https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48596 Wed 22 Mar 2023 08:46:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52191 Wed 15 May 2024 15:47:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16515 Wed 11 Apr 2018 13:10:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21291 in vivo and in AD. Disruption of PP2A/Bα-Tau protein interactions likely contribute to Tau deregulation in AD. Significantly, alterations in one-carbon metabolism that impair PP2A methylation are associated with increased risk for sporadic AD, and enhanced AD-like pathology in animal models. Experimental studies have linked deregulation of PP2A methylation with down-regulation of PP2A/Bα, enhanced phosphorylation of Tau and amyloid precursor protein, Tau mislocalization, microtubule destabilization and neuritic defects. While it remains unclear what are the primary events that underlie "PP2A" dysfunction in AD, deregulation of PP2A enzymes definitely affects key players in the pathogenic process. As such, there is growing interest in developing PP2A-centric therapies for AD, but this may be a daunting task without a better understanding of the regulation and function of specific PP2A enzymes.]]> Wed 11 Apr 2018 12:53:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16003 Wed 11 Apr 2018 12:17:35 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30261 Wed 11 Apr 2018 10:01:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9705 Wed 11 Apr 2018 09:51:44 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39125 p-value thresholds by summing methylation beta-values weighted by individual-CpG effect sizes from the meta-analysis of a previously published schizophrenia EWAS (comprising three separate cohorts with 675 [353 SZ and 322 HC] discovery cohort participants, 847 [414 SZ and 433 HC] replication cohort participants, and 96 monozygotic twin-pairs discordant for SZ). All SZ PMPSs were elevated in SZ participants relative to HCs, with the score calculated at a p-value threshold of 1 x 10⁻⁵ accounting for the greatest amount of variance. All PMPSs were elevated in SZ relative to BD and none of the PMPSs were increased in BD, or in a combined cohort of BD and SZ cases, relative to HCs. PMPSs were also not associated with positive or negative symptom severity. That this SZ-derived PMPSs was elevated in SZ, but not BD, suggests that epigenome-wide methylation patterns may represent distinct pathophysiology that is yet to be elucidated.]]> Wed 01 May 2024 12:58:28 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54378 Tue 20 Feb 2024 20:24:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52582 Tue 17 Oct 2023 15:55:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45945 Tue 15 Nov 2022 14:54:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48290 Tue 14 Mar 2023 11:54:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47078 Tue 13 Dec 2022 16:28:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45953 T was more prevalent in BWS with KCNQ1OT1 TSS-DMR LOM (p < 0.017); however, the relationship was not significant when the Bonferroni correction for multiple testing was applied (significance, p = 0.0036). None of the remaining 13 SNVs were significantly different in the two populations tested. The DNMT1 locus was screened in 53 BWS cases, and three rare missense variants were identified in each of three patients: rs138841970: C>T, rs150331990: A>G and rs757460628: G>A encoding NP_001124295 p.Arg136Cys, p.His1118Arg and p.Arg1223His, respectively. These variants have population frequencies of less than 1 in 1000 and were absent from 100 control cases. Functional characterization using a hemimethylated DNA trapping assay revealed a reduced methyltransferase activity relative to wild-type DNMT1 for each variant ranging from 40 to 70% reduction in activity. Conclusions: This study is the first to examine folate pathway genetics in BWS and to identify rare DNMT1 missense variants in affected individuals. Our data suggests that reduced DNMT1 activity could affect maintenance of methylation at KCNQ1OT1 TSS-DMR in some cases of BWS, possibly via a maternal effect in the early embryo. Larger cohort studies are warranted to further interrogate the relationship between impaired MTHFR enzymatic activity attributable to MTHFR rs1801133: C>T, dietary folate intake and BWS.]]> Tue 08 Nov 2022 14:51:28 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33809 -4). We did not find evidence that SNP genotype was influencing the DMR in this cohort. A smaller MHC DMR was also identified at HCG4B, and two non-MHC DMRs at PM20D1 on chr1 and ERICH1 on chr8 were also identified. Conclusions: The findings from this study confirm our previous results of a DMR at HLA-DRB1 and also suggest hypermethylation in an independent MHC locus, RNF39, is associated with MS. Taken together, our results highlight the importance of epigenetic factors at the MHC locus in MS independent of treatment, age and sex. Prospective studies are now required to discern whether methylation at MHC is involved in influencing risk of disease onset or whether the disease itself has altered the methylation profile.]]> Tue 03 Sep 2019 18:30:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43277 Thu 15 Sep 2022 12:09:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9584 Sat 24 Mar 2018 08:39:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1727 Sat 24 Mar 2018 08:27:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14711 Sat 24 Mar 2018 08:19:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19943 Sat 24 Mar 2018 07:58:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29000 Sat 24 Mar 2018 07:41:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28217 200 within FMR1, termed full mutation (FM), has been associated with promoter methylation, consequent silencing of gene expression and fragile X syndrome (FXS)-a common cause of intellectual disability and co-morbid autism. Unmethylated premutation (55-199 repeats) and FM alleles have been associated with fragile X related tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder. Here we present a 33-year-old male with FXS, with white matter changes and progressive deterioration in gait with cerebellar signs consistent with probable FXTAS; there was no evidence of any other cerebellar pathology. We show that he has tissue mosaicism in blood, saliva, and buccal samples for the size and methylation of his expanded alleles and a de novo, unmethylated microdeletion. This microdeletion involves a ~80 bp sequence in the FMR1 promoter as well as complete loss of the CGG repeat in a proportion of cells. Despite FMR1 mRNA levels in blood within the normal range, the methylation and CGG sizing results are consistent with the diagnosis of concurrent FXS and probable FXTAS. The demonstrated presence of unmethylated FM alleles would explain the manifestation of milder than expected cognitive and behavioral impairments and early onset of cerebellar ataxia. Our case suggests that individuals with FXS, who manifest symptoms of FXTAS, may benefit from more detailed laboratory testing.]]> Sat 24 Mar 2018 07:28:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50787 Sat 05 Aug 2023 11:22:45 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47575 Mon 23 Jan 2023 14:00:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52534 Mon 16 Oct 2023 14:56:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48085 Fri 24 Feb 2023 14:56:04 AEDT ]]>