@article{lawrie_mitchell_deguenon_ponnusamy_reisig_pozo-valdivia_kurtz_roe_2022, title={Characterization of Long Non-Coding RNAs in the Bollworm, Helicoverpa zea, and Their Possible Role in Cry1Ac-Resistance}, volume={13}, ISSN={["2075-4450"]}, url={https://www.mdpi.com/2075-4450/13/1/12}, DOI={10.3390/insects13010012}, abstractNote={Multiple insect pest species have developed field resistance to Bt-transgenic crops. There has been a significant amount of research on protein-coding genes that contribute to resistance, such as the up-regulation of protease activity or altered receptors. However, our understanding of the role of non-protein-coding mechanisms in Bt-resistance is minimal, as is also the case for resistance to chemical pesticides. To address this problem relative to Bt, RNA-seq was used to examine statistically significant, differential gene expression between a Cry1Ac-resistant (~100-fold resistant) and Cry1Ac-susceptible strain of Helicoverpa zea, a prevalent caterpillar pest in the USA. Significant differential expression of putative long non-coding RNAs (lncRNAs) was found in the Cry1Ac-resistant strain (58 up- and 24 down-regulated gene transcripts with an additional 10 found only in resistant and four only in susceptible caterpillars). These lncRNAs were examined as potential pseudogenes and for their genomic proximity to coding genes, both of which can be indicative of regulatory relationships between a lncRNA and coding gene expression. A possible pseudogenic lncRNA was found with similarities to a cadherin. In addition, putative lncRNAs were found significantly proximal to a serine protease, ABC transporter, and CYP coding genes, potentially involved in the mechanism of Bt and/or chemical insecticide resistance. Characterization of non-coding genetic mechanisms in Helicoverpa zea will improve the understanding of the genomic evolution of insect resistance, improve the identification of specific regulators of coding genes in general (some of which could be important in resistance), and is the first step for potentially targeting these regulators for pest control and resistance management (using molecular approaches, such as RNAi and others).}, number={1}, journal={INSECTS}, author={Lawrie, Roger D. and Mitchell, Robert D. and Deguenon, Jean Marcel and Ponnusamy, Loganathan and Reisig, Dominic and Pozo-Valdivia, Alejandro Del and Kurtz, Ryan W. and Roe, Richard Michael}, year={2022}, month={Jan} }
 @article{luan_west_mccord_denhartog_shi_bettermann_li_travanty_mitchell_cave_et al._2021, title={Mosquito-Textile Physics: A Mathematical Roadmap to Insecticide-Free, Bite-Proof Clothing for Everyday Life}, volume={12}, ISSN={2075-4450}, url={http://dx.doi.org/10.3390/insects12070636}, DOI={10.3390/insects12070636}, abstractNote={Garments treated with chemical insecticides are commonly used to prevent mosquito bites. Resistance to insecticides, however, is threatening the efficacy of this technology, and people are increasingly concerned about the potential health impacts of wearing insecticide-treated clothing. Here, we report a mathematical model for fabric barriers that resist bites from Aedes aegypti mosquitoes based on textile physical structure and no insecticides. The model was derived from mosquito morphometrics and analysis of mosquito biting behavior. Woven filter fabrics, precision polypropylene plates, and knitted fabrics were used for model validation. Then, based on the model predictions, prototype knitted textiles and garments were developed that prevented mosquito biting, and comfort testing showed the garments to possess superior thermophysiological properties. Our fabrics provided a three-times greater bite resistance than the insecticide-treated cloth. Our predictive model can be used to develop additional textiles in the future for garments that are highly bite resistant to mosquitoes.}, number={7}, journal={Insects}, publisher={MDPI AG}, author={Luan, Kun and West, Andre J. and McCord, Marian G. and DenHartog, Emiel A. and Shi, Quan and Bettermann, Isa and Li, Jiayin and Travanty, Nicholas V. and Mitchell, Robert D., III and Cave, Grayson L. and et al.}, year={2021}, month={Jul}, pages={636} }
