Methylation Index Research Articles

Sex-Specific Methylation Indices Improve Risk Detection for Kidney Disease in the PROFIL Diabetes Study

Sex-Specific Methylation Indices Improve Risk Detection for Kidney Disease in the PROFIL Diabetes Study

Effects of early-life amino acids supplementation on fish responses to a thermal challenge.

Nutritional programming is a promising concept for promoting metabolic adaptation of fish to challenging conditions, such as the increase in water temperature. The present work evaluates in ovo arginine or glutamine supplementation as enhancers of zebrafish metabolic or absorptive capacity, respectively, at optimum (28 ºC) and challenging temperatures (32 ºC) in the long-term. Growth performance, free amino acids profile, methylation index and the activity levels of digestive and intermediary metabolism enzymes were analysed to assess the metabolic plasticity induced by an early nutritional intervention. Temperature affected fish larvae growth performance. At the end of the experimental period 28 ºC-fish showed higher dry weight than 32 ºC-fish. The effects of the early supplementation were reflected in the larval free amino acids profile at the end of the experiment. Higher methylation potential was observed in the ARG-fish. In ovo amino acid supplementation modulated the metabolic response in zebrafish larvae, however, the magnitude of this effect differed according to the amino acid and the temperature. Overall, arginine supplementation enhanced carbohydrates metabolism at 32 ºC. In conclusion, the present work suggests that in ovo arginine supplementation may promote a better adaptive response to higher temperatures.

LINE-1 methylation index correlates with sister chromatid exchanges and chromatid but not chromosome aberrations in personnel from a nuclear chemical facility with incorporated plutonium-239

LINE-1 methylation index correlates with sister chromatid exchanges and chromatid but not chromosome aberrations in personnel from a nuclear chemical facility with incorporated plutonium-239

Decoupled terrestrial temperature and hydroclimate during the Plio-Pleistocene in the East Asian monsoonal region

The independent reconstructions of temperature and hydroclimate records are crucial to understanding past changes in Earth's climate. However, the temperature and hydroclimate history of East Asia during the late Cenozoic remains largely unknown. Here, we reconstructed terrestrial temperature and hydroclimate patterns in the East Asian monsoonal regions using GDGTs (glycerol dialkyl glycerol tetraethers) in a sediment core from North China spanning 5.5 million years (Ma). Our data show a decoupled terrestrial temperature and hydroclimate evolution over the past 5.5 Ma. The methylation index of branched GDGTs (brGDGTs), i.e. MBT'5ME-inferred temperature, significantly decreases at ∼2.6 Ma and likely reflects a response to Northern Hemisphere glaciation (NHG), in agreement with multiple marine temperature records. The MBT'5ME temperature record shows a decline of approximately 6.5 °C at around 2.6 Ma, which is larger than the decline recorded in marine sequences. Interestingly, this temperature decline occurs much later than the large GDGT-inferred (i.e., Ri/b and GDGT-0/Cren) increase in rainfall at ∼4.0 Ma, which aligns with the strengthening of Pacific zonal and meridional sea surface temperature (SST) gradients as well as the increased marine-land temperature gradients. Our study thus suggests differing mechanisms driving temperature and hydroclimate evolution in East Asia during the Plio-Pleistocene.

Hypermethylation of genes on chromosome 3p as a biomarker for nasopharyngeal carcinoma diagnosis: A Vietnamese case-control study.

The crucial event driving nasopharyngeal tumorigenesis is the hypermethylation of chromosome 3p-located tumor suppressor genes. This case-control study aims to investigate the methylation characteristics of RASSF1A, Blu, ADAMTS9, and DLEC1 to potentially develop effective diagnostic biomarkers for nasopharyngeal carcinoma, either individually or in combination. The methylation of RASSF1A, Blu, ADAMTS9, and DLEC1 in the collection of 93 biopsy samples and 100 healthy swab specimens were evaluated by Nested methylation-specific polymerase chain reaction. The strength of the correlation between candidate genes and nasopharyngeal carcinoma was estimated by the evaluation of odds ratios (ORs). Promoter hypermethylation of RASSF1A, Blu, ADAMTS9, and DLEC1 were found in 60.22%, 80.65%, 62.37%, and 74.19%, respectively, in nasopharyngeal carcinoma tumors. A significant association between the methylation status of candidate genes with nasopharyngeal carcinoma was reported. The methylation of candidate genes significantly increased the risk of nasopharyngeal carcinoma in cancerous samples compared with control samples (OR > 1). Based on the value of the methylation index, methylation of at least one gene was found in 95.70% of nasopharyngeal tumors. Additionally, the methylation index among 93 tumors significantly correlated with advanced stage nasopharyngeal tumors. The study explored a higher frequency of hypermethylation at least one candidate gene. Methylation of a panel of potential genes can be utilized to discriminate between nasopharyngeal carcinoma and non-cancer cells, particularly in the advanced stages of nasopharyngeal carcinoma. Thus, it could serve as a valuable marker for the diagnosis and monitoring of nasopharyngeal carcinoma.

