RESUMO
Inbreeding can lead to the accumulation of homozygous single nucleotide polymorphisms (SNPs) in the genome, which can significantly affect gene expression and phenotype. In this study, we examined the impact of homozygous SNPs resulting from inbreeding on alternative polyadenylation (APA) site selection and the underlying genetic mechanisms using inbred Luchuan pigs. Genome resequencing revealed that inbreeding results in a high accumulation of homozygous SNPs within the pig genome. 3' mRNA-seq on leg muscle, submandibular lymph node, and liver tissues was performed to identify differences in APA events between inbred and outbred Luchuan pigs. We revealed different tissue-specific APA usage caused by inbreeding, which were associated with different biological processes. Furthermore, we explored the role of polyadenylation signal (PAS) SNPs in APA regulation under inbreeding and identified key genes such as PUM1, SCARF1, RIPOR2, C1D, and LRRK2 that are involved in biological processes regulation. This study provides resources and sheds light on the impact of genomic homozygosity on APA regulation, offering insights into genetic characteristics and biological processes associated with inbreeding.
Assuntos
Endogamia , Poliadenilação , Polimorfismo de Nucleotídeo Único , Animais , Poliadenilação/genética , Suínos/genética , Genoma , Homozigoto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Especificidade de Órgãos/genéticaRESUMO
DNA is a remarkable biochemical macromolecule tasked with storing the genetic information that instructs life on planet Earth. However, its inherent chemical instability within the cellular milieu is incompatible with the accurate transmission of genetic information to subsequent generations. Therefore, biochemical pathways that continuously survey and repair DNA are essential to sustain life, and the fundamental mechanisms by which different DNA lesions are repaired have remained well conserved throughout evolution. Nonetheless, the emergence of multicellular organisms led to profound differences in cellular context and physiology, leading to large variations in the predominant sources of DNA damage between different cell types and in the relative contribution of different DNA repair pathways toward genome maintenance in different tissues. While we continue to make large strides into understanding how individual DNA repair mechanisms operate on a molecular level, much less attention is given to these cell type-specific differences. This short review aims to provide a broad overview of DNA damage and repair mechanisms to nonspecialists and to highlight some fundamental open questions in tissue and cell-type-specificity of these processes, which may have profound implications for our understanding of important pathophysiological processes such as cancer, neurodegeneration, and aging.
Assuntos
Dano ao DNA , Reparo do DNA , Humanos , Especificidade de Órgãos , Envelhecimento/genética , DNA/genética , DNA/metabolismoRESUMO
Xanthomonas plant pathogens can infect hundreds of agricultural plants. These bacteria exploit sophisticated molecular strategies based on multiple secretion systems and their associated virulence factors to overcome the plant defenses, including the physical barrier imposed by the plant cell walls and the innate immune system. Xanthomonads are equipped with a broad and diverse repertoire of Carbohydrate-Active enZymes (CAZymes), which besides enabling the utilization of complex plant carbohydrates as carbon and energy source, can also play pivotal roles in virulence and bacterial lifestyle in the host. CAZymes in xanthomonads are often organized in multienzymatic systems similar to the Polysaccharide Utilization Loci (PUL) from Bacteroidetes known as CUT systems (from Carbohydrate Utilization systems associated with TonB-dependent transporters). Xanthomonas bacteria are also recognized to synthesize distinct exopolysaccharides including xanthan gum and untapped exopolysaccharides associated with biofilm formation. Here, we summarize the current knowledge on the multifaceted roles of CAZymes in xanthomonads, connecting their function with pathogenicity and tissue specificity.
Assuntos
Xanthomonas , Especificidade de Órgãos , Bactérias , Virulência , Plantas/microbiologia , CarboidratosRESUMO
SARS-CoV-2, the seventh coronavirus known to infect humans, can cause severe life-threatening respiratory pathologies. To better understand SARS-CoV-2 evolution, genome-wide analyses have been made, including the general characterization of its codons usage profile. Here we present a bioinformatic analysis of the evolution of SARS-CoV-2 codon usage over time using complete genomes collected since December 2019. Our results show that SARS-CoV-2 codon usage pattern is antagonistic to, and it is getting farther away from that of the human host. Further, a selection of deoptimized codons over time, which was accompanied by a decrease in both the codon adaptation index and the effective number of codons, was observed. All together, these findings suggest that SARS-CoV-2 could be evolving, at least from the perspective of the synonymous codon usage, to become less pathogenic.
Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Uso do Códon , Códon , Evolução Molecular , Pandemias , SARS-CoV-2/genética , Betacoronavirus/classificação , Betacoronavirus/genética , Regulação Viral da Expressão Gênica , Genoma Viral , Genômica/métodos , Humanos , Fases de Leitura Aberta , Especificidade de Órgãos , FilogeniaRESUMO
By-products of Capsicum chinense Jacq., var Jaguar could be a source of bioactive compounds. Therefore, we evaluated the anti-inflammatory effect, antioxidant activity, and their relationship with the polyphenol content of extracts of habanero pepper by-products obtained from plants grown on black or red soils of Yucatán, Mexico. Moreover, the impact of the type of extraction on their activities was evaluated. The dry by-product extracts were obtained by maceration (ME), Soxhlet (SOX), and supercritical fluid extraction (SFE). Afterward, the in vivo anti-inflammatory effect (TPA-induced ear inflammation) and the in vitro antioxidant activity (ABTS) were evaluated. Finally, the polyphenolic content was quantified by Ultra-Performance Liquid Chromatography (UPLC), and its correlation with both bioactivities was analyzed. The results showed that the SFE extract of stems of plants grown on red soil yielded the highest anti-inflammatory effect (66.1 ± 3.1%), while the extracts obtained by ME and SOX had the highest antioxidant activity (2.80 ± 0.0052 mM Trolox equivalent) and polyphenol content (3280 ± 15.59 mg·100 g-1 dry basis), respectively. A negative correlation between the anti-inflammatory effect, the antioxidant activity, and the polyphenolic content was found. Overall, the present study proposed C. chinense by-products as a valuable source of compounds with anti-inflammatory effect and antioxidant activity.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Capsicum/química , Extratos Vegetais/química , Polifenóis/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Fracionamento Químico/métodos , Cromatografia com Fluido Supercrítico , Especificidade de Órgãos , Compostos Fitoquímicos/químicaRESUMO
Nitrate is a nutrient and a potent signal that impacts global gene expression in plants. However, the regulatory factors controlling temporal and cell type-specific nitrate responses remain largely unknown. We assayed nitrate-responsive transcriptome changes in five major root cell types of the Arabidopsis thaliana root as a function of time. We found that gene-expression response to nitrate is dynamic and highly localized and predicted cell type-specific transcription factor (TF)-target interactions. Among cell types, the endodermis stands out as having the largest and most connected nitrate-regulatory gene network. ABF2 and ABF3 are major hubs for transcriptional responses in the endodermis cell layer. We experimentally validated TF-target interactions for ABF2 and ABF3 by chromatin immunoprecipitation followed by sequencing and a cell-based system to detect TF regulation genome-wide. Validated targets of ABF2 and ABF3 account for more than 50% of the nitrate-responsive transcriptome in the endodermis. Moreover, ABF2 and ABF3 are involved in nitrate-induced lateral root growth. Our approach offers an unprecedented spatiotemporal resolution of the root response to nitrate and identifies important components of cell-specific gene regulatory networks.
