•Human osteosarcoma cells were exposed to bisphenols BPA, BPAF and BPS for 3months.•These analogs show distinct gene expression profiles, with widest induction for BPS.•They affect genes of the ...cardiovascular and immune systems, and for fetal development.•BPAF/BPS affect bone-related genes, for development of the embryonic skeletal system.•Potential toxicological effects for BPS and BPAF are of greater concern than for BPA.
The bisphenols AF (BPAF) and S (BPS) are structural analogs of the endocrine disruptor bisphenol A (BPA), and are used in common products as a replacement for BPA. To elucidate genome-wide gene expression responses, estrogen-dependent osteosarcoma cells were cultured with 10nM BPA, BPAF, or BPS, for 8h and 3months. Genome-wide gene expression was analyzed using the Illumina Expression BeadChip. Three months exposure had significant effects on gene expression, particularly for BPS, followed by BPAF and BPA, according to the number of differentially expressed genes (1980, 778, 60, respectively), the magnitude of changes in gene expression, and the number of enriched biological processes (800, 415, 33, respectively) and pathways (77, 52, 6, respectively). ‘Embryonic skeletal system development’ was the most enriched bone-related process, which was affected only by BPAF and BPS. Interestingly, all three bisphenols showed highest down-regulation of genes related to the cardiovascular system (e.g., NPPB, NPR3, TXNIP). BPA only and BPA/BPAF/BPS also affected genes related to the immune system and fetal development, respectively. For BPAF and BPS, the ‘isoprenoid biosynthetic process’ was enriched (up-regulated genes: HMGCS1, PDSS1, ACAT2, RCE1, DHDDS). Compared to BPA, BPAF and BPS had more effects on gene expression after long-term exposure. These findings stress the need for careful toxicological characterization of BPA analogs in the future.
Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there ...are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov–Smirnov test, P-value<10–15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (r
S
-values>−0.62), but in girls only 207 (41%) showed inverse correlation (r
S
-values>−0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.
Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal ...tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2-4 in 60 pediatric patients. The cumulative incidence of aGvHD 2-4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2-4 Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3-191.8), respectively, multiple testing corrected p ≤ 0.001. Upon evaluation in an extended cohort (n = 182) with an incidence of aGvHD 2-4 of 22% (n = 40), only MGMT rs10764881 (G>A) remained significant (adjusted HR = 2.05 95% CI: 1.06-3.94; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.
Biodynamic (BD) agriculture became the subject of research efforts during the past decades, whereas a part of the scientific community looks at the BD method with skepticism and marks it as dogmatic. ...Nevertheless, as explored in this review, a fair share of the available peer-reviewed research results of controlled field experiments as well as case studies show effects of BD preparations on yield, soil quality and biodiversity. Moreover, BD preparations express a positive environmental impact in terms of energy use and efficiency. However, the underlying natural science mechanistic principle of BD preparations is still under investigation. In addition, quality determination methods, based on holistic approaches, are increasingly being investigated and recognized. BD farming strives, as manifested in several publications, to positively impact cultural landscape design as well. Summarized data showed that further research is needed and thus encouraged in the field of food quality comparison/determination, food safety, environmental performance (e.g., footprints), and on the effects of BD farming practices on farm animals.
•MiRNA expression in a cohort highly exposed to perfluoroalkyl substances (PFAS)•MiR-101-3p, miR-144-3p and miR-19a-3p were downregulated with increased serum PFAS.•In silico analyses showed 7 target ...genes for these 3 miRNAs to be annotated to PFAS.•Ingenuity pathway analyses suggest these miRNAs associated to several health effects.•This study propose epigenetic mechanisms as a mode of action of PFAS toxicity.
Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. Not much is known about the modes of action of PFAS toxicity, but one likely mechanism is alteration of microRNA expression.
To investigate whether PFAS exposure is associated with altered microRNA expression in serum.
We selected women from the Ronneby cohort, with high exposure to perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), emanating from drinking water contaminated by firefighting foam, and a control group of women from a neighbouring municipality without drinking water contamination. Serum levels of PFAS were analysed using LC/MS/MS. High coverage microRNA expression was analysed by next generation sequencing (NGS) in 53 individuals to screen for microRNAs associated with PFAS exposure. After verification by qPCR, associations between PFAS exposure and expression of 18 selected microRNAs were validated by qPCR in 232 individuals. In silico functional analyses were performed using Ingenuity pathway analysis (IPA).
Three microRNAs were consistently associated with PFAS exposure in the different steps of the study: miR-101-3p, miR-144-3p and miR-19a-3p (all downregulated with increasing exposure). In silico functional analyses suggested that these PFAS-associated microRNAs were annotated to e.g. cardiovascular function and disease, Alzheimer’s disease, growth of cancer cell lines and cancer. Seven predicted target genes for the downregulated microRNAs were annotated to PFAS in IPA knowledge database: DNA methyltransferase 3 alpha (DNMT3a), epidermal growth factor receptor (EGFR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), nuclear receptor subfamily 1, group H, member 3 (NR1H3), peroxisome proliferator-activated receptor alpha (PPARα), prostaglandin-endoperoxide synthase 2 (PTGS2), and tumour growth factor alpha (TGFα).
