RESUMO
Palaemonetes argentinus, an abundant freshwater prawn species in the northern and central region of Argentina, has been used as a bioindicator of environmental pollutants as it displays a very high sensitivity to pollutants exposure. Despite their extraordinary ecological relevance, a lack of genomic information has hindered a more thorough understanding of the molecular mechanisms potentially involved in detoxification processes of this species. Thus, transcriptomic profiling studies represent a promising approach to overcome the limitations imposed by the lack of extensive genomic resources for P. argentinus, and may improve the understanding of its physiological and molecular response triggered by pollutants. This work represents the first comprehensive transcriptome-based characterization of the non-model species P. argentinus to generate functional genomic annotations and provides valuable resources for future genetic studies. Trinity de novo assembly consisted of 24,738 transcripts with high representation of detoxification (phase I and II), anti-oxidation, osmoregulation pathways and DNA replication and bioenergetics. This crustacean transcriptome provides valuable molecular information about detoxification and biochemical processes that could be applied as biomarkers in further ecotoxicology studies.
Assuntos
Desintoxicação Metabólica Fase II/genética , Desintoxicação Metabólica Fase I/genética , Palaemonidae/genética , Palaemonidae/metabolismo , Transcriptoma , Animais , Argentina , Biomarcadores/análiseRESUMO
We conducted a comprehensive study to investigate the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. Genotyping of seven gene polymorphisms was performed on a 384-well plate format on the Sequenom MassARRAY platform in 162 patients with osteosarcoma. We studied the correlation of the seven gene polymorphisms with response to chemotherapy and clinical outcome of patients. Individuals with the ABCB1 TT genotype had a higher probability of responding poorly to chemotherapy, indicated by an odds ratio (OR) of 2.64 (95%CI=1.04-6.83). Similarly, the genotype of GSTP1 GG was significantly associated with improved responses to chemotherapy, indicated by an OR of 3.33 (95%CI=1.26-8.99). The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter overall survival (OS). Our study found that two gene polymorphisms in two transporter genes and one Phase II metabolism enzymes are associated with response to chemotherapy and OS in osteosarcoma patients, suggesting the potential of the two gene polymorphisms as prognostic biomarkers for osteosarcoma.
Assuntos
Neoplasias Ósseas/genética , Glutationa S-Transferase pi/genética , Osteossarcoma/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Biomarcadores Farmacológicos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Criança , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Desintoxicação Metabólica Fase II/genética , Pessoa de Meia-Idade , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Polimorfismo de Nucleotídeo Único , PrognósticoRESUMO
UDP-glucuronosyltransferase 1A4 (UGT1A4) is a phase II drug-metabolizing enzyme that catalyzes the glucuronidation of many clinically-important drugs. Interethnic differences in the genetic polymorphism of UGT1A4 have been reported; however, there is no information in Mexican Mestizos (MMs) and Spaniards (SPs). Furthermore, MM is an admixed population with 26 % of Caucasian genes mainly from Spain. Therefore, this study aimed to investigate the potential differences between 318 SPs and 248 MMs healthy individuals regarding UGT1A4*1b, UGT1A4*2 and UGT1A4*3 alleles and to compare the observed frequencies with those previously reported in different populations. The allelic frequencies of the three UGT1A4 polymorphisms showed interethnic differences between MMs and SPs (p < 0.05). The analyzed SNPs variants in this genetic region were not in linkage disequilibrium (LD) for the MM population, suggesting that these mutations have arisen independently in the same genetic background. In contrast, UGT1A4*2 and UGT1A4*3 were in LD in the SP population. Comparison of present data with other in different ethnic groups revealed that the frequencies of UGT1A4*2 and UGT1A4*3 in SP were similar to other Caucasians and higher than in Asians, whereas in MMs were lower than in Caucasians and higher than in Asians only for UGT1A4*2. Present results could be helpful to improve the use of UGT1A4 drug substrates in order to adjust them to the ethnic background of a given population, specifically for Hispanics.
Assuntos
Estudos de Associação Genética , Glucuronosiltransferase/genética , Desintoxicação Metabólica Fase II/genética , Adulto , Idoso , Povo Asiático , Feminino , Frequência do Gene , Hispânico ou Latino/genética , Humanos , Desequilíbrio de Ligação , Masculino , Americanos Mexicanos/genética , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espanha , População Branca/genéticaRESUMO
The objective of this study was to evaluate the role of human activity factors, such as environmental contamination and habitat changes, as drivers for changing the physiological, biochemical, and genetic diversity of Geoffroy's side-necked turtle populations in one of the most impacted watersheds in southeastern Brazil. The impact of chemical and organic contamination was determined by ecotoxicological analyses to assess the action of some of the major components involved in protection against oxidative stress, phase I and II detoxification metabolism, and antioxidant capacity. The results indicated the influence of domestic and industrial effluents on detoxification metabolism and oxidative stress. However, in spite of increased activity and effect of EROD (CYP1A1) and glutathione S-transferase (GST) activity, GST average values in the urban area agreed with those expected for hypoxic conditions according to the literature. This observation suggests that increased GST in response to ROS production due to the presence of pollutants increases the antioxidant defense network, controlling the oxidative damage caused by hypoxia and reperfusion. To determine the conditions that are reflected in individual ability (fitness), we evaluated the mathematical relationship between weight and length, and found that changes in body shape and weight increase, allowing inferences about animal health and welfare. The data obtained indicate differences in conditions that are associated with the area, but also with sex and reproductive period, and contamination gradient, indicating a strong influence of environmental stressors on the physiology of the specimens. The evaluation of genetic structure among populations of Preto River and Felicidade Stream, based on microsatellites, demonstrated that there was no genetic differentiation, due to extensive gene flow between the areas and high genetic diversity. However, after analysis of intrapopulation structure, we observed the existence of five genetic groups that reflected changes in habitat created by damming and siltation, which initiate separation processes (barriers) between sub-populations. The relationship between the data obtained for biochemical parameters, condition factors and genetic diversity was analyzed by heterozygosity-fitness correlation. The negative relationship observed may be explained by the profile of structural and ecological changes in the populations studied, indicating the important influence of humans on the biology of natural populations. Therefore, Phrynops geoffroanus shows adaptation to environmental contamination, and ecological changes and possible loss of habitat are altering the genetic diversity of the populations studied. This is the first study evaluating all these aspects of P. geoffroanus simultaneously in natural populations in Brazil, using this species as a model.