  2. Animal models of beryllium-induced lung disease

    SciTech Connect

    Finch, G.L.; Hoover, M.D.; Hahn, F.F.

    1996-10-01

    The Inhalation Toxicology Research Institute (ITRI) is conducting research to improve the understanding of chronic beryllium disease (CBD) and beryllium-induced lung cancer. Initial animal studies examined beagle dogs that inhaled BeO calcined at either 500 or 1000{degrees}C. At similar lung burdens, the 500{degrees}C BeO induced more severe and extensive granulomatous pneumonia, lymphocytic infiltration into the lung, and positive Be-specific lymphocyte proliferative responses in vitro than the 1000{degrees}C BeO. However, the progressive nature of human CBD was not duplicated. More recently, Strains A/J and C3H/HeJ mice were exposed to Be metal by inhalation. This produced a marked granulomatous pneumonia, diffuse infiltrates, and multifocal aggregates of interstitial lymphocytes with a pronounced T helper component and pulmonary in situ lymphocyte proliferation. With respect to lung cancer, at a mean lung burden as low as 17 pg Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving {ge}1 year on study. Substantial tumor multiplicity was found, but K-ras and p53 gene mutations were virtually absent. In mice, however, a lung burden of approximately 60 {mu}g ({approximately}300 {mu}g Be/g lung) caused only a slight increase in crude lung tumor incidence and multiplicity over controls in strain A/J mice and no elevated incidence in strain C3H mice. Taken together, this research program constitutes a coordinated effort to understand beryllium-induced lung disease in experimental animal models. 47 refs., 1 fig., 3 tabs.

  3. Thrombotic microangiopathies: from animal models to human disease and cure.

    PubMed

    Caprioli, Jessica; Remuzzi, Giuseppe; Noris, Marina

    2011-01-01

    Thrombotic microangiopathies are a group of microvascular disorders, with reduced organ perfusion and hemolytic anemia. The two most relevant conditions characterized by thrombotic microangiopathic anemia (TMA) are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). In TTP, systemic microvascular aggregation of platelets causes ischemia in the brain and other organs. In HUS, platelet-fibrin thrombi predominantly occlude the renal circulation. TTP can be inherited due to deficiencies in the activity of von Willebrand factor cleaving protease (ADAMTS13) or acquired due to the presence of autoantibodies directed against ADAMTS13. The majority of HUS cases are secondary to infections by strains of Escherichia coli that produce Shiga-like toxins (Stx-HUS), while about 5- 10% of all cases are classified as atypical HUS (aHUS). Genetically derived impaired regulation of the complement system is associated with aHUS. Infusion or the exchange of fresh frozen plasma have ameliorated the prognosis of TMA; however, no specific therapies aimed at preventing or limiting the microangiopathic process have been proven to affect the course of TMA. Large mammals, small animal models, knockout and transgenic mouse models of TTP and both Stx-HUS and aHUS have been developed and have provided outstanding contributions to nearly all areas of TMA research. A better understanding of the key clinical features of the diseases and of the importance of genetic and/or environmental factors involved in the pathogenesis of the diseases have been obtained. These animal models have also allowed the set up of protocols aimed at ameliorating the clinical approach to patients and for the development of new drugs and vaccines. PMID:21252531

  4. Peste des Petits Ruminants, the next eradicated animal disease?

    PubMed

    Albina, Emmanuel; Kwiatek, Olivier; Minet, Cécile; Lancelot, Renaud; Servan de Almeida, Renata; Libeau, Geneviève

    2013-07-26

    Peste des Petits Ruminants (PPR) is a widespread viral disease caused by a Morbillivirus (Paramyxoviridae). There is a single serotype of PPR virus, but four distinct genetic lineages. Morbidity and mortality are high when occurring in naive sheep and goats populations. Cattle and African buffaloes (Syncerus caffer) are asymptomatically infected. Other wild ruminants and camels may express clinical signs and mortality. PPR has recently spread in southern and northern Africa, and in central and far-east Asia. More than one billion sheep and goats worldwide are at risk. PPR is also present in Europe through western Turkey. Because of its clinical incidence and the restrictions on animal movements, PPR is a disease of major economic importance. A live attenuated vaccine was developed in the 1980s, and has been widely used in sheep and goats. Current researches aim (i) to make it more thermotolerant for use in countries with limited cold chain, and (ii) to add a DIVA mark to shorten and reduce the cost of final eradication. Rinderpest virus-another Morbillivirus-was the first animal virus to be eradicated from Earth. PPRV has been proposed as the next candidate. Considering its wide distribution and its multiple target host species which have an intense mobility, it will be a long process that cannot exclusively rely on mass vaccination. PPR specific epidemiological features and socio-economic considerations will also have to be taken into account, and sustained international, coordinated, and funded strategy based on a regional approach of PPR control will be the guarantee toward success. PMID:23313537

  5. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis.

    PubMed

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-01-01

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia's gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

  6. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis

    PubMed Central

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-01-01

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia’s gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

  7. A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks.

    PubMed

    Wu, Chia-Chou; Chen, Bor-Sen

    2016-01-01

    Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications. PMID:26881892

  8. Host-pathogen interactions in malaria: cross-kingdom signaling and mitochondrial regulation.

    PubMed

    Luckhart, Shirley; Pakpour, Nazzy; Giulivi, Cecilia

    2015-10-01

    Malaria parasite-host interactions are complex and have confounded available drugs and the development of vaccines. Further, we now appreciate that interventions for malaria elimination and eradication must include therapeutics with intrinsic transmission blocking activity to treat the patient and prevent disease spread. Studies over the past 15 years have revealed significant conservation in the response to infection in mosquito and human hosts. More recently, we have recognized that conserved cell signaling cascades in mosquitoes and humans dictate infection outcome through the regulation of mitochondrial function and biogenesis, which feed back to host immunity, basic intermediary metabolism, and stress responses. These responses - reflected clearly in the primeval insect host - provide fertile ground for innovative strategies for both treatment and transmission blocking. PMID:26210301

  9. Human enteroids as an ex-vivo model of host-pathogen interactions in the gastrointestinal tract.

    PubMed

    Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C; Ettayebi, Khalil; Blutt, Sarah E; Hyser, Joseph M; Zeng, Xi-Lei; Crawford, Sue E; Broughman, James R; Estes, Mary K; Donowitz, Mark

    2014-09-01

    Currently, 9 out of 10 experimental drugs fail in clinical studies. This has caused a 40% plunge in the number of drugs approved by the US Food and Drug Administration (FDA) since 2005. It has been suggested that the mechanistic differences between human diseases modeled in animals (mostly rodents) and the pathophysiology of human diseases might be one of the critical factors that contribute to drug failure in clinical trials. Rapid progress in the field of human stem cell technology has allowed the in-vitro recreation of human tissue that should complement and expand upon the limitations of cell and animal models currently used to study human diseases and drug toxicity. Recent success in the identification and isolation of human intestinal epithelial stem cells (Lgr5(+)) from the small intestine and colon has led to culture of functional intestinal epithelial units termed organoids or enteroids. Intestinal enteroids are comprised of all four types of normal epithelial cells and develop a crypt-villus differentiation axis. They demonstrate major intestinal physiologic functions, including Na(+) absorption and Cl(-) secretion. This review discusses the recent progress in establishing human enteroids as a model of infectious diarrheal diseases such as cholera, rotavirus, and enterohemorrhagic Escherichia coli, and use of the enteroids to determine ways to correct the diarrhea-induced ion transport abnormalities via drug therapy. PMID:24719375

  10. [Hypothesis of evolutionary origin of several human and animal diseases].

    PubMed

    Pertseva, M N; Shpakov, A O

    2010-01-01

    Studies of our Laboratory in the field of molecular and evolutionary endocrinology have allowed us to put forward a hypothesis about evolutionary origin of endocrine and other diseases of human and animals. This hypothesis is considered using a model of hormonal signal systems. It is based on the concept formulated by the authors about molecular defects in hormonal signal systems as the key causes of endocrine diseases; on evolutionary conservatism of hormonal signal systems, which stems logically from the authors' concept of the prokaryotic origin and endosymbiotic appearance in the course of evolution of chemosignal systems in the higher eukaryotes; from the fact that the process of formation of hormonal signal systems with participation of endosymbiosis including the horizontal transfer of genes is accompanied by transfer not only of normal, but also of the defected genetic material. There are considered examples of the principal possibility of transfer of defected genes between bacteria and eukaryotic organisms. Analysis of the current literature allows suggesting inheritance of pathogenic factors from evolutionary ancestors in the lineage prokaryotes--lower eukaryotes--higher eukaryotes. PMID:20583590

  11. Staphylococcus aureus Aggregation and Coagulation Mechanisms, and Their Function in Host-Pathogen Interactions.

    PubMed

    Crosby, H A; Kwiecinski, J; Horswill, A R

    2016-01-01

    The human commensal bacterium Staphylococcus aureus can cause a wide range of infections ranging from skin and soft tissue infections to invasive diseases like septicemia, endocarditis, and pneumonia. Muticellular organization almost certainly contributes to S. aureus pathogenesis mechanisms. While there has been considerable focus on biofilm formation and its role in colonizing prosthetic joints and indwelling devices, less attention has been paid to nonsurface-attached group behavior like aggregation and clumping. S. aureus is unique in its ability to coagulate blood, and it also produces multiple fibrinogen-binding proteins that facilitate clumping. Formation of clumps, which are large, tightly packed groups of cells held together by fibrin(ogen), has been demonstrated to be important for S. aureus virulence and immune evasion. Clumps of cells are able to avoid detection by the host's immune system due to a fibrin(ogen) coat that acts as a shield, and the size of the clumps facilitates evasion of phagocytosis. In addition, clumping could be an important early step in establishing infections that involve tight clusters of cells embedded in host matrix proteins, such as soft tissue abscesses and endocarditis. In this review, we discuss clumping mechanisms and regulation, as well as what is known about how clumping contributes to immune evasion. PMID:27565579

  12. Complex host-pathogen coevolution in the Apterostigma fungus-growing ant-microbe symbiosis

    PubMed Central

    Gerardo, Nicole M; Mueller, Ulrich G; Currie, Cameron R

    2006-01-01

    Background The fungus-growing ant-microbe symbiosis consists of coevolving microbial mutualists and pathogens. The diverse fungal lineages that these ants cultivate are attacked by parasitic microfungi of the genus Escovopsis. Previous molecular analyses have demonstrated strong phylogenetic congruence between the ants, the ants-cultivated fungi and the garden pathogen Escovopsis at ancient phylogenetic levels, suggesting coevolution of these symbionts. However, few studies have explored cophylogenetic patterns between these symbionts at the recent phylogenetic levels necessary to address whether these parasites are occasionally switching to novel hosts or whether they are diversifying with their hosts as a consequence of long-term host fidelity. Results Here, a more extensive phylogenetic analysis of Escovopsis lineages infecting the gardens of Apterostigma ants demonstrates that these pathogens display patterns of phylogenetic congruence with their fungal hosts. Particular clades of Escovopsis track particular clades of cultivated fungi, and closely-related Escovopsis generally infect closely-related hosts. Discordance between host and parasite phylogenies, however, provides the first evidence for occasional host-switches or acquisitions of novel infections from the environment. Conclusion The fungus-growing ant-microbe association has a complex coevolutionary history. Though there is clear evidence of host-specificity on the part of diverse Escovopsis lineages, these pathogens have switched occasionally to novel host fungi. Such switching is likely to have profound effects on how these host and parasites adapt to one another over evolutionary time scales and may impact how disease spreads over ecological time scales. PMID:17083733

  13. A call to order at the spirochaetal host-pathogen interface.

    PubMed

    Zückert, Wolfram R

    2013-07-01

    As the Lyme disease spirochaete Borrelia burgdorferi shuttles back and forth between arthropod vector and vertebrate host, it encounters vastly different and hostile environments. Major mechanisms contributing to the success of this pathogen throughout this complex transmission cycle are phase and antigenic variation of abundant and serotype-defining surface lipoproteins. These peripherally membrane-anchored virulence factors mediate niche-specific interactions with vector/host factors and protect the spirochaete from the perils of the mammalian immune response. In this issue of Molecular Microbiology, Tilly, Bestor and Rosa redefine the roles of two lipoproteins, OspC and VlsE, during mammalian infection. Using a variety of promoter fusions in combination with a sensitive in vivo 'use it or lose it' gene complementation assay, the authors demonstrate that proper sequential expression of OspC followed by VlsE indeed matters. A previously suggested general functional redundancy between these and other lipoproteins is shown to be limited and dependent on an immunodeficient experimental setting that is arguably of diminished ecological relevance. These data reinforce the notion that OspC plays a unique role during initial infection while the antigenically variant VlsE proteins allow for persistence in the mammalian host. PMID:23750784

  14. A Call to Order at the Spirochetal Host-Pathogen Interface

    PubMed Central

    Zückert, Wolfram R.

    2013-01-01

    Summary As the Lyme disease spirochete Borrelia burgdorferi shuttles back and forth between arthropod vector and vertebrate host, it encounters vastly different and hostile environments. Major mechanisms contributing to the success of this pathogen throughout this complex transmission cycle are phase and antigenic variation of abundant and serotype-defining surface lipoproteins. These peripherally membrane-anchored virulence factors mediate niche-specific interactions with vector/host factors and protect the spirochete from the perils of the mammalian immune response. In this issue of Molecular Microbiology, Tilly, Bestor and Rosa redefine the roles of two lipoproteins, OspC and VlsE, during mammalian infection. Using a variety of promoter fusions in combination with a sensitive in vivo “use it or lose it” gene complementation assay, the authors demonstrate that proper sequential expression of OspC followed by VlsE indeed matters. A previously suggested general functional redundancy between these and other lipoproteins is shown to be limited and dependent on an immunodeficient experimental setting that is arguably of diminished ecological relevance. These data reinforce the notion that OspC plays a unique role during initial infection while the antigenically variant VlsE proteins allow for persistence in the mammalian host. PMID:23750784

  15. Automated Image Analysis of the Host-Pathogen Interaction between Phagocytes and Aspergillus fumigatus

    PubMed Central

    Guthke, Reinhard; Brakhage, Axel A.; Figge, Marc Thilo

    2011-01-01

    Aspergillus fumigatus is a ubiquitous airborne fungus and opportunistic human pathogen. In immunocompromised hosts, the fungus can cause life-threatening diseases like invasive pulmonary aspergillosis. Since the incidence of fungal systemic infections drastically increased over the last years, it is a major goal to investigate the pathobiology of A. fumigatus and in particular the interactions of A. fumigatus conidia with immune cells. Many of these studies include the activity of immune effector cells, in particular of macrophages, when they are confronted with conidia of A. fumigus wild-type and mutant strains. Here, we report the development of an automated analysis of confocal laser scanning microscopy images from macrophages coincubated with different A. fumigatus strains. At present, microscopy images are often analysed manually, including cell counting and determination of interrelations between cells, which is very time consuming and error-prone. Automation of this process overcomes these disadvantages and standardises the analysis, which is a prerequisite for further systems biological studies including mathematical modeling of the infection process. For this purpose, the cells in our experimental setup were differentially stained and monitored by confocal laser scanning microscopy. To perform the image analysis in an automatic fashion, we developed a ruleset that is generally applicable to phagocytosis assays and in the present case was processed by the software Definiens Developer XD. As a result of a complete image analysis we obtained features such as size, shape, number of cells and cell-cell contacts. The analysis reported here, reveals that different mutants of A. fumigatus have a major influence on the ability of macrophages to adhere and to phagocytose the respective conidia. In particular, we observe that the phagocytosis ratio and the aggregation behaviour of pksP mutant compared to wild-type conidia are both significantly increased. PMID

  16. "Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions"

    PubMed Central

    2012-01-01

    Background Leptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira. Pathogenic leptospires have the ability to survive and disseminate to multiple organs after penetrating the host. Leptospires were shown to express surface proteins that interact with the extracellular matrix (ECM) and to plasminogen (PLG). This study examined the interaction of two putative leptospiral proteins with laminin, collagen Type I, collagen Type IV, cellular fibronectin, plasma fibronectin, PLG, factor H and C4bp. Results We show that two leptospiral proteins encoded by LIC11834 and LIC12253 genes interact with laminin in a dose - dependent and saturable mode, with dissociation equilibrium constants (KD) of 367.5 and 415.4 nM, respectively. These proteins were named Lsa33 and Lsa25 (Leptospiral surface adhesin) for LIC11834 and LIC12253, respectively. Metaperiodate - treated laminin reduced Lsa25 - laminin interaction, suggesting that sugar moieties of this ligand participate in this interaction. The Lsa33 is also PLG - binding receptor, with a KD of 23.53 nM, capable of generating plasmin in the presence of an activator. Although in a weak manner, both proteins interact with C4bp, a regulator of complement classical route. In silico analysis together with proteinase K and immunoflorescence data suggest that these proteins might be surface exposed. Moreover, the recombinant proteins partially inhibited leptospiral adherence to immobilized laminin and PLG. Conclusions We believe that these multifunctional proteins have the potential to participate in the interaction of leptospires to hosts by mediating adhesion and by helping the bacteria to escape the immune system and to overcome tissue barriers. To our knowledge, Lsa33 is the first leptospiral protein described to date with the capability of binding laminin, PLG and C4bp in vitro. PMID:22463075

  17. Bright Fluorescent Streptococcus pneumoniae for Live-Cell Imaging of Host-Pathogen Interactions

    PubMed Central

    Kjos, Morten; Aprianto, Rieza; Fernandes, Vitor E.; Andrew, Peter W.; van Strijp, Jos A. G.; Nijland, Reindert

    2014-01-01

    Streptococcus pneumoniae is a common nasopharyngeal resident in healthy people but, at the same time, one of the major causes of infectious diseases such as pneumonia, meningitis, and sepsis. The shift from commensal to pathogen and its interaction with host cells are poorly understood. One of the major limitations for research on pneumococcal-host interactions is the lack of suitable tools for live-cell imaging. To address this issue, we developed a generally applicable strategy to create genetically stable, highly fluorescent bacteria. Our strategy relies on fusing superfolder green fluorescent protein (GFP) or a far-red fluorescent protein (RFP) to the abundant histone-like protein HlpA. Due to efficient translation and limited cellular diffusion of these fusions, the cells are 25-fold brighter than those of the currently best available imaging S. pneumoniae strain. These novel bright pneumococcal strains are fully virulent, and the GFP reporter can be used for in situ imaging in mouse tissue. We used our reporter strains to study the effect of the polysaccharide capsule, a major pneumococcal virulence factor, on different stages of infection. By dual-color live-cell imaging experiments, we show that unencapsulated pneumococci adhere significantly better to human lung epithelial cells than encapsulated strains, in line with previous data obtained by classical approaches. We also confirm with live-cell imaging that the capsule protects pneumococci from neutrophil phagocytosis, demonstrating the versatility and usability of our reporters. The described imaging tools will pave the way for live-cell imaging of pneumococcal infection and help further understanding of the mechanisms of pneumococcal pathogenesis. PMID:25512311

  18. Comparative analysis of Leishmania exoproteomes: implication for host-pathogen interactions.

    PubMed

    Peysselon, Franck; Launay, Guillaume; Lisacek, Frédérique; Duclos, Bertrand; Ricard-Blum, Sylvie

    2013-12-01

    Leishmaniasis is a vector-borne disease caused by the protozoa Leishmania. We have analyzed and compared the sequences of three experimental exoproteomes of Leishmania promastigotes from different species to determine their specific features and to identify new candidate proteins involved in interactions of Leishmania with the host. The exoproteomes differ from the proteomes by a decrease in the average molecular weight per protein, in disordered amino acid residues and in basic proteins. The exoproteome of the visceral species is significantly enriched in sites predicted to be phosphorylated as well as in features frequently associated with molecular interactions (intrinsic disorder, number of disordered binding regions per protein, interaction and/or trafficking motifs) compared to the other species. The visceral species might thus have a larger interaction repertoire with the host than the other species. Less than 10% of the exoproteomes contain heparin-binding and RGD sequences, and ~30% the host targeting signal RXLXE/D/Q. These latter proteins might thus be exported inside the host cell during the intracellular stage of the infection. Furthermore we have identified nine protein families conserved in the three exoproteomes with specific combinations of Pfam domains and selected eleven proteins containing at least three interaction and/or trafficking motifs including two splicing factors, phosphomannomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, the paraflagellar rod protein-1D and a putative helicase. Their role in host-Leishmania interactions warrants further investigation but the putative ATP-dependent DEAD/H RNA helicase, which contains numerous interaction motifs, a host targeting signal and two disordered regions, is a very promising candidate. PMID:24096101

  19. Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.

    PubMed

    Lee, Soo Chan; Li, Alicia; Calo, Silvia; Inoue, Makoto; Tonthat, Nam K; Bain, Judith M; Louw, Johanna; Shinohara, Mari L; Erwig, Lars P; Schumacher, Maria A; Ko, Dennis C; Heitman, Joseph

    2015-09-01

    Calcineurin plays essential roles in virulence and growth of pathogenic fungi and is a target of the natural products FK506 and Cyclosporine A. In the pathogenic mucoralean fungus Mucor circinelloides, calcineurin mutation or inhibition confers a yeast-locked phenotype indicating that calcineurin governs the dimorphic transition. Genetic analysis in this study reveals that two calcineurin A catalytic subunits (out of three) are functionally diverged. Homology modeling illustrates modes of resistance resulting from amino substitutions in the interface between each calcineurin subunit and the inhibitory drugs. In addition, we show how the dimorphic transition orchestrated by calcineurin programs different outcomes during host-pathogen interactions. For example, when macrophages phagocytose Mucor yeast, subsequent phagosomal maturation occurs, indicating host cells respond appropriately to control the pathogen. On the other hand, upon phagocytosis of spores, macrophages fail to form mature phagosomes. Cytokine production from immune cells differs following exposure to yeast versus spores (which germinate into hyphae). Thus, the morphogenic transition can be targeted as an efficient treatment option against Mucor infection. In addition, genetic analysis (including gene disruption and mutational studies) further strengthens the understanding of calcineurin and provides a foundation to develop antifungal agents targeting calcineurin to deploy against Mucor and other pathogenic fungi. PMID:26010100

  20. Genome-Wide Host-Pathogen Interaction Unveiled by Transcriptomic Response of Diamondback Moth to Fungal Infection.

    PubMed

    Chu, Zhen-Jian; Wang, Yu-Jun; Ying, Sheng-Hua; Wang, Xiao-Wei; Feng, Ming-Guang

    2016-01-01

    Genome-wide insight into insect pest response to the infection of Beauveria bassiana (fungal insect pathogen) is critical for genetic improvement of fungal insecticides but has been poorly explored. We constructed three pairs of transcriptomes of Plutella xylostella larvae at 24, 36 and 48 hours post treatment of infection (hptI) and of control (hptC) for insight into the host-pathogen interaction at genomic level. There were 2143, 3200 and 2967 host genes differentially expressed at 24, 36 and 48 hptI/hptC respectively. These infection-responsive genes (~15% of the host genome) were enriched in various immune processes, such as complement and coagulation cascades, protein digestion and absorption, and drug metabolism-cytochrome P450. Fungal penetration into cuticle and host defense reaction began at 24 hptI, followed by most intensive host immune response at 36 hptI and attenuated immunity at 48 hptI. Contrastingly, 44% of fungal genes were differentially expressed in the infection course and enriched in several biological processes, such as antioxidant activity, peroxidase activity and proteolysis. There were 1636 fungal genes co-expressed during 24-48 hptI, including 116 encoding putative secretion proteins. Our results provide novel insights into the insect-pathogen interaction and help to probe molecular mechanisms involved in the fungal infection to the global pest. PMID:27043942

  1. Genome-Wide Host-Pathogen Interaction Unveiled by Transcriptomic Response of Diamondback Moth to Fungal Infection

    PubMed Central

    Chu, Zhen-Jian; Wang, Yu-Jun; Ying, Sheng-Hua; Wang, Xiao-Wei; Feng, Ming-Guang

    2016-01-01

    Genome-wide insight into insect pest response to the infection of Beauveria bassiana (fungal insect pathogen) is critical for genetic improvement of fungal insecticides but has been poorly explored. We constructed three pairs of transcriptomes of Plutella xylostella larvae at 24, 36 and 48 hours post treatment of infection (hptI) and of control (hptC) for insight into the host-pathogen interaction at genomic level. There were 2143, 3200 and 2967 host genes differentially expressed at 24, 36 and 48 hptI/hptC respectively. These infection-responsive genes (~15% of the host genome) were enriched in various immune processes, such as complement and coagulation cascades, protein digestion and absorption, and drug metabolism-cytochrome P450. Fungal penetration into cuticle and host defense reaction began at 24 hptI, followed by most intensive host immune response at 36 hptI and attenuated immunity at 48 hptI. Contrastingly, 44% of fungal genes were differentially expressed in the infection course and enriched in several biological processes, such as antioxidant activity, peroxidase activity and proteolysis. There were 1636 fungal genes co-expressed during 24–48 hptI, including 116 encoding putative secretion proteins. Our results provide novel insights into the insect-pathogen interaction and help to probe molecular mechanisms involved in the fungal infection to the global pest. PMID:27043942

  2. NIH Researchers Find Resveratrol Helps Protect against Cardiovascular Disease in Animal Study

    MedlinePlus

    ... find Resveratrol helps protect against cardiovascular disease in animal study June 3, 2014 Resveratrol, a compound found ... translatable to humans. Multiple studies on resveratrol in animal models, however, have presented ample evidence to support ...

  3. Polyphasic study of Chryseobacterium strains isolated from diseased aquatic animals.

    PubMed

    Bernardet, J F; Vancanneyt, M; Matte-Tailliez, O; Grisez, L; Tailliez, P; Bizet, C; Nowakowski, M; Kerouault, B; Swings, J

    2005-09-01

    Members of most Chryseobacterium species occur in aquatic environments or food products, while strains of some other species are pathogenic to humans and animals. A collection of 52 Chryseobacterium sp. strains isolated from diseased fish, one frog isolate and 22 reference strains were included in a polyphasic taxonomy study. Fourteen clusters of strains were delineated following the comparison of whole-cell protein profiles. Most of these clusters were confirmed when the phenotypic and RAPD profiles and the 16S rRNA gene sequences were compared. Fatty acid composition helped differentiate the Chryseobacterium strains from members of related genera. None of the fish isolates could be allocated to the two species previously reported from fish but two isolates belonged to C. joostei, while the frog isolate was identified as Elizabethkingia meningoseptica, a human pathogen previously included in the genus Chryseobacterium. Three clusters grouping from 3 to 13 isolates will probably constitute the core of new Chryseobacterium species but all other isolates occupied separate or uncertain positions in the genus. This study further demonstrated the overall high similarity displayed by most Chryseobacterium strains whatever the technique used and the resulting difficulty in delineating new species in the genus. Members of this bacterial group should be considered potential emergent pathogens in various fish and frog species, farming conditions and geographical areas. PMID:16156122

  4. Early synaptic dysfunction in Parkinson's disease: Insights from animal models.

    PubMed

    Schirinzi, Tommaso; Madeo, Graziella; Martella, Giuseppina; Maltese, Marta; Picconi, Barbara; Calabresi, Paolo; Pisani, Antonio

    2016-06-01

    The appearance of motor manifestations in Parkinson's disease (PD) is invariably linked to degeneration of nigral dopaminergic neurons of the substantia nigra pars compacta. Traditional views on PD neuropathology have been grounded in the assumption that the prime event of neurodegeneration involves neuronal cell bodies with the accumulation of metabolic products. However, this view has recently been challenged by both clinical and experimental evidence. Neuropathological studies in human brain samples and both in vivo and in vitro models support the hypothesis that nigrostriatal synapses may indeed be affected at the earliest stages of the neurodegenerative process. The mechanisms leading to either structural or functional synaptic dysfunction are starting to be elucidated and include dysregulation of axonal transport, impairment of the exocytosis and endocytosis machinery, altered intracellular trafficking, and loss of corticostriatal synaptic plasticity. The aim of this review is to try to integrate different lines of evidence from both pathogenic and genetic animal models that, to different extents, suggest that early synaptic impairment may represent the key event in PD pathogenesis. Understanding the molecular and cellular events underlying such synaptopathy is a fundamental step toward developing specific biomarkers of early dopaminergic dysfunction and, more importantly, designing novel therapies targeting the synaptic apparatus of selective, vulnerable synapses. © 2016 International Parkinson and Movement Disorder Society. PMID:27193205

  5. The role of the OIE in information exchange and the control of animal diseases, including zoonoses.

    PubMed

    Poissonnier, C; Teissier, M

    2013-08-01

    The growing importance of animal diseases and zoonoses at a time when globalisation has increased movements of people, animals and animal products across the globe, has strengthened the role of the World Organisation for Animal Health (OIE) in animal disease control. The OIE's mandate since its establishment in 1924 has been to facilitate the exchange of public health, animal health and scientific information, and to further the control and eradication of animal diseases. The OIE is recognised by the World Trade Organization Agreement on the Application of Sanitary and Phytosanitary Measures as the international reference organisation for animal diseases and zoonoses, especially for standard setting. The standards adopted by the World Assembly of OIE Delegates on veterinary public health and animal health feature in the OlE Terrestrial Animal Health Code, the Aquatic Animal Health Code, the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals and the Manual of Diagnostic Tests for Aquatic Animals. The OlE is also a reference organisation for the exchange of public and animal health information among Member Countries, through an information, reporting and warning system based on transparent communication between countries. The OIE provides scientific expertise in ascertaining countries' status with regard to notifiable diseases, enabling them to secure official recognition as being free from foot and mouth disease, African horse sickness, contagious bovine pleuropneumonia and bovine spongiform encephalopathy. The OIE also contributes its scientific expertise to stakeholder training on the surveillance and control of animal diseases and zoonoses and to the evaluation of the performance of Veterinary Services, to enhance theirwork asthe cornerstone of their countries' disease control efforts. PMID:24547648

  6. Host-Pathogen Interactions

    PubMed Central

    Ayers, Arthur R.; Ebel, Jürgen; Finelli, Frederick; Berger, Nathan; Albersheim, Peter

    1976-01-01

    Resistance of soybean (Glycine max L.) seedlings to Phytophthora megasperma var. sojae (Pms) is in part due to the accumulation in infected tissue of a compound which is toxic to Pms. The accumulation of this compound, a phytoalexin called glyceollin, is triggered by infection, but it can also be triggered by molecules, “elicitors,” present in cultures of Pms. The ability of the Pms elicitor to stimulate phytoalexin accumulation in soybean tissues has been used as the basis for biological assays of elicitor activity. Two bioassays were developed and characterized in this study of the Pms elicitor. These bioassays use the cotyledons and the hypocotyls of soybean seedlings. The cotyledon assay was used to characterize the extracellular Pms elicitor. This elicitor was isolated from Pms cultures and purified by ion exchange and molecular sieving chromatography. The extracellular Pms elicitor was determined to be a predominantly 3-linked glucan, which is similar in composition and structure to a polysaccharide component of Pms mycelial walls. PMID:16659565

  7. Host-Pathogen Interactions

    PubMed Central

    Cline, Kenneth; Wade, Mark; Albersheim, Peter

    1978-01-01

    A β-glucan isolated from the mycelial walls of Phytophthora megasperma var. sojae and a glucan purified from yeast extract stimulate the accumulation of phytoalexins in red kidney bean, Phaseolus vulgaris, and stimulate the accumulation of the phytoalexin, rishitin, in potato tubers, Solanum tuberosum. These glucans have previously been shown to be potent elicitors of glyceollin accumulation in soybean, Glycine max. Treatment of kidney bean cotyledons with the glucan elicitors resulted in the accumulation of at least five fungistatic compounds. These compounds migrate during thin layer chromatography identically to the fungistatic compounds which accumulate in kidney beans which have been inoculated with Colletotrichum lindemuthianum, a fungal pathogen of kidney beans. Potatoes accumulate as much as 29 micrograms of rishitin per gram fresh weight following exposure to the glucan from Phytophthora megasperma var. sojae and as much as 19.5 micrograms of rishitin per gram fresh weight following exposure to yeast glucan. Potatoes accumulated 28 micrograms of rishitin per gram fresh weight following inoculation with live Phytophthora megasperma var. sojae. ImagesFig. 1 PMID:16660638

  8. Host-Pathogen Interactions

    PubMed Central

    Anderson-Prouty, Anne J.; Albersheim, Peter

    1975-01-01

    A polysaccharide from the fungal pathogen Colletotrichum lindemuthianum causes browning and phytoalexin production when applied to the cut surfaces of bean (Phaseolus vulgaris) cotyledons and hypocotyls. The application of an amount of polysaccharide equivalent to less than 100 ng of glucose will elicit this response in the bean tissues. The polysaccharide has been isolated both from culture filtrates and from the mycelial walls of the fungus. Purification of the polysaccharide involved anion and cation exchange chromatography and gel filtration. The polysaccharide has an apparent molecular weight between 1,000,000 and 5,000,000 daltons, and consists predominantly of 3- and 4-linked glucosyl residues. PMID:16659289

  9. Host-Pathogen Interactions

    PubMed Central

    Ebel, Jürgen; Ayers, Arthur R.; Albersheim, Peter

    1976-01-01

    The glucan elicitor isolated from the mycelial walls of Phytophthora megasperma var. sojae, the fungus which causes stem and root rot in soybeans, stimulates the activity of phenylalanine ammonia-lyase and the accumulation of glyceollin in suspension-cultured soybean cells. Nigeran, a commercially available fungal wall glucan, was the only other compound tested which has any activity in this system. Glyceollin is a phenylpropanoid-derived phytoalexin which is toxic to P. megasperma var. sojae. Evidence is presented to support the hypothesis that the action of elicitors in stimulating phytoalexin synthesis is not species or variety specific but, rather, is part of a general defensive response of plants. PMID:16659568

  10. Host-Pathogen Interactions

    PubMed Central

    Cline, Kenneth; Albersheim, Peter

    1981-01-01

    The fact that fungal glucans will stimulate soybeans to accumulate phytoalexins prompted an investigation of soybean cell β-1,3-glucanases and β-glucosidases, as well as the ability of these enzymes to hydrolyze the fungal glucans. Several β-1,3-glucanases and β-glucosidases can be solubilized from the walls of suspension-cultured soybean cells by treatment with 1.0 molar sodium acetate buffer. An enzyme, which has been termed β-glucosylase I, is the dominant β-1,3-glucanase in the cell wall extracts. Utilizing CM-Sephadex chromatography, hydroxylapatite chromatography, and affinity chromatography, β-glucosylase I has been purified 71-fold, with 39% recovery, from the mixture of cell wall enzymes. The affinity chromatography column material was prepared by covalently attaching p-aminophenyl-1-β-d-glucopyranoside, an analog of a β-glucosylase I substrate, to Sepharose. β-Glucosylase I, purified by this procedure, yields a single band on isoelectric focusing gels (pH 8.9). However, the purified β-glucosylase I yields a darkly-staining protein band at an apparent molecular weight of 69,000 and several lightly-staining protein bands in sodium dodecyl sulfate polyacrylamide gels. Additional purification procedures fail to remove these lightly-staining protein bands. β-Glucosylase I will hydrolyze the β-glucan substrates, laminarin (3-linked) and lichenan (3- and 4-linked), and therefore, possesses β-glucanase activity. Studies of the progressive hydrolysis of laminarin by β-glucosylase I demonstrate that the enzyme hydrolyzes polysaccharide substrates in an exo manner. β-Glucosylase I will also hydrolyze a variety of low molecular weight β-glucosides including various β-linked diglucosides. Thus, β-glucosylase I also possesses β-glucosidase activity. Several lines of evidence are presented that the β-glucanase and the β-glucosidase activities exhibited by purified β-glucosylase I preparations are catalyzed by the same enzyme. This evidence includes inhibition studies which indicate that the β-glucanase and the β-glucosidase activities of β-glucosylase I are catalyzed at the same active site. β-Glucosylase I will also catalyze glucosyl transfer. This catalytic activity is responsible for the observed ability of the enzyme to synthesize di- and trisaccharides from laminarin. The disaccharides formed by β-glucosylase I-catalyzed transglucosylation are the β-anomers of the 6-, 4-, 3-, and 2-linked diglucosides in the relative proportions of 10:1:1:1. The ability of β-glucosylase I to catalyze glucosyl transfer indicates that β-glucosylase I is biochemically more similar to previously studied β-glucosidases than to β-glucanases. This conclusion is supported by the observation that β-glucosylase I is strongly inhibited by 1,5-d-gluconolactone, an inhibitor of β-glucosidases but not of β-glucanases. Images PMID:16661872

  11. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens.

    PubMed

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host-pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host-pathogen interactions. PMID:25699030

  12. Staphylococcus epidermidis Esp Degrades Specific Proteins Associated with Staphylococcus aureus Biofilm Formation and Host-Pathogen Interaction

    PubMed Central

    Iwamoto, Takeo; Takada, Koji; Okuda, Ken-ichi; Tajima, Akiko; Iwase, Tadayuki

    2013-01-01

    Staphylococcus aureus exhibits a strong capacity to attach to abiotic or biotic surfaces and form biofilms, which lead to chronic infections. We have recently shown that Esp, a serine protease secreted by commensal Staphylococcus epidermidis, disassembles preformed biofilms of S. aureus and inhibits its colonization. Esp was expected to degrade protein determinants of the adhesive and cohesive strength of S. aureus biofilms. The aim of this study was to elucidate the substrate specificity and target proteins of Esp and thereby determine the mechanism by which Esp disassembles S. aureus biofilms. We used a mutant Esp protein (EspS235A) with defective proteolytic activity; this protein did not disassemble the biofilm formed by a clinically isolated methicillin-resistant S. aureus (MRSA) strain, thereby indicating that the proteolytic activity of Esp is essential for biofilm disassembly. Esp degraded specific proteins in the biofilm matrix and cell wall fractions, in contrast to proteinase K, which is frequently used for testing biofilm robustness and showed no preference for proteolysis. Proteomic and immunological analyses showed that Esp degrades at least 75 proteins, including 11 biofilm formation- and colonization-associated proteins, such as the extracellular adherence protein, the extracellular matrix protein-binding protein, fibronectin-binding protein A, and protein A. In addition, Esp selectively degraded several human receptor proteins of S. aureus (e.g., fibronectin, fibrinogen, and vitronectin) that are involved in its colonization or infection. These results suggest that Esp inhibits S. aureus colonization and biofilm formation by degrading specific proteins that are crucial for biofilm construction and host-pathogen interaction. PMID:23316041

  13. Mass spectrometric analysis reveals remnants of host-pathogen molecular interactions at the starch granule surface in wheat endosperm.

