De novo transcriptome assembly, functional annotation and differential gene expression analysis of juvenile and adult E. fetida, a model oligochaete used in ecotoxicological studies

BACKGROUND: Earthworms are sensitive to toxic chemicals present in the soil and so are useful indicator organisms for soil health. Eisenia fetida are commonly used in ecotoxicological studies; therefore the assembly of a baseline transcriptome is important for subsequent analyses exploring the impact of toxin exposure on genome wide gene expression. RESULTS: This paper reports on the de novo transcriptome assembly of E. fetida using Trinity, a freely available software tool. Trinotate was used to carry out functional annotation of the Trinity generated transcriptome file and the transdecoder generated peptide sequence file along with BLASTX, BLASTP and HMMER searches and were loaded into a Sqlite3 database. To identify differentially expressed transcripts; each of the original sequence files were aligned to the de novo assembled transcriptome using Bowtie and then RSEM was used to estimate expression values based on the alignment. EdgeR was used to calculate differential expression between the two conditions, with an FDR corrected P value cut off of 0.001, this returned six significantly differentially expressed genes. Initial BLASTX hits of these putative genes included hits with annelid ferritin and lysozyme proteins, as well as fungal NADH cytochrome b5 reductase and senescence associated proteins. At a cut off of P = 0.01 there were a further 26 differentially expressed genes. CONCLUSION: These data have been made publicly available, and to our knowledge represent the most comprehensive available transcriptome for E. fetida assembled from RNA sequencing data. This provides important groundwork for subsequent ecotoxicogenomic studies exploring the impact of the environment on global gene expression in E. fetida and other earthworm species.

Etanol e isopropanol: genotoxicidad y teratogénesis evaluada aplicando el modelo de Drosophila melanogaster / Ethanol and isopropanol: genotoxicity and teratogenicity evaluated using Drosophila melanogaster as a model system

El etanol y el isopropanol son, de los alcoholes alifáticos de cadena corta, los más frecuentemente asociados a la actividad humana tanto a nivel industrial como en el entorno doméstico. En este trabajo se presentan los principales hallazgos reportados en la literatura para ensayos de genotoxicidad y teratogénesis en modelos experimentales de distinto nivel de complejidad, con especial énfasis en Drosophila melanogaster. El metabolismo de estos alcoholes es semejante en Drosophila y en humanos por lo cual la mosca es un buen modelo in vivo para la evaluación de sus potenciales efectos tóxicos, genotóxicos y teratogénicos.

Ethanol and isopropanol are two of the short chain aliphatic alcohols more frequently associated to the human environment, both in the industrial and domestic conditions. The aim of this work was to present the main findings reported in the literature about their genotoxicity and teratogenicity in experimental models of different level of complexity, with special emphasis in Drosophila melanogaster. Taking into account that the metabolism of both alcohols in Drosophila and humans is similar, the fly is a good model for the evaluation of their potentially toxic, genotoxic and teratogenic effects.

Toxicogen¨¦tica del tratamiento antirretroviral (I): lipodistrofia, alteraciones metab¨®licas y arteriosclerosis / Toxicogenetics of antiretroviral treatment (1): Lipodystrophy, metabolic perturbations and atherosclerosis

Entre los efectos adversos del tratamiento antirretroviral, probablemente el m¨¢s trascendente sea la toxicidad metab¨®lica y sobre el tejido adiposo por sus eventuales consecuencias a largo plazo en t¨¦rminos de riesgo cadiovascular. Dado que no todos los pacientes tratados con f¨¢rmacos antirretrovirales la presentan, se ha postulado que debe existir una predisposici¨®n gen¨¦tica. La informaci¨®n actualmente disponible es, a menudo, no concordante. Se ha demostrado de forma consistente que los polimorfismos en los genes que codifican para las apolipoprote¨ªnas A5, C3 y E, para las prote¨ªnas transportadoras de ¨¦steres de colesterol (CETP), y en el cassette de enlace a ATP tipo A1 (ABCA1), modulan la generaci¨®n de la dislipidemia secundaria al tratamiento antirretroviral, especialmente si ¨¦ste contiene inhibidores de la proteasa (IP). En cuanto a los polimorfismos de la prote¨ªna de uni¨®n al elemento regulador de esteroles tipo 1 (SREBP1), no existen evidencias concordantes. En el caso de la redistribuci¨®n de la grasa corporal o lipodistrofia, se ha estudiado si mutaciones en el ADN mitocondrial modulan el riesgo de aparici¨®n, con resultados no concluyentes. Se ha descartado de forma rotunda la existencia de mutaciones en el gen de la lamina. Se han investigado los polimorfismos de genes que codifican para citocinas proinflamatorias, incluyendo el factor de necrosis tumoral alfa (TNF-¦Á), la interleucina 1 beta (IL-1¦Â) y la interleucina 6 (IL-6), con evidencias contradictorias en el caso del TNF-¦Á, negativas en el caso de la IL-6 y datos que sugieren una asociaci¨®n positiva en el caso de la IL-1¦Â. Por otra parte, los polimorfismos en el gen que codifica el factor derivado de c¨¦lulas de la estroma-1 (SDF-1) y la prote¨ªna quimioatractiva de monocitos-1 (MCP-1) se han relacionado con la presencia de arteriosclerosis subcl¨ªnica en pacientes infectados por el VIH-1 que reciben tratamiento antirretroviral(AU)

