Leishmaniasis: A review of the disease and the debate over the origin and dispersal of the causaitive parasite Leishmania

The vector borne disease Leishmaniasis, caused by the Leishmania parasite, is estimated to affect the lives of 12 million people. Manifesting itself into three different clinical forms that center on disfiguring sores and enlargement of several organs, Leishmaniasis is a devastating disease impairing economic productivity and impeding socioeconomic development. The complex life cycle of this parasite, involving a host, vector, and reservoir, has played a major role in defining the dispersal and prevalence of this disease on a global level. The prevalence of Leishmaniasis is highly concentrated due to the close relationship of this parasite and its single vector (the female Phlebotomine sand fly), and the socioeconomic and environmental factors that are beneficial to the sand fly habitat. Yet, there is a wide and varied distribution of Leishmania species. Some species belonging to the subgenera of Leishmania are found in both Old and New Worlds, while others belonging to the subgenera Viannia are found only in the New World. Interest in the origin and dispersal of Leishmania has risen from this disjointed distribution and a need for a complete comprehensive understanding of this parasite in order to determine the best approach in the eradication of this disease. The two main hypotheses from the literature that have become established in this debate are a Palaearctic origin and a Neotropical origin. These hypotheses are presented along with a third hypothesis of an African and Neotropical origin. The conflicts between molecular, entomological, biogeographical, and ecological data, along with insufficient research that have rendered this debate unresolved are also discussed. Complexity of this diseases’ epidemiological cycle demands a comprehensive understanding of the parasite, including its origin and dispersal, to maintain the most effective prevention, treatment, and hopefully eradication

Midwifery benchmarking in Oregon: increasing participation to deliver change

Benchmarking is an evidence based method of quality improvement (QI) supported by the literature. The ACNM Benchmarking Project has been in existence since 2004, but has struggled with increasing member participation, ultimately limiting the strength of the produced data. This project aimed to assess current benchmarking practices in Oregon, identify individual practices for benchmarking assistance, and increase Oregon participation in the national project

A high-throughput screen for the identification of compounds that inhibit nematode gene expression by targeting spliced leader trans-splicing

The work was supported by the Biotechnology and Biological Sciences Research Council [Project grant BB/J007137/1] and a Medical Research Council (MRC) Confidence in Concept (2014) - University of Aberdeen Award (MC_PC_14114v.2). AA was supported by a PhD stipend from the Saudi Arabia. Research data will be made available on requestPeer reviewedPublisher PD

An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly

ACKNOWLEDGEMENTS Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We would also like to thank Prof. Shohei Mitani,at the National Bioresource Project for the Experimental Animal ‘Nematode C. elegans’, Japan, for FX3079. We are grateful to Prof. Tom Blumenthal (University of Colorado, Boulder) for suggestions and support of this work; and to Kathrine Wood for her contribution to the initial stages of part of this work. Author contributions. L.P., G.P., R.F., N.H., J.P. and B.M. performed experiments; B.M., J.P. and B.C. designed and lead the study; B.M. and J.P. drafted the manuscript. All authors reviewed the manuscript. FUNDING Biotechnology and Biological Sciences Research Council (BBSRC) [Project grant BB/J007137/1]; Medical Research Council (MRC) Confidence in Concept 2014 - University of Aberdeen Award(MC PC 14114v.2); University of Aberdeen Elphinstone Scholarship (to R.F.) and TET Fund support through Adekunle Ajasin University, Nigeria (to R.F.). Funding for open access charge: Biotechnology and Biological Sciences Research Council and Medical Research Council.Peer reviewedPublisher PD

Amino acid residue doublet propensity in the protein–RNA interface and its application to RNA interface prediction

Protein–RNA interactions play essential roles in a number of regulatory mechanisms for gene expression such as RNA splicing, transport, translation and post-transcriptional control. As the number of available protein–RNA complex 3D structures has increased, it is now possible to statistically examine protein–RNA interactions based on 3D structures. We performed computational analyses of 86 representative protein–RNA complexes retrieved from the Protein Data Bank. Interface residue propensity, a measure of the relative importance of different amino acid residues in the RNA interface, was calculated for each amino acid residue type (residue singlet interface propensity). In addition to the residue singlet propensity, we introduce a new residue-based propensity, which gives a measure of residue pairing preferences in the RNA interface of a protein (residue doublet interface propensity). The residue doublet interface propensity contains much more information than the sum of two singlet propensities alone. The prediction of the RNA interface using the two types of propensities plus a position-specific multiple sequence profile can achieve a specificity of about 80%. The prediction method was then applied to the 3D structure of two mRNA export factors, TAP (Mex67) and UAP56 (Sub2). The prediction enables us to point out candidate RNA interfaces, part of which are consistent with previous experimental studies and may contribute to elucidation of atomic mechanisms of mRNA export

Mining Predicted Essential Genes of Brugia malayi for Nematode Drug Targets

We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression