Biomedicines. 2021 Feb 22;9(2):224. doi: 10.3390/biomedicines9020224.

ABSTRACT

Age-related macular degeneration (AMD) may cause severe loss of vision or blindness, particularly in elderly people. Exudative AMD is characterized by the angiogenesis of blood vessels growing from underneath the macula, crossing the blood-retina barrier (which comprises Bruch's membrane (BM) and the retinal pigmentation epithelium (RPE)), leaking blood and fluid into the retina and knocking off photoreceptors. Here, we simulate a computational model of angiogenesis from the choroid blood vessels via a cellular Potts model, as well as BM, RPE cells, drusen deposits and photoreceptors. Our results indicate that improving AMD may require fixing the impaired lateral adhesion between RPE cells and with BM, as well as diminishing Vessel Endothelial Growth Factor (VEGF) and Jagged proteins that affect the Notch signaling pathway. Our numerical simulations suggest that anti-VEGF and anti-Jagged therapies could temporarily halt exudative AMD while addressing impaired cellular adhesion, which could be more effective over a longer time-span.

PMID:33671578 | DOI:10.3390/biomedicines9020224

Cancers (Basel). 2021 Feb 17;13(4):847. doi: 10.3390/cancers13040847.

ABSTRACT

Exosomes are lipid membrane-enclosed vesicles released by all cell types that act at the paracrine or endocrine level to favor cell differentiation, tissue homeostasis, organ remodeling and immune regulation. Their biosynthesis begins with a cell membrane invagination which generates an early endosome that matures to a late endosome. By inward budding of the late endosome membrane, a multivesicular body (MVB) with intraluminal vesicles (ILVs) is generated. The fusion of MVBs with the plasma membrane releases ILVs into the extracellular space as exosomes, ranging in size from 30 to 100 nm in diameter. The bilipid exosome membrane is rich in cholesterol, ceramides and phosphatidylserine and can be loaded with DNA, RNA, microRNAs, proteins and lipids. It has been demonstrated that exosome secretion is a common mechanism used by the tumor to generate an immunosuppressive microenvironment that favors cancer development and progression, allowing tumor escape from immune control. Due to their ability to transport proteins, lipids and nucleic acids from the cell that gave rise to them, exosomes can be used as a source of biomarkers with great potential for clinical applications in diagnostic, prognostic or therapeutic areas. This article will review the latest research findings on exosomes and their contribution to cancer development.

PMID:33671415 | DOI:10.3390/cancers13040847

Microorganisms. 2021 Feb 17;9(2):415. doi: 10.3390/microorganisms9020415.

ABSTRACT

Corynebacterium pseudotuberculosis is a Gram-positive, facultative intracellular, pathogenic bacterium that infects several different hosts, yielding serious economic losses in livestock farming. It causes several diseases including oedematous skin disease (OSD) in buffaloes, ulcerative lymphangitis (UL) in horses, and caseous lymphadenitis (CLA) in sheep, goats and humans. Despite its economic and medical-veterinary importance, our understanding concerning this organism's transcriptional regulatory mechanisms is still limited. Here, we review the state of the art knowledge on transcriptional regulatory mechanisms of this pathogenic species, covering regulatory interactions mediated by two-component systems, transcription factors and sigma factors. Key transcriptional regulatory players involved in virulence and pathogenicity of C. pseudotuberculosis, such as the PhoPR system and DtxR, are in the focus of this review, as these regulators are promising targets for future vaccine design and drug development. We conclude that more experimental studies are needed to further understand the regulatory repertoire of this important zoonotic pathogen, and that regulators are promising targets for future vaccine design and drug development.

PMID:33671149 | DOI:10.3390/microorganisms9020415

Metabolites. 2021 Feb 17;11(2):113. doi: 10.3390/metabo11020113.

