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Nat Rev Neurosci,
2012]
Caspases are cysteine proteases that mediate apoptosis, which is a form of regulated cell death that effectively and efficiently removes extra and unnecessary cells during development. In the mature nervous system, caspases are not only involved in mediating cell death but also regulatory events that are important for neural functions, such as axon pruning and synapse elimination, which are necessary to refine mature neuronal circuits. Furthermore, caspases can be reactivated to cause cell death as well as non-lethal changes in neurons during numerous pathological processes. Thus, although a global activation of caspases leads to apoptosis, restricted and localized activation may control normal physiology and pathophysiology in living neurons. This Review explores the multiple roles of caspase activity in neurons.
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Methods Enzymol,
2006]
The major virulence factor produced by the bacterium Bacillus thuringiensis (Bt) is a pore-forming toxin called crystal (Cry) toxin, which targets and kills insects and nematodes. To understand how this bacterial toxin interacts with its invertebrate hosts, a genetic screen in C. elegans for nematodes resistant to Bt toxin was carried out. Four of the five genes that mutated to toxin resistance encode glycosyltransferases. These genes were found to participate in the biosynthesis of C. elegans glycosphingolipids. These glycolipids in turn were shown to directly bind Bt toxin. Thus, resistance to Bt toxin in C. elegans can develop as a result of loss of glycolipid receptors for the toxin. Here we describe the isolation of Bt toxin resistance mutants in C. elegans, isolation of C. elegans glycolipids, and their separation by thin-layer chromatography, overlay assays to demonstrate direct binding of Bt toxin to glycolipids, and the purification of specific C. elegans glycolipid species.
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Int J Med Microbiol,
2004]
The interaction of pathogenic bacteria with a target host is regulated both by bacterial virulence factors and by host components that either protect the host or that promote pathogenesis. The soil nematode Caenorbabditis, elegans is a host for a number of bacterial pathogens, as briefly reviewed here. Bacillus thuringiensis (Bt) is a pathogenic bacteria that C. elegans is likely to encounter naturally in the soil. The pore-forming Crystal (Cry) toxins made by Bt are recognized as the dominant virulence factor in this host-pathogen interaction. Forward genetic screens for C. elegans mutants resistant to the Cry toxin, Cry5B, have identified a host carbohydrate structure that promotes pathogenesis. Data suggest this structure is likely to be a Cry5B receptor expressed in the host intestine. This finding is discussed in light of other carbohydrate receptors for bacterial toxins. To investigate host-toxin interactions on a global level, the response of C. elegans to the pore-forming Cry5B is also being investigated by gene transcription profiling (microarrays). These data are beginning to reveal a diverse intracellular response to toxin exposure. To put these investigations in perspective, host responses to other pore-forming toxins are discussed. Investigations with Cry5B in C. elegans show a promising beginning in helping to elucidate host-toxin and host-pathogen interactions.
[
1980]
The nematodes form a very important group of animals that have received much less study than deserved. They appear to be nearly as important in human health and agriculture as insects, and yet there are ten times as many entries in Biological Abstracts for the latter. Even from a less ethnocentric point of view, nematodes are significant. Hyman (1951) estimates 500,000 nematode species, which is of the same order as is the number of insect species. In soil, where comparisons have been made, the biomass of the two groups is roughly equal. The great disparity in research effort is simply because nematodes are much less visible to the casual observer. As a consequence of this situation, there is a need for basic biological research on nematodes. Much of the required work could be done on any typical nematode species, and since the free-living microphagous forms are most convenient to work with, they are of great interest. One of the areas in which basic knowledge is lacking for this group is that of behavior. This void is particularly surprising in view of the fact that behavior is presumably one of the more important aspects of parasitic lifestyles. It is also unfortunate from the point of view of basic behavioral biology. Nematodes and their close relatives occupy a unique place in the evolution of the nervous system. They are the only readily studied organisms that have been shown to have a centralized nervous system made up of a specific and countable number of neurons. The nematodes that have been examined have about 200 neurons depending on the species. In contrast, two annelids that have been studied have 10*4 and 10*5 neurons, and an arthropod is estimated to have 10*5 neurons. On the other hand, more primitive nervous systems are apparently not eutelic and often consist of a dispersed nerve net. Thus, it is of general biological interest to determine the behavioral capacities of