    PubMed

    Wall, Michael L; Wheeler, Heather L; Smith, Jeffrey; Figeys, Daniel; Altosaar, Illimar

    2010-09-01

    The starch granules of wheat seed are solar energy-driven deposits of fixed carbon and, as such, present themselves as targets of pathogen attack. The seed's array of antimicrobial proteins, peptides, and small molecules comprises a molecular defense against penetrating pathogens. In turn, pathogens exhibit an arsenal of enzymes to facilitate the degradation of the host's endosperm. In this context, the starch granule surface is a relatively unexplored domain in which unique molecular barriers may be deployed to defend against and inhibit the late stages of infection. Therefore, it was compelling to explore the starch granule surface in mature wheat seed, which revealed evidence of host-pathogen molecular interactions that may have occurred during grain development. In this study, starch granules from the soft wheat Triticum aestivum cv. AC Andrew and hard wheat T. turgidum durum were isolated and water washed 20 times, and their surface proteins were digested in situ with trypsin. The peptides liberated into the supernatant and the peptides remaining at the starch granule surface were separately examined. In this way, we demonstrated that the identified proteins have a strong affinity for the starch granule surface. Proteins with known antimicrobial activity were identified, as well as several proteins from the plant pathogens Agrobacterium tumefaciens, Pectobacterium carotovorum, Fusarium graminearum, Magnaporthe grisea, Xanthomonas axonopodis, and X. oryzae. Although most of these peptides corresponded to uncharacterized hypothetical proteins of fungal pathogens, several peptide fragments were identical to cytosolic and membrane proteins of specific microbial pathogens. During development and maturation, wheat seed appeared to have resisted infection and lysed the pathogens where, upon desiccation, the molecular evidence remained fixed at the starch granule surface. PMID:20701481

  14. Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis

    PubMed Central

    2011-01-01

    Background There is a growing realization that alterations in host-pathogen interactions (HPI) can generate disease phenotypes without pathogen invasion. The gut represents a prime region where such HPI can arise and manifest. Under normal conditions intestinal microbial communities maintain a stable, mutually beneficial ecosystem. However, host stress can lead to changes in environmental conditions that shift the nature of the host-microbe dialogue, resulting in escalation of virulence expression, immune activation and ultimately systemic disease. Effective modulation of these dynamics requires the ability to characterize the complexity of the HPI, and dynamic computational modeling can aid in this task. Agent-based modeling is a computational method that is suited to representing spatially diverse, dynamical systems. We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis. Methodology/Principal Findings An agent-based model (ABM) of virulence regulation in Pseudomonas aeruginosa was developed by translating bacterial and host cell sense-and-response mechanisms into behavioral rules for computational agents and integrated into a virtual environment representing the host-microbe interface in the gut. The resulting gut milieu ABM (GMABM) was used to: 1) investigate a potential clinically relevant laboratory experimental condition not yet developed - i.e. non-lethal transient segmental intestinal ischemia, 2) examine the sufficiency of existing hypotheses to explain experimental data - i.e. lethality in a model of major surgical insult and stress, and 3) produce behavior to potentially guide future experimental design - i.e. suggested sample points for a potential laboratory model of non-lethal transient intestinal ischemia. Furthermore, hypotheses were generated to explain certain discrepancies between the behaviors of the GMABM and biological experiments, and new

  15. Crazy like a fox. Validity and ethics of animal models of human psychiatric disease.

    PubMed

    Rollin, Michael D H; Rollin, Bernard E

    2014-04-01

    Animal models of human disease play a central role in modern biomedical science. Developing animal models for human mental illness presents unique practical and philosophical challenges. In this article we argue that (1) existing animal models of psychiatric disease are not valid, (2) attempts to model syndromes are undermined by current nosology, (3) models of symptoms are rife with circular logic and anthropomorphism, (4) any model must make unjustified assumptions about subjective experience, and (5) any model deemed valid would be inherently unethical, for if an animal adequately models human subjective experience, then there is no morally relevant difference between that animal and a human. PMID:24534739

  16. WAHIS-Wild and its interface: the OIE worldwide monitoring system for wild animal diseases.

    PubMed

    Jebara, Karim Ben

    2016-06-30

    Wild animal diseases are a global growing concern, given the threat that they pose to animal health and their zoonotic potential. The World Organisation for Animal Health (OIE) was among the first organisations to recognise the importance of having a comprehensive knowledge of the disease situation in wild animals, collecting information on wildlife diseases worldwide since 1993, when for the first time an annual questionnaire was distribute by OIE to members Countries in order to collect qualitative and quantitative data on selected diseases in wild animals. Starting with 2008 until 2012 an updated version of questionnaire was circulated to allow for identifying wildlife species by their Latin name and by their common names in the 3 OIE official languages (English, French, and Spanish). This specific functionality was then implemented in the World Animal Health Information System (WAHIS) in 2012, when this information was made available to the public through WAHIS-Wild Interface. PMID:27393871

  17. The Arthropod-Borne Animal Diseases Research Laboratory: Research Program Update and Current Status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mission of the Arthropod-Borne Animal Diseases Research Laboratory (ABADRL) located in Laramie, Wyoming, is to solve major endemic, emerging, and exotic arthropod-borne disease problems in U.S. livestock. The ABADRL has three 5-year project plans under two ARS National Research Programs; Animal ...

  18. Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases.

    PubMed

    Youssef, S A; Capucchio, M T; Rofina, J E; Chambers, J K; Uchida, K; Nakayama, H; Head, E

    2016-03-01

    According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases. PMID:26869150

  19. 76 FR 11799 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis...: National Institute of Allergy and Infectious Diseases Special Emphasis Panel; Host-Pathogen...

  20. Agroterrorism, biological crimes, and biowarfare targeting animal agriculture. The clinical, pathologic, diagnostic, and epidemiologic features of some important animal diseases.

    PubMed

    Wilson, T M; Gregg, D A; King, D J; Noah, D L; Perkins, L E; Swayne, D E; Inskeep, W

    2001-09-01

    In the past 100 years, to our knowledge there have been approximately 12 events involving the intentional introduction of microbiologic agents into livestock and animal populations worldwide, of which three were World War I events in the United States. To the best of the authors' knowledge, there has been no recent intentional introduction of microbiologic agents (viruses or bacteria) into livestock and animal populations in the United States. The criminal or terrorist use of chemicals against animals and agriculture products have been more common. With the political, economic, and military new world order, however, the United States must maintain a vigilant posture. The framework for this vigilance must be an intelligence system sensitive to the needs of agriculture and a first-class animal disease diagnostic surveillance and response system. PMID:11572141

  1. Animator

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  2. 9 CFR 71.2 - Secretary to issue rule governing quarantine and interstate movement of diseased animals...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... quarantine and interstate movement of diseased animals, including poultry. 71.2 Section 71.2 Animals and... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS GENERAL PROVISIONS § 71.2 Secretary to issue rule governing quarantine and interstate movement of diseased animals, including poultry. When...

  3. 9 CFR 71.2 - Secretary to issue rule governing quarantine and interstate movement of diseased animals...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... quarantine and interstate movement of diseased animals, including poultry. 71.2 Section 71.2 Animals and... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS GENERAL PROVISIONS § 71.2 Secretary to issue rule governing quarantine and interstate movement of diseased animals, including poultry. When...

  4. 9 CFR 71.2 - Secretary to issue rule governing quarantine and interstate movement of diseased animals...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... quarantine and interstate movement of diseased animals, including poultry. 71.2 Section 71.2 Animals and... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS GENERAL PROVISIONS § 71.2 Secretary to issue rule governing quarantine and interstate movement of diseased animals, including poultry. When...

  5. 9 CFR 71.2 - Secretary to issue rule governing quarantine and interstate movement of diseased animals...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... quarantine and interstate movement of diseased animals, including poultry. 71.2 Section 71.2 Animals and... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS GENERAL PROVISIONS § 71.2 Secretary to issue rule governing quarantine and interstate movement of diseased animals, including poultry. When...

  6. 9 CFR 71.2 - Secretary to issue rule governing quarantine and interstate movement of diseased animals...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... quarantine and interstate movement of diseased animals, including poultry. 71.2 Section 71.2 Animals and... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS GENERAL PROVISIONS § 71.2 Secretary to issue rule governing quarantine and interstate movement of diseased animals, including poultry. When...

  7. A Genomic Approach to Unravel Host-Pathogen Interaction in Chelonians: The Example of Testudinid Herpesvirus 3.

    PubMed

    Origgi, Francesco C; Tecilla, Marco; Pilo, Paola; Aloisio, Fabio; Otten, Patricia; Aguilar-Bultet, Lisandra; Sattler, Ursula; Roccabianca, Paola; Romero, Carlos H; Bloom, David C; Jacobson, Elliott R

    2015-01-01

    information is not only fundamental for the genetic characterization of this virus but is also critical to lay the groundwork for an improved understanding of host-pathogen interactions in chelonians and contribute to tortoise conservation. PMID:26244892

  8. A Genomic Approach to Unravel Host-Pathogen Interaction in Chelonians: The Example of Testudinid Herpesvirus 3

    PubMed Central

    Origgi, Francesco C.; Tecilla, Marco; Pilo, Paola; Aloisio, Fabio; Otten, Patricia; Aguilar-Bultet, Lisandra; Sattler, Ursula; Roccabianca, Paola; Romero, Carlos H.; Bloom, David C.; Jacobson, Elliott R.

    2015-01-01

    information is not only fundamental for the genetic characterization of this virus but is also critical to lay the groundwork for an improved understanding of host-pathogen interactions in chelonians and contribute to tortoise conservation. PMID:26244892

  9. Waterborne Exophiala species causing disease in cold-blooded animals.

    PubMed

    de Hoog, G S; Vicente, V A; Najafzadeh, M J; Harrak, M J; Badali, H; Seyedmousavi, S

    2011-12-01

    The majority of mesophilic waterborne species of the black yeast genus Exophiala (Chaetothyriales) belong to a single clade judging from SSU rDNA data. Most taxa are also found to cause cutaneous or disseminated infections in cold-blooded, water animals, occasionally reaching epidemic proportions. Hosts are mainly fish, frogs, toads, turtles or crabs, all sharing smooth, moist or mucous skins and waterborne or amphibian lifestyles; occasionally superficial infections in humans are noted. Cold-blooded animals with strictly terrestrial life styles, such as reptiles and birds are missing. It is concluded that animals with moist skins, i.e. those being waterborne and those possessing sweat glands, are more susceptible to black yeast infection. Melanin and the ability to assimilate alkylbenzenes are purported general virulence factors. Thermotolerance influences the choice of host. Exophiala species in ocean water mostly have maximum growth temperatures below 30 °C, whereas those able to grow until 33(-36) °C are found in shallow waters and occasionally on humans. Tissue responses vary with the phylogenetic position of the host, the lower animals showing poor granulome formation. Species circumscriptions have been determined by multilocus analyses involving partial ITS, TEF1, BT2 and ACT1. PMID:22403476

  10. ANIMAL MODELS: CARDIOVASCULAR DISEASE, CNS INJURY AND ULTRAFINE PARTICLE BIOKINETICS

    EPA Science Inventory

    The Animal Core studies will help to answer the question of why subpopulations are at increased risk of adverse health outcomes following PM exposure. They will identify the cellular and molecular mechanisms which underlie cardiovascular susceptibility. Exposure-response rel...

  11. Coffee and Alzheimer’s disease - animal & cellular evidences

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increases in lifespan in modern times have put significant social and academic emphasis on age-related pathologies. Of the many chronic, non-acquired diseases, dementias are among the most fiscally and psychologically burdensome to society. Alzheimer’s disease (AD) is the most prevalent and well kno...

  12. An experimental animal model of Kashin-Beck disease.

    PubMed Central

    Zhang, G Q; Liu, J X

    1989-01-01

    Twelve young macaque monkeys were fed with grain and water from areas actively endemic or non-endemic for Kashin-Beck disease. Both dietary grain and water from geographical areas endemic for Kashin-Beck disease induced a sequence of pathological changes in the growth plates and articular cartilage and biochemical changes in the serum and urine of monkeys. These changes are similar to those in human Kashin-Beck disease. It is considered that this may be a simple and valuable model for the further study of this disease and its management and control. The results suggest that the pathogenetic factors of Kashin-Beck disease relate both to grain and to water in the diet in endemic areas. The experiment also shows that certain serum enzyme concentrations correlate with chondronecrosis. Images PMID:2930266

  13. Clostridium perfringens in animal disease: a review of current knowledge.

    PubMed

    Niilo, L

    1980-05-01

    The diseases caused by various types of Clostridium perfringens are critically reviewed in the light of current knowledge. Particular emphasis is placed on information concerning these diseases in Canadian livestock. There are two etiologically clearly-defined acute C. perfringens diseases recognized in Canada: hemorrhagic enteritis of the new born calf, caused by C. perfringens type C, and enterotoxemia of sheep, caused by type D. Clostridium perfringens type A may play a role as a secondary pathological agent in various disease conditions, such as necrotic enteritis of chickens. It may also cause wound infections and may provide a source for human food poisoning outbreaks. There appears to be a considerable lack of knowledge regarding the distribution of C. perfringens types, their pathogenesis, diagnosis and the incidence of diseases caused by this organism. PMID:6253040

  14. How To Become a Top Model: Impact of Animal Experimentation on Human Salmonella Disease Research ▿

    PubMed Central

    Tsolis, Renée M.; Xavier, Mariana N.; Santos, Renato L.; Bäumler, Andreas J.

    2011-01-01

    Salmonella serotypes are a major cause of human morbidity and mortality worldwide. Over the past decades, a series of animal models have been developed to advance vaccine development, provide insights into immunity to infection, and study the pathogenesis of human Salmonella disease. The successive introduction of new animal models, each suited to interrogate previously neglected aspects of Salmonella disease, has ushered in important conceptual advances that continue to have a strong and sustained influence on the ideas driving research on Salmonella serotypes. This article reviews important milestones in the use of animal models to study human Salmonella disease and identify research needs to guide future work. PMID:21343352

  15. Is Mycobacterium avium subsp. paratuberculosis, the cause of Johne's disease in animals, a good candidate for Crohn's disease in man?

    PubMed

    Singh, A V; Singh, S V; Singh, P K; Sohal, J S

    2010-03-01

    Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease or paratuberculosis, a gastro intestinal inflammatory condition in ruminants and other animals, which is similar to Crohn's disease (CD) that occurs in man. The role of MAP in the causation of CD has been under intense investigation in the last few decades. This review summarizes the status of MAP in animals and the food chain and its association with CD in man. PMID:20443099

  16. Host behavior alters spiny lobster-viral disease dynamics: a simulation study.

    PubMed

    Dolan, Thomas W; Butler, Mark J; Shields, Jeffrey D

    2014-08-01

    Social behavior confers numerous benefits to animals but also risks, among them an increase in the spread of pathogenic diseases. We examined the trade-off between risk of predation and disease transmission under different scenarios of host spatial structure and disease avoidance behavior using a spatially explicit, individual-based model of the host pathogen interaction between juvenile Caribbean spiny lobster (Panulirus argus) and Panulirus argus Virus 1 (PaV1). Spiny lobsters are normally social but modify their behavior to avoid diseased conspecifics, a potentially effective means of reducing transmission but one rarely observed in the wild. We found that without lobster avoidance of diseased conspecifics, viral outbreaks grew in intensity and duration in simulations until the virus was maintained continuously at unrealistically high levels. However, when we invoked disease avoidance at empirically observed levels, the intensity and duration of outbreaks was reduced and the disease extirpated within five years. Increased lobster (host) spatial aggregation mimicking that which occurs when sponge shelters for lobsters are diminished by harmful algal blooms, did not significantly increase PaV1 transmission or persistence in lobster populations. On the contrary, behavioral aversion of diseased conspecifics effectively reduced viral prevalence, even when shelters were limited, which reduced shelter availability for all lobsters but increased predation, especially of infected lobsters. Therefore, avoidance of diseased conspecifics selects against transmission by contact, promotes alternative modes of transmission, and results in a more resilient host-pathogen system. PMID:25230484

  17. Animal Models of Polyglutamine Diseases and Therapeutic Approaches*

    PubMed Central

    Marsh, J. Lawrence; Lukacsovich, Tamas; Thompson, Leslie Michels

    2009-01-01

    The dominant gain-of-function polyglutamine repeat diseases, in which the initiating mutation is known, allow development of models that recapitulate many aspects of human disease. To the extent that pathology is a consequence of disrupted fundamental cellular activities, one can effectively study strategies to ameliorate or protect against these cellular insults. Model organisms allow one to identify pathways that affect disease onset and progression, to test and screen for pharmacological agents that affect pathogenic processes, and to validate potential targets genetically as well as pharmacologically. Here, we describe polyglutamine repeat diseases that have been modeled in a variety of organisms, including worms, flies, mice, and non-human primates, and discuss examples of how they have broadened the therapeutic landscape. PMID:18957429

  18. Role of hemostatic factors in hepatic injury and disease: animal models de-liver.

    PubMed

    Kopec, A K; Joshi, N; Luyendyk, J P

    2016-07-01

    Chronic liver damage is associated with unique changes in the hemostatic system. Patients with liver disease often show a precariously rebalanced hemostatic system, which is easily tipped towards bleeding or thrombotic complications by otherwise benign stimuli. In addition, some clinical studies have shown that hemostatic system components contribute to the progression of liver disease. There is a strong basic science foundation for clinical studies with this particular focus. Chronic and acute liver disease can be modeled in rodents and large animals with a variety of approaches, which span chronic exposure to toxic xenobiotics, diet-induced obesity, and surgical intervention. These experimental approaches have now provided strong evidence that, in addition to perturbations in hemostasis caused by liver disease, elements of the hemostatic system have powerful effects on the progression of experimental liver toxicity and disease. In this review, we cover the basis of the animal models that are most often utilized to assess the impact of the hemostatic system on liver disease, and highlight the role that coagulation proteases and their targets play in experimental liver toxicity and disease, emphasizing key similarities and differences between models. The need to characterize hemostatic changes in existing animal models and to develop novel animal models recapitulating the coagulopathy of chronic liver disease is highlighted. Finally, we emphasize the continued need to translate knowledge derived from highly applicable animal models to improve our understanding of the reciprocal interaction between liver disease and the hemostatic system in patients. PMID:27060337

  19. Essential veterinary education in emerging infections, modes of introduction of exotic animals, zoonotic diseases, bioterrorism, implications for human and animal health and disease manifestation.

    PubMed

    Chomel, B B; Marano, N

    2009-08-01

    A fundamental role of the veterinary profession is the protection of human health through wholesome food and control of diseases of animal origin, especially zoonoses. Therefore, training of veterinary students worldwide needs to face the new challenges posed by emerging infections, both from wildlife and domestic animals, as well as risks from bio/agroterrorism. New courses emphasising recognition, response, recovery and prevention must be developed to respond to natural or intentionally induced emerging diseases and zoonoses. Training programmes in applied epidemiology, zoonoses and foreign animal diseases are crucial for the development of a strong workforce to deal with microbial threats. Students should learn the reporting pathways for reportable diseases in their countries or states. Knowledge of the principles of ecology and ecosystems should be acquired during pre-veterinary studies. Elective classes on wildlife diseases, emphasising wildlife zoonotic diseases, should be offered during the veterinary curriculum, as well as a course on risk communication, since veterinarians are frequently in the position of having to convey complex information under adverse circumstances. PMID:20128464

  20. To Your Health: NLM update transcript - Preventing disease spillover from animals to humans

    MedlinePlus

    ... update Transcript Preventing disease spillover from animals to humans : 07/11/2016 To use the sharing features ... accessible by entering the terms 'PREDICT (in all capital letters) - and UC Davis' in any search engine. ...

  1. ANIMAL PATHOGENS THAT MAY CAUSE HUMAN DISEASE THAT ORIGINATE FROM FARM OPERATIONS

    EPA Science Inventory

    The recent increase in concentrated animal feeding operations in the United States has caused renewed concern regarding the infectious diseases that may be passed from farm animals to humans via the environment. It is also known that more than 20 recent epidemics among humans cou...

  2. The rat as an animal model of Alzheimer’s disease

    PubMed Central

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer’s disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that of mice. In recent years, the rat has been making a comeback as an Alzheimer’s disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat as an animal model of Alzheimer’s disease. PMID:19432812

  3. AN UPDATE OF RESEARCH AT THE NATIONAL ANIMAL DISEASE CENTER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella associated human illnesses, linked to consumption of contaminated poultry, have remained significantly above public health targets of the Centers for Disease Control (CDC) whereas E. coli O157:H7, Campylobacter, and Listeria associated morbidities are approaching Healthy People 2010 goals...

  4. Borna disease virus infection in animals and humans.

    PubMed Central

    Richt, J. A.; Pfeuffer, I.; Christ, M.; Frese, K.; Bechter, K.; Herzog, S.

    1997-01-01

    The geographic distribution and host range of Borna disease (BD), a fatal neurologic disease of horses and sheep, are larger than previously thought. The etiologic agent, Borna disease virus (BDV), has been identified as an enveloped nonsegmented negative-strand RNA virus with unique properties of replication. Data indicate a high degree of genetic stability of BDV in its natural host, the horse. Studies in the Lewis rat have shown that BDV replication does not directly influence vital functions; rather, the disease is caused by a virus-induced T-cell mediated immune reaction. Because antibodies reactive with BDV have been found in the sera of patients with neuropsychiatric disorders, this review examines the possible link between BDV and such disorders. Seroepidemiologic and cerebrospinal fluid investigations of psychiatric patients suggest a causal role of BDV infection in human psychiatric disorders. In diagnostically unselected psychiatric patients, the distribution of psychiatric disorders was found to be similar in BDV seropositive and seronegative patients. In addition, BDV-seropositive neurologic patients became ill with lymphocytic meningoencephalitis. In contrast to others, we found no evidence is reported for BDV RNA, BDV antigens, or infectious B DV in peripheral blood cells of psychiatric patients. PMID:9284379

  5. Risk of parasite transmission influences perceived vulnerability to disease and perceived danger of disease-relevant animals.

    PubMed

    Prokop, Pavol; Usak, Muhammet; Fancovicová, Jana

    2010-09-01

    Adaptationist view proposes that emotions were shaped by natural selection and their primary function is to protect humans against predators and/or disease threat. This study examined cross-cultural and inter-personal differences in behavioural immune system measured by disgust, fear and perceived danger in participants from high (Turkey) and low (Slovakia) pathogen prevalence areas. We found that behavioural immune system in Turkish participants was activated more than those of Slovakian participants when exposed to photographs depicting disease-relevant cues, but not when exposed to disease-irrelevant cues. However, participants from Slovakia, where human to human disease transmission is expected to be more prevalent than in Turkey, showed lower aversion in Germ Aversion subscale supporting hypersensitiveness of the behavioural immune system. Having animals at home was less frequent both in Turkey and in participants who perceived higher danger about disease relevant animals. Participants more vulnerable to diseases reported higher incidence of illness last year and considered perceived disease-relevant animals more dangerous than others. Females showed greater fear, disgust and danger about disease-relevant animals than males. Our results further support the finding that cultural and inter-personal differences in human personality are influenced by parasite threat. PMID:20558257

  6. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease.

    PubMed

    Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-01-01

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review. PMID:26329332

  7. Vaccines against diseases transmitted from animals to humans: a one health paradigm.

    PubMed

    Monath, Thomas P

    2013-11-01

    This review focuses on the immunization of animals as a means of preventing human diseases (zoonoses). Three frameworks for the use of vaccines in this context are described, and examples are provided of successes and failures. Framework I vaccines are used for protection of humans and economically valuable animals, where neither plays a role in the transmission cycle. The benefit of collaborations between animal health and human health industries and regulators in developing such products is discussed, and one example (West Nile vaccine) of a single product developed for use in animals and humans is described. Framework II vaccines are indicated for domesticated animals as a means of preventing disease in both animals and humans. The agents of concern are transmitted directly or indirectly (e.g. via arthropod vectors) from animals to humans. A number of examples of the use of Framework II vaccines are provided, e.g. against brucellosis, Escherichia coli O157, rabies, Rift Valley fever, Venezuelan equine encephalitis, and Hendra virus. Framework III vaccines are used to immunize wild animals as a means of preventing transmission of disease agents to humans and domesticated animals. Examples are reservoir-targeted, oral bait rabies, Mycobacterium bovis and Lyme disease vaccines. Given the speed and lost cost of veterinary vaccine development, some interventions based on the immunization of animals could lead to rapid and relatively inexpensive advances in public health. Opportunities for vaccine-based approaches to preventing zoonotic and emerging diseases that integrate veterinary and human medicine (the One Health paradigm) are emphasized. PMID:24060567

  8. Disease Risk Assessments Involving Companion Animals: an Overview for 15 Selected Pathogens Taking a European Perspective.

    PubMed

    Rijks, J M; Cito, F; Cunningham, A A; Rantsios, A T; Giovannini, A

    2016-07-01

    Prioritization of companion animal transmissible diseases was performed by the Companion Animals multisectoriaL interprofessionaL Interdisciplinary Strategic Think tank On zoonoses (CALLISTO) project. The project considered diseases occurring in domesticated species commonly kept as pets, such as dogs and cats, but also included diseases occurring in captive wild animals and production animal species. The prioritization process led to the selection of 15 diseases of prime public health relevance, agricultural economic importance, or both. An analysis was made of the current knowledge on the risk of occurrence and transmission of these diseases among companion animals, and from companion animals to man (zoonoses) or to livestock. The literature was scanned for risk assessments for these diseases. Studies were classified as import risk assessments (IRAs) or risk factor analyses (RFAs) in endemic areas. For those pathogens that are absent from Europe, only IRAs were considered; for pathogens present throughout Europe, only RFAs were considered. IRAs were identified for seven of the eight diseases totally or partially absent from Europe. IRAs for classical rabies and alveolar echinococcosis found an increased risk for introduction of the pathogen into officially disease-free areas as a consequence of abandoning national rules and adopting the harmonized EU rules for pet travel. IRAs for leishmaniosis focused on risk associated with the presence of persistently infected dogs in new geographical areas, taking into consideration the risk of disease establishment should a competent vector arise. IRAs for Crimean-Congo haemorrhagic fever and West Nile fever indicated that the likelihood of introduction via companion animals was low. IRAs for bluetongue paid no attention to the risk of introduction via companion animals, which was also the case for IRAs for foot-and-mouth disease, the only disease considered to be absent from Europe. RFAs dealing with the risk factors for

  9. Proteomic characterization of a natural host-pathogen interaction: repertoire of in vivo expressed bacterial and host surface-associated proteins.

    PubMed

    Rees, Megan A; Kleifeld, Oded; Crellin, Paul K; Ho, Bosco; Stinear, Timothy P; Smith, A Ian; Coppel, Ross L

    2015-01-01

    Interactions between a host and a bacterial pathogen are mediated by cross-talk between molecules present on, or secreted by, pathogens and host binding-molecules. Identifying proteins involved at this interface would provide substantial insights into this interaction. Although numerous studies have examined in vitro models of infection at the level of transcriptional change and proteomic profiling, there is virtually no information available on naturally occurring host-pathogen interactions in vivo. We employed membrane shaving to identify peptide fragments cleaved from surface-expressed bacterial proteins and also detected proteins originating from the infected host. We optimized this technique for media-cultured Corynebacterium pseudotuberculosis, a sheep pathogen, revealing a set of 247 surface proteins. We then studied a natural host-pathogen interaction by performing membrane shaving on C. pseudotuberculosis harvested directly from naturally infected sheep lymph nodes. Thirty-one bacterial surface proteins were identified, including 13 not identified in culture media, suggesting that a different surface protein repertoire is expressed in this hostile environment. Forty-nine host proteins were identified, including immune mediators and antimicrobial peptides such as cathelicidin. This novel application of proteolytic shaving has documented sets of host and pathogen proteins present at the bacterial surface in an infection of the native host. PMID:25329524

  10. Animal genomics in natural reservoirs of infectious diseases.

    PubMed

    Cowled, C; Wang, L-F

    2016-04-01

    Natural virus reservoirs such as wild bats, birds, rodents and non-human primates are generally non-model organisms that have, until recently, presented limited opportunities for in-depth study. Next-generation sequencing provides a way to partially circumvent this limitation, since the methods required for data acquisition and analysis are largely species-independent. Comparative genomics and other 'omics' provide new opportunities to study the structure and function of various biological systems of wild species that are otherwise out of reach. Genomes of natural reservoir hosts can help to identify dominant pathways of virus-host interaction and to reveal differences between susceptible and resistant organisms, populations and species. This is of great scientific interest and may also provide a resource for the rational design of treatments for viral diseases in humans and livestock. In this way, we will 'learn from nature' and one day apply this knowledge to create disease-resistant livestock or develop novel therapeutic and prevention strategies. Reservoir host genomics will also open up possibilities for developing novel vaccines for wildlife, aid in the development of new diagnostic platforms, and have broad implications for developmental and evolutionary biology. In this review, the authors focus on natural reservoir hosts of viral pathogens, although most of the discussion points should be equally applicable to natural reservoirs of pathogenic bacteria, fungi or other parasites. PMID:27217176

  11. Lupus Nephritis: Animal Modeling of a Complex Disease Syndrome Pathology

    PubMed Central

    McGaha, Tracy L; Madaio, Michael P.

    2014-01-01

    Nephritis as a result of autoimmunity is a common morbidity associated with Systemic Lupus Erythematosus (SLE). There is substantial clinical and industry interest in medicinal intervention in the SLE nephritic process; however, clinical trials to specifically treat lupus nephritis have not resulted in complete and sustained remission in all patients. Multiple mouse models have been used to investigate the pathologic interactions between autoimmune reactivity and SLE pathology. While several models bear a remarkable similarity to SLE-driven nephritis, there are limitations for each that can make the task of choosing the appropriate model for a particular aspect of SLE pathology challenging. This is not surprising given the variable and diverse nature of human disease. In many respects, features among murine strains mimic some (but never all) of the autoimmune and pathologic features of lupus patients. Although the diversity often limits universal conclusions relevant to pathogenesis, they provide insights into the complex process that result in phenotypic manifestations of nephritis. Thus nephritis represents a microcosm of systemic disease, with variable lesions and clinical features. In this review, we discuss some of the most commonly used models of lupus nephritis (LN) and immune-mediated glomerular damage examining their relative strengths and weaknesses, which may provide insight in the human condition. PMID:25722732

  12. The Arthropod-borne Animal Diseases Unit: research program update and status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To accomplish the continuing research mission of the Arthropod Borne Animal Diseases Unit (ABADRU) in solving major endemic, emerging, and exotic arthropod-borne disease problems in livestock, the Unit has completed the move to Manhattan, KS. The ABADRU is one of five units at the Center for Grain a...

  13. Synaptic plasticity in animal models of early Alzheimer's disease.

    PubMed Central

    Rowan, Michael J; Klyubin, Igor; Cullen, William K; Anwyl, Roger

    2003-01-01

    Amyloid beta-protein (Abeta) is believed to be a primary cause of Alzheimer's disease (AD). Recent research has examined the potential importance of soluble species of Abeta in synaptic dysfunction, long before fibrillary Abeta is deposited and neurodegenerative changes occur. Hippocampal excitatory synaptic transmission and plasticity are disrupted in transgenic mice overexpressing human amyloid precursor protein with early onset familial AD mutations, and in rats after exogenous application of synthetic Abeta both in vitro and in vivo. Recently, naturally produced soluble Abeta was shown to block the persistence of long-term potentiation (LTP) in the intact hippocampus. Sub-nanomolar concentrations of oligomeric Abeta were sufficient to inhibit late LTP, pointing to a possible reason for the sensitivity of hippocampus-dependent memory to impairment in the early preclinical stages of AD. Having identified the active species of Abeta that can play havoc with synaptic plasticity, it is hoped that new ways of targeting early AD can be developed. PMID:12740129

  14. A historical synopsis of farm animal disease and public policy in twentieth century Britain.

    PubMed

    Woods, Abigail

    2011-07-12

    The diseases suffered by British livestock, and the ways in which they were perceived and managed by farmers, vets and the state, changed considerably over the course of the twentieth century. This paper documents and analyses these changes in relation to the development of public policy. It reveals that scientific knowledge and disease demographics cannot by themselves explain the shifting boundaries of state responsibility for animal health, the diseases targeted and the preferred modes of intervention. Policies were shaped also by concerns over food security and the public's health, the state of the national and livestock economy, the interests and expertise of the veterinary profession, and prevailing agricultural policy. This paper demonstrates how, by precipitating changes to farming and trading practices, public policy could sometimes actually undermine farm animal health. Animal disease can therefore be viewed both as a stimulus to, and a consequence of, twentieth century public policy. PMID:21624915

  15. A historical synopsis of farm animal disease and public policy in twentieth century Britain

    PubMed Central

    Woods, Abigail

    2011-01-01

    The diseases suffered by British livestock, and the ways in which they were perceived and managed by farmers, vets and the state, changed considerably over the course of the twentieth century. This paper documents and analyses these changes in relation to the development of public policy. It reveals that scientific knowledge and disease demographics cannot by themselves explain the shifting boundaries of state responsibility for animal health, the diseases targeted and the preferred modes of intervention. Policies were shaped also by concerns over food security and the public's health, the state of the national and livestock economy, the interests and expertise of the veterinary profession, and prevailing agricultural policy. This paper demonstrates how, by precipitating changes to farming and trading practices, public policy could sometimes actually undermine farm animal health. Animal disease can therefore be viewed both as a stimulus to, and a consequence of, twentieth century public policy. PMID:21624915

  16. Ex-ante economic analysis of animal disease surveillance.

    PubMed

    Tambi, E N; Maina, O W; Mariner, J C

    2004-12-01

    This paper provides an ex-ante economic analysis comparing four alternative intervention strategies for the control and eradication of rinderpest against a scenario of no intervention in a cattle population similar in size to that of Ethiopia. The interventions were three different coverage levels of mass vaccination and one surveillance-based programme where vaccination targeted infected sub-populations. For each scenario, the disease impact was estimated using an open-population, state-transition SEIR ('susceptible', 'exposed', 'infectious', 'recovered') disease transmission model with parameter estimates developed for lineage 1 rinderpest virus. Projected economic surplus gains and costs estimated from the rinderpest eradication programme in Ethiopia were analysed using benefit-cost methods. Social net present values (NPVs) and benefit-cost ratios (BCRs) were calculated. Although the economic model found that BCRs were greater than one for all interventions examined, the scenarios of intensive mass vaccination (75% vaccination coverage) and surveillance with targeted vaccination were economically preferable. The BCRs for these strategies were 5.08 and 3.68, respectively. Sensitivity analysis revealed that an increase in market prices for beef and milk increased the value of economic loss, the economic surplus and returns to investments in terms of NPVs and BCRs. An increase in demand and supply elasticities for beef and milk decreased the value of economic losses. This also had a negative effect on economic surplus and NPVs. The effect of an increase in the discount rate reduced returns to investments, with lower NPVs and BCRs. The authors note that 75% mass vaccination coverage was attempted in Ethiopia in the early 1990s, but failed to eradicate rinderpest because the approach was logistically too difficult to implement in practice. Subsequently, an effective surveillance and epidemiologically targeted vaccination programme was developed and has apparently

  17. New developments in animal models of Alzheimer's disease.

    PubMed

    Janus, C; Phinney, A L; Chishti, M A; Westaway, D

    2001-09-01

    Alzheimer's disease (AD) is characterized by deterioration in mental function leading to dementia, deposition of amyloid plaques and neurofibrillary tangles (NFTs), and neuronal loss. The major component of plaques is the amyloid-beta peptide (A beta), whereas NFTs are assemblies of hyperphosphorylated forms of the microtubule-associated protein tau. Electron microscopy of NFTs reveals structures known as paired helical filaments (PHFs). In familial AD (FAD), mutations in three distinct genes drive A beta synthesis by favoring endoproteolytic secretase cleavages that liberate A beta from the Alzheimer beta-amyloid precursor protein (APP). This suggests that excess A beta initiates a pathogenic cascade in humans that culminates in all the pathologic and cellular hallmarks of AD. Building upon the knowledge of FAD mutations, incremental technical advances have now allowed reproduceable creation of APP transgenic mice that exhibit AD-like amyloid pathology and A beta burdens. These transgenic mouse lines also exhibit deficits in spatial reference and working memory, with immunization against A beta abrogating both AD-associated phenotypes. Besides establishing a proof of principle for A beta-directed therapies, these findings suggest a potential to identify individual elements in the pathogenic pathway that lead to cognitive dysfunction. Furthermore, transgenic APP mice with potent amyloid deposition will likely form a beach-head to capture the final elements of AD neuropathology--cell loss and NFTs composed of PHFs--that are missing from current transgenic models. PMID:11898556

  18. Animal husbandry practices in rural Bangladesh: potential risk factors for antimicrobial drug resistance and emerging diseases.

    PubMed

    Roess, Amira A; Winch, Peter J; Ali, Nabeel A; Akhter, Afsana; Afroz, Dilara; El Arifeen, Shams; Darmstadt, Gary L; Baqui, Abdullah H

    2013-11-01

    Antimicrobial drug administration to household livestock may put humans and animals at risk for acquisition of antimicrobial drug-resistant pathogens. To describe animal husbandry practices, including animal healthcare-seeking and antimicrobial drug use in rural Bangladesh, we conducted semi-structured in-depth interviews with key informants, including female household members (n = 79), village doctors (n = 10), and pharmaceutical representatives, veterinarians, and government officials (n = 27), and performed observations at animal health clinics (n = 3). Prevalent animal husbandry practices that may put persons at risk for acquisition of pathogens included shared housing and water for animals and humans, antimicrobial drug use for humans and animals, and crowding. Household members reported seeking human and animal healthcare from unlicensed village doctors rather than formal-sector healthcare providers and cited cost and convenience as reasons. Five times more per household was spent on animal than on human healthcare. Strengthening animal and human disease surveillance systems should be continued. Interventions are recommended to provide vulnerable populations with a means of protecting their livelihood and health. PMID:24062478

  19. Animal Husbandry Practices in Rural Bangladesh: Potential Risk Factors for Antimicrobial Drug Resistance and Emerging Diseases

    PubMed Central

    Roess, Amira A.; Winch, Peter J.; Ali, Nabeel A.; Akhter, Afsana; Afroz, Dilara; El Arifeen, Shams; Darmstadt, Gary L.; Baqui, Abdullah H.