ABSTRACT

Genome-scale metabolic models are of high interest in a number of different research fields. Flux balance analysis (FBA) and other mathematical methods allow the prediction of the steady-state behavior of metabolic networks under different environmental conditions. However, many existing applications for flux optimizations do not provide a metabolite-centric view on fluxes. Metano is a standalone, open-source toolbox for the analysis and refinement of metabolic models. While flux distributions in metabolic networks are predominantly analyzed from a reaction-centric point of view, the Metano methods of split-ratio analysis and metabolite flux minimization also allow a metabolite-centric view on flux distributions. In addition, we present MMTB (Metano Modeling Toolbox), a web-based toolbox for metabolic modeling including a user-friendly interface to Metano methods. MMTB assists during bottom-up construction of metabolic models by integrating reaction and enzymatic annotation data from different databases. Furthermore, MMTB is especially designed for non-experienced users by providing an intuitive interface to the most commonly used modeling methods and offering novel visualizations. Additionally, MMTB allows users to upload their models, which can in turn be explored and analyzed by the community. We introduce MMTB by two use cases, involving a published model of Corynebacterium glutamicum and a newly created model of Phaeobacter inhibens.

PMID:33671140 | DOI:10.3390/metabo11020113

Molecules. 2021 Feb 28;26(5):1307. doi: 10.3390/molecules26051307.

ABSTRACT

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons. The cause of PD is still unclear. Oxidative stress and mitochondrial dysfunction have been linked to the development of PD. Luteolin, a non-toxic flavonoid, has become interested in an alternative medicine, according to its effects on anti-oxidative stress and anti-apoptosis, although the underlying mechanism of luteolin on PD has not been fully elucidated. This study aims to investigate whether luteolin prevents neurotoxicity induction by 1-methyl-4-phenylpyridinium iodide (MPP+), a neurotoxin in neuroblastoma SH-SY5Y cells. The results reveal that luteolin significantly improved cell viability and reduced apoptosis in MPP+-treated cells. Increasing lipid peroxidation and superoxide anion (O2-), including mitochondrial membrane potential (Δψm) disruption, is ameliorated by luteolin treatment. In addition, luteolin attenuated MPP+-induced neurite damage via GAP43 and synapsin-1. Furthermore, Cdk5 is found to be overactivated and correlated with elevation of cleaved caspase-3 activity in MPP+-exposed cells, while phosphorylation of Erk1/2, Drp1, Fak, Akt and GSK3β are inhibited. In contrast, luteolin attenuated Cdk5 overactivation and supported phosphorylated level of Erk1/2, Drp1, Fak, Akt and GSK3β with reducing in cleaved caspase-3 activity. Results indicate that luteolin exerts neuroprotective effects via Cdk5-mediated Erk1/2/Drp1 and Fak/Akt/GSK3β pathways, possibly representing a potential preventive agent for neuronal disorder.

PMID:33671094 | DOI:10.3390/molecules26051307

Int J Mol Sci. 2021 Feb 28;22(5):2452. doi: 10.3390/ijms22052452.

ABSTRACT

Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.

PMID:33671067 | DOI:10.3390/ijms22052452

Int J Mol Sci. 2021 Feb 28;22(5):2420. doi: 10.3390/ijms22052420.

ABSTRACT

Long non-coding RNAs (lncRNAs) are functional transcripts with more than 200 nucleotides. These molecules exhibit great regulatory capacity and may act at different levels of gene expression regulation. Despite this regulatory versatility, the biology of these molecules is still poorly understood. Computational approaches are being increasingly used to elucidate biological mechanisms in which these lncRNAs may be involved. Co-expression networks can serve as great allies in elucidating the possible regulatory contexts in which these molecules are involved. Herein, we propose the use of the pipeline deposited in the RTN package to build lncRNAs co-expression networks using TCGA breast cancer (BC) cohort data. Worldwide, BC is the most common cancer in women and has great molecular heterogeneity. We identified an enriched co-expression network for the validation of relevant cell processes in the context of BC, including LINC00504. This lncRNA has increased expression in luminal subtype A samples, and is associated with prognosis in basal-like subtype. Silencing this lncRNA in luminal A cell lines resulted in decreased cell viability and colony formation. These results highlight the relevance of the proposed method for the identification of lncRNAs in specific biological contexts.

PMID:33670895 | DOI:10.3390/ijms22052420

Microorganisms. 2021 Feb 18;9(2):422. doi: 10.3390/microorganisms9020422.