 @article{ponnusamy_sutton_mitchell_sonenshine_apperson_roe_2021, title={Tick Ecdysteroid Hormone, Global Microbiota/Rickettsia Signaling in the Ovary versus Carcass during Vitellogenesis in Part-Fed (Virgin) American Dog Ticks, Dermacentor variabilis}, volume={9}, ISSN={["2076-2607"]}, url={https://www.mdpi.com/2076-2607/9/6/1242}, DOI={10.3390/microorganisms9061242}, abstractNote={The transovarial transmission of tick-borne bacterial pathogens is an important mechanism for their maintenance in natural populations and transmission, causing disease in humans and animals. The mechanism for this transmission and the possible role of tick hormones facilitating this process have never been studied. Injections of physiological levels of the tick hormone, 20-hydroxyecdysone (20E), into part-fed (virgin) adult females of the American dog tick, Dermacentor variabilis, attached to the host caused a reduction in density of Rickettsia montanensis in the carcass and an increase in the ovaries compared to buffer-injected controls. This injection initiates yolk protein synthesis and uptake by the eggs but has no effect on blood feeding. Francisella sp. and R. montanensis were the predominant bacteria based on the proportionality in the carcass and ovary. The total bacteria load increased in the carcass and ovaries, and bacteria in the genus Pseudomonas increased in the carcass after the 20E injection. The mechanism of how the Rickettsia species respond to changes in tick hormonal regulation needs further investigation. Multiple possible mechanisms for the proliferation of R. montanensis in the ovaries are proposed.}, number={6}, journal={MICROORGANISMS}, author={Ponnusamy, Loganathan and Sutton, Haley and Mitchell, Robert D. and Sonenshine, Daniel E. and Apperson, Charles S. and Roe, Richard Michael}, year={2021}, month={Jun} }
 @article{leon_mitchell_watson_2020, title={Ectoparasites of Cattle}, volume={36}, ISSN={["1558-4240"]}, DOI={10.1016/j.cvfa.2019.12.004}, abstractNote={Diverse groups of ectoparasitic arthropods cause significant morbidity and mortality in most of the approximately 1.49 billion head of cattle worldwide. Hematophagous ectoparasites (ie, blood-feeding flies, myiasis-causing flies, lice, mites, ticks) are the most important in cattle. Intense use of ectoparasiticides to treat infestations can result in ectoparasite populations becoming resistant to this treatment method. Approaches integrating the use of different technologies are required to manage cattle ectoparasites effectively while addressing societal expectations regarding food safety and environmental health. Assessing the status of coparasitism with ectoparasites and endoparasites in cattle across agroecosystems is critical in advancing integrated parasite management.}, number={1}, journal={VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE}, author={Leon, Adalberto A. and Mitchell, Robert D., III and Watson, David W.}, year={2020}, month={Mar}, pages={173-+} }
 @article{lawrie_mitchell_dhammi_wallace_hodgson_roe_2020, title={Role of long non-coding RNA in DEET- and fipronil-mediated alteration of transcripts associated with Phase I and Phase II xenobiotic metabolism in human primary hepatocytes}, volume={167}, ISSN={["1095-9939"]}, DOI={10.1016/j.pestbp.2020.104607}, abstractNote={Human exposure to environmental chemicals both individually and in combination occurs frequently world-wide most often with unknown consequences. Use of molecular approaches to aide in the assessment of risk involved in chemical exposure is a growing field in toxicology. In this study, we examined the impact of two environmental chemicals used in and around homes, the insect repellent DEET (N,N-diethyl-m-toluamide) and the phenylpyrazole insecticide fipronil (fluocyanobenpyrazole) on transcript levels of enzymes potentially involved in xenobiotic metabolism and on long non-coding RNAs (lncRNAs). Primary human hepatocytes were treated with these two chemicals both individually and in combination. Using RNA-Seq, we found that 10 major enzyme categories involved in phase 1 and phase 2 xenobiotic metabolism were significantly (α = 0.05) up- and down-regulated (i.e., 100 μM DEET–19 transcripts, 89% up and 11% down; 10 μM fipronil–52 transcripts, 53% up and 47% down; and 100 μM DEET +10 μM fipronil–69 transcripts, 43% up and 57% down). The altered genes were then mapped to the human