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Viroids are the smallest pathogens of angiosperms, consisting of non-coding RNAs that cause severe diseases in agronomic crops. Symptoms associated with viroid infection are linked to developmental alterations due to genetic regulation. To understand the global mechanisms of host viroid response, we implemented network approaches to identify master transcription regulators and their differentially expressed targets in tomato infected with mild and severe variants of PSTVd. Our approach integrates root and leaf transcriptomic data, gene regulatory network analysis, and identification of affected biological processes. Our results reveal that specific bHLH, MYB, and ERF transcription factors regulate genes involved in molecular mechanisms underlying critical signaling pathways. Functional enrichment of regulons shows that bHLH-MTRs are linked to metabolism and plant defense, while MYB-MTRs are involved in signaling and hormone-related processes. Strikingly, a member of the bHLH-TF family has a specific potential role as a microprotein involved in the post-translational regulation of hormone signaling events. We found that ERF-MTRs are characteristic of severe symptoms, while ZNF-TF, tf3a-TF, BZIP-TFs, and NAC-TF act as unique MTRs. Altogether, our results lay a foundation for further research on the PSTVd and host genome interaction, providing evidence for identifying potential key genes that influence symptom development in tomato plants.
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Solanum lycopersicum , Viroides , Hormônios , Solanum lycopersicum/metabolismo , Doenças das Plantas/genética , RNA Viral/genética , Fatores de Transcrição/genética , Viroides/genéticaRESUMO
Candida tropicalis, an opportunistic pathogen, ranks among the primary culprits of invasive candidiasis, a condition notorious for its resistance to conventional antifungal drugs. The urgency to combat these drug-resistant infections has spurred the quest for novel therapeutic compounds, with a particular focus on those of natural origin. In this study, we set out to evaluate the impact of isoespintanol (ISO), a monoterpene derived from Oxandra xylopioides, on the transcriptome of C. tropicalis. Leveraging transcriptomics, our research aimed to unravel the intricate transcriptional changes induced by ISO within this pathogen. Our differential gene expression analysis unveiled 186 differentially expressed genes (DEGs) in response to ISO, with a striking 85% of these genes experiencing upregulation. These findings shed light on the multifaceted nature of ISO's influence on C. tropicalis, spanning a spectrum of physiological, structural, and metabolic adaptations. The upregulated DEGs predominantly pertained to crucial processes, including ergosterol biosynthesis, protein folding, response to DNA damage, cell wall integrity, mitochondrial activity modulation, and cellular responses to organic compounds. Simultaneously, 27 genes were observed to be repressed, affecting functions such as cytoplasmic translation, DNA damage checkpoints, membrane proteins, and metabolic pathways like trans-methylation, trans-sulfuration, and trans-propylamine. These results underscore the complexity of ISO's antifungal mechanism, suggesting that it targets multiple vital pathways within C. tropicalis. Such complexity potentially reduces the likelihood of the pathogen developing rapid resistance to ISO, making it an attractive candidate for further exploration as a therapeutic agent. In conclusion, our study provides a comprehensive overview of the transcriptional responses of C. tropicalis to ISO exposure. The identified molecular targets and pathways offer promising avenues for future research and the development of innovative antifungal therapies to combat infections caused by this pathogenic yeast.
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Cultivating Limnospira maxima, renowned for its abundant proteins and valuable pigments, faces substantial challenges rooted in the limited understanding of its optimal growth parameters, associated high costs, and constraints in the procurement of traditional nitrogen sources, particularly NaNO3. To overcome these challenges, we conducted a comprehensive 4 × 3 factorial design study. Factors considered included white, red, blue, and yellow light spectra, along with nitrogen sources NaNO3 and KNO3, as well as a nitrogen-free control, for large-scale implementation. Optimal growth, measured by Optical Density, occurred with white and yellow light combined with KNO3 as the nitrogen source. These conditions also increased dry weight and Chl-a content. Cultures with nitrogen deprivation exhibited high values for these variables, attributed to carbon accumulation in response to nitrogen scarcity. Phycocyanin, a crucial pigment for nutrition and industry, reached its highest levels in cultures exposed to white light and supplemented with KNO3, with an impressive content of 384.11 g kg-1 of dry weight. These results highlight the efficacy and cost-efficiency of using a combination of white light and KNO3 for large-scale L. maxima cultivation. This strategy offers promising opportunities to address global food security challenges and enhance the production of industrially relevant pigments.
