ORCID Profile
0000-0002-7604-2368
Current Organisation
University of Adelaide
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Publisher: Springer Science and Business Media LLC
Date: 23-04-2013
DOI: 10.1038/NCOMMS2656
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-02-2013
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.JSBMB.2005.04.037
Abstract: The objective of this study was to determine the nature and extent of androgen influence on gene expression in the lacrimal gland. Lacrimal glands were obtained from orchiectomized mice that had been treated with testosterone or vehicle for 2 weeks, as well as from testicular feminized mice and their Tabby controls. S les were pooled according to experiment, processed for the isolation of RNA, and analyzed for differentially expressed mRNAs by using primarily CodeLink Bioarrays, GEM 1 and 2 gene chips and quantitative real-time PCR (qPCR) procedures. Gene chip data were analyzed with GeneSifter.Net software. Our results demonstrate that testosterone regulates the expression of over 2000 genes in the lacrimal gland. Gene ontologies most affected by androgen treatment included those related to cell growth, proliferation and metabolism, cell communication and transport, nucleic acid binding, signal transduction and receptor activities. Our findings also indicate that androgen action may be mediated, at least in part, through classical androgen receptors, and may contribute to the sex-related differences in gene expression of lacrimal tissue. Overall, these results support our working hypothesis that androgen action on the lacrimal gland is mediated primarily through a receptor-associated regulation of gene transcription.
Publisher: SAGE Publications
Date: 02-2005
DOI: 10.1177/154405910508400210
Abstract: Sex-related differences exist in the structure and function of the major glands in a variety of species. Moreover, many of these variations appear to be unique to each tissue. We hypothesized that this sexual dimorphism is due, at least in part, to gland-specific differences in gene expression between males and females. Glands were collected from male and female BALB/c mice (n = 5/sex/experiment), and total RNA was isolated. S les were analyzed for differentially expressed mRNAs with CodeLink microarrays, and data were evaluated by GeneSifter. Our results demonstrate that significant (P 0.05) sex-related differences exist in the expression of numerous genes in the major salivary glands, and many of these differences were tissue-specific. These findings support our hypothesis that sex-related differences in the salivary glands are due, at least in part, to tissue-specific variations in gene expression.
Publisher: Wiley
Date: 25-07-2006
DOI: 10.1111/J.1600-0722.2006.00360.X
Abstract: Androgens exert significant effects on the murine submandibular gland. Our objective in this study was to determine the nature and extent of testosterone regulation of gene expression in the female submandibular gland, and to explore the degree to which this control is the same as in male glands. Ovariectomized female BALB/c mice were treated with placebo- or testosterone-containing hormone pellets for 14 d. Glands were collected and total RNA was isolated. S les were analyzed for differential expression of mRNA using CodeLink microarrays, and the data were evaluated using genesifter. Testosterone significantly influenced the expression of over 500 genes, and while many (n = 214) of the genes were similarly differentially expressed in androgen-treated males, there were also many that were unique. These findings support our hypotheses that testosterone extensively influences gene expression in the female submandibular gland, and that the nature of this influence is variable between sexes.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2005
DOI: 10.1167/IOVS.05-0426
Abstract: In prior work, it has been found that the meibomian gland is an androgen target organ, that androgens modulate lipid production within this tissue, and that androgen deficiency is associated with glandular dysfunction and evaporative dry eye. This study's purpose was to test the hypothesis that the androgen control of the meibomian gland involves the regulation of gene expression. Meibomian glands were obtained from orchiectomized mice that were treated with placebo or testosterone for 14 days. Tissues were processed for the analysis of differentially expressed mRNAs by using gene bioarrays, gene chips, and real-time PCR procedures. Bioarray data were analyzed with GeneSifter software (VizX Labs LLC, Seattle, WA). The results show that testosterone influenced the expression of more than 1590 genes in the mouse meibomian gland. This hormone action involved a significant upregulation of 1080 genes (e.g., neuromedin B), and a significant downregulation of 518 genes (e.g., small proline-rich protein 2A). Some of the most significant androgen effects were directed toward stimulation of genes associated with lipid metabolism, sterol biosynthesis, fatty acid metabolism, protein transport, oxidoreductase activity, and peroxisomes. These findings demonstrate that testosterone regulates the expression of numerous genes in the mouse meibomian gland and that many of these genes are involved in lipid metabolic pathways.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-2016
Abstract: Native American population history is reexamined using a large data set of pre-Columbian mitochondrial genomes.
