https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42668 Wed 31 Aug 2022 16:18:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45103 Wed 26 Oct 2022 13:14:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45135 Bifidobacterium are notoriously recalcitrant to genetic manipulation due to their extensive and variable repertoire of Restriction-Modification (R-M) systems. Non-replicating plasmids are currently employed to achieve insertional mutagenesis in Bifidobacterium. One of the limitations of using such insertion vectors is the presence within their sequence of various restriction sites, making them sensitive to the activity of endogenous restriction endonucleases encoded by the target strain. For this reason, vectors have been developed with the aim of methylating and protecting the vector using a methylase-positive Escherichia coli strain, in some cases containing a cloned bifidobacterial methylase. Here, we present a mutagenesis approach based on a modified and synthetically produced version of the suicide vector pORI28 (named pFREM28), where all known restriction sites targeted by Bifidobacterium breve R-M systems were removed by base substitution (thus preserving the codon usage). After validating the integrity of the erythromycin marker, the vector was successfully employed to target an a-galactosidase gene responsible for raffinose metabolism, an alcohol dehydrogenase gene responsible for mannitol utilization and a gene encoding a priming glycosyltransferase responsible for exopolysaccharides (EPS) production in B. breve. The advantage of using this modified approach is the reduction of the amount of time, effort and resources required to generate site-directed mutants in B. breve and a similar approach may be employed to target other (bifido)bacterial species.]]> Wed 26 Oct 2022 13:12:44 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48589 Wed 22 Mar 2023 08:32:47 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47164 Wed 14 Dec 2022 15:49:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53830 Wed 13 Mar 2024 13:47:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54801 Wed 13 Mar 2024 11:41:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13745 Wed 11 Apr 2018 16:02:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16473 Wed 11 Apr 2018 15:33:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26346 Wed 11 Apr 2018 13:23:03 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17266 Wed 11 Apr 2018 10:51:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23271 Wed 11 Apr 2018 10:32:06 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18017 Wed 11 Apr 2018 09:35:25 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10028 Wed 11 Apr 2018 09:21:02 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17847  22 and delta beta >0.06). Results: There were 70 CpG loci, corresponding to 67 genes that were significantly differentially methylated. Twelve CpG loci (11 genes) showed greater than 10% comparative difference in DNA methylation, including hyper-methylated loci of FAM181A, MRI1, PIWIL1, CHFR, DEFA1, MRPL28, AURKA, and hypo-methylated loci of NALP1L5, MAP8KIP3, ACAT2, and PM20D1 in maternal asthma. Methylation of MAPK8IP3 was significantly negatively correlated with maternal blood eosinophils (r = −0.38; P = 0.022), maternal eNO (r = −0.44; P = 0.005), and maternal serum total IgE (r = −0.39, P = 0.015). Methylation of AURKA negatively correlated with maternal hemoglobin (r = −0.43; P = 0.008), infants height (r = −0.51; P < 0.001) and weight (r = −0.36; P = 0.021). Methylation of PM20D1 was lower in infants born to mothers with asthma on inhaled corticosteroid treatment. Methylation of PM20D1 was lower and MRI1 was higher in infants born to atopic mothers without asthma. Conclusions: In an Australian study population, exposure to maternal asthma during pregnancy is associated with differential methylation profiles of infants' peripheral blood DNA, which may act as risk factors for future asthma development.]]> Wed 04 Sep 2019 10:59:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55024 Wed 03 Apr 2024 15:41:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47832 Wed 01 Feb 2023 13:35:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47796 Tue 31 Jan 2023 15:32:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33632 Tue 27 Nov 2018 16:39:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32623 Tue 26 Jun 2018 11:28:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30964 100) epialleles. RNA-polymerase-II (Pol-II) bound only to three particular epialleles in cAMP-stimulated cells, while phospho-cAMP response element-binding protein (pCREB) bound to only one epiallele, which was different from those selected by Pol-II. Binding of TATA-binding protein increased during syncytial differentiation preferentially at epialleles compatible with Pol-II and pCREB binding. Histone-3 acetylation was detected only at epialleles targeted