genome and their proximity (within 1,000,000 bp) to lncRNAs examined. Unique proximities were discovered between altered lncRNA and altered P450s (CYP) and other enzymes (DEET, 2 CYP; Fipronil, 6 CYP and 15 other; and DEET + fipronil, 7 CYP and 21 other). Many of the altered P450 transcripts were in multiple clusters in the genome with proximal altered lncRNAs, suggesting a regulator function for the lncRNA. At the gene level there was high percent identity for lncRNAs near P450 clusters, but this relationship was not found at the transcript level. The role of these altered lncRNAs associated with xenobiotic induction, human diseases and chemical mixtures is discussed.}, journal={PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY}, author={Lawrie, Roger D. and Mitchell, Robert D., III and Dhammi, Anirudh and Wallace, Andrew and Hodgson, Ernest and Roe, R. Michael}, year={2020}, month={Jul} }
 @article{mitchell_wallace_hodgson_roe_2017, title={Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure}, volume={18}, ISSN={["1422-0067"]}, DOI={10.3390/ijms18102104}, abstractNote={While the synthesis and use of new chemical compounds is at an all-time high, the study of their potential impact on human health is quickly falling behind, and new methods are needed to assess their impact. We chose to examine the effects of two common environmental chemicals, the insect repellent N,N-diethyl-m-toluamide (DEET) and the insecticide fluocyanobenpyrazole (fipronil), on transcript levels of long non-protein coding RNAs (lncRNAs) in primary human hepatocytes using a global RNA-Seq approach. While lncRNAs are believed to play a critical role in numerous important biological processes, many still remain uncharacterized, and their functions and modes of action remain largely unclear, especially in relation to environmental chemicals. RNA-Seq showed that 100 µM DEET significantly increased transcript levels for 2 lncRNAs and lowered transcript levels for 18 lncRNAs, while fipronil at 10 µM increased transcript levels for 76 lncRNAs and decreased levels for 193 lncRNAs. A mixture of 100 µM DEET and 10 µM fipronil increased transcript levels for 75 lncRNAs and lowered transcript levels for 258 lncRNAs. This indicates a more-than-additive effect on lncRNA transcript expression when the two chemicals were presented in combination versus each chemical alone. Differentially expressed lncRNA genes were mapped to chromosomes, analyzed by proximity to neighboring protein-coding genes, and functionally characterized via gene ontology and molecular mapping algorithms. While further testing is required to assess the organismal impact of changes in transcript levels, this initial analysis links several of the dysregulated lncRNAs to processes and pathways critical to proper cellular function, such as the innate and adaptive immune response and the p53 signaling pathway.}, number={10}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Mitchell, Robert D., III and Wallace, Andrew D. and Hodgson, Ernest and Roe, R. Michael}, year={2017}, month={Oct} }
 @article{mitchell_zhu_carr_dhammi_cave_sonenshine_roe_2017, title={Infrared light detection by the hailer's organ of adult american dog ticks, Dermacentor variabilis (Ixodida: Ixodidae)}, volume={8}, ISSN={["1877-9603"]}, DOI={10.1016/j.ttbdis.2017.06.001}, abstractNote={The Haller's organ (HO), unique to ticks and mites, is found only on the first tarsus of the front pair of legs. The organ has an unusual morphology consisting of an anterior pit (AP) with protruding sensilla and a posterior capsule (Cp). The current thinking is that the HO's main function is chemosensation analogous to the insect antennae, but the functionality of its atypical structure (exclusive to the Acari) is unexplained. We provide the first evidence that the HO allows the American dog tick, Dermacentor variabilis, to respond to infrared (IR) light. Unfed D. variabilis adults with their HOs present were positively phototactic to IR. However, when the HOs were removed, no IR response was detected. Ticks in these experiments were also attracted to white light with and without the HOs, but were only positively phototactic to white light when the ocelli (primitive eyes) were unobstructed. Covering the eyes did not prevent IR attraction. A