Whole-genome profiling of DNA methylation and hydroxymethylation identifies distinct regulatory programs among innate lymphocytes.

Innate lymphocytes encompass a diverse array of phenotypic identities with specialized functions. DNA methylation and hydroxymethylation are essential for epigenetic fidelity and fate commitment. The landscapes of these modifications are unknown in innate lymphocytes. Here, we characterized the whole-genome distribution of methyl-CpG and 5-hydroxymethylcytosine (5hmC) in mouse innate lymphoid cell 3 (ILC3), ILC2 and natural killer (NK) cells. We identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DHMRs) between ILC and NK cell subsets and correlated them with transcriptional signatures. We associated lineage-determining transcription factors (LDTFs) with demethylation and demonstrated unique patterns of DNA methylation/hydroxymethylation in relationship to open chromatin regions (OCRs), histone modifications and TF-binding sites. We further identified an association between hydroxymethylation and NK cell superenhancers (SEs). Using mice lacking the DNA hydroxymethylase TET2, we showed the requirement for TET2 in optimal production of hallmark cytokines by ILC3s and interleukin-17A (IL-17A) by inflammatory ILC2s. These findings provide a powerful resource for studying innate lymphocyte epigenetic regulation and decode the regulatory logic governing their identity.

A map of cis-regulatory elements and 3D genome structures in zebrafish.

The zebrafish (Danio rerio) has been widely used in the study of human disease and development, and about 70% of the protein-coding genes are conserved between the two species1. However, studies in zebrafish remain constrained by the sparse annotation of functional control elements in the zebrafish genome. Here we performed RNA sequencing, assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing, whole-genome bisulfite sequencing, and chromosome conformation capture (Hi-C) experiments in up to eleven adult and two embryonic tissues to generate a comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin, methylomes and 3D genome organization in the zebrafish Tübingen reference strain. A comparison of zebrafish, human and mouse regulatory elements enabled the identification of both evolutionarily conserved and species-specific regulatory sequences and networks. We observed enrichment of evolutionary breakpoints at topologically associating domain boundaries, which were correlated with strong histone H3 lysine 4 trimethylation (H3K4me3) and CCCTC-binding factor (CTCF) signals. We performed single-cell ATAC-seq in zebrafish brain, which delineated 25 different clusters of cell types. By combining long-read DNA sequencing and Hi-C, we assembled the sex-determining chromosome 4 de novo. Overall, our work provides an additional epigenomic anchor for the functional annotation of vertebrate genomes and the study of evolutionarily conserved elements of 3D genome organization.

A genomic and epigenomic atlas of prostate cancer in Asian populations.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

Epigenomic analysis reveals prevalent contribution of transposable elements to cis-regulatory elements, tissue-specific expression, and alternative promoters in zebrafish.

Transposable elements (TEs) encode regulatory elements that impact gene expression in multiple species, yet a comprehensive analysis of zebrafish TEs in the context of gene regulation is lacking. Here, we systematically investigate the epigenomic and transcriptomic landscape of TEs across 11 adult zebrafish tissues using multidimensional sequencing data. We find that TEs contribute substantially to a diverse array of regulatory elements in the zebrafish genome and that 37% of TEs are positioned in active regulatory states in adult zebrafish tissues. We identify TE subfamilies enriched in highly specific regulatory elements among different tissues. We use transcript assembly to discover TE-derived transcriptional units expressed across tissues. Finally, we show that novel TE-derived promoters can initiate tissue-specific transcription of alternate gene isoforms. This work provides a comprehensive profile of TE activity across normal zebrafish tissues, shedding light on mechanisms underlying the regulation of gene expression in this widely used model organism.

Ambient PM2.5 exposure and rapid population aging: A double threat to public health in the Republic of Korea.

Particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) can infiltrate deep into the respiratory system, posing significant health risks. Notably, the health burden of PM2.5 is more pronounced among the older adult population. With an aging population, the public health burden attributable to PM2.5 could escalate even if the current PM2.5 level remains stable. This study evaluated the number of deaths attributable to long-term PM2.5 exposure in the Republic of Korea between 2020 and 2050 and identified the PM2.5 concentration required at least to maintain the current PM2.5 health burden. To calculate mortality for 2020-2050, we performed a health impact assessment using 3-year (2019-2021) average population-weighted PM2.5 concentrations, age-specific population and mortality rates. In 2020, 33,578 [95% confidence interval (CI) = 31,708-35,448] deaths were attributable to PM2.5 exposure. Projecting forward, if the 2019-2021 average PM2.5 level remains constant, mortality is projected to be 112,953 (95% CI = 109,963-115,943) in 2050, more than three times higher than in 2020. To maintain the same level of health burden in 2050 as in 2020, the PM2.5 concentration needs to be immediately reduced to 5.8 µg/m3. In an age-specific analysis, the proportion of older adults (ages 65+) to total mortality would increase from 83% (2020) to 96% (2050), indicating that the rising mortality is predominantly driven by the aging population. By region, the reduction of PM2.5 concentrations, which is required immediately in 2020 to have the health burden in 2050 equal to that in 2020, varied from 3.6 µg/m3 in Goheung-gun (25% reduction) to 20.8 µg/m3 in Heungdeok-gu (82% reduction). Our study emphasizes the critical need for air quality management to consider aging populations when establishing PM2.5 air quality standards, as well as their associated policies and regulations.

Capabilities of satellite Geostationary Environment Monitoring Spectrometer (GEMS) NO2 data for hourly ambient NO2 exposure modeling.

The Geostationary Environment Monitoring Spectrometer (GEMS) is the world's first geostationary instrument that monitors hourly gaseous air pollutant levels, including nitrogen dioxide (NO2). Using the first-of-its-kind capabilities of GEMS NO2 data, we examined how well GEMS NO2 levels can explain the spatiotemporal variabilities in hourly NO2 concentrations in the Republic of Korea for the year 2022. A correlation analysis between hourly GEMS NO2 levels and ground NO2 concentrations showed a higher spatial correlation [Pearson r = 0.56 (SD = 0.20)] than a temporal one [Pearson r = 0.42 (SD = 0.14)], on average. To take advantage of the enhanced spatial predictability of GEMS NO2 data, we employed a mixed effects model to allow hour-specific relationships between GEMS NO2 and NO2 concentrations on a given day in each region and subsequently estimated hourly NO2 concentrations in all urban and rural areas. The 10-fold cross validation demonstrated R2 = 0.72, mean absolute error (MAE) = 3.7 ppb, and root mean squared error (RMSE) = 5.5 ppb. The hourly variations of the relationships were attributed particularly to those of wind speed among meteorological parameters considered in this study. The spatial distributions of hourly estimated NO2 concentrations were highly correlated between hours [average r = 0.91 (SD = 0.06)]. Nonetheless, they represented the diurnal patterns of urban versus rural NO2 contrasts during the day [urban/rural NO2 ratios from 1.22 (5 p.m.) to 1.37 (12 p.m.)]. The newly retrieved GEMS NO2 data enable temporally as well as spatially resolved NO2 exposure assessment. In combination with the time-activity patterns of individual subjects, the GEMS NO2 data can generate 'sub-population' exposure estimates and therefore enhance health effect studies.

Relationship between short-term ozone exposure, cause-specific mortality, and high-risk populations: A nationwide, time-stratified, case-crossover study.

BACKGROUND: Previous studies reported that short-term exposure to ground-level ozone is associated with mortality risk. However, due to the limited monitored areas, existing studies were limited in assessing the nationwide risk and suggesting specific vulnerable populations to the ozone-mortality risk. METHODS: We performed a nationwide time-stratified case-crossover study to evaluate the association between short-term ozone and cause-specific mortality in South Korea (2015-2019). A machine learning-ensemble prediction model (a test R2 > 0.96) was used to assess the short-term ozone exposure. Stratification analysis was conducted to examine the high-risk populations, and the excess mortality due to non-compliance with the WHO guideline was also assessed. RESULTS: For all-cause mortality (1,343,077 cases), the risk associated with ozone (lag0- 1) was weakly identified (odd ratio: 1.005 with 95% CI: 0.997-1.014), and the risk was prominent in mortality with circulatory system diseases. In addition, based on the point estimates, the ozone-mortality risk was higher in people aged less than 65y, and this pattern was also observed in circulatory system disease deaths and urban areas. CONCLUSIONS: This study provides national estimates of mortality risks associated with short-term ozone. Results showed that the benefits of stricter air quality standards could be greater in vulnerable populations.

