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Cheung, C., Akiyama, T. E., Ward, J. M., Nicol, C. J., Feigenbaum, L., Vinson, C., et al. (2004). Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res, 64(11), 3849–3854.
Abstract: Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators.
Keywords: Animals; Anticholesteremic Agents/pharmacology; Carcinogens/pharmacology; Cell Division; DNA Replication/drug effects; Fatty Acids/metabolism; Hepatocytes/cytology/drug effects/metabolism/*physiology; Humans; Mice; Mice, Transgenic; Oxidation-Reduction; Peroxisome Proliferators/pharmacology; Pyrimidines/pharmacology; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Species Specificity; Transcription Factors/genetics/*physiology
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Chilton, N. B. (2004). The use of nuclear ribosomal DNA markers for the identification of bursate nematodes (order Strongylida) and for the diagnosis of infections. Anim Health Res Rev, 5(2), 173–187.
Abstract: Many bursate nematodes are of major importance to animal health. Animals are often parasitized by multiple species that differ in their prevalence, relative abundance and/or pathogenicity. Implementation of effective management strategies for these parasites requires reliable methods for their detection in hosts, identification to the species level and measurement of intensity of infection. One major problem is the difficulty of accurately identifying and distinguishing many species of bursate nematode because of the remarkable morphological similarity of their eggs and larvae. The inability to identify, with confidence, individual nematodes (irrespective of their life-cycle stage) to the species level by morphological methods has often led to a search for species-specific genetic markers. Studies over the past 15 years have shown that sequences of the internal transcribed spacers of ribosomal DNA provide useful genetic markers, providing the basis for the development of PCR-based diagnostic tools. Such molecular methods represent powerful tools for studying the systematics, epidemiology and ecology of bursate nematodes and, importantly, for the specific diagnosis of infections in animals and humans, thus contributing to improved control and prevention strategies for these parasites.
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Burke, D., Cieplucha, C., Cass, J., Russell, F., & Fry, G. (2002). Win-shift and win-stay learning in the short-beaked echidna (Tachyglossus aculeatus). Anim. Cogn., 5(2), 79–84.
Abstract: Numerous previous investigators have explained species differences in spatial memory performance in terms of differences in foraging ecology. In three experiments we attempted to extend these findings by examining the extent to which the spatial memory performance of echidnas (or “spiny anteaters”) can be understood in terms of the spatio-temporal distribution of their prey (ants and termites). This is a species and a foraging situation that have not been examined in this way before. Echidnas were better able to learn to avoid a previously rewarding location (to “win-shift”) than to learn to return to a previously rewarding location (to “win-stay”), at short retention intervals, but were unable to learn either of these strategies at retention intervals of 90 min. The short retention interval results support the ecological hypothesis, but the long retention interval results do not.
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Nicol, C. J., Yoon, M., Ward, J. M., Yamashita, M., Fukamachi, K., Peters, J. M., et al. (2004). PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis. Carcinogenesis, 25(9), 1747–1755.
Abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis.
Keywords: 9,10-Dimethyl-1,2-benzanthracene/*toxicity; Animals; DNA Primers/chemistry; Disease Susceptibility; Female; Heterozygote; Humans; Mammary Neoplasms, Experimental/chemically induced/*pathology; Mice; Ovarian Neoplasms/chemically induced/*pathology; RNA, Messenger/genetics/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms/chemically induced/*pathology; Survival Rate; Transcription Factors/genetics/*physiology; Zinc Fingers
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Breen, M., Downs, P., Irvin, Z., & Bell, K. (1994). Intrageneric amplification of horse microsatellite markers with emphasis on the Przewalski's horse (E. przewalskii). Anim Genet, 25(6), 401–405.
Abstract: Primer sequences flanking 13 microsatellite loci isolated from the domestic horse (E. caballus) were successfully used to amplify homologous loci in the Przewalski's horse (E. przewalskii). The results demonstrate that the level of polymorphism at all 13 loci in the Przewalski's horse was comparable to that in the domestic horse and the overall exclusion probability in the Przewalski's horse was calculated to be 0.9994. The results suggest that it should be possible to use E. caballus-derived microsatellite markers to provide parentage verification and additional valuable information to the captive management of E. przewalskii. The ability to amplify corresponding loci in the remaining five species of the genus was also confirmed, illustrating the general application of markers isolated from the domestic horse to the evaluation of polymorphism in the other six species of the genus.
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Boucher, J. M., Hanosset, R., Augot, D., Bart, J. M., Morand, M., Piarroux, R., et al. (2005). Detection of Echinococcus multilocularis in wild boars in France using PCR techniques against larval form. Vet Parasitol, 129(3-4), 259–266.
Abstract: Recently, new data have been collected on the distribution and ecology of Echinococcus multilocularis in European countries. Different ungulates species such as pig, goat, sheep, cattle and horse are known to host incomplete development of larval E. multilocularis. We report a case of E. multilocularis portage in two wild boars from a high endemic area in France (Department of Jura). Histological examination was performed and the DNA was isolated from hepatic lesions then amplified by using three PCR methods in two distinct institutes. Molecular characterisation of PCR products revealed 99% nucleotide sequence homology with the specific sequence of the U1 sn RNA gene of E. multilocularis, 99 and 99.9% nucleotide sequence homology with the specific sequence of the cytochrome oxydase gene of Echinococcus genus and 99.9% nucleotide sequence homology with a genomic DNA sequence of Echinococcus genus for the first and the second wild boar, respectively.
