DNA methylation in plants Gallego-Bartolomé, Javier
New phytologist,
07/2020, Letnik:
227, Številka:
1
Journal Article
Recenzirano
Odprti dostop
DNA methylation is an epigenetic mark that regulates multiple processes, such as gene expression and genome stability. Mutants and pharmacological treatments have been instrumental in the study of ...this mark in plants, although their genome-wide effect complicates the direct association between changes in methylation and a particular phenotype. A variety of tools that allow locus-specific manipulation of DNA methylation can be used to assess its direct role in specific processes, as well as to create novel epialleles. Recently, new tools that recruit the methylation machinery directly to target loci through programmable DNA-binding proteins have expanded the tool kit available to researchers. This review provides an overview of DNA methylation in plants and discusses the tools that have recently been developed for its manipulation.
Endoplasmic reticulum (ER) is a dynamic organelle that participates in a number of cellular functions by controlling lipid metabolism, calcium stores, and proteostasis. Under stressful situations, ...the ER environment is compromised, and protein maturation is impaired; this causes misfolded proteins to accumulate and a characteristic stress response named unfolded protein response (UPR). UPR protects cells from stress and contributes to cellular homeostasis re‐establishment; however, during prolonged ER stress, UPR activation promotes cell death. ER stressors can modulate autophagy which in turn, depending of the situation, induces cell survival or death. Interactions of different autophagy‐ and apoptosis‐related proteins and also common signaling pathways have been found, suggesting an interplay between these cellular processes, although their dynamic features are still unknown. A number of pathologies including metabolic, neurodegenerative and cardiovascular diseases, cancer, inflammation, and viral infections are associated with ER stress, leading to a growing interest in targeting components of the UPR as a therapeutic strategy. Melatonin has a variety of antioxidant, anti‐inflammatory, and antitumor effects. As such, it modulates apoptosis and autophagy in cancer cells, neurodegeneration and the development of liver diseases as well as other pathologies. Here, we review the effects of melatonin on the main ER stress mechanisms, focusing on its ability to regulate the autophagic and apoptotic processes. As the number of studies that have analyzed ER stress modulation by this indole remains limited, further research is necessary for a better understanding of the crosstalk between ER stress, autophagy, and apoptosis and to clearly delineate the mechanisms by which melatonin modulates these responses.
: Melatonin is a highly evolutionary conserved endogenous molecule that is mainly produced by the pineal gland, but also by other nonendocrine organs, of most mammals including man. In the recent ...years, a variety of anti‐inflammatory and antioxidant effects have been observed when melatonin is applied exogenously under both in vivo and in vitro conditions. A number of studies suggest that this indole may exert its anti‐inflammatory effects through the regulation of different molecular pathways. It has been documented that melatonin inhibits the expression of the isoforms of inducible nitric oxide synthase and cyclooxygenase and limits the production of excessive amounts of nitric oxide, prostanoids, and leukotrienes, as well as other mediators of the inflammatory process such as cytokines, chemokines, and adhesion molecules. Melatonin’s anti‐inflammatory effects are related to the modulation of a number of transcription factors such as nuclear factor kappa B, hypoxia‐inducible factor, nuclear factor erythroid 2‐related factor 2, and others. Melatonin’s effects on the DNA‐binding capacity of transcription factors may be regulated through the inhibition of protein kinases involved in signal transduction, such as mitogen‐activated protein kinases. This review summarizes recent research data focusing on the modulation of the expression of different inflammatory mediators by melatonin and the effects on cell signaling pathways responsible for the indole’s anti‐inflammatory activity. Although there are a numerous published reports that have analyzed melatonin’s anti‐inflammatory properties, further studies are necessary to elucidate its complex regulatory mechanisms in different cellular types and tissues.
