Veterinary Science Collected Works - Research Publications

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    Virus demyelination
    Fazakerley, JK ; Walker, R (SPRINGER, 2003-04)
    A number of viruses can initiate central nervous system (CNS) diseases that include demyelination as a major feature of neuropathology. In humans, the most prominent demyelinating diseases are progressive multifocal leukoencephalopathy, caused by JC papovirus destruction of oligodendrocytes, and subacute sclerosing panencephalitis, an invariably fatal childhood disease caused by persistent measles virus. The most common neurological disease of young adults in the developed world, multiple sclerosis, is also characterized by lesions of inflammatory demyelination; however, the etiology of this disease remains an enigma. A viral etiology is possible, because most demyelinating diseases of known etiology in both man and animals are viral. Understanding of the pathogenesis of virus-induced demyelination derives for the most part from the study of animal models. Studies with neurotropic strains of mouse hepatitis virus, Theiler's virus, and Semliki Forest virus have been at the forefront of this research. These models demonstrate how viruses enter the brain, spread, persist, and interact with immune responses. Common features are an ability to infect and persist in glial cells, generation of predominantly CD8(+) responses, which control and clear the early phase of virus replication but which fail to eradicate the infection, and lesions of inflammatory demyelination. In most cases demyelination is to a limited extent the result of direct virus destruction of oligodendrocytes, but for the most part is the consequence of immune and inflammatory responses. These models illustrate the roles of age and genetic susceptibility and establish the concept that persistent CNS infection can lead to the generation of CNS autoimmune responses.
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    A bioreactor model of mouse tumor progression
    Thouas, GA ; Sheridan, J ; Hourigan, K (HINDAWI PUBLISHING CORPORATION, 2007)
    The present study represents an investigation of a novel stirred bioreactor for culture of a transformed cell line under defined hydrodynamic conditions in vitro. Cell colonies of the EL-4 mouse lymphoma cell line grown for the first time in a rotating disc bioreactor (RDB), were observed to undergo changes in phenotype in comparison to standard, static flask cultures. RDB cultures, with or without agitation, promoted the formation of adherent EL-4 cell plaques that merged to form contiguous tumor-like masses in longer-term cultures, unlike the unattached spheroid aggregates of flask cultures. Plaques grown under agitated conditions were further altered in morphology and distribution in direct response to fluid mechanical stimuli. Plaque colonies growth in RDBs with or without agitation also exhibited significant increases in production of interleukin-4 (IL-4) and lactate, suggesting an inducible "Warburg effect." Increases in cell biomass in RDB cultures were no different to flask cultures, though a trend toward a marginal increase was observed at specific rotational speeds. The RDB may therefore be a suitable alternative method to study mechanisms of tumor progression and invasiveness in vitro, under more complex physicochemical conditions that may approximate natural tissue environments.
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    A presentation of the differences between the sheep and goat genetic maps
    Maddox, JF (E D P SCIENCES, 2005)
    The current autosomal version (4.2) of the sheep genetic map comprises 1175 loci and spans approximately 3540 cM. This corresponds to almost complete coverage of the sheep genome. Each chromosome is represented by a single linkage group, with the largest gap between adjacent loci being 19.8 cM. In contrast the 1998 goat genetic map (the most recently published) is much less well developed spanning 2737 cM and comprising only 307 loci. Only one of the goat chromosomes appears to have complete coverage (chromosome 27), and 16 of the chromosomes are comprised of two or more linkage groups, or a linkage group and one or more unlinked markers. The two maps share 218 loci, and the maps have been aligned using the shared loci as reference points. Overall there is good agreement between the maps in terms of homologous loci mapping to equivalent chromosomes in the two species, with only four markers mapping to non-equivalent chromosomes. However, there are lots of inversions in locus order between the sheep and goat chromosomes. Whilst some of these differences in locus order may be genuine, the majority are likely to be a consequence of the paucity of genetic information for the goat map.
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    Insertion of EGFP into the replicase gene of Semliki Forest virus results in a novel, genetically stable marker virus
    Tamberg, N ; Lulla, V ; Fragkoudis, R ; Lulla, A ; Fazakerley, JK ; Merits, A (SOC GENERAL MICROBIOLOGY, 2007-04)
    Alphavirus-based vector and replicon systems have been extensively used experimentally and are likely to be used in human and animal medicine. Whilst marker genes can be inserted easily under the control of a duplicated subgenomic promoter, these constructs are often genetically unstable. Here, a novel alphavirus construct is described in which an enhanced green fluorescent protein (EGFP) marker gene is inserted into the virus replicase open reading frame between nsP3 and nsP4, flanked by nsP2 protease-recognition sites. This construct has correct processing of the replicase polyprotein, produces viable virus and expresses detectable EGFP fluorescence upon infection of cultured cells and cells of the mouse brain. In comparison to parental virus, the marker virus has an approximately 1 h delay in virus RNA and infectious virus production. Passage of the marker virus in vitro and in vivo demonstrates good genetic stability. Insertion of different markers into this novel construct has potential for various applications.