    2013-01-01

    Antimicrobial drug administration to household livestock may put humans and animals at risk for acquisition of antimicrobial drug–resistant pathogens. To describe animal husbandry practices, including animal healthcare-seeking and antimicrobial drug use in rural Bangladesh, we conducted semi-structured in-depth interviews with key informants, including female household members (n = 79), village doctors (n = 10), and pharmaceutical representatives, veterinarians, and government officials (n = 27), and performed observations at animal health clinics (n = 3). Prevalent animal husbandry practices that may put persons at risk for acquisition of pathogens included shared housing and water for animals and humans, antimicrobial drug use for humans and animals, and crowding. Household members reported seeking human and animal healthcare from unlicensed village doctors rather than formal-sector healthcare providers and cited cost and convenience as reasons. Five times more per household was spent on animal than on human healthcare. Strengthening animal and human disease surveillance systems should be continued. Interventions are recommended to provide vulnerable populations with a means of protecting their livelihood and health. PMID:24062478

  20. [Development, aims and status quo of the EU animal disease law].

    PubMed

    Bätza, Hans-Joachim

    2012-01-01

    The development of EC legislation is outlined using swine fever and foot and mouth disease as an example, starting with the possibility of vaccinating against both animal diseases in the 1980s without substantially restricting trade with vaccinated animals or products of these animals, right up to a policy of non-vaccination with the realisation of the single market with significant restrictions on intra-Community trade if the option of an emergency vaccination were to be used.The restrictions associated with emergency vaccination are basically tantamount to a vaccination ban. To that extent, vaccination needs to be taken into consideration as an instrument of animal disease control under the EU animal health legislation currently being discussed, the aim being for vaccinated animals that have tested as virus-free to be able to be marketed without any restrictions. This will, however, only be possible if all stakeholders (EU, member states, World Organisation for Animal Health, industry, consumers) achieve a broad consensus. PMID:22372317

  1. Integrative molecular phylogeography in the context of infectious diseases on the human-animal interface.

    PubMed

    Gray, Rebecca R; Salemi, Marco

    2012-12-01

    The rate of new emerging infectious diseases entering the human population has increased over the past century, with pathogens originating from animals or from products of animal origin accounting for the vast majority. Primary risk factors for the emergence and spread of emerging zoonoses include expansion and intensification of animal agriculture and long-distance live animal transport, live animal markets, bushmeat consumption and habitat destruction. Developing effective control strategies is contingent upon the ability to test causative hypotheses of disease transmission within a statistical framework. Broadly speaking, molecular phylogeography offers a framework in which specific hypotheses regarding pathogen gene flow and dispersal within an ecological context can be compared. A number of different methods has been developed for this application. Here, our intent is firstly to discuss the application of a wide variety of statistically based methods (including Bayesian reconstruction, network parsimony analysis and regression) to specific viruses (influenza, salmon anaemia virus, foot and mouth disease and Rift Valley Fever) that have been associated with animal farming/movements; and secondly to place them in the larger framework of the threat of potential zoonotic events as well as the economic and biosecurity implications of pathogen outbreaks among our animal food sources. PMID:22931895

  2. ERAIZDA: a model for holistic annotation of animal infectious and zoonotic diseases.

    PubMed

    Buza, Teresia M; Jack, Sherman W; Kirunda, Halid; Khaitsa, Margaret L; Lawrence, Mark L; Pruett, Stephen; Peterson, Daniel G

    2015-01-01

    There is an urgent need for a unified resource that integrates trans-disciplinary annotations of emerging and reemerging animal infectious and zoonotic diseases. Such data integration will provide wonderful opportunity for epidemiologists, researchers and health policy makers to make data-driven decisions designed to improve animal health. Integrating emerging and reemerging animal infectious and zoonotic disease data from a large variety of sources into a unified open-access resource provides more plausible arguments to achieve better understanding of infectious and zoonotic diseases. We have developed a model for interlinking annotations of these diseases. These diseases are of particular interest because of the threats they pose to animal health, human health and global health security. We demonstrated the application of this model using brucellosis, an infectious and zoonotic disease. Preliminary annotations were deposited into VetBioBase database (http://vetbiobase.igbb.msstate.edu). This database is associated with user-friendly tools to facilitate searching, retrieving and downloading of disease-related information. Database URL: http://vetbiobase.igbb.msstate.edu. PMID:26581408

  3. ERAIZDA: a model for holistic annotation of animal infectious and zoonotic diseases

    PubMed Central

    Buza, Teresia M.; Jack, Sherman W.; Kirunda, Halid; Khaitsa, Margaret L.; Lawrence, Mark L.; Pruett, Stephen; Peterson, Daniel G.

    2015-01-01

    There is an urgent need for a unified resource that integrates trans-disciplinary annotations of emerging and reemerging animal infectious and zoonotic diseases. Such data integration will provide wonderful opportunity for epidemiologists, researchers and health policy makers to make data-driven decisions designed to improve animal health. Integrating emerging and reemerging animal infectious and zoonotic disease data from a large variety of sources into a unified open-access resource provides more plausible arguments to achieve better understanding of infectious and zoonotic diseases. We have developed a model for interlinking annotations of these diseases. These diseases are of particular interest because of the threats they pose to animal health, human health and global health security. We demonstrated the application of this model using brucellosis, an infectious and zoonotic disease. Preliminary annotations were deposited into VetBioBase database (http://vetbiobase.igbb.msstate.edu). This database is associated with user-friendly tools to facilitate searching, retrieving and downloading of disease-related information. Database URL: http://vetbiobase.igbb.msstate.edu PMID:26581408

  4. Sleep disturbances in the rotenone animal model of Parkinson disease.

    PubMed

    García-García, Fabio; Ponce, Sonia; Brown, Richard; Cussen, Victoria; Krueger, James M

    2005-05-01

    Parkinson disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the presence of intracytoplasmatic inclusions known as Lewy bodies. Chronic administration of rotenone (RT) produces Parkinson's-like symptoms in rats. Because PD patients have disrupted sleep patterns, we determined if chronic RT administration produces similar changes in rat sleep. RT was administered for 28 days to rats. Basal and vehicle (VH) rats received saline or dimethyl sulfoxide and polyethylene glycol (1:1), respectively. VH infusion induced a progressive decrease in non-rapid eye movement sleep (NREMS) during the 4-week period of VH infusion and REMS was reduced in the third and fourth week of VH infusion. VH infusion did not induce dopaminergic cell degeneration. Rats receiving RT infusion also showed decreased NREMS during the treatment. REMS was dramatically reduced on day 7 although subsequently on days 13 and 20 REMS was similar to basal values. After 4 weeks of RT infusion, time in REMS was decreased again. In RT-treated rats, progressive dopaminergic cell degeneration occurred in the SNc. After 4 weeks of daily injections of L-dopa in RT-infused rats, NREMS values remained similar to those values obtained after RT alone. L-dopa therapy did, however, induce a recovery of REMS in weeks 3 and 4 of RT infusion. Dopaminergic cell damage persisted in the L-dopa-RT-infused rats. We conclude that the RT-PD rat model is associated with large long-term sleep disruption, however, the vehicle, DMSO/PEG had as large an effect as RT on sleep, thus changes in sleep cannot be ascribed to loss of dopaminergic cells. Such results question the validity of the RT-PD rat model. PMID:15854587

  5. The animal-human interface and infectious disease in industrial food animal production: rethinking biosecurity and biocontainment.

    PubMed

    Graham, Jay P; Leibler, Jessica H; Price, Lance B; Otte, Joachim M; Pfeiffer, Dirk U; Tiensin, T; Silbergeld, Ellen K

    2008-01-01

    Understanding interactions between animals and humans is critical in preventing outbreaks of zoonotic disease. This is particularly important for avian influenza. Food animal production has been transformed since the 1918 influenza pandemic. Poultry and swine production have changed from small-scale methods to industrial-scale operations. There is substantial evidence of pathogen movement between and among these industrial facilities, release to the external environment, and exposure to farm workers, which challenges the assumption that modern poultry production is more biosecure and biocontained as compared with backyard or small holder operations in preventing introduction and release of pathogens. An analysis of data from the Thai government investigation in 2004 indicates that the odds of H5N1 outbreaks and infections were significantly higher in large-scale commercial poultry operations as compared with backyard flocks. These data suggest that successful strategies to prevent or mitigate the emergence of pandemic avian influenza must consider risk factors specific to modern industrialized food animal production. PMID:19006971

  6. Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

    PubMed

    Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

    2015-12-15

    Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

  7. Stem cell transplantation in neurological diseases: improving effectiveness in animal models

    PubMed Central

    Adami, Raffaella; Scesa, Giuseppe; Bottai, Daniele

    2014-01-01

    Neurological diseases afflict a growing proportion of the human population. There are two reasons for this: first, the average age of the population (especially in the industrialized world) is increasing, and second, the diagnostic tools to detect these pathologies are now more sophisticated and can be used on a higher percentage of the population. In many cases, neurological disease has a pharmacological treatment which, as in the case of Alzheimer's disease, Parkinson's disease, Epilepsy, and Multiple Sclerosis can reduce the symptoms and slow down the course of the disease but cannot reverse its effects or heal the patient. In the last two decades the transplantation approach, by means of stem cells of different origin, has been suggested for the treatment of neurological diseases. The choice of slightly different animal models and the differences in methods of stem cell preparation make it difficult to compare the results of transplantation experiments. Moreover, the translation of these results into clinical trials with human subjects is difficult and has so far met with little success. This review seeks to discuss the reasons for these difficulties by considering the differences between human and animal cells (including isolation, handling and transplantation) and between the human disease model and the animal disease model. PMID:25364724

  8. Finding new ways to prevent disease in food-producing animals.

    PubMed

    2016-01-23

    Increasing concern about antimicrobial resistance and moves to restrict the use of antibiotics in food-producing animals mean that farmers will need new ways of preventing and controlling disease in their animals. With its focus on addressing the needs of the farming industry, the Moredun Research Institute sees this as an opportunity to be at the forefront of developing new solutions. Kristy Ebanks reports from an event organised to showcase some of the institute's latest research. PMID:26795855

  9. Turbulent dispersivity under conditions relevant to airborne disease transmission between laboratory animals

    NASA Astrophysics Data System (ADS)

    Halloran, Siobhan; Wexler, Anthony; Ristenpart, William

    2014-11-01

    Virologists and other researchers who test pathogens for airborne disease transmissibility often place a test animal downstream from an inoculated animal and later determine whether the test animal became infected. Despite the crucial role of the airflow in modulating the pathogen transmission, to date the infectious disease community has paid little attention to the effect of airspeed or turbulence intensity on the probability of transmission. Here we present measurements of the turbulent dispersivity under conditions relevant to experimental tests of airborne disease transmissibility between laboratory animals. We used time lapse photography to visualize the downstream transport and turbulent dispersion of smoke particulates released from a point source downstream of a standard axial fan, thus mimicking the release and transport of expiratory aerosols exhaled by an inoculated animal. We demonstrate that the fan speed counterintuitively has no effect on the downstream plume width, a result replicated with a variety of different fan types and configurations. The results point toward a useful simplification in modeling of airborne disease transmission via fan-generated flows.

  10. Managing animal disease risk in Australia: the impact of climate change.

    PubMed

    Black, P F; Murray, J G; Nunn, M J

    2008-08-01

    Climate change is one of a number of factors that are likely to affect the future of Australian agriculture, animal production and animal health, particularly when associated with other factors such as environmental degradation, intensive animal production, an increasing human population, and expanding urbanisation. Notwithstanding the harshness and variability of Australia's climate, significant livestock industries have been developed, with the majority of products from such industries exported throughout the world. A critical factor in achieving market access has been an enviable animal health status, which is underpinned by first class animal health services with a strong legislative basis, well-trained staff, engagement of industry, effective surveillance, good scientific and laboratory support, effective emergency management procedures, a sound quarantine system, and strong political support. However, enhancements still need to be made to Australia's animal health system, for example: re-defining the science-policy interface; refining foresight, risk analysis, surveillance, diagnostics, and emergency management; improving approaches to education, training, technology transfer, communications and awareness; and engaging more with the international community in areas such as capacity building, the development of veterinary services, and disease response systems. A 'one health' approach will be adopted to bring together skills in the fields of animal, public, wildlife and environmental health. These initiatives, if managed correctly, will minimise the risks resulting from global warming and other factors predisposing to disease. PMID:18819678

  11. [Food safety and animal diseases. The French Food Safety Agency, from mad cow disease to bird flu].

    PubMed

    Keck, Frédéric

    2008-01-01

    Why has the French food safety agency been particularly mobilized on zoonoses like bovine spongiform encephalopathy ("mad cow disease") or highly pathogenic avian influenza ("bird flu") ? Because sanitary crisis make explicit an ambivalent relationship between humans and animals (animals being perceived alternatively as providers of goods and as bearers of threats), and to the circulation of life in general (the contaminated blood crises being due to the rapprochement of blood giving and blood receiving). The sociology of risks needs therefore to reintegrate the idea of an intention of the risk bearer (risk with enemy), and the sociology of alimentation needs to reintegrate the analysis of the conditions of production. Mad cow disease is the paradigmatic food safety crisis because it brings together the poles of production and consumption, of animals and humans. It therefore belongs to anthropology. PMID:18198116

  12. Prioritizing Zoonotic Diseases: Differences in Perspectives Between Human and Animal Health Professionals in North America.

    PubMed

    Ng, V; Sargeant, J M

    2016-05-01

    Zoonoses pose a significant burden of illness in North America. Zoonoses represent an additional threat to public health because the natural reservoirs are often animals, particularly wildlife, thus eluding control efforts such as quarantine, vaccination and social distancing. As there are limited resources available, it is necessary to prioritize diseases in order to allocate resources to those posing the greatest public health threat. Many studies have attempted to prioritize zoonoses, but challenges exist. This study uses a quantitative approach, conjoint analysis (CA), to overcome some limitations of traditional disease prioritization exercises. We used CA to conduct a zoonoses prioritization study involving a range of human and animal health professionals across North America; these included epidemiologists, public health practitioners, research scientists, physicians, veterinarians, laboratory technicians and nurses. A total of 699 human health professionals (HHP) and 585 animal health professionals (AHP) participated in this study. We used CA to prioritize 62 zoonotic diseases using 21 criteria. Our findings suggest CA can be used to produce reasonable criteria scores for disease prioritization. The fitted models were satisfactory for both groups with a slightly better fit for AHP compared to HHP (84.4% certainty fit versus 83.6%). Human-related criteria were more influential for HHP in their decision to prioritize zoonoses, while animal-related criteria were more influential for AHP resulting in different disease priority lists. While the differences were not statistically significant, a difference of one or two ranks could be considered important for some individuals. A potential solution to address the varying opinions is discussed. The scientific framework for disease prioritization presented can be revised on a regular basis by updating disease criteria to reflect diseases as they evolve over time; such a framework is of value allowing diseases of

  13. Translational challenges of animal models in Chagas disease drug development: a review

    PubMed Central

    Chatelain, Eric; Konar, Nandini

    2015-01-01

    Chagas disease, or American trypanosomiasis, caused by Trypanosoma cruzi parasite infection is endemic in Latin America and presents an increasing clinical challenge due to migrating populations. Despite being first identified over a century ago, only two drugs are available for its treatment, and recent outcomes from the first clinical trials in 40 years were lackluster. There is a critical need to develop new drugs to treat Chagas disease. This requires a better understanding of the progression of parasite infection, and standardization of animal models designed for Chagas disease drug discovery. Such measures would improve comparison of generated data and the predictability of test hypotheses and models designed for translation to human disease. Existing animal models address both disease pathology and treatment efficacy. Available models have limited predictive value for the preclinical evaluation of novel therapies and need to more confidently predict the efficacy of new drug candidates in clinical trials. This review highlights the overall lack of standardized methodology and assessment tools, which has hampered the development of efficacious compounds to treat Chagas disease. We provide an overview of animal models for Chagas disease, and propose steps that could be undertaken to reduce variability and improve predictability of drug candidate efficacy. New technological developments and tools may contribute to a much needed boost in the drug discovery process. PMID:26316715

  14. A knowledge based approach to matching human neurodegenerative disease and animal models

    PubMed Central

    Maynard, Sarah M.; Mungall, Christopher J.; Lewis, Suzanna E.; Imam, Fahim T.; Martone, Maryann E.

    2013-01-01

    Neurodegenerative diseases present a wide and complex range of biological and clinical features. Animal models are key to translational research, yet typically only exhibit a subset of disease features rather than being precise replicas of the disease. Consequently, connecting animal to human conditions using direct data-mining strategies has proven challenging, particularly for diseases of the nervous system, with its complicated anatomy and physiology. To address this challenge we have explored the use of ontologies to create formal descriptions of structural phenotypes across scales that are machine processable and amenable to logical inference. As proof of concept, we built a Neurodegenerative Disease Phenotype Ontology (NDPO) and an associated Phenotype Knowledge Base (PKB) using an entity-quality model that incorporates descriptions for both human disease phenotypes and those of animal models. Entities are drawn from community ontologies made available through the Neuroscience Information Framework (NIF) and qualities are drawn from the Phenotype and Trait Ontology (PATO). We generated ~1200 structured phenotype statements describing structural alterations at the subcellular, cellular and gross anatomical levels observed in 11 human neurodegenerative conditions and associated animal models. PhenoSim, an open source tool for comparing phenotypes, was used to issue a series of competency questions to compare individual phenotypes among organisms and to determine which animal models recapitulate phenotypic aspects of the human disease in aggregate. Overall, the system was able to use relationships within the ontology to bridge phenotypes across scales, returning non-trivial matches based on common subsumers that were meaningful to a neuroscientist with an advanced knowledge of neuroanatomy. The system can be used both to compare individual phenotypes and also phenotypes in aggregate. This proof of concept suggests that expressing complex phenotypes using formal

  15. Use of proteomics in the study of microbial diseases of small ruminants.

    PubMed

    Katsafadou, A I; Tsangaris, G Th; Billinis, C; Fthenakis, G C

    2015-12-14

    Objective of the paper is to review potential applications of proteomics methodologies in the study of microbial diseases of small ruminants. Proteomics has been employed for the elucidation of pathogenesis of various diseases, i.e., in the study of determinants of microbial agents and the study of host-pathogen interactions, as well as in improved disease diagnosis by the identification of biomarkers. Extensive uses of proteomics in sheep and goat diseases have been applied primarily in mastitis, in reproductive infections, in paratuberculosis, in respiratory infections and in scrapie. Mining deeper into the various proteomes and application of new methodological strategies in clinical studies will provide information about disease processes. Improvement of diagnostic techniques, development of vaccines against diseases and establishment of tools for optimum animal production are key-areas for targeted research. PMID:26233680

  16. The history of the Conference of Research Workers in Animal Diseases (CRWAD) 1920-2014.

    PubMed

    Ellis, Robert P; Ellis, L Susanne Squires; Kohler, Erwin M

    2015-12-01

    The following history has been compiled and written by the authors. The historical facts are available from the Conference of Research Workers in Animal Diseases (CRWAD) archives, dating back to letters and summaries written by the founders, and by a few of the Secretary-Treasurers from the early decades through 2014. THE ORGANIZATION AND PURPOSE: The CRWAD is a non-profit organization and has been since its origin. The sole purpose of CRWAD is to discuss and disseminate the most current research advances in animal diseases. Graduate students and industry and academic professionals present and discuss the most recent advances on subjects of interest to the CRWAD and of importance to the global livestock and companion animal industries. The oral and poster abstracts of new and unpublished data presented at the meeting sessions are published each year in the CRWAD Proceedings (formerly the CRWAD Abstracts). CRWAD publishes, copyrights, and distributes the Proceedings. The presentations are arranged into the following 10 sections, according to the primary topic of the presentation: Bacterial Pathogenesis, Biosafety and Biosecurity, Companion Animal Epidemiology, Ecology and Management of Foodborne Agents, Epidemiology and Animal Health Economics, Immunology, Pathobiology of Enteric and Foodborne Pathogens, Respiratory Diseases, Vector-Borne and Parasitic Diseases, and Viral Pathogenesis. Prospective members should be actively engaged in animal disease research or research administration. Meeting information and membership applications may be obtained by contacting the Executive Director or by visiting the CRWAD website. Annual abstracts are currently available on-line at the On-line Meeting Planner and Itinerary Builder, with access through the CRWAD website. PMID:26690792

  17. Monkeypox disease transmission in an experimental setting: prairie dog animal model.

    PubMed

    Hutson, Christina L; Carroll, Darin S; Gallardo-Romero, Nadia; Weiss, Sonja; Clemmons, Cody; Hughes, Christine M; Salzer, Johanna S; Olson, Victoria A; Abel, Jason; Karem, Kevin L; Damon, Inger K

    2011-01-01

    Monkeypox virus (MPXV) is considered the most significant human public health threat in the genus Orthopoxvirus since the eradication of variola virus (the causative agent of smallpox). MPXV is a zoonotic agent endemic to forested areas of Central and Western Africa. In 2003, MPXV caused an outbreak in the United States due to the importation of infected African rodents, and subsequent sequential infection of North American prairie dogs (Cynomys ludovicianus) and humans. In previous studies, the prairie dog MPXV model has successfully shown to be very useful for understanding MPXV since the model emulates key characteristics of human monkeypox disease. In humans, percutaneous exposure to animals has been documented but the primary method of human-to-human MPXV transmission is postulated to be by respiratory route. Only a few animal model studies of MPXV transmission have been reported. Herein, we show that MPXV infected prairie dogs are able to transmit the virus to naive animals through multiple transmission routes. All secondarily exposed animals were infected with MPXV during the course of the study. Notably, animals secondarily exposed appeared to manifest more severe disease; however, the disease course was very similar to those of experimentally challenged animals including inappetence leading to weight loss, development of lesions, production of orthopoxvirus antibodies and shedding of similar levels or in some instances higher levels of MPXV from the oral cavity. Disease was transmitted via exposure to contaminated bedding, co-housing, or respiratory secretions/nasal mucous (we could not definitively say that transmission occurred via respiratory route exclusively). Future use of the model will allow us to evaluate infection control measures, vaccines and antiviral strategies to decrease disease transmission. PMID:22164263

  18. 9 CFR 71.14 - Slaughter of poultry or other animals to prevent spread of disease; ascertainment of value and...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... to prevent spread of disease; ascertainment of value and compensation. 71.14 Section 71.14 Animals... or other animals to prevent spread of disease; ascertainment of value and compensation. When, in order to prevent the spread of any contagious, infectious, or communicable disease, it becomes...

  19. 9 CFR 71.14 - Slaughter of poultry or other animals to prevent spread of disease; ascertainment of value and...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... to prevent spread of disease; ascertainment of value and compensation. 71.14 Section 71.14 Animals... or other animals to prevent spread of disease; ascertainment of value and compensation. When, in order to prevent the spread of any contagious, infectious, or communicable disease, it becomes...

  20. 9 CFR 71.14 - Slaughter of poultry or other animals to prevent spread of disease; ascertainment of value and...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... to prevent spread of disease; ascertainment of value and compensation. 71.14 Section 71.14 Animals... or other animals to prevent spread of disease; ascertainment of value and compensation. When, in order to prevent the spread of any contagious, infectious, or communicable disease, it becomes...

  1. 9 CFR 71.14 - Slaughter of poultry or other animals to prevent spread of disease; ascertainment of value and...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... to prevent spread of disease; ascertainment of value and compensation. 71.14 Section 71.14 Animals... or other animals to prevent spread of disease; ascertainment of value and compensation. When, in order to prevent the spread of any contagious, infectious, or communicable disease, it becomes...

  2. Household Animal and Human Medicine Use and Animal Husbandry Practices in Rural Bangladesh: Risk Factors for Emerging Zoonotic Disease and Antibiotic Resistance.

    PubMed

    Roess, A A; Winch, P J; Akhter, A; Afroz, D; Ali, N A; Shah, R; Begum, N; Seraji, H R; El Arifeen, S; Darmstadt, G L; Baqui, A H

    2015-11-01

    Animal antimicrobial use and husbandry practices increase risk of emerging zoonotic disease and antibiotic resistance. We surveyed 700 households to elicit information on human and animal medicine use and husbandry practices. Households that owned livestock (n = 265/459, 57.7%) reported using animal treatments 630 times during the previous 6 months; 57.6% obtained medicines, including antibiotics, from drug sellers. Government animal healthcare providers were rarely visited (9.7%), and respondents more often sought animal health care from pharmacies and village doctors (70.6% and 11.9%, respectively), citing the latter two as less costly and more successful based on past performance. Animal husbandry practices that could promote the transmission of microbes from animals to humans included the following: the proximity of chickens to humans (50.1% of households reported that the chickens slept in the bedroom); the shared use of natural bodies of water for human and animal bathing (78.3%); the use of livestock waste as fertilizer (60.9%); and gender roles that dictate that females are the primary caretakers of poultry and children (62.8%). In the absence of an effective animal healthcare system, villagers must depend on informal healthcare providers for treatment of their animals. Suboptimal use of antimicrobials coupled with unhygienic animal husbandry practices is an important risk factor for emerging zoonotic disease and resistant pathogens. PMID:25787116

  3. Epidemiology and Economics Support Decisions about Freedom from Aquatic Animal Disease.

    PubMed

    Peeler, E J; Otte, M J

    2016-06-01

    In this study, we review the application of epidemiology and economics to decision-making about freedom from aquatic animal disease, at national and regional level, and recent examples from Europe. Epidemiological data (e.g. pathogen prevalence and distribution) determine the technical feasibility and cost of eradication. The eradication of pathogens which exist in wild populations, or in a latent state, is technically difficult, uncertain and expensive. Notably, the eradication of diseases of molluscs is rarely attempted because host populations (farmed and wild) cannot be completely removed from open water systems. Doubt about the success of eradication translates into uncertain ex-ante cost estimates. Additionally, the benefits of an official disease-free status cannot be estimated with any accuracy. For example, in Europe, official freedom from epizootic ulcerative syndrome and white spot syndrome virus has not been pursued, arguably because the evidence does not exist for the benefits (reduced risk of disease in wild populations) to be estimated and thus weighed against the costs of maintaining disease freedom (e.g. restriction on imports). Economic analysis must assess not only whether the benefits of disease freedom outweigh costs, but whether it is the economically optimal disease control option. Government may also want to compare investment in aquatic animal health with other opportunities. As resources become scarce, governments have sought to share costs of disease control with industry, and thus to ensure equity, the distribution benefits must be known so costs can be borne by those who benefit. The economic principles to support decisions about disease freedom are well established, but their application is constrained by lack of epidemiological data, which may explain the lack of economic analysis in support of aquatic animal management in Europe. The integration of epidemiology and economics in disease control planning will identify research aimed at

  4. Some virus diseases of domestic animals in the Sultanate of Oman.

    PubMed

    Hedger, R S; Barnett, I T; Gray, D F

    1980-05-01

    Little is known of the occurrence of animal virus diseases in the Sultanate of Oman. This paper reports the results of a countrywide survey carried out in 1978 to establish the prevalence of some important viral pathogens of domestic animals with the dual purpose of providing baselines for future investigations and guidelines for those entrusted with disease control. Foot-and-mouth disease virus type O, previously identified in Oman in 1976, was isolated from clinically affected animals. In addition, virus types A and Asia 1 were isolated from unaffected animals. Serological studies indicated that infection with all 3 types had been widespread. The presence of infectious bovine rhinotracheitis was confirmed by virus isolations and sheep and goat pox, long recognised in Oman, was confirmed by the demonstration of pox particles in dried lesion material. In serological studies antibodies were found to the viruses of peste des petits ruminants, bovine herpes mammillitis, bovine virus diarrhoea, parainfluenza 3 and African horse sickness. There were no significant antibody levels to rinderpest in unvaccinated animals and no antibody to equine infectious anaemia or vesicular stomatitis viruses. PMID:6251586

  5. Transgenic animal models for study of the pathogenesis of Huntington’s disease and therapy

    PubMed Central

    Chang, Renbao; Liu, Xudong; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    Huntington’s disease (HD) is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner. PMID:25931812

  6. Honey bee fungal pathogen, Ascosphaera apis; current understanding of host-pathogen interactions and host mechanisms of resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter provides an overview of the profound knowledge accumulated in recent years from genome and transcriptome-wide attempts to determine host immune responses to honey bee fungal diseases and to identify quantitative trait loci (QTLs) that underline host mechanisms of resistance. Considering...

  7. Management of Ocular Diseases Using Lutein and Zeaxanthin: What Have We Learned from Experimental Animal Studies?

    PubMed

    Xue, Chunyan; Rosen, Richard; Jordan, Adrienne; Hu, Dan-Ning

    2015-01-01

    Zeaxanthin and lutein are two carotenoid pigments that concentrated in the retina, especially in the macula. The effects of lutein and zeaxanthin on the prevention and treatment of various eye diseases, including age-related macular degeneration, diabetic retinopathy and cataract, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, and uveitis, have been studied in different experimental animal models. In these animal models, lutein and zeaxanthin have been reported to have beneficial effects in protecting ocular tissues and cells (especially the retinal neurons) against damage caused by different etiological factors. The mechanisms responsible for these effects of lutein and zeaxanthin include prevention of phototoxic damage by absorption of blue light, reduction of oxidative stress through antioxidant activity and free radical scavenging, and their anti-inflammatory and antiangiogenic properties. The results of these experimental animal studies may provide new preventive and therapeutic procedures for clinical management of various vision-threatening diseases. PMID:26617995

  8. Antisense treatment of caliciviridae: an emerging disease agent of animals and humans.

    PubMed

    Smith, Alvin W; Matson, David O; Stein, David A; Skilling, Douglas E; Kroeker, Andrew D; Berke, Tamas; Iversen, Patrick L

    2002-04-01

    The Earth's oceans are the primary reservoir for an emerging family of RNA viruses, the Caliciviridae, which can cause a spectrum of diseases in marine animals, wildlife, farm animals, pets and humans. Certain members of this family have unusually broad host ranges, and some are zoonotic (transmissible from animals to humans). The RNA virus replicative processes lack effective genetic repair mechanisms, and, therefore, virtually every calicivirus replicate is a mutant. Hence, traditional therapeutics dependent on specific nucleic acid sequences or protein epitopes lack the required diversity of sequence or conformational specificity that would be required to reliably detect, prevent or treat infections from these mutant clusters (quasi-species) of RNA viruses, including the Caliciviridae. Antisense technology using phosphorodiamidate morpholino oligomers shows promise in overcoming these current diagnostic and therapeutic problems inherent with newly emerging viral diseases. PMID:12044040

  9. The control of microbial diseases in animals: alternatives to the use of antibiotics.

    PubMed

    Wierup, M

    2000-05-01

    In animal husbandry the control and prevention of infectious diseases is of basic economic importance. The introduction of antibiotics to treat bacterial infections almost 50 years ago led to a dramatic improvement in animal production. The emergence of antibiotic resistant strains demonstrates that the treatment of bacterial infections can not rely on the use of antibiotics without some critical consideration. Special attention has been paid to the use of antibiotics in animals including antimicrobial growth promoters because these can contribute to the problems with antibiotic resistance in humans. This has strongly emphasized the need to introduce disease preventive methods. A theory and methods for the prevention of diseases is presented that is based upon the effect on the target animal population of microbial exposure, defence and immunity to infections and combinations of these. It is emphasized that antibiotics should be an integral part of other disease preventive methods and used only when other methods have failed. They should not be included in the first line of action. PMID:10794953

  10. Monitoring for the management of disease risk in animal translocation programmes

    USGS Publications Warehouse

    Nichols, James D.; Hollmen, Tuula E.; Grand, James B.

    2016-01-01

    Monitoring is best viewed as a component of some larger programme focused on science or conservation. The value of monitoring is determined by the extent to which it informs the parent process. Animal translocation programmes are typically designed to augment or establish viable animal populations without changing the local community in any detrimental way. Such programmes seek to minimize disease risk to local wild animals, to translocated animals, and in some cases to humans. Disease monitoring can inform translocation decisions by (1) providing information for state-dependent decisions, (2) assessing progress towards programme objectives, and (3) permitting learning in order to make better decisions in the future. Here we discuss specific decisions that can be informed by both pre-release and post-release disease monitoring programmes. We specify state variables and vital rates needed to inform these decisions. We then discuss monitoring data and analytic methods that can be used to estimate these state variables and vital rates. Our discussion is necessarily general, but hopefully provides a basis for tailoring disease monitoring approaches to specific translocation programmes.

  11. Using Earth Observation to Forecast Human and Animal Vector-Borne Disease Outbreaks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Earth observing technologies, including data from with earth-orbiting satellites, coupled with new investigations and a better understanding of the impact of environmental factors on transmission dynamics of mosquito-borne diseases permitted us to forecast Rift Valley fever (RVF) outbreaks in animal...

  12. Tick-borne Diseases in Animals and USDA Research on Tick Control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tick-borne diseases represent a major threat to animal health in the United States. The cattle industry in the United States has benefited greatly from the continued USDA efforts through the Cattle Fever Tick Eradication Program in preventing the re-introduction of cattle ticks and associated pathog...

  13. Mechanisms of Acupuncture Effect on Alzheimer's Disease in Animal- Based Researches.

    PubMed

    Cao, Yan; Zhang, Li-Wen; Wang, Jian; Du, Si-Qi; Xiao, Ling-Yong; Tu, Jian-Feng; Liu, Cun-Zhi

    2016-01-01

    Alzheimer's disease is the most common type of dementia in the aging population worldwide. The etiology and treatment of Alzheimer's disease are still not very clear. Finding a new treatment is urgent due to the increasing population aging. Acupuncture has been practicing in China for more than 3000 years and reported to be beneficial in treating cognitive impairment of Alzheimer's disease. This paper reviews the recent development on the effect of acupuncture on Alzheimer's disease in animal-based researches. It is suggested that acupuncture improves cognitive function of Alzheimer's disease by regulating glucose metabolism, enhancing neurotransmission as well as reducing oxidative stress, Aβ protein deposition, and neuronal apoptosis. However, it is still difficult to clarify which specific signaling pathway contributes to the acupuncture effect. Better designed studies are recommended to investigate the effects of acupuncture on Alzheimer's disease. PMID:26268326

  14. [Use of geographical information systems in parasitic diseases and the importance of animal health economics].

    PubMed

    Ciçek, Hasan; Ciçek, Hatice; Senkul, Cetin; Tandoğan, Murat

    2008-01-01

    In the world, economical losses due to the parasitic diseases reach enormous ratios in animal production. Both developed and developing countries set aside a considerable budget to control these parasitic diseases. This situation aids in the improvement of control methods of parasitic diseases. Also, it causes new ways of investigation that includes observation, evaluation and prevention of parasitic diseases. The Geographical Information System (GIS) has recently become one of the most common methods utilized to provide disease information technology with computer supported technology in many countries. The most important qualities of GIS are the formation of a powerful database, continual updating and rapid provision of coordination related to units. Many factors are evaluated at the same time by the system and also, results from analysis of data related to disease and their causes could reduce or prevent economical losses due to parasitic disease. In this study, possible uses of Geographical Information Systems against parasitic diseases and an approach in terms of animal health economics were presented. PMID:18985590

  15. Animal Models of CNS Viral Disease: Examples from Borna Disease Virus Models

    PubMed Central

    Solbrig, Marylou V.

