cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13377001
title: Targeted disruption of the histone lysine 79 methyltransferase Dot1L in nephron progenitors causes congenital renal dysplasia

description: The epigenetic regulator Dot1, the only known histone H3K79 methyltransferase, has a conserved role in organismal development and homoeostasis. In yeast, <i>Dot1</i> is required for telomeric silencing and genomic integrity. In Drosophila, Dot1 (<i>Grappa</i>) regulates homoeotic gene expression. Dysregulation of <i>DOT1L</i> (human homologue of Dot1) causes leukaemia and is implicated in dilated cardiomyopathy. In mice, germline disruption of <i>Dot1L</i> and loss of H3K79me2 disrupt vascular and haematopoietic development. Targeted inactivation of <i>Dot1L</i> in principal cells of the mature collecting duct affects terminal differentiation and cell type patterning. However, the role of H3K79 methylation in mammalian tissue development has been questioned, as it is dispensable in the intestinal epithelium, a rapidly proliferating tissue. Here, we used lineage-specific Cre recombinase to delineate the role of Dot1L methyltransferase activity in the mouse metanephric kidney, an organ that develops via interactions between ureteric epithelial (Hoxb7) and mesenchymal (Six2) cell lineages. The results demonstrate that Dot1L<sup>Hoxb7</sup> is dispensable for ureteric bud branching morphogenesis. In contrast, Dot1L<sup>Six2</sup> is critical for the maintenance and differentiation of Six2+ progenitors into epithelial nephrons. Dot1LSix2 mutant kidneys exhibit congenital nephron deficit and cystic dysplastic kidney disease. Molecular analysis implicates defects in key renal developmental regulators, such as Lhx1, Pax2 and Notch. We conclude that the developmental functions of Dot1L-H3K79 methylation in the kidney are lineage-restricted. The link between H3K79me and renal developmental pathways reaffirms the importance of chromatin-based mechanisms in organogenesis.
DOI: 10.6084/m9.figshare.13507210
title: Exposure to extracellular vesicles from <i>Pseudomonas aeruginosa</i> result in loss of DNA methylation at enhancer and DNase hypersensitive site regions in lung macrophages

description: Various pathogens use differing strategies to evade host immune response including modulating the host’s epigenome. Here, we investigate if EVs secreted from <i>P. aeruginosa</i> alter DNA methylation in human lung macrophages, thereby potentially contributing to a dysfunctional innate immune response. Using a genome-wide DNA methylation approach, we demonstrate that <i>P. aeruginosa</i> EVs alter certain host cell DNA methylation patterns. We identified 1,185 differentially methylated CpGs (FDR &lt; 0.05), which were significantly enriched for distal DNA regulatory elements including enhancer regions and DNase hypersensitive sites. Notably, all but one of the 1,185 differentially methylated CpGs were hypomethylated in association with EV exposure. Significantly hypomethylated CpGs tracked to genes including <i>AXL, CFB and CCL23</i>. Gene expression analysis identified 310 genes exhibiting significantly altered expression 48 hours post <i>P. aeruginosa</i> EV treatment, with 75 different genes upregulated and 235 genes downregulated. Some CpGs associated with cytokines such as <i>CSF3</i> displayed strong negative correlations between DNA methylation and gene expression. Our infection model illustrates how secreted products (EVs) from bacteria can alter DNA methylation of the host epigenome. Changes in DNA methylation in distal DNA regulatory regions in turn can modulate cellular gene expression and potential downstream cellular processes.
DOI: 10.6084/m9.figshare.13507210.v1
title: Exposure to extracellular vesicles from <i>Pseudomonas aeruginosa</i> result in loss of DNA methylation at enhancer and DNase hypersensitive site regions in lung macrophages