Methylation of Interleukin-1 receptor-associated kinase-3 and the risk of multiple sclerosis relapse/activity

This study retrospectively investigated the impact of interleukin-1 receptor-associated kinase-3 (IRAK-3/IRAK-M) silencing by methylation on the likelihood of multiple sclerosis (MS) activity. This cross-sectional study included 90 patients with MS: 45 with active disease (Group 1), 45 in remission (Group 2), and 45 healthy controls. The study included quantitation of IRAK-3 methylation index (MI%), IRAK-3 mRNA, and myeloid differentiation factor88 (MyD88) and assessment of NF-κB activity.IRAK-3 MI% was significantly higher in group 1 compared to group 2, accompanied by lower IRAK-3 mRNA expression, elevated circulating MyD88, and increased NF-κB activity. IRAK-3 MI% correlated negatively with its transcript and positively with MyD88 and NF-κB activity. A logistic regression model was created to predict active demyelination. The C-index was 0.924, which indicates a very strong prediction model. Within the limitations of current work, IRAK-3 methylation level seems to be a promising candidate biomarker for identifying MS patients at risk of relapse.

Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility

Our study aimed to establish the association of polymorphic variants and disease susceptibility in arsenic-induced metabolic disorders raised due to the variability of arsenic methylation in human population exposed to arsenic in drinking water. Water samples were systematically collected from various regions of Faisalabad, Pakistan, and subjected to arsenic quantification through inductively coupled plasma emission spectrophotometry (ICP-OES). The groundwater exhibited significantly elevated arsenic concentrations (68.18 ± 21.28 μg/L) in comparison to both water and sanitation agency Faisalabad (WASA)-supplied water (9.81 ± 1.2 μg/L) and locally filtered water (8.12 ± 1.42 μg/L), as determined by one-way ANOVA followed by Bonferroni's post-test at P < 0.05. An association was established between arsenic concentration and the incidence of disease, such as diabetes mellitus. A cohort of 120 participants residing in six areas of District Faisalabad was recruited. Urine and blood specimens were collected for analysis. Urine samples underwent ICP-MS analysis in helium collision mode, utilizing germanium as an internal standard. Blood samples were collected for biomarker assessments, including HbA1c, BUN, creatinine, CRP, ALT, AST, GSH, SOD, and MDA, to investigate the evidence of diabetes mellitus. Urinary arsenic concentrations were found to be considerably higher (P < 0.05) in about 22.50 % of the participants, with a mean value of 68.43 ± 16.73 ppb. Biomarker analysis in these participants revealed mean values for BUN (37.19 ± 2.87 mg/dL), creatinine (2.58 ± 0.18 mg/dL), IL-6 (11.35 ± 6.98 pg/mL), CRP (1.90 ± 0.26 mg/dL), MDA (3.70 ± 0.18 nmol/mL), ALT (40.27 ± 5.41 U/L), and AST (38.92 ± 4.72 U/L). Furthermore, the gender-based analysis indicated the higher levels of DMA, MMA, TAs, and TiAs in males compared to females when urine samples were analyzed with HPLC-ICP-MS. Participants with the positive genotype of GSTM exhibited significantly higher levels of TAs, and TiAs concentration in their urine than those with the null genotype of GSTM. Moreover, participants with positive genotypes for GSTT1 and GSTM1 demonstrated elevated levels of DMA in their urine compared to those with genotypes of GSTT1 (−) and GSTM1 (−), although this difference did not attain statistical significance. Participants with the genotype of GSTT1 (+) displayed a considerably higher secondary methylation index than those with genotype of GSTT1 (−). MMA and DMA levels were found to be correlated with the genotypes of GSTT1 and GSTM1 and the amounts of TAs in urine. In conclusion, our findings suggest a linkage between arsenic methylation, particularly levels of DMA and SMI, and GSTT1 and GSTM1 polymorphisms.

