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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.

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 Sa­lento 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.

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.

Magnetic field effects are diffused among living organisms. They are mainly studied with static or extremely low frequency fields, while scarce information is available for pulsed fields. This work is devoted to the study of the interaction between Drosophila melanogaster, both adults and larvae, and pulsed magnetic fields. We exposed the organisms to a peak field of 0.4 T, lasting for about 2 μ s, within an ad hoc designed copper coil. Adult individuals didn't present any deregulation of repetitive sequences in the germ line of Drosophila. Instead, we noticed a marked magnetic field effect in larvae. Polytene chromosomes coming from treated individuals showed the presence of heat shock puffs; the same organisms revealed also an upregulation of the genes encoding for the Hsp70 protein. These observations suggest that the larvae underwent an oxidative stress caused by the modulation of free radicals' yield induced by the magnetic field through a radical pair mechanism.