The Long-Term Dynamics of Mortality Benefits from Improved Water and Sanitation in Less Developed Countries

The problem of inadequate access to water, sanitation and hygiene (WASH) in less-developed nations has received much attention over the last several decades (most recently in the Millennium Development Goals), largely because diseases associated with such conditions contribute substantially to mortality in poor countries. We present country-level projections for WASH coverage and for WASH-related mortality in developing regions over a long time horizon (1975–2050) and provide dynamic estimates of the economic value of potential reductions in this WASH-related mortality, which go beyond the static results found in previous work. Over the historical period leading up to the present, our analysis shows steady and substantial improvements in WASH coverage and declining mortality rates across many developing regions, namely East Asia and the Pacific, Latin America and the Caribbean, Eastern Europe and the Middle East. The economic value of potential health gains from eliminating mortality attributable to poor water and sanitation has decreased substantially, and in the future will therefore be modest in these regions. Where WASH-related deaths remain high (in parts of South Asia and much of Sub-Saharan Africa), if current trends continue, it will be several decades before economic development and investments in improved water and sanitation will result in the capture of these economic benefits. The fact that health losses will likely remain high in these two regions over the medium term suggests that accelerated efforts are needed to improve access to water and sanitation, though the costs and benefits of such efforts in specific locations should be carefully assessed.     

Looks can deceive: Molecular phylogeny of a family of flatworm ectoparasites (Monogenea: Capsalidae) does not reflect current morphological classification

The morphological based taxonomy of highly derived parasite groups is likely to poorly reflect their evolutionary relationships. The taxonomy of the monogenean family Capsalidae, which comprises approximately 180 species of flatworm parasites that predominantly attach to external surfaces of chondrichthyan and teleost fishes, is based mainly on six morphological characters. The phylogenetic history of the family is largely unknown. We reconstructed the phylogenetic relationships of 47 species in 20 genera from eight of the nine subfamilies, from nucleotide sequences of three unlinked nuclear genes, 28S ribosomal RNA, Histone 3 and Elongation Factor 1 α. Our phylogeny was well corroborated, with 75% of branches receiving strong support from both Bayesian posterior probabilities and maximum likelihood bootstrap proportions and all nodes showed positive partitioned likelihood support for each of the three genes. We found that the family was monophyletic, with the Gyrodactylidae and Udonellidae forming the sister group. The Capsalinae was monophyletic, however, our data do not support monophyly for the Benedeniinae, Entobdellinae and Trochopodinae. Monophyly was supported for Capsala, Entobdella, Listrocephalos, Neobenedenia and Tristoma, but Benedenia and Neoentobdella were polyphyletic. Comparisons of the distribution of character states for the small number of morphological characters on the molecular phylogeny show a high frequency of apparent homoplasy. Consequently the current morphological classification shows little correspondence with the phylogenetic relationships within the family.     

Creation of genome-wide protein expression libraries using random activation of gene expression

Here we report the use of random activation of gene expression (RAGE) to create genome-wide protein expression libraries. RAGE libraries containing only 5 x 10(6) individual clones were found to express every gene tested, including genes that are normally silent in the parent cell line. Furthermore, endogenous genes were activated at similar frequencies and expressed at similar levels within RAGE libraries created from multiple human cell lines, demonstrating that RAGE libraries are inherently normalized. Pools of RAGE clones were used to isolate 19,547 human gene clusters, approximately 53% of which were novel when tested against public databases of expressed sequence tag (EST) and complementary DNA (cDNA). Isolation of individual clones confirmed that the activated endogenous genes can be expressed at high levels to produce biologically active proteins. The properties of RAGE libraries and RAGE expression clones are well suited for a number of biotechnological applications including gene discovery, protein characterization, drug development, and protein manufacturing.     

