The article, written by Erika Bistran, M. Evelyn Carpenter and Daniel J. Sprague of the Medical University of South Carolina, focuses on bioaminergic signaling, the system of neurotransmitters that includes serotonin, dopamine, histamine, tyramine and octopamine. These molecules have been implicated in flatworm neuromuscular control for decades, but the authors contend that the field has been stuck cataloging which amines are present and which compounds make worms twitch. What is needed, they say, is mechanistic depth: knowing exactly which receptor detects the signal, which second messenger carries it inside the cell, which tissue hosts the signaling, and which parasite behavior changes when the pathway is disrupted.

To organize that effort, the researchers propose a pathway-to-phenotype framework built on six interconnected areas of investigation. These are the bioamine ligand itself, the receptor or transporter that detects or clears it, the downstream signaling pathway it engages, the cell type or tissue where signaling occurs, the experimental perturbation used to test function, and the resulting parasite phenotype. No single experiment needs to cover all six domains, the authors stress, but each experimentally supported connection between them raises the resolution of the pathway model, moving the field from association toward mechanism.

The clearest proof that this approach works is the serotonin receptor Sm5HTR in Schistosoma mansoni, the blood fluke responsible for schistosomiasis, a disease that afflicts hundreds of millions of people. Serotonin has long been known to excite schistosome movement and potentiate body wall muscle contraction. The characterization of Sm5HTR turned that observation into a complete molecular story. The receptor is a serotonin-responsive G protein-coupled receptor distantly related to human 5-HT7 receptors. When expressed in heterologous systems, it responds to serotonin by raising intracellular cAMP, consistent with a Gαs-coupled mechanism. Immunolocalization places it throughout the parasite nervous system, including the cerebral ganglia, the longitudinal nerve cords and the peripheral innervation of body wall muscle. Crucially, knocking the receptor down with RNA interference in larvae and adults causes marked hypoactivity and blunted responses to exogenous serotonin.

Sm5HTR has also proven pharmaceutically fruitful. Screening campaigns have identified novel agonists and antagonists, including parasite-selective inhibitor classes, and efforts have been made to distinguish schistosome-specific from human-specific ligands. For the authors, this makes Sm5HTR the benchmark against which every other aminergic system in flatworms should be judged: ligand, receptor, second messenger, anatomy, perturbation and phenotype all connected in one system.

Other aminergic pathways in schistosomes are promising but incomplete. Two dopamine-responsive GPCRs, SmD2 and SmGPR-3, are associated with the parasite neuromusculature, yet the full chain from receptor activation to parasite phenotype has not been closed. The dopamine system also delivers a cautionary lesson about assuming that parasite receptors behave like their mammalian counterparts. SmGPR-3 shows a mixed pharmacological profile in which a mammalian dopamine receptor antagonist acts as an agonist. SmD2, meanwhile, resembles human D2 receptors by sequence, but while the mammalian D2 family couples to inhibitory Gαi/o proteins, SmD2 appears to couple to Gαs instead. Such divergences are exactly what the authors argue could create parasite-selective drug targets.

Histamine adds a further twist: not all flatworm aminergic receptors converge on cAMP. A histamine-responsive receptor called SmGPR-1, expressed mainly in body wall muscles, is linked to intracellular calcium mobilization rather than cAMP accumulation, suggesting a Gαq-like pathway. This matters practically, because receptor screens built solely on cAMP readouts will miss or misclassify calcium-linked receptors. A second histamine receptor, SmGPR-2, is upregulated in schistosomula and expressed in the subtegumental nerve plexus, and it carries a striking molecular anomaly. The conserved aspartate residue at position 3.32 in transmembrane helix 3, a linchpin of ligand activation in most Class A GPCRs, is replaced by an asparagine, and many mammalian histamine antagonists are ineffective against it. Histamine is also conceptually intriguing because parasites may encounter it both as their own signal and as a host-derived inflammatory cue, raising the possibility that some aminergic pathways serve in host sensing rather than classical neurotransmission.