description: Various pathogens use differing strategies to evade host immune response including modulating the host’s epigenome. Here, we investigate if EVs secreted from <i>P. aeruginosa</i> alter DNA methylation in human lung macrophages, thereby potentially contributing to a dysfunctional innate immune response. Using a genome-wide DNA methylation approach, we demonstrate that <i>P. aeruginosa</i> EVs alter certain host cell DNA methylation patterns. We identified 1,185 differentially methylated CpGs (FDR &lt; 0.05), which were significantly enriched for distal DNA regulatory elements including enhancer regions and DNase hypersensitive sites. Notably, all but one of the 1,185 differentially methylated CpGs were hypomethylated in association with EV exposure. Significantly hypomethylated CpGs tracked to genes including <i>AXL, CFB and CCL23</i>. Gene expression analysis identified 310 genes exhibiting significantly altered expression 48 hours post <i>P. aeruginosa</i> EV treatment, with 75 different genes upregulated and 235 genes downregulated. Some CpGs associated with cytokines such as <i>CSF3</i> displayed strong negative correlations between DNA methylation and gene expression. Our infection model illustrates how secreted products (EVs) from bacteria can alter DNA methylation of the host epigenome. Changes in DNA methylation in distal DNA regulatory regions in turn can modulate cellular gene expression and potential downstream cellular processes.
DOI: 10.6084/m9.figshare.13498434
title: DNA methylation signatures of adolescent victimization: analysis of a longitudinal monozygotic twin sample

description: Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (<i>P</i> ∆Beta range = −5.5%−5.3%). Age-18 cross-sectional analyses revealed 72 blood (<i>∆Beta range </i>= −2.2%−3.4%) and 42 buccal (<i>∆Beta range </i>= −3.6%−4.6%) suggestive severe adolescent victimization-associated DMPs, with some evidence of convergent signals between these two tissue types. Downstream regional analysis identified significant differentially methylated regions (DMRs) in <i>LGR6</i> and <i>ANK3</i> (Šidák <i>P = </i><i>5</i>e-09 and 4.07e-06), and one upstream of <i>CCL27</i> (Šidák <i>P = </i>2.80e-06) in age-18 blood and buccal EWAS, respectively. Our study represents the first longitudinal MZ twin analysis of DNAm and severe adolescent victimization, providing initial evidence for altered DNA methylomic signatures in individuals exposed to adolescent victimization.
DOI: 10.6084/m9.figshare.13498434.v1
title: DNA methylation signatures of adolescent victimization: analysis of a longitudinal monozygotic twin sample

description: Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (<i>P</i> ∆Beta range = −5.5%−5.3%). Age-18 cross-sectional analyses revealed 72 blood (<i>∆Beta range </i>= −2.2%−3.4%) and 42 buccal (<i>∆Beta range </i>= −3.6%−4.6%) suggestive severe adolescent victimization-associated DMPs, with some evidence of convergent signals between these two tissue types. Downstream regional analysis identified significant differentially methylated regions (DMRs) in <i>LGR6</i> and <i>ANK3</i> (Šidák <i>P = </i><i>5</i>e-09 and 4.07e-06), and one upstream of <i>CCL27</i> (Šidák <i>P = </i>2.80e-06) in age-18 blood and buccal EWAS, respectively. Our study represents the first longitudinal MZ twin analysis of DNAm and severe adolescent victimization, providing initial evidence for altered DNA methylomic signatures in individuals exposed to adolescent victimization.
DOI: 10.6084/m9.figshare.17104547.v1
title: Daftar Isi

description: this is a part of my thesis
DOI: 10.6084/m9.figshare.17104547
title: Daftar Isi

description: this is a part of my thesis
DOI: 10.5281/zenodo.5746798
title: Material flow analysis of asphalt used in roads for an Austrian municipality

description: Circular economy gain increasing popularity to ensure a sustainable development. The road construction sector has a major contribution to the circular approach as asphalt has high recycling rates and waste materials have potential application in the production of asphalt mixtures. A study on the asphalt flow in an Austrian municipality was conducted and the underlying material flow analysis model and primary data construction and demolition data of the study are presented. In addition, transfer coefficients and the particle emission model are included.
DOI: 10.5281/zenodo.5746797
title: Material flow analysis of asphalt used in roads for an Austrian municipality

description: Circular economy gain increasing popularity to ensure a sustainable development. The road construction sector has a major contribution to the circular approach as asphalt has high recycling rates and waste materials have potential application in the production of asphalt mixtures. A study on the asphalt flow in an Austrian municipality was conducted and the underlying material flow analysis model and primary data construction and demolition data of the study are presented. In addition, transfer coefficients and the particle emission model are included.
DOI: 10.5281/zenodo.5746820
title: msd-errors - Data for the LLZO figure

description: Data for the figure showing the diffusion and Arrhenius plots for a short simulation of LLZO. <br><br>Created using showyourwork from this GitHub repo.
DOI: 10.6084/m9.figshare.17102651
title: Database for Léonard et al. Was the last bacterial common ancestor a monoderm after all?