Publisher: Public Library of Science (PLoS)
Date: 04-02-2019
Publisher: American Society for Clinical Investigation
Date: 07-1995
DOI: 10.1172/JCI118067
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 27-11-2018
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.EXER.2005.11.026
Abstract: We hypothesize that androgens regulate lipogenesis in the meibomian gland. To test this hypothesis, we sought to determine whether androgens increase the mRNA levels of key lipogenic enzymes involved in the synthesis of cholesterol and fatty acids. In addition, we examined whether androgens stimulate the expression of genes for sterol regulatory element binding proteins (SREBP) 1 and 2, which are transcription factors that play an important role in the coordinate regulation of lipogenic enzymes. Meibomian glands were obtained from castrated mice, that were treated with vehicle or testosterone for 2 weeks. Tissues were processed for the analysis of selected mRNAs by real-time PCR. Our results show that testosterone increases the mRNA levels of critical lipogenic enzymes, including those related to ATP-citrate lyase, acetyl-CoA-synthase, acetyl-CoA-carboxylase, acetoacetyl-CoA-synthase and 3-hydroxy-3-methylglutaryl CoA synthase 1. Our findings also demonstrate that androgens upregulate the expression of genes encoding the transcription factors SREBPs 1 and 2. Our results indicate that androgens may control multiple aspects of lipogenesis in the meibomian gland.
Publisher: SAGE Publications
Date: 12-2005
DOI: 10.1177/154405910508401218
Abstract: Androgens have profound effects on the murine submandibular gland. Our objective was to determine the nature and extent of androgen control of gene expression in the submandibular gland, and to explore the degree to which this might account for known sex differences. Orchiectomized male BALB/c mice were treated with placebo- or testosterone-containing hormone pellets for 14 days. Glands were collected, and total RNA was isolated. S les were analyzed for differentially expressed mRNAs by CodeLink microarrays, and the data were evaluated with GeneSifter. Androgens significantly (p 0.05) influenced the expression of over 1300 genes, and many (n = 366) of the genes differentially regulated by androgen treatment were also differentially expressed in males compared with the females in our previous study. These findings support our hypotheses that testosterone extensively influences gene expression in the male submandibular gland, and that many of the sex differences are due to androgens.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-05-2019
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 25-04-2011
DOI: 10.1167/IOVS.10-6482
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2008
DOI: 10.1167/IOVS.07-1458
Abstract: The purpose of the study was to test the hypothesis that estrogen and progesterone regulate gene expression in the meibomian gland. Meibomian glands were obtained from young adult, ovariectomized mice that were administered 17beta-estradiol, progesterone, 17beta-estradiol plus progesterone, or vehicle for 14 days. Glands were pooled according to treatment, processed for the extraction of RNA, and analyzed for differentially expressed mRNAs by using mouse gene microarrays. Bioarray data were evaluated with sophisticated bioinformatics software and statistical programs. The expression of selected genes was confirmed with gene chips and quantitative real-time PCR techniques. The findings show that 17beta-estradiol, progesterone, or both hormones administered together significantly influenced the expression of numerous genes in the mouse meibomian gland. Notable were the effects of 17beta-estradiol on genes related to lipid metabolism, tyrosine kinases, immune factors, extracellular matrix components, steroidogenesis, and prolactin dynamics. Also very significant were the actions of progesterone or 17beta-estradiol plus progesterone on ribosome or localization gene ontologies, respectively. The various hormone treatments led to many analogous, opposite, or unique effects on gene expression. These findings support the study hypothesis that estrogen and progesterone modulate gene expression in the meibomian gland.
Publisher: Springer Science and Business Media LLC
Date: 18-10-2016
DOI: 10.1038/NCOMMS13158
Abstract: The two living species of bison (European and American) are among the few terrestrial megafauna to have survived the late Pleistocene extinctions. Despite the extensive bovid fossil record in Eurasia, the evolutionary history of the European bison (or wisent, Bison bonasus ) before the Holocene ( .7 thousand years ago (kya)) remains a mystery. We use complete ancient mitochondrial genomes and genome-wide nuclear DNA surveys to reveal that the wisent is the product of hybridization between the extinct steppe bison ( Bison priscus ) and ancestors of modern cattle (aurochs, Bos primigenius ) before 120 kya, and contains up to 10% aurochs genomic ancestry. Although undetected within the fossil record, ancestors of the wisent have alternated ecological dominance with steppe bison in association with major environmental shifts since at least 55 kya. Early cave artists recorded distinct morphological forms consistent with these replacement events, around the Last Glacial Maximum (LGM, ∼21–18 kya).