ABSTRACT

An immunostimulatory glycolipid molecule from the intestinal protozoan parasite Entamoeba histolytica (Eh) and its synthetic analogs derived from its phosphatidylinositol-b-anchor (EhPIb) previously showed considerable immunotherapeutic effects against Leishmania major infection in vitro and in vivo. Here, we describe a high content screening assay, based on primary murine macrophages. Parasites detection is based on a 90 kDA heat shock protein-specific staining, enabling the detection of several Leishmania species. We validated the assay using L. major, L. braziliensis, L. donovani, and L. infantum as well as investigated the anti-leishmanial activity of six immunostimulatory EhPIb-compounds (Eh-1 to Eh-6). Macrophages infected with dermotropic species were more sensitive towards treatment with the compounds as their viability showed a stronger reduction compared to macrophages infected with viscerotropic species. Most compounds caused a significant reduction of the infection rates and the parasite burdens depending on the infecting species. Only compound Eh-6 was found to have activity against all Leishmania species. Considering the challenges in anti-leishmanial drug discovery, we developed a multi-species screening assay capable of utilizing non-recombinant parasite strains, and demonstrated its usefulness by screening macrophage-targeting EhPIb-compounds showing their potential for the treatment of cutaneous and visceral leishmaniasis.

PMID:33670713 | DOI:10.3390/microorganisms9020422

Toxins (Basel). 2021 Feb 18;13(2):160. doi: 10.3390/toxins13020160.

ABSTRACT

Disseminated intravascular coagulation, a severe clinical condition caused by an underlying disease, involves a markedly continuous and widespread activation of coagulation in the circulating blood and the formation of numerous microvascular thrombi. A snakebite, including that of the Yamakagashi (Rhabdophis tigrinus), demonstrates this clinical condition. Thus, an animal model using Yamakagashi venom was constructed. Yamakagashi venom was administered to rats, and its lethality and the changes in blood coagulation factors were detected after venom injection. When 300 μg venom was intramuscularly administered to 12-week-old rats, (1) they exhibited hematuria with plasma hemolysis and died within 48 h; (2) Thrombocytopenia in the blood was observed in the rats; (3) irreversible prolongation of prothrombin time in the plasma to the measurement limit occurred; (4) fibrinogen concentration in the plasma irreversibly decreased below the measurement limit; and (5) A transient increase in the plasma concentration of D-dimer was observed. In this model, a fixed amount of Rhabdophis tigrinus venom injection resulted in the clinical symptom similar to the human pathology with snakebite. The use of the rat model is very effective in validating the therapeutic effect of human disseminated intravascular coagulation condition due to snakebite.

PMID:33670557 | DOI:10.3390/toxins13020160

Int J Mol Sci. 2021 Feb 18;22(4):2003. doi: 10.3390/ijms22042003.

ABSTRACT

Interferons (IFNs) are a crucial component in the innate immune response. Especially the IFN-β signaling operates in most cell types and plays a key role in the first line of defense upon pathogen intrusion. The induction of IFN-β should be tightly controlled, because its hyperactivation can lead to tissue damage or autoimmune diseases. Activation of the IFN-β promoter needs Interferon Regulatory Factor 3 (IRF3), together with Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Activator Protein 1 (AP-1). Here we report that a human noncoding RNA, nc886, is a novel suppressor for the IFN-β signaling and inflammation. Upon treatment with several pathogen-associated molecular patterns and viruses, nc886 suppresses the activation of IRF3 and also inhibits NF-κB and AP-1 via inhibiting Protein Kinase R (PKR). These events lead to decreased expression of IFN-β and resultantly IFN-stimulated genes. nc886's role might be to restrict the IFN-β signaling from hyperactivation. Since nc886 expression is regulated by epigenetic and environmental factors, nc886 might explain why innate immune responses to pathogens are variable depending on biological settings.

PMID:33670458 | DOI:10.3390/ijms22042003

Toxins (Basel). 2021 Feb 11;13(2):133. doi: 10.3390/toxins13020133.