putative TRPA1 receptor was characterized from a D. variabilis-specific HO transcriptome we constructed. This receptor was homologous to transient receptor potential cation channel, subfamily A, member 1 (TRPA1) from the pit organ of the pit viper, python, and boa families of snakes, the only receptor identified so far for IR detection. HO scanning electron microscopy (SEM) studies in the American dog tick showed the AP and Cp but also novel structures not previously described; the potential role of these structures in IR detection is discussed. The ability of ticks to use IR for host finding is consistent with their obligatory hematophagy and has practical applications in tick trapping and the development of new repellents.}, number={5}, journal={TICKS AND TICK-BORNE DISEASES}, author={Mitchell, Robert D., III and Zhu, Jiwei and Carr, Ann L. and Dhammi, Anirudh and Cave, Grayson and Sonenshine, Daniel E. and Roe, R. Michael}, year={2017}, pages={764–771} }
 @article{carr_mitchell_dhammi_bissinger_sonenshine_roe_2017, title={Tick Haller's Organ, a New Paradigm for Arthropod Olfaction: How Ticks Differ from Insects}, volume={18}, ISSN={["1422-0067"]}, DOI={10.3390/ijms18071563}, abstractNote={Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller’s organ, not found in any other animals, presumed to function like the insect antennae in chemosensation but morphologically very different. The mechanism of tick chemoreception is unknown. Utilizing next-generation sequencing and comparative transcriptomics between the 1st and 4th legs (the latter without the Haller’s organ), we characterized 1st leg specific and putative Haller’s organ specific transcripts from adult American dog ticks, Dermacentor variabilis. The analysis suggested that the Haller’s organ is involved in olfaction, not gustation. No known odorant binding proteins like those found in insects, chemosensory lipocalins or typical insect olfactory mechanisms were identified; with the transcriptomic data only supporting a possible olfactory G-protein coupled receptor (GPCR) signal cascade unique to the Haller’s organ. Each component of the olfactory GPCR signal cascade was identified and characterized. The expression of GPCR, Gαo and β-arrestin transcripts identified exclusively in the 1st leg transcriptome, and putatively Haller’s organ specific, were examined in unfed and blood-fed adult female and male D. variabilis. Blood feeding to repletion in adult females down-regulated the expression of all three chemosensory transcripts in females but not in males; consistent with differences in post-feeding tick behavior between sexes and an expected reduced chemosensory function in females as they leave the host. Data are presented for the first time of the potential hormonal regulation of tick chemosensation; behavioral assays confirmed the role of the Haller’s organ in N,N-diethyl-meta-toluamide (DEET) repellency but showed no role for the Haller’s organ in host attachment. Further research is needed to understand the potential role of the GPCR cascade in olfaction.}, number={7}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Carr, Ann L. and Mitchell, Robert D., III and Dhammi, Anirudh and Bissinger, Brooke W. and Sonenshine, Daniel E. and Roe, R. Michael}, year={2017}, month={Jul} }
 @article{mitchell_dhammi_wallace_hodgson_roe_2016, title={Impact of Environmental Chemicals on the Transcriptome of Primary Human Hepatocytes: Potential for Health Effects}, volume={30}, ISSN={1095-6670}, url={http://dx.doi.org/10.1002/JBT.21801}, DOI={10.1002/jbt.21801}, abstractNote={New paradigms for human health risk assessment of environmental chemicals emphasize the use of molecular methods and human‐derived cell lines. In this study, we examined the effects of the insect repellent DEET (N,N‐diethyl‐m‐toluamide) and the phenylpyrazole insecticide fipronil (fluocyanobenpyrazole) on transcript levels in primary human hepatocytes. These chemicals were tested individually and as a mixture. RNA‐Seq showed that 100 μM DEET significantly increased transcript levels (α = 0.05) for 108 genes and lowered transcript levels for 64 genes and fipronil at 10 μM increased the levels of 2246 transcripts and decreased the levels for 1428 transcripts. Fipronil was 21‐times more effective than DEET