Publisher: Springer Science and Business Media LLC
Date: 08-03-2017
DOI: 10.1038/NATURE21416
Abstract: Aboriginal Australians represent one of the longest continuous cultural complexes known. Archaeological evidence indicates that Australia and New Guinea were initially settled approximately 50 thousand years ago (ka) however, little is known about the processes underlying the enormous linguistic and phenotypic ersity within Australia. Here we report 111 mitochondrial genomes (mitogenomes) from historical Aboriginal Australian hair s les, whose origins enable us to reconstruct Australian phylogeographic history before European settlement. Marked geographic patterns and deep splits across the major mitochondrial haplogroups imply that the settlement of Australia comprised a single, rapid migration along the east and west coasts that reached southern Australia by 49-45 ka. After continent-wide colonization, strong regional patterns developed and these have survived despite substantial climatic and cultural change during the late Pleistocene and Holocene epochs. Remarkably, we find evidence for the continuous presence of populations in discrete geographic areas dating back to around 50 ka, in agreement with the notable Aboriginal Australian cultural attachment to their country.
Publisher: BMJ
Date: 03-2006
Publisher: Bentham Science Publishers Ltd.
Date: 27-02-2009
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 2006
DOI: 10.1167/IOVS.05-1003
Abstract: The hypothesis tested in the study was that the effect of estrogen and progesterone on the lacrimal gland is mediated through specific receptors and that hormonal effects involve the regulation of gene expression and protein synthesis. Lacrimal glands were collected from young adult, ovariectomized mice, that were treated with 17beta-estradiol, progesterone, 17beta-estradiol plus progesterone or vehicle for 2 weeks. Glands were pooled according to treatment, processed for the isolation of RNA, and evaluated for differentially expressed mRNAs by using gene microarrays. Bioarray data were analyzed with sophisticated bioinformatics and statistical programs. The expression of selected genes was verified by using gene chips and quantitative real-time PCR methods. The results demonstrate that 17beta-estradiol, progesterone, or both hormones together significantly influences the expression of hundreds of genes in the mouse lacrimal gland. Sex steroid treatment led to numerous alterations in gene activities related to transcriptional control, cell growth and/or maintenance, cell communication, signal transduction, enzyme catalysis, immune expression, and the binding and metabolism of nucleic acids and proteins. A number of the 17beta-estradiol, progesterone or 17beta-estradiol plus progesterone effects on gene expression were similar, but most were unique to each treatment. Of particular interest was the finding that these hormones seem to contribute little to the known sex-related differences in gene expression of the lacrimal gland. These results support the hypothesis that estrogen's and progesterone's action on the lacrimal gland involves the regulation of numerous genes. However, these hormone effects do not appear to represent a major factor underlying the sexual dimorphism of gene expression in lacrimal tissue.
Publisher: Wiley
Date: 06-2002
DOI: 10.1111/J.1749-6632.2002.TB04217.X
Abstract: We have recently discovered that women with primary and secondary Sjögren's syndrome are androgen-deficient. We hypothesize that this hormone insufficiency contributes to the meibomian gland dysfunction, tear film instability, and evaporative dry eye that are characteristic of this autoimmune disorder. If our hypothesis is correct, we predict: (1) that androgens regulate meibomian gland function, control the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer and (2) that androgen deficiency, due to an attenuation in androgen synthesis (e.g., during Sjögren's syndrome, menopause, aging, complete androgen-insensitivity syndrome [CAIS] and anti-androgen use), will lead to meibomian gland dysfunction and evaporative dry eye. The following studies were designed to test these predictions. Experimental procedures included clinical studies, animal models, and histological, biochemical, molecular biological, and biomedical engineering techniques. Our results demonstrate that: (1) androgens regulate the meibomian gland. This tissue contains androgen receptor mRNA, androgen receptor protein within acinar epithelial cell nuclei, and Types 1 and 2 5alpha-reductase mRNAs. Moreover, androgens appear to modulate lipid production and gene expression in mouse and/or rabbit meibomian glands and (2) androgen deficiency may lead to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, tear film instability, and evaporative dry eye. Thus, we have found that anti-androgen therapy in men is associated with meibomian gland disease, a decreased tear film breakup time, and functional dry eye. Furthermore, we have discovered that androgen receptor dysfunction in women with CAIS is associated with meibomian gland changes and a significant increase in the signs and symptoms of dry eye. Of interest, we have also found that androgen deficiency is associated with significant and striking alterations in the neutral and polar lipid patterns of human meibomian gland secretions. Our findings show that the meibomian gland is an androgen target organ and that androgen deficiency may promote meibomian gland dysfunction and evaporative dry eye. Overall, these results support our hypothesis that androgen deficiency may be an important etiologic factor in the pathogenesis of evaporative dry eye in women with Sjögren's syndrome.
Publisher: Springer Science and Business Media LLC
Date: 18-06-2018
Publisher: Elsevier BV
Date: 10-2014
Publisher: American Medical Association (AMA)
Date: 06-2013
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Stephen M Richards.