    2010-01-01

    Borna disease (BD), caused by the neurotropic RNA virus, Borna Disease virus, is an affliction ranging from asymptomatic to fatal meningoencephalitis across naturally and experimentally infected warmblooded (mammalian and bird) species. More than 100 years after the first clinical descriptions of Borna disease in horses and studies beginning in the 1980's linking Borna disease virus to human neuropsychiatric diseases, experimentally infected rodents have been used as models for examining behavioral, neuropharmacological, and neurochemical responses to viral challenge at different stages of life. These studies have contributed to understanding the role of CNS viral injury in vulnerability to behavioral, developmental, epileptic, and neurodegenerative diseases and aided evaluation of the proposed and still controversial links to human disease. PMID:20204069

  16. Animal viral diseases and global change: bluetongue and West Nile fever as paradigms.

    PubMed

    Jiménez-Clavero, Miguel Á

    2012-01-01

    Environmental changes have an undoubted influence on the appearance, distribution, and evolution of infectious diseases, and notably on those transmitted by vectors. Global change refers to environmental changes arising from human activities affecting the fundamental mechanisms operating in the biosphere. This paper discusses the changes observed in recent times with regard to some important arboviral (arthropod-borne viral) diseases of animals, and the role global change could have played in these variations. Two of the most important arboviral diseases of animals, bluetongue (BT) and West Nile fever/encephalitis (WNF), have been selected as models. In both cases, in the last 15 years an important leap forward has been observed, which has lead to considering them emerging diseases in different parts of the world. BT, affecting domestic ruminants, has recently afflicted livestock in Europe in an unprecedented epizootic, causing enormous economic losses. WNF affects wildlife (birds), domestic animals (equines), and humans, thus, beyond the economic consequences of its occurrence, as a zoonotic disease, it poses an important public health threat. West Nile virus (WNV) has expanded in the last 12 years worldwide, and particularly in the Americas, where it first occurred in 1999, extending throughout the Americas relentlessly since then, causing a severe epidemic of disastrous consequences for public health, wildlife, and livestock. In Europe, WNV is known long time ago, but it is since the last years of the twentieth century that its incidence has risen substantially. Circumstances such as global warming, changes in land use and water management, increase in travel, trade of animals, and others, can have an important influence in the observed changes in both diseases. The following question is raised: What is the contribution of global changes to the current increase of these diseases in the world? PMID:22707955

  17. Animal viral diseases and global change: bluetongue and West Nile fever as paradigms

    PubMed Central

    Jiménez-Clavero, Miguel Á

    2012-01-01

    Environmental changes have an undoubted influence on the appearance, distribution, and evolution of infectious diseases, and notably on those transmitted by vectors. Global change refers to environmental changes arising from human activities affecting the fundamental mechanisms operating in the biosphere. This paper discusses the changes observed in recent times with regard to some important arboviral (arthropod-borne viral) diseases of animals, and the role global change could have played in these variations. Two of the most important arboviral diseases of animals, bluetongue (BT) and West Nile fever/encephalitis (WNF), have been selected as models. In both cases, in the last 15 years an important leap forward has been observed, which has lead to considering them emerging diseases in different parts of the world. BT, affecting domestic ruminants, has recently afflicted livestock in Europe in an unprecedented epizootic, causing enormous economic losses. WNF affects wildlife (birds), domestic animals (equines), and humans, thus, beyond the economic consequences of its occurrence, as a zoonotic disease, it poses an important public health threat. West Nile virus (WNV) has expanded in the last 12 years worldwide, and particularly in the Americas, where it first occurred in 1999, extending throughout the Americas relentlessly since then, causing a severe epidemic of disastrous consequences for public health, wildlife, and livestock. In Europe, WNV is known long time ago, but it is since the last years of the twentieth century that its incidence has risen substantially. Circumstances such as global warming, changes in land use and water management, increase in travel, trade of animals, and others, can have an important influence in the observed changes in both diseases. The following question is raised: What is the contribution of global changes to the current increase of these diseases in the world? PMID:22707955

  18. From animal models to human disease: a genetic approach for personalized medicine in ALS.

    PubMed

    Picher-Martel, Vincent; Valdmanis, Paul N; Gould, Peter V; Julien, Jean-Pierre; Dupré, Nicolas

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10 % of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases. PMID:27400686

  19. Computational Prediction of Alzheimer's and Parkinson's Disease MicroRNAs in Domestic Animals.

    PubMed

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

    2016-06-01

    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

  20. Currently important animal disease management issues in sub-Saharan Africa.

    PubMed

    Thomson, G R

    2009-03-01

    The present international approach to management of transboundary animal diseases (TADs) is based on the assumption that most can be eradicated; consequently, that is the usual objective adopted by international organizations concerned with animal health. However, for sub-Saharan Africa and southern Africa more particularly, eradication of most TADs is impossible for the foreseeable future for a variety of technical, financial and logistical reasons. Compounding this, the present basis for access to international markets for products derived from animals requires that the area of origin (country or zone) is free from trade-influencing TADs. The ongoing development of transfrontier conservation areas (TFCAs), extending across huge areas of southern Africa, therefore presents a development conundrum because it makes creation of geographic areas free from TADs more difficult and brings development based on wildlife conservation on the one hand and that based on livestock production on the other into sharp conflict. Sub-Saharan Africa is consequently confronted by a complex problem that contributes significantly to retarded rural development which, in turn, impedes poverty alleviation. In southern Africa specifically, foot-and-mouth disease (FMD) presents the greatest problem in relation to access to international markets for animal products. However, it is argued that this problem could be overcome by a combination between (1) implementation of a commodity-based approach to trade in products derived from animals and (2) amendment of the international standards for FMD specifically (i.e. the FMD chapter in the Terrestrial Animal Health Code of the World Organisation for Animal Health [OIE]) so that occurrence of SAT serotype viruses in free-living African buffalo need not necessarily mean exclusion of areas where buffalo occur from international markets for animal products. This would overcome a presently intractable constraint to market access for southern African

  1. Rapid Cohort Generation and Analysis of Disease Spectrum of Large Animal Model of Cone Dystrophy

    PubMed Central

    Kostic, Corinne; Lillico, Simon Geoffrey; Crippa, Sylvain Vincent; Grandchamp, Nicolas; Pilet, Héloïse; Philippe, Stéphanie; Lu, Zen; King, Tim James; Mallet, Jacques; Sarkis, Chamsy; Arsenijevic, Yvan; Whitelaw, Christopher Bruce Alexander

    2013-01-01

    Large animal models are an important resource for the understanding of human disease and for evaluating the applicability of new therapies to human patients. For many diseases, such as cone dystrophy, research effort is hampered by the lack of such models. Lentiviral transgenesis is a methodology broadly applicable to animals from many different species. When conjugated to the expression of a dominant mutant protein, this technology offers an attractive approach to generate new large animal models in a heterogeneous background. We adopted this strategy to mimic the phenotype diversity encounter in humans and generate a cohort of pigs for cone dystrophy by expressing a dominant mutant allele of the guanylate cyclase 2D (GUCY2D) gene. Sixty percent of the piglets were transgenic, with mutant GUCY2D mRNA detected in the retina of all animals tested. Functional impairment of vision was observed among the transgenic pigs at 3 months of age, with a follow-up at 1 year indicating a subsequent slower progression of phenotype. Abnormal retina morphology, notably among the cone photoreceptor cell population, was observed exclusively amongst the transgenic animals. Of particular note, these transgenic animals were characterized by a range in the severity of the phenotype, reflecting the human clinical situation. We demonstrate that a transgenic approach using lentiviral vectors offers a powerful tool for large animal model development. Not only is the efficiency of transgenesis higher than conventional transgenic methodology but this technique also produces a heterogeneous cohort of transgenic animals that mimics the genetic variation encountered in human patients. PMID:23977029

  2. Regional and international approaches on prevention and control of animal transboundary and emerging diseases.

    PubMed

    Domenech, J; Lubroth, J; Eddi, C; Martin, V; Roger, F

    2006-10-01

    Transboundary animal diseases pose a serious risk to the world animal agriculture and food security and jeopardize international trade. The world has been facing devastating economic losses from major outbreaks of transboundary animal diseases (TADs) such as foot-and-mouth disease, classical swine fever, rinderpest, peste des petits ruminants (PPR), and Rift Valley fever. Lately the highly pathogenic avian influenza (HPAI) due to H5N1 virus, has become an international crisis as all regions around the world can be considered at risk. In the past decades, public health authorities within industrialized countries have been faced with an increasing number of food safety issues. The situation is equally serious in developing countries. The globalization of food (and feed) trade, facilitated by the liberalization of world trade, while offering many benefits and opportunities, also represents new risks. The GF-TADs Global Secretariat has carried out several regional consultations for the identification of priority diseases and best ways for their administration, prevention and control. In the questionnaires carried out and through the consultative process, it was noted that globally, FMD was ranked as the first and foremost priority. Rift Valley fever, and today highly pathogenic avian influenza, are defined as major animal diseases which also affect human health. PPR and CBPP, a disease which is particularly serious in Africa and finally, African swine fever (ASF) and classical swine fever (CSF) are also regionally recognised as top priorities on which the Framework is determined to work. The FAO philosophy--shared by the OIE--embraces the need to prevent and control TADs and emerging diseases at their source, which is most of the time in developing countries. Regional and international approaches have to be followed, and the FAO and OIE GF-TADs initiative provides the appropriate concepts and objectives as well as an organizational framework to link international and

  3. Evidence-based early clinical detection of emerging diseases in food animals and zoonoses: two cases.

    PubMed

    Saegerman, Claude; Humblet, Marie-France; Porter, Sarah Rebecca; Zanella, Gina; Martinelle, Ludovic

    2012-03-01

    If diseases of food-producing animals or zoonoses (re-)emerge, early clinical decision making is of major importance. In this particular condition, it is difficult to apply a classic evidence-based veterinary medicine process, because of a lack of available published data. A method based on the partition of field clinical observations (evidences) could be developed as an interesting alternative approach. The classification and regression tree (CART) analysis was used to improve the early clinical detection in two cases of emerging diseases: bovine spongiform encephalopathy (mad cow disease) and bluetongue due to the serotype 8-virus in cattle. PMID:22374122

  4. Multidisciplinary and Evidence-based Method for Prioritizing Diseases of Food-producing Animals and Zoonoses

    PubMed Central

    Humblet, Marie-France; Vandeputte, Sébastien; Albert, Adelin; Gosset, Christiane; Kirschvink, Nathalie; Haubruge, Eric; Fecher-Bourgeois, Fabienne; Pastoret, Paul-Pierre

    2012-01-01

    To prioritize 100 animal diseases and zoonoses in Europe, we used a multicriteria decision-making procedure based on opinions of experts and evidence-based data. Forty international experts performed intracategory and intercategory weighting of 57 prioritization criteria. Two methods (deterministic with mean of each weight and probabilistic with distribution functions of weights by using Monte Carlo simulation) were used to calculate a score for each disease. Consecutive ranking was established. Few differences were observed between each method. Compared with previous prioritization methods, our procedure is evidence based, includes a range of fields and criteria while considering uncertainty, and will be useful for analyzing diseases that affect public health. PMID:22469519

  5. Risk-based methods for fish and terrestrial animal disease surveillance.

    PubMed

    Oidtmann, Birgit; Peeler, Edmund; Lyngstad, Trude; Brun, Edgar; Bang Jensen, Britt; Stärk, Katharina D C

    2013-10-01

    Over recent years there have been considerable methodological developments in the field of animal disease surveillance. The principles of risk analysis were conceptually applied to surveillance in order to further develop approaches and tools (scenario tree modelling) to design risk-based surveillance (RBS) programmes. In the terrestrial animal context, examples of risk-based surveillance have demonstrated the substantial potential for cost saving, and a similar benefit is expected also for aquatic animals. RBS approaches are currently largely absent for aquatic animal diseases. A major constraint in developing RBS designs in the aquatic context is the lack of published data to assist in the design of RBS: this applies to data on (i) the relative risk of farm sites becoming infected due to the presence or absence of a given risk factor; (ii) the sensitivity of diagnostic tests (specificity is often addressed by follow-up investigation and re-testing and therefore less of a concern); (iii) data on the variability of prevalence of infection for fish within a holding unit, between holding units and at farm level. Another constraint is that some of the most basic data for planning surveillance are missing, e.g. data on farm location and animal movements. In Europe, registration or authorisation of fish farms has only recently become a requirement under EU Directive 2006/88. Additionally, the definition of the epidemiological unit (at site or area level) in the context of aquaculture is a challenge due to the often high level of connectedness (mainly via water) of aquaculture facilities with the aquatic environment. This paper provides a review of the principles, methods and examples of RBS in terrestrial, farmed and wild animals. It discusses the special challenges associated with surveillance for aquatic animal diseases (e.g. accessibility of animals for inspection and sampling, complexity of rearing systems) and provides an overview of current developments relevant

  6. Systems Approaches to Animal Disease Surveillance and Resource Allocation: Methodological Frameworks for Behavioral Analysis

    PubMed Central

    Rich, Karl M.; Denwood, Matthew J.; Stott, Alistair W.; Mellor, Dominic J.; Reid, Stuart W. J.; Gunn, George J.

    2013-01-01

    While demands for animal disease surveillance systems are growing, there has been little applied research that has examined the interactions between resource allocation, cost-effectiveness, and behavioral considerations of actors throughout the livestock supply chain in a surveillance system context. These interactions are important as feedbacks between surveillance decisions and disease evolution may be modulated by their contextual drivers, influencing the cost-effectiveness of a given surveillance system. This paper identifies a number of key behavioral aspects involved in animal health surveillance systems and reviews some novel methodologies for their analysis. A generic framework for analysis is discussed, with exemplar results provided to demonstrate the utility of such an approach in guiding better disease control and surveillance decisions. PMID:24348922

  7. Recent advances using zebrafish animal models for muscle disease drug discovery

    PubMed Central

    Maves, Lisa

    2015-01-01

    Introduction Animal models have enabled great progress in the discovery and understanding of pharmacological approaches for treating muscle diseases like Duchenne muscular dystrophy. Areas covered With this article, the author provides the reader with a description of the zebrafish animal model, which has been employed to identify and study pharmacological approaches to muscle disease. In particular, the author focuses on how both large-scale chemical screens and targeted drug treatment studies have established zebrafish as an important model for muscle disease drug discovery. Expert opinion There are a number of opportunities arising for the use of zebrafish models for further developing pharmacological approaches to muscle diseases, including studying drug combination therapies and utilizing genome editing to engineer zebrafish muscle disease models. It is the author’s particular belief that the availability of a wide range of zebrafish transgenic strains for labeling immune cell types, combined with live imaging and drug treatment of muscle disease models, should allow for new elegant studies demonstrating how pharmacological approaches might influence inflammation and the immune response in muscle disease. PMID:24931439

  8. Animal models for probing the developmental basis of disease and dysfunction paradigm.

    PubMed

    Heindel, Jerrold J

    2008-02-01

    There is a major paradigm shift taking place in science that while simple is profound. The new paradigm suggests that susceptibility to disease is set in utero or neonatally as a result of the influences of nutrition and exposures to environmental stressors/toxicants. In utero nutrition and/or in utero or neonatal exposures to environmental toxicants alter susceptibility to disease later in life as a result of their ability to affect the programming of tissue function that occurs during development. This concept, which is still a hypothesis undergoing scientific testing and scrutiny, is called the developmental basis of health and disease. If true, then it says that the focus on disease prevention and intervention must change from the time of disease onset to perhaps decades prior: during the in utero and neonatal period. Perhaps the reason it has been so difficult to link environmental exposure to disease susceptibility is that scientists have been looking at the wrong time! Certainly, not all exposures that result in increased disease or dysfunction occur during development. This paradigm shift just suggests that this is a sensitive window of exposure that should be examined more thoroughly. This overview focuses on animal models for the assessment of this new scientific paradigm and the animal data that now supports it. PMID:18226058

  9. Current neuroimaging techniques in Alzheimer's disease and applications in animal models

    PubMed Central

    Zhang, Linda; Chang, Raymond Chuen-Chung; Chu, Leung-Wing; Mak, Henry Ka-Fung

    2012-01-01

    With Alzheimer’s disease (AD) quickly becoming the most costly disease to society, and with no disease-modifying treatment currently, prevention and early detection have become key points in AD research. Important features within this research focus on understanding disease pathology, as well as finding biomarkers that can act as early indicators and trackers of disease progression or potential treatment. With the advances in neuroimaging technology and the development of new imaging techniques, the search for cheap, noninvasive, sensitive biomarkers becomes more accessible. Modern neuroimaging techniques are able to cover most aspects of disease pathology, including visualization of senile plaques and neurofibrillary tangles, cortical atrophy, neuronal loss, vascular damage, and changes in brain biochemistry. These methods can provide complementary information, resulting in an overall picture of AD. Additionally, applying neuroimaging to animal models of AD could bring about greater understanding in disease etiology and experimental treatments whilst remaining in vivo. In this review, we present the current neuroimaging techniques used in AD research in both their human and animal applications, and discuss how this fits in to the overall goal of understanding AD. PMID:23133824

  10. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming.

    PubMed

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-02-26

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  11. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming

    PubMed Central

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-01-01

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  12. Imaging Techniques for Small Animal Models of Pulmonary Disease: MR Microscopy

    PubMed Central

    Driehuys, Bastiaan; Hedlund, Laurence W.

    2009-01-01

    In vivo magnetic resonance microscopy (MRM) of the small animal lung has become a valuable research tool, especially for preclinical studies. MRM offers a noninvasive and nondestructive tool for imaging small animals longitudinally and at high spatial resolution. We summarize some of the technical and biologic problems and solutions associated with imaging the small animal lung and describe several important pulmonary disease applications. A major advantage of MR is direct imaging of the gas spaces of the lung using breathable gases such as helium and xenon. When polarized, these gases become rich MR signal sources. In animals breathing hyperpolarized helium, the dynamics of gas distribution can be followed and airway constrictions and obstructions can be detected. Diffusion coefficients of helium can be calculated from diffusion-sensitive images, which can reveal micro-structural changes in the lungs associated with pathologies such as emphysema and fibrosis. Unlike helium, xenon in the lung is absorbed by blood and exhibits different frequencies in gas, tissue, or erythrocytes. Thus, with MR imaging, the movement of xenon gas can be tracked through pulmonary compartments to detect defects of gas transfer. MRM has become a valuable tool for studying morphologic and functional changes in small animal models of lung diseases. PMID:17325972

  13. Host behaviour-parasite feedback: an essential link between animal behaviour and disease ecology.

    PubMed

    Ezenwa, Vanessa O; Archie, Elizabeth A; Craft, Meggan E; Hawley, Dana M; Martin, Lynn B; Moore, Janice; White, Lauren

    2016-04-13

    Animal behaviour and the ecology and evolution of parasites are inextricably linked. For this reason, animal behaviourists and disease ecologists have been interested in the intersection of their respective fields for decades. Despite this interest, most research at the behaviour-disease interface focuses either on how host behaviour affects parasites or how parasites affect behaviour, with little overlap between the two. Yet, the majority of interactions between hosts and parasites are probably reciprocal, such that host behaviour feeds back on parasites and vice versa. Explicitly considering these feedbacks is essential for understanding the complex connections between animal behaviour and parasite ecology and evolution. To illustrate this point, we discuss how host behaviour-parasite feedbacks might operate and explore the consequences of feedback for studies of animal behaviour and parasites. For example, ignoring the feedback of host social structure on parasite dynamics can limit the accuracy of predictions about parasite spread. Likewise, considering feedback in studies of parasites and animal personalities may provide unique insight about the maintenance of variation in personality types. Finally, applying the feedback concept to links between host behaviour and beneficial, rather than pathogenic, microbes may shed new light on transitions between mutualism and parasitism. More generally, accounting for host behaviour-parasite feedbacks can help identify critical gaps in our understanding of how key host behaviours and parasite traits evolve and are maintained. PMID:27053751

  14. Host behaviour–parasite feedback: an essential link between animal behaviour and disease ecology

    PubMed Central

    Archie, Elizabeth A.; Craft, Meggan E.; Hawley, Dana M.; Martin, Lynn B.; Moore, Janice; White, Lauren

    2016-01-01

    Animal behaviour and the ecology and evolution of parasites are inextricably linked. For this reason, animal behaviourists and disease ecologists have been interested in the intersection of their respective fields for decades. Despite this interest, most research at the behaviour–disease interface focuses either on how host behaviour affects parasites or how parasites affect behaviour, with little overlap between the two. Yet, the majority of interactions between hosts and parasites are probably reciprocal, such that host behaviour feeds back on parasites and vice versa. Explicitly considering these feedbacks is essential for understanding the complex connections between animal behaviour and parasite ecology and evolution. To illustrate this point, we discuss how host behaviour–parasite feedbacks might operate and explore the consequences of feedback for studies of animal behaviour and parasites. For example, ignoring the feedback of host social structure on parasite dynamics can limit the accuracy of predictions about parasite spread. Likewise, considering feedback in studies of parasites and animal personalities may provide unique insight about the maintenance of variation in personality types. Finally, applying the feedback concept to links between host behaviour and beneficial, rather than pathogenic, microbes may shed new light on transitions between mutualism and parasitism. More generally, accounting for host behaviour–parasite feedbacks can help identify critical gaps in our understanding of how key host behaviours and parasite traits evolve and are maintained. PMID:27053751

  15. Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease

    PubMed Central

    Chinnadurai, Raghavan; Ng, Spencer; Velu, Vijayakumar; Galipeau, Jacques

    2015-01-01

    Utilization of mesenchymal stromal cells (MSCs) for the treatment of Crohn’s disease and ulcerative colitis is of translational interest. Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated. Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials. However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation: (1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases (IBD). The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and (2) Species specific differences in the functionality of MSCs derived from mice versus humans. MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation. Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials. In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD. We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic. PMID:25944991

  16. Interaction of the role of Concentrated Animal Feeding Operations (CAFOs) in Emerging Infectious Diseases (EIDS).

    PubMed

    Hollenbeck, James E

    2016-03-01

    Most significant change in the evolution of the influenza virus is the rapid growth of the Concentrated Animal Feeding Operations (CAFOs) on a global scale. These industrial agricultural operations have the potential of housing thousands of animals in a relatively small area. Emerging Infectious Diseases (EIDs) event can be considered as a shift in the pathogen-host-environment interplay characteristics described by Engering et al. (2013). These changes in the host-environment and the disease ecology are key to creating novel transmission patterns and selection of novel pathogens with a modification of genetic traits. With the development of CAFOs throughout the world, the need for training of animal caretakers to observe, identify, treat, vaccinate and cull if necessary is important to safeguard public health. The best defense against another pandemic of Emerging Infectious Diseases (EIDs) is the constant monitoring of the livestock and handlers of CAFOs and the live animal markets. These are the most likely epicenter of the next pandemic. PMID:26656834

  17. Beyond bushmeat: Animal contact, injury, and zoonotic disease risk in western Uganda

    PubMed Central

    Paige, Sarah B.; Frost, Simon D.W.; Gibson, Mhairi A.; Holland, James; Shankar, Anupama; Switzer, William M.; Ting, Nelson

    2014-01-01

    Zoonotic pathogens cause an estimated 70% of emerging and re-emerging infectious diseases in humans. In sub-Saharan Africa, bushmeat hunting and butchering is considered the primary risk factor for human-wildlife contact and zoonotic disease transmission, particularly for the transmission of simian retroviruses. However, hunting is only one of many activities in sub-Saharan Africa that bring people and wildlife into contact. Here, we examine human-animal interaction in western Uganda, identifying patterns of injuries from animals and contact with nonhuman primates. Additionally, we identify individual-level risk factors associated with contact. Nearly 20% (246/ 1,240) of participants reported either being injured by an animal or having contact with a primate over their lifetimes. The majority (51.7%) of injuries were dog bites that healed with no long term medical consequences. The majority (76.8%) of 125 total primate contacts involved touching a carcass; however, butchering (20%), hunting (10%), and touching a live primate (10%) were also reported. Red colobus (Piliocolobus rufomitratus tephrosceles) accounted for most primate contact events. Multivariate logistic regression indicated that men who live adjacent to forest fragments are at elevated risk of animal contact and specifically primate contact. Our results provide a useful comparison to West and Central Africa where “bushmeat hunting” is the predominant paradigm for human-wildlife contact and zoonotic disease transmission. PMID:24845574

  18. B Cells with Regulatory Function in Animal Models of Autoimmune and Non-Autoimmune Diseases

    PubMed Central

    Lin, Mei; Wang, Zuomin; Han, Xiaozhe

    2015-01-01

    Although the identification of B cell subsets with negative regulatory functions and the definition of their mechanisms of action are recent events, the important negative regulatory roles of B cells in immune responses are now broadly recognized. There is an emerging appreciation for the pivotal role played by B cells in several areas of human diseases including autoimmune diseases and non-autoimmune diseases such as parasite infections and cancer. The recent research advancement of regulatory B cells in human disease coincides with the vastly accelerated pace of research on the bridging of innate and adaptive immune system. Current study and our continued research may provide better understanding of the mechanisms that promote regulatory B10 cell function to counteract exaggerated immune activation in autoimmune as well as non-autoimmune conditions. This review is focused on the current knowledge of BREG functions studied in animal models of autoimmune and non-autoimmune diseases. PMID:26236565

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

    PubMed

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

    2015-07-01

    There is increasing interest in nonrodent 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 and 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

  20. Contrasting host-pathogen interactions and genome evolution in two generalist and specialist microsporidian pathogens of mosquitoes.

    PubMed

    Desjardins, Christopher A; Sanscrainte, Neil D; Goldberg, Jonathan M; Heiman, David; Young, Sarah; Zeng, Qiandong; Madhani, Hiten D; Becnel, James J; Cuomo, Christina A

    2015-01-01

    Obligate intracellular pathogens depend on their host for growth yet must also evade detection by host defenses. Here we investigate host adaptation in two Microsporidia, the specialist Edhazardia aedis and the generalist Vavraia culicis, pathogens of disease vector mosquitoes. Genomic analysis and deep RNA-Seq across infection time courses reveal fundamental differences between these pathogens. E. aedis retains enhanced cell surface modification and signalling capacity, upregulating protein trafficking and secretion dynamically during infection. V. culicis is less dependent on its host for basic metabolites and retains a subset of spliceosomal components, with a transcriptome broadly focused on growth and replication. Transcriptional profiling of mosquito immune responses reveals that response to infection by E. aedis differs dramatically depending on the mode of infection, and that antimicrobial defensins may play a general role in mosquito defense against Microsporidia. This analysis illuminates fundamentally different evolutionary paths and host interplay of specialist and generalist pathogens. PMID:25968466

  1. Streptococcus pyogenes SpyCEP Influences Host-Pathogen Interactions during Infection in a Murine Air Pouch Model

    PubMed Central

    Chiappini, Nico; Seubert, Anja; Telford, John L.; Grandi, Guido; Serruto, Davide; Margarit, Immaculada; Janulczyk, Robert

    2012-01-01

    Streptococcus pyogenes is a major human pathogen worldwide, responsible for both local and systemic infections. These bacteria express the subtilisin-like protease SpyCEP which cleaves human IL-8 and related chemokines. We show that localization of SpyCEP is growth-phase and strain dependent. Significant shedding was observed only in a strain naturally overexpressing SpyCEP, and shedding was not dependent on SpyCEP autoproteolytic activity. Surface-bound SpyCEP in two different strains was capable of cleaving IL-8. To investigate SpyCEP action in vivo, we adapted the mouse air pouch model of infection for parallel quantification of bacterial growth, host immune cell recruitment and chemokine levels in situ. In response to infection, the predominant cells recruited were neutrophils, monocytes and eosinophils. Concomitantly, the chemokines KC, LIX, and MIP-2 in situ were drastically increased in mice infected with the SpyCEP knockout strain, and growth of this mutant strain was reduced compared to the wild type. SpyCEP has been described as a potential vaccine candidate against S. pyogenes, and we showed that surface-associated SpyCEP was recognized by specific antibodies. In vitro, such antibodies also counteracted the inhibitory effects of SpyCEP on chemokine mediated PMN recruitment. Thus, α-SpyCEP antibodies may benefit the host both directly by enabling opsonophagocytosis, and indirectly, by neutralizing an important virulence factor. The animal model we employed shows promise for broad application in the study of bacterial pathogenesis. PMID:22848376

  2. Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease

    PubMed Central

    Parker, Krystal L.; Kim, Youngcho; Alberico, Stephanie L.; Emmons, Eric B.; Narayanan, Nandakumar S.

    2016-01-01

    Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases. PMID:27069384

  3. Infection of Brachypodium distachyon by formae speciales of Puccinia graminis: early infection events and host-pathogen incompatibility.

    PubMed

    Figueroa, Melania; Alderman, Stephen; Garvin, David F; Pfender, William F

    2013-01-01

    Puccinia graminis causes stem rust, a serious disease of cereals and forage grasses. Important formae speciales of P. graminis and their typical hosts are P. graminis f. sp. tritici (Pg-tr) in wheat and barley, P. graminis f. sp. lolii (Pg-lo) in perennial ryegrass and tall fescue, and P. graminis f. sp. phlei-pratensis (Pg-pp) in timothy grass. Brachypodium distachyon is an emerging genetic model to study fungal disease resistance in cereals and temperate grasses. We characterized the P. graminis-Brachypodium pathosystem to evaluate its potential for investigating incompatibility and non-host resistance to P. graminis. Inoculation of eight Brachypodium inbred lines with Pg-tr, Pg-lo or Pg-pp resulted in sporulating lesions later accompanied by necrosis. Histological analysis of early infection events in one Brachypodium inbred line (Bd1-1) indicated that Pg-lo and Pg-pp were markedly more efficient than Pg-tr at establishing a biotrophic interaction. Formation of appressoria was completed (60-70% of germinated spores) by 12 h post-inoculation (hpi) under dark and wet conditions, and after 4 h of subsequent light exposure fungal penetration structures (penetration peg, substomatal vesicle and primary infection hyphae) had developed. Brachypodium Bd1-1 exhibited pre-haustorial resistance to Pg-tr, i.e. infection usually stopped at appressorial formation. By 68 hpi, only 0.3% and 0.7% of the Pg-tr urediniospores developed haustoria and colonies, respectively. In contrast, development of advanced infection structures by Pg-lo and Pg-pp was significantly more common; however, Brachypodium displayed post-haustorial resistance to these isolates. By 68 hpi the percentage of urediniospores that only develop a haustorium mother cell or haustorium in Pg-lo and Pg-pp reached 8% and 5%, respectively. The formation of colonies reached 14% and 13%, respectively. We conclude that Brachypodium is an apt grass model to study the molecular and genetic components of incompatiblity

  4. Infection of Brachypodium distachyon by Formae Speciales of Puccinia graminis: Early Infection Events and Host-Pathogen Incompatibility

    PubMed Central

    Figueroa, Melania; Alderman, Stephen; Garvin, David F.; Pfender, William F.

    2013-01-01

    Puccinia graminis causes stem rust, a serious disease of cereals and forage grasses. Important formae speciales of P. graminis and their typical hosts are P. graminis f. sp. tritici (Pg-tr) in wheat and barley, P. graminis f. sp. lolii (Pg-lo) in perennial ryegrass and tall fescue, and P. graminis f. sp. phlei-pratensis (Pg-pp) in timothy grass. Brachypodium distachyon is an emerging genetic model to study fungal disease resistance in cereals and temperate grasses. We characterized the P. graminis-Brachypodium pathosystem to evaluate its potential for investigating incompatibility and non-host resistance to P. graminis. Inoculation of eight Brachypodium inbred lines with Pg-tr, Pg-lo or Pg-pp resulted in sporulating lesions later accompanied by necrosis. Histological analysis of early infection events in one Brachypodium inbred line (Bd1-1) indicated that Pg-lo and Pg-pp were markedly more efficient than Pg-tr at establishing a biotrophic interaction. Formation of appressoria was completed (60–70% of germinated spores) by 12 h post-inoculation (hpi) under dark and wet conditions, and after 4 h of subsequent light exposure fungal penetration structures (penetration peg, substomatal vesicle and primary infection hyphae) had developed. Brachypodium Bd1-1 exhibited pre-haustorial resistance to Pg-tr, i.e. infection usually stopped at appressorial formation. By 68 hpi, only 0.3% and 0.7% of the Pg-tr urediniospores developed haustoria and colonies, respectively. In contrast, development of advanced infection structures by Pg-lo and Pg-pp was significantly more common; however, Brachypodium displayed post-haustorial resistance to these isolates. By 68 hpi the percentage of urediniospores that only develop a haustorium mother cell or haustorium in Pg-lo and Pg-pp reached 8% and 5%, respectively. The formation of colonies reached 14% and 13%, respectively. We conclude that Brachypodium is an apt grass model to study the molecular and genetic components of incompatiblity

  5. Associations between animal characteristic and environmental risk factors and bovine respiratory disease in Australian feedlot cattle.

    PubMed

    Hay, K E; Morton, J M; Mahony, T J; Clements, A C A; Barnes, T S

    2016-03-01

    A prospective longitudinal study was conducted in a population of Australian feedlot cattle to assess associations between animal characteristic and environmental risk factors and risk of bovine respiratory disease (BRD). Animal characteristics were recorded at induction, when animals were individually identified and enrolled into study cohorts (comprising animals in a feedlot pen). Environmental risk factors included the year and season of induction, source region and feedlot region and summary variables describing weather during the first week of follow-up. In total, 35,131 animals inducted into 170 cohorts within 14 feedlots were included in statistical analyses. Causal diagrams were used to inform model building and multilevel mixed effects logistic regression models were fitted within the Bayesian framework. Breed, induction weight and season of induction were significantly and strongly associated with risk of BRD. Compared to Angus cattle, Herefords were at markedly increased risk (OR: 2.0, 95% credible interval: 1.5-2.6) and tropically adapted breeds and their crosses were at markedly reduced risk (OR: 0.5, 95% credible interval: 0.3-0.7) of developing BRD. Risk of BRD declined with increased induction weight, with cattle in the heaviest weight category (≥480kg) at moderately reduced risk compared to cattle weighing <400kg at induction (OR: 0.6, 95% credible interval: 0.5-0.7). Animals inducted into feedlots during summer (OR: 2.4, 95% credible interval: 1.4-3.8) and autumn (OR: 2.1, 95% credible interval: 1.2-3.2) were at markedly increased risk compared to animals inducted during spring. Knowledge of these risk factors may be useful in predicting BRD risk for incoming groups of cattle in Australian feedlots. This would then provide the opportunity for feedlot managers to tailor management strategies for specific subsets of animals according to predicted BRD risk. PMID:26830058

  6. Companion animal disease surveillance: a new solution to an old problem?

    PubMed

    Ward, M P; Kelman, M

    2011-09-01

    Infectious disease surveillance in companion animals has a long history. However, it has mostly taken the form of ad hoc surveys, or has focused on adverse reactions to pharmaceuticals. In 2006 a Blue Ribbon Panel was convened by the U.S. White House Office of Science and Technology Policy to discuss the potential utility of a national companion animal health surveillance system. Such a system could provide fundamental information about disease occurrence, transmission and risk factors; and could facilitate industry-supported pharmaco-epidemiological studies and post-market surveillance. Disease WatchDog, a prospective national disease surveillance project, was officially launched in January 2010 to capture data on diseases in dogs and cats throughout Australia. Participation is encouraged by providing registrants real-time disease maps and material for improved communication between veterinarians and clients. From January to mid-November 2010, an estimated 31% of veterinary clinics Australia-wide joined the project. Over 1300 disease cases - including Canine Parvovirus (CPV), Canine Distemper, Canine Hepatitis, Feline Calicivirus, Feline Herpesvirus, and Tick Paralysis - were reported. In New South Wales alone, 552 CPV cases in dogs were reported from 89 postcode locations. New South Wales data was scanned using the space-time permutation test. Up to 24 clusters (P<0.01) were identified, occurring in all months except March. The greatest number of clusters (n=6) were identified in April. The most likely cluster was identified in western Sydney, where 36 cases of CPV were reported from a postcode in February. Although the project is still in its infancy, already new information on disease distribution has been produced. Disease information generated could facilitate targeted control and prevention programs. PMID:22748174

  7. Conservation Physiology and Conservation Pathogens: White-Nose Syndrome and Integrative Biology for Host-Pathogen Systems.

    PubMed

    Willis, Craig K R

    2015-10-01

    Conservation physiology aims to apply an understanding of physiological mechanisms to management of imperiled species, populations, or ecosystems. One challenge for physiologists hoping to apply their expertise to conservation is connecting the mechanisms we study, often in the laboratory, with the vital rates of populations in the wild. There is growing appreciation that infectious pathogens can threaten populations and species, and represent an important issue for conservation. Conservation physiology has much to offer in terms of addressing the threat posed to some host species by infectious pathogens. At the same time, the well-developed theoretical framework of disease ecology could provide a model to help advance the application of physiology to a range of other conservation issues. Here, I use white-nose syndrome (WNS) in hibernating North American bats as an example of a conservation problem for which integrative physiological research has been a critical part of research and management. The response to WNS highlights the importance of a well-developed theoretical framework for the application of conservation physiology to a particular threat. I review what is known about physiological mechanisms associated with mortality from WNS and emphasize the value of combining a strong theoretical background with integrative physiological studies in order to connect physiological mechanisms with population processes and thereby maximize the potential benefits of conservation physiology. PMID:26307096

  8. In Silico Designing and Analysis of Inhibitors against Target Protein Identified through Host-Pathogen Protein Interactions in Malaria

    PubMed Central

    Samant, Monika; Chadha, Nidhi; Tiwari, Anjani K.; Hasija, Yasha

    2016-01-01

    Malaria, a life-threatening blood disease, has been a major concern in the field of healthcare. One of the severe forms of malaria is caused by the parasite Plasmodium falciparum which is initiated through protein interactions of pathogen with the host proteins. It is essential to analyse the protein-protein interactions among the host and pathogen for better understanding of the process and characterizing specific molecular mechanisms involved in pathogen persistence and survival. In this study, a complete protein-protein interaction network of human host and Plasmodium falciparum has been generated by integration of the experimental data and computationally predicting interactions using the interolog method. The interacting proteins were filtered according to their biological significance and functional roles. α-tubulin was identified as a potential protein target and inhibitors were designed against it by modification of amiprophos methyl. Docking and binding affinity analysis showed two modified inhibitors exhibiting better docking scores of −10.5 kcal/mol and −10.43 kcal/mol and an improved binding affinity of −83.80 kJ/mol and −98.16 kJ/mol with the target. These inhibitors can further be tested and validated in vivo for their properties as an antimalarial drug. PMID:27057354

  9. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... institutions in surveillance of pesticides spray programs; and (3) State cattle and sheep sanitary or...

  10. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... institutions in surveillance of pesticides spray programs; and (3) State cattle and sheep sanitary or...

  11. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... institutions in surveillance of pesticides spray programs; and (3) State cattle and sheep sanitary or...

  12. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... institutions in surveillance of pesticides spray programs; and (3) State cattle and sheep sanitary or...

  13. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... institutions in surveillance of pesticides spray programs; and (3) State cattle and sheep sanitary or...