Among the adverse effects attributed to antiretroviral therapy, one of the most striking is probably the appearance of the lipodystrophy syndrome and its associated metabolic derangements, given its potential long-term effect as a cardiovascular risk factor. Since not all patients who receive antiretroviral drugs experience these adverse effects, a host genetic predisposition has been postulated. However, currently available data on this issue is inconclusive and preliminary. It has been consistently demonstrated that polymorphisms in the genes that encode for apolipoproteins A5, C3 and E, for the cholesterol ester transporter proteins (CETP), and in the ATP binding cassette type A1 (ABCA1) influence the development of dyslipidemia in patients treated with antiretroviral drugs, particularly if the therapeutic regimen includes protease inhibitors. Data on the effect of polymorphisms in the sterol regulatory ester binding protein type 1 (SREBP1) are inconsistent. The effect of mitochondrial DNA mutations on the risk of lipodystrophy has been assessed, with inconclusive data. No polymorphisms in the lamin A gene have been detected. Investigations have assessed the effect of diverse polymorphisms in the genes that encode for several proinflammatory cytokines such as tumour necrosis factor alpha (TNF-¦Á), interleukin-1-beta (IL-1¦Â) and interleukin-6 (IL-6). The results show inconsistent data in the case of TNF-¦Á, no association in the case of IL-6, and preliminary positive associations in IL-1¦Â. In contrast, polymorphisms in the genes encoding for stromal derived factor 1 (SDF-1) and for monocyte chemoattractant protein 1 (MCP-1) have been shown to influence the development of subclinical atherosclerosis in HIV-1-infected patients treated with antiretroviral drugs(AU)

Toxicogenética del tratamiento antirretroviral (y II): neurotoxicidad, hepatotoxicidad, acidosis láctica, daño renal y otros efectos adversos del tratamiento antirretroviral / Toxicogenetics of antiretroviral treatment (II): Neurotoxicity, hepatotoxicity, lactic acidosis, kidney damage, and other adverse effects of antiretroviral drugs

Diversos estudios farmacogenéticos han analizado la influencia de determinados polimorfismos genéticos en la toxicidad del tratamiento antirretroviral. En esta revisión se describen algunos de los efectos adversos de los fármacos antirretrovirales en los que se ha documentado que puede existir una predisposición genética: la toxicidad neurológica en pacientes en tratamiento con efavirenz, por lo general asociada al polimorfismo 516G>T de la isoenzima hepática 2B6 del sistema del citocromo P450 (CYP2B6); las reacciones de hipersensibilidad a nevirapina asociadas con alelos específicos del complejo mayor de histocompatibilidad (HLA), principalmente el alelo HLADRB1* 0101 que, en combinación con un recuento elevado de linfocitos CD4, se ha asociado a reacciones sistémicas y hepatitis en pacientes de raza caucásica, y el alelo HLACw8 asociado con las reacciones de hipersensibilidad en personas de la isla italiana de Cerdeña y de Japón; la hepatotoxidad con nevirapina (NVP) asociada al polimorfismo C>T en la posición 3435T del gen ABCB1 (MDR-1) que codifica la glucoproteína P (gp- P) (protector); la hiperbilirrubinemia en pacientes expuestos a atazanavir o indinavir portadores del polimorfismo UGT1A1*28; la neuropatía periférica con análogos de nucleósidos asociada al haplogrupo T del genoma mitocondrial (mayor riesgo) y al genotipo HFE C282Y del gen de la hemocromatosis (protector); la mutación en el codón 964 (R964C) del gen POLG que codifica la ADN polimerasa mitocondrial gamma descrita en un paciente tailandés con acidosis láctica; los haplotipos ABCC2 asociados con la tubulopatía proximal inducida por tenofovir, y el riesgo de pancreatitis en las personas con mutaciones en los genes CFTR y SPINK-1(AU)

Several pharmacogenetics studies have analyzed the influence of specific genetic polymorphisms on the toxicity of antiretroviral treatment. The present review describes some of the adverse effects of antiretroviral drugs in which a genetic predisposition may be involved: efavirenz-induced neurological toxicity, generally associated with the 516G>T polymorphism of liver enzyme cytochrome P450 2B6 (CYP2B6); hypersensitivity reactions to nevirapine, associated with specific alleles of major histocompatibility complex, mainly the HLADRB1* 0101 allele, which, in combination with a high CD4 lymphocyte count, has been associated with systemic reactions and hepatitis in Caucasians, and the HLA-Cw8 allele, which is associated with hypersensitivity reactions in persons from the Italian island of Sardinia and from Japan; nevirapine-induced hepatotoxicity associated with the C>T polymorphism in position 3435T of the ABCB1 (MDR-1) gene codifying for glycoprotein P (lower risk); hyperbilirubinemia in patients exposed to atazanavir or indinavir carrying the UGT1A1*28 polymorphism; peripheral neuropathy with nucleoside analogues associated with haplogroup T of the mitochondrial genome (higher risk) and with the HFE C282Y genotype of the hemochromatosis gene (lower risk); the mutation in codon 964 (R964C) of the POLG gene that codifies the mitochondrial polymerase DNA gamma described in a Thai patient with lactic acidosis; the ABCC2 gene haplotypes associated with tenofovir-induced proximal tubulopathy, and the risk of pancreatitis in persons with mutations in the CFTR and SPINK-1 genes(AU)