Assuntos
Proteínas de Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica de Plantas , Nitratos/metabolismo , Fenômenos Fisiológicos Vegetais , Fatores de Transcrição/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Biologia Computacional/métodos , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Modelos Biológicos , Especificidade de Órgãos/genética , Raízes de Plantas/fisiologia , Fatores de Transcrição/metabolismo , TranscriptomaRESUMO
BACKGROUND: Aedes aegypti and Ae. albopictus are vectors of numerous arboviruses that adversely affect human health. In mosquito vectors of disease, the bacterial microbiota influence several physiological processes, including fertility and vector competence, making manipulation of the bacterial community a promising method to control mosquito vectors. In this study, we describe the reproductive tract tissue microbiota of lab-reared virgin Ae. aegypti and Ae. albopictus males, and virgin, mated, and mated + blood-fed females of each species, comparing the bacterial composition found there to the well-described gut microbiota. METHODS: We performed metabarcoding of the 16S rRNA isolated from the gut, upper reproductive tract (URT; testes or ovaries), and lower reproductive tract (LRT; males: seminal vesicles and accessory glands; females: oviduct, spermathecae, and bursa) for each species, and evaluated the influence of host species, tissue, nutritional status, and reproductive status on microbiota composition. Finally, based on the identified taxonomic profiles of the tissues assessed, bacterial metabolic pathway abundance was predicted. RESULTS: The community structure of the reproductive tract is unique compared to the gut. Asaia is the most prevalent OTU in the LRTs of both Ae. aegypti and Ae. albopictus. In the URT, we observed differences between species, with Wolbachia OTUs being dominant in the Ae. albopictus URT, while Enterobacter and Serratia were dominant in Ae. aegypti URT. Host species and tissue were the best predictors of the community composition compared to reproductive status (i.e., virgin or mated) and nutritional status (i.e., sugar or blood-fed). The predicted functional profile shows changes in the abundance of specific microbial pathways that are associated with mating and blood-feeding, like energy production in mated tissues and siderophore synthesis in blood-fed female tissues. CONCLUSIONS: Aedes aegypti and Ae. albopictus have distinct differences in the composition of microbiota found in the reproductive tract. The distribution of the bacterial taxonomic groups indicates that some bacteria have tissue-specific tropism for reproductive tract tissue, such as Asaia and Wolbachia. No significant differences in the taxonomic composition were observed in the reproductive tract between virgin, mated, and mated + blood-fed females, but changes in the abundance of specific metabolic pathways were found in the predicted microbial functional profiles in mated and blood-fed females.
Assuntos
Aedes/microbiologia , Bactérias/classificação , Microbiota , Mosquitos Vetores/parasitologia , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Código de Barras de DNA Taxonômico , Feminino , Genitália/microbiologia , Humanos , Especificidade de Órgãos , RNA Bacteriano/genética , RNA Ribossômico 16S/genéticaRESUMO
Innate lymphoid cells (ILCs) are the most recently described group of lymphoid subpopulations. These tissue-resident cells display a heterogeneity resembling that observed on different groups of T cells, hence their categorization as cytotoxic NK cells and helper ILCs type 1, 2 and 3. Each one of these groups is highly diverse and expresses different markers in a context-dependent manner. Type 2 innate lymphoid cells (ILC2s) are activated in response to helminth parasites and regulate the immune response. They are involved in the etiology of diseases associated with allergic responses as well as in the maintenance of tissue homeostasis. Markers associated with their identification differ depending on the tissue and model used, making the study and understanding of these cells a cumbersome task. This review compiles evidence for the heterogeneity of ILC2s as well as discussion and analyses of molecular markers associated with their identity, function, tissue-dependent expression, and how these markers contribute to the interaction of ILC2s with specific microenvironments to maintain homeostasis or respond to pathogenic challenges.
Assuntos
Antígenos de Diferenciação/análise , Subpopulações de Linfócitos/imunologia , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/patologia , Animais , Citocinas/metabolismo , Helmintíase/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Homeostase , Humanos , Imunofenotipagem , Inflamação , Intestinos/imunologia , Pulmão/imunologia , Subpopulações de Linfócitos/química , Camundongos , Nutrientes , Especificidade de Órgãos , Proteínas Proto-Oncogênicas c-kit/imunologia , Receptores de Superfície Celular/imunologia , Pele/imunologia , Fator de Células-Tronco/imunologiaRESUMO
The relationship between menopause and the development of metabolic diseases is well established. In postmenopause women, there is an expansion of visceral white adipose tissue (WATv), which highly contributes to the rise of circulating lipids. Meanwhile, muscle glucose uptake decreases and hepatic glucose production increases. Consequently, in the pancreas, lipotoxicity and glycotoxicity lead to deficient insulin production. These factors initiate an energy imbalance and enhance the probability of developing cardiovascular and metabolic diseases. Although the activation of estradiol receptors (ER) has been shown to be beneficial for the WAT stock pattern, leading to the insulin-sensitive phenotype, authors have described the risk of these receptors' activation, contributing to neoplasia development. The selective activation of beta-type ER (ERß) seems to be a promising strategy in the treatment of energy imbalance, acting on several tissues of metabolic importance and allowing an intervention with less risk for the development of estrogen-dependent neoplasia. However, the literature on the risks and benefits of selective ERß activation still needs to increase. In this review, several aspects related to ERß were considered, such as its physiological role in tissues of energy importance, beneficial effects, and risks of its stimulation during menopause. PubMed, SciELO, Cochrane, and Medline/Bireme databases were used in this study.