Octopamine and tyramine may offer the largest selectivity window of all, because these tyrosine-derived amines are prominent in invertebrate neuromodulation but peripheral to mammalian neurobiology. Anatomical, phenotypic and pharmacological evidence supports octopamine signaling in S. mansoni, and octopamine-related compounds alter schistosomulum motility and length. But no octopamine or tyramine receptor has yet been functionally profiled, leaving the field unable to say whether these signals travel through cAMP, calcium, inhibitory G proteins or biased pathways. Until the receptors are deorphanized and compared with host targets, the authors note, parasite selectivity remains a hypothesis rather than a fact.

The perspective also warns against a schistosome-centric view. Serotonin-responsive GPCRs have been cloned and characterized from tapeworms such as Echinococcus and Mesocestoides, including a set of 5-HT7-like receptors that stimulate cAMP production and a novel class of 5-HT1-like receptors deorphanized through a promiscuous Gα15 effector and calcium-flux assays. Serotonin boosts larval motility in cestodes, and receptor localization near the suckers of Echinococcus granulosus larvae hints that the same signaling may influence attachment as well as movement. In liver flukes, recent work in Fasciola hepatica has localized serotonin receptors and transporters and used RNAi to probe their function, while dopaminergic antagonists disrupt bile chemotaxis and egg production in the carcinogenic fluke Clonorchis sinensis, even though no aminergic receptor from that parasite has been cloned. Comparing these lineages, the authors argue, will reveal which signaling features are broadly conserved targets and which are lineage-specific opportunities.

Transporters form the underdeveloped half of the story. By clearing serotonin, dopamine and other amines from the extracellular space, transporters control signal duration and receptor desensitization, and inhibiting them could disrupt multiple receptor pathways at once. Candidate and characterized transporters exist in schistosomes, F. hepatica and C. sinensis, but their substrate specificity, inhibitor sensitivity, expression patterns and whole-parasite consequences remain poorly mapped. Any transporter-directed strategy will demand careful selectivity profiling, since host monoamine transporters are the pharmacologically sensitive targets of drugs such as antidepressants. Looking forward, the authors highlight three unresolved questions: what intracellular signaling machinery parasite receptors actually use outside heterologous systems, whether the worms are sensing their own neurotransmitters or host-derived chemical cues, and how aminergic pathways crosstalk with neuropeptidergic and cholinergic networks. The most promising future drug targets, they conclude, will combine functional importance, parasite-selective pharmacology and measurable whole-parasite consequences, and the Sm5HTR story provides the template for finding them.

Subject of Research: Bioaminergic GPCR signaling pathways and drug discovery in parasitic flatworms

Article Title: Bioaminergic signaling in parasitic flatworms: a perspective for linking GPCRs to behavior and drug discovery

Article References: Bioaminergic signaling in parasitic flatworms: a perspective for linking GPCRs to behavior and drug discovery. (n.d.). https://doi.org/10.3389/fpara.2026.1933406

Image Credits: AI Generated

DOI: 10.3389/fpara.2026.1933406

Keywords: parasitic flatworms, schistosomiasis, G protein-coupled receptors, serotonin, dopamine, histamine, octopamine, neurotransmitter transporters, anthelmintics, drug discovery, Schistosoma mansoni, trematodes

The research, led by Samuel Appleyard-Sanderson of the University of Bristol together with colleagues, set out to test a concept known as targeted selective treatment, or TST. Instead of blanketing an entire herd with anthelmintics, TST treats only the animals carrying the most clinically significant parasite burdens, leaving the rest untreated. The idea was originally developed to slow the evolution of drug resistance in gastrointestinal parasites, by maintaining a reservoir of drug-susceptible worms on the pasture. But ecologists have proposed a second benefit: untreated animals produce uncontaminated dung, which could act as a refuge and recolonisation source for the flies and beetles that breed in cattle faeces and perform the vital ecosystem service of breaking it down.