PFAS exposure was associated with downregulation of specific microRNAs. Further, in silico functional analyses suggest potential links between the specific PFAS-associated microRNAs, specific microRNA target genes and possibly also health effects.
As the importance of information about food quality dependent on agriculture production methods has increased among many consumers, some internal quality parameters of white cabbage were investigated ...on samples from a field experiment carried out in the northeast of Slovenia. In 2008, sensory properties, mineral composition, and content of vitamin C were investigated in the samples from the control treatment and from conventional, integrated, organic, and bio-dynamic farming systems. Farming system significantly influenced the content of iron, zinc, phosphorous, potassium, manganese, and ash in fresh and dry samples, magnesium only in fresh and sodium only in dry samples. The content of ascorbic acid was higher in samples from control and biodynamic treatments compared to other three treatments. Untrained evaluators scored their preference for four characteristics (colour, odour, taste, and overall acceptability) using a nine-point hedonic scale. Statistically significant differences were shown for all characteristics. According to the overall acceptability, samples were ranked control = integrated = organic > conventional = biodynamic.
•DNA methylation in women upon exposure to perfluoroalkyl substances (PFAS)•117 differentially methylated positions (DMPs) were associated with PFAS exposure.•A near-significantly differentially ...methylated region in S100A13 was identified.•PFAS exposure was not associated with epigenetic age acceleration.•In silico analyses suggest several canonical pathways associated to genes with DMPs.
Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFAS is via epigenetic changes, such as DNA methylation. However, few studies have evaluated associations between PFAS exposure and DNA methylation among adults, and data is especially scarce for women. Furthermore, exposure to environmental pollutants has been associated with epigenetic age acceleration, but no studies have yet evaluated whether PFAS is associated with epigenetic age acceleration.
To investigate whether exposure to PFAS is associated with alteration of DNA methylation and epigenetic age acceleration among women.
In this observational pilot study, 59 women (aged 20–47 years at enrollment in 2014) from Ronneby, Sweden, an area with historically high PFAS exposure due to local drinking water contamination, were divided into three PFAS exposure groups (low, medium, and high). Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip. Ingenuity Pathway Analysis was used for in silico functional assessment. Epigenetic age acceleration was derived from the DNA methylation data using Horvath’s epigenetic skin and blood clock.
117 differentially methylated positions (q < 0.017) and one near-significantly differentially methylated region (S100A13, FWER = 0.020) were identified. In silico functional analyses suggested that genes with altered DNA methylation (q < 0.05) were annotated to cancer, endocrine system disorders, reproductive system disease, as well as pathways such as estrogen receptor signaling, cardiac hypertrophy signaling, PPARα/RXRα activation and telomerase signaling. No differences in epigenetic age acceleration between PFAS exposure groups were noted (p = 0.43).
The data suggests that PFAS exposure alters DNA methylation in women highly exposed to PFAS from drinking water. The observed associations should be verified in larger cohorts, and it should also be further investigated whether these changes in methylation also underlie potential phenotypic changes and/or adverse health effects of PFAS.
Amaranth is a pseudocereal of potential economic interest in Europe, but due to its small seed size it requires shallow sowing and maintenance of optimal soil surface conditions for sufficient and ...uniform emergence. In this study, two experiments in a glasshouse, and two in a growth chamber were conducted to determine the effect of various factors on percentage of live seed emergence (PLSE) and seedling weight of four amaranth species:
Amaranthus mantegazzianus Paserini,
A. hypocondriacus L. cv. G5,
A. cruentus L. cv. G6 and
A. caudatus L. Emergence factors included soil texture (loam, silt loam, sandy loam and sand), sowing depth (0,
5,
15,
30 and 45 mm), soil water regimes (water potentials of −10 to −20, −40 to −50 and −60 to −70 kPa), temperature (from 11 to 25
°C in 2
°C increments) and light regimes (photoperiod 0,
12 and 24 h). The 15 mm sowing depth gave the highest seedling weight on sand and the highest PLSE on loam. On the sandy loam the PLSE was not affected by sowing depth up to 15 mm.
A. caudatus gave the highest PLSE whereas
A. cruentus gave the lowest PLSE but the heaviest seedlings. PLSE was severely reduced on the loam where topsoil crusting occurred after a decrease in soil moisture content from field capacity to −60 to −70 kPa, but not on the silt loam even when dry conditions were maintained throughout the experiment. PLSE was above 80% with temperatures >21
°C. Light regime with 12 h illumination gave the highest PLSE.
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