RESUMEN

Aedes aegypti is an important vector of arboviruses, including dengue, chikungunya and Zika. The application of synthetic insecticides is a frequently used strategy to control this insect. Malathion is an organophosphate insecticide that was widely used in Brazil in the 1980s and 1990s to control the adult form of A. aegypti. In situations where resistance to currently used insecticides is detected, the use of malathion may be resumed as a control measure. Many studies have confirmed resistance to malathion, however, comparative studies of differential gene expression of the entire transcriptome of resistant and susceptible insects are scarce. Therefore, understanding the molecular basis of resistance to this insecticide in this species is extremely important. In this paper, we present the first transcriptomic description of susceptible and resistant strains of A. aegypti challenged with malathion. Guided transcriptome assembly resulted in 39,904 transcripts, where 2133 differentially expressed transcripts were detected, and three were validated by RT-qPCR. Enrichment analysis for these identified transcripts resulted in 13 significant pathways (padj < 0.05), 8 associated with down-regulated and 5 with up-regulated transcripts in treated resistant insects. It was possible to divide the transcripts according to the mechanism of action into three main groups: (i) genes involved in detoxification metabolic pathways; (ii) genes of proteins located in the membrane/extracellular region; and (iii) genes related to DNA integration/function. These results are important in advancing knowledge of genes related to resistance mechanisms in this insect, enabling the development of effective technologies and strategies for managing insecticide resistance.

Asunto(s)

Aedes , Resistencia a los Insecticidas , Insecticidas , Malatión , Transcriptoma , Malatión/farmacología , Animales , Aedes/genética , Aedes/efectos de los fármacos , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Transcriptoma/efectos de los fármacos , Transcriptoma/genética , Perfilación de la Expresión Génica/métodos , Mosquitos Vectores/genética , Mosquitos Vectores/efectos de los fármacos , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo

RESUMEN

Plant Snakin/GASA and defensin peptides are cysteine-rich molecules with a wide range of biological functions. They are included within the large family of plant antimicrobial peptides (AMPs), characterized by their structural stability, broad spectrum of activity, and diverse mechanisms of action. The Dilatata group of Paspalum includes five allotetraploids that share an equivalent genomic formula IIJJ. From RNA-seq data of seedling tissues, we performed an in silico characterization of the defensin and Snakin/GASA genes in these species and diploids with a II and JJ genome formula and studied the evolutionary consequences of polyploidy on the expression of the two AMPs families. A total of 107 defensins (distributed in eight groups) and 145 Snakin/GASA (grouped in three subfamilies) genes were identified. Deletions, duplications and/or gene silencing seem to have mediated the evolution of these genes in the allotetraploid species. In defensin genes, the IIJJ allopolyploids retained the I subgenome defensin copies in some of the identified groups supporting the closeness of their nuclear genome with the I subgenome species. In both AMPs families, orthologous genes in tetraploids exhibit higher similarity to each other than with diploids. This data supports the theory of a single origin for the allotetraploids. Several copies of both defensin and Snakin/GASA genes were detected in the five polyploids which could have arisen due to duplication events occurring independently during the diploidization processes in the allotetraploid taxa.

Asunto(s)

Defensinas , Diploidia , Proteínas de Plantas , Tetraploidía , Defensinas/genética , Defensinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poaceae/genética , Poaceae/metabolismo , Transcriptoma , Regulación de la Expresión Génica de las Plantas , Poliploidía , Filogenia , Perfilación de la Expresión Génica , Evolución Molecular

RESUMEN

Drought stress is a key limitation for plant growth and colonization of arid habitats. We study the evolution of gene expression response to drought stress in a wild tomato, Solanum chilense, naturally occurring in dry habitats in South America. We conduct a transcriptome analysis under standard and drought experimental conditions to identify drought-responsive gene networks and estimate the age of the involved genes. We identify two main regulatory networks corresponding to two typical drought-responsive strategies: cell cycle and fundamental metabolic processes. The metabolic network exhibits a more recent evolutionary origin and a more variable transcriptome response than the cell cycle network (with ancestral origin and higher conservation of the transcriptional response). We also integrate population genomics analyses to reveal positive selection signals acting at the genes of both networks, revealing that genes exhibiting selective sweeps of older age also exhibit greater connectivity in the networks. These findings suggest that adaptive changes first occur at core genes of drought response networks, driving significant network re-wiring, which likely underpins species divergence and further spread into drier habitats. Combining transcriptomics and population genomics approaches, we decipher the timing of gene network evolution for drought stress response in arid habitats.