  14. An overview of animal models of pain: disease models and outcome measures

    PubMed Central

    Gregory, N; Harris, AL; Robinson, CR; Dougherty, PM; Fuchs, PN; Sluka, KA

    2013-01-01

    Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience including reflexive hyperalgesia measures, sensory and affective dimensions of pain and impact of pain on function and quality of life. In this review we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes, as well as the main behavioral tests for assessing pain in each model. PMID:24035349

  15. Efficacy of experimental animal and vegetable oil-emulsion vaccines for Newcastle disease and avian influenza.

    PubMed

    Stone, H D

    1993-01-01

    Acceptable oil-emulsion vaccines were sought to replace mineral oil-emulsion vaccines that, by regulations, require a 42-day minimum holding period for poultry between injection and slaughter for consumption. Water-in-oil emulsions were prepared using animal or vegetable oils in a ratio of 4 parts oil to 1 part Newcastle disease or avian influenza aqueous antigen. Beeswax particles suspended in the oil at the 5% or 10% level (wt:vol) served as the oil-phase surfactant. Hemagglutination-inhibition titers induced by mineral-oil vaccines were not significantly different from those induced by the most efficacious formulations prepared from animal and vegetable oils. Tissue reaction from injection of animal- and vegetable-oil vaccines was less than that induced by mineral-oil vaccines. An inactivated avian influenza vaccine formulated from peanut oil induced protection against morbidity and death when vaccinated chickens were challenged with a virulent isolate of avian influenza virus. PMID:8363505

  16. Subcellular proteomic analysis of host-pathogen interactions using human monocytes exposed to Yersinia pestis and Yersinia pseudotuberculosis

    SciTech Connect

    Zhang, C G; Gonzales, A D; Choi, M W; Chromy, B A; Fitch, J P; McCutchen-Maloney, S L

    2004-05-20

    Yersinia pestis, the etiological agent of plague, is of concern to human health both from an infectious disease and a civilian biodefense perspective. While Y. pestis and Y. pseudotuberculosis share more than 90% DNA homology, they have significantly different clinical manifestations. Plague is often fatal if untreated, yet Y. pseudotuberculosis causes severe intestinal distress and is rarely fatal. A better understanding of host response to these closely related pathogens may help explain the different mechanisms of virulence and pathogenesis that result in such different clinical outcomes. The aim of this study was to characterize host protein expression changes in human monocyte-like U937 cells after exposure to Y. pestis and Y. pseudotuberculosis. In order to gain global proteomic coverage of host response, proteins from cytoplasmic, nuclear and membrane fractions of host cells were studied by 2-dimensional differential gel electrophoresis (2-D DIGE) and relative protein expression differences were quantitated. Differentially expressed proteins, with at least 1.5 fold expression changes and p values of 0.01 or less, were identified by MALDI-MS or LC/MS/MS. With these criteria, differential expression was detected in 16 human proteins after Y. pestis exposure and 13 human proteins after Y. pseudotuberculosis exposure, of which only two of the differentially expressed proteins identified were shared between the two exposures. Proteins identified in this study are reported to be involved in a wide spectrum of cellular functions and host defense mechanisms including apoptosis, cytoskeletal rearrangement, protein synthesis and degradation, DNA replication and transcription, metabolism, protein folding, and cell signaling. Notably, the differential expression patterns observed can distinguish the two pathogen exposures from each other and from unexposed host cells. The functions of the differentially expressed proteins identified provide insight on the different

  17. Articular Osteochondrosis: A Comparison of Naturally-Occurring Human and Animal Disease

    PubMed Central

    McCoy, Annette M; Toth, Ferenc; Dolvik, Nils I; Ekman, Stina; Ellermann, Jutta; Olstad, Kristin; Ytrehus, Bjornar; Carlson, Cathy S

    2013-01-01

    Background Osteochondrosis (OC) is a common developmental orthopedic disease affecting both humans and animals. Despite increasing recognition of this disease among children and adolescents, its pathogenesis is incompletely understood because clinical signs are often not apparent until lesions have progressed to end-stage, and examination of cadaveric early lesions is not feasible. In contrast, both naturally-occurring and surgically-induced animal models of disease have been extensively studied, most notably in horses and swine, species in which OC is recognized to have profound health and economic implications. The potential for a translational model of human OC has not been recognized in the existing human literature. Objective The purpose of this review is to highlight the similarities in signalment, predilection sites and clinical presentation of naturally-occurring OC in humans and animals and to propose a common pathogenesis for this condition across species. Study Design Review Methods The published human and veterinary literature for the various manifestations of OC was reviewed. Peer-reviewed original scientific articles and species-specific review articles accessible in PubMed (US National Library of Medicine) were eligible for inclusion. Results A broad range of similarities exists between OC affecting humans and animals, including predilection sites, clinical presentation, radiographic/MRI changes, and histological appearance of the end stage lesion, suggesting a shared pathogenesis across species. Conclusion This proposed shared pathogenesis for OC between species implies that naturally-occurring and surgically-induced models of OC in animals may be useful in determining risk factors and for testing new diagnostic and therapeutic interventions that can be used in humans. PMID:23954774

  18. The Impact of Farmers’ Strategic Behavior on the Spread of Animal Infectious Diseases

    PubMed Central

    Hammitt, James K.; Thomas, Alban; Raboisson, Didier

    2016-01-01

    One of the main strategies to control the spread of infectious animal diseases is the implementation of movement restrictions. This paper shows a loss in efficiency of the movement restriction policy (MRP) when behavioral responses of farmers are taken into account. Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The results are validated in a parameterized network via Monte Carlo simulations and measures to mitigate the loss of efficiency of the MRP are discussed. Financial aid to farmers can be justified by public health concerns, not only for equity. This paper contributes to developing an interdisciplinary analytical framework regarding the expansion of infectious diseases combining economic and epidemiologic dimensions. PMID:27300368

  19. Diabetes Mellitus Induces Alzheimer’s Disease Pathology: Histopathological Evidence from Animal Models

    PubMed Central

    Kimura, Nobuyuki

    2016-01-01

    Alzheimer’s disease (AD) is the major causative disease of dementia and is characterized pathologically by the accumulation of senile plaques (SPs) and neurofibrillary tangles (NFTs) in the brain. Although genetic studies show that β-amyloid protein (Aβ), the major component of SPs, is the key factor underlying AD pathogenesis, it remains unclear why advanced age often leads to AD. Interestingly, several epidemiological and clinical studies show that type II diabetes mellitus (DM) patients are more likely to exhibit increased susceptibility to AD. Moreover, growing evidence suggests that there are several connections between the neuropathology that underlies AD and DM, and there is evidence that the experimental induction of DM can cause cognitive dysfunction, even in rodent animal models. This mini-review summarizes histopathological evidence that DM induces AD pathology in animal models and discusses the possibility that aberrant insulin signaling is a key factor in the induction of AD pathology. PMID:27058526

  20. Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease.

    PubMed

    Wang, He Joe; Murray, Gary J; Jung, Mary Katherine

    2015-01-01

    Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed. PMID:26293978

  1. Stenotrophomonas maltophilia isolated from the airways of animals with chronic respiratory disease.

    PubMed

    Albini, S; Abril, C; Franchini, M; Hüssy, D; Filioussis, G

    2009-07-01

    Stenotrophomonas maltophilia (S. maltophilia) is a nonfermentative bacterium, which is naturally resistant against a panel of commonly-used antibiotics. It is frequently isolated from humans with chronic respiratory disease, e.g. cystic fibrosis or chronic obstructive pulmonary disease. In veterinary medicine S. maltophilia is perceived to be a mere coloniser. We herewith report 7 strains of S. maltophilia isolated from animals, of which 5 strains were harvested from 3 horses, a dog and a cat with chronic respiratory disease. The dog isolate showed resistance to trimethoprim / sulphamethoxazole, which was confirmed by detection of the sul 1 gene. Analysis with pulsed field gel electrophoresis revealed that 2 horses, which were boarded in the same clinic but two years apart, harboured the same strain of S. maltophilia. This is indicative of a hospital acquired colonisation / infection, which contradicts involvement in the pre-existing chronic disease. PMID:19565454

  2. Opportunities and challenges in developing relevant animal models for Alzheimer's disease.

    PubMed

    De Felice, Fernanda G; Munoz, Douglas P

    2016-03-01

    A major impediment to the development of safe and effective therapeutics in Alzheimer's disease (AD) lies in difficulties in translating research findings across species: therapies that work in rodents often do not translate to humans. A route to bridge the gap between promising rodent research and the human clinical condition consists in using non-human primates (NHPs), which are phylogenetically much closer to humans. In this article, we discuss the importance of investigating disease mechanisms from cell culture, through different animal models of disease. We highlight that developing a viable, validated NHP AD model will likely be a key step toward understanding AD-relevant pathogenic mechanisms and for developing therapies that will effectively translate to the human disease condition. PMID:26829469

  3. Uncertainties in the governance of animal disease: an interdisciplinary framework for analysis

    PubMed Central

    Fish, Robert; Austin, Zoe; Christley, Robert; Haygarth, Philip M.; Heathwaite, Louise A.; Latham, Sophia; Medd, William; Mort, Maggie; Oliver, David M.; Pickup, Roger; Wastling, Jonathan M.; Wynne, Brian

    2011-01-01

    Uncertainty is an inherent feature of strategies to contain animal disease. In this paper, an interdisciplinary framework for representing strategies of containment, and analysing how uncertainties are embedded and propagated through them, is developed and illustrated. Analysis centres on persistent, periodic and emerging disease threats, with a particular focus on cryptosporidiosis, foot and mouth disease and avian influenza. Uncertainty is shown to be produced at strategic, tactical and operational levels of containment, and across the different arenas of disease prevention, anticipation and alleviation. The paper argues for more critically reflexive assessments of uncertainty in containment policy and practice. An interdisciplinary approach has an important contribution to make, but is absent from current real-world containment policy. PMID:21624922

  4. Towards an understanding of the role of Clostridium perfringens toxins in human and animal disease

    PubMed Central

    Uzal, Francisco A; Freedman, John C; Shrestha, Archana; Theoret, James R; Garcia, Jorge; Awad, Milena M; Adams, Vicki; Moore, Robert J; Rood, Julian I; McClane, Bruce A

    2014-01-01

    Clostridium perfringens uses its arsenal of >16 toxins to cause histotoxic and intestinal infections in humans and animals. It has been unclear why this bacterium produces so many different toxins, especially since many target the plasma membrane of host cells. However, it is now established that C. perfringens uses chromosomally encoded alpha toxin (a phospholipase C) and perfringolysin O (a pore-forming toxin) during histotoxic infections. In contrast, this bacterium causes intestinal disease by employing toxins encoded by mobile genetic elements, including C. perfringens enterotoxin, necrotic enteritis toxin B-like, epsilon toxin and beta toxin. Like perfringolysin O, the toxins with established roles in intestinal disease form membrane pores. However, the intestinal disease-associated toxins vary in their target specificity, when they are produced (sporulation vs vegetative growth), and in their sensitivity to intestinal proteases. Producing many toxins with diverse characteristics likely imparts virulence flexibility to C. perfringens so it can cause an array of diseases. PMID:24762309

  5. The importance of muscarinic receptors in domestic animal diseases and therapy: Current and future perspectives.

    PubMed

    Abraham, Getu

    2016-02-01

    This review provides an overview of the early and current literature including contributions that highlight the parasympathetic cholinergic receptor systems in domestic animal tissues. Muscarinic acetylcholine receptors (mAChRs) belong to the subfamily of G protein-coupled receptors and regulate many fundamental functions of the central and peripheral nervous systems and have been subject to research over at least 40 years. Nonetheless, there are few studies specifying mAChRs in domestic animal tissues. This review focuses on the pharmacology of muscarinic acetylcholine receptor (mAChR) system and its pathological as well as the therapeutic importance in organ systems of domestic animals. Illustration and discussion of recent advances in distribution, function, biochemistry and pharmacology of mAChRs are followed by summaries of the involvement of this family of receptors in cardiovascular, respiratory, neurological, gastrointestinal (GI) and urological diseases as well as in anaesthesia and toxicology. Specific functions of mAChRs are described in detail including subtype characterization, smooth muscle functions, signal transduction and regulation. Due to their wide tissue distribution, mAChRs have shown promise as targets for the treatment of some animal diseases such as equine recurrent airway obstruction, glaucoma, abnormalities of gastric acid secretion and GI disturbances including colic. PMID:26654844

  6. Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals

    PubMed Central

    Liew, Pit Sze; Hair-Bejo, Mohd

    2015-01-01

    Plants have been studied for the production of pharmaceutical compounds for more than two decades now. Ever since the plant-made poultry vaccine against Newcastle disease virus made a breakthrough and went all the way to obtain regulatory approval, research to use plants for expression and delivery of vaccine proteins for animals was intensified. Indeed, in view of the high production costs of veterinary vaccines, plants represent attractive biofactories and offer many promising advantages in the production of recombinant vaccine proteins. Furthermore, the possibility of conducting immunogenicity and challenge studies in target animals has greatly exaggerated the progress. Although there are no edible plant-produced animal vaccines in the market, plant-based vaccine technology has great potentials. In this review, development, uses, and advantages of plant-based recombinant protein production in various expression platforms are discussed. In addition, examples of plant-based veterinary vaccines showing strong indication in terms of efficacy in animal disease prevention are also described. PMID:26351454

  7. Spontaneous appearance of Tay-Sachs disease in an animal model.

    PubMed

    Zeng, B J; Torres, P A; Viner, T C; Wang, Z H; Raghavan, S S; Alroy, J; Pastores, G M; Kolodny, E H

    2008-01-01

    Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of beta-hexosaminidase A (Hex A). Deficiency of Hex A in TSD is caused by a defect of the alpha-subunit resulting from mutations of the HEXA gene. To date, there is no effective treatment for TSD. Animal models of genetic diseases, similar to those known to exist in humans, are valuable and essential research tools for the study of potentially effective therapies. However, there is no ideal animal model of TSD available for use in therapeutic trials. In the present study, we report an animal model (American flamingo; Phoenicopterus ruber) of TSD with Hex A deficiency occurring spontaneously in nature, with accumulation of G(M2)-ganglioside, deficiency of Hex A enzymatic activity, and a homozygous P469L mutation in exon 12 of the hexa gene. In addition, we have isolated the full-length cDNA sequence of the flamingo, which consists of 1581 nucleotides encoding a protein of 527 amino acids. Its coding sequence indicates approximately 71% identity at the nucleotide level and about 72.5% identity at the amino acid level with the encoding region of the human HEXA gene. This animal model, with many of the same features as TSD in humans, could represent a valuable resource for investigating therapy of TSD. PMID:18693054

  8. Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals.

    PubMed

    Liew, Pit Sze; Hair-Bejo, Mohd

    2015-01-01

    Plants have been studied for the production of pharmaceutical compounds for more than two decades now. Ever since the plant-made poultry vaccine against Newcastle disease virus made a breakthrough and went all the way to obtain regulatory approval, research to use plants for expression and delivery of vaccine proteins for animals was intensified. Indeed, in view of the high production costs of veterinary vaccines, plants represent attractive biofactories and offer many promising advantages in the production of recombinant vaccine proteins. Furthermore, the possibility of conducting immunogenicity and challenge studies in target animals has greatly exaggerated the progress. Although there are no edible plant-produced animal vaccines in the market, plant-based vaccine technology has great potentials. In this review, development, uses, and advantages of plant-based recombinant protein production in various expression platforms are discussed. In addition, examples of plant-based veterinary vaccines showing strong indication in terms of efficacy in animal disease prevention are also described. PMID:26351454

  9. Obstructive Sleep Apnea, Oxidative Stress and Cardiovascular Disease: Lessons from Animal Studies

    PubMed Central

    Heitmann, Joerg; Seeger, Werner; Weissmann, Norbert; Schulz, Richard

    2013-01-01

    Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) diseases such as arterial hypertension, heart failure, and stroke. Based on human research, sympathetic activation, inflammation, and oxidative stress are thought to play major roles in the pathophysiology of OSA-related CV diseases. Animal models of OSA have shown that endothelial dysfunction, vascular remodelling, and systemic and pulmonary arterial hypertension as well as heart failure can develop in response to chronic intermittent hypoxia (CIH). The available animal data are clearly in favour of oxidative stress playing a key role in the development of all of these CV manifestations of OSA. Presumably, the oxidative stress is due to an activation of NADPH oxidase and other free oxygen radicals producing enzymes within the CV system as evidenced by data from knockout mice and pharmacological interventions. It is hoped that animal models of OSA-related CV disease will continue to contribute to a deeper understanding of their underlying pathophysiology and will foster the way for the development of cardioprotective treatment options other than conventional CPAP therapy. PMID:23533685

  10. Time-restricted feeding and risk of metabolic disease: a review of human and animal studies.

    PubMed

    Rothschild, Jeff; Hoddy, Kristin K; Jambazian, Pera; Varady, Krista A

    2014-05-01

    Time-restricted feeding (TRF), a key component of intermittent fasting regimens, has gained considerable attention in recent years. TRF allows ad libitum energy intake within controlled time frames, generally a 3-12 hour range each day. The impact of various TRF regimens on indicators of metabolic disease risk has yet to be investigated. Accordingly, the objective of this review was to summarize the current literature on the effects of TRF on body weight and markers of metabolic disease risk (i.e., lipid, glucoregulatory, and inflammatory factors) in animals and humans. Results from animal studies show TRF to be associated with reductions in body weight, total cholesterol, and concentrations of triglycerides, glucose, insulin, interleukin 6, and tumor necrosis factor-α as well as with improvements in insulin sensitivity. Human data support the findings of animal studies and demonstrate decreased body weight (though not consistently), lower concentrations of triglycerides, glucose, and low-density lipoprotein cholesterol, and increased concentrations of high-density lipoprotein cholesterol. These preliminary findings show promise for the use of TRF in modulating a variety of metabolic disease risk factors. PMID:24739093

  11. Disease spread models in wild and feral animal populations: application of artificial life models.

    PubMed

    Ward, M P; Laffan, S W; Highfield, L D

    2011-08-01

    The role that wild and feral animal populations might play in the incursion and spread of important transboundary animal diseases, such as foot and mouth disease (FMD), has received less attention than is warranted by the potential impacts. An artificial life model (Sirca) has been used to investigate this issue in studies based on spatially referenced data sets from southern Texas. An incursion of FMD in which either feral pig or deer populations were infected could result in between 698 and 1557 infected cattle and affect an area of between 166 km2 and 455 km2 after a 100-day period. Although outbreak size in deer populations can be predicted bythe size of the local deer population initially infected, the resulting outbreaks in feral pig populations are less predictable. Also, in the case of deer, the size of potential outbreaks might depend on the season when the incursion occurs. The impact of various mitigation strategies on disease spread has also been investigated. The approach used in the studies reviewed here explicitly incorporates the spatial distribution and relationships between animal populations, providing a new framework to explore potential impacts, costs, and control strategies. PMID:21961216

  12. Labeling of the pathogenic bacterium Staphylococcus aureus with gold or ferric oxide-core nanoparticles highlights new capabilities for investigation of host-pathogen interactions.

    PubMed

    Depke, Maren; Surmann, Kristin; Hildebrandt, Petra; Jehmlich, Nico; Michalik, Stephan; Stanca, Sarmiza E; Fritzsche, Wolfgang; Völker, Uwe; Schmidt, Frank

    2014-02-01

    Throughout the world, infections caused by bacteria such as Staphylococcus aureus are a major cause of morbidity and mortality. In order to gain some understanding of the complicated physiological link between host and pathogen, modern techniques such as confocal microscopy and sophisticated OMICs technologies are suitable. However, labeling of pathogens such as S. aureus with green fluorescent protein, for example, or the generation of a reliable antibody, which are prerequisites for the application of reproducible isolation techniques, does not always succeed. Here, we present a universal approach for monitoring pathogen traffic after internalization into host cells by fluorescence microscopy and for isolation of bacteria from host-pathogen interaction assays using gold or ferric oxide-core, poly(vinyl alcohol) coated, and fluorescence-labeled nanoparticles (NP). The incubation of S. aureus HG001 with those NP had only minor effects on the bacterial growth in vitro. Quantitative proteome analysis after 24 h of NP incubation revealed that presence of NP provoked only marginal changes in the proteome pattern. The method presented enabled us to investigate the behavior of S. aureus HG001 during infection of S9 human epithelial cells by means of fluorescence microscopy and proteomics using magnetic separation or cell sorting. PMID:24347542

  13. Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

    PubMed Central

    Hickey, Raymond D.; Mao, Shennen A.; Glorioso, Jaime; Lillegard, Joseph B.; Fisher, James E.; Amiot, Bruce; Rinaldo, Piero; Harding, Cary O.; Marler, Ronald; Finegold, Milton J.; Grompe, Markus; Nyberg, Scott L.

    2014-01-01

    Hereditary tyrosinemia type I (HT1) is caused by deficiency in fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the last step of tyrosine metabolism. The most severe form of the disease presents acutely during infancy, and is characterized by severe liver involvement, most commonly resulting in death if untreated. Generation of FAH+/− pigs was previously accomplished by adeno-associated virus-mediated gene knockout in fibroblasts and somatic cell nuclear transfer. Subsequently, these animals were outbred and crossed to produce the first FAH−/− pigs. FAH-deficiency produced a lethal defect in utero that was corrected by administration of 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione (NTBC) throughout pregnancy. Animals on NTBC were phenotypically normal at birth; however, animals were euthanized approximately four weeks after withdrawal of NTBC due to clinical decline and physical examination findings of severe liver injury and encephalopthy consistent with acute liver failure. Biochemical and histological analyses, characterized by diffuse and severe hepatocellular damage, confirmed the diagnosis of severe liver injury. FAH−/− pigs provide the first genetically engineered large animal model of a metabolic liver disorder. Future applications of FAH−/− pigs include discovery research as a large animal model of HT1 and spontaneous acute liver failure, and preclinical testing of efficacy of liver cell therapies, including transplantation of hepatocytes, liver stem cells, and pluripotent stem cell-derived hepatocytes. PMID:24879068

  14. Studying human respiratory disease in animals--role of induced and naturally occurring models.

    PubMed

    Williams, Kurt; Roman, Jesse

    2016-01-01

    Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance. PMID:26467890

  15. Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges

    PubMed Central

    Ney, Denise M.; Sigalet, David L.; Vegge, Andreas; Burrin, Douglas

    2014-01-01

    Intestinal failure (IF), due to short bowel syndrome (SBS), results from surgical resection of a major portion of the intestine, leading to reduced nutrient absorption and need for parenteral nutrition (PN). The incidence is highest in infants and relates to preterm birth, necrotizing enterocolitis, atresia, gastroschisis, volvulus, and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, and nutritional and pharmacological interventions. Animal studies are needed to carefully evaluate the cellular mechanisms, safety, and translational relevance of new procedures. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult). Clinically relevant therapies have recently been suggested from studies in preterm and term PN-dependent SBS piglets, with or without a functional colon. Studies in rats and mice have specifically addressed the fundamental physiological processes underlying adaptation at the cellular level, such as regulation of mucosal proliferation, apoptosis, transport, and digestive enzyme expression, and easily allow exogenous or genetic manipulation of growth factors and their receptors (e.g., glucagon-like peptide 2, growth hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g., PN, milk diets, long-/short-chain lipids, pre- and probiotics). Conversely, newborn pigs (preterm or term) and weanling rats provide better insights into the developmental aspects of treatment for SBS in infants owing to their immature intestines. The review shows that a balance among practical, economical, experimental, and ethical constraints will determine the

  16. Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges.

    PubMed

    Sangild, Per T; Ney, Denise M; Sigalet, David L; Vegge, Andreas; Burrin, Douglas

    2014-12-15

    Intestinal failure (IF), due to short bowel syndrome (SBS), results from surgical resection of a major portion of the intestine, leading to reduced nutrient absorption and need for parenteral nutrition (PN). The incidence is highest in infants and relates to preterm birth, necrotizing enterocolitis, atresia, gastroschisis, volvulus, and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, and nutritional and pharmacological interventions. Animal studies are needed to carefully evaluate the cellular mechanisms, safety, and translational relevance of new procedures. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult). Clinically relevant therapies have recently been suggested from studies in preterm and term PN-dependent SBS piglets, with or without a functional colon. Studies in rats and mice have specifically addressed the fundamental physiological processes underlying adaptation at the cellular level, such as regulation of mucosal proliferation, apoptosis, transport, and digestive enzyme expression, and easily allow exogenous or genetic manipulation of growth factors and their receptors (e.g., glucagon-like peptide 2, growth hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g., PN, milk diets, long-/short-chain lipids, pre- and probiotics). Conversely, newborn pigs (preterm or term) and weanling rats provide better insights into the developmental aspects of treatment for SBS in infants owing to their immature intestines. The review shows that a balance among practical, economical, experimental, and ethical constraints will determine the

  17. The occurrence of cpb2-toxigenic Clostridium perfringens and the possible role of the beta2-toxin in enteric disease of domestic animals, wild animals and humans.

    PubMed

    van Asten, Alphons J A M; Nikolaou, Georgios N; Gröne, Andrea

    2010-02-01

    The virulence of Clostridium perfringens, a bacterium causing enteritis and enterotoxaemia in domestic and wild animals and humans, results largely from its ability to produce toxins. In 1997, an unknown toxin of C. perfringens, the beta2-toxin, and its encoding gene cpb2 were described. Since that time numerous studies have been published dealing with a possible association of cpb2-harbouring strains of C. perfringens and the occurrence of enteric disease in domestic and wild animals and humans. This article offers an overview of the current literature on the spread and pathological significance of cpb2-harbouring C. perfringens. Unambiguous conclusions on the prevalence of cpb2 and the contribution of beta2-toxin to the disease cannot be drawn from existing studies but in some animal species a strong correlation between the presence of cpb2-harbouring C. perfringens, the beta2-toxin and enteric disease has been reported. PMID:19101180

  18. Double Roles of Macrophages in Human Neuroimmune Diseases and Their Animal Models

    PubMed Central

    Fan, Xueli; Zhang, Hongliang; Cheng, Yun; Jiang, Xinmei; Zhu, Jie

    2016-01-01

    Macrophages are important immune cells of the innate immune system that are involved in organ-specific homeostasis and contribute to both pathology and resolution of diseases including infections, cancer, obesity, atherosclerosis, and autoimmune disorders. Multiple lines of evidence point to macrophages as a remarkably heterogeneous cell type. Different phenotypes of macrophages exert either proinflammatory or anti-inflammatory roles depending on the cytokines and other mediators that they are exposed to in the local microenvironment. Proinflammatory macrophages secrete detrimental molecules to induce disease development, while anti-inflammatory macrophages produce beneficial mediators to promote disease recovery. The conversion of the phenotypes of macrophages can regulate the initiation, development, and recovery of autoimmune diseases. Human neuroimmune diseases majorly include multiple sclerosis (MS), neuromyelitis optica (NMO), myasthenia gravis (MG), and Guillain-Barré syndrome (GBS) and macrophages contribute to the pathogenesis of these neuroimmune diseases. In this review, we summarize the double roles of macrophage in neuroimmune diseases and their animal models to further explore the mechanisms of macrophages involved in the pathogenesis of these disorders, which may provide a potential therapeutic approach for these disorders in the future. PMID:27034594

  19. Translating Therapies for Huntington’s Disease from Genetic Animal Models to Clinical Trials

    PubMed Central

    Hersch, Steven M.; Ferrante, Robert J.

    2004-01-01

    Summary: Genetic animal models of inherited neurological diseases provide an opportunity to test potential treatments and explore their promise for translation to humans experiencing these diseases. Therapeutic trials conducted in mouse models of Huntington’s disease have identified a growing number of potential therapies that are candidates for clinical trials. Although it is very exciting to have these candidates, there has been increasing concern about the feasibility and desirability of taking all of the compounds that may work in mice and testing them in patients with HD. There is a need to begin to prioritize leads emerging from transgenic mouse studies; however, it is difficult to compare results between compounds and laboratories, and there are also many additional factors that can affect translation to humans. Among the important issues are what constitutes an informative genetic model, what principals should be followed in designing and conducting experiments using genetic animal models, how can results from different laboratories and in different models be compared, what body of evidence is desirable to fully inform clinical decision making, and what factors contribute to the equipoise in determining whether preclinical information about a therapy makes clinical study warranted. In the context of Huntington’s disease, we will review the current state of genetic models and their successes in putting forward therapeutic leads, provide a guide to assessing studies in mouse models, and discuss some of the salient issues related to translation from mice to humans. PMID:15717031

  20. The influence of the young microbiome on inflammatory diseases--Lessons from animal studies.

    PubMed

    Bendtsen, Katja M; Fisker, Line; Hansen, Axel K; Hansen, Camilla H F; Nielsen, Dennis S

    2015-12-01

    Chronic inflammatory diseases are on the rise in the Westernized world. This rise has been correlated to a range of environmental factors, such as birth mode, rural versus urban living conditions, and use of antibiotics. Such environmental factors also influence early life gut microbiota (GM) colonization and maturation--and there is growing evidence that the negative effects of these factors on human health are mediated via GM alterations. Colonization of the gut initiates priming of the immune system from birth, driving tolerance towards non-harmful microorganisms and dietary antigens and proper reactions towards invading pathogens. This early colonization is crucial for the establishment of a healthy GM, and throughout life the balanced interaction of GM and immune system is a key element in maintaining health. An immune system out of balance increases the risk for later life inflammatory diseases. Animal models are indispensable in the studies of GM influence on disease mechanisms and progression, and focus points include studies of GM modification during pregnancy and perinatal life. Here, we present an overview of animal studies which have contributed to our understanding of GM functions in early life and how alterations affect risk and expression of certain inflammatory diseases with juvenile onset, including interventions, such as birth mode, antibiotics, and probiotics. PMID:26663871

  1. Derivation of neural stem cells from an animal model of psychiatric disease.

    PubMed

    de Koning, A; Walton, N M; Shin, R; Chen, Q; Miyake, S; Tajinda, K; Gross, A K; Kogan, J H; Heusner, C L; Tamura, K; Matsumoto, M

    2013-01-01

    Several psychiatric and neurological diseases are associated with altered hippocampal neurogenesis, suggesting differing neural stem cell (NSC) function may play a critical role in these diseases. To investigate the role of resident NSCs in a murine model of psychiatric disease, we sought to isolate and characterize NSCs from alpha-calcium-/calmodulin-dependent protein kinase II heterozygous knockout (CaMK2α-hKO) mice, a model of schizophrenia/bipolar disorder. These mice display altered neurogenesis, impaired neuronal development and are part of a larger family possessing phenotypic and behavioral correlates of schizophrenia/bipolar disorder and a shared pathology referred to as the immature dentate gyrus (iDG). The extent to which NSCs contribute to iDG pathophysiology remains unclear. To address this, we established heterogeneous cultures of NSCs isolated from the hippocampal neuropoietic niche. When induced to differentiate, CaMK2α-hKO-derived NSCs recapitulate organotypic hippocampal neurogenesis, but generate larger numbers of immature neurons than wild-type (WT) littermates. Furthermore, mutant neurons fail to assume mature phenotypes (including morphology and MAP2/calbindin expression) at the same rate observed in WT counterparts. The increased production of immature neurons which fail to mature indicates that this reductionist model retains key animal- and iDG-specific maturational deficits observed in animal models and human patients. This is doubly significant, as these stem cells lack several developmental inputs present in vivo. Interestingly, NSCs were isolated from animals prior to the emergence of overt iDG pathophysiology, suggesting mutant NSCs may possess lasting intrinsic alterations and that altered NSC function may contribute to iDG pathophysiology in adult animals. PMID:24193728

  2. Loop mediated isothermal amplification: An innovative gene amplification technique for animal diseases

    PubMed Central

    Sahoo, Pravas Ranjan; Sethy, Kamadev; Mohapatra, Swagat; Panda, Debasis

    2016-01-01

    India being a developing country mainly depends on livestock sector for its economy. However, nowadays, there is emergence and reemergence of more transboundary animal diseases. The existing diagnostic techniques are not so quick and with less specificity. To reduce the economy loss, there should be a development of rapid, reliable, robust diagnostic technique, which can work with high degree of sensitivity and specificity. Loop mediated isothermal amplification assay is a rapid gene amplification technique that amplifies nucleic acid under an isothermal condition with a set of designed primers spanning eight distinct sequences of the target. This assay can be used as an emerging powerful, innovative gene amplification diagnostic tool against various pathogens of livestock diseases. This review is to highlight the basic concept and methodology of this assay in livestock disease. PMID:27284221

  3. Animal models of disease shed light on Nipah virus pathogenesis and transmission

    PubMed Central

    de Wit, Emmie; Munster, Vincent J.

    2014-01-01

    Nipah virus is an emerging virus infection that causes yearly disease outbreaks with high case fatality rates in Bangladesh. Nipah virus causes encephalitis and systemic vasculitis, sometimes in combination with respiratory disease. Pteropus species fruit bats are the natural reservoir of Nipah virus and zoonotic transmission can occur directly or via an intermediate host; human-to-human transmission occurs regularly. In this review we discuss the current state of knowledge on the pathogenesis and transmission of Nipah virus, focusing on dissemination of the virus through its host, known determinants of pathogenicity and routes of zoonotic and human-to-human transmission. Since data from human cases are sparse, this knowledge is largely based on the results of studies performed in animal models that recapitulate Nipah virus disease in humans. PMID:25229234

  4. Loop mediated isothermal amplification: An innovative gene amplification technique for animal diseases.

    PubMed

    Sahoo, Pravas Ranjan; Sethy, Kamadev; Mohapatra, Swagat; Panda, Debasis

    2016-05-01

    India being a developing country mainly depends on livestock sector for its economy. However, nowadays, there is emergence and reemergence of more transboundary animal diseases. The existing diagnostic techniques are not so quick and with less specificity. To reduce the economy loss, there should be a development of rapid, reliable, robust diagnostic technique, which can work with high degree of sensitivity and specificity. Loop mediated isothermal amplification assay is a rapid gene amplification technique that amplifies nucleic acid under an isothermal condition with a set of designed primers spanning eight distinct sequences of the target. This assay can be used as an emerging powerful, innovative gene amplification diagnostic tool against various pathogens of livestock diseases. This review is to highlight the basic concept and methodology of this assay in livestock disease. PMID:27284221

  5. Morphological and functional changes in a new animal model of Ménière's disease.

    PubMed

    Egami, Naoya; Kakigi, Akinobu; Sakamoto, Takashi; Takeda, Taizo; Hyodo, Masamitsu; Yamasoba, Tatsuya

    2013-09-01

    The purpose of this study was to clarify the underlying mechanism of vertiginous attacks in Ménière's disease (MD) while obtaining insight into water homeostasis in the inner ear using a new animal model. We conducted both histopathological and functional assessment of the vestibular system in the guinea-pig. In the first experiment, all animals were maintained 1 or 4 weeks after electrocauterization of the endolymphatic sac of the left ear and were given either saline or desmopressin (vasopressin type 2 receptor agonist). The temporal bones from both ears were harvested and the extent of endolymphatic hydrops was quantitatively assessed. In the second experiment, either 1 or 4 weeks after surgery, animals were assessed for balance disorders and nystagmus after the administration of saline or desmopressin. In the first experiment, the proportion of endolymphatic space in the cochlea and the saccule was significantly greater in ears that survived for 4 weeks after surgery and were given desmopressin compared with other groups. In the second experiment, all animals that underwent surgery and were given desmopressin showed spontaneous nystagmus and balance disorder, whereas all animals that had surgery but without desmopressin administration were asymptomatic. Our animal model induced severe endolymphatic hydrops in the cochlea and the saccule, and showed episodes of balance disorder along with spontaneous nystagmus. These findings suggest that administration of desmopressin can exacerbate endolymphatic hydrops because of acute V2 (vasopressin type 2 receptor)-mediated effects, and, when combined with endolymphathic sac dysfunction, can cause temporary vestibular abnormalities that are similar to the vertiginous attacks in patients with MD. PMID:23877650

  6. NLR proteins: integral members of innate immunity and mediators of inflammatory diseases

    PubMed Central

    Wilmanski, Jeanette M.; Petnicki-Ocwieja, Tanja; Kobayashi, Koichi S.

    2012-01-01

    The innate immune system is the first line of defense against microorganisms and is conserved in both plants and animals. The NLR protein family is a recent addition to the members of innate immunity effector molecules. These proteins are characterized by a central oligomerization domain termed NACHT (or NBD/NOD) and a protein interaction domain, LRRs (Leucine rich repeats) at the C-terminus. It has been shown that NLR proteins are localized to the cytoplasm and recognize microbial products. To date, it is known that Nod1 and Nod2 detect bacterial cell wall components, whereas IPAF and NAIP detect bacterial flagellin and NALP1 has been shown to detect anthrax lethal toxin. NLR proteins comprise a diverse protein family (over 20 in humans), indicating that NLRs have evolved to acquire specificity to various pathogenic microorganisms, thereby controlling host-pathogen interactions. Activation of NLR proteins results in inflammatory responses mediated either by NF-κB, MAPK or Caspase-1 activation, accompanied by subsequent secretion of pro-inflammatory cytokines. Mutations in several members of the NLR protein family have been linked to inflammatory diseases, suggesting these molecules play important roles in maintaining host-pathogen interaction and inflammatory responses. Therefore, understanding NLR signaling is important for the therapeutic intervention of various infectious and inflammatory diseases. PMID:17875812

  7. Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease.

    PubMed

    Newman, Christopher L; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S; Tian, Nannan; Hammond, Max A; Wallace, Joseph M; Brown, Drew M; Chen, Neal; Moe, Sharon M; Allen, Matthew R

    2016-01-01

    Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties. PMID:26489025

  8. Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

    PubMed Central

    Newman, Christopher L.; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S.; Tian, Nannan; Hammond, Max A.; Wallace, Joseph M.; Brown, Drew M.; Chen, Neal; Moe, Sharon M.; Allen, Matthew R.

    2015-01-01

    Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild anti-resorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared to normal controls as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. While it had little effect on cortical bone geometry it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole bone mechanical properties in CKD through its impact on skeletal material properties. PMID:26489025

  9. Partial gene deletion in LEC rat: An animal model for Wilson disease

    SciTech Connect

    Wu, J.; Forbes, J.R.; Cox, D.W.

    1994-09-01

    Wilson disease is an inherited disorder of copper transport in which incorporation of copper into ceruloplasmin and excretion of copper into bile are greatly reduced. Copper accumulates to a toxic level in the liver and also in the brain and kidney, causing a spectrum of hepatic and neurological abnormalities. We have recently cloned the gene for Wilson disease (designated ATP7B), which encodes a putative copper-transporting P-type ATPase. The inbred mutant Long-Evans Cinnamon (LEC) rat strain shows similarity to Wilson disease in many clinical and biochemical features. We have cloned cDNAs for the rat homologue (Atp7b) of the human Wilson disease gene (ATP7B) and have shown that the two genes have {approximately}82% identity at the amino acid sequence level. Rat cDNA sequences were used to identify a partial deletion in the Atp7b gene in the LEC rat. The deletion removes at least 750 bp of the coding region at the 3{prime} end, which includes the crucial ATP binding domain and extends downstream of the gene. The proximal breakpoint has been precisely localized at the cDNA level. Our results provide convincing evidence that the LEC rat is an animal model for Wilson disease. This model will be important for studying liver pathophysiology, for developing therapy for Wilson disease, and for studying the pathway of copper transport and its possible interaction with other heavy metals.