Late Miocene cooling and uplift recorded by bacterial H-GDGTs in the Xining Basin, northeastern Tibetan Plateau

The uplift history of the Tibetan Plateau (TP) remains uncertain despite many scientific studies. The development of a novel paleoaltimeter may provide a crucial tool for addressing this issue. H-shaped glycerol dialkyl glycerol tetraethers (H-GDGTs) are analogs of GDGTs and considered to have potential in paleotemperature reconstructions, becoming, in turn, a potential indicator of paleoaltitude. This study analyzed the H-GDGTs in Late Miocene sediments from the Mojiazhuang (MJZ) Section in the Xining Basin (XB) and evaluated the potential of these less-explored biomarkers in paleotemperature and paleoaltitude reconstructions. Only branched H-GDGTs (H-brGDGTs) were detected; their relative abundance in relation to brGDGTs (%H-brGDGTs) exhibited a strong correlation with proxy-based palaeotemperature. However, their exceptionally elevated values necessarily impose limitations on the feasibility of quantitatively reconstructing paleotemperatures based on %H-brGDGTs, rendering them suitable solely as a qualitative temperature indicator. The methylation index of H-brGDGTs (H-MBTacyclic) can be effectively used to quantitatively reconstruct paleotemperatures. The challenge H-MBTacyclic poses is its potentially limited use for lower temperatures, as it may exhibit incomplete detection of H-brGDGT components. These provisos being the case, both %H-brGDGTs and H-MBTacyclic were nonetheless effectively used to document the cooling and TP uplift event in the XB during the ∼10.5–8 Ma period, aligning with the reconstruction based on brGDGTs. The quantitative paleoaltitude reconstruction using H-MBTacyclic values indicated an uplift amplitude of ∼1 km. As an independent proxy of paleotemperature and paleoaltitude, H-brGDGTs once again would appear to underscore the presence and significance of this Late Miocene uplift event. Given the challenges encountered when using H-brGDGT-based proxies, further investigations into modern samples and evaluations of deep-time samples are imperative for any future application.

Effect of Lead Exposure and Lifestyle Factors on Methylation Index Markers Among Pb-Exposed Workers.

S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and the ratio of SAM and SAH in Pb-exposed workers need to be assessed. In this study, we investigated the effects of Pb exposure on SAM, SAH, and methylation index (MI) in Pb-exposed workers with contemplation of lifestyle factors. Blood lead levels (BLLs), SAM, SAH, MI, and lifestyle factors were assessed in 338 male Pb-exposed workers. BLLs are estimated by ICP-OES method. SAM and SAH levels in serum were determined by ELISA method. The MI was calculated using SAM and SAH individual values. The lifestyle factors were collected using standard questionnaire. Levels of SAM and MI were significantly decreased with increased age, experience > 5 years, habits of tobacco chewing, smoking, alcohol consumption, and BLLs 10-30, 30-50, and > 50 µg/dL. Levels of SAH were significantly increased with increased age, habits of tobacco chewing and smoking, and BLLs 10-30, 30-50, and > 50 µg/dL. The association between BLLs and methylation index markers (SAM and MI) was reported as negative and significant. The association between BLLs and SAH was noted positive and significant. The influence of BLLs and lifestyle factors on SAM was noted at 12%, SAH at 35%, and MI at 27%, respectively. The highest percentage of influence was noted in SAH, followed by MI and SAM. In the workers exposed to Pb, lifestyle factors resulted in decreased SAM and MI and increased SAH levels. Adaptation of healthy lifestyle factors, personal hygiene practices, and use of PPE were suggested to minimize the reduction of methylation index markers.

