26 resultados para Equine Laminitis MMP Hyperinsulinaemia Horse ADAMTS

em Deakin Research Online - Australia


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This historical sociological analysis of the training of horses for competition in early modernity draws from the sociology of the body to suggest that animals as we know them are constructed through human social processes. Contemporary horse-care publications are used to demonstrate how equine bodies were shaped through an application of humoral physiological theory. That is, they were made suitable for the human requirements of the time through preparatory procedures informed by models of somatic functioning used widely to understand humans and animals alike. The broader issue canvassed here is that ‘embodiment’ should include animal as well as human bodies. Through selective breeding, raising and care, animals have bodies that are shaped to human requirements – they embody human social processes.

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In August 2007 Australia experienced its first outbreak of equine influenza. The disease occurred first in a quarantine station for imported horses near Sydney and subsequently escaped into the general horse population. After an extensive campaign the disease was eradicated and Australia is again recognised as free of this disease. Equine influenza was then, and is now, recognised to be the major disease risk associated with live horse imports into Australia and measures designed to mitigate this risk formed the basis of the quarantine protocols then in place. Subsequent investigations into the cause of the outbreak identified failures in compliance with these quarantine requirements as a contributing factor. It is also likely that the immunity of horses vaccinated as part of the import protocol was less than optimal, and that this had a significant role to play in the escape of the disease from quarantine.

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Webcasting in Australia is currently the domain of national broadcasters, independent and community radio stations and the two leading football codes. This paper reports on the findings of a content analysis of 20 leading webcasters as to the content and genres they provide. In examining the factors affecting the 'slow' adoption of webcasting in Australia such as the absence ofa high speed broadband infrastructure, the paper analyses and how its various discourses were framed by the parties concerned, and how the clash of conflicting agendas shaped the negotiations between the main stakeholders, taking on the characteristics of a 'horse trade '. Thereafter, the paper critically examines how other technologies such as mobile phones and Pay TV has begun to take on webcasting, instead of waitingfor the major commercial broadcasters to do so or a new broadband network and a national broadband strategy to be implemented.

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The matrix metalloproteases (MMPs) and the ADAMs (A Disintegrin And Metalloprotease domain) are proteolytic enzyme families containing a catalytic zinc ion, that are implicated in a variety of normal and pathological processes involving tissue remodeling and cancer. Synthetic MMP inhibitors have been designed for applications in pathological situations. However, a greater understanding of substrate binding and the catalytic mechanism is required so that more effective and selective inhibitors may be developed for both experimental and clinical purposes. By modeling a natural substrate spanning P4-P4‘ in complex with the catalytic domains, we aim to compare substrate-specificities between Stromelysin-1 (MMP-3), ADAM-9 and ADAM–10, with the aid of molecular dynamics simulations. Our results show that the substrate retains a favourable antiparallel beta-sheet conformation on the P-side in addition to the well-known orientation of the P'-region of the scissile bond, and that the primary substrate selectivity is dominated by the sidechains in the S1' pocket and the S2/S3 region. ADAM-9 has a hydrophobic residue as the central determinant in the S1' pocket, while ADAM-10 has an amphiphilic residue, which suggests a different primary specificity. The S2/S3 pocket is largely hydrophobic in all three enzymes. Inspired by our molecular dynamics calculations and supported by a large body of literature, we propose a novel, hypothetical, catalytic mechanism where the Zn-ion polarizes the oxygens from the catalytic glutamate to form a nucleophile, leading to a tetrahedral oxyanion anhydride transition state.

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Muscle invasive transitional cell carcinoma (TCC) of the bladder is associated with a high frequency of metastasis, resulting in poor prognosis for patients presenting with this disease. Models that capture and demonstrate step-wise enhancement of elements of the human metastatic cascade on a similar genetic background are useful research tools. We have utilized the transitional cell carcinoma cell line TSU-Pr1 to develop an in vivo experimental model of bladder TCC metastasis. TSU-Pr1 cells were inoculated into the left cardiac ventricle of SCID mice and the development of bone metastases was monitored using high resolution X-ray. Tumor tissue from a single bone lesion was excised and cultured in vitro to generate the TSU-Pr1-B1 subline. This cycle was repeated with the TSU-Pr1-B1 cells to generate the successive subline TSU-Pr1-B2. DNA profiling and karyotype analysis confirmed the genetic relationship of these three cell lines. In vitro, the growth rate of these cell lines was not significantly different. However, following intracardiac inoculation TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2 exhibited increasing metastatic potential with a concomitant decrease in time to the onset of radiologically detectable metastatic bone lesions. Significant elevations in the levels of mRNA expression of the matrix metalloproteases (MMPs) membrane type 1-MMP (MT1-MMP), MT2-MMP and MMP-9, and their inhibitor, tissue inhibitor of metalloprotease-2 (TIMP-2), across the progressively metastatic cell lines, were detected by quantitative PCR. Given the role of MT1-MMP and TIMP-2 in MMP-2 activation, and the upregulation of MMP-9, these data suggest an important role for matrix remodeling, particularly basement membrane, in this progression. The TSU-Pr1-B1/B2 model holds promise for further identification of important molecules.