ABSTRACT

Due to increased frequency of cyanobacterial blooms and emerging evidence of cyanotoxicity in biofilm, reliable methods for early cyanotoxin threat detection are of major importance for protection of human, animal and environmental health. To complement the current methods of risk assessment, this study aimed to evaluate selected qPCR assays for detection of potentially toxic cyanobacteria in environmental samples. In the course of one year, 25 plankton and 23 biofilm samples were collected from 15 water bodies in Slovenia. Three different analyses were performed and compared to each other; qPCR targeting mcyE, cyrJ and sxtA genes involved in cyanotoxin production, LC-MS/MS quantifying microcystin, cylindrospermopsin and saxitoxin concentration, and microscopic analyses identifying potentially toxic cyanobacterial taxa. qPCR analyses detected potentially toxic Microcystis in 10 lake plankton samples, and potentially toxic Planktothrix cells in 12 lake plankton and one lake biofilm sample. A positive correlation was observed between numbers of mcyE gene copies and microcystin concentrations. Potential cylindrospermopsin- and saxitoxin-producers were detected in three and seven lake biofilm samples, respectively. The study demonstrated a potential for cyanotoxin production that was left undetected by traditional methods in both plankton and biofilm samples. Thus, the qPCR method could be useful in regular monitoring of water bodies to improve risk assessment and enable timely measures.

PMID:33670338 | DOI:10.3390/toxins13020133

Microorganisms. 2021 Feb 11;9(2):354. doi: 10.3390/microorganisms9020354.

ABSTRACT

The rise in the number of antibiotic-resistant bacteria has become a serious threat to health, making it important to identify, characterize and optimize new molecules to help us to overcome the infections they cause. It is well known that Acinetobacter baumannii has a significant capacity to evade the actions of antibacterial drugs, leading to its emergence as one of the bacteria responsible for hospital and community-acquired infections. Nonetheless, how this pathogen infects and survives inside the host cell is unclear. In this study, we analyze the time-resolved transcriptional profile changes observed in human epithelial HeLa cells after infection by A. baumannii, demonstrating how it survives in host cells and starts to replicate 4 h post infection. These findings were achieved by sequencing RNA to obtain a set of Differentially Expressed Genes (DEGs) to understand how bacteria alter the host cells' environment for their own benefit. We also determine common features observed in this set of genes and identify the protein-protein networks that reveal highly-interacted proteins. The combination of these findings paves the way for the discovery of new antimicrobial candidates for the treatment of multidrug-resistant bacteria.

PMID:33670223 | DOI:10.3390/microorganisms9020354

Antioxidants (Basel). 2021 Feb 11;10(2):277. doi: 10.3390/antiox10020277.

ABSTRACT

Climate change is an invisible, silent killer with calamitous effects on living organisms. As the sessile organism, plants experience a diverse array of abiotic stresses during ontogenesis. The relentless climatic changes amplify the intensity and duration of stresses, making plants dwindle to survive. Plants convert 1-2% of consumed oxygen into reactive oxygen species (ROS), in particular, singlet oxygen (1O2), superoxide radical (O2•-), hydrogen peroxide (H2O2), hydroxyl radical (•OH), etc. as a byproduct of aerobic metabolism in different cell organelles such as chloroplast, mitochondria, etc. The regulatory network comprising enzymatic and non-enzymatic antioxidant systems tends to keep the magnitude of ROS within plant cells to a non-damaging level. However, under stress conditions, the production rate of ROS increases exponentially, exceeding the potential of antioxidant scavengers instigating oxidative burst, which affects biomolecules and disturbs cellular redox homeostasis. ROS are similar to a double-edged sword; and, when present below the threshold level, mediate redox signaling pathways that actuate plant growth, development, and acclimatization against stresses. The production of ROS in plant cells displays both detrimental and beneficial effects. However, exact pathways of ROS mediated stress alleviation are yet to be fully elucidated. Therefore, the review deposits information about the status of known sites of production, signaling mechanisms/pathways, effects, and management of ROS within plant cells under stress. In addition, the role played by advancement in modern techniques such as molecular priming, systems biology, phenomics, and crop modeling in preventing oxidative stress, as well as diverting ROS into signaling pathways has been canvassed.

PMID:33670123 | DOI:10.3390/antiox10020277

Metabolites. 2021 Feb 11;11(2):103. doi: 10.3390/metabo11020103.