Accumulative Charge Separation in a Modular Quaterpyridine Bridging Ligand Platform and Multielectron Transfer Photocatalysis of π-Linked Dinuclear Ir(III)-Re(I) Complex for CO2 Reduction.

Four sterically distorted quaterpyridyl (qpy) ligand-bridged Ir(III)-Re(I) heterometallic complexes (Ir-qpymm-Re, Ir-qpymp-Re, Ir-qpypm-Re, and Ir-qpypp-Re), in which the position of the coupling pyridine unit of the two 2,2'-bipyridine ligands was varied (meta (m)- or para (p)-position), pypyx-pyxpy (x = m and m, qpymm; x = m and p, qpymp; x = p and m, qpypm; x = p and p, qpypp), were prepared, along with the fully π-conjugated Ir(III)-[π linker]-Re(I) complexes (π linker = 2,2'-bipyrimidine (bpm), Ir-bpm-Re; π linker = 2,5-di(pyridin-2-yl)pyrazine (dpp), Ir-dpp-Re) to elucidate the electron mediating and accumulative charge separation properties of the bridging π-linker in a bimetallic system (photosensitizer-π linker-catalytic center). From the photophysical and electrochemical studies, it was found that the quaterpyridyl (qpy) bridging ligand (BL), in which the two planar Ir/Re metalated bipyridine (bpy) ligands were connected but slightly canted relative to each other, linking the heteroleptic Ir(III) photosensitizer, [(piqC^N)2IrIII(bpy)]+, and catalytic Re(I) complex, (bpy)ReI(CO)3Cl, minimized the energy lowering of the qpy BL, which hampers the forward photoinduced electron transfer (PET) process from [(piqC^N)2IrIII(N^N)]+ to (N^N)ReI(CO)3Cl (Ered1 = -(0.85-0.93) V and Ered2 = -(1.15-1.30) V vs SCE). This result contrasts with the fully π-delocalized bimetallic systems (Ir-bpm-Re and Ir-dpp-Re) that show a significant energy reduction due to the considerable π-extension and deshielding effect caused by the neighboring Lewis acidic metals (Ir and Re) on the electrochemical scale (Ered1 = -0.37 V and Ered2 = -1.02 and -0.99 V vs SCE). Based on a series of anion absorption studies and spectroelectrochemical (SEC) analyses, all Ir(III)-BL-Re(I) bimetallic complexes were found to exist as dianionic form (Ir(III)-[BL]2--Re(I)) after a fast reductive-quenching process in the presence of excess electron donor. In the photolysis experiment, the four Ir-qpy-Re complexes displayed the reasonable photochemical CO2-to-CO conversion activities (TON of 366-588 for 19 h) owing to the moderated electronic coupling between two functional Ir(III) and Re(I) centers through the slightly distorted qpy ligand, whereas Ir-bpm-Re and Ir-dpp-Re displayed negligible performances as a result of the strong electronic coupling via π-conjugation between the two functional components resulting in the energetic constraints for PET and an unwanted side reactions competing with the forward processes. These results confirm that the qpy unit can be utilized as an efficient BL platform in π-linked bimetallic systems.

Drought and ozone air quality in California: Identifying susceptible regions in the preparedness of future drought.

California experienced extreme and prolonged drought conditions during the early 2010s. To date, little is known regarding the influence of drought on air quality. Our study quantified site-specific associations between drought (defined by the Standardized Precipitation-Evapotranspiration Index; SPEI) and daily maximum 8-h ozone (O3) concentrations for California, USA, and then pooled these associations for the years 2009-2015. Overall, ambient O3 concentration was higher during droughts by 1.18 ppb (95% confidence interval (CI) = 1.00-1.36). The sensitivity of O3 to drought was greater during the warm season than during the cool season (1.73 ppb versus 0.79 ppb higher O3 during droughts) with substantial regional variation. In a pooled analysis with meteorological parameters as potential effect modifiers, the spatial heterogeneity of drought-O3 associations was explained strongly by average relative humidity for each season (71.9% (warm season) and 73.4% (cool season) of the drought-O3 associations explained), followed by the drought-related changes in relative humidity (47.6% (warm season)) and temperature (53.6% (cool season)). The pooled regression further identified regions susceptible for drought-related O3 increases as those with relatively low average relative humidity (10-25th percentiles or 44.3-47.3%) and larger drought-related decrease in relative humidity and increase in temperature. As the drought events are projected to occur with increased frequency and intensity in the era of climate change, the excess health burdens from O3 exposures attributed to the projected drought events need to be taken into account when allocating air quality and health resources. The impacts of O3 on health during droughts would confound the health burdens from the drought itself.

