Characterization of novel ligand-gated chloride channel subunits from «Haemonchus contortus»
Bibliographic record
Abstract
Ligand-gated chloride channels (LGCCs) are key components that form the inhibitory neurotransmission system in animals.Nematodes possess LGCCs that are gated by unique ligands such glutamate, serotonin and acetylcholine.Higher living forms such as mammals are not known to possess similar receptors.Hence nematodes can be deemed to comprise a phylum with a divergent inhibitory neurotransmission system.Based on this premise, the current project aimed to better understand the inhibitory nervous system of the parasitic nematode, Haemonchus contortus through the characterization of novelLGCC subunits and the localization of relevant ligands believed to function as inhibitory neurotransmitters.The first novel LGCC subunit gene to be isolated was named Hco- GGR-3 (previously named as HcGGR3). Electrophysiological analyses of this subunit inXenopus laevis oocytes revealed the homomeric assembly of the channel which was predominately gated by dopamine (DA).Immuno-staining of H. contortus adult worms using antibodies raised against a peptide exclusive to Hco-GGR-3 showed that this subunit localized to deirid (cervical papilla) socket and sheath cells.Gender specific differences in localization of this subunit were also observed.In addition, a single nucleotide polymorphism located in the 3' untranslated region (UTR) of Hco-ggr-3 was found to be associated with the selection for resistance towards macrocyclic lactones (MLs) -moxidectin (MOF) and ivermectin (IVM) in H. contortus.A second amine-gated chloride channel gene called Hco-lgc-55 was also isolated.Electrophysiology of this subunit revealed that this channel was gated mainly by tyramine (TA) [EC 50 5.8 1.0 M (n=5)] and a lesser extent by dopamine (DA) and octopamine (OA).Semi-quantitative reverse transcription polymerase chain reaction (SqRT-PCR) showed the presence of mRNA for Hco-lgc-55 in all the life-cycle stages of the parasite.A detailed examination of the localization and characterization of dopamine (DA) and serotonin [5-hydroxy tryptamine (5-HT)], two key neurotransmitters that have been shown to be ligands for LGCCs, was also performed.5-HT was found mainly in the amphidial and pharyngeal neurons in both sexes; in males, neurons located in the bursa as well as in a few cell bodies of the ventral cord possessed 5-HT.DA was detected in the neuronal commissures restricted to the mid body region on the lateral sides, in both the sexes.Furthermore, an experiment where female adult worms were exposed to exogenously III supplied DA, 5-HT or TA revealed that each molecule had an effect on worm movement.However, the most profound effect was seen in the case of DA, which paralyzed the mid body of the worm.These studies provide novel information on unique LGICs and the role of novel LGIC ligands in an important parasitic nematode.I would like to thank my supervisors Drs.Sean Forrester and Roger Prichard for providing me the opportunity to perform research in their labs.I am grateful to both of them for their
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".