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    Using comparative genomics to reorder the human genome sequence into a virtual sheep genome
    Dalrymple, BP ; Kirkness, EF ; Nefedov, M ; McWilliam, S ; Ratnakumar, A ; Barris, W ; Zhao, S ; Shetty, J ; Maddox, JF ; O'Grady, M ; Nicholas, F ; Crawford, AM ; Smith, T ; de Jong, PJ ; McEwan, J ; Oddy, VH ; Cockett, NE (BMC, 2007)
    BACKGROUND: Is it possible to construct an accurate and detailed subgene-level map of a genome using bacterial artificial chromosome (BAC) end sequences, a sparse marker map, and the sequences of other genomes? RESULTS: A sheep BAC library, CHORI-243, was constructed and the BAC end sequences were determined and mapped with high sensitivity and low specificity onto the frameworks of the human, dog, and cow genomes. To maximize genome coverage, the coordinates of all BAC end sequence hits to the cow and dog genomes were also converted to the equivalent human genome coordinates. The 84,624 sheep BACs (about 5.4-fold genome coverage) with paired ends in the correct orientation (tail-to-tail) and spacing, combined with information from sheep BAC comparative genome contigs (CGCs) built separately on the dog and cow genomes, were used to construct 1,172 sheep BAC-CGCs, covering 91.2% of the human genome. Clustered non-tail-to-tail and outsize BACs located close to the ends of many BAC-CGCs linked BAC-CGCs covering about 70% of the genome to at least one other BAC-CGC on the same chromosome. Using the BAC-CGCs, the intrachromosomal and interchromosomal BAC-CGC linkage information, human/cow and vertebrate synteny, and the sheep marker map, a virtual sheep genome was constructed. To identify BACs potentially located in gaps between BAC-CGCs, an additional set of 55,668 sheep BACs were positioned on the sheep genome with lower confidence. A coordinate conversion process allowed us to transfer human genes and other genome features to the virtual sheep genome to display on a sheep genome browser. CONCLUSION: We demonstrate that limited sequencing of BACs combined with positioning on a well assembled genome and integrating locations from other less well assembled genomes can yield extensive, detailed subgene-level maps of mammalian genomes, for which genomic resources are currently limited.
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    The Future of Small-holder Dairying
    Falvey, J (Asian-Australasian Association of Animal Production Societies, 2000)
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    The Role of Smallholders in Thai Agricultural Development
    Falvey, J (Kasetsart University Research and Development Institute (KURDI), 2000)
    The role of smallholders in underpinning the Thai economy through exported and domestic product and supporting their 70 percent of the population without government welfare is emphasised in a review of the needs for smallholder development. Economic development models are discussed in a context of agriculture fuelling economic growth with a revision of assumptions that family farms can be viewed as a phase toward large-scale commercial agriculture. Intensive smallholder agriculture permits production of high quality produce, efficient use of by- and waste products in integrated systems, and maintenance of cultural values. The review concludes that specific attention to smallholders is a primary responsibility of government and requires policies based on alternative agriculture, self-sufficiency and social welfare as distinct from the commercial policies of agribusiness.
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    Early origins of agriculture in Thailand
    FALVEY, JL (Asian Agri-History Foundation, 2001)
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    The Tai and Thai Agriculture
    Falvey, J (Asian Agri-History Foundation, 2001)
    Beginning as lowland wet rice growers in China more than a millennium ago, the Tai brought in their southward migration, glutinous rice associated with their muang fai irrigation technology, which with refinement proved sustainable into the 20th century. Integrating with the existing Mon-Khmer system, the Tai widened their agricultural capabilities and administrative system to utilize water from larger northern Thai rivers. They evolved a complex blend of animism and Buddhism, which incorporated traditional ceremonies relating to rice and agriculture from their own, and the cultures blending to form the Thai. Despite modern searches for Tai historical environmental values, modification of the natural environment seems to have been more important than its preservation, although retention of holy wood lots and spirit worship may indicate a level of interest in forests above that of other agricultural communities. This is the second of four papers dealing with the history of Thai agriculture.
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    Beginnings of Thai agricultural expansion from 1200AD
    FALVEY, JL (Asian Agri-History Foundation, 2001)