Benefits of High Resolution PM2.5 Prediction using Satellite MAIAC AOD and Land Use Regression for Exposure Assessment: California Examples.

This study estimated annual average ambient fine particulate matter (PM2.5) concentrations at 1 km resolution using satellite Multi-Angle Implementation of Atmospheric Correction (MAIAC) aerosol optical depth (AOD), land use parameters, and meteorology in California for the year 2016 (cross-validation R2 = 0.73 (site-based) and 0.81 (observation-based)). Using these high-resolution PM2.5 estimates, regionally varying urban enhancements of PM2.5 concentrations, 1.43-2.77 µg/m3 (23.9-36.2%), were identified in the densely populated air basins of San Francisco Bay Area, San Joaquin Valley, and South Coast. On the other hand, within-urban PM2.5 variability was found to be 31.4-35.6% of between-urban variability across California. However, this pattern was not consistent from region to region, even showing higher within-urban variability (e.g., San Francisco Bay Area). In addition, satellite-based PM2.5 concentrations were statistically significantly associated with demographic factors (i.e., % people of color, % poverty, and % low education) with the strongest positive association with % people of color (1.05 and 2.72 µg/m3 increases per interquartile range (IQR) and range increases, respectively). The fine-scale PM2.5 estimates enabled the assessment of long-term PM2.5 exposures for all populations particularly benefiting rural populations and socially vulnerable populations widely distributed in each urban area. This study provided evidence of regionally varying exposure misclassification that would arise without accounting for rural and within-urban exposure variabilities.

Balanced Strain Compensation of In0.07GaAs/Al0.2GaAs/GaAsP0.06 for Improving 940 nm Infrared Light-Emitting Diodes.

Optimum strain compensation structures for In0.07GaAs-based MQWs were investigated to obtain a higher output power for infrared lighting-emitting diodes (IR-LEDs) requiring a 940 nm wave-length. A GaAsP0.06 tensile strain material for compensating the compressive strain of In0.07GaAs quantum wells was used as a quantum barrier. To improve upon the excessive unbalance strain condition caused due to the In0.07GaAs quantum well and GaAsP0.06 quantum barrier, a conditioned Al0.2GaAs strain balancing barrier was also investigated. Through subsequent photoluminescence (PL) measurements, it was found that the GaAsP0.06 tensile strain barrier could effectively compensate for the compressive strain of In0.07GaAs quantum wells. Furthermore, the PL intensity of In0.07GaAs/GaAsP0.06 MQWs was observed to be markedly improved by using an Al0.2GaAs strain balancing barrier. A fabricated IR-LED chip, having In0.07GaAs/GaAsP0.06 MQWs with an Al0.2GaAs strain balancing barrier, showed a 60% higher light output power than conventional MQWs. These results subsequently suggest that using GaAsP0.06 and Al0.2GaAs barriers effectively improved unbalanced strain conditions of lattice-mismatched In0.07GaAs based MQWs requiring a 940 nm emitting wavelength.

Spatial analysis of concentrations of multiple air pollutants using NASA DISCOVER-AQ aircraft measurements: Implications for exposure assessment.