  10. Farm-level plans and husbandry measures for aquatic animal disease emergencies.

    PubMed

    Mohan, C V; Phillips, M J; Bhat, B V; Umesh, N R; Padiyar, P A

    2008-04-01

    Disease is one of the gravest threats to the sustainability of the aquaculture industry. A good understanding of biosecurity and disease causation is essential for developing and implementing farm-level plans and husbandry measures to respond to disease emergencies. Using epidemiological approaches, it is possible to identify pond- and farm-level risk factors for disease outbreaks and develop intervention strategies. Better management practices (BMPs) should be simple, science-based, cost-effective and appropriate to their context if farmers are to adopt and implement them. As part of a regional initiative by the Network of Aquaculture Centres in Asia-Pacific (NACA) to control aquatic animal diseases, effective extension approaches to promote the widespread adoption of BMPs have been developed in India, Indonesia, Vietnam and Thailand, and have proved their worth. A highly successful programme, which addresses rising concerns about the effect of disease on the sustainability of shrimp farming in India, is now in its seventh year. In this paper, the authors present a brief insight into the details of the programme, its outcomes and impact, the lessons learned and the way forward. PMID:18666486

  11. Host-Pathogen Interactions 1

    PubMed Central

    Cervone, Felice; Hahn, Michael G.; De Lorenzo, Giulia; Darvill, Alan; Albersheim, Peter

    1989-01-01

    This paper describes the effect of a plant-derived polygalacturonase-inhibiting protein (PGIP) on the activity of endopolygalacturonases isolated from fungi. PGIP's effect on endopolygalacturonases is to enhance the production of oligogalacturonides that are active as elicitors of phytoalexin (antibiotic) accumulation and other defense reactions in plants. Only oligogalacturonides with a degree of polymerization higher than nine are able to elicit phytoalexin synthesis in soybean cotyledons. In the absence of PGIP, a 1-minute exposure of polygalacturonic acid to endopolygalacturonase resulted in the production of elicitor-active oligogalacturonides. However, the enzyme depolymerized essentially all of the polygalacturonic acid substrate to elicitor-inactive oligogalacturonides within 15 minutes. When the digestion of polygalacturonic acid was carried out with the same amount of enzyme but in the presence of excess PGIP, the rate of production of elicitor-active oligogalacturonides was dramatically altered. The amount of elicitor-active oligogalacturonide steadily increased for 24 hours. It was only after about 48 hours that the enzyme converted the polygalacturonic acid into short, elicitor-inactive oligomers. PGIP is a specific, reversible, saturable, high-affinity receptor for endopolygalacturonase. Formation of the PGIP-endopolygalacturonase complex results in increased concentrations of oligogalacturonides that activate plant defense responses. The interaction of the plant-derived PGIP with fungal endopolygalacturonases may be a mechanism by which plants convert endopolygalacturonase, a factor important for the virulence of pathogens, into a factor that elicits plant defense mechanisms. PMID:16666805

  12. Clinical application of Patlak plot CT-GFR in animals with upper urinary tract disease.

    PubMed

    Alexander, Kate; Dunn, Marilyn; Carmel, Eric Norman; Lavoie, Jean-Pierre; Del Castillo, Jérôme R E

    2010-01-01

    Glomerular filtration rate (GFR), an important parameter of renal function, is difficult to assess clinically. Serum creatinine and blood urea nitrogen measurements lack sensitivity, whereas radionuclide determination of GFR is not always available and requires postinjection patient isolation. GFR can be determined using computed tomography (CT), most commonly via Patlak plot analysis. Four adult cats, two adult dogs, and a foal underwent abdominal CT under general anesthesia for various diseases of the upper urinary tract. CT-GFR was measured with a single-slice dynamic acquisition and Patlak plot analysis. In five animals, the total CT-GFR appeared to be below normal, corresponding with mild (two animals) and moderate (two animals) increases of serum creatinine in four. In the two animals with normal or increased CT-GFR, serum creatinine was within the reference values. A significant negative logarithmic relationship was found between CT-GFR and serum creatinine values (P = 0.008; r2 = 0.75). No complications occurred during or following CT-GFR. CT examination provided clinically relevant information in 3/5 patients with possible ureteral obstruction and in 3/3 patients with suspected ureteral calculi. Single-slice dynamic CT-GFR was practical and provided clinically useful information in this small series of patients undergoing CT of the upper urinary tract. There was a significant relationship between CT-GFR and serum creatinine values, which supports the clinical potential of CT-GFR and justifies further investigation of this technique. PMID:20806874

  13. 9 CFR 71.14 - Slaughter of poultry or other animals to prevent spread of disease; ascertainment of value and...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... or other animals to prevent spread of disease; ascertainment of value and compensation. When, in order to prevent the spread of any contagious, infectious, or communicable disease, it becomes necessary... to prevent spread of disease; ascertainment of value and compensation. 71.14 Section 71.14...

  14. [Application of CRISPR-Cas9 genome editing for constructing animal models of human diseases].

    PubMed

    Ou, Zhanhui; Sun, Xiaofang

    2016-08-10

    The CRISPR-Cas9 system is a new targeted nuclease for genome editing, which can directly introduce modifications at the targeted genomic locus. The system utilizes a short single guide RNA (sgRNA) to direct the endonuclease Cas9 in the genome. Upon targeting, Cas9 can generate DNA double-strand breaks (DSBs). As such DSBs are repaired by non-homologous end joining (NHEJ) or homology directed repair (HDR), therefore facilitates introduction of random or specific mutations, repair of endogenous mutations, or insertion of DNA elements. The system has been successfully used to generate gene targeted cell lines including those of human, animals and plants. This article reviews recent advances made in this rapidly evolving technique for the generation of animal models for human diseases. PMID:27455021

  15. A Guide to Neurotoxic Animal Models of Parkinson’s Disease

    PubMed Central

    Tieu, Kim

    2011-01-01

    Parkinson’s disease (PD) is a neurological movement disorder primarily resulting from damage to the nigrostriatal dopaminergic pathway. To elucidate the pathogenesis, mechanisms of cell death, and to evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. The primary objectives of this article are twofold: First, to assist new investigators who are contemplating embarking on PD research to navigate through the available animal models. Emphasis will be placed on common neurotoxic murine models in which toxic molecules are used to lesion the nigrostriatal dopaminergic system. And second, to provide an overview of basic technical requirements for assessing the pathology, structure, and function of the nigrostriatal pathway. PMID:22229125

  16. Newcastle disease oil emulsion vaccines prepared with animal, vegetable, and synthetic oils.

    PubMed

    Stone, H D

    1997-01-01

    Animal, vegetable, and synthetic oils were tested as potential replacements for mineral oil in Newcastle disease oil emulsion vaccines. Emulsifying surfactants of seed oil origin comprised 10% of the the oil phase that was used to prepare water-in-oil emulsion vaccines that contained a final concentration of 20% aqueous antigen. The hemagglutination inhibition responses of chickens inoculated with 46 of the newly formulated oil vaccines were, in most cases, not significantly different from those of control chickens inoculated with mineral oil vaccine. Tissue reactions associated with animal, vegetable, and synthetic oil vaccines were less severe than those associated with mineral oil vaccines. Viscosity of the mineral oil formulations ranged from 1/2 to 3 1/2 times that of the mineral oil control vaccines. These findings indicate that any of several oils may be more suitable than mineral oil for preparation of immune adjuvants for poultry vaccines. PMID:9356704

  17. A branching model for the spread of infectious animal diseases in varying environments.

    PubMed

    Trapman, Pieter; Meester, Ronald; Heesterbeek, Hans

    2004-12-01

    This paper is concerned with a stochastic model, describing outbreaks of infectious diseases that have potentially great animal or human health consequences, and which can result in such severe economic losses that immediate sets of measures need to be taken to curb the spread. During an outbreak of such a disease, the environment that the infectious agent experiences is therefore changing due to the subsequent control measures taken. In our model, we introduce a general branching process in a changing (but not random) environment. With this branching process, we estimate the probability of extinction and the expected number of infected individuals for different control measures. We also use this branching process to calculate the generating function of the number of infected individuals at any given moment. The model and methods are designed using important infections of farmed animals, such as classical swine fever, foot-and-mouth disease and avian influenza as motivating examples, but have a wider application, for example to emerging human infections that lead to strict quarantine of cases and suspected cases (e.g. SARS) and contact and movement restrictions. PMID:15565446

  18. Arranging the bouquet of disease: floral traits and the transmission of plant and animal pathogens.

    PubMed

    McArt, Scott H; Koch, Hauke; Irwin, Rebecca E; Adler, Lynn S

    2014-05-01

    Several floral microbes are known to be pathogenic to plants or floral visitors such as pollinators. Despite the ecological and economic importance of pathogens deposited in flowers, we often lack a basic understanding of how floral traits influence disease transmission. Here, we provide the first systematic review regarding how floral traits attract vectors (for plant pathogens) or hosts (for animal pathogens), mediate disease establishment and evolve under complex interactions with plant mutualists that can be vectors for microbial antagonists. Attraction of floral visitors is influenced by numerous phenological, morphological and chemical traits, and several plant pathogens manipulate floral traits to attract vectors. There is rapidly growing interest in how floral secondary compounds and antimicrobial enzymes influence disease establishment in plant hosts. Similarly, new research suggests that consumption of floral secondary compounds can reduce pathogen loads in animal pollinators. Given recent concerns about pollinator declines caused in part by pathogens, the role of floral traits in mediating pathogen transmission is a key area for further research. We conclude by discussing important implications of floral transmission of pathogens for agriculture, conservation and human health, suggesting promising avenues for future research in both basic and applied biology. PMID:24528408

  19. Modeling HCV disease in animals: virology, immunology and pathogenesis of HCV and GBV-B infections

    PubMed Central

    Manickam, Cordelia; Reeves, R. Keith

    2014-01-01

    Hepatitis C virus (HCV) infection has become a global public health burden costing billions of dollars in health care annually. Even with rapidly advancing scientific technologies this disease still poses a significant threat due to a lack of vaccines and affordable treatment options. The immune correlates of protection and predisposing factors toward chronicity remain major obstacles to development of HCV vaccines and immunotherapeutics due, at least in part, to lack of a tangible infection animal model. This review discusses the currently available animal models for HCV disease with a primary focus on GB virus B (GBV-B) infection of New World primates that recapitulates the dual Hepacivirus phenotypes of acute viral clearance and chronic pathologic disease. HCV and GBV-B are also closely phylogenetically related and advances in characterization of the immune systems of New World primates have already led to the use of this model for drug testing and vaccine trials. Herein, we discuss the benefits and caveats of the GBV-B infection model and discuss potential avenues for future development of novel vaccines and immunotherapies. PMID:25538700

  20. Modeling vector-borne disease risk in migratory animals under climate change.

    PubMed

    Hall, Richard J; Brown, Leone M; Altizer, Sonia

    2016-08-01

    Recent theory suggests that animals that migrate to breed at higher latitudes may benefit from reduced pressure from natural enemies, including pathogens ("migratory escape"), and that migration itself weeds out infected individuals and lowers infection prevalence ("migratory culling"). The distribution and activity period of arthropod disease vectors in temperate regions is expected to respond rapidly to climate change, which could reduce the potential for migratory escape. However, climate change could have the opposite effect of reducing transmission if differential responses in the phenology and distribution of migrants and disease vectors reduce their overlap in space and time. Here we outline a simple modeling framework for exploring the influence of climate change on vector-borne disease dynamics in a migratory host. We investigate two scenarios under which pathogen transmission dynamics might be mediated by climate change: (1) vectors respond more rapidly than migrants to advancing phenology at temperate breeding sites, causing peak susceptible host density and vector emergence to diverge ("migratory mismatch") and (2) reduced migratory propensity allows increased nonbreeding survival of infected hosts and larger breeding-site epidemics (loss of migratory culling, here referred to as "sedentary amplification"). Our results highlight the need for continued surveillance of climate-induced changes to migratory behavior and vector activity to predict pathogen prevalence and its impacts on migratory animals. PMID:27252225

  1. From superspreaders to disease hotspots: linking transmission across hosts and space

    PubMed Central

    Paull, Sara H.; Song, Sejin; McClure, Katherine M.; Sackett, Loren C.; Kilpatrick, A. Marm; Johnson, Pieter T. J.

    2012-01-01

    Since the identification and imprisonment of “Typhoid Mary,” a woman who infected at least 47 people with typhoid in the early 1900s, epidemiologists have recognized that ‘superspreading’ hosts play a key role in disease epidemics. Such variability in transmission also exists among species within a community (amplification hosts) and among habitat patches across a landscape (disease ‘hotspots’), underscoring the need for an integrative framework for studying transmission heterogeneity. Here, we synthesize literature on human, plant, and animal diseases to evaluate the relative contributions of host, pathogen, and environmental factors in driving transmission heterogeneity across hosts and space. We show that host and spatial heterogeneity are closely linked and that quantitatively assessing the contribution of infectious individuals, species, or environmental patches to overall transmission can aid management strategies. We conclude by posing hypotheses regarding how pathogen natural history influences transmission heterogeneity and highlight emerging frontiers in the study of transmission heterogeneity. PMID:23482675

  2. From superspreaders to disease hotspots: linking transmission across hosts and space.

    PubMed

    Paull, Sara H; Song, Sejin; McClure, Katherine M; Sackett, Loren C; Kilpatrick, A Marm; Johnson, Pieter T J

    2012-03-01

    Since the identification and imprisonment of "Typhoid Mary," a woman who infected at least 47 people with typhoid in the early 1900s, epidemiologists have recognized that 'superspreading' hosts play a key role in disease epidemics. Such variability in transmission also exists among species within a community (amplification hosts) and among habitat patches across a landscape (disease 'hotspots'), underscoring the need for an integrative framework for studying transmission heterogeneity. Here, we synthesize literature on human, plant, and animal diseases to evaluate the relative contributions of host, pathogen, and environmental factors in driving transmission heterogeneity across hosts and space. We show that host and spatial heterogeneity are closely linked and that quantitatively assessing the contribution of infectious individuals, species, or environmental patches to overall transmission can aid management strategies. We conclude by posing hypotheses regarding how pathogen natural history influences transmission heterogeneity and highlight emerging frontiers in the study of transmission heterogeneity. PMID:23482675

  3. Emerging and exotic zoonotic disease preparedness and response in the United States - coordination of the animal health component.

    PubMed

    Levings, Randall L

    2012-09-01

    For the response to a zoonotic disease outbreak to be effective, animal health authorities and disease specialists must be involved. Animal health measures are commonly directed at known diseases that threaten the health of animals and impact owners. The measures have long been applied to zoonotic diseases, including tuberculosis and brucellosis, and can be applied to emerging diseases. One Health (veterinary, public, wildlife and environmental health) and all-hazards preparedness work have done much to aid interdisciplinary understanding and planning for zoonotic diseases, although further improvements are needed. Actions along the prevention, preparedness, response and recovery continuum should be considered. Prevention of outbreaks consists largely of import controls on animals and animal products and biosecurity. Preparedness includes situational awareness, research, tool acquisition, modelling, training and exercises, animal movement traceability and policy development. Response would include detection systems and specialized personnel, institutions, authorities, strategies, methods and tools, including movement control, depopulation and vaccination if available and appropriate. The specialized elements would be applied within a general (nationally standardized) system of response. Recovery steps begin with continuity of business measures during the response and are intended to restore pre-event conditions. The surveillance for novel influenza A viruses in swine and humans and the preparedness for and response to the recent influenza pandemic illustrate the cooperation possible between the animal and public health communities. PMID:22958252

  4. Fetal programming of CVD and renal disease: animal models and mechanistic considerations.

    PubMed

    Langley-Evans, Simon C

    2013-08-01

    The developmental origins of health and disease hypothesis postulates that exposure to a less than optimal maternal environment during fetal development programmes physiological function, and determines risk of disease in adult life. Much evidence of such programming comes from retrospective epidemiological cohorts, which demonstrate associations between birth anthropometry and non-communicable diseases of adulthood. The assertion that variation in maternal nutrition drives these associations is supported by studies using animal models, which demonstrate that maternal under- or over-nutrition during pregnancy can programme offspring development. Typically, the offspring of animals that are undernourished in pregnancy exhibit a relatively narrow range of physiological phenotypes that includes higher blood pressure, glucose intolerance, renal insufficiency and increased adiposity. The observation that common phenotypes arise from very diverse maternal nutritional insults has led to the proposal that programming is driven by a small number of mechanistic processes. The remodelling of tissues during development as a consequence of maternal nutritional status being signalled by endocrine imbalance or key nutrients limiting processes in the fetus may lead to organs having irreversibly altered structures that may limit their function with ageing. It has been proposed that the maternal diet may impact upon epigenetic marks that determine gene expression in fetal tissues, and this may be an important mechanism connecting maternal nutrient intakes to long-term programming of offspring phenotype. The objective for this review is to provide an overview of the mechanistic basis of fetal programming, demonstrating the critical role of animal models as tools for the investigation of programming phenomena. PMID:23312451

  5. MALDI imaging mass spectrometry to investigate endogenous peptides in an animal model of Usher's disease.

    PubMed

    Chatterji, Bijon; Dickhut, Clarissa; Mielke, Svenja; Krüger, Jonas; Just, Ingo; Glage, Silke; Meier, Martin; Wedekind, Dirk; Pich, Andreas

    2014-07-01

    Imaging MS (MSI) has emerged as a valuable tool to study the spatial distribution of biomolecules in the brain. Herein, MALDI-MSI was used to determine the distribution of endogenous peptides in a rat model of Usher's disease. This rare disease is considered as a leading cause of deaf-blindness in humans worldwide. Cryosections of brain tissue were analyzed by MALDI-MSI to differentiate between healthy and diseased rats. MSI results were highly reproducible. Tissue-specific peptides were identified by MS/MS using LC-Orbitrap and MALDI-TOF/TOF analyses. These peptides were proposed for histological classification due to their particular spatial distribution in the brain, for example, substantia nigra, corpus callosum, and hippocampus. Several endogenous peptides showed significantly increased ion densities, particularly in the colliculi superiores and in the substantia nigra of diseased rats, including peptides derived from Fsd1, dystrobrevin-β, and ProSAAS. Furthermore, several proteolytic degradation products of the myelin basic protein were identified, of which one peptide is most likely mediated by calpain-2. Our findings contribute to the characterization of this animal model and include possible peptide markers of disease. PMID:24841751

  6. 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

  7. Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential

    PubMed Central

    Lin, Jenny B.; Phillips, Evan H.; Riggins, Ti’Air E.; Sangha, Gurneet S.; Chakraborty, Sreyashi; Lee, Janice Y.; Lycke, Roy J.; Hernandez, Clarissa L.; Soepriatna, Arvin H.; Thorne, Bradford R. H.; Yrineo, Alexa A.; Goergen, Craig J.

    2015-01-01

    Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic. PMID:25993289

  8. Matrix Metalloproteinases Contribute to Neuronal Dysfunction in Animal Models of Drug Dependence, Alzheimer's Disease, and Epilepsy

    PubMed Central

    Mizoguchi, Hiroyuki; Yamada, Kiyofumi; Nabeshima, Toshitaka

    2011-01-01

    Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) remodel the pericellular environment by regulating the cleavage of extracellular matrix proteins, cell surface components, neurotransmitter receptors, and growth factors that mediate cell adhesion, synaptogenesis, synaptic plasticity, and long-term potentiation. Interestingly, increased MMP activity and dysregulation of the balance between MMPs and TIMPs have also been implicated in various pathologic conditions. In this paper, we discuss various animal models that suggest that the activation of the gelatinases MMP-2 and MMP-9 is involved in pathogenesis of drug dependence, Alzheimer's disease, and epilepsy. PMID:22235372

  9. Regulatory acceptance of animal models of disease to support clinical trials of medicines and advanced therapy medicinal products.

    PubMed

    Cavagnaro, Joy; Silva Lima, Beatriz

    2015-07-15

    The utility of animal models of disease for assessing the safety of novel therapeutic modalities has become an increasingly important topic of discussion as research and development efforts focus on improving the predictive value of animal studies to support accelerated clinical development. Medicines are approved for marketing based upon a determination that their benefits outweigh foreseeable risks in specific indications, specific populations, and at specific dosages and regimens. No medicine is 100% safe. A medicine is less safe if the actual risks are greater than the predicted risks. The purpose of preclinical safety assessment is to understand the potential risks to aid clinical decision-making. Ideally preclinical studies should identify potential adverse effects and design clinical studies that will minimize their occurrence. Most regulatory documents delineate the utilization of conventional "normal" animal species to evaluate the safety risk of new medicines (i.e., new chemical entities and new biological entities). Animal models of human disease are commonly utilized to gain insight into the pathogenesis of disease and to evaluate efficacy but less frequently utilized in preclinical safety assessment. An understanding of the limitations of the animal disease models together with a better understanding of the disease and how toxicity may be impacted by the disease condition should allow for a better prediction of risk in the intended patient population. Importantly, regulatory authorities are becoming more willing to accept and even recommend data from experimental animal disease models that combine efficacy and safety to support clinical development. PMID:25814257

  10. Coffee and cardiovascular disease: in vitro, cellular, animal, and human studies.

    PubMed

    Bonita, Jennifer Stella; Mandarano, Michael; Shuta, Donna; Vinson, Joe

    2007-03-01

    Coffee is a commonly consumed beverage with potential health benefits. This review will focus on cardiovascular disease. There are three preparations of coffee that are commonly consumed and thus worthy of examination; boiled unfiltered coffee, filtered coffee, and decaffeinated coffee. Coffee has over a thousand chemicals, many formed during the roasting process. From a physiological point of view, the potential bioactives are caffeine, the diterpenes cafestol and kahweol found in the oil, and the polyphenols, most notably chlorogenic acid. We will examine coffee and its bioactives and their connection with and effect on the risk factors which are associated with heart disease such as lipids, blood pressure, inflammation, endothelial function, metabolic syndrome and potentially protective in vivo antioxidant activity. These will be critically examined by means of in vitro studies, cell experiments, animal supplementation, epidemiology, and the most definitive evidence, human trials. PMID:17368041

  11. Preclinical efficacy and mechanisms of mesenchymal stem cells in animal models of autoimmune diseases.

    PubMed

    Lee, Hong Kyung; Lim, Sang Hee; Chung, In Sung; Park, Yunsoo; Park, Mi Jeong; Kim, Ju Young; Kim, Yong Guk; Hong, Jin Tae; Kim, Youngsoo; Han, Sang-Bae

    2014-04-01

    Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-β, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms. PMID:24851097

  12. Naloxone reverses L-dopa induced overstimulation effects in a Parkinson's disease animal model analogue.

    PubMed

    Carey, R J

    1991-01-01

    Chronic L-DOPA treatment of Parkinson's disease frequently leads to the development of motoric overstimulation and hyperkinetic movements. To investigate this problem in the laboratory, rats surgically altered by unilateral 6-hydroxydopamine lesions (6-OHDA) were chronically treated with one L-DOPA (10 mg/kg i.p.) injection per day for 20 days. In this 6-OHDA rotation model, the unilateral dopamine denervation results in a profound contralateral sensory-motor neglect and the animals spontaneously rotate in a direction ipsilateral to the dopamine depleted hemisphere. Initially, the L-DOPA treatment did not alter the response bias but after several weeks, the response bias was reversed and the animals rotated in the formerly akinetic direction, contralaterally, at a significantly higher level. Using this overstimulation effect as an analogue of the clinically observed L-DOPA overstimulation, animals were given naloxone in conjunction with the L-DOPA treatment. Naloxone (0.10, 0.25 and 0.50 mg/kg i.p.) produced a dose related decrease in the L-DOPA induced contralateral rotation. Consistent with an expected selective effect on the L-DOPA induced rotation, a dose related increase in ipsilateral rotation was observed. These results suggest that naloxone can attenuate the overstimulation effect of L-DOPA and that this effect is not attributable to non-specific response suppression effects. PMID:1900558

  13. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    PubMed Central

    Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

    2015-01-01

    Objective(s): Neurodegenerative Alzheimer’s disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion: The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals. PMID:26949505

  14. Chronic Neuroinflammation in Alzheimer's Disease: New Perspectives on Animal Models and Promising Candidate Drugs

    PubMed Central

    Millington, Christopher; Aldrich-Wright, Janice R.; Campbell, Iain L.; Münch, Gerald

    2014-01-01

    Chronic neuroinflammation is now considered one of the major factors in the pathogenesis of Alzheimer's disease (AD). However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau) do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system), and cognitive decline that is comparable with the human disease. Hence a more suitable animal model is needed to more closely mimic the resulting cognitive decline and memory loss in humans in order to investigate the effects of neuroinflammation on neurodegeneration. One of these models is the glial fibrillary acidic protein-interleukin 6 (GFAP-IL6) mouse, in which chronic neuroinflammation triggered constitutive expression of the cytokine interleukin-6 (IL-6) in astrocytes. These transgenic mice show substantial and progressive neurodegeneration as well as a decline in motor skills and cognitive function, starting from 6 months of age. This animal model could serve as an excellent tool for drug discovery and validation in vivo. In this review, we have also selected three potential anti-inflammatory drugs, curcumin, apigenin, and tenilsetam, as candidate drugs, which could be tested in this model. PMID:25025046

  15. Multi Criteria Decision Making to evaluate control strategies of contagious animal diseases.

    PubMed

    Mourits, M C M; van Asseldonk, M A P M; Huirne, R B M

    2010-09-01

    The decision on which strategy to use in the control of contagious animal diseases involves complex trade-offs between multiple objectives. This paper describes a Multi Criteria Decision Making (MCDM) application to illustrate its potential support to policy makers in choosing the control strategy that best meets all of the conflicting interests. The presented application focused on the evaluation of alternative strategies to control Classical Swine Fever (CSF) epidemics within the European Union (EU) according to the preferences of the European Chief Veterinary Officers (CVO). The performed analysis was centred on the three high-level objectives of epidemiology, economics and social ethics. The appraised control alternatives consisted of the EU compulsory control strategy, a pre-emptive slaughter strategy, a protective vaccination strategy and a suppressive vaccination strategy. Using averaged preference weights of the elicited CVOs, the preference ranking of the control alternatives was determined for six EU regions. The obtained results emphasized the need for EU region-specific control. Individual CVOs differed in their views on the relative importance of the various (sub)criteria by which the performance of the alternatives were judged. Nevertheless, the individual rankings of the control alternatives within a region appeared surprisingly similar. Based on the results of the described application it was concluded that the structuring feature of the MCDM technique provides a suitable tool in assisting the complex decision making process of controlling contagious animal diseases. PMID:20633939

  16. Omics approaches to probe markers of disease resistance in animal sciences.

    PubMed

    Guillemin, N; Horvatić, A; Kuleš, J; Galan, A; Mrljak, Vladimir; Bhide, M

    2016-06-21

    Omics technologies have been developed in recent decades and used in different thematics. More advancements were done in human and plant thematics. Omics is the conjugation of different techniques, studying all biological molecules (DNA, RNA, proteins, metabolites, etc.). Omics is then able to study entire pathways, elucidating phenotypes and their control. Thus, thanks to Omics, it is possible to have a broad overview of the linkage between genotypes and phenotypes. Disease phenotypes (tolerance or resistance) are important to understand in both production and health. Nowadays a plethora of research articles are presenting results in the field of natural disease resistance of animals using Omics technologies. Moreover, thanks to advanced high throughput technologies novel modes of infections (infection pathways) are coming to the surface. Such pathways are complex (hundreds to thousands of molecules implied, with complicated control mechanisms), and Omics can generate useful knowledge to understand those pathways. Here we aim to review several angles of Omics used to probe markers of disease resistance with recent publications and data on the field, and present perspectives and its utilization for a better understanding of diseases. PMID:27197117

  17. Current understanding of dysbiosis in disease in human and animal models

    PubMed Central

    DeGruttola, Arianna K.; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-01-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects over two million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed “dysbiosis”. In spite of the extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, we have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments in order to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases. PMID:27070911

  18. Current Understanding of Dysbiosis in Disease in Human and Animal Models.

    PubMed

    DeGruttola, Arianna K; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-05-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed "dysbiosis." Despite extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in patients with IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, the authors have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases. PMID:27070911

  19. A novel method to identify herds with an increased probability of disease introduction due to animal trade.

    PubMed

    Frössling, Jenny; Nusinovici, Simon; Nöremark, Maria; Widgren, Stefan; Lindberg, Ann

    2014-11-15

    In the design of surveillance, there is often a desire to target high risk herds. Such risk-based approaches result in better allocation of resources and improve the performance of surveillance activities. For many contagious animal diseases, movement of live animals is a main route of transmission, and because of this, herds that purchase many live animals or have a large contact network due to trade can be seen as a high risk stratum of the population. This paper presents a new method to assess herd disease risk in animal movement networks. It is an improvement to current network measures that takes direction, temporal order, and also movement size and probability of disease into account. In the study, the method was used to calculate a probability of disease ratio (PDR) of herds in simulated datasets, and of real herds based on animal movement data from dairy herds included in a bulk milk survey for Coxiella burnetii. Known differences in probability of disease are easily incorporated in the calculations and the PDR was calculated while accounting for regional differences in probability of disease, and also by applying equal probability of disease throughout the population. Each herd's increased probability of disease due to purchase of animals was compared to both the average herd and herds within the same risk stratum. The results show that the PDR is able to capture the different circumstances related to disease prevalence and animal trade contact patterns. Comparison of results based on inclusion or exclusion of differences in risk also highlights how ignoring such differences can influence the ability to correctly identify high risk herds. The method shows a potential to be useful for risk-based surveillance, in the classification of herds in control programmes or to represent influential contacts in risk factor studies. PMID:25139432

  20. MicroRNAs are potential therapeutic targets in fibrosing kidney disease: lessons from animal models.

    PubMed

    Duffield, Jeremy S; Grafals, Monica; Portilla, Didier

    2013-01-01

    Chronic disease of the kidneys has reached epidemic proportions in industrialized nations. New therapies are urgently sought. Using a combination of animal models of kidney disease and human biopsy samples, a pattern of dysregulated microRNA expression has emerged which is common to chronic diseases. A number of these dysregulated microRNA have recently been shown to have functional consequences for the disease process and therefore may be potential therapeutic targets. We highlight microRNA-21, the most comprehensively studied microRNA in the kidney so far. MicroRNA-21 is expressed widely in healthy kidney but studies from knockout mice indicate it is largely inert. Although microRNA-21 is upregulated in many cell compartments including leukocytes, epithelial cells and myofibroblasts, the inert microRNA-21 also appears to become activated, by unclear mechanisms. Mice lacking microRNA-21 are protected from kidney injury and fibrosis in several distinct models of kidney disease, and systemically administered oligonucleotides that specifically bind to the active site in microRNA-21, inhibiting its function, recapitulate the genetic deletion of microRNA-21, suggesting inhibitory oligonucleotides may have therapeutic potential. Recent studies of microRNA-21 targets in kidney indicate that it normally functions to silence metabolic pathways including fatty acid metabolism and pathways that prevent Reactive Oxygen Species generation in peroxisomes and mitochondria in epithelial cells and myofibroblasts. Targeting specific pathogenic microRNAs in a specific manner is feasible in vivo and may be a new therapeutic target in disease of the kidney. PMID:25018773

  1. Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation

    PubMed Central

    Mungall, Christopher J.; Ashburner, Michael; Westerfield, Monte; Lewis, Suzanna E.

    2009-01-01

    and animal models of human disease, which may shorten the lengthy path to identification and understanding of the genetic basis of human disease. PMID:19956802

  2. MicroRNAs are potential therapeutic targets in fibrosing kidney disease: lessons from animal models

    PubMed Central

    Duffield, Jeremy S; Grafals, Monica; Portilla, Didier

    2012-01-01

    Chronic disease of the kidneys has reached epidemic proportions in industrialized nations. New therapies are urgently sought. Using a combination of animal models of kidney disease and human biopsy samples, a pattern of dysregulated microRNA expression has emerged which is common to chronic diseases. A number of these dysregulated microRNA have recently been shown to have functional consequences for the disease process and therefore may be potential therapeutic targets. We highlight microRNA-21, the most comprehensively studied microRNA in the kidney so far. MicroRNA-21 is expressed widely in healthy kidney but studies from knockout mice indicate it is largely inert. Although microRNA-21 is upregulated in many cell compartments including leukocytes, epithelial cells and myofibroblasts, the inert microRNA-21 also appears to become activated, by unclear mechanisms. Mice lacking microRNA-21 are protected from kidney injury and fibrosis in several distinct models of kidney disease, and systemically administered oligonucleotides that specifically bind to the active site in microRNA-21, inhibiting its function, recapitulate the genetic deletion of microRNA-21, suggesting inhibitory oligonucleotides may have therapeutic potential. Recent studies of microRNA-21 targets in kidney indicate that it normally functions to silence metabolic pathways including fatty acid metabolism and pathways that prevent Reactive Oxygen Species generation in peroxisomes and mitochondria in epithelial cells and myofibroblasts. Targeting specific pathogenic microRNAs in a specific manner is feasible in vivo and may be a new therapeutic target in disease of the kidney PMID:25018773

  3. Reverse Zoonotic Disease Transmission (Zooanthroponosis): A Systematic Review of Seldom-Documented Human Biological Threats to Animals

    PubMed Central

    Messenger, Ali M.; Barnes, Amber N.; Gray, Gregory C.

    2014-01-01

    Background Research regarding zoonotic diseases often focuses on infectious diseases animals have given to humans. However, an increasing number of reports indicate that humans are transmitting pathogens to animals. Recent examples include methicillin-resistant Staphylococcus aureus, influenza A virus, Cryptosporidium parvum, and Ascaris lumbricoides. The aim of this review was to provide an overview of published literature regarding reverse zoonoses and highlight the need for future work in this area. Methods An initial broad literature review yielded 4763 titles, of which 4704 were excluded as not meeting inclusion criteria. After careful screening, 56 articles (from 56 countries over three decades) with documented human-to-animal disease transmission were included in this report. Findings In these publications, 21 (38%) pathogens studied were bacterial, 16 (29%) were viral, 12 (21%) were parasitic, and 7 (13%) were fungal, other, or involved multiple pathogens. Effected animals included wildlife (n = 28, 50%), livestock (n = 24, 43%), companion animals (n = 13, 23%), and various other animals or animals not explicitly mentioned (n = 2, 4%). Published reports of reverse zoonoses transmission occurred in every continent except Antarctica therefore indicating a worldwide disease threat. Interpretation As we see a global increase in industrial animal production, the rapid movement of humans and animals, and the habitats of humans and wild animals intertwining with great complexity, the future promises more opportunities for humans to cause reverse zoonoses. Scientific research must be conducted in this area to provide a richer understanding of emerging and reemerging disease threats. As a result, multidisciplinary approaches such as One Health will be needed to mitigate these problems. PMID:24586500

  4. They see a rat, we seek a cure for diseases: the current status of animal experimentation in medical practice.

    PubMed

    Kehinde, Elijah O

    2013-01-01

    The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. The use of laboratory animals in scientific research continues to generate intense public debate. Their use can be justified today in the following areas of research: basic scientific research, use of animals as models for human diseases, pharmaceutical research and development, toxicity testing and teaching of new surgical techniques. This is because there are inherent limitations in the use of alternatives such as in vitro studies, human clinical trials or computer simulation. However, there are problems of transferability of results obtained from animal research to humans. Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible. PMID:24217224

  5. Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease

    PubMed Central

    Duty, Susan; Jenner, Peter

    2011-01-01

    Animal models of Parkinson's disease (PD) have proved highly effective in the discovery of novel treatments for motor symptoms of PD and in the search for clues to the underlying cause of the illness. Models based on specific pathogenic mechanisms may subsequently lead to the development of neuroprotective agents for PD that stop or slow disease progression. The array of available rodent models is large and ranges from acute pharmacological models, such as the reserpine- or haloperidol-treated rats that display one or more parkinsonian signs, to models exhibiting destruction of the dopaminergic nigro-striatal pathway, such as the classical 6-hydroxydopamine (6-OHDA) rat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models. All of these have provided test beds in which new molecules for treating the motor symptoms of PD can be assessed. In addition, the emergence of abnormal involuntary movements (AIMs) with repeated treatment of 6-OHDA-lesioned rats with L-DOPA has allowed for examination of the mechanisms responsible for treatment-related dyskinesia in PD, and the detection of molecules able to prevent or reverse their appearance. Other toxin-based models of nigro-striatal tract degeneration include the systemic administration of the pesticides rotenone and paraquat, but whilst providing clues to disease pathogenesis, these are not so commonly used for drug development. The MPTP-treated primate model of PD, which closely mimics the clinical features of PD and in which all currently used anti-parkinsonian medications have been shown to be effective, is undoubtedly the most clinically-relevant of all available models. The MPTP-treated primate develops clear dyskinesia when repeatedly exposed to L-DOPA, and these parkinsonian animals have shown responses to novel dopaminergic agents that are highly predictive of their effect in man. Whether non-dopaminergic drugs show the same degree of predictability of response is a matter of debate. As our

  6. Transcriptional Analysis of Host-Pathogen Interaction in Genetically Disparate Chicken Lines Showing Different Levels of Disease Susceptibility to Necrotic Enteritis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Necrotic enteritis (NE) has reemerged as a significant problem as a result of the growing concern over antibiotic resistance in human pathogens and restrictions on the use of antibiotics. It is difficult to reproduce NE by C. perfringens alone, therefore, a well established co-infection model using ...

  7. Pathogenic landscapes: Interactions between land, people, disease vectors, and their animal hosts

    PubMed Central

    2010-01-01

    Background Landscape attributes influence spatial variations in disease risk or incidence. We present a review of the key findings from eight case studies that we conducted in Europe and West Africa on the impact of land changes on emerging or re-emerging vector-borne diseases and/or zoonoses. The case studies concern West Nile virus transmission in Senegal, tick-borne encephalitis incidence in Latvia, sandfly abundance in the French Pyrenees, Rift Valley Fever in the Ferlo (Senegal), West Nile Fever and the risk of malaria re-emergence in the Camargue, and rodent-borne Puumala hantavirus and Lyme borreliosis in Belgium. Results We identified general principles governing landscape epidemiology in these diverse disease systems and geographic regions. We formulated ten propositions that are related to landscape attributes, spatial patterns and habitat connectivity, pathways of pathogen transmission between vectors and hosts, scale issues, land use and ownership, and human behaviour associated with transmission cycles. Conclusions A static view of the "pathogenecity" of landscapes overlays maps of the spatial distribution of vectors and their habitats, animal hosts carrying specific pathogens and their habitat, and susceptible human hosts and their land use. A more dynamic view emphasizing the spatial and temporal interactions between these agents at multiple scales is more appropriate. We also highlight the complementarity of the modelling approaches used in our case studies. Integrated analyses at the landscape scale allows a better understanding of interactions between changes in ecosystems and climate, land use and human behaviour, and the ecology of vectors and animal hosts of infectious agents. PMID:20979609

  8. Disease Spread through Animal Movements: A Static and Temporal Network Analysis of Pig Trade in Germany

    PubMed Central

    Lentz, Hartmut H. K.; Koher, Andreas; Hövel, Philipp; Gethmann, Jörn; Sauter-Louis, Carola; Selhorst, Thomas; Conraths, Franz J.