by Pol-II and pCREB, while gene activating histone-4 acetylation and histone-3-lysine-4 trimethylation occurred at CRH epialleles not associated with Pol-II or pCREB. The suppressive histone-3-lysine-27 trimethyl and-lysine-9 trimethyl modifications showed little or no epiallele preference. The epiallele selectivity of activating histone modifications and transcription factor binding demonstrates the epigenetic and functional diversity of the CRH gene in trophoblasts, which is controlled predominantly by the patterns, not the overall extent, of promoter methylation. We propose that conditions impacting on epiallele distribution influence the number of transcriptionally active CRH gene copies in the trophoblast cell population determining the gestational trajectory of placental CRH production in normal and pathological pregnancies.]]> Tue 24 Apr 2018 15:36:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39718 270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.]]> Tue 21 Mar 2023 17:20:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44611 Tue 18 Oct 2022 08:44:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52750 Tue 14 Nov 2023 11:55:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45586 Tue 08 Nov 2022 15:02:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45857 p level: 1.06 × 10^-7), that were associated with maternal smoking during pregnancy, including associated genes AHRR (cancer development), FTO (obesity), CNTNAP2 (developmental processes), CYP1A1 (detoxification), MYO1G (cell signalling) and FRMD4A (nicotine dependence). A sensitivity analysis showed a dose dependent relationship between maternal smoking and offspring methylation. These results changed little following adjustment for paternal, passive or offspring smoking and there were no CpGs identified that associated with these variables. Two of the 23 identified CpGs (cg00253568 (FTO) and cg00213123 (CYP1A1)) were associated with either TG (males and females), diastolic blood pressure (females only) or HDL-C (males only), after Bonferroni correction. Discussion: This study demonstrates a critical timing of cigarette smoke exposure over the life-course for establishing persistent changes in DNA methylation into adolescence in a dose dependent manner. There were significant associations between offspring CpG methylation and adolescent cardiovascular risk factors, namely TG, HDL-C and diastolic blood pressure. Future studies on current smoking habits and DNA methylation should consider the importance of maternal smoking during pregnancy and explore how the persistent DNA methylation effects of in utero smoke exposure increase cardiometabolic risk.]]> Tue 08 Nov 2022 08:25:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42900 Tue 06 Sep 2022 15:14:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39670 Thu 28 Jul 2022 08:10:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29462 IRAKM, PCDH1, ORMDL3/GSDMB, IL-33, CDHR3 and CST1 in airway epithelial cells. Recent studies on epigenetic regulatory factors have further provided novel insights to the field, particularly their effect on regulation of some of the asthma susceptibility genes (e.g. methylation of ADAM33). Among the epigenetic regulatory mechanisms, microRNA networks have been shown to regulate a major portion of post-transcriptional gene regulation. Particularly, miR-19a may have some therapeutic potential.]]> Thu 24 Mar 2022 11:32:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51627 Thu 23 Nov 2023 14:26:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35858 Thu 21 Oct 2021 12:45:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44508 Thu 16 May 2024 08:36:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45991 Thu 10 Nov 2022 10:14:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30829 Thu 09 Dec 2021 11:04:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:6984 Sat 24 Mar 2018 08:37:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17503 Sat 24 Mar 2018 08:04:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21178 BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (OSE) samples using methylation-specific headloop suppression PCR. Results: The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign OSE, with the exception of SFN which was methylated in all HGSOC and benign OSE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10–11.07), p = 0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign OSE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated. Conclusions: This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC.]]