Increased Alu RNA processing in Alzheimer brains is linked to gene expression changes.

Despite significant steps in our understanding of Alzheimer's disease (AD), many of the molecular processes underlying its pathogenesis remain largely unknown. Here, we focus on the role of non-coding RNAs produced by small interspersed nuclear elements (SINEs). RNAs from SINE B2 repeats in mouse and SINE Alu repeats in humans, long regarded as "junk" DNA, control gene expression by binding RNA polymerase II and suppressing transcription. They also possess self-cleaving activity that is accelerated through their interaction with certain proteins disabling this suppression. Here, we show that similar to mouse SINE RNAs, human Alu RNAs, are processed, and the processing rate is increased in brains of AD patients. This increased processing correlates with the activation of genes up-regulated in AD patients, while increased intact Alu RNA levels correlate with down-regulated gene expression in AD. In vitro assays show that processing of Alu RNAs is accelerated by HSF1. Overall, our data show that RNAs from SINE elements in the human brain show a similar pattern of deregulation during amyloid beta pathology as in mouse.

SCNVSim: somatic copy number variation and structure variation simulator.

BACKGROUND: Somatically acquired structure variations (SVs) and copy number variations (CNVs) can induce genetic changes that are directly related to tumor genesis. Somatic SV/CNV detection using next-generation sequencing (NGS) data still faces major challenges introduced by tumor sample characteristics, such as ploidy, heterogeneity, and purity. A simulated cancer genome with known SVs and CNVs can serve as a benchmark for evaluating the performance of existing somatic SV/CNV detection tools and developing new methods. RESULTS: SCNVSim is a tool for simulating somatic CNVs and structure variations SVs. Other than multiple types of SV and CNV events, the tool is capable of simulating important features related to tumor samples including aneuploidy, heterogeneity and purity. CONCLUSIONS: SCNVSim generates the genomes of a cancer cell population with detailed information of copy number status, loss of heterozygosity (LOH), and event break points, which is essential for developing and evaluating somatic CNV and SV detection methods in cancer genomics studies.

Pollutants from primary sources dominate the oxidative potential of water-soluble PM2.5 in Hong Kong in terms of dithiothreitol (DTT) consumption and hydroxyl radical production.

Increasing scientific findings show that the adverse health effects of PM2.5 are related not only to its mass but also PM2.5 sources and chemical compositions. Here, we conducted a comprehensive characterization and source apportionment of oxidative potential (OP) of water-soluble PM2.5 collected in Hong Kong for one year. Two OP indicators, namely dithiothreitol (DTT) consumption and ∙OH formation, were quantified. Six PM2.5 sources, i.e. secondary sulfate, biomass burning, secondary organic aerosol (SOA), vehicle emissions, marine vessels, and a metal-related factor, were apportioned and identified to be DTT active. The four primary sources accounted for 83.5% of DTT activity of water-soluble PM2.5, with the metal-related factor and marine vessels as the leading contributors. However, only three sources, i.e. metal-related factor, vehicle emissions, and SOA, showed ∙OH generation ability, with a predominant contribution of 96.2% from the two primary sources, especially the metal-related factor (84.5%). Based on the source apportionment results, we further evaluate the intrinsic OP of water-soluble PM2.5 from each source. Marine vessels exhibited the highest intrinsic DTT activity; while metal-related factor was most effective in ∙OH generation.

Speciation of carboxylic components in humic-like substances (HULIS) and source apportionment of HULIS in ambient fine aerosols (PM2.5) collected in Hong Kong.

Humic-like substances (HULIS) are an important mixture of organic compounds, which account for a great part of water-soluble organic compounds in ambient aerosols. In this study, individual carboxylic and hydroxylic species in HULIS extracts of PM2.5 samples collected in Hong Kong during summer were measured by gas chromatography mass spectrometry with prior chemical derivatization. Significantly higher levels of HULIS were observed on days mainly impacted by regional pollution (regional days, 4.11 ± 1.76 µg m-3) than on days under local emission influences (local days, 0.56 ± 0.30 µg m-3). Positive matrix factorization was applied to identify the major sources and apportion their contributions to HULIS. Simultaneous monitoring and analysis data from four different sampling sites showed that sources of HULIS in Hong Kong were mainly regional with small spatial variations. Secondary aerosol formation (both organic and inorganic) had a predominant contribution (52.7%) to HULIS during the whole sampling period. It accounted for 1.88 ± 0.91 µg m-3 of HULIS on regional days, which was about 5 times higher than its contribution (0.39 ± 0.34 µg m-3) on local days. Of the three identified primary sources, biomass burning had the largest contribution on both regional (34.9%) and local days (24.6%). Marine vessels were also a significant contributor, especially on local days (20.3%). Vehicle exhaust, on the other hand, showed a negligible contribution to HULIS (2.1%) in Hong Kong in this study.