Amphipathic benzoic acid derivatives: synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC

The first committed step in lipid A biosynthesis is catalyzed by uridine diphosphate-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase (LpxC), a zinc-dependent deacetylase, and inhibitors of LpxC may be useful in the development of antibacterial agents targeting a broad spectrum of Gram-negative bacteria. Here, we report the design of amphipathic benzoic acid derivatives that bind in the hydrophobic tunnel in the active site of LpxC. The hydrophobic tunnel accounts for the specificity of LpxC toward substrates and substrate analogues bearing a 3-O-myristoyl substituent. Simple benzoic acid derivatives bearing an aliphatic 'tail' bind in the hydrophobic tunnel with micromolar affinity despite the lack of a glucosamine ring like that of the substrate. However, although these benzoic acid derivatives each contain a negatively charged carboxylate 'warhead' intended to coordinate to the active site zinc ion, the 2.25A resolution X-ray crystal structure of LpxC complexed with 3-(heptyloxy)benzoate reveals 'backward' binding in the hydrophobic tunnel, such that the benzoate moiety does not coordinate to zinc. Instead, it binds at the outer end of the hydrophobic tunnel. Interestingly, these ligands bind with affinities comparable to those measured for more complicated substrate analogue inhibitors containing glucosamine ring analogues and hydroxamate 'warheads' that coordinate to the active site zinc ion. We conclude that the intermolecular interactions in the hydrophobic tunnel dominate enzyme affinity in this series of benzoic acid derivatives.     

Empruthotrema dasyatidis n. sp. (Monogenea: Monocotylidae) from the olfactory sacs of Dasyatis fluviorum (Rajiformes: Dasyatidae) from Moreton Bay,Queensland

The monocotylid monogenean Empruthotrema dasyatidis n. sp. is reported from the olfactory sacs of the brown stingray, Dasyatis fluviorum Ogilby, 1908, from Moreton Bay, Queensland, Australia. This is the first record of Empruthotrema from the family Dasyatidae. E. dasyatidis n. sp. differs from other species of Empruthotrema by possessing eye pigment, which may be scattered, and by its small size. The generic diagnosis for Empruthotrema is amended.     

An annotated list of fish parasites (Isopoda, Copepoda, Monogenea, Digenea, Cestoda, Nematoda) collected from Snappers and Bream (Lutjanidae, Nemipteridae, Caesionidae) in New Caledonia confirms high parasite biodiversity on coral reef fish

ABSTRACT: BACKGROUND: Coral reefs are areas of maximum biodiversity, but the parasites of coral reef fishes, and especially their species richness, are not well known. Over an 8-year period, parasites were collected from 24 species of Lutjanidae, Nemipteridae and Caesionidae off New Caledonia, South Pacific. RESULTS: Host-parasite and parasite-host lists are provided, with a total of 207 host-parasite combinations and 58 parasite species identified at the species level, with 27 new host records. Results are presented for isopods, copepods, monogeneans, digeneans, cestodes and nematodes. When results are restricted to well-sampled reef fish species (sample size[THIN SPACE]>[THIN SPACE]30), the number of host-parasite combinations is 20[EN DASH]25 per fish species, and the number of parasites identified at the species level is 9[EN DASH]13 per fish species. Lutjanids include reef-associated fish and deeper sea fish from the outer slopes of the coral reef: fish from both milieus were compared. Surprisingly, parasite biodiversity was higher in deeper sea fish than in reef fish (host-parasite combinations: 12.50 vs 10.13, number of species per fish 3.75 vs 3.00); however, we identified four biases which diminish the validity of this comparison. Finally, these results and previously published results allow us to propose a generalization of parasite biodiversity for four major families of reef-associated fishes (Lutjanidae, Nemipteridae, Serranidae and Lethrinidae): well-sampled fish have a mean of 20 host-parasite combinations per fish species, and the number of parasites identified at the species level is 10 per fish species. CONCLUSIONS: Since all precautions have been taken to minimize taxon numbers, it is safe to affirm than the number of fish parasites is at least ten times the number of fish species in coral reefs, for species of similar size or larger than the species in the four families studied; this is a major improvement to our estimate of biodiversity in coral reefs. Our results suggest that extinction of a coral reef fish species would eventually result in the coextinction of at least ten species of parasites.     

