scholarly journals Information theory tests critical predictions of plant defense theory for specialized metabolism

2020 ◽  
Vol 6 (24) ◽  
pp. eaaz0381 ◽  
Author(s):  
Dapeng Li ◽  
Rayko Halitschke ◽  
Ian T. Baldwin ◽  
Emmanuel Gaquerel
Keyword(s):  
Information Theory ◽  
Plant Defense ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Nicotiana Attenuata ◽  
Closely Related Species ◽  
Specialized Metabolism ◽  
Information Components ◽  
Defense Theory ◽  
Theory Framework

Different plant defense theories have provided important theoretical guidance in explaining patterns in plant specialized metabolism, but their critical predictions remain to be tested. Here, we systematically explored the metabolomes of Nicotiana attenuata, from single plants to populations, as well as of closely related species, using unbiased tandem mass spectrometry (MS/MS) analyses and processed the abundances of compound spectrum–based MS features within an information theory framework to test critical predictions of optimal defense (OD) and moving target (MT) theories. Information components of plant metabolomes were consistent with the OD theory but contradicted the main prediction of the MT theory for herbivory-induced dynamics of metabolome compositions. From micro- to macroevolutionary scales, jasmonate signaling was confirmed as the master determinant of OD, while ethylene signaling provided fine-tuning for herbivore-specific responses annotated via MS/MS molecular networks.

scholarly journals Information theory tests critical predictions of plant defense theory for specialized metabolism

2020 ◽  
Author(s):  
Dapeng Li ◽  
Rayko Halitschke ◽  
Ian T. Baldwin ◽  
Emmanuel Gaquerel
Keyword(s):  
Information Theory ◽  
Plant Defense ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Nicotiana Attenuata ◽  
Closely Related Species ◽  
Specialized Metabolism ◽  
Information Components ◽  
Defense Theory ◽  
Theory Framework

AbstractDifferent plant defense theories have provided important theoretical guidance in explaining patterns in plant specialized metabolism, but their critical predictions remain to be tested. Here, we systematically explored the metabolomes of Nicotiana attenuata, from single plants to populations, as well as of closely-related species, using unbiased MS/MS analyses and processed the abundances of compound-spectrum-based MS features within an information theory framework to test critical predictions of Optimal Defense (OD) and Moving Target (MT) theories. Information components of herbivory-elicited plant metabolomes were fully consistent with the OD theory predictions and contradicted the main prediction of the MT theory. From micro- to macro-evolutionary scales, jasmonate signaling was identified as the master determinant of OD while ethylene signaling provided fine-tuning for herbivore-specific responses annotated via MS/MS molecular networks.One-sentence summaryInformation theory tests defense theory predictions by providing a common currency for comparison of specialized metabolomes

scholarly journals Competing Endogenous RNAs in Cervical Carcinogenesis: A New Layer of Complexity

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 991
Author(s):  
Fernanda Costa Brandão Berti ◽  
Sara Cristina Lobo-Alves ◽  
Camila de Freitas Oliveira-Toré ◽  
Amanda Salviano-Silva ◽  
Karen Brajão de Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Cervical Carcinogenesis ◽  
Molecular Changes ◽  
Cellular Processes ◽  
Target Mrnas ◽  
Competing Endogenous Rnas ◽  
Cervical Cells ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) regulate gene expression by binding to complementary sequences within target mRNAs. Apart from working ‘solo’, miRNAs may interact in important molecular networks such as competing endogenous RNA (ceRNA) axes. By competing for a limited pool of miRNAs, transcripts such as long noncoding RNAs (lncRNAs) and mRNAs can regulate each other, fine-tuning gene expression. Several ceRNA networks led by different lncRNAs—described here as lncRNA-mediated ceRNAs—seem to play essential roles in cervical cancer (CC). By conducting an extensive search, we summarized networks involved in CC, highlighting the major impacts of such dynamic molecular changes over multiple cellular processes. Through the sponging of distinct miRNAs, some lncRNAs as HOTAIR, MALAT1, NEAT1, OIP5-AS1, and XIST trigger crucial molecular changes, ultimately increasing cell proliferation, migration, invasion, and inhibiting apoptosis. Likewise, several lncRNAs seem to be a sponge for important tumor-suppressive miRNAs (as miR-140-5p, miR-143-3p, miR-148a-3p, and miR-206), impairing such molecules from exerting a negative post-transcriptional regulation over target mRNAs. Curiously, some of the involved mRNAs code for important proteins such as PTEN, ROCK1, and MAPK1, known to modulate cell growth, proliferation, apoptosis, and adhesion in CC. Overall, we highlight important lncRNA-mediated functional interactions occurring in cervical cells and their closely related impact on cervical carcinogenesis.

scholarly journals Network Analysis of Inflammatory Bowel Disease Reveals PTPN2 As New Monogenic Cause of Intestinal Inflammation