Asunto(s)

Sequías , Redes Reguladoras de Genes , Solanum , Estrés Fisiológico , Solanum/genética , Estrés Fisiológico/genética , Transcriptoma/genética , Adaptación Fisiológica/genética , Perfilación de la Expresión Génica , Ecosistema , Evolución Molecular , Regulación de la Expresión Génica de las Plantas , América del Sur , Selección Genética

RESUMEN

In this study, we identified miRNAs and their potential mRNA targets that are intricately linked to primary chemotherapy response in patients with invasive ductal carcinomas. A cohort of individuals diagnosed with advanced invasive breast ductal carcinoma who underwent primary chemotherapy served as the cornerstone of our study. We conducted a comparative analysis of microRNA expression among patients who either responded or did not respond to primary systemic therapy. To analyze the correlation between the expression of the whole transcriptome and the 24 differentially expressed (DE) miRNAs, we harnessed the extensive repository of The Cancer Genome Atlas (TCGA) database. We mapped molecular mechanisms associated with these miRNAs and their targets from TCGA breast carcinomas. The resultant expression profile of the 24 DE miRNAs emerged as a potent and promising predictive model, offering insights into the intricate dynamics of chemotherapy responsiveness of advanced breast tumors. The discriminative analysis based on the principal component analysis identified the most representative miRNAs across breast cancer samples (miR-210, miR-197, miR-328, miR-519a, and miR-628). Moreover, the consensus clustering generated four possible clusters of TCGA patients. Further studies should be conducted to advance these findings.

Asunto(s)

Biomarcadores de Tumor , Neoplasias de la Mama , Carcinoma Ductal de Mama , MicroARNs , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , MicroARNs/análisis , Biomarcadores de Tumor/análisis , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patología , Persona de Mediana Edad , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Adulto , Anciano , Transcriptoma

RESUMEN

The Andean domesticated common beans (Phaseolus vulgaris) are significant sources of phenolic compounds associated with health benefits. However, the regulation of biosynthesis of these compounds during bean seed development remains unclear. To elucidate the gene expression patterns involved in the regulation of the flavonoid pathway, we conducted a transcriptome analysis of two contrasting Chilean varieties, Negro Argel (black bean) and Coscorron (white bean), at three developmental stages associated with seed color change, as well as different flavonoid compound accumulations. Our study reveals that phenolic compound synthesis initiates during seed filling, although it exhibits desynchronization between both varieties. We identified 10,153 Differentially Expressed Genes (DEGs) across all comparisons. The KEGG pathway 'Flavonoid biosynthesis' showed enrichment of induced DEGs in Negro Argel (PV172), consistent with the accumulation of delphinidin, petunidin, and malvidin hexosides in their seeds, while catechin glucoside, procyanidin and kaempferol derivatives were predominantly detected in Coscorrón (PV24). Furthermore, while the flavonoid pathway was active in both varieties, our results suggest that enzymes involved in the final steps, such as ANS and UGT, were crucial, inducing anthocyanin formation in Negro Argel. Additionally, during active anthocyanin biosynthesis, the accumulation of reserve proteins or those related to seed protection and germination was induced. These findings provide valuable insights and serve as a guide for plant breeding aimed at enhancing the health and nutritional properties of common beans.

