Differential Positions Research Articles

Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study

BackgroundExposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear. ObjectiveWe aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm). MethodThis study included 285 mother–child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm. ResultsUrinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P < 0.05). ConclusionOur results revealed that prenatal exposure to EDCs was associated with a higher risk of childhood obesity, with specific DNAm acting as a partial mediator.

Genome-Wide 5-Formylcytosine Redistribution in KCl-Stimulated Mouse Primary Cortical Neurons is Associated with Neuronal Activity.

An abundant accumulation of DNA demethylation intermediates has been identified in mammalian neurons. While the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in neuronal function have been extensively studied, little is known about 5-formylcytosine (5fC) in neurons. Therefore, this study was to investigate the genome-wide distribution and potential functions of 5fC in neurons. In an in vitro culture model of mouse primary cortical neurons, we observed a dynamic increase in the total 5fC level in the neuronal genome after potassium chloride (KCl) stimulation. Subsequently, we employed chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to examine the 5fC distribution at a single-base resolution. Bioinformatic analysis revealed that 5fC was enriched in promoter regions, and gene ontology (GO) analysis indicated that the differential formylation positions (DFP) were correlated with neuronal activities. Additionally, integration with previously published nascent RNA-seq data revealed a positive correlation between gene formylation and mRNA expression levels. As well, 6 neuro-activity-related genes with a positive correlation were validated. Furthermore, we observed higher chromatin accessibility and RNA pol II binding signals near the 5fC sites through multiomics analysis. Motif analysis identified potential reader proteins for 5fC. In conclusion, our work provides a valuable resource for studying the dynamic changes and functional roles of 5fC in activated mammalian neurons.

COMPOSITION AND THE RELATIVE STABILITY OF SULFUR DIOXIDE INTERACTION PRODUCTS WITH POTASSIUM AND MONOETHANOLAMMONIUM TAURATES AQUEOUS SOLUTIONS. PROLONGED-ACTION CHEMOSORBENT

Much research attention has been paid to amino acids as an alternative to amino alcohols for capture of sulfur dioxide. Taurine (Tau) occupies a special place among amino acids. This study was stimulated by the limited literature data on the nature of the interaction of SO2 with Tau salts aqueous solutions, the composition and relative stability of the corresponding reaction products. Chrono-pH-, chrono-redox- and chrono-conductometric studies of SO2 chemisorption with potassium taurate (TauK) and monoethanolammonium (TauMEA) aqueous 0.1 M solutions were carried out in the temperature range 293–313 K to study these processes. The maxima on the differential pH-metric titration curves positions coincide with the positions of the jumps on the integral and maxima on the redox-metric titration differential curves, as well as with breaks on the conductometric curves position. Δk negative values indicate the formation of weakly dissociated particles or less mobile ions in the solutions under study that is confirmed by the data of mathematical calculations. Using a mathematical model that takes into account the law of mass action, material balance and electrical neutrality principle, SO2 – TauK – H2O solutions ion-molecular composition and ionic strength were calculated. With an increase in the chemisotption SO2 amount, the taurate anions concentration decreases due to the hydrolytic transformation into zwitter ions +NH3CH2CH2SO2O - and the sequential transformation of hydrotaurate-sulfite (4:1 and 2:1; I and II), taurate-sulfite (2:1; III), hydrotaurate-hydrosulfite (2:1; IV) and taurate-hydrosulfite (1:1; V) associates. The concentration and thermodynamic constants for the formation ionic associates I–V were calculated. TauK input into impregnated fibrous chemisorbents (IFCS) composition obtained by impregnating viscose fibers with monoethanolamine aqueous 0.25 M solutions (IFCS-0.25MEA) leads to a synergistic increase in quantity of adsorbed SO2. IFCS-0.25MEA-TauK are long-acting sulfur dioxide chemisorbents, and TauK itself serves as a promoter-modifier towards IFCS-0.25MEA preventing the MEA removal from IFCS surface by the GPS flow due to the ionic associates formation and promoting deeper HOCH2CH2NH2 «response».

Maternal adverse childhood experiences (ACEs) and DNA methylation of newborns in cord blood

BackgroundAdverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers’ childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1–3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates.ResultsData on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Šidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function.ConclusionsMaternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health.

Historical role preparedness: A Bourdieusian analysis of the differential positions of professional staff and academics in an Australian managerialised university

This study examines the historical role preparation experiences of professional staff and academics in a managerialised university field. Semi-structured interviews were used to identify the impact of these experiences on the individual's ability to ‘play the game’ of the managerialised university field. The Bourdieusian concepts of habitus, doxa and illusio were used to analyse the data. The results showed that professional staff had a more advantageous position in the managerialised university field due to their pre-existing mastery of the rules of the game, which was attributed to their similarly structured educative role preparation experiences. Conversely, academics had a less advantageous position due to their lack of understanding of the managerialised nature of the university administrative field. This manifests as a heterodoxy, in which academics feel abandoned, disregarded and subordinated by managerial orthodoxy. The results of this case study reveal that managerialised universities in the Anglosphere are in crisis. It is argued that recognising academic heterodoxy could pave the way for their situation to alter and improve.

Epigenome-wide DNA methylation analysis of myasthenia gravis.

Myasthenia gravis (MG) is a common neuromuscular junction (NMJ) disorder and autoimmune disease mediated by several antibodies. Several studies have shown that genetic factors play an important role in MG pathogenesis. To gain insight into the epigenetic factors affecting MG, we report here genome-scale DNA methylation profiles of MG. DNA was extracted from 8 MG patients and 4 healthy controls for genome-wide DNA methylation analysis using the Illumina HumanMethylation 850K BeadChip. Verification of pyrosequencing was conducted based on differential methylation positions (DMPs). Subsequently, C2C12 and HT22 cell lines (derived from mouse) were treated with demethylation drugs. Transcribed mRNA of the screened differential genes were detected using quantitative Real-time PCR. The control and MG group were compared, and two key probe positions were selected. The corresponding genes were CAMK1D and CREB5 (P<0.05). Similarly, the myasthenic crisis (MC) and non-MC group were compared and four key probe positions were selected. The corresponding genes were SAV1, STK3, YAP1 and WWTR1 (P<0.05). Subsequently, pyrosequencing was performed for verification, revealing that hypomethylation of CAMK1D was significantly different between the MG and control group (P<0.001). Moreover, transcription of CREB5, PKD, YAP1 and STK3 genes in the C2C12 cells was downregulated (P<0.05) after drug treatment, but only YAP1 mRNA was downregulated in HT22 cells (P<0.05). This is the first study to investigate genome-scale DNA methylation profiles of MG using 850K BeadChip. The identified molecular markers of methylation may aid in the prevention, diagnosis, treatment and prognosis of MG.

Community treatment orders: A qualitative study of stakeholder perspectives

IntroductionFor people with a serious mental disorder, a community treatment order (CTO) is a legal response that requires them to undergo psychiatric treatment unwillingly under certain conditions. Qualitative studies have explored the perspectives of individuals involved in CTOs, including persons with lived experiences of a CTO, family members and mental health care providers, who are directly involved in these procedures. However, few studies have integrated their different perspectives. MethodThis descriptive and qualitative study aimed to explore the experience associated with a CTO in hospital and community settings among individuals with a history of CTO, relatives, and mental health care providers. Using a participatory research approach, individual semi-structured interviews were conducted with 35 participants. The data were reviewed using content analysis. ResultsThree themes and seven sub-themes were identified: 1) differential positions as a function of meaning conferred to CTOs; 2) a risk management tool; and 3) coping strategies used to deal with CTOs. Overall, relatives' and mental health care providers' perspectives tended to be in opposition to those who went under a CTO. ConclusionsIn a context of recovery-oriented care, more research is needed to reconcile the seemingly contradictory positions of individual with experiential knowledge and the legal leverage that deprives them of their fundamental right to autonomy.

Epigenome wide association study in peripheral blood of pregnant women identifies potential metabolic pathways related to gestational diabetes

ABSTRACT Gestational diabetes mellitus (GDM) increases the risk of developing metabolic disorders in both pregnant women and their offspring. Factors such as nutrition or the intrauterine environment may play an important role, through epigenetic mechanisms, in the development of GDM. The aim of this work is to identify epigenetic marks involved in the mechanisms or pathways related to gestational diabetes. A total of 32 pregnant women were selected, 16 of them with GDM and 16 non-GDM. DNA methylation pattern was obtained from Illumina Methylation Epic BeadChip, from peripheral blood samples at the diagnostic visit (26–28 weeks). Differential methylated positions (DMPs) were extracted using ChAMP and limma package in R 2.9.10, with a threshold of FDR <0.05, deltabeta >|5|% and B >0. A total of 1.141 DMPs were found, and 714 were annotated in genes. A functional analysis was performed, and we found 23 genes significantly related to carbohydrate metabolism. Finally, a total of 27 DMPs were correlated with biochemical variables such as glucose levels at different points of oral glucose tolerance test, fasting glucose, cholesterol, HOMAIR and HbA1c, at different visits during pregnancy and postpartum. Our results show that there is a differentiated methylation pattern between GDM and non-GDM. Furthermore, the genes annotated to the DMPs could be implicated in the development of GDM as well as in alterations in related metabolic variables.

Rapid identification of early renal damage in asymptomatic hyperuricemia patients based on urine Raman spectroscopy and bioinformatics analysis.

Objective: The issue of when to start treatment in patients with hyperuricemia (HUA) without gout and chronic kidney disease (CKD) is both important and controversial. In this study, Raman spectroscopy (RS) was used to analyze urine samples, and key genes expressed differentially CKD were identified using bioinformatics. The biological functions and regulatory pathways of these key genes were preliminarily analyzed, and the relationship between them as well as the heterogeneity of the urine components of HUA was evaluated. This study provides new ideas for the rapid evaluation of renal function in patients with HUA and CKD, while providing an important reference for the new treatment strategy of HUA disease. Methods: A physically examined population in 2021 was recruited as the research subjects. There were 10 cases with normal blood uric acid level and 31 cases with asymptomatic HUA diagnosis. The general clinical data were collected and the urine samples were analyzed by Raman spectroscopy. An identification model was also established by using the multidimensional multivariate method of orthogonal partial least squares discriminant analysis (OPLS-DA) model for statistical analysis of the data, key genes associated with CKD were identified using the Gene Expression Omnibus (GEO) database, and key biological pathways associated with renal function damage in CKD patients with HUA were analyzed. Results: The Raman spectra showed significant differences in the levels of uric acid (640cm-1), urea, creatinine (1,608, 1,706cm-1), proteins/amino acids (642, 828, 1,556, 1,585, 1,587, 1,596, 1,603, 1,615cm-1), and ketone body (1,643cm-1) (p < 0.05). The top 10 differentially expressed genes (DEGs) associated with CKD (ALB, MYC, IL10, FOS, TOP2A, PLG, REN, FGA, CCNA2, and BUB1) were identified. Compared with the differential peak positions analyzed by the OPLS-DA model, it was found that the peak positions of glutathione, tryptophan and tyrosine may be important markers for the diagnosis and progression of CKD. Conclusion: The progression of CKD was related to the expression of the ALB, MYC, IL10, PLG, REN, and FGA genes. Patients with HUA may have abnormalities in glutathione, tryptophan, tyrosine, and energy metabolism. The application of Raman spectroscopy to analyze urine samples and interpret the heterogeneity of the internal environment of asymptomatic HUA patients can be combined with the OPLS-DA model to mine the massive clinical and biochemical examination information on HUA patients. The results can also provide a reference for identifying the right time for intervention for uric acid as well as assist the early detection of changes in the internal environment of the body. Finally, this approach provides a useful technical supplement for exploring a low-cost, rapid evaluation and improving the timeliness of screening. Precise intervention of abnormal signal levels of internal environment and energy metabolism may be a potential way to delay renal injury in patients with HUA.

DNA methylation-based patterns for early diagnostic prediction and prognostic evaluation in colorectal cancer patients with high tumor mutation burden.

Immune checkpoint inhibitor (ICI) therapy has proven to be a promising treatment for colorectal cancer (CRC). We aim to investigate the relationship between DNA methylation and tumor mutation burden (TMB) by integrating genomic and epigenetic profiles to precisely identify clinical benefit populations and to evaluate the effect of ICI therapy. A total of 536 CRC tissues from the Cancer Genome Atlas (TCGA) with mutation data were collected and subjected to calculate TMB. 80 CRC patients with high TMB and paired normal tissues were selected as training sets and developed the diagnostic and prognostic methylation models, respectively. In the validation set, the diagnostic model was validated in our in-house 47 CRC tissues and 122 CRC tissues from the Gene Expression Omnibus (GEO) datasets, respectively. And a total of 38 CRC tissues with high TMB from the COLONOMICS dataset verified the prognostic model. A positive correlation between differential methylation positions and TMB level was observed in TCGA CRC cohort (r=0.45). The diagnostic score that consisted of methylation levels of four genes (ADHFE1, DOK6, GPR75, and MAP3K14-AS1) showed high diagnostic performance in the discovery (AUC=1.000) and two independent validation (AUC=0.946, AUC=0.857) datasets. Additionally, these four genes showed significant positive correlations with NK cells. The prognostic score containing three genes (POU3F3, SYN2, and TMEM178A) had significantly poorer survival in the high-risk TMB samples than those in the low-risk TMB samples (P=0.016). CRC patients with low-risk scores combined with TMB levels represent a favorable survival. By integrating analyses of methylation and mutation data, it is suggested that DNA methylation patterns combined with TMB serve as a novel potential biomarker for early screening in more high-TMB populations and for evaluating the prognostic effect of CRC patients with ICI therapy.