description: SQL dump for the MySQL database
DOI: 10.6084/m9.figshare.17102651.v1
title: Database for Léonard et al. Was the last bacterial common ancestor a monoderm after all?

description: SQL dump for the MySQL database
DOI: 10.5281/zenodo.5746846
title: Figures and datasets of paper titled "Bulk carrier lifetime surpassing 600 us in Upgraded Metallurgical-grade Silicon multicrystalline wafers after Phosphorus Diffusion Gettering"

description: Datasets and figures of paper titled "Figures and datasets of paper titled "Bulk carrier lifetime surpassing 600 us in Upgraded Metallurgical-grade Silicon multicrystalline wafers after Phosphorus Diffusion Gettering" published in arXiv (https://arxiv.org/abs/2111.13522).
DOI: 10.5281/zenodo.5746845
title: Figures and datasets of paper titled "Bulk carrier lifetime surpassing 600 us in Upgraded Metallurgical-grade Silicon multicrystalline wafers after Phosphorus Diffusion Gettering"

description: Datasets and figures of paper titled "Figures and datasets of paper titled "Bulk carrier lifetime surpassing 600 us in Upgraded Metallurgical-grade Silicon multicrystalline wafers after Phosphorus Diffusion Gettering" published in arXiv (https://arxiv.org/abs/2111.13522).
DOI: 10.6084/m9.figshare.13379042.v1
title: Characterization of glucocorticoid-induced loss of DNA methylation of the stress-response gene <i>Fkbp5</i> in neuronal cells

description: Exposure to stress or glucocorticoids (GCs) is associated with epigenetic and transcriptional changes in genes that either mediate or are targets of GC signalling. <i>FKBP5</i> (FK506 binding protein 5) is one such gene that also plays a central role in negative feedback regulation of GC signalling and several stress-related psychiatric disorders. In this study, we sought to examine how the mouse <i>Fkbp5</i> gene is regulated in a neuronal context and identify requisite factors that can mediate the epigenetic sequelae of excess GC exposure. Mice treated with GCs were used to establish the widespread changes in DNA methylation (DNAm) and expression of <i>Fkbp5</i> across four brain regions. Then two cell lines were used to test the persistence, decay, and functional significance of GC-induced methylation changes near two GC response elements (GREs) in the fifth intron of <i>Fkbp5</i>. We also tested the involvement of DNMT1, cell proliferation, and MeCP2 in mediating the effect of GCs on DNAm and gene activation. DNAm changes at some CpGs persist while others decay, and reduced methylation states are associated with a more robust transcriptional response. Importantly, the ability to undergo GC-induced DNAm loss is tied to DNMT1 function during cell division. Further, GC-induced DNAm loss is associated with reduced binding of MeCP2 at intron 5 and a physical interaction between the fifth intron and promoter of <i>Fkbp5</i>. Our results highlight several key factors at the <i>Fkbp5</i> locus that may have important implications for GC- or stress-exposure during early stages of neurodevelopment.
DOI: 10.6084/m9.figshare.13377011
title: DNA methylation ageing clocks and pancreatic cancer risk: pooled analysis of three prospective nested case-control studies

