scholarly journals Ultraviolet radiation modulates DNA methylation in melanocytes

2021 ◽  
Author(s):  
Sarah Preston-Alp ◽  
Jaroslav Jelinek ◽  
Jean-Pierre Issa ◽  
M. Raza Zaidi

Ultraviolet radiation (UVR) is the principal causal factor for melanoma; albeit the underlying mechanisms remain unclear. While the mutagenic properties of UVR are irrefutable, the role of UVR-induced mutations in the initiation of melanoma is controversial which highlights the gap in our knowledge of the initial critical molecular mechanisms of UVR-induced melanomagenesis. To investigate the potential non-mutational mechanisms of UVR-induced melanomagenesis, we studied the role of UVR in modulating DNA methylation changes in melanocytes via next-generation sequencing-based methodologies. Here we show that UVR directly causes stable changes in the DNA methylome and transcriptome, one month after exposure. Genomic features associated with transcription were protected from 5mC alterations whereas CpG sites found in intergenic regions were more likely to be affected. Additionally, the long-term effects of UVR seem to perturb signaling pathways important for melanocyte biology. Interestingly, UVR-sensitive CpG sites were found to be prognostic of overall patient survival and highlighted a subset of CpG sites that may be relevant in melanomagenesis.

2015 ◽  
Vol 6 (2) ◽  
pp. 105-117 ◽  
Author(s):  
Giusi Taormina ◽  
Mario G. Mirisola

AbstractMany aging theories and their related molecular mechanisms have been proposed. Simple model organisms such as yeasts, worms, fruit flies and others have massively contributed to their clarification, and many genes and pathways have been associated with longevity regulation. Among them, insulin/IGF-1 plays a key and evolutionary conserved role. Interestingly, dietary interventions can modulate this pathway. Calorie restriction (CR), intermittent fasting, and protein and amino acid restriction prolong the lifespan of mammals by IGF-1 regulation. However, some recent findings support the hypothesis that the long-term effects of diet also involve epigenetic mechanisms. In this review, we describe the best characterized aging pathways and highlight the role of epigenetics in diet-mediated longevity.


2020 ◽  
Vol 22 (10) ◽  
Author(s):  
Domenico D’Amario ◽  
Massimiliano Camilli ◽  
Stefano Migliaro ◽  
Francesco Canonico ◽  
Mattia Galli ◽  
...  

Abstract Purpose of Review The aim of this report is to describe the main aspects of sex-related differences in non-ischemic dilated cardiomyopathies (DCM), focusing on chemotherapy-induced heart failure (HF) and investigating the possible therapeutic implications and clinical management applications in the era of personalized medicine. Recent Findings In cardio-oncology, molecular and multimodality imaging studies confirm that sex differences do exist, affecting the therapeutic cardioprotective strategies and, therefore, the long-term outcomes. Interestingly, compelling evidences suggest that sex-specific characteristics in drug toxicity might predict differences in the therapeutic response, most likely due to the tangled interplay between cancer and HF, which probably share common underlying mechanisms. Summary Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestations, from sex-determined differential gene expression to sex hormone interaction with their receptors in the heart. Non-ischemic DCM is an umbrella definition that incorporates several etiologies, including chemotherapy-induced cardiomyopathies. The role of sex as a risk factor for cardiotoxicity is poorly explored. However, understanding the various features of disease manifestation and outcomes is of paramount importance for a prompt and tailored evaluation.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 260-261
Author(s):  
Eveline M Ibeagha-Awemu ◽  
Suraj Bhattarai ◽  
Pier-Luc Dedemaine ◽  
Mengqi Wang ◽  
Stephanie D McKay ◽  
...  

Abstract Several investigations on disease progression of Mycobacterium avium subsp. paratuberculosis (MAP) infection in dairy cows have revealed molecular mechanisms including genes and pathways implicated in MAP pathogenesis. Epigenetic processes including DNA methylation are known to regulate the expression of genes and many biological processes. However, limited studies have examined the role of DNA methylation in the pathogenesis of Johne’s disease (JD). This study examined the impact of subclinical MAP infection on DNA methylation profile in the ileum of cows, the site of initial interaction between MAP and host. DNA from ileum tissues from five cows positive for MAP (direct fecal qPCR and blood ELISA test; MAP+/+) and 5 cows negative for MAP (MAP-/-) were subjected to whole genome bisulfite sequencing and bioinformatics analysis. 2000 differentially methylated cytosines (DMCs; FDR< 0.05) and 205 differentially methylated regions (DMRs; P < 0.01) were detected. Majority of DMCs and DMRs are located in intergenic regions (87.2% and 57.1%) followed by intronic regions (12.8% and 30.7%) of genes, respectively. Some DMCs are located on 250 genes including genes that were previously identified to be associated with JD (e.g. IL-12RB2, CD38). Interestingly, CD38, known to play roles in the effective containment of mycobacteria within granulomata in cows and genetic polymorphisms in IL-12RB2 are associated with JD and human Crohn’s disease. Also, several genes of the solute carrier family including SLC13A3, SLC15A1, SLC17A7, SLC25A21, SLC25A38 and SLC9A9 harbored DMCs. Some members of this gene family participate in pathogen clearance and have associations with JD. Our data suggest that DNA methylation changes may have regulatory roles in host (ileum) response to MAP infection. Our data therefore suggest that DNA methylation changes contribute to the regulation of host response to MAP pathogenesis and may be one of the mechanisms that MAP uses to subvert host immune responses for its survival.


2019 ◽  
Author(s):  
Christian M Page ◽  
Vera Djordjilović ◽  
Therese H Nøst ◽  
Reza Ghiasvand ◽  
Torkjel M Sandanger ◽  
...  