    2016-01-01

    Background Animal trade plays an important role for the spread of infectious diseases in livestock populations. The central question of this work is how infectious diseases can potentially spread via trade in such a livestock population. We address this question by analyzing the underlying network of animal movements. In particular, we consider pig trade in Germany, where trade actors (agricultural premises) form a complex network. Methodology The considered pig trade dataset spans several years and is analyzed with respect to its potential to spread infectious diseases. Focusing on measurements of network-topological properties, we avoid the usage of external parameters, since these properties are independent of specific pathogens. They are on the contrary of great importance for understanding any general spreading process on this particular network. We analyze the system using different network models, which include varying amounts of information: (i) static network, (ii) network as a time series of uncorrelated snapshots, (iii) temporal network, where causality is explicitly taken into account. Findings We find that a static network view captures many relevant aspects of the trade system, and premises can be classified into two clearly defined risk classes. Moreover, our results allow for an efficient allocation strategy for intervention measures using centrality measures. Data on trade volume do barely alter the results and is therefore of secondary importance. Although a static network description yields useful results, the temporal resolution of data plays an outstanding role for an in-depth understanding of spreading processes. This applies in particular for an accurate calculation of the maximum outbreak size. PMID:27152712

  9. [Animal models of human retinal and optic nerve diseases analysed using electroretinography].

    PubMed

    Kondo, Mineo

    2010-03-01

    Investigations of animal models with diseases found in humans are important to the understanding of their pathophysiology and for developing new treatments. Both naturally occurring and genetically-manipulated animal models of human retinal and optic nerve diseases have been studied in this manner. Electroretinography (ERG) is valuable for the evaluation of the visual function of animal models, because a layer-by-layer assessment of the retina can be done objectively. We used ERGs to analyze the visual functions of animal models of human retinal and and optic nerve diseases. To investigate the contribution of the cone ON- and OFF-pathways to the mouse photopic ERGs, we studied the properties of the photopic ERGs of metabotropic glutamate receptor subtype 6-deficient mice. The results of the ERG and the effect of an intravitreous injection of cis-2,3 piperidine dicarboxylic acid (PDA) in these mice suggest that the contribution of the post-synaptic ON-pathway to the photopic ERG of mice is larger than that of the OFF-pathway. The ERGs of pikachurin-deficient mice had normal a-waves with severely delayed b-waves, indicating that the signal transmission from the photoreceptors to the bipolar cells was impaired in these mutant mice. We also generated a rabbit model of retinitis pigmentosa (RP), the rhodopsin P347L transgenic (Tg) rabbit, by using bacterial artificial chromosome (BAC) transgenesis. These rabbits showed a rod-dominant, progressive retinal degeneration with marked regional variations in the loss of photoreceptors. All ERG components of the Tg rabbits decreased progressively with the a-waves more affected than the b-waves, and with the oscillatory potentials (OPs) the best preserved. Interestingly, the OP amplitudes of young Tg rabbits were significantly larger than those of wild-type rabbits. Pharmacological experiments showed that the significantly larger OPs in young Tg rabbits resulted from secondary alterations in the inner retinal function. This type

  10. Aspergillus and aspergilloses in wild and domestic animals: a global health concern with parallels to human disease.

    PubMed

    Seyedmousavi, Seyedmojtaba; Guillot, Jacques; Arné, Pascal; de Hoog, G Sybren; Mouton, Johan W; Melchers, Willem J G; Verweij, Paul E

    2015-11-01

    The importance of aspergillosis in humans and various animal species has increased over the last decades. Aspergillus species are found worldwide in humans and in almost all domestic animals and birds as well as in many wild species, causing a wide range of diseases from localized infections to fatal disseminated diseases, as well as allergic responses to inhaled conidia. Some prevalent forms of animal aspergillosis are invasive fatal infections in sea fan corals, stonebrood mummification in honey bees, pulmonary and air sac infection in birds, mycotic abortion and mammary gland infections in cattle, guttural pouch mycoses in horses, sinonasal infections in dogs and cats, and invasive pulmonary and cerebral infections in marine mammals and nonhuman primates. This article represents a comprehensive overview of the most common infections reported by Aspergillus species and the corresponding diseases in various types of animals. PMID:26316211

  11. Problems in Diagnosing Scabies, a Global Disease in Human and Animal Populations

    PubMed Central

    Walton, Shelley F.; Currie, Bart J.

    2007-01-01

    Scabies is a worldwide disease and a major public health problem in many developing countries, related primarily to poverty and overcrowding. In remote Aboriginal communities in northern Australia, prevalences of up to 50% among children have been described, despite the availability of effective chemotherapy. Sarcoptic mange is also an important veterinary disease engendering significant morbidity and mortality in wild, domestic, and farmed animals. Scabies is caused by the ectoparasitic mite Sarcoptes scabiei burrowing into the host epidermis. Clinical symptoms include intensely itchy lesions that often are a precursor to secondary bacterial pyoderma, septicemia, and, in humans, poststreptococcal glomerulonephritis. Although diagnosed scabies cases can be successfully treated, the rash of the primary infestation takes 4 to 6 weeks to develop, and thus, transmission to others often occurs prior to therapy. In humans, the symptoms of scabies infestations can mimic other dermatological skin diseases, and traditional tests to diagnose scabies are less than 50% accurate. To aid early identification of disease and thus treatment, a simple, cheap, sensitive, and specific test for routine diagnosis of active scabies is essential. Recent developments leading to the expression and purification of S. scabiei recombinant antigens have identified a number of molecules with diagnostic potential, and current studies include the investigation and assessment of the accuracy of these recombinant proteins in identifying antibodies in individuals with active scabies and in differentiating those with past exposure. Early identification of disease will enable selective treatment of those affected, reduce transmission and the requirement for mass treatment, limit the potential for escalating mite resistance, and provide another means of controlling scabies in populations in areas of endemicity. PMID:17428886

  12. Animal models related to congenital heart disease and clinical research in pulmonary hypertension.

    PubMed

    Loukanov, Tsvetomir; Geiger, Ralf; Agrawal, Rahul

    2010-01-01

    There are several animal models for studying human pulmonary hypertension (PH). An increased flow model in pigs was developed at the University Hospital in Heidelberg in order to simulate congenital heart disease. The high pulmonary blood flow is achieved by installation of a Blalock-Taussig anastomosis. In order to further improve this model by adding a pressure component, the left pulmonary artery is ligated. An acute model, which is used at the Innsbruck Medical University, addresses another disease entity. Human meconium is placed deeply into the trachea of the pigs in order to induce an acute respiratory distress syndrome-like response in the lungs. Animals were randomly assigned to four treatment groups. Inhaled iloprost, due to its pulmonary and intrapulmonary selectivity, was the only substance that significantly reduced intrapulmonary shunt volumes. In humans, PH encompasses multiple disease subtypes. Pulmonary arterial hypertension (PAH) accounts for only 6% of PH cases, however, all existing treatments are indicated only for PAH. This means that for 94% of patients with PH, no specific medication is available. Therefore, huge efforts have been made to better understand the pathophysiology of PH and to detect new signalling pathways that may allow new compounds to be developed that will ultimately improve the prognosis of PAH and non-PAH PH patients. Promising new substances include riociguat, a stimulator of the soluble guanylate cyclase (sGC), as well as cinaciguat, a sGC activator, and an elastase inhibitor. Riociguat (BAY 63-2521) is an oral agent that targets the intact/native form of sGC. It enhances the sensitivity of sGC to low levels of bioavailable nitric oxide (NO) and is also capable of stimulating native sGC independently of NO. Thus, unlike phosphodiesterase-5 inhibitors, the effect of riociguat is not limited by low NO levels. In a multicentre open-label phase II study, riociguat exerted strong and significant effects on pulmonary

  13. Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson's disease.

    PubMed

    Herrera, Andrea; Muñoz, Patricia; Paris, Irmgard; Díaz-Veliz, Gabriela; Mora, Sergio; Inzunza, Jose; Hultenby, Kjell; Cardenas, Cesar; Jaña, Fabián; Raisman-Vozari, Rita; Gysling, Katia; Abarca, Jorge; Steinbusch, Harry W M; Segura-Aguilar, Juan

    2016-09-01

    L-Dopa continues to be the gold drug in Parkinson's disease (PD) treatment from 1967. The failure to translate successful results from preclinical to clinical studies can be explained by the use of preclinical models which do not reflect what happens in the disease since these induce a rapid and extensive degeneration; for example, MPTP induces a severe Parkinsonism in only 3 days in humans contrasting with the slow degeneration and progression of PD. This study presents a new anatomy and develops preclinical model based on aminochrome which induces a slow and progressive dysfunction of dopaminergic neurons. The unilateral injection of aminochrome into rat striatum resulted in (1) contralateral rotation when the animals are stimulated with apomorphine; (2) absence of significant loss of tyrosine hydroxylase-positive neuronal elements both in substantia nigra and striatum; (3) cell shrinkage; (4) significant reduction of dopamine release; (5) significant increase in GABA release; (6) significant decrease in the number of monoaminergic presynaptic vesicles; (7) significant increase of dopamine concentration inside of monoaminergic vesicles; (8) significant increase of damaged mitochondria; (9) significant decrease of ATP level in the striatum (10) significant decrease in basal and maximal mitochondrial respiration. These results suggest that aminochrome induces dysfunction of dopaminergic neurons where the contralateral behavior can be explained by aminochrome-induced ATP decrease required both for anterograde transport of synaptic vesicles and dopamine release. Aminochrome could be implemented as a new model neurotoxin to study Parkinson's disease. PMID:27001668

  14. Follicular Helper CD4+ T Cells in Human Neuroautoimmune Diseases and Their Animal Models

    PubMed Central

    Fan, Xueli; Lin, Chenhong; Han, Jinming; Jiang, Xinmei; Zhu, Jie; Jin, Tao

    2015-01-01

    Follicular helper CD4+ T (TFH) cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC) formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models. PMID:26300592

  15. Disease control through fertility control: Secondary benefits of animal birth control in Indian street dogs.

    PubMed

    Yoak, Andrew J; Reece, John F; Gehrt, Stanley D; Hamilton, Ian M

    2014-01-01

    We sought to (1) survey sexually intact street dogs for a wide range of diseases in three cities in Rajasthan, India and (2) evaluate links between the health of non-treated dogs and both the presence and duration of animal birth control (ABC) programs. ABC regimes sterilize and vaccinate stray dogs in an attempt to control their population and the spread of rabies. They are commonly suggested to improve the health of those dogs they serve, but here we provide evidence that these benefits also extend to untreated dogs in the community. Viral and bacterial disease seroprevalences were assessed in 240 sexually intact street dogs from Jaipur, Jodhpur, and Sawai Madhopur cities in October and September 2011. Those individuals and 50 additional dogs were assessed for the presence of ticks, fleas, fight wounds, and given body condition scores. Dogs in cities with an ABC program had with significantly (p<0.05) higher overall body condition scores, lower prevalence of open wounds likely caused by fighting, flea infestations, infectious canine hepatitis, Ehrlichia canis, Leptospira interrogans serovars, and canine distemper virus antibodies. However, those same dogs in cities with ABC programs had significantly higher prevalence of Brown Dog Tick (Rhipicephalus sanguineus) infestations. Canine parvovirus and Brucella canis prevalences were not significantly different between cities. This study is the first to demonstrate the health benefits of ABC on non-vaccinated diseases and non-treated individuals. PMID:24239212

  16. Scenario tree model for animal disease freedom framed in the OIE context using the example of a generic swine model for Aujeszky's disease in commercial swine in Canada.

    PubMed

    Christensen, Jette; Vallières, André

    2016-01-01

    "Freedom from animal disease" is an ambiguous concept that may have a different meaning in trade and science. For trade alone, there are different levels of freedom from OIE listed diseases. A country can: be recognized by OIE to be "officially free"; self-declare freedom, with no official recognition by the OIE; or report animal disease as absent (no occurrence) in six-monthly reports. In science, we apply scenario tree models to calculate the probability of a population being free from disease at a given prevalence to provide evidence of freedom from animal disease. Here, we link science with application by describing how a scenario tree model may contribute to a country's claim of freedom from animal disease. We combine the idea of a standardized presentation of scenario tree models for disease freedom and having a similar model for two different animal diseases to suggest that a simple generic model may help veterinary authorities to build and evaluate scenario tree models for disease freedom. Here, we aim to develop a generic scenario tree model for disease freedom that is: animal species specific, population specific, and has a simple structure. The specific objectives were: to explore the levels of freedom described in the OIE Terrestrial Animal Health Code; to describe how scenario tree models may contribute to a country's claim of freedom from animal disease; and to present a generic swine scenario tree model for disease freedom in Canada's domestic (commercial) swine applied to Aujeszky's disease (AD). In particular, to explore how historical survey data, and data mining may affect the probability of freedom and to explore different sampling strategies. Finally, to frame the generic scenario tree model in the context of Canada's claim of freedom from AD. We found that scenario tree models are useful to support a country's claim of freedom either as "recognized officially free" or as part of a self-declaration but the models should not stand alone in a

  17. Emerging Animal Parasitic Diseases: A Global Overview and Appropriate Strategies for their Monitoring and Surveillance in Nigeria

    PubMed Central

    Atehmengo, Ngongeh L; Nnagbo, Chiejina S

    2014-01-01

    Emerging animal parasitic diseases are reviewed and appropriate strategies for efficient monitoring and surveillance in Nigeria are outlined. Animal and human parasitic infections are distinguished. Emerging diseases have been described as those diseases that are being recognised for the first time or diseases that are already recorded but their frequency and/or geographic range is being increased tremendously. Emergence of new diseases may be due to a number of factors such as the spread of a new infectious agent, recognition of an infection that has been in existence but undiagnosed, or when it is realised that an established disease has an infectious origin. The terms could also be used to describe the resurgence of a known infection after its incidence had been known to have declined. Emerging infections are compounding the control of infectious diseases and huge resources are being channeled to alleviate the rising challenge. The diseases are numerous and include helminth, protozoal / rickettsial and entomological. A list of parasitic emerging diseases in Nigeria is included. Globally occurring emerging parasitic diseases are also outlined. Emerging and re-emerging infections can be brought about by many factors including climate change and global warming, changes in biodiversity, population mobility, movement of animals, globalisation of commerce/trade and food supply, social and cultural factors such as food eating habits, religious beliefs, farming practices, trade of infected healthy animals, reduction in the available land for animals, immune-suppressed host and host density and misuse or over use of some drugs leading to drug resistance. PMID:25328553

  18. Emerging Animal Parasitic Diseases: A Global Overview and Appropriate Strategies for their Monitoring and Surveillance in Nigeria.

    PubMed

    Atehmengo, Ngongeh L; Nnagbo, Chiejina S

    2014-01-01

    Emerging animal parasitic diseases are reviewed and appropriate strategies for efficient monitoring and surveillance in Nigeria are outlined. Animal and human parasitic infections are distinguished. Emerging diseases have been described as those diseases that are being recognised for the first time or diseases that are already recorded but their frequency and/or geographic range is being increased tremendously. Emergence of new diseases may be due to a number of factors such as the spread of a new infectious agent, recognition of an infection that has been in existence but undiagnosed, or when it is realised that an established disease has an infectious origin. The terms could also be used to describe the resurgence of a known infection after its incidence had been known to have declined. Emerging infections are compounding the control of infectious diseases and huge resources are being channeled to alleviate the rising challenge. The diseases are numerous and include helminth, protozoal / rickettsial and entomological. A list of parasitic emerging diseases in Nigeria is included. Globally occurring emerging parasitic diseases are also outlined. Emerging and re-emerging infections can be brought about by many factors including climate change and global warming, changes in biodiversity, population mobility, movement of animals, globalisation of commerce/trade and food supply, social and cultural factors such as food eating habits, religious beliefs, farming practices, trade of infected healthy animals, reduction in the available land for animals, immune-suppressed host and host density and misuse or over use of some drugs leading to drug resistance. PMID:25328553

  19. Animal models of pediatric chronic kidney disease. Is adenine intake an appropriate model?

    PubMed

    Claramunt, Débora; Gil-Peña, Helena; Fuente, Rocío; Hernández-Frías, Olaya; Santos, Fernando

    2015-01-01

    Pediatric chronic kidney disease (CKD) has peculiar features. In particular, growth impairment is a major clinical manifestation of CKD that debuts in pediatric age because it presents in a large proportion of infants and children with CKD and has a profound impact on the self-esteem and social integration of the stunted patients. Several factors associated with CKD may lead to growth retardation by interfering with the normal physiology of growth plate, the organ where longitudinal growth rate takes place. The study of growth plate is hardly possible in humans and justifies the use of animal models. Young rats made uremic by 5/6 nephrectomy have been widely used as a model to investigate growth retardation in CKD. This article examines the characteristics of this model and analyzes the utilization of CKD induced by high adenine diet as an alternative research protocol. PMID:26522663

  20. Animal-induced injuries and disease, neonatal jaundice, immunizations, and viral infections.

    PubMed

    Gerson, W T

    1996-08-01

    Highlights from the past years' literature on the topics of animal-induced injuries and diseases, neonatal jaundice, immunizations, and viral infections are discussed from the perspective of the general pediatrician. An effort is made to place recent advances in care or understanding of clinical problems into the context of the pediatric office practice. The current reality of health care-be it managed care, care for the underserved, or the recent pressures on academic and hospital-based medicine-does not alter the importance of the delivery of quality care at the office level. Although it is now popular to define quality of health care in cute advertising copy, as if we are selling durable goods, excellence in pediatric office-based practice continues to require broad strokes of medical knowledge coupled with a unswerving commitment to and advocacy for the needs and well-being of infants, children, and young adults. PMID:8954278

  1. Evaluation of methods for the euthanasia of cattle in a foreign animal disease outbreak.

    PubMed Central

    Baker, H J; Scrimgeour, H J

    1995-01-01

    In anticipation of the need to euthanize large numbers of cattle in the event of a foreign animal disease outbreak, two models of captive bolt gun and various firearms and ammunition loads were tested in order to assess their suitability. In the first phase of the project, two models of captive bolt stunner were used in an abattoir, and assessed for effectiveness. In the second phase, several firearms and ammunition were used on isolated bovine heads and assessed for effectiveness. Little difference was found between the two captive bolt stunners. Of the firearms and ammunition evaluated, the Ruger Mini-14 and the Core-Shot round, a prefragmented projectile, were determined to be most suitable. In situations where large herds of livestock are to be depopulated, and where the restraint required for the use of captive bolt stunners is not practical, there are commercially available firearms and ammunition that are suitable for this purpose. PMID:7757921

  2. Evaluation of methods for the euthanasia of cattle in a foreign animal disease outbreak.

    PubMed

    Baker, H J; Scrimgeour, H J

    1995-03-01

    In anticipation of the need to euthanize large numbers of cattle in the event of a foreign animal disease outbreak, two models of captive bolt gun and various firearms and ammunition loads were tested in order to assess their suitability. In the first phase of the project, two models of captive bolt stunner were used in an abattoir, and assessed for effectiveness. In the second phase, several firearms and ammunition were used on isolated bovine heads and assessed for effectiveness. Little difference was found between the two captive bolt stunners. Of the firearms and ammunition evaluated, the Ruger Mini-14 and the Core-Shot round, a prefragmented projectile, were determined to be most suitable. In situations where large herds of livestock are to be depopulated, and where the restraint required for the use of captive bolt stunners is not practical, there are commercially available firearms and ammunition that are suitable for this purpose. PMID:7757921

  3. Morphological changes of glutamatergic synapses in animal models of Parkinson’s disease

    PubMed Central

    Villalba, Rosa M.; Mathai, Abraham; Smith, Yoland

    2015-01-01

    The striatum and the subthalamic nucleus (STN) are the main entry doors for extrinsic inputs to reach the basal ganglia (BG) circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is anatomical, functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and STN of animal models of Parkinson’s disease (PD) and that these changes may contribute to aberrant network neuronal activity in the BG-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and STN in models of PD. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined. PMID:26441550

  4. DNA vaccines targeting human papillomavirus-associated diseases: progresses in animal and clinical studies

    PubMed Central

    Han, Kyusun Torque

    2013-01-01

    Human papillomavirus (HPV) infection is a major cause of cervical cancer and its precancerous diseases. Cervical cancer is the second deadliest cancer killer among women worldwide. Moreover, HPV is also known to be a causative agent of oral, pharyngeal, anal and genital cancer. Recent application of HPV structural protein (L1)-targeted prophylactic vaccines (Gardasil® and Cervarix®) is expected to reduce the incidence of HPV infection and cervical cancer, and possibly other HPV-associated cancers. However, the benefit of the prophylactic vaccines for treating HPV-infected patients is unlikely, underscoring the importance of developing therapeutic vaccines against HPV infection. In this regard, numerous types of therapeutic vaccine approaches targeting the HPV regulatory proteins, E6 and E7, have been tested for their efficacy in animals and clinically. In this communication, we review HPV vaccine types, in particular DNA vaccines, their designs and delivery by electroporation and their immunologic and antitumor efficacy in animals and humans, along with the basics of HPV and its pathogenesis. PMID:23858401

  5. Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease.

    PubMed

    Jung, Jun-Sub; Yan, Ji-Jing; Li, Hong-Mei; Sultan, Md Tipu; Yu, Jaehoon; Lee, Hee-Sul; Shin, Kye-Jung; Song, Dong-Keun

    2016-07-01

    Ferulic acid is a compound with potent anti-oxidant and anti-inflammatory activities. We previously reported the protective effects of ferulic acid administration against two animal models of Alzheimer's disease (AD): intracerebroventricular (i.c.v.) injection of Aß1-42 in mice and APP/PS1 mutant transgenic mice. In this study using the same AD animal models, we examined the effect of KMS4001, one of dimeric derivatives of ferulic acid. Intragastric pretreatment of mice with KMS4001 (30mg/kg/day) for 5 days significantly attenuated the Aß1-42 (i.c.v.)-induced memory impairment both in passive avoidance test and in Y-maze test. APP/PS1 mutant transgenic mice at KMS4001 doses of 3 and 30mg/kg/day via drinking water showed the significantly enhanced novel-object recognition memory at both 1.5 and 3 months after the start of KMS4001 treatment. Treatment of APP/PS1 mutant transgenic mice with KMS4001 for 3 months at the doses of 3 and 30mg/kg/day markedly decreased Aβ1-40 and Aβ1-42 levels in the frontal cortex. The KMS4001 dose-response relationships for Aβ decrease and for improvement in novel-object recognition test corresponded to each other. Taken together, these results suggest that KMS4001 could be an effective drug candidate against AD. PMID:27118174

  6. Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson's Disease

    PubMed Central

    Panicker, Nikhil; Saminathan, Hariharan; Jin, Huajun; Neal, Matthew; Harischandra, Dilshan S.; Gordon, Richard; Kanthasamy, Kavin; Lawana, Vivek; Sarkar, Souvarish; Luo, Jie; Anantharam, Vellareddy; Kanthasamy, Anumantha G.

    2015-01-01

    Sustained neuroinflammation mediated by resident microglia is recognized as a key pathophysiological contributor to many neurodegenerative diseases, including Parkinson's disease (PD), but the key molecular signaling events regulating persistent microglial activation have yet to be clearly defined. In the present study, we examined the role of Fyn, a non-receptor tyrosine kinase, in microglial activation and neuroinflammatory mechanisms in cell culture and animal models of PD. The well-characterized inflammogens LPS and TNFα rapidly activated Fyn kinase in microglia. Immunocytochemical studies revealed that activated Fyn preferentially localized to the microglial plasma membrane periphery and the nucleus. Furthermore, activated Fyn phosphorylated PKCδ at tyrosine residue 311, contributing to an inflammogen-induced increase in its kinase activity. Notably, the Fyn-PKCδ signaling axis further activated the LPS- and TNFα-induced MAP kinase phosphorylation and activation of the NFκB pathway, implying that Fyn is a major upstream regulator of proinflammatory signaling. Functional studies in microglia isolated from wild-type (Fyn+/+) and Fyn knock-out (Fyn−/−) mice revealed that Fyn is required for proinflammatory responses, including cytokine release as well as iNOS activation. Interestingly, a prolonged inflammatory insult induced Fyn transcript and protein expression, indicating that Fyn is upregulated during chronic inflammatory conditions. Importantly, in vivo studies using MPTP, LPS, or 6-OHDA models revealed a greater attenuation of neuroinflammatory responses in Fyn−/− and PKCδ −/− mice compared with wild-type mice. Collectively, our data demonstrate that Fyn is a major upstream signaling mediator of microglial neuroinflammatory processes in PD. SIGNIFICANCE STATEMENT Parkinson's disease (PD) is a complex multifactorial disease characterized by the progressive loss of midbrain dopamine neurons. Sustained microglia-mediated neuroinflammation has

  7. Scientific literature on infectious diseases affecting livestock animals, longitudinal worldwide bibliometric analysis.

    PubMed

    Ducrot, Christian; Gautret, Marjolaine; Pineau, Thierry; Jestin, André

    2016-01-01

    The objectives of this bibliometric analysis of the scientific literature were to describe the research subjects and the international collaborations in the field of research on infectious diseases in livestock animals including fishes and honeybees. It was based on articles published worldwide from 2006 through 2013. The source of data was the Web of Science, Core collection(®) and only papers fully written in English were considered. Queries were built that combined 130 descriptors related to animal species and 1213 descriptors related to diseases and pathogens. To refine and assess the accuracy of the extracted database, supplementary filters were applied to discard non-specific terms and neighbouring topics, and numerous tests were carried out on samples. For pathogens, annotation was done using a thematic terminology established to link each disease with its corresponding pathogen, which was in turn classified according to its family. A total of 62,754 articles were published in this field during this 8-year period. The average annual growth rate of the number of papers was 5%. This represents the reference data to which we compared the average annual growth rate of articles produced in each of the sub-categories that we defined. Thirty-seven percent of the papers were dedicated to ruminant diseases. Poultry, pigs and fishes were covered by respectively 21, 13 and 14% of the total. Thirty-seven percent of papers concerned bacteria, 33% viruses, 19% parasites, 2% prions, the remaining being multi-pathogens. Research on virology, especially on pigs and poultry, is increasing faster than the average. There also is increasing interest in monogastric species, fish and bees. The average annual growth rate for Asia was 10%, which is high compared to 3% for Europe and 2% for the Americas, indicating that Asia is currently playing a leading role in this field. There is a well established network of international collaborations. For 75% of the papers, the co

  8. The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease

    PubMed Central

    Graham, Melanie L.; Prescott, Mark J.

    2015-01-01

    Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value. PMID:25823812

  9. The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease.

    PubMed

    Graham, Melanie L; Prescott, Mark J

    2015-07-15

    Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value. PMID:25823812

  10. Defining European preparedness and research needs regarding emerging infectious animal diseases: results from a Delphi expert consultation.

    PubMed

    Wentholt, M T A; Cardoen, S; Imberechts, H; Van Huffel, X; Ooms, B W; Frewer, L J

    2012-02-01

    Emerging and major infectious animal diseases can have significant international impact on social, economic and environmental level, and are being driven by various factors. Prevention and control measures should be prepared at both national and international level to mitigate these disease risks. Research to support such policy development is mostly carried out at national level and dedicated transnational research programmes are still in its infancy. This research reports on part of a process to develop a common strategic research agenda on emerging and major infectious diseases of livestock in Europe, covering a 5-15-year time span. A two round online Delphi study was conducted to explore the views of experts on issues relating to research needs on emerging infectious diseases of livestock in Europe. Drivers that may influence the incidence of emerging infectious animal diseases in both the short (next 5 years) and medium term (10-15 years) were identified. Drivers related to regulatory measures and biological science developments were thought to decrease the incidence, and socio-economic factors to increase the incidence of emerging infectious animal diseases. From the first round a list of threats to animal health was compiled and participants combined these threats with relevant drivers in the second round. Next to identifying threats to animal health, also possible mitigatory actions to reduce the negative impact of these threats were identified. Participants emphasised that interdisciplinary research is needed to understand drivers of emerging infectious animal diseases, as well as to develop prevention and control measures which are both socio-economic and technical. From this it can be concluded that interdisciplinary research combining both natural and social research themes is required. Some of the European member states research budget needs to be allocated so that effective prevention and mitigation strategies can be developed. PMID:22000288

  11. Animal Ownership and Touching Enrich the Context of Social Contacts Relevant to the Spread of Human Infectious Diseases

    PubMed Central

    Kifle, Yimer Wasihun; Goeyvaerts, Nele; Van Kerckhove, Kim; Willem, Lander; Faes, Christel; Leirs, Herwig; Hens, Niel; Beutels, Philippe

    2015-01-01

    Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0–9 years) and adults (25–54 years) have the highest potential to cause a major zoonotic outbreak. PMID:26193480

  12. Prebiotics in food animals: A potential to reduce foodborne pathogens and disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Animals can be seriously impacted by bacterial pathogens that affect their growth efficiency and overall health, as well as food safety of animal-derived products. Some pathogenic bacteria, such as Salmonella, can be a shared problem for both human and animal health and can be found in many animal ...

  13. Prebiotics in food animals, a potential to reduce foodborne pathogens and disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Animals can be seriously impacted by bacterial pathogens that affect their growth efficiency and overall health, as well as food safety of animal-derived products. Some pathogenic bacteria, such as Salmonella, can be a shared problem for both human and animal health and can be found in many animal ...

  14. Advances in Neuroprotective Ingredients of Medicinal Herbs by Using Cellular and Animal Models of Parkinson's Disease

    PubMed Central

    More, Sandeep Vasant; Kumar, Hemant; Kang, Seong Mook; Song, Soo-Yeol; Lee, Kippeum; Choi, Dong-Kug

    2013-01-01

    Parkinson's disease (PD) is a multifactorial disorder, which is neuropathologically identified by age-dependent neurodegeneration of dopaminergic neurons in the substantia nigra. Development of symptomatic treatments has been partly successful for PD research, but there remain a number of inadequacies in therapeutic strategies for the disease. The pathogenesis of PD remains intricate, and the present anti-PD treatments appears to be clinically insufficient. Comprehensive research on discovery of novel drug candidates has demonstrated that natural products, such as medicinal herbs, plant extracts, and their secondary metabolites, have great potential as therapeutics with neuroprotective activity in PD. Recent preclinical studies suggest that a number of herbal medicines and their bioactive ingredients can be developed into optimum pharmaceuticals for treating PD. In many countries, traditional herbal medicines are used to prevent or treat neurodegenerative disorders, and some have been developed as nutraceuticals or functional foods. Here we focus on recent advances of the evidence-linked neuroprotective activity of bioactive ingredients of herbal origin in cellular and animal models of PD research. PMID:24073012

  15. The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?

    PubMed

    Faller, Kiterie M E; Bras, Jose; Sharpe, Samuel J; Anderson, Glenn W; Darwent, Lee; Kun-Rodrigues, Celia; Alroy, Joseph; Penderis, Jacques; Mole, Sara E; Gutierrez-Quintana, Rodrigo; Guerreiro, Rita J

    2016-04-01

    Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age. Postmortem examination revealed marked accumulation of autofluorescent intracellular inclusions within the brain, characteristic of NCL. Whole-genome sequencing was performed on one of the affected dogs. After sequence alignment and variant calling against the canine reference genome, variants were identified in the coding region or splicing regions of four previously known NCL genes (CLN6, ARSG, CLN2 [=TPP1], and CLN7 [=MFSD8]). Subsequent segregation analysis within the family (two affected dogs, both parents, and three relatives) identified MFSD8:p.Phe282Leufs13*, which had previously been identified in one Chinese crested dog with no available ancestries, as the causal mutation. Because of the similarities of the clinical signs and histopathological changes with the human form of the disease, we propose that the Chihuahua dog could be a good animal model of CLN7 disease. PMID:26762174

  16. Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges.

    PubMed

    Kerkis, Irina; Haddad, Monica Santoro; Valverde, Cristiane Wenceslau; Glosman, Sabina

    2015-01-01

    Huntington's disease (HD) is an inherited disease that causes progressive nerve cell degeneration. It is triggered by a mutation in the HTT gene that strongly influences functional abilities and usually results in movement, cognitive and psychiatric disorders. HD is incurable, although treatments are available to help manage symptoms and to delay the physical, mental and behavioral declines associated with the condition. Stem cells are the essential building blocks of life, and play a crucial role in the genesis and development of all higher organisms. Ablative surgical procedures and fetal tissue cell transplantation, which are still experimental, demonstrate low rates of recovery in HD patients. Due to neuronal cell death caused by accumulation of the mutated huntingtin (mHTT) protein, it is unlikely that such brain damage can be treated solely by drug-based therapies. Stem cell-based therapies are important in order to reconstruct damaged brain areas in HD patients. These therapies have a dual role: stem cell paracrine action, stimulating local cell survival, and brain tissue regeneration through the production of new neurons from the intrinsic and likely from donor stem cells. This review summarizes current knowledge on neural stem/progenitor cell and mesenchymal stem cell transplantation, which has been carried out in several animal models of HD, discussing cell distribution, survival and differentiation after transplantation, as well as functional recovery and anatomic improvements associated with these approaches. We also discuss the usefulness of this information for future preclinical and clinical studies in HD. PMID:26667114

  17. Sociality and health: impacts of sociality on disease susceptibility and transmission in animal and human societies

    PubMed Central

    Kappeler, Peter M.; Cremer, Sylvia; Nunn, Charles L.

    2015-01-01

    This paper introduces a theme issue presenting the latest developments in research on the impacts of sociality on health and fitness. The articles that follow cover research on societies ranging from insects to humans. Variation in measures of fitness (i.e. survival and reproduction) has been linked to various aspects of sociality in humans and animals alike, and variability in individual health and condition has been recognized as a key mediator of these relationships. Viewed from a broad evolutionary perspective, the evolutionary transitions from a solitary lifestyle to group living have resulted in several new health-related costs and benefits of sociality. Social transmission of parasites within groups represents a major cost of group living, but some behavioural mechanisms, such as grooming, have evolved repeatedly to reduce this cost. Group living also has created novel costs in terms of altered susceptibility to infectious and non-infectious disease as a result of the unavoidable physiological consequences of social competition and integration, which are partly alleviated by social buffering in some vertebrates. Here, we define the relevant aspects of sociality, summarize their health-related costs and benefits, and discuss possible fitness measures in different study systems. Given the pervasive effects of social factors on health and fitness, we propose a synthesis of existing conceptual approaches in disease ecology, ecological immunology and behavioural neurosciences by adding sociality as a key factor, with the goal to generate a broader framework for organismal integration of health-related research. PMID:25870402

  18. Refinement and use of Certificates of Veterinary Inspection (Health Certificates) for optimal assurance of disease freedom in aquatic animals.

    PubMed

    Starling, D E; Palić, D; Scarfe, A D

    2007-01-01

    Certificates of Veterinary Inspection (CVI), generally termed "Health Certificates", are pivotal for ensuring that translocated animals are not diseased or do not harbour significant pathogens. While used very successfully with terrestrial animal movement for decades, CVIs for aquatic animals are not well refined, understood or used, despite the availability of several aquatic animal "certification processes", "permits" and "health certificates", including the OIE model health certificates. Correctly designed CVIs provide the single most economical and effective assurance of disease status (generally freedom from specific diseases or pathogens) for individuals or lots of animals, at any point in time. When issued by a qualified independent third-party (typically a licensed and government accredited veterinarian) they provide the official level of assurance necessary for intrastate, interstate and international trade. Tailored modifications of CVIs are also useful for other purposes requiring the evaluation of animal health (e.g. specific pathogen-free (SPF) assurance for premises, risk-mitigating assurance necessary for insurance policies, breeding soundness assurance of broodstock, etc.). Here we discuss necessary information for aquatic animal CVIs: animal, ownership and location; standardized diagnostic results and their interpretation; and language contained in CVIs. Also addressed is the viability for use with multiple aquatic species and diseases/pathogens of interest, and their use in conjunction with established veterinary inspection procedures. A revised model aquatic CVI, with broad potential use for individual operations, states or countries, is offered for discussion, comment and refinement. In addition an optimally designed model CVI may be of use with electronic systems that are evolving in, for example, Europe, the USA and Australia/New Zealand (e.g. TRACES, e-CVI, e-Certs). PMID:18306523

  19. Fumonisin exposure in women linked to inhibition of an enzyme that is a key event in farm and laboratory animal diseases.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin B1 (FB1) is a toxic chemical produced by molds. The molds that produce fumonisin are common in corn. Consumption of contaminated corn by farm animals has been shown to be the cause of animal disease. The proximate cause (key event) in the induction of diseases in animals is inhibition of t...

  20. Arthritis, a complex connective and synovial joint destructive autoimmune disease: animal models of arthritis with varied etiopathology and their significance.

    PubMed

    Naik, S R; Wala, S M

    2014-01-01

    Animal models play a vital role in simplifying the complexity of pathogenesis and understanding the indefinable processes and diverse mechanisms involved in the progression of disease, and in providing new knowledge that may facilitate the drug development program. Selection of the animal models has to be carefully done, so that there is morphologic similarity to human arthritic conditions that may predict as well as augment the effective screening of novel antiarthritic agents. The review describes exclusively animal models of rheumatoid arthritis (RA) and osteoarthritis (OA). The development of RA has been vividly described using a wide variety of animal models with diverse insults (viz. collagen, Freund's adjuvant, proteoglycan, pristane, avridine, formaldehyde, etc.) that are able to simulate/trigger the cellular, biochemical, immunological, and histologic alterations, which perhaps mimic, to a great extent, the pathologic conditions of human RA. Similarly, numerous methods of inducing animal models with OA have also been described (such as spontaneous, surgical, chemical, and physical methods including genetically manipulated animals) which may give an insight into the events of alteration in connective tissues and their metabolism (synovial membrane/tissues along with cartilage) and bone erosion. The development of such arthritic animal models may throw light for better understanding of the etiopathogenic mechanisms of human arthritis and give new impetus for the drug development program on arthritis, a crippling disease. PMID:25121375

  1. Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson's Disease.

