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1. Non-invasive cancer detection in canine urine through Caenorhabditis elegans chemotaxis

   https://doi.org/10.3389/fvets.2022.932474  

   Namgong, Chan ; Kim, Jong Hyuk ; Lee, Myon Hee ; Midkiff, Daniel ( August 2022 , Frontiers in Veterinary Science)

   Cancer is the leading cause of death in companion animals, and successful early treatment has been a challenge in the veterinary field. We have developed the Non-Invasive Cancer Screening (N.C.S.) Study to perform cancer detection through the analysis of canine urine samples. The test makes use of the strong olfactory system of the nematode Caenorhabditis elegans , which was previously shown to positively respond to urine samples from human cancer patients. We performed a proof-of-concept study to optimize the detection capability in urine samples obtained from dogs with naturally occurring cancers. In this study, we established a scale for identifying the cancer risk based on the magnitude of the chemotaxis index of C. elegans toward a canine urine sample. Through validation, the N.C.S. Study achieved a sensitivity of 85%, showing that it is highly sensitive to indicate the presence of cancer across multiple types of common canine cancers. The test also showed a 90% specificity to cancer samples, indicating a low rate of over-identifying cancer risk. From these results, we have demonstrated the ability to perform low-cost, non-invasive cancer detection in companion animals—a method that can increase the ability to perform cancer diagnosis and treatment. 

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2. Chip Technologies for Screening Chemical and Biological Agents Against Plant-Parasitic Nematodes

   https://doi.org/10.1094/PHYTO-06-16-0224-R  

   Beeman, Augustine Q. ; Njus, Zach L. ; Pandey, Santosh ; Tylka, Gregory L. ( December 2016 , Phytopathology®)

   Plant-parasitic nematodes cause substantial damage to agricultural crops worldwide. Long-term management of these pests requires novel strategies to reduce infection of host plants. Disruption of nematode chemotaxis to root systems has been proposed as a potential management approach, and novel assays are needed to test the chemotactic behavior of nematodes against a wide range of synthetic chemicals and root exudates. Two microfluidic chips were developed that measure the attraction or repulsion of nematodes to chemicals (“chemical chip”) and young plant roots (“root chip”). The chip designs allowed for chemical concentration gradients to be maintained up to 24 h, the nematodes to remain physically separate from the chemical reservoirs, and for images of nematode populations to be captured using either a microscope or a flatbed scanner. In the experiments using the chemical chips, seven ionic solutions were tested on second-stage juveniles (J2s) of Meloidogyne incognita and Heterodera glycines. Results were consistent with previous reports of repellency of M. incognita to a majority of the ionic solutions, including NH 4 NO 3 , KNO 3 , KCl, MgCl 2 , and CaCl 2 . H. glycines was found to be attracted to both NH 4 NO 3 and KNO 3 , which has not been reported previously. A software program was written to aid in monitoring the location of nematodes at regular time intervals using the root chip. In experiments with the root chip, H. glycines J2s were attracted to roots of 3-day-old, susceptible (cultivar Williams 82) soybean seedlings, and attraction of H. glycines to susceptible soybean was similar across the length of the root. Attraction to resistant (cultivar Jack) soybean seedlings relative to the water only control was inconsistent across runs, and H. glycines J2s were not preferentially attracted to the roots of resistant or susceptible cultivars when both were placed on opposite sides of the same root chip. The chips developed allow for direct tests of plant-parasitic nematode chemotaxis to chemicals and roots with minimal human intervention. 

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3. Feeding state sculpts a circuit for sensory valence in Caenorhabditis elegans

   https://doi.org/10.1073/pnas.1807454116  

   Rengarajan, Sophie ; Yankura, Kristen A. ; Guillermin, Manon L. ; Fung, Wendy ; Hallem, Elissa A. ( January 2019 , Proceedings of the National Academy of Sciences)

   Hunger affects the behavioral choices of all animals, and many chemosensory stimuli can be either attractive or repulsive depending on an animal’s hunger state. Although hunger-induced behavioral changes are well documented, the molecular and cellular mechanisms by which hunger modulates neural circuit function to generate changes in chemosensory valence are poorly understood. Here, we use the CO₂response of the free-living nematodeCaenorhabditis elegansto elucidate how hunger alters valence. We show that CO₂response valence shifts from aversion to attraction during starvation, a change that is mediated by two pairs of interneurons in the CO₂circuit, AIY and RIG. The transition from aversion to attraction is regulated by biogenic amine signaling. Dopamine promotes CO₂repulsion in well-fed animals, whereas octopamine promotes CO₂attraction in starved animals. Biogenic amines also regulate the temporal dynamics of the shift from aversion to attraction such that animals lacking octopamine show a delayed shift to attraction. Biogenic amine signaling regulates CO₂response valence by modulating the CO₂-evoked activity of AIY and RIG. Our results illuminate a new role for biogenic amine signaling in regulating chemosensory valence as a function of hunger state.

    

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4. Mitochondrial mutations in Caenorhabditis elegans show signatures of oxidative damage and an AT-bias

   https://doi.org/10.1093/genetics/iyab116  

   Waneka, Gus ; Svendsen, Joshua M ; Havird, Justin C ; Sloan, Daniel B ( August 2021 , Genetics)

   Surtees, J A (Ed.)

   Abstract Rapid mutation rates are typical of mitochondrial genomes (mtDNAs) in animals, but it is not clear why. The difficulty of obtaining measurements of mtDNA mutation that are not biased by natural selection has stymied efforts to distinguish between competing hypotheses about the causes of high mtDNA mutation rates. Several studies which have measured mtDNA mutations in nematodes have yielded small datasets with conflicting conclusions about the relative abundance of different substitution classes (i.e., the mutation spectrum). We therefore leveraged Duplex Sequencing, a high-fidelity DNA sequencing technique, to characterize de novo mtDNA mutations in Caenorhabditis elegans. This approach detected nearly an order of magnitude more mtDNA mutations than documented in any previous nematode mutation study. Despite an existing extreme AT bias in the C. elegans mtDNA (75.6% AT), we found that a significant majority of mutations increase genomic AT content. Compared to some prior studies in nematodes and other animals, the mutation spectrum reported here contains an abundance of CG→AT transversions, supporting the hypothesis that oxidative damage may be a driver of mtDNA mutations in nematodes. Furthermore, we found an excess of G→T and C→T changes on the coding DNA strand relative to the template strand, consistent with increased exposure to oxidative damage. Analysis of the distribution of mutations across the mtDNA revealed significant variation among protein-coding genes and as well as among neighboring nucleotides. This high-resolution view of mitochondrial mutations in C. elegans highlights the value of this system for understanding relationships among oxidative damage, replication error, and mtDNA mutation. 

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5. Two novel loci underlie natural differences in Caenorhabditis elegans abamectin responses

   https://doi.org/10.1371/journal.ppat.1009297  

   Evans, Kathryn S. ; Wit, Janneke ; Stevens, Lewis ; Hahnel, Steffen R. ; Rodriguez, Briana ; Park, Grace ; Zamanian, Mostafa ; Brady, Shannon C. ; Chao, Ellen ; Introcaso, Katherine ; et al ( March 2021 , PLOS Pathogens)

   Nutman, Thomas B. (Ed.)

   Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C . elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel ( glc-1 ). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C . elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C . elegans as a model to better understand ML resistance in parasitic nematodes. 

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