Genetics of tolerance in honeybees to the neonicotinoid clothianidin.

The effects of neonicotinoid insecticides (NNIs) on honeybee health are intensely debated, with numerous studies showing negative effects of exposure, while others report no such effects. We carried out experiments to study the genetic and molecular basis of NNI tolerance in honeybees, which may underlie the discrepancies observed in the literature. We discovered that worker survival post-exposure to an acute oral dose of clothianidin is heritable (H 2 = 37.8%). Tolerance to clothianidin was not associated with differences in the expression of detoxification enzymes in our experiments. Instead, mutations in the primary neonicotinoid detoxification genes CYP9Q1 and CYP9Q3 were strongly associated with worker survival post-clothianidin exposure. In some instances, the strong association between CYP9Q haplotypes and worker survival was associated with the protein's predicted binding affinity for clothianidin. Our findings have implications regarding future toxicological studies utilizing honeybees as a model pollinator.

In vitro exposure of human lens epithelial cells to X-rays at varied dose-rates leads to protein-level changes relevant to cataractogenesis.

BACKGROUND: Accumulated body of evidence shows that ionizing radiation increases the risk of cataracts. The mechanisms are not clear and the International Commission on Radiological Protection indicates a need for research into understanding the process, particularly at low doses and low dose rates of exposure. PURPOSE: This study was designed to examine protein-level modifications in a human lens epithelial (HLE) cell-line following radiation exposures. MATERIALS AND METHODS: HLE cell-line was subjected to X-irradiation at varied doses (0-5 Gy) and dose-rates (1.62 cGy/min and 38.2 cGy/min). Cells were collected 20 h post-exposure, lysed and proteins were clarified following fractionation by a molecular weight cut-off filtration method. Fractionated cellular proteins were enzymatically digested and subjected to mass spectrometry analysis. RESULTS: Statistically significant radiation dose-related protein changes compared to the control group were identified. Heatmap and hierarchical clustering analysis showed dose-rate dependant responses. Pathway analysis mapped the proteins to biological functions of mitochondrial dysfunction, reactive oxygen species generation, cell death, cancer, organismal injury and amyloidosis. CONCLUSION: Overall findings suggest that ionizing radiation exposure of HLE cells by mediating dose rate-dependant oxidative stress and cell death-related mechanisms, can be relevant to cataractogenesis.

Long-Term Sequelae and Health-Related Quality of Life Associated With Lyme Disease: A Systematic Review.

Lyme disease (LD) is the most commonly reported vector-borne disease, but its clinical consequences remain uncertain. We conducted a systematic review of the long-term sequelae and health-related quality of life (HRQoL) associated with LD in North America and Europe. We performed searches in 6 electronic databases up to December 2018 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including observational studies reporting long-term sequelae, HRQoL, and prognostic factors. We included 46 studies, published between 1994 and 2019. Based on 21 studies reporting attributable outcomes, higher proportions of sequelae reported from exposed patients were: neck pain, myalgia, arthralgia, paresthesia, sleep disorder, poor appetite, and concentration difficulties. Patients with PTLDS reported impaired HRQoL compared to the general US population. Included studies were highly heterogeneous in terms of study design, settings, patient characteristics, and quality. Patients with LD are more likely to report nonspecific long-term sequelae, especially those experiencing persistent symptoms posttreatment. Opportunities exist for prospective longitudinal studies to better understand LD outcomes.

Oxidative and nitrative stress-related changes in human lens epithelial cells following exposure to X-rays.

PURPOSE: There is limited understanding of the mechanistic effects of ionizing radiation (IR) exposure in cataract formation. In this study, we explored the effects of IR on reactive oxygen/nitrogen species (ROS and RNS) generation in human lens epithelial (HLE) cells as an early key event to long-term damage. MATERIALS AND METHODS: HLE cell-line was exposed to X-rays at varied doses (0-5 Gy) and dose-rates. Cell lysates and supernatants were collected 20 h post-exposure and analysed for viability, cell cycling and metabolites of ROS (p, m-, o-, tyrosines, 3-chlorotyrosine (cl-tyrosine), 8-hydroxy deoxyguanosine, (8-OH-dG) and RNS (3-nitrotyrosine). RESULTS AND CONCLUSIONS: HLE cell-line exhibited a bi-phasic response in terms of cell viability, ROS and RNS profiles. At doses <0.5 Gy, ROS and RNS levels were lower than control and at higher doses (>0.5 Gy) a steady increase was observed in each metabolite. This response was observed irrespective of dose-rate. Among the associations tested, cl, p, m-tyrosine and 3-nitrotyrosine revealed changes (p < .05) at 5 Gy compared exclusively to 0.05 and 0.01 Gy. In addition, dose-rate related differences were observed. Overall, the data suggests that ROS and RNS are key events in radiation induced damage and this response is dependent on the dose and dose-rate of IR exposure.