TNFRSF13B Genetic variability an anthropological - evolutionary approach to Biomedical Research

In the recent years TNFRSF13B coding variants have been implicated by clinical genetics studies in Common Variable Immunodeficiency (CVID), the most common clinically relevant primary immunodeficiency in individuals of European ancestry, but their functional effects in relation to the development of the disease have not been entirely established. To examine the potential contribution of such variants to CVID, the more comprehensive perspective of an evolutionary approach was applied in this study, underling the belief that evolutionary genetics methods can play a role in dissecting the origin, causes and diffusion of human diseases, representing a powerful tool also in human health research. For this purpose, TNFRSF13B coding region was sequenced in 451 healthy individuals belonging to 26 worldwide populations, in addition to 96 control, 77 CVID and 38 Selective IgA Deficiency (IgAD) individuals from Italy, leading to the first achievement of a global picture of TNFRSF13B nucleotide diversity and haplotype structure and making suggestion of its evolutionary history possible. A slow rate of evolution, within our species and when compared to the chimpanzee, low levels of genetic diversity geographical structure and the absence of recent population specific selective pressures were observed for the examined genomic region, suggesting that geographical distribution of its variability is more plausibly related to its involvement also in innate immunity rather than in adaptive immunity only. This, together with the extremely subtle disease/healthy samples differences observed, suggests that CVID might be more likely related to still unknown environmental and genetic factors, rather than to the nature of TNFRSF13B variants only.

Sublethal effects of a common neonicotinoid pesticide, thiamethoxam, on honey bees: impact on locomotion and thermoregulation

Neonicotinoids have been pointed to as a factor responsible for the increased honey bee colony losses in the last decades. Many studies have investigated the effects of the first marketed neonicotinoid, imidacloprid, while fewer have focused on thiamethoxam. One recent study showed that sublethal doses of thiamethoxam lead to colony failure by decreasing forager homing flight success. We thus decided to investigate the mechanism which caused this phenomenon. Our hypothesis was that this effect was caused by impairment of forager locomotion abilities. Therefore we tested the effects of sublethal acute and chronic exposures to thiamethoxam on forager walking (Chapter 2) and flight (Chapter 3) performances. The acute treatment (1.34 ng/bee) affected walking locomotion firstly triggering hyperactivity (30 min post-treatment) and then impairing motor functioning (60 min post-treatment). 2-day continuous exposures to thiamethoxam (32.5, 45 ppb) elicited fewer effects on walking locomotion, however both exposure modes elicited an increased positive phototaxis. Similarly, in flight experiments, the single dose (1.34 ng/bee) elicited hyperactivity shortly after intoxication (increased flight duration and distance), while longer and continuous exposures (32.5, 45 ppb) impaired forager motor functions (decreased flight duration, distance, velocity). It is known that flight muscles temperature needs to be precisely regulated by bees during flight. Therefore, we further hypothesized that the impaired flight performances of neonicotinoid intoxicated bees were caused also by thermoregulation anomalies. We tested the effects that acute thiamethoxam exposures (0.2, 1, 2 ng/bee) elicit on forager thorax temperature (Chapter 4). Foragers treated with high doses exhibited hyperthermia or hypothermia when respectively exposed to high or low environmental temperatures. In summary, we show that sublethal doses of thiamethoxam affected forager walking and flight locomotion, phototaxis and thermoregulation. We also display the intricate mode of action of thiamethoxam which triggered, at different extents, inverse sublethal effects in relation to time and dose.