Scott AL (1996) Parasitol Today "Nematode sperm."

Scott AL

[Parasitol Today, 1996]

Parasitic nematode infections remain a major public health problem in many parts of the world. Because most of the current strategies aimed at controlling parasitic nematode infections have met with only limited success, it may be time to consider alternative approaches. An aspect of nematode biology that has drawn little attention as a target for control is the reproductive process. Although there are numerous facets of the overall reproductive biology of nematodes that hold potential as targets for intervention, Alan Scott here focuses on the male reproductive system, and outlines some of the known unique processes and characteristics of sperm formation and sperm function that could be exploited to block fertilization.

Kuwabara PE et al. (2000) Parasitol Today "RNAi--prospects for a general technique for determining gene function."

Kuwabara PE, Coulson AR

[Parasitol Today, 2000]

Gene discovery programs centred around expressed sequence tag (EST) and genome sequencing projects have predictably led to an exponential surge in the number of parasite gene sequences deposited in public databases. To take advantage of this wealth of sequence information, it is essential to develop rapid methods for elucidating the biological function or mode of action of individual genes. Here, Patricia Kuwabara and Alan Coulson discuss the virtues of a powerful epigenetic gene disruption technique, RNA-mediated interference (RNAi), which was originally developed for the nematode Caenorhabditis elegans. It is anticipated that this technique will not only provide insights into gene function, but also help investigators to mine the genome for candidate drug intervention or vaccine development targets, some of which may not be readily apparent on the basis of sequence information alone.

Freude S et al. (2009) Curr Alzheimer Res "The role of IGF-1 receptor and insulin receptor signaling for the pathogenesis of Alzheimer's disease: from model organisms to human disease."

Schilbach K, Schubert M, Freude S

[Curr Alzheimer Res, 2009]

In different clinical studies, an association of type 2 diabetes and Alzheimer's disease (AD) has been described. However, the underlying mechanisms are still unclear. One explanation could be that vascular complications of diabetes result in neurodegeneration. Alternatively, the mechanism might be directly related to insulin and insulin-like growth factor(IGF)-1 signaling, leading to the proposal that AD is a "brain-type diabetes". Furthermore, postmortem analyses of brains from patients with AD revealed a markedly downregulated expression of insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1 and IRS-2, and these changes progress with severity of neurodegeneration. These findings raise the question, whether this phenomenon is cause or consequence of neurodegeneration. Recently, Cohen and coworkers have show that knocking down DAF-2 in C. elegans, the homolog of the mammalian IR/IGF-1R, reduces beta-amyloid(Abeta)(1-42) toxicity. Cell based experiments suggest a specific role for the IGF 1/IRS-2 signaling pathway in regulating alpha-/beta-secretase activity. Moreover circulating IGF-1 might influence Abeta clearance from the brain by promoting Abeta transport over the blood brain barrier. Interestingly, brain specific deletion of IRS-2 increases life span, suggesting that long term neuronal IGF-1R signaling might be harmful. Taken together, the data from humans and different model organisms indicate a role of IR/IGF-1R signaling in Abeta metabolism, and clearance as well as longevity. Since more studies are needed to elucidate the impact of insulin and/or IGF-1 treatment in AD, the time to propose these hormones as a potential treatment option for AD has not come yet.

Coulson AR et al. (1995) Methods Cell Biol "The physical map of the Caenorhabditis elegans genome."

Kozono Y, Shownkeen R, Coulson AR, Huynh C

[Methods Cell Biol, 1995]

The clone-based physical map of the 100-Mb Caenorhabditis elegans genome has evolved over a number of years. Although the detection of clone overlaps and construction of the map have of necessity been carried out centrally, it has been essentially a community project. Without the provision of cloned markers and relevant map information by the C. elegans community as a whole, the map would lack the genetic anchor points and coherent structure that make it a viable entity. Currently, the map consists of 13 mapped contigs totaling in excess of 95 Mb and 2 significant unmapped contigs totaling 1.3 Mb. Telomeric clones are not yet in place. The map carries 600 physically mapped loci, of which 262 have genetic map data. With one exception, the physical extents of the remaining gaps are not known. The exception is the remaining gap on linkage group (LG) II. This has been shown to be bridged by a 225-kb Sse83871 fragment. Because the clones constituting the map are a central resource, there is essentially no necessity for individuals to construct cosmid and yeast artificial chromosome (YAC) libraries. Consequently, such protocols are not included here. Similarly, protocols for clone fingerprinting, which forms the basis of the determination of cosmid overlaps and the mapping of clones received from outside sources and has to be a centralized operation, and YAC linkage are not give here. What follows is essentially a "user's guide" to the physical map. Details of map construction are given where required for interpretation of the map as distributed. The physical mapping has been a collaboration between the MRC Laboratory of Molecular Biology, Cambridge, United Kingdom (now at The Sanger Centre, Cambridge, UK) and Washington University School of Medicine, St. Louis, Missouri. Inquiries regarding map interpretation, information, and materials should be addressed to alan@sanger.ac.uk or rw@nematode.wustl.edu.