In recent years, multipollutant approaches have been employed to investigate the association with health outcomes to better represent real-world conditions than more traditional analysis that considers a single pollutant. With regard to the exposure assessment of a mixture of air pollutants, it is critical to understand the spatial variability in multipollutant relations in order to assess their potential health implications. In this study, we investigated the spatial relations of multiple pollutant concentrations (i.e., NOx, NOy, black carbon, carbon monoxide, acetaldehyde, formaldehyde, toluene, xylenes/ethylbenzene, ozone, water-soluble organic carbon, and aerosol extinction) observed from the P-3B aircraft in the 2011 NASA field campaign in Baltimore/Washington D.C. areas during July 2011. The between-pollutant Pearson correlations and Z-scores (calculated from log-transformed concentrations) between near-highways and non-highways and between near-urban centers and non-urban centers varied by pollutant pair and space. We found generally lower correlations between NOx and other pollutants for near-highways (average r = 0.36) than for non-highways (average r = 0.41) and also for non-urban centers (average r = 0.37) than for near-urban centers (average r = 0.41). This indicated that the temporal associations between NOx and health outcomes might be less affected by other pollutants, which were also related to same health outcomes, for near-highways and non-urban centers. The analysis of between-pollutant Z-scores showed varying spatial relations for popular traffic-related pollutants with the Z-score differences of 0.43 (NOx-carbon monoxide), 0.29 (NOx-black carbon), and 0.17 (black carbon-carbon monoxide) between near-highways and non-highways. This result exhibited heterogeneous traffic-related pollutant mixtures with the proximity to highways, potentially leading to the diverse extent of health associations. Furthermore, a mixed effects model presented pollutant-specific associations between the concentrations and the proximity to highways and urban centers, showing larger declines for NOx, xylenes/ethylbenzene, toluene, and NOy than those for the pollutants related to secondary pollutant formation. The model also demonstrated the different sensitivity of each pollutant to meteorological parameters, which may modify the spatial and temporal variability in the relations between the pollutants. Our findings provide insights for exposure assessment studies to better understand the cumulative health consequences associated with multiple air pollutants simultaneously.

Study on Strain Compensation for Multiple-Quantum Well in Infrared Light-Emitting Diode Using the InxGa1-xP Strain Barrier.

Strain compensation for multiple-quantum wells (MQWs) relative to the efficiency improvement of infrared light-emitting diodes (IR-LEDs) was investigated through the use of an InxGa1-xP strain barrier. The InxGa1-xP barrier, which was inserted between the n-confinement and active regions, developed for the reduction of lattice-mismatched strains in GaAs/AlGaAs and InGaAs/GaAs MQWs. Through photoluminescence, improved intensity was displayed in InGaAs/GaAs MQWs having InxGa1-xP strain barriers, with a significant increase in the intensity observed at the In0.47GaP strain barrier. This result is attributed to strain compensation between the In0.47GaP tensile strain barrier used and the In0.07GaAs compressive strain in MQWs. Through results based on InGaAs/GaAs MQWs, the highest output power of 6 mW was obtained at the In0.47GaP strain barrier, which shows a relative increase of almost 20% as compared to conventional MQWs.

Prognostic value of decision criteria for emergency liver transplantation in patients with wild mushroom induced acute liver injury.

BACKGROUND: The reported mortality rate of mushroom-induced acute liver failure with conventional treatment is 1.4%-16.9%. Emergency liver transplantation may be indicated and can be the only curative treatment option. This study aimed to assess the prognostic value of criteria for emergency liver transplantation in predicting 28-day mortality in patients with mushroom-induced acute liver injury. METHODS: A retrospective cohort study was performed between January 2005 and December 2015. All adult patients aged≥18 years admitted with mushroom intoxication at our emergency department were evaluated. All patients with acute liver injury, defined as elevation of serum liver enzymes (>5 times the upper limit of normal, ULN) or moderate coagulopathy (INR > 2.0) were included. The ability of the King's College, Ganzert's, and Escudié's criteria to predict 28-day mortality was evaluated. RESULTS: Of the 23 patients with acute liver injury following mushroom intoxication, 10 (43.5%) developed acute liver failure and subsequently died. The mean time interval from ingestion to death was 11.3 ±â€¯6.6 days. Eight patients fulfilled Ganzert's criteria, while 10 patients fulfilled the King's College and Escudié's criteria for emergency liver transplantation. King's College and Escudié's criteria had 100% accuracy in predicting 28-day mortality; however, Escudié's criteria were able to identify fatal cases earlier. CONCLUSIONS: Escudié's criteria demonstrated the best performance with 100% accuracy and the ability to promptly identify fatal cases of mushroom-induced acute liver failure.

