2,147 research outputs found
A pro-tumourigenic loop at the human prostate tumour interface orchestrated by oestrogen, CXCL12 and mast cell recruitment
No full textArticle first published online: 9 JUL 2014Abstract not availableStuart J Ellem, Renea A Taylor, Luc Furic, Ola Larsson, Mark Frydenberg, David Pook, John Pedersen, Bree Cawsey, Andrew Trotta, Eleanor Need, Grant Buchanan and Gail P Risbridge
Origin of the eastern brownsnake, Pseudonaja textilis (Duméril, Bibron and Duméril) (Serpentes: Elapidae: Hydrophiinae) in New Guinea: evidence of multiple dispersals from Australia, and comments on the status of Pseudonaja textilis pughi Hoser 2003
No full textWilliams, David J., O'Shea, Mark, Daguerre, Roland L., Pook, Catharine E., Wüster, Wolfgang, Hayden, Christopher J., Mcvay, John D., Paiva, Owen, Matainaho, Teatu- Lohi, Winkel, Kenneth D., Austin, Christopher C. (2008): Origin of the eastern brownsnake, Pseudonaja textilis (Duméril, Bibron and Duméril) (Serpentes: Elapidae: Hydrophiinae) in New Guinea: evidence of multiple dispersals from Australia, and comments on the status of Pseudonaja textilis pughi Hoser 2003. Zootaxa 1703 (1): 47-61, DOI: 10.11646/zootaxa.1703.1.3, URL: https://biotaxa.org/Zootaxa/article/view/zootaxa.1703.1.
The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases
No full textCopyright © 2014 Al-Mahdawi, Anjomani Virmouni and Pook. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.This article has been made available through the Brunel Open Access Publishing Fund.DNA methylation primarily occurs within human cells as a 5-methylcytosine (5mC) modification of the cytosine bases in CpG dinucleotides. 5mC has proven to be an important epigenetic mark that is involved in the control of gene transcription for processes such as development and differentiation. However, recent studies have identified an alternative modification, 5-hydroxymethylcytosine (5hmC), which is formed by oxidation of 5mC by ten-eleven translocation (TET) enzymes. The overall levels of 5hmC in the mammalian genome are approximately 10% of 5mC levels, although higher levels have been detected in tissues of the central nervous system (CNS). The functions of 5hmC are not yet fully known, but evidence suggests that 5hmC may be both an intermediate product during the removal of 5mC by passive or active demethylation processes and also an epigenetic modification in its own right, regulating chromatin or transcriptional factors involved in processes such as neurodevelopment or environmental stress response. This review highlights our current understanding of the role that 5hmC plays in neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), fragile X-associated tremor/ataxia syndrome (FXTAS), Friedreich ataxia (FRDA), Huntington's disease (HD), and Parkinson's disease (PD).Sara Anjomani Virmouni was supported by funding to Mark A. Pook from the Friedreich’s Ataxia Research Alliance(FARA)
Improving Imputation Quality in BEAGLE for Crop and Livestock Data
No full textImputation is one of the key steps in the preprocessing and quality control protocol of any genetic study. Most imputation algorithms were originally developed for the use in human genetics and thus are optimized for a high level of genetic diversity. Different versions of BEAGLE were evaluated on genetic datasets of doubled haploids of two European maize landraces, a commercial breeding line and a diversity panel in chicken, respectively, with different levels of genetic diversity and structure which can be taken into account in BEAGLE by parameter tuning. Especially for phasing BEAGLE 5.0 outperformed the newest version (5.1) which in turn also lead to improved imputation. Earlier versions were far more dependent on the adaption of parameters in all our tests. For all versions, the parameter ne (effective population size) had a major effect on the error rate for imputation of ungenotyped markers, reducing error rates by up to 98.5%. Further improvement was obtained by tuning of the parameters affecting the structure of the haplotype cluster that is used to initialize the underlying Hidden Markov Model of BEAGLE. The number of markers with extremely high error rates for the maize datasets were more than halved by the use of a flint reference genome (F7, PE0075 etc.) instead of the commonly used B73. On average, error rates for imputation of ungenotyped markers were reduced by 8.5% by excluding genetically distant individuals from the reference panel for the chicken diversity panel. To optimize imputation accuracy one has to find a balance between representing as much of the genetic diversity as possible while avoiding the introduction of noise by including genetically distant individuals
Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich Ataxia
No full textCopyright © 2014 Anjomani Virmouni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats), YG8R (90 and 190 GAA repeats) and YG22R (190 GAA repeats).
Methodology/Principal Findings - We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH) analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R.