The alleviation effect and its mechanism of Niuhuang Jiedu prescription on realgar-induced genotoxicity in mice

Ethnopharmacological relevanceRealgar (As2S2 or As4S4) is a traditional Chinese medicine (TCM) containing arsenic. Existing studies have shown that it has genotoxicity under long-term use with large doses. Niuhuang Jiedu (NHJD) is a Chinese medicine prescription containing realgar and seven other TCMs. Whether the multiple TCMs combination in NHJD can reduce the genotoxicity induced by realgar in equivalent doses is still unknown. Aim of the studyTo research the effect of NHJD on realgar's genotoxicity and the possible mechanism involved based on the arsenic methylation metabolic pathway. Material and methodsSix groups (control, realgar (0.8 g/kg), NHJD (12.48 g/kg), as well as Glycyrrhiza uralensis Fisch (GU), Scutellaria baicalensis Georg (SB), Rheum palmatum L (RP) plus equivalent doses of realgar, respectively) were set up. ICR mice were intragastric administered for 12 weeks. First, genotoxicology tests were conducted to evaluate the effect of NHJD, GU, SB, and RP on reducing realgar's genotoxicity. The inorganic arsenic (iAs), dimethyl arsenic acid (DMA), and monomethyl arsenic acid (MMA) were determined by HPLC-AFS, and the iAs%, MMA%, DMA%, primary methylation index (PMI), etc. Were calculated. Meanwhile, the S-adenosyl methionine (SAM) and arsenate reductase (ARR) levels, the arsenic (+3)methyltransferase (As3MT), purine-nucleoside phosphorylase (PNP), glutathione S-transfer omega1 (GSTO1) gene expression were detected, aimed to explore the possible alleviation mechanisms of NHJD. ResultsThe combination of multiple TCMs in NHJD decreased the levels of MN‰, SPA%, and DNA damage caused by realgar, with similar effects observed when SB, RP, and GU were used separately with realgar. Notably, the iAs% significantly decreased, while DMA% and PMI notably increased in the NHJD and realgar + SB (or RP) groups compared to the realgar-only group (P < 0.05). Increases in SAM and ARR levels were observed across various groups, but only the ARR increase in the NHJD group was statistically significant. Moreover, significant increases in As3MT mRNA and GSTO1 mRNA were noted in the NHJD group, and PNP mRNA levels significantly rose in the realgar + SB group. ConclusionsThis study revealed that NHJD could attenuate the genotoxic effects of realgar. The botanicals SB, RP, and GU within NHJD may be key contributors to this effect. Enhancements in arsenic methylation capabilities through increased levels of SAM and ARR and elevated gene expressions of As3MT, PNP, and GSTO1 suggest potential mechanisms behind these findings.

Distributions of bacterial branched tetraether lipids associated with bacterial communities in hummock and hollow soils from Southern Tibetan peatland

Branched glycerol dialkyl glycerol tetraethers (brGDGTs), special membrane-spanning lipids derived from some bacteria, are widely used as molecular tools in paleoenvironmental studies to reconstruct terrestrial temperature and pH conditions. However, the impact of microtopography discrepancies on the accuracy and applicability of brGDGT-based proxies remains unclear. Here we investigated the distributional patterns of brGDGTs and bacterial communities within the hummock-hollow microtopography in the mid-southern Tibetan peatlands. Our results show that the methylation index of C5-methyl brGDGTs (MBT′5ME) values are significantly correlated with the local mean annual air temperature (MAAT). However, the peat-specific temperature calibration exhibits an underestimation of MAATpeat compared to the present MAAT. We find the MBT′5ME values are significantly lower in the moist hollows than that in the drier hummocks. This discrepancy could be primarily attributed to the shifts in bacterial communities and the physiological adaptation of brGDGT-producing bacteria driven by the high soil water content. These findings highlight the remarkable variability of MBT′5ME values at small spatial scales, which holds profound implications for paleotemperature reconstruction in alpine peatlands.

Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children

BackgroundInorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth. MethodsA total of 240 participants (8–11 years, 53 % female) drinking from wells with arsenic concentrations > 50 μg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 μg FA + 5 μg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine. ResultsAt baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 μg/L and 91.2 ± 89.5 μg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and −1.10% (95% CI: −1.73, −0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline. ConclusionThis RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status.

