Identification of Plasmodium vivax Proteins with Potential Role in Invasion Using Sequence Redundancy Reduction and Profile Hidden Markov Models

BACKGROUND: This study describes a bioinformatics approach designed to identify Plasmodium vivax proteins potentially involved in reticulocyte invasion. Specifically, different protein training sets were built and tuned based on different biological parameters, such as experimental evidence of secretion and/or involvement in invasion-related processes. A profile-based sequence method supported by hidden Markov models (HMMs) was then used to build classifiers to search for biologically-related proteins. The transcriptional profile of the P. vivax intra-erythrocyte developmental cycle was then screened using these classifiers. RESULTS: A bioinformatics methodology for identifying potentially secreted P. vivax proteins was designed using sequence redundancy reduction and probabilistic profiles. This methodology led to identifying a set of 45 proteins that are potentially secreted during the P. vivax intra-erythrocyte development cycle and could be involved in cell invasion. Thirteen of the 45 proteins have already been described as vaccine candidates; there is experimental evidence of protein expression for 7 of the 32 remaining ones, while no previous studies of expression, function or immunology have been carried out for the additional 25. CONCLUSIONS: The results support the idea that probabilistic techniques like profile HMMs improve similarity searches. Also, different adjustments such as sequence redundancy reduction using Pisces or Cd-Hit allowed data clustering based on rational reproducible measurements. This kind of approach for selecting proteins with specific functions is highly important for supporting large-scale analyses that could aid in the identification of genes encoding potential new target antigens for vaccine development and drug design. The present study has led to targeting 32 proteins for further testing regarding their ability to induce protective immune responses against P. vivax malaria

Diversity of HIV-1 Subtype B: Implications to the Origin of BF Recombinants

BACKGROUND: The HIV-1 subtype B epidemic in Brazil is peculiar because of the high frequency of isolates having the GWGR tetramer at V3 loop region. It has been suggested that GWGR is a distinct variant and less pathogenic than other subtype B isolates. METHODOLOGY/PRINCIPAL FINDINGS: Ninety-four percent of the HIV-1 subtype B worldwide sequences (7689/8131) obtained from the Los Alamos HIV database contain proline at the tetramer of the V3 loop of the env gene (GPGR) and only 0.74% (60/8131) have tryptophan (GWGR). By contrast, 48.4% (161/333) of subtype B isolates from Brazil have proline, 30.6% (102/333) contain tryptophan and 10.5% (35/333) have phenylalanine (F) at the second position of the V3 loop tip. The proportion of tryptophan and phenylalanine in Brazilian isolates is much higher than in worldwide subtype B sequences (chi-square test, p = 0.0001). The combined proportion of proline, tryptophan and phenylalanine (GPGR+GWGR+GFGR) of Brazilian isolates corresponds to 89% of all amino acids in the V3 loop. Phylogenetic analysis revealed that almost all subtype B isolates in Brazil have a common origin regardless of their motif (GWGR, GPGR, GGGR, etc.) at the V3 tetramer. This shared ancestral origin was also observed in CRF28_BF and CRF29_BF in a genome region (free of recombination) derived from parental subtype B. These results imply that tryptophan substitution (e.g., GWGR-to-GxGR), which was previously associated with the change in the coreceptor usage within the host, also occurs at the population level. CONCLUSIONS/SIGNIFICANCE: Based on the current findings and previous study showing that tryptophan and phenylalanine in the V3 loop are related with coreceptor usage, we propose that tryptophan and phenylalanine in subtype B isolates in Brazil are kept by selective mechanisms due to the distinct coreceptor preferences in target cells of GWGR, GFGR and GFGR viruses

Global Analysis of Proline-Rich Tandem Repeat Proteins Reveals Broad Phylogenetic Diversity in Plant Secretomes

Cell walls, constructed by precisely choreographed changes in the plant secretome, play critical roles in plant cell physiology and development. Along with structural polysaccharides, secreted proline-rich Tandem Repeat Proteins (TRPs) are important for cell wall function, yet the evolutionary diversity of these structural TRPs remains virtually unexplored. Using a systems-level computational approach to analyze taxonomically diverse plant sequence data, we identified 31 distinct Pro-rich TRP classes targeted for secretion. This analysis expands upon the known phylogenetic diversity of extensins, the most widely studied class of wall structural proteins, and demonstrates that extensins evolved before plant vascularization. Our results also show that most Pro-rich TRP classes have unexpectedly restricted evolutionary distributions, revealing considerable differences in plant secretome signatures that define unexplored diversity