> Sat 24 Mar 2018 07:58:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18790 Sat 24 Mar 2018 07:51:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35542 Mon 26 Aug 2019 15:28:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29660 CYP2R1, CYP27B1 and CYP24A1) and the Vitamin D receptor gene (VDR). This analysis was conducted in the context of dietary Vitamin D, and background methyl donor related biochemistry, with adjustment for several dietary and lifestyle variables. Percentage methylation at CpG sites was assessed in peripheral blood cells using methylation sensitive and dependent enzymes and qPCR. Standard analytical techniques were used to determine plasma 25(OH)D and homocysteine, and serum folate and B12, with the relationship to methylation status assessed using multi-variable regression analysis. CYP2R1 and VDR methylation were found to be independent predictors of plasma 25(OH)D, when adjusted for Vitamin D intake and other lifestyle variables. CYP24A1 was related to plasma 25(OH)D directly, but not in the context of Vitamin D intake. Methyl-group donor biochemistry was associated with the methylation status of some genes, but did not alter the relationship between methylation and plasma 25(OH)D. Modulation of methylation status of CYP2R1, CYP24A1 and VDR in response to plasma 25(OH)D may be part of feedback loops involved in maintaining Vitamin D homeostasis, and may explain a portion of the variance in plasma 25(OH)D levels in response to intake and sun exposure. Methyl-group donor biochemistry, while a potential independent modulator, did not alter this effect.]]> Mon 26 Apr 2021 10:02:52 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22021 Mon 24 Sep 2018 13:40:15 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33803 Mon 23 Sep 2019 13:59:39 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33608 Mon 23 Sep 2019 11:15:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42333 Mon 22 Aug 2022 11:06:25 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53246 Mon 20 Nov 2023 10:14:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52306 Mon 09 Oct 2023 10:16:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40279 Mon 08 Aug 2022 11:55:28 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38008 Fri 23 Jul 2021 15:13:02 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40086 in utero cigarette smoke exposure. Methods: We used machine learning methods to create a score reflecting exposure to maternal smoking during pregnancy. This score is based on peripheral blood measurements of DNA methylation (Illumina’s Infinium HumanMethylation450K BeadChip). The score was developed and tested in the Raine Study with data from 995 white 17-y-old participants using 10-fold cross-validation. The score was further tested and validated in independent data from the Northern Finland Birth Cohort 1986 (NFBC1986) (16-y-olds) and 1966 (NFBC1966) (31-y-olds). Further, three previously proposed DNA methylation scores were applied for comparison. The final score was developed with 204 CpGs using elastic net regression. Results: Sensitivity and specificity values for the best performing previously developed classifier (“Reese Score”) were 88% and 72% for Raine, 87% and 61% for NFBC1986 and 72% and 70% for NFBC1966, respectively; corresponding figures using the elastic net regression approach were 91% and 76% (Raine), 87% and 75% (NFBC1986), and 72% and 78% for NFBC1966. Conclusion: We have developed a DNA methylation score for exposure to maternal smoking during pregnancy, outperforming the three previously developed scores. One possible application of the current score could be for model adjustment purposes or to assess its association with distal health outcomes where part of the effect can be attributed to maternal smoking. Further, it may provide a biomarker for fetal exposure to maternal smoking.]]> Fri 22 Jul 2022 13:24:59 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35158 in vitro and in vivo. Exit from pluripotency and priming for differentiation into somatic lineages is associated with genome-wide de novo DNA methylation. We show that during this phase, co-expression of enzymes required for DNA methylation turnover, DNMT3s and TETs, promotes cell-to-cell variability in this epigenetic mark. Using a combination of single-cell sequencing and quantitative biophysical modeling, we show that this variability is associated with coherent, genome-scale oscillations in DNA methylation with an amplitude dependent on CpG density. Analysis of parallel single-cell transcriptional and epigenetic profiling provides evidence for oscillatory dynamics both in vitro and in vivo. These observations provide insights into the emergence of epigenetic heterogeneity during early embryo development, indicating that dynamic changes in DNA methylation might influence early cell fate decisions.]]> Fri 21 Jun 2019 15:13:02 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44495 Fri 14 Oct 2022 09:46:45 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37082 Fri 14 Aug 2020 14:27:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22586 Fri 10 Aug 2018 15:35:14 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37039 Fri 07 Aug 2020 12:28:15 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52991 Fri 03 Nov 2023 16:05:35 AEDT ]]>