Strong linkage between benthic oxygen uptake and bacterial tetraether lipids in deep-sea trench regions

Oxygen in marine sediments regulates many key biogeochemical processes, playing a crucial role in shaping Earth’s climate and benthic ecosystems. In this context, branched glycerol dialkyl glycerol tetraethers (brGDGTs), essential biomarkers in paleoenvironmental research, exhibit an as-yet-unresolved association with sediment oxygen conditions. Here, we investigated brGDGTs in sediments from three deep-sea regions (4045 to 10,100 m water depth) dominated by three respective trench systems and integrated the results with in situ oxygen microprofile data. Our results demonstrate robust correlations between diffusive oxygen uptake (DOU) obtained from microprofiles and brGDGT methylation and isomerization degrees, indicating their primary production within sediments and their strong linkage with microbial diagenetic activity. We establish a quantitative relationship between the Isomerization and Methylation index of Branched Tetraethers (IMBT) and DOU, suggesting its potential validity across deep-sea environments. Increased brGDGT methylation and isomerization likely enhance the fitness of source organisms in deep-sea habitats. Our study positions brGDGTs as a promising tool for quantifying benthic DOU in deep-sea settings, where DOU is a key metric for assessing sedimentary organic carbon degradation and microbial activity.

LINE-1 Methylation Index Correlates with Sister Chromatid Exchanges and Chromatid but Not Chromosome Aberrations in Personnel from a Nuclear Chemical Facility with Incorporated Plutonium-239

LINE-1 Methylation Index Correlates with Sister Chromatid Exchanges and Chromatid but Not Chromosome Aberrations in Personnel from a Nuclear Chemical Facility with Incorporated Plutonium-239

Combined DNA Methylation and Gastric Microbiome Marker Predicts Helicobacter pylori-Negative Gastric Cancer.

While DNA methylation and gastric microbiome are each associated with gastric cancer (GC), their combined role in predicting GC remains unclear. This study investigated the potential of a combined DNA methylation and gastric microbiome signature to predict Helicobacter pylori-negative GC. In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of DKK3, SFRP1, EMX1, NKX6-1, MIR124-3, and TWIST1 in the gastric mucosa from 75 H. pylori-negative patients, including chronic gastritis (CG), intestinal metaplasia (IM), and GC. A combined analysis of DNA methylation and gastric microbiome, using 16S rRNA gene sequencing, was performed in 30 of 75 patients. The methylation levels of DKK3, SFRP1, EMX1, MIR124-3, and TWIST1 were significantly higher in patients with GC than in controls (all q<0.05). MIR124-3 and TWIST1 methylation levels were higher in patients with IM than those with CG and also in those with GC than in those with IM (all q<0.05). A higher methylation level of TWIST1 was an independent predictor for H. pylori-negative GC after adjusting for age, sex, and atrophy (odds ratio [OR], 15.15; 95% confidence interval [CI], 1.58 to 145.46; p=0.018). The combination of TWIST1 methylation and GC microbiome index (a microbiome marker) was significantly associated with H. pylori-negative GC after adjusting for age, sex, and atrophy (OR, 50.00; 95% CI, 1.69 to 1,476; p=0.024). The combination of TWIST1 methylation and GC microbiome index may offer potential as a biomarker for predicting H. pylori-negative GC.

Peatland warming influences the abundance and distribution of branched tetraether lipids: Implications for temperature reconstruction