This paper presents a system for the detection of ships and oil spills using side-looking airborne radar (SLAR) images. The proposed method employs a two-stage architecture composed of three pairs of ...convolutional neural networks (CNNs). Each pair of networks is trained to recognize a single class (ship, oil spill, and coast) by following two steps: a first network performs a coarse detection, and then, a second specialized CNN obtains the precise localization of the pixels belonging to each class. After classification, a postprocessing stage is performed by applying a morphological opening filter in order to eliminate small look-alikes, and removing those oil spills and ships that are surrounded by a minimum amount of coast. Data augmentation is performed to increase the number of samples, owing to the difficulty involved in obtaining a sufficient number of correctly labeled SLAR images. The proposed method is evaluated and compared to a single multiclass CNN architecture and to previous state-of-the-art methods using accuracy, precision, recall, F-measure, and intersection over union. The results show that the proposed method is efficient and competitive, and outperforms the approaches previously used for this task.
Understanding genomic functions requires site-specific manipulation of loci via efficient protein effector targeting systems. However, few approaches for targeted manipulation of the epigenome are ...available in plants. Here, we adapt the dCas9-SunTag system to engineer targeted gene activation and DNA methylation in Arabidopsis. We demonstrate that a dCas9-SunTag system utilizing the transcriptional activator VP64 drives robust and specific activation of several loci, including protein coding genes and transposable elements, in diverse chromatin contexts. In addition, we present a CRISPR-based methylation targeting system for plants, utilizing a SunTag system with the catalytic domain of the Nicotiana tabacum DRM methyltransferase, which efficiently targets DNA methylation to specific loci, including the FWA promoter, triggering a developmental phenotype, and the SUPERMAN promoter. These SunTag systems represent valuable tools for the site-specific manipulation of plant epigenomes.
The automatic classification of ships from aerial images is a considerable challenge. Previous works have usually applied image processing and computer vision techniques to extract meaningful ...features from visible spectrum images in order to use them as the input for traditional supervised classifiers. We present a method for determining if an aerial image of visible spectrum contains a ship or not. The proposed architecture is based on Convolutional Neural Networks (CNN), and it combines neural codes extracted from a CNN with a k-Nearest Neighbor method so as to improve performance. The kNN results are compared to those obtained with the CNN Softmax output. Several CNN models have been configured and evaluated in order to seek the best hyperparameters, and the most suitable setting for this task was found by using transfer learning at different levels. A new dataset (named MASATI) composed of aerial imagery with more than 6000 samples has also been created to train and evaluate our architecture. The experimentation shows a success rate of over 99% for our approach, in contrast with the 79% obtained with traditional methods in classification of ship images, also outperforming other methods based on CNNs. A dataset of images (MWPU VHR-10) used in previous works was additionally used to evaluate the proposed approach. Our best setup achieves a success ratio of 86% with these data, significantly outperforming previous state-of-the-art ship classification methods.
Exercise‐released exosomes have been identified as novel players to mediate cell‐to‐cell communication in promoting systemic beneficial effects. This review aimed to systematically investigate the ...effects of exercise on exosome release and cargo, as well as provide an overview of their physiological implications. Among the 436 articles obtained in the database search (WOS, Scopus, and PubMed), 19 articles were included based on eligibility criteria. Results indicate that exercise promotes the release of exosomes without modification of its vesicle size. The literature has primarily shown an exercise‐driven increase in exosome markers (Alix, CD63, CD81, and Flot‐1), along with other exosome‐carried proteins, into circulation. However, exosome isolation, characterization, and phenotyping methodology, as well as timing of sample recovery following exercise can influence the analysis and interpretation of findings. Moreover, a large number of exosome‐carried microRNAs (miRNAs), including miR‐1, miR‐133a, miR‐133b, miR‐206, and miR‐486, in response to exercise are involved in the modulation of proliferation and differentiation of skeletal muscle tissue, although antigen‐presenting cells, leukocytes, endothelial cells, and platelets are the main sources of exosome release into the circulation. Collectively, with the physiological implications as evidenced by the ex vivo trials, the release of exercise‐promoted exosomes and their cargo could provide the potential therapeutic applications via the role of intercellular communication.
This review systematically investigate all available evidence from in vivo and ex vivo studies in which acute or chronic exercise effects on exosome release and cargo were evaluated in human and animal models, as well as summarize these outcomes with an overview of their physiological implications. This systematic review is especially noteworthy in exploring the evidence on the potential therapeutic role of exersomes in pathological conditions as well as the mechanisms by which the effects are implemented.
Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ...ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as main hepatic histological finding. Increased accumulation of intrahepatic lipids was associated with altered gene expression related to lipid metabolism, as a result of deregulation of their major modulators. Quercetin supplementation decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition was determined via 16S ribosomal RNA Illumina next-generation sequencing. Metagenomic studies revealed HFD-dependent differences at phylum, class and genus levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically increased detection of Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-κB signaling pathway activation was associated with inflammasome initiation response and reticulum stress pathway induction. Quercetin reverted gut microbiota imbalance and related endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of inflammasome response and reticulum stress pathway activation, leading to the blockage of lipid metabolism gene expression deregulation. Our results support the suitability of quercetin as a therapeutic approach for obesity-associated NAFLD via its anti-inflammatory, antioxidant and prebiotic integrative response.
•Dysbiosis is accompanied by gut-liver axis alteration in HFD-induced NAFLD.•Quercetin prevents dysbiosis-induced TLR4-mediated inflammation and lipotoxicity.•Quercetin counteracts inflammasome and reticulum stress pathway activation.•Modulatory effects displayed by quercetin counteract lipid metabolism deregulation.•Quercetin improves NAFLD via an integrative response including its prebiotic effect.
Sorafenib, a multikinase inhibitor with antiproliferative, antiangiogenic, and proapoptotic properties, constitutes the only effective first-line drug approved for the treatment of advanced ...hepatocellular carcinoma (HCC). Despite its capacity to increase survival in HCC patients, its success is quite low in the long term owing to the development of resistant cells through several mechanisms. Among these mechanisms, the antiangiogenic effects of sustained sorafenib treatment induce a reduction of microvessel density, promoting intratumoral hypoxia and hypoxia-inducible factors (HIFs)-mediated cellular responses that favor the selection of resistant cells adapted to the hypoxic microenvironment. Clinical data have demonstrated that overexpressed HIF-1α and HIF-2α in HCC patients are reliable markers of a poor prognosis. Thus, the combination of current sorafenib treatment with gene therapy or inhibitors against HIFs have been documented as promising approaches to overcome sorafenib resistance both in vitro and in vivo. Because the depletion of one HIF-α subunit elevates the expression of the other HIF-α isoform through a compensatory loop, targeting both HIF-1α and HIF-2α would be a more interesting strategy than therapies that discriminate among HIF-α isoforms. In conclusion, there is a marked correlation between the hypoxic microenvironment and sorafenib resistance, suggesting that targeting HIFs is a promising way to increase the efficiency of treatment.
Scope
Modulation of intestinal microbiota has emerged as a new therapeutic approach for non‐alcoholic fatty liver disease (NAFLD). Herein, it is addressed whether gut microbiota modulation by ...quercetin and intestinal microbiota transplantation can influence NAFLD development.
Methods and results
Gut microbiota donor mice are selected according to their response to high‐fat diet (HFD) and quercetin in terms of obesity and NAFLD‐related biomarkers. Germ‐free recipients displayed metabolic phenotypic differences derived from interactions between microbiota transplanted, diets, and quercetin. Based on the evaluation of hallmark characteristics of NAFLD, it is found that gut microbiota transplantation from the HFD‐non‐responder donor and the HFD‐fed donor with the highest response to quercetin results in a protective phenotype against HFD‐induced NAFLD, in a mechanism that involves gut–liver axis alteration blockage in these receivers. Gut microbiota from the HFD‐responder donor predisposed transplanted germ‐free mice to NAFLD. Divergent protective and deleterious metabolic phenotypes exhibited are related to definite microbial profiles in recipients, highlighting the predominant role of Akkermansia genus in the protection from obesity‐associated NAFLD development.
Conclusions
The results provide scientific support for the prebiotic capacity of quercetin and the transfer of established metabolic profiles through gut microbiota transplantation as a protective strategy against the development of obesity‐related NAFLD.
A potential preventive strategy of quercetin intake and intestinal microbiota transplantation on obesity‐associated non‐alcoholic fatty liver disease (NAFLD) is reported. Hight‐fat diet and quercetin administration result in different metabolic phenotypes, which are transmissible through gut microbiota transplantation to germ‐free mice. The interplay between intestinal microbiota profiles transplanted, diet, and quercetin results in metabolic phenotype transfer associated with protection or predisposition to develop obesity and NAFLD.
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