Asunto(s)

Flavonoides , Perfilación de la Expresión Génica , Phaseolus , Semillas , Semillas/genética , Semillas/metabolismo , Semillas/crecimiento & desarrollo , Phaseolus/genética , Phaseolus/metabolismo , Flavonoides/biosíntesis , Flavonoides/metabolismo , Regulación de la Expresión Génica de las Plantas , Transcriptoma

RESUMEN

Nestmate recognition in ants is regulated through the detection of cuticular hydrocarbons by odorant receptors (ORs) in the antennae. These ORs are crucial for maintaining colony cohesion that allows invasive ant species to dominate colonized environments. In the invasive Argentine ant, Linepithema humile, ORs regulating nestmate recognition are thought to be present in a clade of nine-exon odorant receptors, but the identity of the specific genes remains unknown. We sought to narrow down the list of candidate genes using transcriptomics and phylostratigraphy. Comparative transcriptomic analyses were conducted on the antennae, head, thorax, and legs of Argentine ant workers. We have identified a set of twenty-one nine-exon odorant receptors enriched in the antennae compared to the other tissues, allowing for downstream verification of whether they can detect Argentine ant cuticular hydrocarbons. Further investigation of these ORs could allow us to further understand the mechanisms underlying nestmate recognition and colony cohesion in ants.

Asunto(s)

Hormigas , Filogenia , Receptores Odorantes , Animales , Hormigas/genética , Hormigas/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Transcriptoma , Perfilación de la Expresión Génica , Antenas de Artrópodos/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo

RESUMEN

Background: The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Methods: Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. Results: The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. Conclusion: The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.

Asunto(s)

Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Transcriptoma , Humanos , Neoplasias Pulmonares/microbiología , Neoplasias Pulmonares/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Biología Computacional , Pulmón/microbiología , Pulmón/patología , Boca/microbiología , Transducción de Señal , Microbioma Gastrointestinal/genética , Microbiota/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/genética , Regulación Neoplásica de la Expresión Génica

RESUMEN

BACKGROUND: Tumour dormancy, a resistance mechanism employed by cancer cells, is a significant challenge in cancer treatment, contributing to minimal residual disease (MRD) and potential relapse. Despite its clinical importance, the mechanisms underlying tumour dormancy and MRD remain unclear. In this study, we employed two syngeneic murine models of myeloid leukemia and melanoma to investigate the genetic, epigenetic, transcriptomic and protein signatures associated with tumour dormancy. We used a multiomics approach to elucidate the molecular mechanisms driving MRD and identify potential therapeutic targets. RESULTS: We conducted an in-depth omics analysis encompassing whole-exome sequencing (WES), copy number variation (CNV) analysis, chromatin immunoprecipitation followed by sequencing (ChIP-seq), transcriptome and proteome investigations. WES analysis revealed a modest overlap of gene mutations between melanoma and leukemia dormancy models, with a significant number of mutated genes found exclusively in dormant cells. These exclusive genetic signatures suggest selective pressure during MRD, potentially conferring resistance to the microenvironment or therapies. CNV, histone marks and transcriptomic gene expression signatures combined with Gene Ontology (GO) enrichment analysis highlighted the potential functional roles of the mutated genes, providing insights into the pathways associated with MRD. In addition, we compared "murine MRD genes" profiles to the corresponding human disease through public datasets and highlighted common features according to disease progression. Proteomic analysis combined with multi-omics genetic investigations, revealed a dysregulated proteins signature in dormant cells with minimal genetic mechanism involvement. Pathway enrichment analysis revealed the metabolic, differentiation and cytoskeletal remodeling processes involved in MRD. Finally, we identified 11 common proteins differentially expressed in dormant cells from both pathologies. CONCLUSIONS: Our study underscores the complexity of tumour dormancy, implicating both genetic and nongenetic factors. By comparing genomic, transcriptomic, proteomic, and epigenomic datasets, our study provides a comprehensive understanding of the molecular landscape of minimal residual disease. These results provide a robust foundation for forthcoming investigations and offer potential avenues for the advancement of targeted MRD therapies in leukemia and melanoma patients, emphasizing the importance of considering both genetic and nongenetic factors in treatment strategies.