Abstract Background Ultraviolet radiation (UVR) exposure is a leading cause of skin cancers and an ubiquitous environmental exposure. However, the molecular mechanisms relating UVR exposure to melanoma is not fully understood. We aimed to investigate if lifetime UVR exposure influences DNA methylation, and if individual CpG sites could be robustly associated with UVR exposures.Methods We assessed DNA methylation in whole blood in three data sets (N = 183, 191, and 125) from the Norwegian Women and Cancer cohort, using Illumina methylation platforms (450k & EPIC). We studied genome-wide DNA methylation, targeted analyses of CpG sites indicated in the literature, global methylation (average over all CpGs and imputation of LINE-1 specific CpGs), and accelerated aging. Lifetime history of UVR exposure (residential ambient UVR, sunburns, sunbathing vacations and indoor tanning) was collected by questionnaires. Cumulative UVR exposure was calculated by adding sunbathing vacations and indoor tanning. We used one data set for discovery and the other two for replication. Results One CpG site showed a genome-wide significant association between cumulative UVR exposure and DNA methylation (cg01884057) (pnominal=3.96e-08), but was not replicated in any of the two replication sets (pnominal≥0.42). Four CpG sites (cg05860019, cg00033666, cg18984282, cg25792367) showed suggestive associations with the other UVR exposures. Conclusion We performed extensive analyses of the association between long-term UVR exposure and DNA methylation in lymphocytes. There was no indication of a robust effect of past UVR exposure on DNA methylation, and our results do not suggest mediation of UVR effects on melanoma risk by DNA methylation.


2021 ◽  
pp. 048661342097642
Author(s):  
Juan E. Santarcángelo ◽  
Juan Manuel Padín

Argentina’s right-wing shift in the 2015 presidential election concluded twelve years of center-left rule. The elected president, Mauricio Macri, claimed that the economy would experience normalization of existing imbalances and recover its strength in a “new political era.” However, the new administration quickly restored the dominance of neoliberal economic policies through a comprehensive set of initiatives, which centrally included the return to international financial debt and equity markets and submission to the International Monetary Fund’s (IMF) rules. This article analyzes Argentina’s external-debt-growth process and discusses its objectives and long-term effects. This paper posits that the indebtedness process carried out by the Macri administration—and its modality—not only increased the relevance of financial capital in the Argentine economy but also structurally conditioned any future nonorthodox alternative path of development. This outcome cannot be understood without taking into account the deliberate role of the United States, the IMF, and the top companies that operate in Argentina, as well as the complicity of many political sectors. JEL Classification: H63, F34, F63


Biochar ◽  
2021 ◽  
Author(s):  
Qian Yang ◽  
Yongjie Wang ◽  
Huan Zhong

AbstractThe transformation of mercury (Hg) into the more toxic and bioaccumulative form methylmercury (MeHg) in soils and sediments can lead to the biomagnification of MeHg through the food chain, which poses ecological and health risks. In the last decade, biochar application, an in situ remediation technique, has been shown to be effective in mitigating the risks from Hg in soils and sediments. However, uncertainties associated with biochar use and its underlying mechanisms remain. Here, we summarize recent studies on the effects and advantages of biochar amendment related to Hg biogeochemistry and its bioavailability in soils and sediments and systematically analyze the progress made in understanding the underlying mechanisms responsible for reductions in Hg bioaccumulation. The existing literature indicates (1) that biochar application decreases the mobility of inorganic Hg in soils and sediments and (2) that biochar can reduce the bioavailability of MeHg and its accumulation in crops but has a complex effect on net MeHg production. In this review, two main mechanisms, a direct mechanism (e.g., Hg-biochar binding) and an indirect mechanism (e.g., biochar-impacted sulfur cycling and thus Hg-soil binding), that explain the reduction in Hg bioavailability by biochar amendment based on the interactions among biochar, soil and Hg under redox conditions are highlighted. Furthermore, the existing problems with the use of biochar to treat Hg-contaminated soils and sediments, such as the appropriate dose and the long-term effectiveness of biochar, are discussed. Further research involving laboratory tests and field applications is necessary to obtain a mechanistic understanding of the role of biochar in reducing Hg bioavailability in diverse soil types under varying redox conditions and to develop completely green and sustainable biochar-based functional materials for mitigating Hg-related health risks.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Monica del C. Gomez-Alonso ◽  
Anja Kretschmer ◽  
Rory Wilson ◽  
Liliane Pfeiffer ◽  
Ville Karhunen ◽  
...  

Abstract Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.


2018 ◽  
Vol 168 (1) ◽  
pp. 122-139 ◽  
Author(s):  
Catherine Archer ◽  
Kai-Ti Kao

Many mothers can find themselves increasingly isolated and overwhelmed after giving birth to a new baby. This period can be a source of extreme stress, anxiety and depression, which can not only have an economic impact on national health services, but can also have long-term effects on the development of the child. At the same time, social media use among most new mothers has become ubiquitous. This research investigates the role of social media, potentially as a mechanism for social support, among Australian mothers of young children aged from birth to 4 years. The findings indicate that participants had mixed responses to their social media use. While social support was deemed a benefit, there were also some negative aspects to social media use identified. The findings highlight the need to critically interrogate social media’s ability to act as a source of social support for new mothers.


2021 ◽  
Vol 131 ◽  
pp. 105496
Author(s):  
M. Mazzelli ◽  
N. Cattane ◽  
V. Begni ◽  
M. Papp ◽  
M.A. Riva ◽  
...  

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.


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