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Finch M.L.,University of Western Australia | Marquardt J.U.,Johannes Gutenberg University Mainz | Yeoh G.C.,University of Western Australia | Yeoh G.C.,Harry Perkins Institute of Medical Research | Callus B.A.,University of Western Australia
International Journal of Biochemistry and Cell Biology | Year: 2014

Since their discovery more than a decade ago microRNAs have been demonstrated to have profound effects on almost every aspect of biology. Numerous studies in recent years have shown that microRNAs have important roles in development and in the etiology and progression of disease. This review is focused on microRNAs and the roles they play in liver development, regeneration and liver disease; particularly chronic liver diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, viral hepatitis and primary liver cancer. The key microRNAs identified in liver development and chronic liver disease will be discussed together with, where possible, the target messenger RNAs that these microRNAs regulate to profoundly alter these processes. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution. © 2014 Elsevier Ltd. All rights reserved. Source

Li Kwok Cheong J.D.,University of Western Australia | Croft K.D.,University of Western Australia | Henry P.D.,University of Western Australia | Matthews V.,Harry Perkins Institute of Medical Research | And 2 more authors.
Archives of Biochemistry and Biophysics | Year: 2014

We have investigated the effects of the major polyphenol in coffee, chlorogenic acid (CGA), on obesity, glucose intolerance, insulin resistance, systemic oxidative stress and endothelial dysfunction in a mouse model of the metabolic syndrome. Thirty C57BL6 mice were randomly divided into (n = 10/group) (i) normal diet (ND), (ii) high fat diet (HFD), or (iii) high fat diet supplemented with 0.5% w/w green coffee bean extract (GCE) rich in chlorogenic acid (HFD + GCE). The high fat diet consisted of 28% fat and all animals were maintained on their diets for 12 weeks. The mice fed a HFD and HFD + GCE displayed symptoms of the metabolic syndrome compared to their normal fed counterparts, although no endothelial dysfunction was detected in the abdominal aortas after 12 weeks. GCE did not attenuate HFD-induced obesity, glucose intolerance, insulin resistance or systemic oxidative stress. Furthermore, GCE did not protect against ex vivo oxidant (hypochlorous acid)-induced endothelial dysfunction. © 2014 Elsevier Inc. All rights reserved. Source

Grimmer M.R.,University of Southern California | Grimmer M.R.,University of California at Davis | Stolzenburg S.,University of North Carolina at Chapel Hill | Stolzenburg S.,University of Western Australia | And 6 more authors.
Nucleic Acids Research | Year: 2014

Artificial transcription factors (ATFs) and genomic nucleases based on a DNA binding platform consisting of multiple zinc finger domains are currently being developed for clinical applications. However, no genome-wide investigations into their binding specificity have been performed. We have created sixfinger ATFs to target two different 18 nt regions of the human SOX2 promoter; each ATF is constructed such that it contains or lacks a super KRAB domain (SKD) that interacts with a complex containing repressive histone methyltransferases. ChIP-seq analysis of the effector-free ATFs in MCF7 breast cancer cells identified thousands of binding sites, mostly in promoter regions; the addition of an SKD domain increased the number of binding sites ∼5-fold, with a majority of the new sites located outside of promoters. De novo motif analyses suggest that the lack of binding specificity is due to subsets of the finger domains being used for genomic interactions. Although the ATFs display widespread binding, few genes showed expression differences; genes repressed by the ATF-SKD have stronger binding sites and are more enriched for a 12 nt motif. Interestingly, epigenetic analyses indicate that the transcriptional repression caused by the ATF-SKD is not due to changes in active histone modifications. © The Author(s) 2014. Source

Mullins R.J.,John James Medical Center | Brown S.G.A.,University of Western Australia | Brown S.G.A.,Harry Perkins Institute of Medical Research
Medical Journal of Australia | Year: 2014

Jack jumper ant (JJA) venom allergy is an important cause of anaphylaxis in south-eastern Australia. The efficacy and real-world effectiveness of JJA venom immunotherapy (VIT) to prevent anaphylaxis in allergic patients are now well established, with an evidence base that is at least equivalent to that supporting VIT for allergy to other insect species. The tolerability and safety of JJA VIT are comparable with those of honeybee VIT. Source

Knott G.J.,University of Western Australia | Bond C.S.,University of Western Australia | Fox A.H.,University of Western Australia | Fox A.H.,Harry Perkins Institute of Medical Research
Nucleic Acids Research | Year: 2016

Nuclear proteins are often given a concise title that captures their function, such as 'transcription factor,' 'polymerase' or 'nuclear-receptor.' However, for members of the Drosophila behavior/human splicing (DBHS) protein family, no such clean-cut title exists. DBHS proteins are frequently identified engaging in almost every step of gene regulation, including but not limited to, transcriptional regulation, RNA processing and transport, and DNA repair. Herein, we present a coherent picture of DBHS proteins, integrating recent structural insights on dimerization, nucleic acid binding modalities and oligomerization propensity with biological function. The emerging paradigm describes a family of dynamic proteins mediating a wide range of protein-protein and protein-nucleic acid interactions, on the whole acting as a multipurpose molecular scaffold. Overall, significant steps toward appreciating the role of DBHS proteins have been made, but we are only beginning to understand the complexity and broader importance of this family in cellular biology. © 2016 The Author(s). Source

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