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Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes: STAT1, IRF7, ISG15, MX1 and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.
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COVID-19 , Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/genética , COVID-19/genética , SARS-CoV-2 , Rim , Expressão GênicaRESUMO
Viroids are single-stranded, circular RNA molecules (234-406 nt) that infect a wide range of crop species and cause economic losses in agriculture worldwide. They are characterized by the existence of a population of sequence variants, attributed to the low fidelity of RNA polymerases involved in their transcription, resulting in high mutation rates. Therefore, these biological entities exist as quasispecies. This feature allows them to replicate within a wide range of host plants, both monocots and dicots. Viroid hosts include economically important crops such as tomato, citrus, and fruit trees such as peach and avocado. Given the high risk of introducing viroids to viroid disease-free countries, these pathogens have been quarantined globally. As discussed herein, Mexico represents a geographical landscape of viroids linked to their origin and comprises considerable biodiversity. The biological features of viroid species endemic to Mexico are highlighted in this communication. In addition, we report the phylogenetic relationships among viroid and viroid strains, their economic impact, geographical distribution, and epidemiological features, including a broad host range and possible long-distance, seed, or insect-mediated transmission. In summary, this review could be helpful for a better understanding of the biology of viroid diseases and future programs on control of movement and spread to avoid economic losses in agricultural industries.
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Citrus , Solanum lycopersicum , Viroides , Viroides/genética , Filogenia , México/epidemiologiaRESUMO
BACKGROUND: Down syndrome (DS) is the most common chromosomal survival aneuploidy. The increase in DS life expectancy further heightens the risk of dementia, principally early-onset Alzheimer's disease (AD). AD risk in DS is higher, considering that this population may also develop metabolic diseases such as obesity, dyslipidemias, and diabetes mellitus. The extra genetic material that characterizes DS causes an imbalance in the genetic dosage, including over-expression of AD's key pathophysiological molecules and the gene expression regulators, the microRNAs (miRNAs). Two miRNAs, chromosome 21-encoded, miR-155, and let-7c, are associated with cognitive impairment and dementia in adults; but, expression dynamics and relationship with clinical variables during the DS's lifespan had remained hitherto unexplored. METHODS: The anthropometric, clinical, biochemical, and profile expression of circulating miR-155 and let-7c were analyzed in a population of 52 control and 50 DS subjects divided into the young group (Aged ≤20 years) and the adult group (Aged ≥21 years). RESULTS: The expression changes for miR-155 were not significant; nevertheless, a negative correlation with HDL-Cholesterol concentrations was observed. Notably, let-7c was over-expressed in DS from young and old ages. CONCLUSION: Overall, our results suggest that let-7c plays a role from the early stages of DS's cognitive impairment while overexpression of miR-155 may be related to lipid metabolism changes. Further studies of both miRNAs will shed light on their potential as therapeutic targets to prevent or delay DS's cognitive impairment.
