Expression of Transposable Elements in the Brain of the Drosophila melanogaster Model for Fragile X Syndrome.

Fragile X syndrome is a neuro-developmental disease affecting intellectual abilities and social interactions. Drosophila melanogaster represents a consolidated model to study neuronal pathways underlying this syndrome, especially because the model recapitulates complex behavioural phenotypes. Drosophila Fragile X protein, or FMRP, is required for a normal neuronal structure and for correct synaptic differentiation in both the peripheral and central nervous systems, as well as for synaptic connectivity during development of the neuronal circuits. At the molecular level, FMRP has a crucial role in RNA homeostasis, including a role in transposon RNA regulation in the gonads of D. m. Transposons are repetitive sequences regulated at both the transcriptional and post-transcriptional levels to avoid genomic instability. De-regulation of transposons in the brain in response to chromatin relaxation has previously been related to neurodegenerative events in Drosophila models. Here, we demonstrate for the first time that FMRP is required for transposon silencing in larval and adult brains of Drosophila "loss of function" dFmr1 mutants. This study highlights that flies kept in isolation, defined as asocial conditions, experience activation of transposable elements. In all, these results suggest a role for transposons in the pathogenesis of certain neurological alterations in Fragile X as well as in abnormal social behaviors.

Testing the Influence of Incomplete DNA Barcode Libraries on Ecological Status Assessment of Mediterranean Transitional Waters.

The ecological assessment of European aquatic ecosystems is regulated under the framework directives on strategy for water and marine environments. Benthic macroinvertebrates are the most used biological quality element for ecological assessment of rivers, coastal-marines, and transitional waters. The morphological identification of benthic macroinvertebrates is the current tool for their assessment. Recently, DNA-based tools have been proposed as effective alternatives. The main current limits of DNA-based applications include the incompleteness of species recorded in the DNA barcode reference libraries and the primers bias. Here, we analysed the influence of the incompleteness of DNA barcode databases on species diversity indices, ecological indicators, and ecological assessment in transitional waters of the southeast Mediterranean, taking into account the availability of commonly sequenced and deposited genomic regions for listed species. The ecological quality status assigned through the potential application of both approaches to the analysed transitional water ecosystems was different in 27% of sites. We also analysed the inter-specific genetic distances to evaluate the potential application of the DNA metabarcoding method. Overall, this work highlights the importance to expand the barcode databases and to analyse, at the regional level, the gaps in the DNA barcodes.

Assessment of CYP2C9, CYP2C19, and CYP2D6 Polymorphisms in Allergic Patients with Chemical Sensitivity.

BACKGROUND: Self-reported chemical sensitivity (SCS) is characterized by adverse effects due to exposure to low levels of chemical substances. The clinical manifestations of SCS are similar to the allergy, and a high percentage of individuals with both diseases have been found. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with SCS. OBJECTIVES: The purpose of this study was to investigate whether allergic individuals with chemical sensitivity differed from allergic patients without chemical sensitivity with regard to the distribution of genotype and phenotype of CYP2C9, CYP2C19, and CYP2D6 polymorphisms. METHODS: A total of 180 patients were enrolled for this study. A questionnaire was employed to collect information on individual chemical sensitivity, while the Skin prick test and the PATCH test were used to verify the presence of an allergic condition against inhalants or contact allergens, respectively. For the evaluation of the CYP2C9, CYP2C19, and CYP2D6 polymorphisms, we used a strategy based on the amplification of the entire gene coupled to direct genomic DNA sequencing analysis. RESULTS: Overall, a total of 15 different CYP2C9, CYP2C19, and CYP2D6 haplotypes were identified in our population. If the 5 CYP2C9 and the 2 CYP2C19 identified alleles correspond to the previously described ones, 4 of the 8 CYP2D6 haplotypes, detected in the study group, present new SNPs combinations. These new suballeles were categorized as CYP2D6*2M Sa-lento Variant 1, CYP2D6*35B Salento Variant 2, CYP2D6*41 Salento Variant 3, and CYP2D6*4P Salento Variant 4 due to the presence of the key SNPs 2,850 C>T, 31G>A, 2,988 G>A, and 1,846 G>A, respectively. When the allergic individuals are divided into 2 groups according to their SCS score, we observed that the distribution of the CYP2D6 phenotypes was significantly different between the 2 groups. CONCLUSIONS: Our idea is that the application of the questionnaire that we have adopted has enabled us to diagnose a degree of chemical sensitivity, which results as comorbid of the allergic disease and in which a condition of poor or intermediate metabolizes for the detrimental CYP2D6 alleles, could represent a discriminant between the chemical sensitivity and the health state.

Drosophila melanogaster as a Model to Study the Multiple Phenotypes, Related to Genome Stability of the Fragile-X Syndrome.

Fragile-X syndrome is one of the most common forms of inherited mental retardation and autistic behaviors. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Patients exhibit a variety of symptoms predominantly linked to the function of FMRP protein in the nervous system like autistic behavior and mild-to-severe intellectual disability. Fragile-X (FraX) individuals also display cellular and morphological traits including branched dendritic spines, large ears, and macroorchidism. The dFmr1 gene is the Drosophila ortholog of the human Fmr1 gene. dFmr1 mutant flies exhibit synaptic abnormalities, behavioral defects as well as an altered germline development, resembling the phenotypes observed in FraX patients. Therefore, Drosophila melanogaster is considered a good model to study the physiopathological mechanisms underlying the Fragile-X syndrome. In this review, we explore how the multifaceted roles of the FMRP protein have been addressed in the Drosophila model and how the gained knowledge may open novel perspectives for understanding the molecular defects causing the disease and for identifying novel therapeutical targets.

dFmr1 Plays Roles in Small RNA Pathways of Drosophila melanogaster.

Fragile-X syndrome is the most common form of inherited mental retardation accompanied by other phenotypes, including macroorchidism. The disorder originates with mutations in the Fmr1 gene coding for the FMRP protein, which, with its paralogs FXR1 and FXR2, constitute a well-conserved family of RNA-binding proteins. Drosophila melanogaster is a good model for the syndrome because it has a unique fragile X-related gene: dFmr1. Recently, in addition to its confirmed role in the miRNA pathway, a function for dFmr1 in the piRNA pathway, operating in Drosophila gonads, has been established. In this review we report a summary of the piRNA pathways occurring in gonads with a special emphasis on the relationship between the piRNA genes and the crystal-Stellate system; we also analyze the roles of dFmr1 in the Drosophila gonads, exploring their genetic and biochemical interactions to reveal some unexpected connections.