Getting around the roundworms: Identifying knowledge gaps and research priorities for the ascarids.

The ascarids are a large group of parasitic nematodes that infect a wide range of animal species. In humans, they cause neglected diseases of poverty; many animal parasites also cause zoonotic infections in people. Control measures include hygiene and anthelmintic treatments, but they are not always appropriate or effective and this creates a continuing need to search for better ways to reduce the human, welfare and economic costs of these infections.

Diethylcarbamazine elicits Ca signals through TRP-2 channels that are potentiated by emodepside in muscles.

Filarial nematode infections are a major health concern in several countries. Lymphatic filariasis is caused by and spp. affecting over 120 million people.

Diethylcarbamazine elicits Ca signals through TRP-2 channels that are potentiated by emodepside in muscles.

Filarial nematode infections are a major health concern in several countries. Lymphatic filariasis is caused by and affecting over 120 million people. Heavy infections can lead to elephantiasis having serious effects on individuals’ lives.

Diethylcarbamazine, TRP channels and Ca signaling in cells of the Ascaris intestine.

The nematode parasite intestine absorbs nutrients, is involved in innate immunity, can metabolize xenobiotics and as we show here, is also a site of action of the anthelmintic, diethylcarbamazine. Diethylcarbamazine (DEC) is used to treat lymphatic filariasis and activates TRP-2, GON-2 & CED-11 TRP channels in Brugia malayi muscle cells producing spastic paralysis. DEC also has stimulatory effects on ascarid nematode parasites.

Diethylcarbamazine mediated potentiation of emodepside induced paralysis requires TRP-2 in adult Brugia malayi.

Human and veterinary filarial nematode infections are a major health concern in tropical countries. They are transmitted by biting insects and mosquitoes. Lymphatic filariasis, a group of filarial infections caused by Brugia spp.

Nodulisporic acid produces direct activation and positive allosteric modulation of AVR-14B, a glutamate-gated chloride channel from adult .

Glutamate-gated chloride channels (GluCls) are unique to invertebrates and are targeted by macrocyclic lactones. In this study, we cloned an AVR-14B GluCl subunit from adult , a causative agent of lymphatic filariasis in humans. To elucidate this channel's pharmacological properties, we used oocytes for expression and performed two-electrode voltage-clamp electrophysiology.

High concentrations of the anthelmintic diethylcarbamazine paralyze independently of TRP-2.

Diethylcarbamazine (DEC) has been used to treat lymphatic filariasis in tropical countries since the 1940s. Its mode of action is still unclear, with several reports suggesting a host immune system-mediated mechanism. We previously demonstrated that DEC causes transient spastic paralysis in the filarial nematode due to the activation of TRP-2.

Advances in our understanding of nematode ion channels as potential anthelmintic targets.

Ion channels are specialized multimeric proteins that underlie cell excitability. These channels integrate with a variety of neuromuscular and biological functions. In nematodes, the physiological behaviors including locomotion, navigation, feeding and reproduction, are regulated by these protein entities.

Anthelmintic resistance and homeostatic plasticity (Brugia malayi).

Homeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in parasitic nematodes when treated with therapeutic drugs. Here we have studied the adaptation of Brugia malayi to exposure to the anthelmintic, levamisole that activates muscle AChR ion-channels.

Author Correction: Diethylcarbamazine activates TRP channels including TRP-2 in filaria, Brugia malayi.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Diethylcarbamazine activates TRP channels including TRP-2 in filaria, Brugia malayi.

Diethylcarbamazine is an important classic drug used for prevention and treatment of lymphatic filariasis and loiasis, diseases caused by filarial nematodes. Despite many studies, its site of action has not been established. Until now, the consensus has been that diethylcarbamazine works by activating host immune systems, not by a direct action on the parasites.

Emodepside has sex-dependent immobilizing effects on adult Brugia malayi due to a differentially spliced binding pocket in the RCK1 region of the SLO-1 K channel.

Filariae are parasitic nematodes that are transmitted to their definitive host as third-stage larvae by arthropod vectors like mosquitoes. Filariae cause diseases including: lymphatic filariasis with distressing and disturbing symptoms like elephantiasis; and river blindness. Filarial diseases affect millions of people in 73 countries throughout the topics and sub-tropics.

A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning.

The Pam/Highwire/RPM-1 (PHR) proteins are conserved intracellular signaling hubs that regulate synapse formation and axon termination. The C. elegans PHR protein, called RPM-1, acts as a ubiquitin ligase to inhibit the DLK-1 and MLK-1 MAP kinase pathways.

Functional genomics in reveal diverse muscle nAChRs and differences between cholinergic anthelmintics.

Many techniques for studying functional genomics of important target sites of anthelmintics have been restricted to because they have failed when applied to animal parasites. To overcome these limitations, we have focused our research on the human nematode parasite which causes elephantiasis. Here, we combine single-cell PCR, whole muscle cell patch clamp, motility phenotyping (Worminator), and dsRNA for RNAi for functional genomic studies that have revealed, in vivo, four different muscle nAChRs ( and ).

Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression.

The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue.

Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression.

Background: Many neurodegenerative diseases are associated with protein misfolding/aggregation. Treatments mitigating the effects of such common pathological processes, rather than disease-specific symptoms, therefore have general therapeutic potential.

Results: Here we report that the anti-epileptic drug ethosuximide rescues the short lifespan and chemosensory defects exhibited by C.

Anthelmintics: The best way to predict the future is to create it.

'The best way to predict the future is to create it.' When we look at drugs that are used to control parasites, we see that new knowledge has been created (discovered) about their modes of action. This knowledge will allow us to predict combinations of drugs which can be used together rationally to increase the spectrum of action and to slow the development of anthelmintic resistance.

Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective drug screening and identifies a SIR-2.1-independent action of resveratrol.

Adult onset neuronal lipofuscinosis (ANCL) is a human neurodegenerative disorder characterized by progressive neuronal dysfunction and premature death. Recently, the mutations that cause ANCL were mapped to the DNAJC5 gene, which encodes cysteine string protein alpha. We show here that mutating dnj-14, the Caenorhabditis elegans orthologue of DNAJC5, results in shortened lifespan and a small impairment of locomotion and neurotransmission.

Rab-3 and unc-18 interactions in alcohol sensitivity are distinct from synaptic transmission.

The molecular mechanisms underlying sensitivity to alcohol are incompletely understood. Recent research has highlighted the involvement of two presynaptic proteins, Munc18 and Rab3. We have previously characterised biochemically a number of specific Munc18 point mutations including an E466K mutation that augments a direct Rab3 interaction.