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Doença de Alzheimer , MicroRNA Circulante , Síndrome de Down , MicroRNAs , Adulto , Doença de Alzheimer/genética , Cromossomos Humanos Par 21/genética , Síndrome de Down/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Glioblastoma (GBM) is the most aggressive and common brain cancer in adults with the lowest life expectancy. The current neuro-oncology practice has incorporated genes involved in key molecular events that drive GBM tumorigenesis as biomarkers to guide diagnosis and design treatment. This study summarizes findings describing the significant heterogeneity of GBM at the transcriptional and genomic levels, emphasizing 18 driver genes with clinical relevance. A pattern was identified fitting the stem cell model for GBM ontogenesis, with an upregulation profile for MGMT and downregulation for ATRX, H3F3A, TP53 and EGFR in the mesenchymal subtype. We also detected overexpression of EGFR, NES, VIM and TP53 in the classical subtype and of MKi67 and OLIG2 genes in the proneural subtype. Furthermore, we found a combination of the four biomarkers EGFR, NES, OLIG2 and VIM with a remarkable differential expression pattern which confers them a strong potential to determine the GBM molecular subtype. A unique distribution of somatic mutations was found for the young and adult population, particularly for genes related to DNA repair and chromatin remodelling, highlighting ATRX, MGMT and IDH1. Our results also revealed that highly lesioned genes undergo differential regulation with particular biological pathways for young patients. This multi-omic analysis will help delineate future strategies related to the use of these molecular markers for clinical decision-making in the medical routine.
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The structure of eukaryotic genes is generally a combination of exons interrupted by intragenic non-coding DNA regions (introns) removed by RNA splicing to generate the mature mRNA. A fraction of genes, however, comprise a single coding exon with introns in their untranslated regions or are intronless genes (IGs), lacking introns entirely. The latter code for essential proteins involved in development, growth, and cell proliferation and their expression has been proposed to be highly specialized for neuro-specific functions and linked to cancer, neuropathies, and developmental disorders. The abundant presence of introns in eukaryotic genomes is pivotal for the precise control of gene expression. Notwithstanding, IGs exempting splicing events entail a higher transcriptional fidelity, making them even more valuable for regulatory roles. This work aimed to infer the functional role and evolutionary history of IGs centered on the mouse genome. IGs consist of a subgroup of genes with one exon including coding genes, non-coding genes, and pseudogenes, which conform approximately 6% of a total of 21,527 genes. To understand their prevalence, biological relevance, and evolution, we identified and studied 1,116 IG functional proteins validating their differential expression in transcriptomic data of embryonic mouse telencephalon. Our results showed that overall expression levels of IGs are lower than those of MEGs. However, strongly up-regulated IGs include transcription factors (TFs) such as the class 3 of POU (HMG Box), Neurog1, Olig1, and BHLHe22, BHLHe23, among other essential genes including the ß-cluster of protocadherins. Most striking was the finding that IG-encoded BHLH TFs fit the criteria to be classified as microproteins. Finally, predicted protein orthologs in other six genomes confirmed high conservation of IGs associated with regulating neural processes and with chromatin organization and epigenetic regulation in Vertebrata. Moreover, this study highlights that IGs are essential modulators of regulatory processes, such as the Wnt signaling pathway and biological processes as pivotal as sensory organ developing at a transcriptional and post-translational level. Overall, our results suggest that IG proteins have specialized, prevalent, and unique biological roles and that functional divergence between IGs and MEGs is likely to be the result of specific evolutionary constraints.
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As part of a routine screening for the possible presence of the necrotic strains of potato virus Y affecting potatoes in Mexico, five PVY isolates were submitted to biological and molecular analysis. Considering their serological properties, two belong to the common strain (O) and three to the necrotic strain (N). All the isolates induced vein necrosis in Nicotiana tabacum. To characterize the isolates, 5' NTR and P1 genes were sequenced and compared with sequences from GenBank database. Nucleotide sequence similarity ranged from 47-100% in the 5' NTR and from 63-100% in the P1 coding region. The lowest amino acid similarity between sequences of P1 gene was 55%. In phylogenetic trees of 5'NTR analysis, two PVY(O) Mexican isolates clustered with other PVY(O) isolates. In turn, the three PVY(N) isolates grouped with PVY(N-NTN) isolates. The phylogenetic analysis of P1 sequences (nucleotide and amino acid) showed two PVY(O) isolates grouping next to N-NTN cluster. A detailed analysis of the PVY(O) isolates showed two potential recombination regions in the P1 gene, in contrast to 5'NTR where no recombination was detected.