Asunto(s)

Modelos Animales de Enfermedad , Melanoma , Neoplasia Residual , Animales , Melanoma/genética , Melanoma/patología , Ratones , Leucemia/genética , Leucemia/patología , Variaciones en el Número de Copia de ADN , Secuenciación del Exoma , Ratones Endogámicos C57BL , Proteómica , Transcriptoma , Perfilación de la Expresión Génica , Multiómica

RESUMEN

Osmoregulation, the physiological regulation of water and ion balance, is vital for the survival of both aquatic and terrestrial insects. In freshwater aquatic insects, such as those within the Lampyridae family, this function is important due to the natural variation of aquatic habitats. Aquaporins play a key role in this process by facilitating the rapid transport of water molecules across cell membranes, maintaining cellular water balance, and adapting to changes in external salinity. In this study, I investigate the genetic diversity and expression levels of aquaporins in Elateroidea, particularly focusing on the Lampyridae family, using transcriptomic data and in silico analyses. The results reveal the diversity of aquaporins and compare gene expression patterns between freshwater aquatic Lampyridae and terrestrial Elateroidea species, such as Lycidae, Phengodidae, and Elateridae. Phylogenetic analyses identify seven distinct clades of aquaporins and uncovered gene duplication events related to the diversification of Elateridae and Lampyridae. A comparative abundance analysis indicated higher aquaporin expression in aquatic fireflies, aligning with the need for efficient osmoregulation in aquatic environments. Additionally, stage-specific expression patterns in Aspisoma lineatum (Neotropical firefly) and Aquatica lateralis (Paleartic firefly) suggest species-specific strategies for coping with osmotic challenges during development. This study provides insights into the evolutionary adaptations of aquaporins in Elateroidea, highlighting their importance in both aquatic and terrestrial insect physiology.

Asunto(s)

Acuaporinas , Filogenia , Animales , Acuaporinas/genética , Acuaporinas/metabolismo , RNA-Seq , Transcriptoma , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Osmorregulación/genética , Variación Genética , Insectos/genética , Insectos/metabolismo

RESUMEN

Confronting environments with low relative humidity is one of the main challenges faced by insects with expanding distribution ranges. Anastrepha ludens (the Mexican fruit fly) has evolved to cope with the variable conditions encountered during its lifetime, which allows it to colonise a wide range of environments. However, our understanding of the mechanisms underpinning the ability of this species to confront environments with low relative humidity is incomplete. In this sense, omic approaches such as transcriptomics can be helpful for advancing our knowledge on how this species copes with desiccation stress. Considering this, in this study, we performed transcriptomic analyses to compare the molecular responses of laboratory-reared A. ludens exposed and unexposed to desiccation. Data from the transcriptome analyses indicated that the responses to desiccation are shared by both sexes. We identified the up-regulation of transcripts encoding proteins involved in lipid metabolism and membrane remodelling, as well as proteases and cuticular proteins. Our results provide a framework for understanding the response to desiccation stress in one of the most invasive fruit fly species in the world.

Asunto(s)

Desecación , Tephritidae , Animales , Tephritidae/genética , Tephritidae/fisiología , Femenino , Masculino , Transcriptoma , Perfilación de la Expresión Génica , Estrés Fisiológico

RESUMEN

In samples of harmful algal blooms (HABs), seawater can contain a high abundance of microorganisms and elemental ions. Along with the hardness of the walls of key HAB dinoflagellates such as Prorocentrum triestinum, this makes RNA extraction very difficult. These components interfere with RNA isolation, causing its degradation, in addition to the complex seawater properties of HABs that could hinder RNA isolation for effective RNA sequencing and transcriptome profiling. In this study, an RNA isolation technique was established through the modification of the Trizol method by applying the Micropestle System on cell pellets of P. triestinum frozen at -20 °C, obtained from 400 mL of culture with a total of 107 cells/mL. The results of the modified Trizol protocol generated quality RNA samples for transcriptomics sequencing, as determined by their measurement in Analyzer Agilent 4150.