Correction to: Speciation of carboxylic components in humic-like substances (HULIS) and source apportionment of HULIS in ambient fine aerosols (PM2.5) collected in Hong Kong.

The correct name of the 3rd Author is presented in this paper.

Increased processing of SINE B2 ncRNAs unveils a novel type of transcriptome deregulation in amyloid beta neuropathology.

The functional importance of many non-coding RNAs (ncRNAs) generated by repetitive elements and their connection with pathologic processes remains elusive. B2 RNAs, a class of ncRNAs of the B2 family of SINE repeats, mediate through their processing the transcriptional activation of various genes in response to stress. Here, we show that this response is dysfunctional during amyloid beta toxicity and pathology in the mouse hippocampus due to increased levels of B2 RNA processing, leading to constitutively elevated B2 RNA target gene expression and high Trp53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in hippocampal cells and is activated during amyloid toxicity, accelerating the processing of SINE RNAs and gene hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer's disease (AD).

Optical properties, source apportionment and redox activity of humic-like substances (HULIS) in airborne fine particulates in Hong Kong.

Humic-like substances (HULIS) account for a considerable fraction of water-soluble organic matter (WSOM) in ambient fine particulates (PM2.5) over the world. However, systemic studies regarding the chemical characteristics, sources and redox activity of HULIS are still limited. In this study, the mass concentration, optical properties, and reactive oxygen species (ROS)-generation potential of HULIS were investigated in PM2.5 samples collected in Hong Kong during 2011-2012, and they all showed higher levels on days under regional pollution than on days under long range transport (LRT) pollution and local emissions. Positive matrix factorization (PMF) analysis was conducted regarding the mass concentration and dithiothreitol (DTT) activity of HULIS. Four primary sources (i.e. marine vessels, industrial exhaust, biomass burning, and vehicle emissions), and two secondary sources (i.e. secondary organic aerosol formation and secondary sulfate) were identified. Most sources showed higher contributions to both the mass concentration and DTT activity of HULIS on regional days than on LRT and local days, except that marine vessels had a higher contribution on local days than the other two synoptic conditions. Secondary processes were the major contributor to HULIS (54.9%) throughout the year, followed by biomass burning (27.4%) and industrial exhaust (14.7%). As for the DTT activity of HULIS, biomass burning (62.9%) and secondary processes (25.4%) were found to be the top two contributors. Intrinsic ROS-generation potential of HULIS was also investigated by normalizing the DTT activity by HULIS mass in each source. HULIS from biomass burning were the most DTT-active, followed by marine vessels; while HULIS formed through secondary processes were the least DTT-active. For the optical properties of HULIS, multiple linear regression model was adopted to evaluate the contributions of various sources to the light absorbing ability of HULIS. Biomass burning was found to be the only source significantly associated with the light absorbing property of HULIS.

A quantitative assessment of source contributions to fine particulate matter (PM2.5)-bound polycyclic aromatic hydrocarbons (PAHs) and their nitrated and hydroxylated derivatives in Hong Kong.

Atmospheric polycyclic aromatic hydrocarbons (PAHs) and their derivatives are of great concern due to their adverse health effects. However, source identification and apportionment of these compounds, particularly their nitrated and hydroxylated derivatives (i.e., NPAHs and OHPAHs), in fine particulate matter (PM2.5) in Hong Kong are still lacking. In this study, we conducted a 1-year observation at an urban site in Hong Kong. PM2.5-bound PAHs and their derivatives were measured, with median concentrations of 4590, 44.4 and 31.6 pg m-3 for ∑21PAHs, ∑13NPAHs, and ∑12OHPAHs, respectively. Higher levels were observed on regional pollution days than on long regional transport (LRT) or local emission days. Based on positive matrix factorization analysis, four sources were determined: marine vessels, vehicle emissions, biomass burning, and a mixed source of coal combustion and NPAHs secondary formation. Coal combustion and biomass burning were the major sources of PAHs, contributing over 85% of PAHs on regional and LRT days. Biomass burning was the predominant source of OHPAHs throughout the year, while NPAHs mainly originated from secondary formation and fuel combustion. For benzo[a]pyrene (BaP)-based PM2.5 toxicity, the mixed source of coal combustion and NPAHs secondary formation was the major contributor, followed by biomass burning and vehicle emissions.