description: DNA methylation (DNAm) age may reflect age-related variations in biological changes and abnormalities related to ageing. DNAm age acceleration measures have been associated with a number of cancers, but to our knowledge, have not been examined in relation to pancreatic cancer risk or survival. DNAm levels in leukocytes of prediagnostic blood samples of 393 pancreatic cancer cases and 431 matched controls, pooled from three large prospective cohort studies, were used to estimate DNAm age, epigenetic age acceleration (AA), and intrinsic epigenetic age acceleration (IEAA) metrics. Logistic regression and Cox proportional hazard regression models were used to examine the relationship between the various AA and IEAA metrics and pancreatic cancer risk and survival, respectively. The results showed that pancreatic cancer risk was significantly increased across all IEAA metrics, ranging from 83% to 95% increased risk when comparing the third and highest quartiles to the lowest quartile of IEAA. Consistent with these findings, the results from multivariate spline regression analyses showed non-linear relationships between all three IEAA metrics and pancreatic cancer risk with apparent threshold effect including two turning points at minimal and at maximal risks, respectively. There is no evidence of a significant association between pancreatic cancer survival and any of the epigenetic AA or IEAA metrics. Our results indicate DNAm age acceleration, measured in blood prior to cancer diagnosis, is associated with an increased risk of pancreatic cancer in a complex nonlinear, dose–response manner. Epigenetic IEAA metrics may be a useful addition to current methods for pancreatic cancer risk prediction.
DOI: 10.6084/m9.figshare.13379042
title: Characterization of glucocorticoid-induced loss of DNA methylation of the stress-response gene <i>Fkbp5</i> in neuronal cells

description: Exposure to stress or glucocorticoids (GCs) is associated with epigenetic and transcriptional changes in genes that either mediate or are targets of GC signalling. <i>FKBP5</i> (FK506 binding protein 5) is one such gene that also plays a central role in negative feedback regulation of GC signalling and several stress-related psychiatric disorders. In this study, we sought to examine how the mouse <i>Fkbp5</i> gene is regulated in a neuronal context and identify requisite factors that can mediate the epigenetic sequelae of excess GC exposure. Mice treated with GCs were used to establish the widespread changes in DNA methylation (DNAm) and expression of <i>Fkbp5</i> across four brain regions. Then two cell lines were used to test the persistence, decay, and functional significance of GC-induced methylation changes near two GC response elements (GREs) in the fifth intron of <i>Fkbp5</i>. We also tested the involvement of DNMT1, cell proliferation, and MeCP2 in mediating the effect of GCs on DNAm and gene activation. DNAm changes at some CpGs persist while others decay, and reduced methylation states are associated with a more robust transcriptional response. Importantly, the ability to undergo GC-induced DNAm loss is tied to DNMT1 function during cell division. Further, GC-induced DNAm loss is associated with reduced binding of MeCP2 at intron 5 and a physical interaction between the fifth intron and promoter of <i>Fkbp5</i>. Our results highlight several key factors at the <i>Fkbp5</i> locus that may have important implications for GC- or stress-exposure during early stages of neurodevelopment.
DOI: 10.6084/m9.figshare.13516898
title: <i>NMU</i> DNA methylation in blood is associated with metabolic and inflammatory indices: results from the Moli-sani study

description: Neuromedin U (NMU) is a neuropeptide involved in gut-brain axis, energy balance and immune response. We aimed at analysing the association between <i>NMU</i> epigenetic variability and metabolic indices and the potential mediating role of low-grade inflammation in a general population of Italian adults. <i>NMU</i> Blood DNA methylation levels at two CpG islands (<i>NMU76</i> and <i>NMU32</i>) were analysed using pyrosequencing in a randomly selected sub-cohort of 1,160 subjects from the Moli-sani study (≥35years; 49.20% men). Multivariable regressions adjusted for age, sex, smoking, alcohol and vegetable consumption were performed to estimate the associations between methylation and metabolic phenotypes (BMI, waist-to-hip ratio, blood pressure, glucose, HOMA-IR, lipids, lipoprotein(a) and apolipoproteins). Mediation analysis was performed to identify the influence of low-grade inflammation in the association using a composite index based on C reactive protein, granulocyte-to-lymphocyte ratio (GLR), platelet and white blood cell counts (INFLA-score). Using principal component analysis four methylation factors were identified: <i>NMU76-F1, NMU76-F2, NMU32-F1</i> and <i>NMU32-F2</i>. <i>NMU76-F1</i> was FDR significantly associated with total cholesterol (for 1 SD increase: β = 4.5 ± 1.4 mg/dL of, R<sup>2</sup> = 10.8%, p = 0.001), ApoB (0.03 ± 0.01 g/L, 12.2%, p = 0.0004), with INFLA-score (1.05 ± 0.22, <i>p</i> = 2.7E-6) and GLR (-0.27 ± 0.03, 30.4%, <i>p</i> = 1.3E-20). GLR and lymphocyte numbers mediate the association of <i>NMU76-F1</i> with cholesterol (24.0% of total effect, Sobel p = 0.013) and ApoB (42.6%, p = 9E-7), respectively. These findings suggest that <i>NMU</i> promoter methylation patterns could mark a pathway linking lipids with haematopoiesis and systemic inflammation.
DOI: 10.6084/m9.figshare.13516898.v1
title: <i>NMU</i> DNA methylation in blood is associated with metabolic and inflammatory indices: results from the Moli-sani study

