Flea-borne infections are emerging or re-emerging throughout the world, and their incidence is on the rise. Furthermore, their distribution and that of their vectors is shifting and expanding. This publication reviews general flea biology and the distribution of the flea-borne diseases of public health importance throughout the world, their principal flea vectors, and the extent of their public health burden. Such an overall review is necessary to understand the importance of this group of infections and the resources that must be allocated to their control by public health authorities to ensure their timely diagnosis and treatment.

Siphonaptera (fleas) is a highly specialized order of holometabolous insects comprising 2500 species placed in 16 families. Despite a long history of extensive work on flea classification and biology, phylogenetic relationships among fleas are virtually unknown. We present the first formal analysis of flea relationships based on a molecular matrix of four loci (18S ribosomal DNA, 28S ribosomal DNA, Cytochrome Oxidase II, and Elongation Factor 1-alpha) for 128 flea taxa from around the world representing 16 families, 25 subfamilies, 26 tribes, and 83 flea genera with eight outgroups. Trees were reconstructed using direct optimization and maximum likelihood techniques. Our analysis supports Tungidae as the most basal flea lineage, sister group to the remainder of the extant fleas. Pygiopsyllomorpha is monophyletic, as are the constituent families Lycopsyllidae, Pygiopsyllidae, and Stivaliidae, with a sister group relationship between the latter two families. Macropsyllidae is resolved as sister group to Coptopsyllidae with moderate nodal support. Stephanociricidae is monophyletic, as are the two constituent subfamilies Stephanocircinae and Craneopsyllinae. Vermipsyllidae is placed as sister group to Jordanopsylla. Rhopalopsyllidae is monophyletic as are the two constituent subfamilies Rhopalopsyllinae and Parapsyllinae. Hystrichopsyllidae is paraphyletic with Hystrichopsyllini placed as sister to some species of Anomiopsyllini and Ctenopariini placed as sister to Carterettini. Ctenophthalmidae is grossly paraphyletic with the family broken into seven lineages dispersed on the tree. Most notably, Anomiopsyllini is paraphyletic. Pulicidae and Chimaeropsyllidae are both monophyletic and these families are sister groups. Ceratophyllomorpha is monophyletic and includes Ischnopsyllidae, Ceratophyllidae, and Leptopsyllidae. Leptopsyllidae is paraphyletic as are its constituent subfamilies Amphipsyllinae and Leptopsyllinae and the tribes Amphipsyllini and Leptopsyllini. Ischnopsyllidae is monophyletic. Ceratophyllidae is monophyletic, with a monophyletic Dactypsyllinae nested within Ceratophyllinae, rendering the latter group paraphyletic. Mapping of general host associations on our topology reveals an early association with mammals with four independent shifts to birds.

The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is induced as part of the IFN response in mammals and acts to shut down protein synthesis by the phosphorylation of eukaryotic initiation factor 2␣ (eIF2␣). In fish, a PKR-like kinase activity has been detected, but the enzyme responsible has eluded characterization. Here, we describe a PKR-like kinase from zebrafish. Phylogenetic analysis shows that the C-terminal kinase domain is more closely related to the kinase domain of PKR than to any of the other three known eIF2␣ kinases. Surprisingly, instead of the two dsRNA binding domains found at the N terminus of PKR, there are two Z␣ domains. Z␣ domains specifically bind dsDNA and RNA in the left-handed Z conformation, often with high affinity. They have been found previously in two other IFN-inducible proteins, the dsRNA editing enzyme, ADAR1, and Z-DNA binding protein 1 (ZBP1), as well as in the poxvirus virulence factor, E3L. This previously undescribed kinase, designated PKZ (protein kinase containing Z-DNA binding domains), is transcribed constitutively at low levels and is highly induced after injection of poly(inosinic)-poly(cytidylic) acid, which simulates viral infection. Binding of Z-DNA by the Z␣ domain of PKZ was demonstrated by circular dichroism. PKZ inhibits translation in transfected cells; site-directed mutagenesis indicates that this inhibition depends on its catalytic activity. Identification of a gene combining Z␣ domains with a PKR-like kinase domain strengthens the hypothesis that the ability to bind left-handed nucleic acid plays a role in the host response to viruses.E3L ͉ interferon response ͉ viral infection ͉ Z-RNA ͉ Z␣ domain

Background: ADP-ribosylation is an enzyme-catalyzed posttranslational protein modification in which mono(ADP-ribosyl)transferases (mARTs) and poly(ADP-ribosyl)transferases (pARTs) transfer the ADPribose moiety from NAD onto specific amino acid side chains and/or ADP-ribose units on target proteins.

Protein kinase PKR is activated during viral infection and phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2), leading to inhibition of translation and viral replication. We report fast evolution of the PKR kinase domain in vertebrates, coupled with positive selection of specific sites. Substitution of positively selected residues in human PKR with residues found in related species altered sensitivity to PKR inhibitors from different poxviruses. Species-specific differences in sensitivity to poxviral pseudosubstrate inhibitors were identified between human and mouse PKR, which were traced to positively-selected residues near the eIF2α-binding site. Our findings indicate how an antiviral protein evolved to evade viral inhibition while maintaining its primary function. Moreover, the identified species-specific differences in the susceptibility to viral inhibitors have important implications for studying human infections in non-human model systems.

The Smithsonian Venezuela Project (SVP) conducted extensive surveys of mammals and ectoparasites in the 1960s. The 25 238 individuals and 130 species of bat collected by SVP hosted 36 663 streblid bat flies, representing 116 species of these ectoparasitic dipterans. Roosts of bat species differ in durability and protection, and bat flies separate from the host to pupate in the roost. We predicted higher levels of parasitism and more parasitic associates for bats roosting in more permanent structures (e.g. caves, tunnels) that would facilitate their association with hosts. We also predicted wing development of flies should correlate inversely with roost duration, restricting flightless forms to bats in permanent roosts. Ranking roosting structures by durability and protection, we sought correlations among bat species in prevalence, mean intensity and number of associated fly species. All three measures of parasitism were positively and significantly related to roosting habits: bats roosting in more permanent, enclosed structures were more likely to be infested, to carry heavier parasite loads, and to harbour more species of ectoparasitic flies. However, roosting habits were not correlated with the average wing development of bat flies. Although other factors affect parasitism rates in bats, the study provides a compelling example of both ecological and evolutionary responses of parasites to features of the host's environment.

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Gene duplication is postulated to have played a major role in the evolution of biological novelty. Here, gene duplication is examined across levels of biological organization in an attempt to create a unified picture of the mechanistic process by which gene duplication can have played a role in generating biodiversity. Neofunctionalization and subfunctionalization have been proposed as important processes driving the retention of duplicate genes. These models have foundations in population genetic theory, which is now being refined by explicit consideration of the structural constraints placed upon genes encoding proteins through physical chemistry. Further, such models can be examined in the context of comparative genomics, where an integration of genelevel evolution and species-level evolution allows an assessment of the frequency of duplication and the fate of duplicate genes. This process, of course, is dependent upon the biochemical role that duplicated genes play in biological systems, which is in turn dependent upon the mechanism of duplication: whole genome duplication involving a co-duplication of interacting partners vs. single gene duplication. Lastly, the role that these processes may have played in driving speciation is examined.