Tissue-specific DNA methylation is conserved across human, mouse, and rat, and driven by primary sequence conservation.

BACKGROUND: Uncovering mechanisms of epigenome evolution is an essential step towards understanding the evolution of different cellular phenotypes. While studies have confirmed DNA methylation as a conserved epigenetic mechanism in mammalian development, little is known about the conservation of tissue-specific genome-wide DNA methylation patterns. RESULTS: Using a comparative epigenomics approach, we identified and compared the tissue-specific DNA methylation patterns of rat against those of mouse and human across three shared tissue types. We confirmed that tissue-specific differentially methylated regions are strongly associated with tissue-specific regulatory elements. Comparisons between species revealed that at a minimum 11-37% of tissue-specific DNA methylation patterns are conserved, a phenomenon that we define as epigenetic conservation. Conserved DNA methylation is accompanied by conservation of other epigenetic marks including histone modifications. Although a significant amount of locus-specific methylation is epigenetically conserved, the majority of tissue-specific DNA methylation is not conserved across the species and tissue types that we investigated. Examination of the genetic underpinning of epigenetic conservation suggests that primary sequence conservation is a driving force behind epigenetic conservation. In contrast, evolutionary dynamics of tissue-specific DNA methylation are best explained by the maintenance or turnover of binding sites for important transcription factors. CONCLUSIONS: Our study extends the limited literature of comparative epigenomics and suggests a new paradigm for epigenetic conservation without genetic conservation through analysis of transcription factor binding sites.

Pregnancy and Lifetime Exposure to Fine Particulate Matter and Infant Mortality in Massachusetts, 2001-2007.

Many studies have found associations between particulate matter having an aerodynamic diameter of ≤2.5 µm (PM2.5) and adult mortality. Comparatively few studies evaluated particles and infant mortality, although infants and children are particularly vulnerable to pollution. Moreover, existing studies mostly focused on short-term exposure to larger particles. We investigated PM2.5 exposure during pregnancy and lifetime and postneonatal infant mortality. The study included 465,682 births with 385 deaths in Massachusetts (2001-2007). Exposures were estimated from PM2.5-prediction models based on satellite imagery. We applied extended Cox proportional hazards modeling with time-dependent covariates to total, respiratory, and sudden infant death syndrome mortality. Exposure was calculated from birth to death (or end of eligibility for outcome, at age 1 year) and pregnancy (gestation and each trimester). Models adjusted for sex, birth weight, gestational length, season of birth, temperature, relative humidity, and maternal characteristics. Hazard ratios for total, respiratory, and sudden infant death syndrome mortality per-interquartile-range increase (1.3 µg/m3) in lifetime PM2.5 exposure were 2.66 (95% confidence interval (CI): 2.11, 3.36), 3.14 (95% CI: 2.39, 4.13), and 2.50 (95% CI: 1.56, 4.00), respectively. We did not observe a statistically significant relationship between gestational exposure and mortality. Our findings provide supportive evidence that lifetime exposure to PM2.5 increases risk of infant mortality.

Development of a model for particulate matter pollution in Australia with implications for other satellite-based models.

Estimating exposure to particulate matter (PM10) air pollution concentrations in Australia is challenging due to relatively few monitoring sites relative to the geographic distribution of the population. We modelled daily ground-level PM10 concentrations for the period 2006-2011 for Australia using linear mixed models with satellite remote-sensed AOD, land-use and geographical variables as predictors. The variation in daily PM10 explained by the model was 51% for Australia overall, and ranged from 51% for Tasmania to 78% for South Australia. Cross-validation indicated that the models were most suitable for prediction in New South Wales and Victoria and least suitable for prediction in Western Australia, the Australian Capital Territory and Tasmania. Most of the variation in PM10 concentrations was explained by temporal rather than spatial variation. The inclusion of AOD and other predictors did not substantially improve model performance. Temporal models were sufficient to account for daily PM10 variation recorded by statutory monitors.

Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm.