To test this idea, the team built a spatially explicit simulation of a temperate pasture, represented as a 20-by-20 grid of 400 cells, each capable of holding a single dung pat. The model tracked three functional guilds of dung-inhabiting insects: dung-breeding flies such as the yellow dung fly Scathophaga stercoraria and sepsid flies, endocoprid beetles that live and feed within the pat, and paracoprid beetles such as Onthophagus and Geotrupes species that haul dung underground to breed in the soil beneath. Each guild was parameterised with life-history data drawn from published field and laboratory studies, capturing differences in fecundity, development time, lifespan, dispersal and, crucially, sensitivity to anthelmintic residues at different life stages.

The biological contrasts between the guilds are stark. Flies develop from egg to adult in roughly 20 days, lay around 95 eggs per clutch and live only about 24 days, but they remove very little dung individually and are highly sensitive to ivermectin at every life stage. Beetles are slower and longer-lived, with development periods ranging from about 45 days for endocoprid Aphodius species to 100 days for paracoprids, and much lower fecundity, but they are the workhorses of dung removal, with paracoprid larvae capable of processing nearly half a gram of dung per individual per day. In the model, larvae in contaminated pats suffered complete mortality, adult flies entering contaminated pats died outright, and adult beetles experienced variable mortality, while dung removal by larvae in contaminated pats was halved to reflect documented sublethal effects.

Each simulation ran for 1,000 daily timesteps, representing roughly five continuous grazing seasons. For the first 500 days, the insect communities established themselves without any drug exposure. Treatment then began, with newly deposited pats assigned as contaminated or clean according to the TST level, which ranged from zero, meaning every animal was treated, to one, meaning no animals were treated. The researchers ran ten replicate simulations for every combination of TST level and stocking density of 5, 10 or 15 animals per hectare, producing 330 individual runs in total. The model deliberately assumed that residues in dung remained at full strength until the pat degraded, a conservative choice that maximises lethal and sublethal effects over time.

The results reveal a genuinely complicated picture. As the proportion of untreated animals increased, total insect community density first dipped slightly and then climbed steeply, driven overwhelmingly by flies, which went from being the scarcest guild under full treatment to the most abundant when no animals were treated. Endocoprid beetles also increased, though more slowly. Paracoprid beetles, however, declined gradually as TST rose, a counterintuitive outcome the authors attribute to the breadth of species aggregated into that guild, which may have produced overgeneralised parameters. They note that paracoprid populations are naturally smaller than fly populations, so a community dominated by flies at maximum TST may actually resemble a more natural state rather than a degraded one.

Stocking density proved to be a critical modifier of these patterns. At the lowest density of 5 animals per hectare, insect numbers rose exponentially with increasing TST. At 10 animals per hectare, densities dipped slightly up to a TST of 0.5 before climbing sharply. At the highest density of 15 animals per hectare, insect numbers were actually greatest under full treatment, declined as TST increased, and only recovered partially as untreated levels approached one. The authors suggest this may reflect density-dependent competition: abundant dung at high stocking density initially supports large insect populations, which then rapidly degrade pats and trigger overcompensatory competitive exclusion. They caution that the densities modelled represent the upper end of UK grazing intensity and may be most applicable to intensive or rotationally managed systems.

Perhaps the most encouraging finding concerns dung removal itself, the ecosystem service with the most direct consequences for pasture health. Mean standing pat biomass decreased exponentially as the proportion of untreated animals rose, with reductions of roughly 13 percent at low stocking density, 20 percent at medium density and 31 percent at high density. In other words, leaving more animals untreated meant more insects survived to break down dung, so pats disappeared faster. This aligns with earlier empirical work showing that ivermectin contamination can cut dung removal rates by around a third to a half. For farmers worried that reducing treatment might leave pastures littered with undecomposed faeces, the model offers reassurance that the opposite is more likely to occur.

The study also identified an apparent threshold: reducing the treated proportion of the herd below roughly 50 percent seemed to bring comparatively little additional benefit for beetle populations, although the authors stress that this figure is sensitive to parameter values that remain poorly constrained empirically and should be treated as indicative rather than a precise management target. Fly populations, by contrast, continued to respond positively to reduced treatment well beyond that point, though flies contribute least to dung removal. The authors frame their findings as a theoretical foundation for promoting targeted selective treatment as a compromise between parasite control and biodiversity conservation within precision livestock farming, with direct relevance for agri-environment policy.