ABSTRACT

Related metabolites can be grouped into sets in many ways, e.g., by their participation in series of chemical reactions (forming metabolic pathways), or based on fragmentation spectral similarities or shared chemical substructures. Understanding how such metabolite sets change in relation to experimental factors can be incredibly useful in the interpretation and understanding of complex metabolomics data sets. However, many of the available tools that are used to perform this analysis are not entirely suitable for the analysis of untargeted metabolomics measurements. Here, we present PALS (Pathway Activity Level Scoring), a Python library, command line tool, and Web application that performs the ranking of significantly changing metabolite sets over different experimental conditions. The main algorithm in PALS is based on the pathway level analysis of gene expression (PLAGE) factorisation method and is denoted as mPLAGE (PLAGE for metabolomics). As an example of an application, PALS is used to analyse metabolites grouped as metabolic pathways and by shared tandem mass spectrometry fragmentation patterns. A comparison of mPLAGE with two other commonly used methods (overrepresentation analysis (ORA) and gene set enrichment analysis (GSEA)) is also given and reveals that mPLAGE is more robust to missing features and noisy data than the alternatives. As further examples, PALS is also applied to human African trypanosomiasis, Rhamnaceae, and American Gut Project data. In addition, normalisation can have a significant impact on pathway analysis results, and PALS offers a framework to further investigate this. PALS is freely available from our project Web site.

PMID:33670102 | DOI:10.3390/metabo11020103

Animals (Basel). 2021 Feb 19;11(2):541. doi: 10.3390/ani11020541.

ABSTRACT

Structural variations (SVs) are large DNA segments of deletions, duplications, copy number variations, inversions and translocations in a re-sequenced genome compared to a reference genome. They have been found to be associated with several complex traits in dairy cattle and could potentially help to improve genomic prediction accuracy of dairy traits. Imputation of SVs was performed in individuals genotyped with single-nucleotide polymorphism (SNP) panels without the expense of sequencing them. In this study, we generated 24,908 high-quality SVs in a total of 478 whole-genome sequenced Holstein and Jersey cattle. We imputed 4489 SVs with R2 > 0.5 into 35,568 Holstein and Jersey dairy cattle with 578,999 SNPs with two pipelines, FImpute and Eagle2.3-Minimac3. Genome-wide association studies for production, fertility and overall type with these 4489 SVs revealed four significant SVs, of which two were highly linked to significant SNP. We also estimated the variance components for SNP and SV models for these traits using genomic best linear unbiased prediction (GBLUP). Furthermore, we assessed the effect on genomic prediction accuracy of adding SVs to GBLUP models. The estimated percentage of genetic variance captured by SVs for production traits was up to 4.57% for milk yield in bulls and 3.53% for protein yield in cows. Finally, no consistent increase in genomic prediction accuracy was observed when including SVs in GBLUP.

PMID:33669735 | DOI:10.3390/ani11020541

Viruses. 2021 Feb 16;13(2):308. doi: 10.3390/v13020308.

ABSTRACT

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.

PMID:33669264 | DOI:10.3390/v13020308

Cells. 2021 Feb 16;10(2):402. doi: 10.3390/cells10020402.

ABSTRACT

Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies that are the leading cause of cancer-related death worldwide. Although many NSCLC-related genes and pathways have been identified, there remains an urgent need to mechanistically understand how these genes and pathways drive NSCLC. Here, we propose a knowledge-guided and network-based integration method, called the node and edge Prioritization-based Community Analysis, to identify functional modules and their candidate targets in NSCLC. The protein-protein interaction network was prioritized by performing a random walk with restart algorithm based on NSCLC seed genes and the integrating edge weights, and then a "community network" was constructed by combining Girvan-Newman and Label Propagation algorithms. This systems biology analysis revealed that the CCNB1-mediated network in the largest community provides a modular biomarker, the second community serves as a drug regulatory module, and the two are connected by some contextual signaling motifs. Moreover, integrating structural information into the signaling network suggested novel protein-protein interactions with therapeutic significance, such as interactions between GNG11 and CXCR2, CXCL3, and PPBP. This study provides new mechanistic insights into the landscape of cellular functions in the context of modular networks and will help in developing therapeutic targets for NSCLC.

PMID:33669233 | DOI:10.3390/cells10020402

Polymers (Basel). 2021 Feb 25;13(5):687. doi: 10.3390/polym13050687.