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are bacterial membrane lipids whose distribution in peatland soils serves as an important proxy for past climate changes due to strong linear correlations with temperature in modern environments. However, commonly used brGDGT-based temperature models are characterized by high uncertainty (ca. 4 °C) and these calibrations can show implausible correlations when applied at an ecosystem level. This lack of accuracy is often attributed to our limited understanding of the exact mechanisms behind the relationship between brGDGTs and temperature and the potential effect of temperature-independent factors on brGDGT distribution. Here, we examine the abundance and distribution of brGDGTs in a boreal peatland after four years of in-situ warming (+0, +2.25, +4.5, +6.75 and +9 °C). We observed that with warming, concentrations of total brGDGTs increased. Furthermore, we determined a shift in brGDGT distribution in the surface aerobic layers of the acrotelm (0–30 cm depth), whereas no detectable change was observed at deeper anaerobic depths (>40 cm), possibly due to limited microbial activity. The response of brGDGTs to warming was also reflected by a strong increase in the methylation index of 5-methyl brGDGTs (MBT′5Me), classically used as a temperature proxy. Further, the relationship between the MBT′5Me index and soil temperature differed between 0–10, 10–20 and 20–30 cm depth, highlighting depth-specific response of brGDGTs to warming, which should be considered in paleoenvironmental and paleoecological studies. As the bacterial community composition was generally unaltered, the rapid changes in brGDGT distribution argue for a physiological adaptation of the microorganisms producing these lipids. Finally, soil temperature and water table depth were better predictors of brGDGT concentration and distribution, highlighting the potential for these drivers to impact brGDGT-based proxies. To summarize, our results provide insights on the response of brGDGT source microorganisms to soil warming and underscore brGDGTs as viable temperature proxies for better understanding of climatic perturbation in peatlands.

Associations of arsenic exposure and arsenic metabolism with the risk of non-alcoholic fatty liver disease

Growing evidences supported that arsenic exposure contributes to non-alcoholic fatty liver disease (NAFLD) risk, but findings were still inconsistent. Additionally, once absorbed, arsenic is methylated into monomethyl and dimethyl arsenicals. However, no studies investigated the association of arsenic metabolism with NAFLD. Our objectives were to evaluate the associations of arsenic exposure and arsenic metabolism with NAFLD prevalence. We conducted a case-control study with 1790 participants derived from Dongfeng-Tongji cohort and measured arsenic species (arsenite, arsenate, monomethylarsonate [MMA], dimethylarsinate [DMA], and arsenobetaine) in urine. Arsenic exposure (∑As) was defined as the sum of inorganic arsenic (iAs), MMA, and DMA. Arsenic metabolism was evaluated as the proportions of inorganic-related species (iAs%, MMA%, and DMA%) and methylation efficiency ratios (primary methylation index [PMI], secondary methylation index [SMI]). NAFLD was diagnosed by liver ultrasound. Logistic regression was used to evaluate the associations. The median of ∑As was 13.24 μg/g creatinine. The ∑As showed positive and nonlinear association with moderate/severe NAFLD (OR: per log-SD = 1.33, 95% CI: [1.03,1.71]; Pfor nonlinearity = 0.021). The iAs% (OR: per SD = 1.16, 95% CI: [1.03,1.30]) and SMI (OR: per log-SD = 1.16, 95% CI: [1.03,1.31]) showed positive while MMA% (OR: per SD = 0.80, 95% CI: [0.70,0.91]) and PMI (OR: per log-SD = 0.86, 95% CI: [0.77,0.96]) showed inverse associations with NAFLD. Moreover, the ORs (95% CI) of NAFLD for each 5% increase in iAs% was 1.36 (1.17,1.58) when MMA% decreased and 1.07 (1.01,1.13) when DMA% decreased; and for each 5% increase in MMA%, it was 0.74 (0.63,0.86) and 0.79 (0.69,0.91) when iAs% and DMA% decreased, respectively. The results suggest that inorganic arsenic exposure is positively associated with NAFLD risk and arsenic methylation efficiency plays a role in the NAFLD. The findings provide clues to explore potential interventions for the prevention of NAFLD. Prospective studies are needed to validate our findings.

Positive Association of Urinary Dimethylarsinic Acid (DMAV) with Serum 25(OH)D in Adults Living in an Area of Water-Borne Arsenicosis in Shanxi, China.

Limited studies have demonstrated that inorganic arsenic exposure is positively associated with serum vitamin D levels, although the correlation between urinary arsenic species and serum vitamin D has not been investigated in areas of water-borne arsenicosis. A cross-sectional study of 762 participants was conducted in Wenshui Country, Shanxi Province, a water-borne arsenicosis area. The results showed a positive relationship between urinary arsenic species (inorganic arsenic (iAs), methylarsonic acid (MMAV), dimethylarsinic acid (DMAV) and serum 25(OH)D. Log-binomial regression analysis indicated a 0.4% increase in the risk of vitamin D excess for every 1-unit increment in the Box-Cox transformed urinary DMAV after adjustment for covariates. After stratifying populations by inorganic arsenic methylation metabolic capacity, serum 25(OH)D levels in the populations with iAs% above the median and primary methylation index (PMI) below the median increased by 0.064 ng/mL (95% CI: 0.032 to 0.096) for every one-unit increase in the Box-Cox transformed total arsenic (tAs) levels. Serum 25(OH)D levels increased by 0.592 ng/mL (95% CI: 0.041 to 1.143) for every one-unit rise in the Box-Cox transformed iAs levels in people with skin hyperkeratosis. Overall, our findings support a positive relationship between urinary arsenic species and serum 25(OH)D. It was recommended that those residing in regions with water-borne arsenicosis should take moderate vitamin D supplements to avoid vitamin D poisoning.