Asunto(s)

Dinoflagelados , Dinoflagelados/genética , ARN/aislamiento & purificación , ARN/genética , Guanidinas/química , Análisis de Secuencia de ARN/métodos , Floraciones de Algas Nocivas , Perfilación de la Expresión Génica/métodos , Transcriptoma , Nucleótidos/genética , Nucleótidos/aislamiento & purificación , Agua de Mar , Fenoles

RESUMEN

To further understand the impact of deficiency of the autoimmune regulator (Aire) gene during the adhesion of medullary thymic epithelial cells (mTECs) to thymocytes, we sequenced single-cell libraries (scRNA-seq) obtained from Aire wild-type (WT) (Airewt/wt ) or Aire-deficient (Airewt/mut ) mTECs cocultured with WT single-positive (SP) CD4+ thymocytes. Although the libraries differed in their mRNA and long noncoding RNA (lncRNA) profiles, indicating that mTECs were heterogeneous in terms of their transcriptome, UMAP clustering revealed that both mTEC lines expressed their specific markers, i.e., Epcam, Itgb4, Itga6, and Casp3 in resting mTECs and Ccna2, Pbk, and Birc5 in proliferative mTECs. Both cocultured SP CD4+ thymocytes remained in a homogeneous cluster expressing the Il7r and Ccr7 markers. Comparisons of the two types of cocultures revealed the differential expression of mRNAs that encode transcription factors (Zfpm2, Satb1, and Lef1), cell adhesion genes (Itgb1) in mTECs, and Themis in thymocytes, which is associated with the regulation of positive and negative selection. At the single-cell sequencing resolution, we observed that Aire acts on both Aire WT and Aire-deficient mTECs as an upstream controller of mRNAs, which encode transcription factors or adhesion proteins that, in turn, are posttranscriptionally controlled by lncRNAs, for example, Neat1, Malat1, Pvt1, and Dancr among others. Under Aire deficiency, mTECs dysregulate the expression of MHC-II, CD80, and CD326 (EPCAM) protein markers as well as metabolism and cell cycle-related mRNAs, which delay the cell cycle progression. Moreover, when adhered to mTECs, WT SP CD4+ or CD8+ thymocytes modulate the expression of cell activation proteins, including CD28 and CD152/CTLA4, and the expression of cellular metabolism mRNAs. These findings indicate a complex mechanism through which an imbalance in Aire expression can affect mTECs and thymocytes during adhesion.

Asunto(s)

Proteína AIRE , Adhesión Celular , Células Epiteliales , ARN Largo no Codificante , Timocitos , Factores de Transcripción , Transcriptoma , ARN Largo no Codificante/genética , Animales , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ratones , Timocitos/metabolismo , Timocitos/inmunología , Timocitos/citología , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , Timo/citología , Timo/inmunología , Timo/metabolismo , Análisis de la Célula Individual , Redes Reguladoras de Genes , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Técnicas de Cocultivo , Perfilación de la Expresión Génica , Ratones Noqueados

RESUMEN

This study aimed to evaluate the localised effects of intrauterine ozone therapy on endometrial recovery in mares with endometritis. Our investigation assessed changes in gene expression profiles of anti-inflammatory (IL-1RA and IL-10), proinflammatory (IL-R1B3i and TNFα) and pleiotropic (IL-6) cytokines, along with detailed histological measurements of epithelial and endometrial thickness and the glandular area ratio. Twenty mares were assigned to a 2 × 2 factorial design based on endometritis diagnosis and treatment (control or 42 µg/mL ozone insufflation), resulting in four groups: NC (negative for endometritis/control), NO (negative/ozone), PC (positive/control) and PO (positive/ozone). Oestrus was induced with 2 mg of oestradiol benzoate on Days -1, 1 and 3, plus 1 mg on Day 5. Day 0 marked the initial uterine treatment, followed by insufflations on Days 1 and 2 with O3 (ozone) or O2 (control). Uterine biopsies were taken before treatment on Day 0 and Day 6 for histological analysis and gene expression assessment. Data were analysed using a statistical model that included endometritis status, treatment type, biopsy times (D0 and D6) and their interactions, analysed with Proc Glimmix. Regardless of treatment or endometritis status, significant biopsy effects (p < 0.01) indicated increased epithelial height and endometrial thickness in Day 6 samples. Analysis of IL-1 and TNFα revealed a significant interaction (p < 0.05) among endometritis, treatment and biopsy, with higher IL-1B3i expression on Day 6 in the PC group. The treatment effect (p < 0.04) showed a higher frequency (p < 0.01) of animals with positive modulation in the PC group (66.7%) versus the PO group (0.0%). An interaction effect (p = 0.08) between endometritis and treatment resulted from higher IL-1RA expression on Day 6 in the PC group compared to the PO group. Biopsy effect was significant for IL-10 (p < 0.01), indicating higher values in the second sample associated with tissue repair. In the short-term evaluation, ozone therapy did not influence endometrial morphology and may modulate cytokine expression, specifically the reduction in IL-1 and TNFα levels. Therefore, this therapy appears to be a safe and potentially effective treatment for modulating the inflammatory response in mares with endometritis.