ABSTRACT

The possibility of utilizing lignocellulosic agro-industrial waste products such as cassava peel hydrolysate (CPH) as carbon sources for polyhydroxybutyrate (PHB) biosynthesis and characterization by Amazonian microalga Stigeoclonium sp. B23. was investigated. Cassava peel was hydrolyzed to reducing sugars to obtain increased glucose content with 2.56 ± 0.07 mmol/L. Prior to obtaining PHB, Stigeoclonium sp. B23 was grown in BG-11 for characterization and Z8 media for evaluation of PHB nanoparticles' cytotoxicity in zebrafish embryos. As results, microalga produced the highest amount of dry weight of PHB with 12.16 ± 1.28 (%) in modified Z8 medium, and PHB nanoparticles exerted some toxicity on zebrafish embryos at concentrations of 6.25-100 µg/mL, increased mortality (<35%) and lethality indicators as lack of somite formation (<25%), non-detachment of tail, and lack of heartbeat (both <15%). Characterization of PHB by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimeter (DSC), and thermogravimetry (TGA) analysis revealed the polymer obtained from CPH cultivation to be morphologically, thermally, physically, and biologically acceptable and promising for its use as a biomaterial and confirmed the structure of the polymer as PHB. The findings revealed that microalgal PHB from Stigeoclonium sp. B23 was a promising and biologically feasible new option with high commercial value, potential for biomaterial applications, and also suggested the use of cassava peel as an alternative renewable resource of carbon for PHB biosynthesis and the non-use of agro-industrial waste and dumping concerns.

PMID:33668862 | DOI:10.3390/polym13050687

Genes (Basel). 2021 Feb 25;12(3):332. doi: 10.3390/genes12030332.

ABSTRACT

Soil salinity is a major abiotic stress, limiting lentil productivity worldwide. Understanding the genetic basis of salt tolerance is vital to develop tolerant varieties. A diversity panel consisting of 276 lentil accessions was screened in a previous study through traditional and image-based approaches to quantify growth under salt stress. Genotyping was performed using two contrasting methods, targeted (tGBS) and transcriptome (GBS-t) genotyping-by-sequencing, to evaluate the most appropriate methodology. tGBS revealed the highest number of single-base variants (SNPs) (c. 56,349), and markers were more evenly distributed across the genome compared to GBS-t. A genome-wide association study (GWAS) was conducted using a mixed linear model. Significant marker-trait associations were observed on Chromosome 2 as well as Chromosome 4, and a range of candidate genes was identified from the reference genome, the most plausible being potassium transporters, which are known to be involved in salt tolerance in related species. Detailed mineral composition performed on salt-treated and control plant tissues revealed the salt tolerance mechanism in lentil, in which tolerant accessions do not transport Na+ ions around the plant instead localize within the root tissues. The pedigree analysis identified two parental accessions that could have been the key sources of tolerance in this dataset.

PMID:33668850 | DOI:10.3390/genes12030332

Plants (Basel). 2021 Feb 13;10(2):364. doi: 10.3390/plants10020364.

ABSTRACT

Upon sensing developmental or environmental cues, epigenetic regulators transform the chromatin landscape of a network of genes to modulate their expression and dictate adequate cellular and organismal responses. Knowledge of the specific biological processes and genomic loci controlled by each epigenetic regulator will greatly advance our understanding of epigenetic regulation in plants. To facilitate hypothesis generation and testing in this domain, we present EpiNet, an extensive gene regulatory network (GRN) featuring epigenetic regulators. EpiNet was enabled by (i) curated knowledge of epigenetic regulators involved in DNA methylation, histone modification, chromatin remodeling, and siRNA pathways; and (ii) a machine-learning network inference approach powered by a wealth of public transcriptome datasets. We applied GENIE3, a machine-learning network inference approach, to mine public Arabidopsis transcriptomes and construct tissue-specific GRNs with both epigenetic regulators and transcription factors as predictors. The resultant GRNs, named EpiNet, can now be intersected with individual transcriptomic studies on biological processes of interest to identify the most influential epigenetic regulators, as well as predicted gene targets of the epigenetic regulators. We demonstrate the validity of this approach using case studies of shoot and root apical meristem development.

PMID:33668664 | DOI:10.3390/plants10020364