2019 ◽  
Author(s):  
Marianna Parlato ◽  
Julia Pazmandi ◽  
Qing Nian ◽  
Fabienne Charbit-Henrion ◽  
Bernadette Bègue ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Random Walk ◽  
Bowel Disease ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Genome Wide Association Studies ◽  
Causal Genes ◽  
Disease Module ◽  
Inflammatory Bowel ◽  
Stat Pathway

ABSTRACTBACKGROUND & AIMSGenome-wide association studies (GWAS) have uncovered multiple loci associated with inflammatory bowel disease (IBD), yet delineating functional consequences is complex. We used a network-based approach to uncover traits common to monogenic and polygenic forms of IBD in order to reconstruct disease relevant pathways and prioritize causal genes.METHODSWe have used an iterative random walk with restart to explore network neighborhood around the core monogenic IBD cluster and disease-module cohesion to identify functionally relevant GWAS genes. Whole exome sequencing was used to screen a cohort of monogenic IBD for germline mutations in top GWAS genes. One mutation was identified and validated by a combination of biochemical approaches.RESULTSMonogenic IBD genes clustered siginificantly on the molecular networks and had central roles in network topology. Iterative random walk from these genes allowed to rank the GWAS genes, among which 14 had high disease-module cohesion and were selected as putative causal genes. As a proof of concept, a germline loss of function mutation was identified in PTPN2, one of the top candidates, as a novel genetic etiology of early-onset intestinal autoimmunity. The mutation abolished the catalytic activity of the enzyme, resulting in haploinsufficiency and hyper-activation of the JAK/STAT pathway in lymphocytes.CONCLUSIONSOur network-based approach bridges the gap between large-scale network medicine prediction and single-gene defects and underscores the crucial need of fine tuning the JAK/STAT pathway to preserve intestinal immune homeostasis. Our data provide genetic-based rationale for using drugs targeting the JAK/STAT pathway in IBD.

scholarly journals Illuminating a plant’s tissue-specific metabolic diversity using computational metabolomics and information theory

2016 ◽  
Vol 113 (47) ◽  
pp. E7610-E7618 ◽  
Author(s):  
Dapeng Li ◽  
Sven Heiling ◽  
Ian T. Baldwin ◽  
Emmanuel Gaquerel
Keyword(s):  
Information Theory ◽  
Secondary Metabolism ◽  
Gene Function ◽  
Tissue Level ◽  
Two Dimensions ◽  
Molecular Networks ◽  
Specific Gene ◽  
Theory Analysis ◽  
Tissue Specific ◽  
Metabolite Diversity

Secondary metabolite diversity is considered an important fitness determinant for plants’ biotic and abiotic interactions in nature. This diversity can be examined in two dimensions. The first one considers metabolite diversity across plant species. A second way of looking at this diversity is by considering the tissue-specific localization of pathways underlying secondary metabolism within a plant. Although these cross-tissue metabolite variations are increasingly regarded as important readouts of tissue-level gene function and regulatory processes, they have rarely been comprehensively explored by nontargeted metabolomics. As such, important questions have remained superficially addressed. For instance, which tissues exhibit prevalent signatures of metabolic specialization? Reciprocally, which metabolites contribute most to this tissue specialization in contrast to those metabolites exhibiting housekeeping characteristics? Here, we explore tissue-level metabolic specialization in Nicotiana attenuata, an ecological model with rich secondary metabolism, by combining tissue-wide nontargeted mass spectral data acquisition, information theory analysis, and tandem MS (MS/MS) molecular networks. This analysis was conducted for two different methanolic extracts of 14 tissues and deconvoluted 895 nonredundant MS/MS spectra. Using information theory analysis, anthers were found to harbor the most specialized metabolome, and most unique metabolites of anthers and other tissues were annotated through MS/MS molecular networks. Tissue–metabolite association maps were used to predict tissue-specific gene functions. Predictions for the function of two UDP-glycosyltransferases in flavonoid metabolism were confirmed by virus-induced gene silencing. The present workflow allows biologists to amortize the vast amount of data produced by modern MS instrumentation in their quest to understand gene function.

scholarly journals Blockade of pro-fibrotic response mediated by the miR-143/-145 cluster prevents targeted therapy-induced phenotypic plasticity and resistance in melanoma

2021 ◽  
Author(s):  
Serena Diazzi ◽  
Alberto Baeri ◽  
Julien Fassy ◽  
Margaux Lecacheur ◽  
Oskar Marin-Bejar ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Phenotypic Plasticity ◽  
Mature Mirnas ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Common Mechanism ◽  
Clinical Model ◽  
Ecm Remodeling