Conclusions/Significance - Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.European Union, Ataxia UK and FARA
Supplementary Material for Pook et al., 2019
No full textTable S1 UM imputation error for the commercial breeding line in chicken by changing a single imputing parameter with ne = 100 for BEAGLE 5.1, ne = 300 for BEAGLE 5.0 and ne = 10,000 for BEAGLE 4.1. * BEAGLE crashed for this dataset when using phase-segment > 10, phase-states 5.Table S2 UM imputation error for the diversity panel in chicken by changing a single imputing parameter with ne = 300 for BEAGLE 5.1, ne = 3,000 for BEAGLE 5.0 and ne = 10,000 for BEAGLE 4.1. * BEAGLE crashed for this dataset when using phase-segment > 10 or phasestates Table S3 Phasing error, as number of heterozygous markers per switch error, for Pseudo S0 generated based on the KE DH-lines by changing a single imputing parameter.Table S4 Inference error rates using different reference genomes compared to B73 for PE DH-lines. Only markers mapped on both the flint reference genome & B73v4 (Jiao et al. 2017) are considered for "critical" markers (error rate > 10%).Table S5 List of "critical" markers for Kemater Landmais Gelb using different reference genomes.Table S6 List of "critical" markers for Petkuser Ferdinand Rot using different reference genomes.Table S7 Error rates for UM imputation for different reference panels, including A (same subpopulation), C (all other subpopulation), D (below average Nei distant subpopulations), E (All subpopulation with reduced error rate when testing A + B compared to A as the reference panel).Table S8 Assignments to subpopulations for the chicken diversity panel based on Nei standard genetic distances (Nei 1972).Table S9 Minimal obtained error rates and used parameter settings for inference and UM imputation. Deviations from the ideal single parameter settings are caused by BEAGLE crashing when changing parameters jointly.Figure S1 Neighbor-joining-tree for ten subpopulations in the chicken diversity panel. For a detailed list on which individual is assigned to which subpopulation we refer to Supplementary Table S8.Figure S2 Relationship between region error rate and LD (r2) on chromosome 9 in the maize data. Outliers are corrected for by using a Nadaraya-Watson-estimator (Nadaraya 1964), using a Gaussian kernel and a bandwidth of 3,000 markers in both cases.Figure S3 Total number of errors per marker (50 repetitions) for BEAGLE 4.0 using buildwindow of 10 and 1200 (default) in the maize data.Figure S4 DR2 values in relation to the obtained number of error per marker after fitting of ne (A) and on default (B) in BEAGLE 5.0 for the commercial chicken line. 100 / 788 lines were used for study / reference sample.Figure S5 DR2 values in relation to the obtained number of error per marker after fitting of ne (A) and on default (B) in BEAGLE 5.0 for the chicken diversity panel. 100 / 1710 lines were used for study / reference sample.Figure S6 – Figure S24 Effect of the different parameter on the inference error rates for the maize data in BEAGLE. Default settings are indicated by the vertical line.Figure S25 – Figure S45 Effect of the different parameter on the inference and phasing error rates for chromosome 10 of 250 Pseudo S0 generated based on the maize data in BEAGLE. Default settings are indicated by the vertical line.Figure S46 – Figure S74 Effect of the different parameter on the UM imputation error rate for the maize data, the commercial chicken line and the chicken diversity panel in BEAGLE. Default settings are indicated by the vertical line.</div
Overall survival of men with metachronous metastatic hormone-sensitive prostate cancer treated with enzalutamide and androgen deprivation therapy
No full textAbstract not available.Christopher J. Sweeney, Andrew J. Martin, Martin R. Stockler, Stephen Begbie, Kim N. Chi, Simon Chowdhury, Xanthi Coskinas, Mark Frydenberg, Wendy E. Hague, Lisa G. Horvath, Anthony M. Joshua, Nicola J. Lawrence, Gavin M. Marx, John McCaffrey, Ray McDermott, Margaret McJannett, Scott A. North, Francis Parnis, Wendy Parulekar, David W. Pook, M. Neil Reaume, Shahneen K. Sandhu, Alvin Tan, Thean Hsiang Tan, Alastair Thomson, Emily Tu, Francisco Vera-Badillo, Scott G. Williams, Sonia Yip, Alison Y. Zhang, Robert R. Zielinski, Ian D. Davis, for the ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Supplementary material 1 from: Pook V, Sharkey M, Wahl D (2016) Key to the species of Megarhyssa (Hymenoptera, Ichneumonidae, Rhyssinae) in America, north of Mexico. Deutsche Entomologische Zeitschrift 63(1): 137-148. https://doi.org/10.3897/dez.63.7619
No full textDelta Editor Character Matrix
Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich's ataxia
No full text© The Author 2014. Published by Oxford University Press
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.An inherited deficiency of the mitochondrial protein frataxin causes Friedreich's ataxia (FRDA); the mechanism by which this deficiency triggers neuro- and cardio-degeneration is unclear. Microarrays of neural tissue of animal models of the disease showed decreases in antioxidant genes, and increases in inflammatory genes. Cyclooxygenase (COX)-derived oxylipins are important mediators of inflammation. We measured oxylipin levels using tandem mass spectrometry and ELISAs in multiple cell and animal models of FRDA. Mass spectrometry revealed increases in concentrations of prostaglandins, thromboxane B2, 15-HETE and 11-HETE in cerebellar samples of knockin knockout mice. One possible explanation for the elevated oxylipins is that frataxin deficiency results in increased COX activity. While constitutive COX1 was unchanged, inducible COX2 expression was elevated over 1.35-fold (P < 0.05) in two Friedreich's mouse models and Friedreich's lymphocytes. Consistent with higher COX2 expression, its activity was also increased by 58% over controls. COX2 expression is driven by multiple transcription factors, including activator protein 1 and cAMP response element-binding protein, both of which were elevated over 1.52-fold in cerebella. Taken together, the results support the hypothesis that reduced expression of frataxin leads to elevation of COX2-mediated oxylipin synthesis stimulated by increases in transcription factors that respond to increased reactive oxygen species. These findings support a neuroinflammatory mechanism in FRDA, which has both pathomechanistic and therapeutic implications.The study was supported by NIH grants NS077777, EY012245 and AG025532 to G.A.C., and USDA-ARS Intramural Projects 5306-51530-019-00D and 1 U24 DK097154-01 to J.W.N. Funding to pay the Open Access publication charges for this article was provided by the NIH
- …
