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CCCTC-binding factor (CTCF) sites interact with each other in the chromatin environment, establishing chromatin domains. Our previous study showed that interaction between CTCF sites is cell type-specific around the β-globin locus and is dependent on erythroid-specific activator GATA-1. To find out molecular mechanisms of the cell type-specific interaction, we directly inhibited GATA-1 binding to the β-globin enhancers by deleting its binding motifs and found that histone H3K27 acetylation (H3K27ac) was decreased at CTCF sites surrounding the β-globin locus, even though CTCF binding itself was maintained at the sites. Forced H3K27ac by Trichostatin A treatment or CBP/p300 KD affected the interactions between CTCF sites around the β-globin locus without changes in CTCF binding. Analysis of public ChIA-PET data revealed that H3K27ac is higher at CTCF sites forming short interactions than long interactions. GATA-1 was identified as a representative transcription factor that relates with genes present inside the short interactions in erythroid K562 cells. Depletion of GATA-1-reduced H3K27ac at CTCF sites near erythroid-specific enhancers. These results indicate that H3K27ac at CTCF sites is required for cell type-specific chromatin interactions between them. Tissue-specific activator GATA-1 appears to play a role in H3K27ac at CTCF sites in erythroid cells.

Leukemia/lymphoma-related factor (LRF; a hematopoietic transcription factor) has been suggested to repress fetal γ-globin genes in the human adult stage β-globin locus. Here, to study the role of LRF in the fetal stage β-globin locus, we knocked out its expression in erythroid K562 cells, in which the γ-globin genes are mainly transcribed. The γ-globin transcription was reduced in LRF knock-out cells, and transcription factor binding to the β-globin locus control region hypersensitive sites (LCR HSs) and active histone organization in the LCR HSs were disrupted by the depletion of LRF. In contrast, LRF loss in the adult stage β-globin locus did not affect active chromatin structure in the LCR HSs and induced the fetal γ-globin transcription. These results indicate that LRF may act as an activator and repressor of the human β-like globin gene transcription in a manner dependent on developmental stage.

Currently, wood is attracting attention as an eco-friendly building material that has advantages such as high insulation performance and low CO2 emission. However, it is vulnerable to moisture. Therefore, the objective of this study was to develop wood-lime boards using lime as resins that is known to be excellent in moisture control. Hygrothermal behaviors of such wood-lime boards were then analyzed to confirm their applicability as building materials. Results of hygrothermal behavior analysis revealed that they had higher insulation performance and higher water vapor resistance factor. Simulation analysis results also indicated that both total water content and mold growth risk were reduced when wood-lime boards were used in comparison with existing layers. Therefore, wood-lime boards were applicable as building materials.

Biodiversity in the city is becoming important as cities are expanded. Thus, the cost-efficient and accurate methodology for the investigation of biota has been consistently demanded. Environmental DNA (eDNA) is one of the emerging tools to supplement traditional survey methods and improve the efficiency of the survey. Summer (from July to August) is the monsoon period in South Korea, so it is excluded from the survey period because of the unstable aquatic environment, the safety of investigators, and accessibility to study sites. On the other hand, spring and autumn (from March to October), excluding the flooding season, are considered suitable times for the survey. This study compared fish composition and distribution by season in summer and autumn using eDNA to identify the change of fish composition and determine the suitability of the eDNA survey for seasonal fish investigation at urban streams. The number of eDNA reads, fish composition, and their community structures was changed according to the season. The total eDNA read was 2.3 times more in October (1,419,062) than in July (3,202,626). In addition, compared to the summer when 13 families and 33 species were detected, 13 families and 35 species were detected in fall. A total of 13 families and 32 species were detected in common. Three species (Acheilognathus rhombeus, Tachysurus fulvidraco, Pungtungia herzi) more were identified, and one (Hemiculter leucisculus) was not detected in October. The result described that the distribution rate of fish species has changed in the study area. Especially, the appearance of invasive species increased from 14 to 20 sites and the habitat range of invasive species was extended in October than July. However, there was no significant difference in richness and diversity except for abundance among fish community structures. This result revealed that eDNA survey methods can identify changes in the composition and distribution of fish by season. Furthermore, based on the little fluctuation in the species appearing according to the season, the study suggested that eDNA can be used to complement traditional survey methods by conducting fish surveys regardless of the survey period.

