Effects of cholinergic drugs on longitudinal muscle contractions of Fasciola hepatica

Acetylcholine, cholinergic agonists and acetylcholinesterase inhibitors significantly decrease the amplitude and frequency of spontaneous longitudinal muscle contractions in Fasciola hepatica. In order of their effects on the inhibition of muscle contractions, the cholinergic agonists can be ranked as nicotine greater than carbachol greater than acetylcholine. High calcium ion concentration also causes a significant inhibition of contractions. Atropine, a cholinergic antagonist that acts on muscarinic receptors, significantly increases the amplitude and frequency of spontaneous contractions and completely reverses the effects of cholinomimetic drugs, including nicotine. In adult F. hepatica, the levels of acetylcholine and its precursor choline are 3.14 +/- 0.55 and 13.75 +/- 3.72 pmol/mg wet weight, respectively. The activities of choline acetyltransferase, specific acetylcholinesterase and the nonspecific cholinesterase are 1.25 +/- 0.19, 238.0 +/- 13.0, and 83.0 +/- 33.0 nmol/hr/mg protein, respectively.     

Histochemical localization of acetylcholinesterase in the cerebral ganglia of Fasciola hepatica, a parasitic flatworm

Acetylcholinesterase activity was found in the cell bodies and extracellularly in the neuropile of the cerebral ganglia of the adult trematode parasite, Fasciola hepatica. Within neuronal cell bodies of the cerebral ganglion, acetylcholinesterase reaction product was found in the endoplasmic reticulum, in the cisternae of the Golgi apparatus, and in secretory vesicles near the inner (releasing face) cisternae. Acetylcholinesterase reaction product was not seen intracellularly within any nerve processes. The reaction product was found around the somatic cell membranes and in the extracellular space between closely apposed nerve processes in the neuropile. Acetylcholinesterase reaction product was associated with synaptic endings that contained clear spheroidal synaptic vesicles, and the reaction product was localized at the site of synaptic contact between the zone of apposition of the pre- and postsynaptic terminals. This intracellular and extracellular distribution of the enzyme is consistent with its function as the degrading enzyme in cholinergic transmission.     

mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species

Reconstructions of the human-African great ape phylogeny by using mitochondrial DNA (mtDNA) have been subject to considerable debate. One confounding factor may be the lack of data on intraspecific variation. To test this hypothesis, we examined the effect of intraspecific mtDNA diversity on the phylogenetic reconstruction of another Plio- Pleistocene radiation of higher primates, the fascicularis group of macaque (Macaca) monkey species. Fifteen endonucleases were used to identify 10 haplotypes of 40-47 restriction sites in M. mulatta, which were compared with similar data for the other members of this species group. Interpopulational, intraspecific mtDNA diversity was large (0.5%- 4.5%), and estimates of divergence time and branching order incorporating this variation were substantially different from those based on single representatives of each species. We conclude that intraspecific mtDNA diversity is substantial in at least some primate species. Consequently, without prior information on the extent of genetic diversity within a particular species, intraspecific variation must be assessed and accounted for when reconstructing primate phylogenies. Further, we question the reliability of hominoid mtDNA phylogenies, based as they are on one or a few representatives of each species, in an already depauperate superfamily of primates.      

Habitat selection by helminths: a hypothesis

How do liver worms find the liver? Why are heartworms always found in the heart? Attempts to answer these questions have invariably yielded inconclusive results. A major problem has been the use of models or hypotheses derived from studies of free-living organisms. The parasite's environment is distinct from free-living environments in several fundamental ways and these differences will impact on the evolution of parasite behaviours. In this article, Michael Sukhdeo outlines a hypothesis for habitat selection behavior of helminths that is based on the specific environmental conditions within the host.     

Estimating transmission potential in gastrointestinal nematodes (order: Strongylida)

Microparasite virulence (the potential to cause harm in the host) is thought to be regulated by a direct trade-off with pathogen transmission potential, but it is unclear whether similar trade-offs occur in macroparasites (helminths). In this analysis, the transmission potentials of 5 nematode species (order Strongylida), known to differ in their virulence, were estimated using an index based on egg production and larval survivability. Virulence estimates were based on the minimum number of worms that cause host death. In nematode species where mature adults cause pathology (trichonematidic development), there is a direct relationship between virulence and transmission, suggesting that high virulence is related to parasite fitness in these worms. However, in nematodes where the juvenile stages produce pathology during migration and development (strongylidic development), virulence is not correlated with transmission. These data suggest that trade-offs between transmission and virulence in nematode parasites are not analogous for all species and may depend on the developmental strategy and mechanism of pathogenicity of the parasites.     

Combinatorial synthesis of substituted 3-(2-indolyl)piperidines and 2-phenyl indoles as inhibitors of ZipA-FtsZ interaction

The ZipA-FtsZ protein-protein interaction is a potential target for antibacterial therapy. The design and parallel synthesis of a combinatorial library of small molecules, which target the FtsZ binding area on ZipA are described. Compounds were demonstrated to bind to the FtsZ binding domain of ZipA by HSQC NMR and to inhibit cell division in a cell elongation assay.     

Fixed behaviours and migration in parasitic flatworms

This paper considers how fixed behaviours may play a role in post-larval migrations of Entobdella soleae. A general argument is that a shift away from the paradigm of orientation is required to elucidate the mechanisms that parasites use to navigate on the surface of their hosts. Some migrations may rely on fixed behaviours (genetically programmed stereotyped behaviours) that often evolve under predictable environmental conditions with reliable signals. In turbulent and stochastic free-living environments, homeostatic hosts present very predictable topological substrates and physico-chemical characteristics to their parasites. Over the course of evolution on these predictable host substrates, adaptive behaviours in the parasites can become fixed. Examples of endoparasite migration behaviour, particularly that of the common liver fluke, Fasciola hepatica, will be used to develop an approach based on the perceptual worlds of migrating parasites. An important conclusion is that multi-disciplinary approaches, firmly rooted in an understanding of each parasite's natural history, are requisite to successful interpretation of migration behaviours on the host.     

Intestinal distribution of worms and host ingesta in Nippostrongylus brasiliensis.

The gastrointestinal nematode Nippostrongylus brasiliensis is thought to feed on host ingesta, and it is generally thought that the presence of ingesta determines the distribution of this parasite within the host intestine. However, these assertions have not been supported by direct evidence. The purpose of this study was to test the hypothesis that N. brasiliensis worms are preferentially found in regions of the host small intestine containing ingesta. The relationship between worm and ingesta distribution was investigated using mice infected with N. brasiliensis and killed on day 8 postinfection at 0130, 0730, 1330, or 1930 hr. There was an inverse relationship between worm and ingesta distributions, and the worms were distributed significantly more anteriad in the intestine than host ingesta, at all times during the 24 hr. To determine what the worms fed on, host ingesta, tissue, and blood were differentially labeled with the fluorescent dyes rhodamine B and Fluoresbrite. The results of this study suggest that N. brasiliensis feeds on the host's intestinal wall, and that habitat distribution of this parasite within the small intestine is not directly related to the presence of luminal ingesta.     

Glioma development: where did it all go wrong?

Investigating the family tree of a tumor to identify its cellular origins is a daunting task. Liu et al. (2011) now use an elegant lineage tracing technique (MADM) to visualize glioma from its earliest stages. They show that mutations originally induced in neural stem cells lie dormant and only trigger malignant transformation following differentiation into oligodendrocyte precursor cells.