Keywords: Animals; Base Sequence; DNA, Helminth/chemistry/genetics; Echinococcosis/parasitology/pathology/*veterinary; Echinococcus multilocularis/*isolation & purification; Electron Transport Complex IV/chemistry/genetics; France; Histocytochemistry/veterinary; Liver/parasitology/pathology; Male; Molecular Sequence Data; Polymerase Chain Reaction/veterinary; Sequence Alignment; Sus scrofa/*parasitology; Swine Diseases/*parasitology/pathology
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Sebastiani, F., Meiswinkel, R., Gomulski, L. M., Guglielmino, C. R., Mellor, P. S., Malacrida, A. R., et al. (2001). Molecular differentiation of the Old World Culicoides imicola species complex (Diptera, Ceratopogonidae), inferred using random amplified polymorphic DNA markers. Mol Ecol, 10(7), 1773–1786.
Abstract: Samples of seven of the 10 morphological species of midges of the Culicoides imicola complex were considered. The importance of this species complex is connected to its vectorial capacity for African horse sickness virus (AHSV) and bluetongue virus (BTV). Consequently, the risk of transmission may vary dramatically, depending upon the particular cryptic species present in a given area. The species complex is confined to the Old World and our samples were collected in Southern Africa, Madagascar and the Ivory Coast. Genomic DNA of 350 randomly sampled individual midges from 19 populations was amplified using four 20-mer primers by the random amplified polymorphic DNA (RAPD) technique. One hundred and ninety-six interpretable polymorphic bands were obtained. Species-specific RAPD profiles were defined and for five species diagnostic RAPD fragments were identified. A high degree of polymorphism was detected in the species complex, most of which was observed within populations (from 64 to 76%). Principal coordinate analysis (PCO) and cluster analysis provided an estimate of the degree of variation between and within populations and species. There was substantial concordance between the taxonomies derived from morphological and molecular data. The amount and the different distributions of genetic (RAPD) variation among the taxa can be associated to their life histories, i.e. the abundance and distribution of the larval breeding sites and their seasonality.
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Muscatello, G., Anderson, G. A., Gilkerson, J. R., & Browning, G. F. (2006). Associations between the ecology of virulent Rhodococcus equi and the epidemiology of R. equi pneumonia on Australian thoroughbred farms. Appl Environ Microbiol, 72(9), 6152–6160.
Abstract: The ecology of virulent strains of Rhodococcus equi on horse farms is likely to influence the prevalence and severity of R. equi pneumonia in foals. This study examined the association between the ecology of virulent R. equi and the epidemiology of R. equi pneumonia by collecting air and soil samples over two breeding seasons (28 farm-year combinations) on Thoroughbred breeding farms with different reported prevalences of R. equi pneumonia. Colony blotting and DNA hybridization were used to detect and measure concentrations of virulent R. equi. The prevalence of R. equi pneumonia was associated with the airborne burden of virulent R. equi (both the concentration and the proportion of R. equi bacteria that were virulent) but was not associated with the burden of virulent R. equi in the soil. Univariable screening and multivariable model building were used to evaluate the effect of environmental and management factors on virulent R. equi burdens. Lower soil moisture concentrations and lower pasture heights were significantly associated with elevated airborne concentrations of virulent R. equi, as were the holding pens and lanes, which typically were sandy, dry, and devoid of pasture cover. Few variables appeared to influence concentrations of virulent R. equi in soil. Acidic soil conditions may have contributed to an elevated proportion of virulent strains within the R. equi population. Environmental management strategies that aim to reduce the level of exposure of susceptible foals to airborne virulent R. equi are most likely to reduce the impact of R. equi pneumonia on endemically affected farms.
Keywords: Actinomycetales Infections/epidemiology/microbiology/*veterinary; Air Microbiology; Animal Husbandry; Animals; Animals, Newborn; Australia/epidemiology; Colony Count, Microbial; DNA, Bacterial/genetics; Ecosystem; Horse Diseases/epidemiology/*microbiology; Horses; Pneumonia, Bacterial/epidemiology/microbiology/*veterinary; Rhodococcus equi/genetics/isolation & purification/*pathogenicity; Soil Microbiology; Virulence
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Ishida, N., Oyunsuren, T., Mashima, S., Mukoyama, H., & Saitou, N. (1995). Mitochondrial DNA sequences of various species of the genus Equus with special reference to the phylogenetic relationship between Przewalskii's wild horse and domestic horse. J Mol Evol, 41(2), 180–188.
Abstract: The noncoding region between tRNAPro and the large conserved sequence block is the most variable region in the mammalian mitochondrial DNA D-loop region. This variable region (ca. 270 bp) of four species of Equus, including Mongolian and Japanese native domestic horses as well as Przewalskii's (or Mongolian) wild horse, were sequenced. These data were compared with our recently published Thoroughbred horse mitochondrial DNA sequences. The evolutionary rate of this region among the four species of Equus was estimated to be 2-4 x 10(-8) per site per year. Phylogenetic trees of Equus species demonstrate that Przewalskii's wild horse is within the genetic variation among the domestic horse. This suggests that the chromosome number change (probably increase) of the Przewalskii's wild horse occurred rather recently.
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Wallner, B., Brem, G., Muller, M., & Achmann, R. (2003). Fixed nucleotide differences on the Y chromosome indicate clear divergence between Equus przewalskii and Equus caballus. Anim Genet, 34(6), 453–456.
Abstract: The phylogenetic relationship between Equus przewalskii and E. caballus is often a matter of debate. Although these taxa have different chromosome numbers, they do not form monophyletic clades in a phylogenetic tree based on mtDNA sequences. Here we report sequence variation from five newly identified Y chromosome regions of the horse. Two fixed nucleotide differences on the Y chromosome clearly display Przewalski's horse and domestic horse as sister taxa. At both positions the Przewalski's horse haplotype shows the ancestral state, in common with the members of the zebra/ass lineage. We discuss the factors that may have led to the differences in mtDNA and Y-chromosomal observations.
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