in eliciting changes, even though the treatment concentration was 10‐fold lower for fipronil versus DEET. The mixture of DEET and fipronil produced a more than additive effect (levels increased for 3017 transcripts and decreased for 2087 transcripts). The transcripts affected for all chemical treatments were classified by GO analysis and mapped to chromosomes. The overall treatment responses, specific pathways, and individual transcripts affected were discussed at different levels of fold‐change. Changes found in transcript levels in response to treatments will require further research to understand their importance in overall cellular, organ, and organismic function.}, number={8}, journal={Journal of Biochemical and Molecular Toxicology}, publisher={Wiley}, author={Mitchell, Robert D., III and Dhammi, Anirudh and Wallace, Andrew and Hodgson, Ernest and Roe, R. Michael}, year={2016}, month={Apr}, pages={375–395} }
 @article{zhu_khalil_mitchell_bissinger_egekwu_sonenshine_roe_2016, title={Mevalonate-Farnesal Biosynthesis in Ticks: Comparative Synganglion Transcriptomics and a New Perspective}, volume={11}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0141084}, abstractNote={Juvenile hormone (JH) controls the growth, development, metamorphosis, and reproduction of insects. For many years, the general assumption has been that JH regulates tick and other acarine development and reproduction the same as in insects. Although researchers have not been able to find the common insect JHs in hard and soft tick species and JH applications appear to have no effect on tick development, it is difficult to prove the negative or to determine whether precursors to JH are made in ticks. The tick synganglion contains regions which are homologous to the corpora allata, the biosynthetic source for JH in insects. Next-gen sequencing of the tick synganglion transcriptome was conducted separately in adults of the American dog tick, Dermacentor variabilis, the deer tick, Ixodes scapularis, and the relapsing fever tick, Ornithodoros turicata as a new approach to determine whether ticks can make JH or a JH precursor. All of the enzymes that make up the mevalonate pathway from acetyl-CoA to farnesyl diphosphate (acetoacetyl-CoA thiolase, HMG-S, HMG-R, mevalonate kinase, phosphomevalonate kinase, diphosphomevalonate decarboxylase, and farnesyl diphosphate synthase) were found in at least one of the ticks studied but most were found in all three species. Sequence analysis of the last enzyme in the mevalonate pathway, farnesyl diphosphate synthase, demonstrated conservation of the seven prenyltransferase regions and the aspartate rich motifs within those regions typical of this enzyme. In the JH branch from farnesyl diphosphate to JH III, we found a putative farnesol oxidase used for the conversion of farnesol to farnesal in the synganglion transcriptome of I. scapularis and D. variabilis. Methyltransferases (MTs) that add a methyl group to farnesoic acid to make methyl farnesoate were present in all of the ticks studied with similarities as high as 36% at the amino acid level to insect JH acid methyltransferase (JHAMT). However, when the tick MTs were compared to the known insect JHAMTs from several insect species at the amino acid level, the former lacked the farnesoic acid binding motif typical in insects. The P450s shown in insects to add the C10,11 epoxide to methyl farnesoate, are in the CYP15 family; this family was absent in our tick transcriptomes and in the I. scapularis genome, the only tick genome available. These data suggest that ticks do not synthesize JH III but have the mevalonate pathway and may produce a JH III precursor.}, number={3}, journal={PLOS ONE}, author={Zhu, Jiwei and Khalil, Sayed M. and Mitchell, Robert D. and Bissinger, Brooke W. and Egekwu, Noble and Sonenshine, Daniel E. and Roe, R. Michael}, year={2016}, month={Mar} }
 @article{terrapon_li_robertson_ji_meng_booth_chen_childers_glastad_gokhale_et al._2014, title={Molecular traces of alternative social organization in a termite genome}, volume={5}, journal={Nature Communications}, author={Terrapon, N. and Li, C. and Robertson, H. M. and Ji, L. and Meng, X. H. and Booth, W. and Chen, Z. S. and Childers, C. P. and Glastad, K. M. and Gokhale, K. and et al.}, year={2014} }