The model is not without limitations, which the authors discuss candidly. It includes only three guilds, omitting predators, parasites and the seasonal dynamics that govern real temperate communities, and it assumes constant residue concentrations and simplified colonisation rules, with flies restricted to one-day-old pats and beetles to pats up to five days old. Dispersal was modelled as purely distance-dependent, excluding long-range recolonisation. Residues in reality decline over time, so the model likely exaggerates long-term mortality, though the authors argue this would change the magnitude rather than the direction of their conclusions. What is now needed, they conclude, is empirical field testing of targeted selective treatment across whole farms, which would supply the species-specific dispersal and life-history data required to refine future models. Until then, the simulations offer the clearest picture yet that how, and how many, animals are treated may matter as much as the drugs themselves.

Subject of Research: Ecological effects of targeted selective anthelmintic treatment on dung-inhabiting insect communities in temperate pastures

Article Title: Simulated Targeted Anthelmintic Treatment Maintains Dung Removal but Not Dung‐Inhabiting Insect Communities

Article References: Appleyard‐Sanderson, S., Lurgi, M., Wall, R., & Clements, C. F. (2026). Simulated Targeted Anthelmintic Treatment Maintains Dung Removal but Not Dung‐Inhabiting Insect Communities. Ecology and Evolution, 16(10), Article e74477. https://doi.org/10.1002/ece3.74477

Image Credits: AI Generated

DOI: 10.1002/ece3.74477

Keywords: anthelmintics, ivermectin, targeted selective treatment, dung beetles, dung flies, livestock, ecosystem services, dung removal, simulation model, biodiversity, pasture management, endectocides

A team at Korea’s National Institute of Food and Drug Safety Evaluation, led by Ye-Bin Jang and corresponding author Mi-Ok Kim, has now closed that gap. Writing in Food Science of Animal Resources, the researchers describe an optimized liquid chromatography–tandem mass spectrometry (LC–MS/MS) method that simultaneously quantifies 18 structurally diverse anthelmintic and antiparasitic compounds across nine animal-derived food matrices: beef, pork, chicken, eggs, milk, porcine fat, flatfish, eel, and shrimp. Beyond niclosamide, the method brings rarely monitored compounds such as derquantel, bithionol, and nitroxinil into quantitative reach, expanding both the chemical and the biological scope of routine residue surveillance.

The analytical challenge is formidable because the target compounds span six major chemical classes with very different physicochemical personalities. Benzimidazoles such as triclabendazole attack larval and adult parasites alike; salicylanilides including closantel, rafoxanide, and niclosamide also knock down ectoparasites like ticks; tetrahydropyrimidines such as morantel and pyrantel act as nicotinic receptor agonists; imidazothiazoles like levamisole target roundworms; and the macrocyclic lactones—abamectin, ivermectin, doramectin, eprinomectin, and moxidectin—are large, extremely lipophilic molecules that cling stubbornly to fatty tissue. Add praziquantel and nitroxinil to the list, and a single run must coax compounds ranging from small polar bases to sprawling lipid-like structures through the same column and ion source.

Sample preparation began with the QuEChERS approach—Quick, Easy, Cheap, Effective, Rugged, and Safe—which uses salt-induced phase separation to pull analytes from homogenized tissue into acetonitrile. The team compared three salt formulations: the unbuffered Original method with magnesium sulfate and sodium chloride, the citrate-buffered EN 15662 version, and the acetate-buffered AOAC variant. The verdict was decisive. In flatfish, the buffered methods produced calibration curves for abamectin with coefficients of determination of just 0.2304 and 0.0385—essentially useless—while the Original salts delivered R² values above 0.99 for all 18 compounds. The researchers attribute the failure of buffered systems to citrate and acetate ions altering salting-out efficiency and promoting co-extraction of lipids, proteins, and phospholipids, which then suppress ionization of the lipophilic macrocyclic lactones during electrospray.