Asunto(s)

Citocinas , Endometritis , Enfermedades de los Caballos , Ozono , Útero , Animales , Femenino , Ozono/farmacología , Endometritis/veterinaria , Endometritis/tratamiento farmacológico , Caballos , Enfermedades de los Caballos/tratamiento farmacológico , Útero/patología , Citocinas/genética , Citocinas/metabolismo , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/patología , Estradiol/farmacología , Estradiol/análogos & derivados , Transcriptoma

RESUMEN

Spiders of Loxosceles genus, or Brown spiders produce a potent venom with minimal volume and protein content. Among its toxins, phospholipases D (PLDs) are notable for causing primary local and systemic manifestations observed following envenomation. They degrade cellular phospholipids, mainly sphingomyelin and lysophosphatidylcholine. We present a robust and detailed analysis of PLD transcripts from venom glands of three major clinically relevant South American species-L. intermedia, L. laeta, and L. gaucho-using next-generation sequencing. Results confirmed that PLDs are the most highly expressed toxins, accounting for 65.4 % of expression in L. intermedia, 71.8 % in L. gaucho, and 50.4 % in L. laeta. These findings further support the idea that these enzymes form a protein family both within and across species. Eighteen contigs for PLDs were found for L. gaucho, 24 for L. intermedia, and 21 for L. laeta. A detailed analysis revealed that, although all contigs display conserved amino acid residues directly involved in catalysis, magnesium coordination, and substrate affinity, they also possess distinct primary sequences with important substitutions. Such data reinforces the hypothesis that these toxins may act synergistically. Furthermore, new PLD sequences were identified within the contigs. For L. intermedia, 14 potential new isoforms were identified; 16 for L gaucho; and 16 novel sequences for L. laeta. This indicates that there is still a wealth of undisclosed information about these toxins. These data will help identify structural and functional differences among these proteins, support future functional studies, and to the comprehensive understanding of the mechanism of action of PLDs.

Asunto(s)

Fosfolipasa D , Venenos de Araña , Fosfolipasa D/genética , Fosfolipasa D/metabolismo , Fosfolipasa D/química , Animales , Venenos de Araña/genética , Venenos de Araña/enzimología , Filogenia , Secuencia de Aminoácidos , Isoenzimas/genética , Isoenzimas/metabolismo , Arañas/genética , Arañas/enzimología , Especificidad de la Especie , Araña Reclusa Parda , Perfilación de la Expresión Génica , Transcriptoma , Isoformas de Proteínas/genética , Hidrolasas Diéster Fosfóricas

RESUMEN

INTRODUCTION: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive. METHODS: Here, we integrated [18F]FDG-PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel-wise linear regression analysis. RESULTS: Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG-PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak-t(223) = 4.86, P value < 0.001) and zinc-finger-related regulatory units (peak-t(223) = 3.90, P value < 0.001). DISCUSSION: By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity-associated genes and zinc-finger-related regulatory units are highly associated with brain metabolic changes in AD. HIGHLIGHTS: We conducted an integrated analysis of system-based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) at the voxel level in Alzheimer's disease (AD). The biological process of serine/threonine kinase activity was the most associated with [18F]FDG-PET in the AD brain. Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG-PET. Zinc-finger transcription factor targets were associated with AD brain [18F]FDG-PET metabolism.