    PubMed

    Ghosh, Anamitra; Langley, Monica R; Harischandra, Dilshan S; Neal, Matthew L; Jin, Huajun; Anantharam, Vellareddy; Joseph, Joy; Brenza, Timothy; Narasimhan, Balaji; Kanthasamy, Arthi; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G

    2016-06-01

    Mitochondrial dysfunction, oxidative stress and neuroinflammation have been implicated as key mediators contributing to the progressive degeneration of dopaminergic neurons in Parkinson's disease (PD). Currently, we lack a pharmacological agent that can intervene in all key pathological mechanisms, which would offer better neuroprotective efficacy than a compound that targets a single degenerative mechanism. Herein, we investigated whether mito-apocynin (Mito-Apo), a newly-synthesized and orally available derivative of apocynin that targets mitochondria, protects against oxidative damage, glial-mediated inflammation and nigrostriatal neurodegeneration in cellular and animal models of PD. Mito-Apo treatment in primary mesencephalic cultures significantly attenuated the 1-methyl-4-phenylpyridinium (MPP(+))-induced loss of tyrosine hydroxylase (TH)-positive neuronal cells and neurites. Mito-Apo also diminished MPP(+)-induced increases in glial cell activation and inducible nitric oxide synthase (iNOS) expression. Additionally, Mito-Apo decreased nitrotyrosine (3-NT) and 4-hydroxynonenol (4-HNE) levels in primary mesencephalic cultures. Importantly, we assessed the neuroprotective property of Mito-Apo in the MPTP mouse model of PD, wherein it restored the behavioral performance of MPTP-treated mice. Immunohistological analysis of nigral dopaminergic neurons and monoamine measurement further confirmed the neuroprotective effect of Mito-Apo against MPTP-induced nigrostriatal dopaminergic neuronal loss. Mito-Apo showed excellent brain bioavailability and also markedly attenuated MPTP-induced oxidative markers in the substantia nigra (SN). Furthermore, oral administration of Mito-Apo significantly suppressed MPTP-induced glial cell activation, upregulation of proinflammatory cytokines, iNOS and gp91phox in IBA1-positive cells of SN. Collectively, these results demonstrate that the novel mitochondria-targeted compound Mito-Apo exhibits profound neuroprotective effects in

  2. Animal Disease Import Risk Analysis--a Review of Current Methods and Practice.

    PubMed

    Peeler, E J; Reese, R A; Thrush, M A

    2015-10-01

    The application of risk analysis to the spread of disease with international trade in animals and their products, that is, import risk analysis (IRA), has been largely driven by the Sanitary and Phytosanitary (SPS) agreement of the World Trade Organization (WTO). The degree to which the IRA standard established by the World Organization for Animal Health (OIE), and associated guidance, meets the needs of the SPS agreement is discussed. The use of scenario trees is the core modelling approach used to represent the steps necessary for the hazard to occur. There is scope to elaborate scenario trees for commodity IRA so that the quantity of hazard at each step is assessed, which is crucial to the likelihood of establishment. The dependence between exposure and establishment suggests that they should fall within the same subcomponent. IRA undertaken for trade reasons must include an assessment of consequences to meet SPS criteria, but guidance is sparse. The integration of epidemiological and economic modelling may open a path for better methods. Matrices have been used in qualitative IRA to combine estimates of entry and exposure, and consequences with likelihood, but this approach has flaws and better methods are needed. OIE IRA standards and guidance indicate that the volume of trade should be taken into account, but offer no detail. Some published qualitative IRAs have assumed current levels and patterns of trade without specifying the volume of trade, which constrains the use of IRA to determine mitigation measures (to reduce risk to an acceptable level) and whether the principle of equivalence, fundamental to the SPS agreement, has been observed. It is questionable whether qualitative IRA can meet all the criteria set out in the SPS agreement. Nevertheless, scope exists to elaborate the current standards and guidance, so they better serve the principle of science-based decision-making. PMID:24237667

  3. Applying evolutionary concepts to wildlife disease ecology and management

    PubMed Central

    Vander Wal, Eric; Garant, Dany; Calmé, Sophie; Chapman, Colin A; Festa-Bianchet, Marco; Millien, Virginie; Rioux-Paquette, Sébastien; Pelletier, Fanie

    2014-01-01

    Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio-economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host–pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco-evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment–disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management. PMID:25469163

  4. Characterization of ESBL- and AmpC-Producing Enterobacteriaceae from Diseased Companion Animals in Europe.

    PubMed

    Bogaerts, Pierre; Huang, Te-Din; Bouchahrouf, Warda; Bauraing, Caroline; Berhin, Catherine; El Garch, Farid; Glupczynski, Youri

    2015-12-01

    The study aimed to characterize beta-lactam resistance mechanisms of Enterobacteriaceae isolates recovered from diseased dogs and cats between 2008 and 2010 in a European surveillance program (ComPath I) for the antibiotic susceptibility of bacterial pathogens. A total of 608 non-duplicated Enterobacteriaceae isolates were obtained prior antibiotic treatment from diseased dogs (n=464) and cats (n=144). Among the 608 Enterobacteriaceae isolates, 22 presented a minimal inhibitory concentration against cefotaxime above EUCAST breakpoints of susceptibility. All the 22 isolates remained susceptible to carbapenems. Ten isolates were confirmed as extended-spectrum-beta-lactamase (ESBL) producers by PCR-sequencing of bla coding genes including 9 blaCTX-M (CTX-M-1, 14, 15, 32,…) and 1 blaTEM-52 and 12 were AmpC-producing isolates (10 plasmidic CMY-2 group and 2 isolates overexpressing their chromosomal AmpC). ESBLs and plasmid-mediated AmpC (pAmpC)-producing isolates were mainly recovered from dogs (n=17) suffering from urinary tract infections (n=13) and originated from eight different countries. ESBL-bearing plasmids were mostly associated with IncFII incompatibility groups while CMY-2 was predominantly associated with plasmid of the IncI1 group. ESBL/pAmpC-producing Escherichia coli belonged to phylogroup A (n=5), B2 (n=4), and D (n=5). Multilocus sequence typing analysis revealed that among three CTX-M-15-producing E. coli, two belong to sequence type (ST) 131 and one to ST405. The presence of CTX-M-15 including on IncFII plasmids in E. coli ST131-B2 has also been described in isolates of human origin. This suggests the possibility of exchanges of these isolates from humans to companion animals or vice-versa. PMID:26098354

  5. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer

    PubMed Central

    Asgharpour, Amon; Cazanave, Sophie C.; Pacana, Tommy; Seneshaw, Mulugeta; Vincent, Robert; Banini, Bubu A.; Kumar, Divya Prasanna; Daita, Kalyani; Min, Hae-Ki; Mirshahi, Faridoddin; Bedossa, Pierre; Sun, Xiaochen; Hoshida, Yujin; Koduru, Srinivas V.; Contaifer, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S.; Sanyal, Arun J.

    2016-01-01

    Background & Aims The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development. Methods A stable isogenic cross between C57BL/6J (B6) and 129S1/SvImJ (S129) mice were fed a high fat diet with ad libitum consumption of glucose and fructose in physiologically relevant concentrations and compared to mice fed a chow diet and also to both parent strains. Results Following initiation of the obesogenic diet, B6/129 mice developed obesity, insulin resistance, hypertriglyceridemia and increased LDL-cholesterol. They sequentially also developed steatosis (4–8 weeks), steatohepatitis (16–24 weeks), progressive fibrosis (16 weeks onwards) and spontaneous hepatocellular cancer (HCC). There was a strong concordance between the pattern of pathway activation at a transcriptomic level between humans and mice with similar histological phenotypes (FDR 0.02 for early and 0.08 for late time points). Lipogenic, inflammatory and apoptotic signaling pathways activated in human NASH were also activated in these mice. The HCC gene signature resembled the S1 and S2 human subclasses of HCC (FDR 0.01 for both). Only the B6/129 mouse but not the parent strains recapitulated all of these aspects of human NAFLD. Conclusions We here describe a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND) that recapitulates the key physiological, metabolic, histologic, transcriptomic and cell-signaling changes seen in humans with progressive NASH. Lay summary We have developed a diet-induced mouse model of non-alcoholic steatohepatitis (NASH) and hepatic cancers in a cross between two mouse strains (129S1/SvImJ and C57Bl/6J). This model mimics all the physiological, metabolic, histological, transcriptomic gene signature and clinical endpoints of human NASH and can facilitate preclinical development of therapeutic targets for NASH. PMID:27261415

  6. Detection of Helicobacter felis in a cat with gastric disease in laboratory animal facility

    PubMed Central

    Hong, Sunhwa; Chung, Yungho; Kang, Won-Guk

    2016-01-01

    A 3-month-old male cat in the animal facility was presented for investigation of anorexia and occasional vomiting. We collected the specimens from gastroscopic biopsy and stool collection. The gastroscopic biopsy specimens were tested using a rapid urease test, CLO Helicobacter-detection kits. Stool specimens were gathered and evaluated using the commercially available SD Bioline H. pylori Ag kit according to the manufacturer's instructions. Genomic DNAs from gastroscopic biopsy and stool specimens of the cat were extracted and submitted to the consensus PCR to amplify Helicobacter rpoB gene. Then the DNAs from gastroscopic biopsy and stool specimens were conducted a multiplex species-specific PCR to amplify urease B gene for H. heilmannii, H. pylori and H. felis. As the results, the rapid urease test with gastroscopic biopsy was revealed positive reaction. The result of H. pylori Stool Ag assay was one red line, negative for H. pylori. The gastroscopic biopsy and stool specimen were positive reactions by the consensus PCR reaction using the RNA polymerase beta-subunit-coding gene (rpoB) to detect Helicobacter species. By multiplex species-specific PCR with gastroscopic biopsy and stool specimens, no amplification products corresponding to either H. heilmannii or H. pylori were detected, but the specimens tested were positive for H. felis. This case was confirmed as gastroenteric disease induced by H. felis infection. On our knowledge, this is a very rare report about H. felis-induced gastroenteric disease in cat and may provide a valuable data on the study of feline Helicobacter infection. PMID:27382381

  7. Natural Non-Trasgenic Animal Models for Research in Alzheimer’s Disease

    PubMed Central

    Sarasa, Manuel; Pesini, Pedro

    2009-01-01

    The most common animal models currently used for Alzheimer disease (AD) research are transgenic mice that express a mutant form of human Aβ precursor protein (APP) and/or some of the enzymes implicated in their metabolic processing. However, these transgenic mice carry their own APP and APP-processing enzymes, which may interfere in the production of different amyloid-beta (Aβ) peptides encoded by the human transgenes. Additionally, the genetic backgrounds of the different transgenic mice are a possible confounding factor with regard to crucial aspects of AD that they may (or may not) reproduce. Thus, although the usefulness of transgenic mice is undisputed, we hypothesized that additional relevant information on the physiopathology of AD could be obtained from other natural non-transgenic models. We have analyzed the chick embryo and the dog, which may be better experimental models because their enzymatic machinery for processing APP is almost identical to that of humans. The chick embryo is extremely easy to access and manipulate. It could be an advantageous natural model in which to study the cell biology and developmental function of APP and a potential assay system for drugs that regulate APP processing. The dog suffers from an age-related syndrome of cognitive dysfunction that naturally reproduces key aspects of AD including Aβ cortical pathology, neuronal degeneration and learning and memory disabilities. However, dense core neuritic plaques and neurofibrillary tangles have not been consistently demonstrated in the dog. Thus, these species may be natural models with which to study the biology of AD, and could also serve as assay systems for Aβ-targeted drugs or new therapeutic strategies against this devastating disease. PMID:19355852

  8. Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

    PubMed Central

    Darcet, Flavie; Gardier, Alain M.; Gaillard, Raphael; David, Denis J.; Guilloux, Jean-Philippe

    2016-01-01

    Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. PMID:26901205

  9. Micro-RNAs in abdominal aortic aneurysms: insights from animal models and relevance to human disease.

    PubMed

    Raffort, Juliette; Lareyre, Fabien; Clement, Marc; Mallat, Ziad

    2016-05-15

    Abdominal aortic aneurysm (AAA) is a major health concern and may be associated with high rates of mortality linked to acute complications. Diagnosis and treatment are, respectively, based on imaging and surgical techniques. Drug-based therapies are still mostly ineffective, which highlight a real unmet need. Major pathophysiological mechanisms leading to aneurysm formation involve inflammatory processes, degradation of the extracellular matrix, and loss of smooth muscle cells. However, the precise cellular and molecular pathways are still poorly understood. Recently, microRNAs have emerged as major intracellular players in a wide range of biological processes, and their stability in extracellular medium within microvesicles has led to propose them as mediators of intercellular crosstalk and as potential biomarkers and therapeutic targets in a variety of disease settings. To date, several studies have been performed to address the involvement of micro-RNAs (miRs) in aneurysm formation and complications. Here, we discuss the roles and implications of miRs in animal models and their relevance to human AAA. PMID:26965051

  10. Developmental Origins of Health and Disease in swine: implications for animal production and biomedical research.

    PubMed

    Gonzalez-Bulnes, A; Astiz, S; Ovilo, C; Lopez-Bote, C J; Torres-Rovira, L; Barbero, A; Ayuso, M; Garcia-Contreras, C; Vazquez-Gomez, M

    2016-07-01

    The concept of Developmental Origins of Health and Disease (DOHaD) addresses, from a large set of epidemiological evidences in human beings and translational studies in animal models, both the importance of genetic predisposition and the determinant role of maternal nutrition during pregnancy on adult morphomics and homeostasis. Compelling evidences suggest that both overnutrition and undernutrition may modify the intrauterine environment of the conceptus and may alter the expression of its genome and therefore its phenotype during prenatal and postnatal life. In fact, the DOHaD concept is an extreme shift in the vision of the factors conditioning adult phenotype and supposes a drastic change from a gene-centric perspective, only modified by lifestyle and nutritional strategies during juvenile development and adulthood, to a more holistic approach in which environmental, parental, and prenatal conditions are strongly determining postnatal development and homeostasis. The implications of DOHaD are profound in all the mammalian species and the present review summarizes current knowledge on causes and consequences of DOHaD in pigs, both for meat production and as a well-recognized model for biomedicine research. PMID:27238437

  11. Leptin Dysfunction and Alzheimer's Disease: Evidence from Cellular, Animal, and Human Studies.

    PubMed

    McGuire, Matthew J; Ishii, Makoto

    2016-03-01

    There is accumulating evidence from epidemiological studies that changes in body weight are associated with Alzheimer's disease (AD) from mid-life obesity increasing the risk of developing AD to weight loss occurring at the earliest stages of AD. Therefore, factors that regulate body weight are likely to influence the development and progression of AD. The adipocyte-derived hormone leptin has emerged as a major regulator of body weight mainly by activating hypothalamic neural circuits. Leptin also has several pleotropic effects including regulating cognitive function and having neuroprotective effects, suggesting a potential link between leptin and AD. Here, we will examine the relationship between leptin and AD by reviewing the recent evidence from cellular and animal models to human studies. We present a model where leptin has a bidirectional role in AD. Not only can alterations in leptin levels and function worsen cognitive decline and progression of AD pathology, but AD pathology, in of itself, can disrupt leptin signaling, which together would lead to a downward spiral of progressive neurodegeneration and worsening body weight and systemic metabolic deficits. Collectively, these studies serve as a framework to highlight the importance of understanding the molecular mechanisms underlying the body weight and systemic metabolic deficits in AD, which has the potential to open new avenues that may ultimately lead to novel therapeutic targets and diagnostic tools. PMID:26993509

  12. MOZ and MORF acetyltransferases: Molecular interaction, animal development and human disease.

    PubMed

    Yang, Xiang-Jiao

    2015-08-01

    Lysine residues are subject to many forms of covalent modification and one such modification is acetylation of the ε-amino group. Initially identified on histone proteins in the 1960s, lysine acetylation is now considered as an important form of post-translational modification that rivals phosphorylation. However, only about a dozen of human lysine acetyltransferases have been identified. Among them are MOZ (monocytic leukemia zinc finger protein; a.k.a. MYST3 and KAT6A) and its paralog MORF (a.k.a. MYST4 and KAT6B). Although there is a distantly related protein in Drosophila and sea urchin, these two enzymes are vertebrate-specific. They form tetrameric complexes with BRPF1 (bromodomain- and PHD finger-containing protein 1) and two small non-catalytic subunits. These two acetyltransferases and BRPF1 play key roles in various developmental processes; for example, they are important for development of hematopoietic and neural stem cells. The human KAT6A and KAT6B genes are recurrently mutated in leukemia, non-hematologic malignancies, and multiple developmental disorders displaying intellectual disability and various other abnormalities. In addition, the BRPF1 gene is mutated in childhood leukemia and adult medulloblastoma. Therefore, these two acetyltransferases and their partner BRPF1 are important in animal development and human disease. PMID:25920810

  13. Neuroprotection of pramipexole in UPS impairment induced animal model of Parkinson's disease.

    PubMed

    Li, Chao; Guo, Yuan; Xie, Wenjie; Li, Xingang; Janokovic, Joseph; Le, Weidong

    2010-10-01

    Pramipexole (PPX), a dopamine (DA) receptor D3 preferring agonist, has been used as monotherapy or adjunct therapy to treat Parkinson's disease (PD) for many years. Several in vitro and in vivo studies in neurotoxin-induced DA neuron injury models have reported that PPX may possess neuroprotective properties. The present study is to evaluate the neuroprotection of PPX in a sustained DA neuron degeneration model of PD induced by ubiquitin-proteasome system (UPS) impairment. Adult C57BL/6 mice were treated with PPX (low dose 0.1 mg/kg or high dose 0.5 mg/kg, i.p, twice a day) started 7 days before, and continued after microinjection of proteasome inhibitor lactacystin in the medial forebrain bundle for a total 4 weeks. Animal behavior observation, and pathological and biochemical assays were conducted to determine the neuroprotective effects of PPX. We report here that PPX treatment significantly improves rotarod performance, attenuates DA neuron loss and striatal DA reduction, and alleviates proteasomal inhibition and microglial activation in the substantia nigra of lactacystin-lesioned mice. PPX can increase the levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor and induce an activation of autophagy. Furthermore, pretreatment with D3 receptor antagonist U99194 can significantly block the PPX-mediated neuroprotection. These results suggest that multiple molecular pathways may be attributed to the neuroprotective effects of PPX in the UPS impairment model of PD. PMID:20635141

  14. Potential large animal models for gene therapy of human genetic diseases of immune and blood cell systems.

    PubMed

    Bauer, Thomas R; Adler, Rima L; Hickstein, Dennis D

    2009-01-01

    Genetic mutations involving the cellular components of the hematopoietic system--red blood cells, white blood cells, and platelets--manifest clinically as anemia, infection, and bleeding. Although gene targeting has recapitulated many of these diseases in mice, these murine homologues are limited as translational models by their small size and brief life span as well as the fact that mutations induced by gene targeting do not always faithfully reflect the clinical manifestations of such mutations in humans. Many of these limitations can be overcome by identifying large animals with genetic diseases of the hematopoietic system corresponding to their human disease counterparts. In this article, we describe human diseases of the cellular components of the hematopoietic system that have counterparts in large animal species, in most cases carrying mutations in the same gene (CD18 in leukocyte adhesion deficiency) or genes in interacting proteins (DNA cross-link repair 1C protein and protein kinase, DNA-activated catalytic polypeptide in radiation-sensitive severe combined immunodeficiency). Furthermore, we describe the potential of these animal models to serve as disease-specific preclinical models for testing the efficacy and safety of clinical interventions such as hematopoietic stem cell transplantation or gene therapy before their use in humans with the corresponding disease. PMID:19293460

  15. Potential Large Animal Models for Gene Therapy of Human Genetic Diseases of Immune and Blood Cell Systems

    PubMed Central

    Bauer, Thomas R.; Adler, Rima L.; Hickstein, Dennis D.

    2009-01-01

    Genetic mutations involving the cellular components of the hematopoietic system—red blood cells, white blood cells, and platelets—manifest clinically as anemia, infection, and bleeding. Although gene targeting has recapitulated many of these diseases in mice, these murine homologues are limited as translational models by their small size and brief life span as well as the fact that mutations induced by gene targeting do not always faithfully reflect the clinical manifestations of such mutations in humans. Many of these limitations can be overcome by identifying large animals with genetic diseases of the hematopoietic system corresponding to their human disease counterparts. In this article, we describe human diseases of the cellular components of the hematopoietic system that have counterparts in large animal species, in most cases carrying mutations in the same gene (CD18 in leukocyte adhesion deficiency) or genes in interacting proteins (DNA cross-link repair 1C protein and protein kinase, DNA-activated, catalytic polypeptide in radiation-sensitive severe combined immunodeficiency). Furthermore, we describe the potential of these animal models to serve as disease-specific, preclinical models for testing the efficacy and safety of clinical interventions such as hematopoietic stem cell transplantation or gene therapy approaches before their use in humans with the corresponding disease. PMID:19293460

  16. "How sick must your mouse be? " - An analysis of the use of animal models in Huntington's disease research.

    PubMed

    Franco, Nuno H; Olsson, I Anna S

    2012-10-01

    Refinement measures to improve animal welfare can ease the ethical dilemma between human benefit and animal harm in research with animal models of neurodegenerative diseases. To evaluate the potential for refinement, as well as its implementation in research, we analysed papers on murine models of Huntington's disease (HD) published between 1999 and 2009 (n = 233). Each study was classified according to a four-level severity scale, in terms of the disease stage that animals were allowed to reach, the execution of invasive procedures, and the implementation of refinement. Reports of ethical approval, and regulatory compliance in general, followed a clear rising trend over the years reviewed (p <0.001). However, the proportion of high-severity studies did not change over that period. Also, of the studies for which approval was reported (n = 120), 36% were attributed the highest severity level. The observed discrepancy between the rising motivation to affirm regulatory compliance, and the unaltered proportion of studies allowing animals to reach severely distressful stages, raises both ethical and methodological issues, which we discuss in this paper. PMID:23215663

  17. Compendium of measures to prevent disease associated with animals in public settings, 2011: National Association of State Public Health Veterinarians, Inc.

    PubMed

    2011-05-01

    Certain venues encourage or permit the public to be in contact with animals, resulting in millions of human-animal interactions each year. These settings include county or state fairs, petting zoos, animal swap meets, pet stores, feed stores, zoologic institutions, circuses, carnivals, educational farms, livestock-birthing exhibits, educational exhibits at schools and child-care facilities, and wildlife photo opportunities. Although human-animal contact has many benefits, human health problems are associated with these settings, including infectious diseases, exposure to rabies, and injuries. Infectious disease outbreaks have been caused by Escherichia coli O157:H7, Salmonella species, Cryptosporidium species, Coxiella burnetii, Mycobacterium tuberculosis, ringworm, and other pathogens. Such outbreaks have substantial medical, public health, legal, and economic effects. This report provides recommendations for public health officials, veterinarians, animal venue staff members, animal exhibitors, visitors to animal venues, physicians, and others concerned with minimizing risks associated with animals in public settings. The recommendation to wash hands is the most important for reducing the risk for disease transmission associated with animals in public settings. Other important recommendations are that venues prohibit food in animal areas and include transition areas between animal areas and nonanimal areas, visitors receive information about disease risk and prevention procedures, and animals be properly cared for and managed. These updated 2011 guidelines provide new information on the risks associated with amphibians and with animals in day camp settings, as well as the protective role of zoonotic disease education. PMID:21546893

  18. HIGHLIGHTS, INSIGHTS, AND PERSPECTIVES ON INFECTIOUS DISEASE AGENTS IN SEWAGE SLUDGE AND ANIMAL MANURE IN THE U.S.

    EPA Science Inventory

    The purpose of this chapter is: 1) Highlight the core principles and findings from the Workshop on Emerging Infectious Disease Agents and Issues Associated With Sewage Sludge, Animal Manures and Other Organic By-Products held June 4-6, 2001, Cincinnati, Ohio, so that all readers,...

  19. Dynamics of endemic infectious diseases of animal and human importance on three dairy herds in the northeastern United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endemic infectious diseases in dairy cattle are of significant concern to the industry as well as for public health due to their potential impact on animal and human health, milk and meat production, food safety, and economics. We sought to provide insight into the dynamics of important endemic infe...

  20. 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

  1. Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review

    PubMed Central

    Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

    2015-01-01

    Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction. PMID:26587586

  2. Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review.

    PubMed

    Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

    2015-11-01

    Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction. PMID:26587586

  3. Animal welfare and the refinement of neuroscience research methods--a case study of Huntington's disease models.

    PubMed

    Olsson, I Anna S; Hansen, Axel K; Sandøe, Peter

    2008-07-01

    The use of animals in biomedical and other research presents an ethical dilemma: we do not want to lose scientific benefits, nor do we want to cause laboratory animals to suffer. Scientists often refer to the potential human benefits of animal models to justify their use. However, even if this is accepted, it still needs to be argued that the same benefits could not have been achieved with a mitigated impact on animal welfare. Reducing the adverse effects of scientific protocols ('refinement') is therefore crucial in animal-based research. It is especially important that researchers share knowledge on how to avoid causing unnecessary suffering. We have previously demonstrated that even in studies in which animal use leads to spontaneous death, scientists often fail to report measures to minimize animal distress (Olsson et al. 2007). In this paper, we present the full results of a case study examining reports, published in peer-reviewed journals between 2003 and 2004, of experiments employing animal models to study the neurodegenerative disorder Huntington's disease. In 51 references, experiments in which animals were expected to develop motor deficits so severe that they would have difficulty eating and drinking normally were conducted, yet only three references were made to housing adaptation to facilitate food and water intake. Experiments including end-stages of the disease were reported in 14 papers, yet of these only six referred to the euthanasia of moribund animals. If the reference in scientific publications reflects the actual application of refinement, researchers do not follow the 3Rs (replacement, reduction, refinement) principle. While in some cases, it is clear that less-than-optimal techniques were used, we recognize that scientists may apply refinement without referring to it; however, if they do not include such information in publications, it suggests they find it less relevant. Journal publishing policy could play an important role: first, in

  4. National biosecurity approaches, plans and programmes in response to diseases in farmed aquatic animals: evolution, effectiveness and the way forward.

    PubMed

    Håstein, T; Binde, M; Hine, M; Johnsen, S; Lillehaug, A; Olesen, N J; Purvis, N; Scarfe, A D; Wright, B

    2008-04-01

    The rapid increase in aquaculture production and trade, and increased attention to the negative effects of disease, are becoming stimuli for developing national biosecurity strategies for farmed fisheries, for which the World Organisation for Animal Health (OIE) Aquatic Animal Health Code and Manual of Diagnostic Tests for Aquatic Animals serve as an excellent framework. Using examples from a few countries and selected diseases, this paper provides a general overview of the development of approaches to implementing biosecurity strategies, including those emerging in the national legislation and regulations of some countries, and those being initiated by industries themselves. The determination of disease status in different epidemiological units (from a farm to a nation), appropriate approaches for preventing the introduction of disease and developing contingencies for disease control and eradication are also discussed. Important to the effectiveness of such strategies are provision of financial, personnel and other resources to implement them, including incentives such as indemnification or compensation in eradication programmes, and practical linkage to regulatory or government policy initiatives. PMID:18666484

  5. Comparative Global Gene Expression Profiling Between rMd5- and rMd5deltaMeq-Infected Chickens: Host-Pathogen Interaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease virus (MDV), an oncogenic alpha-herpesvirus, is the etiological agent of Marek’s disease (MD), a highly contagious lymphoproliferative disease of domestic chickens. MDV encodes a basic leucine zipper protein, meq (MDV Eco Q), which is homologous to the Jun/Fos family of transcriptio...

  6. Learning from outbreaks of bovine tuberculosis near Riding Mountain National Park: Applications to a foreign animal disease outbreak

    PubMed Central

    2004-01-01

    Abstract Riding Mountain National Park, Manitoba, is home to a population of free-roaming elk (Cervus elaphus manitobensis) that have been found to be infected with Mycobacterium bovis, the agent of bovine tuberculosis (TB). The disease has also been found in a number of cattle herds near the Park and, as a result, Manitoba has been assigned a split status for bovine TB. A number of government agencies, with input from representatives from the wildlife and agricultural sectors, have responded by devising a program to detect, investigate, control, eradicate, and prevent TB in both wild and domestic animals. Experience from these efforts can be applied to the control of other diseases, such a foreign animal disease, elsewhere in Canada. PMID:14992251

  7. A needs-assessment and demographic survey of infection-control and disease awareness in western US animal shelters.

    PubMed

    Steneroden, Kay K; Hill, Ashley E; Salman, M D

    2011-01-01

    A cross-sectional needs-assessment survey was used to characterize animal shelters in a 6-state region in the western US and describe infection-control practices and disease awareness. Survey questions focused on shelter demographics, infection-control practices and policies, awareness and concern over infectious and zoonotic diseases, staff and volunteer training relating to infection-control and disease awareness, use of diagnostic tools, and isolation procedures and protocols. Fifty percent of shelters responded to the survey and represented a wide variety of shelter types, sizes and locations. The top-three diseases of concern to shelters were feline upper respiratory disease (FURD), canine parvovirus and ringworm. Concern over these diseases was greater in open-admission shelters (compared to limited admission or no-kill/sanctuary) (OR 3.7, 95% CI 1.1-12.5) and in shelters with a desire for more zoonotic-disease training (OR=6.1, 95% CI 1.5-24.8) (compared to shelters desiring infectious-disease training, training on cleaning and disinfection or those who have no need for further training). In 45% of responding shelters many to most animals arrive with infectious diseases. Written protocols for preventive medicine exist in 88% of shelters, cleaning and disinfection protocols in 75%, specific disease protocols for outbreak situations in 36% and infection-control manuals in 15%. Veterinarians are in charge of infection-control in 6% of shelters. Approximately 45% of shelters vaccinate dogs and cats for rabies. Infectious-disease training is provided to 30% of staff and 35% of volunteers upon hire. Overall, volunteers received less training in infectious- and zoonotic-disease identification, prevention and control than staff members. Ninety percent of shelters said they would benefit from training in infectious and zoonotic disease. Results from this study can be used to assess and address needs in animal shelters relating to infection-control, infectious and

  8. Validation of Abeta1-40 administration into mouse cerebroventricles as an animal model for Alzheimer disease.

    PubMed

    Takeda, Shuko; Sato, Naoyuki; Niisato, Kazue; Takeuchi, Daisuke; Kurinami, Hitomi; Shinohara, Mitsuru; Rakugi, Hiromi; Kano, Masanobu; Morishita, Ryuichi

    2009-07-14

    Valid animal models for a specific human disease are indispensable for development of new therapeutic agents. The conclusions drawn from animal models largely depend on the validity of the model. Several studies have shown that administration of Abeta into the brain causes some of the pathological events observed in Alzheimer disease (AD). However, the validity of these models has not fully been examined. In this present study, we further characterized and validated Abeta1-40 injected mice as an animal model for AD, based on three major criteria: face, construct and predictive validity. Intracerebroventricular (i.c.v.) injection of Abeta1-40 into mice significantly impaired memory acquisition, but not memory retrieval, which implies similarity to the episodic anterograde memory deficit observed in the early stage of AD. Electrophysiological assessment showed that i.c.v. administration of Abeta1-40 significantly attenuated hippocampal long-term potentiation. Treatment with galantamine, a drug currently in clinical use for AD, significantly improved cognitive dysfunction in this model. These results demonstrate that i.c.v. injection of Abeta1-40 caused specific dysfunction of memory processes, which at least partly fulfills three validity criteria for AD. Symptomatic and pathophysiological similarities of this model to AD are quite important in considering the usefulness of this animal model. This validated animal model could be useful to develop and evaluate potential new drugs for AD. PMID:19464276

  9. Prevalence of dipterous flies associated with human and animal diseases in Matruh and South Sinai Governorates, Egypt.

    PubMed

    Abd El-Halim, Azza S; Soliman, M I; Mikhail, M W

    2009-12-01

    The present study identified the dipterous flies associated with human and animal diseases in Matruh and South Sinai Governorates. The results indicated that 49817 belonging to 13 families, 24 genera and 33 species were trapped from Matruh Governorate and 3708 flies belonging to 9 families, 13 genera and 16 species were trapped from South Sinai Governorate from January to December 2009. M. domestica was the most abundant in both Governorates. Statistical analysis showed that species of all families were significantly higher in Matruh Governorate than South Sinai Governorate due to spread of garbage, fermented fruits and human & animal excreta. PMID:20120746

  10. Angiotensin-(1-7) is Reduced and Inversely Correlates with Tau Hyperphosphorylation in Animal Models of Alzheimer's Disease.

    PubMed

    Jiang, Teng; Zhang, Ying-Dong; Zhou, Jun-Shan; Zhu, Xi-Chen; Tian, You-Yong; Zhao, Hong-Dong; Lu, Huan; Gao, Qing; Tan, Lan; Yu, Jin-Tai

    2016-05-01

    As a recently identified bioactive peptide of brain renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)] along with its metabolic enzyme angiotensin-converting enzyme (ACE) 2 and its receptor Mas forms ACE2/Ang-(1-7)/Mas axis. Accumulating evidence suggests an essential role of ACE2/Ang-(1-7)/Mas axis in maintaining normal cognitive functions in both animals and human subjects, and dysregulation of this axis contributed to the pathogenesis of several neurodegenerative diseases such as hypertension-induced neurodegeneration and vascular dementia. To date, whether this axis was associated with the etiology and progression of Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly, remains unclear. In the current study, by using senescence-accelerated mouse prone 8 (SAMP8) mice, an animal model of sporadic AD, we showed for the first time that the level of Ang-(1-7) in the brain was significantly reduced during disease progression. More importantly, an inverse correlation was found between Ang-(1-7) level and tau hyperphosphorylation, a pathological hallmark of AD, in cerebral cortex and hippocampus of SAMP8 mice. Meanwhile, this has been further confirmed in P301S mice, an animal model of pure tauopathy. All these findings suggested that Ang-(1-7), the main effector of brain ACE2/Ang-(1-7)/Mas axis, might be implicated in the etiology and progression of AD, possibly via modulation of tau hyperphosphorylation. PMID:26044748

  11. A Review of Exotic Animal Disease in Great Britain and in Scotland Specifically between 1938 and 2007

    PubMed Central

    Peiso, Onneile O.; de C. Bronsvoort, Barend M.; Handel, Ian G.; Volkova, Victoriya V.

    2011-01-01

    Background Incursions of contagious diseases of livestock into disease-free zones are inevitable as long as the diseases persist elsewhere in the world. Knowledge of where, when and how incursions have occurred helps assess the risks, and regionalize preventative and reactive measures. Methodology Based on reports of British governmental veterinary services, we review occurrence of the former OIE List A diseases, and of Aujeszky's disease, anthrax and bovine tuberculosis (bTB) in farm-animals in Great Britain (GB) between 1938 and 2007. We estimate incidence of each disease on GB agricultural holdings and fraction of susceptible farm-animals culled to control the disease each year. We then consider the frequency and incidence of the diseases in Scotland alone. The limitations of available data on historical disease occurrence and denominator populations are detailed in Text S2. Conclusions The numbers of livestock and poultry farmed in GB grew over the years 1938–2007; the number of agricultural holdings decreased. An amalgamation of production on larger holdings took place from the 1940s to the 1980s. The maximum annual incidence of a reviewed disease in GB 1938–2007 was reported for bTB, 1.69% of holdings in 1961. This was followed by Newcastle disease, 1.50% of holdings in 1971, and classical swine fever, 1.09% of holdings in 1940. The largest fractional cull of susceptible livestock in a single year in each of the four decades 1950s–1980s was due to a viral disease primarily affecting swine. During the periods 1938–1949 and 2000–2007 this was due to outbreaks of foot and mouth disease. In the absence of incursions of the former OIE List A diseases in the 1990s, this was due to bTB. Over the 70 years, the diseases were reported with lower frequency and lower annual incidence in Scotland, as compared to when these statistics are considered for GB as a whole. PMID:21818292

  12. The Microbiome: The Trillions of Microorganisms That Maintain Health and Cause Disease in Humans and Companion Animals.

    PubMed

    Rodrigues Hoffmann, A; Proctor, L M; Surette, M G; Suchodolski, J S

    2016-01-01

    The microbiome is the complex collection of microorganisms, their genes, and their metabolites, colonizing the human and animal mucosal surfaces, digestive tract, and skin. It is now well known that the microbiome interacts with its host, assisting in digestion and detoxification, supporting immunity, protecting against pathogens, and maintaining health. Studies published to date have demonstrated that healthy individuals are often colonized with different microbiomes than those with disease involving various organ systems. This review covers a brief history of the development of the microbiome field, the main objectives of the Human Microbiome Project, and the most common microbiomes inhabiting the human respiratory tract, companion animal digestive tract, and skin in humans and companion animals. The main changes in the microbiomes in patients with pulmonary, gastrointestinal, and cutaneous lesions are described. PMID:26220947

  13. Factors associated with development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics

    PubMed Central

    Joffe, Daniel J.; Lelewski, Roxana; Weese, J. Scott; Mcgill-Worsley, Jamie; Shankel, Catharine; Mendonca, Sonia; Sager, Tara; Smith, Michael; Poljak, Zvonimir

    2016-01-01

    This study investigated the association between presence of respiratory pathogens and development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics. In total, 86 dogs were tested using a commercial PCR respiratory panel; 64 dogs were considered as cases and 22 were control dogs matched by veterinary clinic. No control animals (0/22) were positive for canine parainfluenza virus (CPIV), whereas 27/64 (42%) CIRDC cases were positive. Furthermore, 81% of case dogs tested positive for Mycoplasma cynos, compared with 73% of control dogs. Canine respiratory corona virus (CRCoV) was detected in no control dogs compared with 9.4% of clinical dogs. No animals were positive for any influenza virus type A present in the diagnostic panel. Presence of CPIV was associated (P < 0.01) with the occurrence of CIRDC after adjustment for demographic factors and presence of CRCoV (P = 0.09). PMID:26740697

  14. Factors associated with development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics.

    PubMed

    Joffe, Daniel J; Lelewski, Roxana; Weese, J Scott; Mcgill-Worsley, Jamie; Shankel, Catharine; Mendonca, Sonia; Sager, Tara; Smith, Michael; Poljak, Zvonimir

    2016-01-01

    This study investigated the association between presence of respiratory pathogens and development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics. In total, 86 dogs were tested using a commercial PCR respiratory panel; 64 dogs were considered as cases and 22 were control dogs matched by veterinary clinic. No control animals (0/22) were positive for canine parainfluenza virus (CPIV), whereas 27/64 (42%) CIRDC cases were positive. Furthermore, 81% of case dogs tested positive for Mycoplasma cynos, compared with 73% of control dogs. Canine respiratory corona virus (CRCoV) was detected in no control dogs compared with 9.4% of clinical dogs. No animals were positive for any influenza virus type A present in the diagnostic panel. Presence of CPIV was associated (P < 0.01) with the occurrence of CIRDC after adjustment for demographic factors and presence of CRCoV (P = 0.09). PMID:26740697

  15. Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model

    PubMed Central

    Massé, Priscilla G; Boskey, Adele L; Ziv, Israel; Hauschka, Peter; Donovan, Sharon M; Howell, David S; Cole, David EC

    2003-01-01

    Background Classical homocystinuria is an autosomal recessive disorder caused by cystathionine β-synthase (CBS) deficiency and characterized by distinctive alterations of bone growth and skeletal