Extraction used acetonitrile acidified with 0.1% formic acid, a combination known to improve recovery and precision for veterinary drugs in animal tissue. Clean-up followed with dispersive solid-phase extraction, and here the sorbent recipe mattered enormously. C18 alone left chlorfluazuron, levamisole, triclabendazole, and keto-triclabendazole with substandard linearity; PSA alone failed for chlorfluazuron and triclabendazole. Only the pairing of 400 milligrams of PSA with 400 milligrams of C18, plus 1,200 milligrams of magnesium sulfate, achieved R² values of at least 0.99 across the entire panel. PSA’s amino groups mop up organic acids and sugars, while C18 adsorbs nonpolar fats and fat-soluble interferences—a synergy the team standardized by purifying a fixed 8-milliliter extract volume for every matrix.

On the instrument side, chromatographic separation ran on a Waters Xbridge C18 column with a gradient of water containing 5 millimolar ammonium formate and 0.1% formic acid against acetonitrile with 0.1% formic acid. Retention times spanned from 1.9 minutes for morantel to 6.4 minutes for ivermectin. Detection used a Shimadzu LCMS-8060 triple quadrupole in multiple reaction monitoring mode, switching between positive and negative electrospray ionization, with precursor ions, product ions, and collision energies optimized by direct infusion of standards. The most intense transition served for quantification while secondary transitions confirmed identity.

Matrix effects proved to be the method’s central analytical adversary. Co-extracted lipids and proteins distort electrospray ionization, and the team measured signal changes of at least 20% for most analytes. Ion suppression dominated, ranging down to −96.08%, with abamectin, levamisole, pyrantel, and triclabendazole suppressed in every single matrix. Moxidectin, by contrast, showed ion enhancement in several foods, including chicken, milk, and all three fishery products. Rather than turning to isotope-labeled internal standards—impractical and costly for an 18-compound panel—the researchers built matrix-matched calibration curves in blank extracts of each food, so standards and samples ionize under identical chemical conditions and systematic signal bias cancels out at the quantification stage.

Validated under CODEX guideline CAC/GL-71, the method met every performance criterion. Matrix-matched calibration curves exceeded R² of 0.99 for all compounds in all nine matrices. Limits of quantification ranged from 0.0033 to 0.0054 milligrams per kilogram, all below half of the established MRLs. Intraday recovery and precision across the matrices fell between 72.0 and 119.1% with coefficients of variation no higher than 18.2%, comfortably inside CODEX windows, and interday testing on three consecutive days with two analysts held recoveries between 72.0 and 118.7% with CVs at or below 19.0%.

To test real-world utility, the team analyzed 60 market samples—30 livestock and 30 fishery products chosen for high Korean consumption. None of the 18 target analytes was detected, a reassuring snapshot of the domestic supply, though the authors stress that continued surveillance remains essential. The method’s true significance lies in what it enables going forward: quantitative enforcement for drugs like niclosamide that previously escaped numeric scrutiny, a single validated workflow spanning meat, dairy, eggs, and seafood, and a technical foundation for setting and revising safety standards. As veterinary drug use intensifies globally and resistant parasites push dosing upward, tools like this one turn regulatory limits from paper promises into measurable, enforceable protections for the food supply.

Subject of Research: Development and validation of a QuEChERS-based LC–MS/MS method for quantifying multiclass veterinary anthelmintic residues in animal-derived foods

Article Title: Optimized LC–MS/MS method for simultaneous determination of multiclass veterinary anthelmintic residues in animal-derived matrices

Article References: Optimized LC–MS/MS method for simultaneous determination of multiclass veterinary anthelmintic residues in animal-derived matrices. (n.d.). https://doi.org/10.1007/s44463-026-00098-1

Image Credits: AI Generated

DOI: 10.1007/s44463-026-00098-1

Keywords: anthelmintics, LC-MS/MS, veterinary drug residues, QuEChERS, food safety, maximum residue limits, matrix-matched calibration, livestock products, fishery products, niclosamide, mass spectrometry, residue monitoring