Genome-wide epigenetic and mRNA-expression profiling followed by CRISPR/Cas9-mediated gene-disruptions corroborate the MIR141/MIR200C-ZEB1/ZEB2-FGFR1 axis in acquired EMT-associated EGFR TKI-resistance in NSCLC cells.

Epithelial-mesenchymal-transition (EMT) is an epigenetic-based mechanism contributing to the acquired treatment resistance against receptor tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) cells harboring epidermal growth factor receptor (EGFR)-mutations. Delineating the exact epigenetic and gene-expression alterations in EMT-associated EGFR TKI-resistance (EMT-E-TKI-R) is vital for improved diagnosis and treatment of NSCLC patients. We characterized genome-wide changes in mRNA-expression, DNA-methylation and the histone-modification H3K36me3 in EGFR-mutated NSCLC HCC827 cells in result of acquired EMT-E-TKI-R. CRISPR/Cas9 was used to functional examine key findings from the omics analyses. Acquired EMT-E-TKI-R was analyzed with three omics approaches. RNA-sequencing identified 2,233 and 1,972 up- and down-regulated genes, respectively, and among these were established EMT-markers. DNA-methylation EPIC array analyses identified 14,163 and 7,999 hyper- and hypo-methylated, respectively, differential methylated positions of which several were present in EMT-markers. Finally, H3K36me3 chromatin immunoprecipitation (ChIP)-sequencing detected 2,873 and 3,836 genes with enrichment and depletion, respectively, and among these were established EMT-markers. Correlation analyses showed that EMT-E-TKI-R mRNA-expression changes correlated better with H3K36me3 changes than with DNA-methylation changes. Moreover, the omics data supported the involvement of the MIR141/MIR200C-ZEB1/ZEB2-FGFR1 signaling axis for acquired EMT-E-TKI-R. CRISPR/Cas9-mediated analyses corroborated the importance of ZEB1 in acquired EMT-E-TKI-R, MIR200C and MIR141 to be in an EMT-E-TKI-R-associated auto-regulatory loop with ZEB1, and FGFR1 to mediate cell survival in EMT-E-TKI-R. The current study describes the synchronous genome-wide changes in mRNA-expression, DNA-methylation, and H3K36me3 in NSCLC EMT-E-TKI-R. The omics approaches revealed potential novel diagnostic markers and treatment targets. Besides, the study consolidates the functional impact of the MIR141/MIR200C-ZEB1/ZEB2-FGFR1-signaling axis in NSCLC EMT-E-TKI-R.

Justice should be at the centre of assessments of climate change impacts on health

Several reports, such as the Lancet Countdown on health and climate change,1,2 analyse and quantify the impacts of a changing climate on human health, bring attention to the compounding effects of climate stressors on health, and call for reducing the use of fossil fuels as an important mitigation measure with health co-benefits. However, the health community should not treat climate change as an equalising threat separate from the historical injustices that affect the differential positions of people in relation to health risks at both global and local levels.

Genome-wide placental DNA methylations in fetal overgrowth and associations with leptin, adiponectin and fetal growth factors