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Potyvirus/genética , Potyvirus/isolamento & purificação , Solanum tuberosum/virologia , Regiões 5' não Traduzidas , Análise por Conglomerados , México , Dados de Sequência Molecular , Filogenia , Doenças das Plantas/virologia , Potyvirus/classificação , RNA Viral/genética , Análise de Sequência de DNA , Homologia de Sequência , Sorotipagem , Nicotiana/virologia , Proteínas Virais/genéticaRESUMO
Viroids are unencapsidated, single-stranded, covalently-closed circular, highly structured, noncoding RNAs of 239â»401 nucleotides that cause disease in several economically important crop plants. In tomato (Solanum lycopersicum cv. Rutgers), symptoms of pospiviroid infection include stunting, reduced vigor, flower abortion, and reduced size and number of fruits, resulting in significant crop losses. Dramatic alterations in plant development triggered by viroid infection are the result of differential gene expression; in our study, we focused on the effect of tomato planta macho viroid (TPMVd) and Mexican papita viroid (MPVd) infection on gene networks associated with the regulation of flower and fruit development. The expression of several of the genes were previously reported to be affected by viroid infection, but two genes not previously studied were included. Changes in gene expression of SlBIGPETAL1 (bHLH transcription factor) and SlOVA6 (proline-like tRNA synthetase) are involved in petal morphology and fertility, respectively. Expression of SlOVA6 was down-regulated in flowers of TPMVd- and MPVd-infected plants, while expression of SlBIGPETAL1 was up-regulated in flowers. Up-regulation of SlBIGPETAL1 and down-regulation of SlOVA6 were positively correlated with symptoms such as reduced petal size and flower abortion. Expression analysis of additional tomato genes and a prediction of a global network association of genes involved in flower and fruit development and impacted by viroid infection may further elucidate the pathways underlying viroid pathogenicity.
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Flores/crescimento & desenvolvimento , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/virologia , Vírus de Plantas/genética , Solanum lycopersicum/virologia , Sequência de Bases , Genes de Plantas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fenótipo , RNA Viral/genética , RNA Viral/metabolismoRESUMO
Viroids are small, covalently closed, circular non-coding RNA pathogens of flowering plants. It is proposed that the symptoms of viroid pathogenesis result from a direct interaction between the viroid genomic RNA and unknown host plant factors. Using a comparative genomic approach we took advantage of the detailed annotation of the Arabidopsis thaliana (Arabidopsis) genome to identify sequence homologies between putative viroid-derived small RNAs (vd-sRNAs) and coding regions in the plant genome. A pool of sequence homologies among 29 species of the Pospiviroidae family and the Arabidopsis genome was analyzed. Using this strategy we identified putative host gene targets that may be involved in symptom expression in viroid-infected plants. In this communication, we report the in silico prediction and the experimental validation of pospiviroid-derived sRNAs conserved in the lower strand of the pathogenicity domain of seven viroid species infecting tomato; those vd-sRNAs targeted for cleavage the host mRNA encoding a conserved tomato WD40-repeat protein (SolWD40-repeat; SGN_U563134). Analysis of SolWD40-repeat expression indicated that this gene is down-regulated in tomato plants infected with tomato planta macho viroid (TPMVd). Furthermore, 5' RLM-RACE revealed that the SolWD40-repeat mRNA is cleaved at the predicted target site showing complementarity to a corresponding TPMVd-sRNA identified in silico. Our approach proved to be useful for the identification of natural host genes containing sequence homologies with segments of the Pospiviroidae genome. Using this strategy we identified a functionally conserved gene in Arabidopsis and tomato, whose expression was modified during viroid infection in the host genome; regulation of this gene expression could be guided by vd-sRNA:mRNA complementarity, suggesting that the comparison of the Arabidopsis genome to viroid sequences could lead to the identification of unexpected interactions between viroid RNAs and their host.