Lineage dedifferentiation towards a mesenchymal-like state is a common mechanism of adaptive response and resistance to targeted therapy in melanoma. Yet, the transcriptional network driving this phenotypic plasticity remains elusive. Remarkably, this cellular state displays myofibroblast and fibrotic features and escapes MAPK inhibitors (MAPKi) through extracellular matrix (ECM) remodeling activities. Here we show that the anti-fibrotic drug Nintedanib/BIBF1120 is active to normalize the fibrous ECM network, enhance the efficacy of MAPK-targeted therapy and delay tumor relapse in a pre-clinical model of melanoma. We also uncovered the molecular networks that regulate the acquisition of this resistant phenotype and its reversion by Nintedanib, pointing the miR-143/-145 pro-fibrotic cluster as a driver of the therapy-resistant mesenchymal-like phenotype. Upregulation of the miR-143/-145 cluster under BRAFi/MAPKi therapy was observed in melanoma cells in vitro and in vivo and was associated with an invasive/undifferentiated profile of resistant cells. The 2 mature miRNAs generated from this cluster, miR-143-3p and miR-145-5p collaborated to mediate phenotypic transition towards a drug resistant undifferentiated mesenchymal-like state by targeting Fascin actin-bundling protein 1 (FSCN1), modulating the dynamic crosstalk between the actin cytoskeleton and the ECM through the regulation of focal adhesion dynamics as well as contributing to a fine-tuning of mechanotransduction pathways. Our study brings insights into a novel miRNA-mediated regulatory network that contributes to non-genetic adaptive drug resistance and provides proof-of-principle that preventing MAPKi-induced pro-fibrotic stromal response is a viable therapeutic opportunity for patients on targeted therapy.

scholarly journals The Impact of miRNAs in Health and Disease of Retinal Pigment Epithelium

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniela Intartaglia ◽  
Giuliana Giamundo ◽  
Ivan Conte
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Therapeutic Approaches ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Non Coding Rnas ◽  
The Impact

MicroRNAs (miRNAs), a class of non-coding RNAs, are essential key players in the control of biological processes in both physiological and pathological conditions. miRNAs play important roles in fine tuning the expression of many genes, which often have roles in common molecular networks. miRNA dysregulation thus renders cells vulnerable to aberrant fluctuations in genes, resulting in degenerative diseases. The retinal pigment epithelium (RPE) is a monolayer of polarized pigmented epithelial cells that resides between the light-sensitive photoreceptors (PR) and the choriocapillaris. The demanding physiological functions of RPE cells require precise gene regulation for the maintenance of retinal homeostasis under stress conditions and the preservation of vision. Thus far, our understanding of how miRNAs function in the homeostasis and maintenance of the RPE has been poorly addressed, and advancing our knowledge is central to harnessing their potential as therapeutic agents to counteract visual impairment. This review focuses on the emerging roles of miRNAs in the function and health of the RPE and on the future exploration of miRNA-based therapeutic approaches to counteract blinding diseases.

scholarly journals NaMYC2 transcription factor regulates a subset of plant defense responses in Nicotiana attenuata

2013 ◽  
Vol 13 (1) ◽  
pp. 73 ◽  
Author(s):  
Melkamu G Woldemariam ◽  
Son Truong Dinh ◽  
Youngjoo Oh ◽  
Emmanuel Gaquerel ◽  
Ian T Baldwin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Plant Defense ◽  
Defense Responses ◽  
Nicotiana Attenuata ◽  
Plant Defense Responses

scholarly journals Cyst Nematode Infection Elicits Alteration in the Level of Reactive Nitrogen Species, Protein S-Nitrosylation and Nitration, and Nitrosoglutathione Reductase in Arabidopsis thaliana Roots

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 795
Author(s):  
Mateusz Labudda ◽  
Elżbieta Różańska ◽  
Marta Gietler ◽  
Justyna Fidler ◽  
Ewa Muszyńska ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Plant Defense ◽  
Reactive Nitrogen Species ◽  
Protein S ◽  
Cyst Nematode ◽  
Nematode Infection ◽  
Fine Tuning ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Beet Cyst Nematode

Reactive nitrogen species (RNS) are redox molecules important for plant defense against pathogens. The aim of the study was to determine whether the infection by the beet cyst nematode Heterodera schachtii disrupts RNS balance in Arabidopsis thaliana roots. For this purpose, measurements of nitric oxide (NO), peroxynitrite (ONOO−), protein S-nitrosylation and nitration, and nitrosoglutathione reductase (GSNOR) in A. thaliana roots from 1 day to 15 days post-inoculation (dpi) were performed. The cyst nematode infection caused generation of NO and ONOO− in the infected roots. These changes were accompanied by an expansion of S-nitrosylated and nitrated proteins. The enzyme activity of GSNOR was decreased at 3 and 15 dpi and increased at 7 dpi in infected roots, whereas the GSNOR1 transcript level was enhanced over the entire examination period. The protein content of GSNOR was increased in infected roots at 3 dpi and 7 dpi, but at 15 dpi, did not differ between uninfected and infected roots. The protein of GSNOR was detected in plastids, mitochondria, cytoplasm, as well as endoplasmic reticulum and cytoplasmic membranes. We postulate that RNS metabolism plays an important role in plant defense against the beet cyst nematode and helps the fine-tuning of the infected plants to stress sparked by phytoparasitic nematodes.

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