BackgroundFetal overgrowth “programs” an elevated risk of type 2 diabetes in adulthood. Epigenetic alterations may be a mechanism in programming the vulnerability. We sought to characterize genome-wide alterations in placental gene methylations in fetal overgrowth and the associations with metabolic health biomarkers including leptin, adiponectin and fetal growth factors.ResultsComparing genome-wide placental gene DNA methylations in large-for-gestational-age (LGA, an indicator of fetal overgrowth, n = 30) versus optimal-for-gestational-age (OGA, control, n = 30) infants using the Illumina Infinium Human Methylation-EPIC BeadChip, we identified 543 differential methylation positions (DMPs; 397 hypermethylated, 146 hypomethylated) at false discovery rate < 5% and absolute methylation difference > 0.05 after adjusting for placental cell-type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. Twenty-five DMPs annotated to 20 genes (QSOX1, FCHSD2, LOC101928162, ADGRB3, GCNT1, TAP1, MYO16, NAV1, ATP8A2, LBXCOR1, EN2, INCA1, CAMTA2, SORCS2, SLC4A4, RPA3, UMAD1,USP53, OR2L13 and NR3C2) could explain 80% of the birth weight variations. Pathway analyses did not detect any statistically significant pathways after correcting for multiple tests. We validated a newly discovered differentially (hyper-)methylated gene-visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (LGA 47, OGA 47). Our data confirmed a hypermethylated gene—cadherin 13 (CDH13) reported in a previous epigenome-wide association study. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while leptin and fetal growth factors (insulin, IGF-1, IGF-2) were not.ConclusionsFetal overgrowth may be associated with a large number of altered placental gene methylations. Placental VSX1 and CDH13 genes are hypermethylated in fetal overgrowth. Placental ADIPOQ gene methylations and fetal circulating adiponectin levels were correlated, suggesting the contribution of placenta-originated adiponectin to cord blood adiponectin.

Integrated genome-wide methylation and expression analyses provide predictors of diagnosis and early response to antidepressant in panic disorder

BackgroundWe investigated differentially methylated and expressed genes between panic disorder (PD) and healthy controls (HCs) to determine whether DNA methylation and expression level of candidate genes can be used as biomarkers for diagnosis and early response. MethodsIllumina infiniun Methylation EPIC (850 k) Beadchip for genome-wide methylation screening and mRNA sequencing was conducted in a discovery set (30 patients with PD and 30 matched HCs). The candidate gene loci methylation and expression were verified in an independent validation sample (101 PD patients and 107 HCs). ResultsIn the discovery set, there were 3613 differentially methylated cytosine phosphate guanosine sites and these differential methylation positions were located within 1938 unique genes, including 1758 hypermethylated genes, 150 hypomethylated genes, and the coexistence of hypermethylation and hypomethylation sites were found in 30 genes. There were 1111 differential transcripts in PD compared to normal controls (850 down-regulated and 261 up-regulated). Further, 212 differentially expressed genes were screened (40 up-regulated and 172 down-regulated). In the validation set, compared with HCs, there was no significant difference in DNA methylation level of Casitas B-lineage lymphoma (CBL) gene loci (cg07123846). The expression level of CBL gene in PD patients was lower (vs. HCs). After four weeks' treatment, the baseline expression level of CBL gene in the responders was higher than nonresponders. LimitationsThe sample size was limited. We only chose CBL as a candidate gene. Follow-up periods were short. ConclusionsThere are differences in genome-wide DNA methylation and mRNA expression between PD patients and HCs. The changes in expression level of CBL gene may be an important molecular marker for PD diagnosis and early response.

Reading young adult South Africans’ reading of national television news

This article introduces a theoretical perspective on young adults’ television news-viewing choicesgrounded in the synthesis of reception aesthetics, socialisation theory and qualitative researchmethodology. It argues that this theoretical framework allows for a deeper contextual reading of thereader-text relationship and for the argument that, despite post-apartheid social transformation,young adult South Africans’ readings of locally produced television news texts are still ideologicallysituated sociocultural imports traceable to their differential class, race and gender positions in thecountry’s social structure. Evidence produced through focus-group interviews is used to supportthe position of the introduced theoretical framework.

Bioinformatic analysis and experimental validation identified DNA methylation-Related biomarkers and immune-cell infiltration of atherosclerosis.

Background: DNA methylation is an important form of epigenetic regulation and is closely related to atherosclerosis (AS). The purpose of this study was to identify DNA methylation–related biomarkers and explore the immune-infiltrate characteristics of AS based on methylation data. Methods: DNA methylation data of 15 atherosclerotic and paired healthy tissues were obtained from Gene Expression Omnibus database. Differential methylation positions (DMPs) and differential methylation regions (DMRs) were screened by the ChAMP R package. The methylation levels of DMPs located on CpG islands of gene promoter regions were averaged. The limma R package was used to screen differentially methylated genes in the CpG islands of the promoter regions. The diagnostic values of the methylation levels were evaluated using the pROC R package. The EpiDISH algorithm was applied to quantify the infiltration levels of seven types of immune cells. Subsequently, three pairs of clinical specimens of coronary atherosclerosis with Stary’s pathological stage III were collected, and the methylation levels were detected by the methylation-specific PCR (MS-PCR) assay. Western blot was performed to detect the protein expression levels of monocyte markers. Results: A total of 110, 695 DMPs, and 918 DMRs were screened in the whole genome. Also, six genes with significant methylation differences in the CpG islands of the promoter regions were identified, including 49 DMPs. In total, three genes (GRIK2, HOXA2, and HOXA3) had delta beta greater than 0.2. The infiltration level of monocytes was significantly upregulated in AS tissues. MS-PCR assay confirmed the methylation status of the aforementioned three genes in AS samples. The Western blot results showed that the expression levels of the monocyte marker CD14 and M1-type macrophage marker CD86 were significantly increased in AS while M2-type macrophage marker protein CD206 was significantly decreased. Conclusion: This study identified potential DNA methylation–related biomarkers and revealed the role of monocytes in early AS.