Phylogenomic species delimitation and host‐symbiont coevolution in the fungus‐farming ant genus Sericomyrmex Mayr (Hymenoptera: Formicidae): ultraconserved elements (UCEs) resolve a recent radiation

Ants in the Neotropical genus Sericomyrmex Mayr cultivate fungi for food. Both ants and fungi are obligate, coevolved symbionts. The taxonomy of Sericomyrmex is problematic because the morphology of the worker caste is generally homogeneous across all of the species within the genus, species limits are vague, and the relationships between them are unknown. We used ultraconserved elements (UCEs) as genome‐scale markers to reconstruct evolutionary history and to infer species boundaries in Sericomyrmex. We recovered an average of ～990 UCE loci for 88 Sericomyrmex samples from across the geographical range of the genus as well as for five outgroup taxa. Using maximum likelihood and species‐tree approaches, we recovered nearly identical topologies across datasets with 50–95% matrix completeness. We identify nine species‐level lineages in Sericomyrmex, including two new species. This is less than the previously described 19 species, even accounting for two species for which we had no UCE samples, which brings the total number of Sericomyrmex species to 11. Divergence‐dating analyses recovered 4.3 Ma as the crown‐group age estimates for Sericomyrmex, indicating a recent, rapid radiation. We also sequenced mitochondrial cytochrome oxidase subunit I (COI) for 125 specimens. Resolution and support for clades in our COI phylogeny are weak, indicating that COI is not an appropriate species‐delimitation tool. However, taxa within species consistently cluster together, suggesting that COI is useful as a species identification (‘DNA barcoding’) tool. We also sequenced internal transcribed spacer (ITS) and large subunit (LSU) for 32 Sericomyrmex fungal cultivars. The fungal phylogeny confirms that Sericomyrmex fungi are generalized higher‐attine cultivars, interspersed with Trachymyrmex‐associated fungal species, indicating cultivar sharing and horizontal transfer between these two genera. Our results indicate that UCEs offer immense potential for delimiting and resolving relationships of problematic, recently diverged species.     

Euzetia occultum n. g., n. sp. (Euzetiinae n. subf.), a monocotylid monogenean from the gills of Rhinoptera neglecta (Rhinopteridae) from Moreton Bay,Queensland, Australia

Euzetia occultum n. g., n. sp. (Monogenea: Monocotylidae) is described from the gills of the Australian cownose ray Rhinoptera neglecta Ogilby collected in Moreton Bay, Queensland, Australia. Euzetia has one central and ten peripheral loculi, which is similar to species in Decacotyle Young, 1967. However Euzetia is distinguished from other genera in the family by the presence of an additional loculus on either side of the central loculus. Because Euzetia does not fit into any of the six existing subfamilies in the Monocotylidae Taschenberg, 1879, as currently recognised, we propose the Euzetiinae n. subf. to accommodate the new genus. Euzetia occultum is described and illustrated fully. This is the first published record of a monocotylid from a species of Rhinoptera Cuvier.     

Morphology and development of the haptors among the Monocotylidae (Monogenea)

Monocotylid monogeneans inhabit a wide diversity of sites on their chondrichthyan hosts including the skin, gills, nasal fossae, urogenital system and coelom. The large variation in the morphology of the haptor appears to reflect this diversity in attachment sites. We demonstrate that the complexity of the haptor can be related to the habitat of the parasite. Generally, those parasites which live in habitats subject to strong water currents such as the gills and dorsal skin surface have more complex haptors than those in environments exposed to weaker or no water currents including the nasal fossae, urogenital system and body cavity. However, there can be considerable variation in haptoral components, even among congeners, living on the ‘gills’ of their hosts. The microhabitat was determined for Monocotyle helicophallus and M. spiremae, both from the gills of the pink whipray, Himantura fai, and M. corali from the gills of the cowtail ray, Pastinachus sephen. We demonstrate that differences in the morphology of the hamuli and the number and morphology of septal sclerites and marginal papillae among these species of Monocotyle can be related directly to their microhabitat. It also appears that different haptoral structures are important for attachment to the host at different stages in the development of the parasite, based on studies on the development and distribution of Neoheterocotyle rhinobatidis from the gills of the common shovelnose ray Rhinobatos typus. This revised version was published online in July 2006 with corrections to the Cover Date.     

Multiple histone modifications in euchromatin promote heterochromatin formation by redundant mechanisms in Saccharomyces cerevisiae

Background  

Methylation of lysine 79 on histone H3 by Dot1 is required for maintenance of heterochromatin structure in yeast and humans. However, this histone modification occurs predominantly in euchromatin. Thus, Dot1 affects silencing by indirect mechanisms and does not act by the recruitment model commonly proposed for histone modifications. To better understand the role of H3K79 methylation gene silencing, we investigated the silencing function of Dot1 by genetic suppressor and enhancer analysis and examined the relationship between Dot1 and other global euchromatic histone modifiers.