Background lncRNAs have important roles in regulating cancer biology. Accumulating evidence has established a link between the dysregulation of lncRNAs and microRNA in cancer progression. In previous studies, miR-7-5p has been found to be significantly down-regulated in mesenchymal-like lung cancer cell lines and directly regulated EGFR. In this work, we investigated the lncRNA partner of miR-7-5p in the progression of lung cancer. Methods We investigated the expression of miR-7-5p and the lncRNA after transfection with an miR-7-5p mimics using a microarray. The microarray results were validated using quantitative real time-polymerase Chain Reaction (qRT-PCR). The regulatory effects of lncRNA on miR-7-5p and its target were evaluated by changes in the expression of miR-7-5p after transfection with siRNAs for lncRNA and the synthesis of full-length lncRNA. The effect of miR-7-5p on lncRNA and the miRNA target was evaluated after transfection with miRNA mimic and inhibitor. The role of lncRNA in cancer progression was determined using invasion and migration assays. The level of lncRNA and EGFR in lung cancer and normal lung tissue was analyzed using TCGA data. Results We found that LINC00240 was downregulated in lung cancer cell line after miR-7-5p transfection with an miR-7-5p mimic. Further investigations revealed that the knockdown of LINC00240 induced the overexpression of miR-7-5p. The overexpression of miR-7-5p diminished cancer invasion and migration. The EGFR expression was down regulated after siRNA treatment for LINC00240. Silencing LINC00240 suppressed the invasion and migration of lung cancer cells, whereas LINC00240 overexpression exerted the opposite effect. The lower expression of LINC00240 in squamous lung cancer was analyzed using TCGA data. Conclusions Taken together, LINC00240 acted as a sponge for miR-7-5p and induced the overexpression of EGFR. LINC00240 may represent a potential target for the treatment of lung cancer.

To obtain high thermal performance composite phase change materials (PCMs), various other supporting materials have been utilized to encapsulate organic PCMs. In this study, four carbon materials (biochar, activated carbon, carbon nanotubes, and expanded graphite) were introduced to support heptadecane. The composite PCMs were designed using vacuum impregnation techniques. The structural stability, chemical compatibility, thermal stability, and thermal energy storage capacity of the as-prepared materials were systematically characterized using differential scanning calorimetry, Fourier-transform infrared spectroscopy, etc. Among the supporting materials, expanded graphite had a high PCM content of 94.5%, whereas it was low for biochar-supported PCM (25.7%). Meanwhile, the latent heat storage capacity ranged from 53.3 J/g to 195.9 J/g. It was observed that the intermolecular interactions between the PCM and supporting materials and the surface functionality of the encapsulating agents play a leading role in the thermal performance of the composite PCMs. Furthermore, pore structures such as specific surface area, total pore volume, and pore size distribution have a combined effect on the crystallinity of heptadecane in the composite PCMs. The study will provide insight into developing and designing carbon-based composite PCMs for heat-storage purposes.

Early identification of patients at risk of developing preeclampsia (PE) would allow providers to tailor their prenatal management and adopt preventive strategies, such as low-dose aspirin. Nevertheless, no mid-trimester biomarkers have as yet been proven useful for prediction of PE. This study investigates the ability of metabolomic biomarkers in mid-trimester maternal plasma to predict PE. A case–control study was conducted including 33 pregnant women with mid-trimester maternal plasma (gestational age [GA], 16–24 weeks) who subsequently developed PE and 66 GA-matched controls with normal outcomes (mid-trimester cohort). Plasma samples were comprehensively profiled for primary metabolic and lipidomic signatures based on gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). A potential biomarker panel was computed based on binary logistic regression and evaluated using receiver operating characteristic (ROC) analysis. To evaluate whether this panel can be also used in late pregnancy, a retrospective cohort study was conducted using plasma collected from women who delivered in the late preterm period because of PE (n = 13) or other causes (n = 21) (at-delivery cohort). Metabolomic biomarkers were compared according to the indication for delivery. Performance of the metabolomic panel to identify patients with PE was compared also to a commonly used standard, the plasma soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio. In the mid-trimester cohort, a total of 329 metabolites were identified and semi-quantified in maternal plasma using GC-TOF MS and LC-Orbitrap-MS. Binary logistic regression analysis proposed a mid-trimester biomarker panel for the prediction of PE with five metabolites (SM C28:1, SM C30:1, LysoPC C19:0, LysoPE C20:0, propane-1,3-diol). This metabolomic model predicted PE better than PlGF (AUC [95% CI]: 0.868 [0.844–0.891] vs 0.604 [0.485–0.723]) and sFlt-1/PlGF ratio. Analysis of plasma from the at-delivery cohort confirmed the ability of this biomarker panel to distinguish PE from non-PE, with comparable discrimination power to that of the sFlt-1/PlGF ratio. In conclusion, an integrative metabolomic biomarker panel in mid-trimester maternal plasma can accurately predict the development of PE and showed good discriminatory power in patients with PE at delivery.

Background: Despite a recent preventive evidence of Lactobacillus and Pediococcus on non-alcoholic fatty liver disease (NAFLD) progression, the underlying mechanistic is less understood. We explored the causality of L. lactis and P. pentosaceus on the gut-metabolomic modulation in the prevention of NAFLD progression in mouse model and subsequently discovered metabolic biomarkers based on NAFLD patients.Results: Six-week-old male C57BL/6J mice were divided into 4 groups (control, Western diet [WD], and 2 WD with strains [L. lactis and P. pentosaceus]). Given completely reproduced data (liver/body ratio, pathology, and metagenomic profiles), comorbid etiologies including inflammation and diabetes were significantly amended by 2 strains. The comprehensive metabolomic profiles of the mouse cecum revealed unique compositional characteristic according to the groups. L. lactis and P. pentosaceus supplementation restored the dysregulation in short chain fatty acids (SCFAs), bile acids, and tryptophan metabolites. Indole derivatives (indole-3-acetic acid, indole-3-propionic acid, and indole-3-acrylic acid) showed anti-inflammatory activities by suppressing pro-inflammation cytokines. Human data (healthy control [n=30] and NAFLD patients [n=74]) were analyzed for clinical association and biomarker. The Fermicutes/Bacteroidetes ratio of NAFLD (4.3) was significantly higher compared with control (0.6)(pConclusion: L. lactis and P. pentosaceus ameliorate NAFLD by modulating gut metabolic environment, particularly the indole pathway, of the gut-liver axis. NAFLD progression was associated with metabolic deterioration in the SCFAs, bile acid, and indole pathways. ClinicalTrials.gov: NCT04339725

Gypsum board as a wall and ceiling finishing material can be used to reduce building energy consumption. To optimally use gypsum board as building material, methods are needed to reduce mold and condensation that frequently found on the material and inner surfaces of the board. The influence of gypsum board on hygrothermal behavior of building needs to be confirmed first. The objective of this study was to reduce gypsum boards’ thermal conductivity and improve their moisture properties. Their effect on the hygrothermal behavior and performance of buildings were then evaluated. Specifically, gypsum board was applied to a concrete wall in this study. Porous materials such as expanded vermiculite (EV), expanded perlite (EP), and three xGnP of different surface areas (C-300, C-500 and C-750) were used to improve the thermal and moisture performance of the gypsum board. Gypsum boards’ density, thermal conductivity, water vapor resistance factor, and water content of gypsum board by relative humidity were then evaluated. The influence of hygrothermal behavior of walls when gypsum boards adding porous materials were used as interior finishing materials on concrete wall were then examined.

// Alexander A. Goldberg 1, 2 , Kwang-Bo Joung 1, 2 , Asma Mansuri 1, 2 , Yujin Kang 1, 2 , Raquel Echavarria 1, 2 , Ljiljana Nikolajev 3, 4 , Yang Sun 5 , Jane J. Yu 5 , Stephane A. Laporte 3, 4 , Adel Schwertani 6 , Arnold S. Kristof 1, 2 1 Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Montreal, Quebec, Canada 2 Department of Critical Care Medicine, McGill University Health Centre Research Institute, Montreal, Quebec, Canada 3 Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada 4 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada 5 College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA 6 Division of Cardiology, Montreal General Hospital, Montreal, Quebec, Canada Correspondence to: Arnold S. Kristof, email: arnold.kristof@mcgill.ca Keywords: TSC2, mTOR, urotensin, lymphangioleiomyomatosis, angiomyolipoma Received: May 20, 2016 Accepted: July 01, 2016 Published: July 21, 2016 ABSTRACT Lymphangioleiomyomatosis (LAM) is a destructive lung disease that can arise sporadically or in adults suffering from the tumor syndrome tuberous sclerosis complex (TSC). Microscopic tumors (‘LAM nodules’) in the lung interstitium arise from lymphatic invasion and metastasis. These consist of smooth muscle-like cells (LAM cells) that exhibit markers of neural crest differentiation and loss of the tumor suppressor protein ‘tuberous sclerosis complex-2’ (TSC2). Consistent with a neural phenotype, expression of the neuropeptide urotensin-II and its receptor was detected in LAM nodules. We hypothesized that loss of TSC2 sensitizes cells to the oncogenic effects of urotensin-II. TSC2-deficient Eker rat uterine leiomyoma ELT3 cells were stably transfected with empty vector or plasmid for the expression of TSC2. Urotensin-II increased cell viability and proliferation in TSC2-deficient cells, but not in TSC2-reconstituted cells. When exposed to urotensin-II, TSC2-deficient cells exhibited greater migration, anchorage-independent cell growth, and matrix invasion. The effects of urotensin-II on TSC2-deficient cells were blocked by the urotensin receptor antagonist SB657510, and accompanied by activation of Erk mitogen-activated protein kinase and focal adhesion kinase. Urotensin-II-induced proliferation and migration were reproduced in TSC2-deficient human angiomyolipoma cells, but not in those stably expressing TSC2. In a mouse xenograft model, SB657510 blocked the growth of established ELT3 tumors, reduced the number of circulating tumor cells, and attenuated the production of VEGF-D, a clinical biomarker of LAM. Urotensin receptor antagonists may be selective therapeutic agents for the treatment of LAM or other neural crest-derived neoplasms featuring loss of TSC2 or increased expression of the urotensin receptor.

Consumption of alcohol injures DNA, and such damage is considered to be a primary cause for the development of cancer and many other diseases essentially due to reactive oxygen species generated from alcohol. To sensitively detect alcohol-induced DNA lesions in a biological system, we introduced a novel analytical platform for visualization of single genomic DNA molecules using E. coli. By fluorescently labelling the DNA lesions, our approach demonstrated, with the highest sensitivity, that we could count the number of DNA lesions induced by alcohol metabolism in a single bacterial cell. Moreover, our results showed a linear relationship between ethanol concentration and the number of DNA lesions: 0.88 lesions per 1% ethanol. Using this approach, we quantitatively analysed the DNA damage induced by exposure to alcoholic beverages such as beer (5% ethanol), rice wine (13%), soju (20%), and whisky (40%).

Regular monitoring of latent tuberculosis (TB) infection in healthcare workers (HCWs) is recommended, but the view about the effective method and performance of serial monitoring is controversial. The aim of this study was to determine differences in conversion rates according to TB exposure risk using the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT), and to evaluate the reproducibility and within-subject variability of the QFT-GIT in South Korea. Fifty-three HCWs were grouped according to their risk for TB exposure: group 1, high risk (n = 21); group 2, low risk (n = 32). Baseline and follow-up TSTs and QFT-GITs were performed from June 2009 to July 2011. Enzyme-linked immunosorbent assays (ELISAs) were repeated for the second QFT-GIT and a third QFT-GIT was performed after 8 weeks when discordant results of the second TST and QFT-GIT or a conversion or reversion were observed. No difference in the QFT-GIT conversion rate was evident between the two groups (15.4 vs. 6.5 %, p = 0.57), and no TST conversion was observed. The rate of QFT-GIT positivity was higher in the high-risk group (first QFT-GIT: 38.1 vs. 3.1 %, p = 0.002; second QFT-GIT: 33.3 vs. 9.4 %, p = 0.039). The re-test reproducibility of QFT-GIT results was high (100 %), and the within-subject results of repetitive QFT-GITs were variable. Stricter prevention strategies remain necessary in HCWs at high risk of TB exposure, and serial interferon-γ release assays (IGRAs) should be interpreted with caution in HCWs.