Comparative Study of Seismic Analysis of Multi- Story Buildings with Floating Columns on Differential Positions and Floors in ZONE IV and ZONE V

Abstract: In urban area nowadays commercial as well as residential buildings on its lower floors require large spaces for banquet hall, malls, parking area and for other amenities. For fulfilling these requirements floating columns are generally provided to gain ample space in building structure. As per IS Code 1893:2016 clause no-7.1. The criteria of providing floating column is prohibited, but there is no limitation and restriction for research work. This study highlights the seismic response of a building and to analyze the structure in which there will be less damages to the structure with the presence of the floating column. This study features the significance of unequivocally perceiving the presence of the drifting section in the examination of building. It deals with the software model which validate with literature studies with RC G+12 building model in seismic zone IV and V with different case studies and floating column is provided in columns exterior, interior and core columns consequently. Time history analysis method for seismic analysis of models, various seismic parameters such as time histor of floor displacement, inter storey drift, base shear, overturning moment are compared to find out the most optimized solution. An Evaluation package of ETABS 2016 has been utilized for analyzing the above Building Structure. To keep away from unfriendly impact of seismic power, substitute measures, including firmness equilibrium of the main story and the story above, are proposed to lessen the abnormality presented by the drifting sections by concentrating on various utilization of appropriate technique.

867 Epigenomic and gene expression defects in sezary syndrome

Sezary syndrome (SS) is an aggressive cutaneous T-cell lymphoma with significant dysregulated gene expression. To understand the role of epigenetic alterations in SS, we interrogated the DNA methylome in SS and normal T cells using Illumina 850k Methylation Beadchip for differential DNA methylation which affects the transcriptome. The study identified significant differential methylated positions (DMP)(10%) with beta-values that differ between the SS cohort compared to normal cohort were identified.

Analyzing differences between parent- and self-report measures with a latent space approach

We explore potential cross-informant discrepancies between child- and parent-report measures with an example of the Child Behavior Checklist (CBCL) and the Youth Self Report (YSR), parent- and self-report measures on children’s behavioral and emotional problems. We propose a new way of examining the parent- and child-report differences with an interaction map estimated using a Latent Space Item Response Model (LSIRM). The interaction map enables the investigation of the dependency between items, between respondents, and between items and respondents, which is not possible with the conventional approach. The LSIRM captures the differential positions of items and respondents in the latent spaces for CBCL and YSR and identifies the relationships between each respondent and item according to their dependent structures. The results suggest that the analysis of item response in the latent space using the LSIRM is beneficial in uncovering the differential structures embedded in the response data obtained from different perspectives in children and their parents. This study also argues that the differential hidden structures of children and parents’ responses should be taken together to evaluate children’s behavioral problems.

DNA Methylation-Related circRNA_0116449 Is Involved in Lipid Peroxidation in Traumatic Brain Injury.

Circular ribonucleic acid (circRNA) has a critical effect in central nervous diseases; however, the exact role of circRNAs in human traumatic brain injury (TBI) remains elusive. Epigenetic modifications, such as DNA methylation, can modify the mRNA level of genes without changing their related DNA sequence in response to brain insults. We hypothesized that DNA methylation-related circRNAs may be implicated in the mechanisms of TBI. The methylation-related circ_0116449 was identified from differential methylation positions and shown to reduce the neuronal loss and lipid markers. Mechanical study indicated that circ_0116449 functions as a miR-142-3p sponge and increases the expression of its target gene: NR1D2, together with NR1D1 and RORA to suppress lipid peroxidation both in vitro and in vivo. Our study suggests that DNA methylation-related circ_0116449 may be a novel target for regulating lipid metabolism in TBI.