Institution
University of Western Australia
Education•Perth, Western Australia, Australia•
About: University of Western Australia is a education organization based out in Perth, Western Australia, Australia. It is known for research contribution in the topics: Population & Poison control. The organization has 29613 authors who have published 87405 publications receiving 3064466 citations. The organization is also known as: UWA & University of WA.
Topics: Population, Poison control, Galaxy, Context (language use), Medicine
Papers published on a yearly basis
Papers
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TL;DR: The rationale for the design and use of gold compounds that have specific and selective targets in cells to alleviate the symptoms of a range of human diseases is discussed and discoveries to show that gold compounds can be developed to become versatile and powerful drugs for diseases caused by dysfunction of selenol and thiol containing proteins are summarised.
Abstract: The application of gold in medicine is traceable for several thousand years and Au(I) compounds have been used clinically to treat rheumatoid arthritis since the last century. Recently research into gold-based drugs for a range of human diseases has seen a renaissance. Old as well as new Au(I) and Au(III) compounds have been used and designed with an aim of targeting cellular components that are implicated in the onset or progression of cancers, rheumatoid arthiritis, viral and parasitic diseases. In addition, new disease targets have been found for gold compounds that have given insight into the mechanism of action of these compounds, as well as in the molecular pathophysiology of human diseases. Here we discuss the rationale for the design and use of gold compounds that have specific and selective targets in cells to alleviate the symptoms of a range of human diseases. We summarise the most recent findings in this research and our own discoveries to show that gold compounds can be developed to become versatile and powerful drugs for diseases caused by dysfunction of selenol and thiol containing proteins.
390 citations
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Swiss Institute of Bioinformatics1, University of Copenhagen2, University of Bern3, Griffith University4, Pompeu Fabra University5, Instituto Gulbenkian de Ciência6, Wellcome Trust Sanger Institute7, Aarhus University8, University of California, Berkeley9, Max Planck Society10, Technical University of Denmark11, University of Cambridge12, King Abdullah University of Science and Technology13, ETH Zurich14, Monash University Malaysia Campus15, Centre national de la recherche scientifique16, University of Porto17, University College London18, Papua New Guinea Institute of Medical Research19, University of Papua New Guinea20, University of Otago21, Wellcome Trust Centre for Human Genetics22, Estonian Biocentre23, University of Oxford24, University of Western Australia25, Yale University26, University of California, San Francisco27
TL;DR: A population expansion in northeast Australia during the Holocene epoch associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama–Nyungan languages is inferred.
Abstract: The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama–Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25–40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated ~10–32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama–Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51–72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.
389 citations
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University of Western Australia1, Murdoch University2, Harvard University3, University of Mainz4, University of Helsinki5, Royal Perth Hospital6, Humboldt University of Berlin7, University of Sydney8, University of Würzburg9, Hammersmith Hospital10, Boston Children's Hospital11, University of South Florida12
TL;DR: Mutations in the human skeletal muscle α-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess of thin myofilaments' (actin myopathy) and nemaline myopathy, characterized by structural abnormalities of the muscle fibres and variable degrees of muscle weakness.
Abstract: Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess of thin myofilaments' (actin myopathy) and nemaline myopathy. Both diseases are characterized by structural abnormalities of the muscle fibres and variable degrees of muscle weakness. We have identified 15 different missense mutations resulting in 14 different amino acid changes. The missense mutations in ACTA1 are distributed throughout all six coding exons, and some involve known functional domains of actin. Approximately half of the patients died within their first year, but two female patients have survived into their thirties and have children. We identified dominant mutations in all but 1 of 14 families, with the missense mutations being single and heterozygous. The only family showing dominant inheritance comprised a 33-year-old affected mother and her two affected and two unaffected children. In another family, the clinically unaffected father is a somatic mosaic for the mutation seen in both of his affected children. We identified recessive mutations in one family in which the two affected siblings had heterozygous mutations in two different exons, one paternally and the other maternally inherited. We also identified de novo mutations in seven sporadic probands for which it was possible to analyse parental DNA.
389 citations
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TL;DR: Results identify tryptophan metabolism by Ido as a new pathway contributing to the regulation of vascular tone and the control of blood pressure in spontaneously hypertensive rats.
Abstract: Control of blood vessel tone is central to vascular homeostasis. Here we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (Ido) expressed in endothelial cells contributes to arterial vessel relaxation and the control of blood pressure. Infection of mice with malarial parasites (Plasmodium berghei) or induction of endotoxemia in mice led to endothelial expression of Ido, decreased plasma tryptophan concentration, increased kynurenine concentration and hypotension. Pharmacological inhibition of Ido increased blood pressure in systemically inflamed mice but not in mice deficient in Ido or interferon-gamma, which is required for Ido induction. Both tryptophan and kynurenine dilated preconstricted porcine coronary arteries; the dilating effect of tryptophan required the presence of active Ido and an intact endothelium, whereas the effect of kynurenine was endothelium independent. The arterial relaxation induced by kynurenine was mediated by activation of the adenylate and soluble guanylate cyclase pathways. Kynurenine administration decreased blood pressure in a dose-dependent manner in spontaneously hypertensive rats. Our results identify tryptophan metabolism by Ido as a new pathway contributing to the regulation of vascular tone.
389 citations
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TL;DR: The genetic basis of ALS is reviewed, highlighting factors that have contributed to the elusiveness of genetic heritability and future directions for research that may lead to effective treatment strategies outlined.
Abstract: The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with the disease risk and pathogenesis, and the cellular processes involved, continues to grow. Despite decades of intense research and over 50 potentially causative or disease-modifying genes identified, etiology remains unexplained and treatment options remain limited for the majority of ALS patients. Various factors have contributed to the slow progress in understanding and developing therapeutics for this disease. Here, we review the genetic basis of ALS, highlighting factors that have contributed to the elusiveness of genetic heritability. The most commonly mutated ALS-linked genes are reviewed with an emphasis on disease-causing mechanisms. The cellular processes involved in ALS pathogenesis are discussed, with evidence implicating their involvement in ALS summarized. Past and present therapeutic strategies and the benefits and limitations of the model systems available to ALS researchers are discussed with future directions for research that may lead to effective treatment strategies outlined.
389 citations
Authors
Showing all 29972 results
Name | H-index | Papers | Citations |
---|---|---|---|
Nicholas G. Martin | 192 | 1770 | 161952 |
Cornelia M. van Duijn | 183 | 1030 | 146009 |
Kay-Tee Khaw | 174 | 1389 | 138782 |
Steven N. Blair | 165 | 879 | 132929 |
David W. Bates | 159 | 1239 | 116698 |
Mark E. Cooper | 158 | 1463 | 124887 |
David Cameron | 154 | 1586 | 126067 |
Stephen T. Holgate | 142 | 870 | 82345 |
Jeremy K. Nicholson | 141 | 773 | 80275 |
Xin Chen | 139 | 1008 | 113088 |
Graeme J. Hankey | 137 | 844 | 143373 |
David Stuart | 136 | 1665 | 103759 |
Joachim Heinrich | 136 | 1309 | 76887 |
Carlos M. Duarte | 132 | 1173 | 86672 |
David Smith | 129 | 2184 | 100917 |