description: Neuromedin U (NMU) is a neuropeptide involved in gut-brain axis, energy balance and immune response. We aimed at analysing the association between <i>NMU</i> epigenetic variability and metabolic indices and the potential mediating role of low-grade inflammation in a general population of Italian adults. <i>NMU</i> Blood DNA methylation levels at two CpG islands (<i>NMU76</i> and <i>NMU32</i>) were analysed using pyrosequencing in a randomly selected sub-cohort of 1,160 subjects from the Moli-sani study (≥35years; 49.20% men). Multivariable regressions adjusted for age, sex, smoking, alcohol and vegetable consumption were performed to estimate the associations between methylation and metabolic phenotypes (BMI, waist-to-hip ratio, blood pressure, glucose, HOMA-IR, lipids, lipoprotein(a) and apolipoproteins). Mediation analysis was performed to identify the influence of low-grade inflammation in the association using a composite index based on C reactive protein, granulocyte-to-lymphocyte ratio (GLR), platelet and white blood cell counts (INFLA-score). Using principal component analysis four methylation factors were identified: <i>NMU76-F1, NMU76-F2, NMU32-F1</i> and <i>NMU32-F2</i>. <i>NMU76-F1</i> was FDR significantly associated with total cholesterol (for 1 SD increase: β = 4.5 ± 1.4 mg/dL of, R<sup>2</sup> = 10.8%, p = 0.001), ApoB (0.03 ± 0.01 g/L, 12.2%, p = 0.0004), with INFLA-score (1.05 ± 0.22, <i>p</i> = 2.7E-6) and GLR (-0.27 ± 0.03, 30.4%, <i>p</i> = 1.3E-20). GLR and lymphocyte numbers mediate the association of <i>NMU76-F1</i> with cholesterol (24.0% of total effect, Sobel p = 0.013) and ApoB (42.6%, p = 9E-7), respectively. These findings suggest that <i>NMU</i> promoter methylation patterns could mark a pathway linking lipids with haematopoiesis and systemic inflammation.
DOI: 10.6084/m9.figshare.13377011.v2
title: DNA methylation ageing clocks and pancreatic cancer risk: pooled analysis of three prospective nested case-control studies

description: DNA methylation (DNAm) age may reflect age-related variations in biological changes and abnormalities related to ageing. DNAm age acceleration measures have been associated with a number of cancers, but to our knowledge, have not been examined in relation to pancreatic cancer risk or survival. DNAm levels in leukocytes of prediagnostic blood samples of 393 pancreatic cancer cases and 431 matched controls, pooled from three large prospective cohort studies, were used to estimate DNAm age, epigenetic age acceleration (AA), and intrinsic epigenetic age acceleration (IEAA) metrics. Logistic regression and Cox proportional hazard regression models were used to examine the relationship between the various AA and IEAA metrics and pancreatic cancer risk and survival, respectively. The results showed that pancreatic cancer risk was significantly increased across all IEAA metrics, ranging from 83% to 95% increased risk when comparing the third and highest quartiles to the lowest quartile of IEAA. Consistent with these findings, the results from multivariate spline regression analyses showed non-linear relationships between all three IEAA metrics and pancreatic cancer risk with apparent threshold effect including two turning points at minimal and at maximal risks, respectively. There is no evidence of a significant association between pancreatic cancer survival and any of the epigenetic AA or IEAA metrics. Our results indicate DNAm age acceleration, measured in blood prior to cancer diagnosis, is associated with an increased risk of pancreatic cancer in a complex nonlinear, dose–response manner. Epigenetic IEAA metrics may be a useful addition to current methods for pancreatic cancer risk prediction.