DNA methylation plays key roles in diverse biological processes such as X chromosome inactivation, transposable element repression, genomic imprinting, and tissue-specific gene expression. Sequencing-based DNA methylation profiling provides an unprecedented opportunity to map and compare complete DNA methylomes. This includes one of the most widely applied technologies for measuring DNA methylation: methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq), coupled with a complementary method, methylation-sensitive restriction enzyme sequencing (MRE-seq). A computational approach that integrates data from these two different but complementary assays and predicts methylation differences between samples has been unavailable. Here, we present a novel integrative statistical framework M&M (for integration of MeDIP-seq and MRE-seq) that dynamically scales, normalizes, and combines MeDIP-seq and MRE-seq data to detect differentially methylated regions. Using sample-matched whole-genome bisulfite sequencing (WGBS) as a gold standard, we demonstrate superior accuracy and reproducibility of M&M compared to existing analytical methods for MeDIP-seq data alone. M&M leverages the complementary nature of MeDIP-seq and MRE-seq data to allow rapid comparative analysis between whole methylomes at a fraction of the cost of WGBS. Comprehensive analysis of nineteen human DNA methylomes with M&M reveals distinct DNA methylation patterns among different tissue types, cell types, and individuals, potentially underscoring divergent epigenetic regulation at different scales of phenotypic diversity. We find that differential DNA methylation at enhancer elements, with concurrent changes in histone modifications and transcription factor binding, is common at the cell, tissue, and individual levels, whereas promoter methylation is more prominent in reinforcing fundamental tissue identities.

Spatial Variability of AERONET Aerosol Optical Properties and Satellite Data in South Korea during NASA DRAGON-Asia Campaign.

We investigated spatial variability in aerosol optical properties, including aerosol optical depth (AOD), fine-mode fraction (FMF), and single scattering albedo (SSA), observed at 21 Aerosol Robotic Network (AERONET) sites and satellite remote sensing data in South Korea during the spring of 2012. These dense AERONET networks established in a National Aeronautics and Space Administration (NASA) field campaign enabled us to examine the spatially detailed aerosol size distribution and composition as well as aerosol levels. The springtime particle air quality was characterized by high background aerosol levels and high contributions of coarse-mode aerosols to total aerosols. We found that between-site correlations and coefficient of divergence for AOD and FMF strongly relied on the distance between sites, particularly in the south-north direction. Higher AOD was related to higher population density and lower distance from highways, and the aerosol size distribution and composition reflected source-specific characteristics. The ratios of satellite NO2 to AOD, which indicate the relative contributions of local combustion sources to aerosol levels, represented higher local contributions in metropolitan Seoul and Pusan. Our study demonstrates that the aerosol levels were determined by both local and regional pollution and that the relative contributions of these pollutions to aerosols generated spatial heterogeneity in the particle air quality.

Enhancing the Applicability of Satellite Remote Sensing for PM2.5 Estimation Using MODIS Deep Blue AOD and Land Use Regression in California, United States.

We estimated daily ground-level PM2.5 concentrations combining Collection 6 deep blue (DB) Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol optical depth (AOD) data (10 km resolution) with land use regression in California, United States, for the period 2006-2012. The Collection 6 DB method for AOD provided more reliable data retrievals over California's bright surface areas than previous data sets. Our DB AOD and PM2.5 data suggested that the PM2.5 predictability could be enhanced by temporally varying PM2.5 and AOD relations at least at a seasonal scale. In this study, we used a mixed effects model that allowed daily variations in DB AOD-PM2.5 relations. Because DB AOD might less effectively represent local source emissions compared to regional ones, we added geographic information system (GIS) predictors into the mixed effects model to further explain PM2.5 concentrations influenced by local sources. A cross validation (CV) mixed effects model revealed reasonably high predictive power for PM2.5 concentrations with R(2) = 0.66. The relations between DB AOD and PM2.5 considerably varied by day, and seasonally varying effects of GIS predictors on PM2.5 suggest season-specific source emissions and atmospheric conditions. This study indicates that DB AOD in combination with land use regression can be particularly useful to generate spatially resolved PM2.5 estimates. This may reduce exposure errors for health effect studies in California. We expect that more detailed PM2.5 concentration patterns can help air quality management plan to meet air quality standards more effectively.