Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif

To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens

HelmCoP: An Online Resource for Helminth Functional Genomics and Drug and Vaccine Targets Prioritization

A vast majority of the burden from neglected tropical diseases result from helminth infections (nematodes and platyhelminthes). Parasitic helminthes infect over 2 billion, exerting a high collective burden that rivals high-mortality conditions such as AIDS or malaria, and cause devastation to crops and livestock. The challenges to improve control of parasitic helminth infections are multi-fold and no single category of approaches will meet them all. New information such as helminth genomics, functional genomics and proteomics coupled with innovative bioinformatic approaches provide fundamental molecular information about these parasites, accelerating both basic research as well as development of effective diagnostics, vaccines and new drugs. To facilitate such studies we have developed an online resource, HelmCoP (Helminth Control and Prevention), built by integrating functional, structural and comparative genomic data from plant, animal and human helminthes, to enable researchers to develop strategies for drug, vaccine and pesticide prioritization, while also providing a useful comparative genomics platform. HelmCoP encompasses genomic data from several hosts, including model organisms, along with a comprehensive suite of structural and functional annotations, to assist in comparative analyses and to study host-parasite interactions. The HelmCoP interface, with a sophisticated query engine as a backbone, allows users to search for multi-factorial combinations of properties and serves readily accessible information that will assist in the identification of various genes of interest. HelmCoP is publicly available at: http://www.nematode.net/helmcop.html

Two sisters with Rett syndrome and non-identical paternally-derived microdeletions in the MECP2 gene

The unique case of two sisters with symptoms of RTT and two quite distinct, novel, and apparently de novo microdeletions of the MECP2 gene is described. One sister possessed an 18 base-pair (bp) deletion (c.1155_1172del18) within the deletion hotspot region of exon 4, whereas the other sister exhibited a 43 bp deletion at a different location in the same exon (c.1448_1461del14+29). Although these lesions occurred on the same paternally-derived X chromosome, this is probably due to chance co-occurrence owing to the relatively high mutation rate of the MECP2 gene rather than to a constitutional mutator phenotype

Bird community variation across Polylepis woodland fragments and matrix habitats: implications for biodiversity conservation within a high Andean landscape

The scattered and dwindling Polylepis woodlands of the high Andean global hotspot have been identified as being of particular importance to biodiversity conservation, and yet little is known of the make-up of their faunal communities, how these vary across landscapes, and how well species might tolerate matrix/edge habitats. We examined the bird communities and vegetation characteristics of Polylepis woodlands and the surrounding matrix habitats at three sites in the Cordillera Vilcanota, southern Perú (3,400–4,500 m). The vegetation structure of woodlands varied significantly across the three sites but all were dominated by two Polylepis tree species, with mossy ground cover. Matrix habitats were treeless and dominated by ground-level puna grass-steppe or boulder scree vegetation. Bird species richness and diversity, encounter rates and the number of globally-threatened and restricted-range bird species were consistently higher in the Polylepis forests, than in matrix habitat. We used canonical correspondence analysis (CCA) to identify habitat gradients across the landscape, and to classify bird species according to their association with Polylepis, the matrix or Polylepis-matrix interface. There were few matrix-restricted bird species, but around half the bird community, including fourteen threatened or restricted-range species, were Polylepis-dependant. Many of these species had very narrow niches. The Polylepis-matrix interface was dominated by species traditionally considered invasive ecological generalists. Our study illustrates the overriding importance of Polylepis interior habitats, indicating that conservation strategies for high Andean birds must focus on patch size maintenance/enlargement, enhancement of within-patch habitat quality, and efforts to safeguard connectivity of suitable habitat across what is essentially an inhospitable puna/scree matrix