Asunto(s)

Enfermedad de Alzheimer , Encéfalo , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/diagnóstico por imagen , Humanos , Fluorodesoxiglucosa F18/metabolismo , Masculino , Femenino , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Anciano , Transcriptoma , Hipocampo/metabolismo , Hipocampo/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/genética , Disfunción Cognitiva/diagnóstico por imagen , Anciano de 80 o más Años

RESUMEN

Wood serves crucial functions in plants, yet our understanding of the mechanisms governing the composition, arrangement, and dimensions of its cells remains limited. The abrupt transition from nonlianescent to lianescent xylem in lianas represents an excellent model to address the underlying mechanisms, although consistent triggering factors for this process remain uncertain. In this study we examined how physical support attachment impacts the development of lianescent xylem in Bignonia magnifica (Bignoniaceae), employing a comprehensive approach integrating detailed anatomical analysis with gene expression profiling of cambium and differentiating xylem. Our findings demonstrate that attachment to physical supports triggers the formation of lianescent xylem, leading to increased vessel size, broader vessel distribution, reduced fibre content, and higher potential specific water conductivity than nonlianescent xylem. These shifts in wood anatomy coincide with the downregulation of genes associated with cell division and cell wall biosynthesis, and the upregulation of transcription factors, defense/cell death, and hormone-responsive genes in the lianescent xylem. Our findings provide insights into the regulation of xylem differentiation, driven by response to environmental stimuli. Additionally, they shed light on the mechanisms underlying the adaptation of lianas to climbing.

Asunto(s)

Cámbium , Regulación de la Expresión Génica de las Plantas , Xilema , Xilema/fisiología , Xilema/anatomía & histología , Cámbium/genética , Cámbium/crecimiento & desarrollo , Transcriptoma , Madera/anatomía & histología , Madera/genética , Madera/fisiología , Diferenciación Celular/genética , Perfilación de la Expresión Génica , Pared Celular/metabolismo

RESUMEN

Oil palm (Elaeis guineensis Jacq.) is a highly productive crop economically significant for food, cosmetics, and biofuels. Abiotic stresses such as low water availability, salt accumulation, and high temperatures severely impact oil palm growth, physiology, and yield by restricting water flux among soil, plants, and the environment. While drought stress's physiological and biochemical effects on oil palm have been extensively studied, the molecular mechanisms underlying drought stress tolerance remain unclear. Under water deficit conditions, this study investigates two commercial E. guineensis cultivars, IRHO 7001 and IRHO 2501. Water deficit adversely affected the physiology of both cultivars, with IRHO 2501 being more severely impacted. After several days of water deficit, there was a 40% reduction in photosynthetic rate (A) for IRHO 7001 and a 58% decrease in IRHO 2501. Further into the drought conditions, there was a 75% reduction in A for IRHO 7001 and a 91% drop in IRHO 2501. Both cultivars reacted to the drought stress conditions by closing stomata and reducing the transpiration rate. Despite these differences, no significant variations were observed between the cultivars in stomatal conductance, transpiration, or instantaneous leaf-level water use efficiency. This indicates that IRHO 7001 is more tolerant to drought stress than IRHO 2501. A differential gene expression and network analysis was conducted to elucidate the differential responses of the cultivars. The DESeq2 algorithm identified 502 differentially expressed genes (DEGs). The gene coexpression network for IRHO 7001 comprised 274 DEGs and 46 predicted HUB genes, whereas IRHO 2501's network included 249 DEGs and 3 HUB genes. RT-qPCR validation of 15 DEGs confirmed the RNA-Seq data. The transcriptomic profiles and gene coexpression network analysis revealed a set of DEGs and HUB genes associated with regulatory and transcriptional functions. Notably, the zinc finger protein ZAT11 and linoleate 13S-lipoxygenase 2-1 (LOX2.1) were overexpressed in IRHO 2501 but under-expressed in IRHO 7001. Additionally, phytohormone crosstalk was identified as a central component in the response and adaptation of oil palm to drought stress.

