To our knowledge this study is the first
To our knowledge, this study is the first to construct a whole-body transcriptome of D. variabilis. Most of the data currently accessible in NCBI are derived from a midgut EST database consisting of 1679 transcripts (Anderson et al., 2008) and about 20,000 mRNA sequences from the testis-vas deferens-male accessory gland. Illumina read data is also available for ticks starved at different durations. First and fourth leg transcriptomes have been described (Carr et al., 2017); however, the sequence information is currently unavailable and inaccessible. Nonetheless, our transcriptome expands on the molecular resources for future genetic studies of the American dog tick.
In conclusion, this study begins to characterize the molecular basis for DEET avoidance by ticks. Although the modes of action and underlying mechanisms have not been fully disentangled, we present transcriptomic data indicating that, at the molecular level, DEET acts as an abrupt inhibitor of cytochrome P450 s and AChE. We propose that DEET may induce impaired host-seeking in ticks through its effects as both a confusant and mild pesticide; however, further targeted studies are needed to substantiate this model. Our results lend some support to recent studies in Aedes, thereby suggesting the mode of action could in fact be similar among ticks and insects. Future studies are now needed to elucidate the specific genes, pathways, Metoprolol Succinate and cell types involved in P450 and AChE inhibition. Future experiments will help determine the sensory tissues involved in the repellence, as well as the relative role of DEET as a spatial and tactile repellent and may uncover sex-specific differences.
Conﬂicts of interest
Acknowledgements We thank Kate Broadhead for assistance with functional annotation. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grants Program awarded to Bryan Cassone (RGPIN-2016-04335).
Introduction Alzheimer’s disease (AD) is the most common neurodegenerative disorder that causes dementia. Neuropathological hallmarks of this disease include β-amyloid (Aβ) plaques and tau neurofibrillary tangles (NFTs) which are required indicators for definitive diagnosis of AD, post-mortem. Since AD can exhibit many clinical symptoms in common with other forms of dementia, it is imperative to develop methods to aid in early definitive diagnosis of AD during life to effect timely treatment of the disease. Much effort has been devoted to developing imaging agents to detect Aβ in plaques or tau in NFTs.5, 6, 7, 8, 9, 10 Three Positron Emission Tomography (PET) imaging agents were recently approved for use in imaging Aβ deposits but were not approved as specific agents for diagnosing AD because AD pathology can also occur in the brain tissue of up to 30% of cognitively normal older individuals.12, 13 Therefore, the use of specific Aβ or tau imaging agents could generate many false positive indications of AD and are insufficient for a definitive AD diagnosis during life. The cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), are co-regulators of acetylcholine. These enzymes have been found to co-localize with Aβ plaques that accumulate in various regions of AD brains, especially in the cerebral cortex.15, 16, 17, 18 In the normal human brain BuChE activity is associated with certain populations of neurons distinct from those with AChE activity.19, 20, 21 In AD, there is an association of cholinesterase activity, particularly that of BuChE, with Aβ plaques.15, 16, 17, 18 Imaging of cholinesterase activity in Aβ plaques has the potential to permit differentiation between such plaques in the brains of cognitively normal older adults from those in AD brains. Investigations into the distribution of cholinesterases in the brain have been conducted with radiolabelled ligands. A number of 11C cholinesterase-targeting radioligand substrates have been prepared and tested for the ability to image brain cholinesterase activity. These include N-11C-methylpiperidyl acetate and N-11C-methylpiperidyl propionate24, 25 for detection of AChE and N-11C-methylpiperidyl butyrate24, 26, 27, 28 for detection of BuChE. However, these agents have yielded only partial recapitulation of known cholinesterase distribution in human brains.23, 26, 27, 28 These substrate-radiotracers, however, have provided proof-of-concept that a sufficient amount survives hydrolysis by cholinesterases in the periphery, crosses the blood–brain-barrier, and binds to and is hydrolyzed by cholinesterases, to provide PET images through metabolic trapping.