Branched GDGT source shift identification allows improved reconstruction of an 8,000-year warming trend on Sumatra

Branched Glycerol Dialkyl Glycerol Tetraethers (brGDGTs) in sedimentary archives are increasingly used for paleotemperature reconstructions due to their strong correlation with mean annual air temperature. However, environmental factors can influence the brGDGT producing bacterial community, potentially affecting the brGDGT-temperature relationship and introducing fundamental errors in reconstructions. Here we assess the reliability of the methylation index of brGDGTs (MBT′5ME) in sediments as a paleotemperature proxy by tracking provenance differences based on brGDGT fractional abundances in a short lake core, two peat cores and surface soils on Sumatra (n = 333 in total). Then, we attempt to reconstruct the Holocene paleotemperatures on Sumatra using the two peat cores. Our results indicate distinct brGDGT and H-shaped brGDGT (H-GDGT) compositions in soil, lake and peat environments, suggesting production by different bacterial communities. We introduce a new index, the isomerization of H-GDGTs (IRH) that can distinguish between these environments. In an 11,000-year long peat core from Diatas, we find that brGDGT composition changes are dominated by bacterial community shifts rather than temperature changes. In contrast, a core from the nearby Padang peatland can be robustly used for a brGDGT-based paleotemperature reconstruction since there are no signs of past environmental or brGDGT source shifts. The results from Padang indicate a gradual warming trend over the past 8,000 years, consistent with climate model simulations and nearby sea surface temperature reconstructions. However, current MBT′5ME calibrations yield larger warming trends compared to simulations and other proxy studies, suggesting the need for tropical and/or peat-specific brGDGT temperature calibrations. Our findings demonstrate the importance of assessing environmental shifts and bacterial source community changes when employing brGDGT paleothermometry. The methodological framework outlined in this study can be used in future research for reliable down-core brGDGT temperature reconstructions. Our proxy reconstruction over the past 8,000 years offers novel insights into the Holocene temperature evolution from a region with low climate seasonality.

Quadrato Motor Training (QMT) is associated with DNA methylation changes at DNA repeats: A pilot study.

The control of non-coding repeated DNA by DNA methylation plays an important role in genomic stability, contributing to health and healthy aging. Mind-body practices can elicit psychophysical wellbeing via epigenetic mechanisms, including DNA methylation. However, in this context the effects of movement meditations have rarely been examined. Consequently, the current study investigates the effects of a specifically structured movement meditation, called the Quadrato Motor Training (QMT) on psychophysical wellbeing and on the methylation level of repeated sequences. An 8-week daily QMT program was administered to healthy women aged 40-60 years and compared with a passive control group matched for gender and age. Psychological well-being was assessed within both groups by using self-reporting scales, including the Meaning in Life Questionnaire [MLQ] and Psychological Wellbeing Scale [PWB]). DNA methylation profiles of repeated sequences (ribosomal DNA, LINE-1 and Alu) were determined in saliva samples by deep-sequencing. In contrast to controls, the QMT group exhibited increased Search for Meaning, decreased Presence of Meaning and increased Positive Relations, suggesting that QMT may lessen the automatic patterns of thinking. In the QMT group, we also found site-specific significant methylation variations in ribosomal DNA and LINE-1 repeats, consistent with increased genome stability. Finally, the correlations found between changes in methylation and psychometric indices (MLQ and PWB) suggest that the observed epigenetic and psychological changes are interrelated. Collectively, the current results indicate that QMT may improve psychophysical health trajectories by influencing the DNA methylation of specific repetitive sequences.