Asunto(s)

Arecaceae , Sequías , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico , Transcriptoma , Estrés Fisiológico/genética , Arecaceae/genética , Arecaceae/fisiología , Arecaceae/metabolismo , Perfilación de la Expresión Génica , Fotosíntesis/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo

RESUMEN

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.

Asunto(s)

Biomarcadores de Tumor , Neoplasias de la Mama , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Terapia Neoadyuvante , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Resistencia a Antineoplásicos/genética , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Perfilación de la Expresión Génica , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Transcriptoma

RESUMEN

Here, we performed single-cell RNA sequencing of S1 and receptor binding domain protein-specific B cells from convalescent COVID-19 patients with different clinical manifestations. This study aimed to evaluate the role and developmental pathway of atypical memory B cells (MBCs) in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The results revealed a proinflammatory signature across B cell subsets associated with disease severity, as evidenced by the upregulation of genes such as GADD45B, MAP3K8, and NFKBIA in critical and severe individuals. Furthermore, the analysis of atypical MBCs suggested a developmental pathway similar to that of conventional MBCs through germinal centers, as indicated by the expression of several genes involved in germinal center processes, including CXCR4, CXCR5, BCL2, and MYC. Additionally, the upregulation of genes characteristic of the immune response in COVID-19, such as ZFP36 and DUSP1, suggested that the differentiation and activation of atypical MBCs may be influenced by exposure to SARS-CoV-2 and that these genes may contribute to the immune response for COVID-19 recovery. Our study contributes to a better understanding of atypical MBCs in COVID-19 and the role of other B cell subsets across different clinical manifestations.

Asunto(s)

COVID-19 , Células B de Memoria , SARS-CoV-2 , Análisis de la Célula Individual , Humanos , COVID-19/inmunología , COVID-19/virología , COVID-19/genética , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Células B de Memoria/inmunología , Masculino , Adulto , Femenino , Persona de Mediana Edad , Perfilación de la Expresión Génica , Transcriptoma , Centro Germinal/inmunología , Linfocitos B/inmunología , Anciano

RESUMEN

OBJECTIVE: This study aimed to assess the influence of smoking on the subgingival metatranscriptomic profile of young patients affected by stage III/IV and generalized periodontal disease. METHODOLOGY: In total, six young patients, both smokers and non-smokers (n=3/group), who were affected by periodontitis were chosen. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for case-control reporting were followed. Periodontal clinical measurements and subgingival biofilm samples were collected. RNA was extracted from the biofilm and sequenced via Illumina HiSeq. Differential expression analysis used Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and differentially expressed genes were identified using the Sleuth package in R, with a statistical cutoff of ≤0.05. RESULTS: This study found 3351 KEGGs in the subgingival biofilm of both groups. Smoking habits altered the functional behavior of subgingival biofilm, resulting in 304 differentially expressed KEGGs between groups. Moreover, seven pathways were modulated: glycan degradation, galactose metabolism, glycosaminoglycan degradation, oxidative phosphorylation, peptidoglycan biosynthesis, butanoate metabolism, and glycosphingolipid biosynthesis. Smoking also altered antibiotic resistance gene levels in subgingival biofilm by significantly overexpressing genes related to beta-lactamase, permeability, antibiotic efflux pumps, and antibiotic-resistant synthetases. CONCLUSION: Due to the limitations of a small sample size, our data suggest that smoking may influence the functional behavior of subgingival biofilm, modifying pathways that negatively impact the behavior of subgingival biofilm, which may lead to a more virulent community.

Asunto(s)

Biopelículas , Fumar , Humanos , Proyectos Piloto , Masculino , Femenino , Adulto , Fumar/efectos adversos , Periodontitis/microbiología , Estudios de Casos y Controles , Adulto Joven , Perfilación de la Expresión Génica , Encía/microbiología , Transcriptoma