Translating upwards: linking the neural and social sciences via neuroeconomics

The social and neural sciences share a common interest in understanding the mechanisms that underlie human behaviour. However, interactions between neuroscience and social science disciplines remain strikingly narrow and tenuous. We illustrate the scope and challenges for such interactions using the paradigmatic example of neuroeconomics. Using quantitative analyses of both its scientific literature and the social networks in its intellectual community, we show that neuroeconomics now reflects a true disciplinary integration, such that research topics and scientific communities with interdisciplinary span exert greater influence on the field. However, our analyses also reveal key structural and intellectual challenges in balancing the goals of neuroscience with those of the social sciences. To address these challenges, we offer a set of prescriptive recommendations for directing future research in neuroeconomics

Molecular Typing and Phenotype Characterization of Methicillin-Resistant Staphylococcus aureus Isolates from Blood in Taiwan

BACKGROUND: Staphylococcus aureus causes a variety of severe infections such as bacteremia and sepsis. At present, 60-80% of S. aureus isolates from Taiwan are methicillin resistant (MRSA). It has been shown that certain MRSA clones circulate worldwide. The goals of this study were to identify MRSA clones in Taiwan and to correlate the molecular types of isolates with their phenotypes. METHODS: A total of 157 MRSA isolates from bacteremic patients were collected from nine medical centers. They were typed based on polymorphisms in agr, SCCmec, MLST, spa, and dru. Phenotypes characterized included Panton-Valentine leucocidin (pvl), inducible macrolide-lincosamide-streptogramin B resistance (MLSBi), vancomycin (VA) and daptomycin (DAP) minimal inhibitory concentrations (MIC), and superantigenic toxin gene profiles. Difference between two consecutive samples was determined by Mann-Whitney-U test, and difference between two categorical variables was determined by Fisher's exact test. RESULTS: Four major MRSA clone complexes CC1, CC5, CC8, and CC59 were found, including 4 CC1, 9 CC5, 111 CC8, and 28 CC59 isolates. These clones had the following molecular types: CC1: SCCmecIV and ST573; CC5: SCCmecII and ST5; CC8: SCCmecIII, ST239, and ST241, and CC59: SCCmecIV, SCCmecV(T), ST59, and ST338. The toxin gene profiles of these clones were CC1: sec-seg-(sei)-sell-selm-(seln)-selo; CC5: sec-seg-sei-sell-selm-(seln)-selp-tst1; CC8: sea-selk-selq, and CC59: seb-selk-selq. Most isolates with SCCmecV(T), ST59, spat437, and dru11 types were pvl(+) (13 isolates), while multidrug resistance (≥4 antimicrobials) were associated with SCCmecIII, ST239, spa t037, agrI, and dru14 (119 isolates) (p<0.001). One hundred and twenty four isolates with the following molecular types had higher VA MIC: SCCmecII and SCCmecIII; ST5, ST239, and ST241; spa t002, t037, and t421; dru4, dru10, dru12, dru13, and dru14 (p<0.05). No particular molecular types were found to be associated with MLSBi phenotype. CONCLUSIONS: Four major MRSA clone complexes were found in Taiwan. Further studies are needed to delineate the evolution of MRSA isolates

Nuclear Scaffold Attachment Sites within ENCODE Regions Associate with Actively Transcribed Genes

The human genome must be packaged and organized in a functional manner for the regulation of DNA replication and transcription. The nuclear scaffold/matrix, consisting of structural and functional nuclear proteins, remains after extraction of nuclei and anchors loops of DNA. In the search for cis-elements functioning as chromatin domain boundaries, we identified 453 nuclear scaffold attachment sites purified by lithium-3,5-iodosalicylate extraction of HeLa nuclei across 30 Mb of the human genome studied by the ENCODE pilot project. The scaffold attachment sites mapped predominately near expressed genes and localized near transcription start sites and the ends of genes but not to boundary elements. In addition, these regions were enriched for RNA polymerase II and transcription factor binding sites and were located in early replicating regions of the genome. We believe these sites correspond to genome-interactions mediated by transcription factors and transcriptional machinery immobilized on a nuclear substructure

Species Specificity in Major Urinary Proteins by Parallel Evolution

Species-specific chemosignals, pheromones, regulate social behaviors such as aggression, mating, pup-suckling, territory establishment, and dominance. The identity of these cues remains mostly undetermined and few mammalian pheromones have been identified. Genetically-encoded pheromones are expected to exhibit several different mechanisms for coding 1) diversity, to enable the signaling of multiple behaviors, 2) dynamic regulation, to indicate age and dominance, and 3) species-specificity. Recently, the major urinary proteins (Mups) have been shown to function themselves as genetically-encoded pheromones to regulate species-specific behavior. Mups are multiple highly related proteins expressed in combinatorial patterns that differ between individuals, gender, and age; which are sufficient to fulfill the first two criteria. We have now characterized and fully annotated the mouse Mup gene content in detail. This has enabled us to further analyze the extent of Mup coding diversity and determine their potential to encode species-specific cues

Two Novel Parvoviruses in Frugivorous New and Old World Bats

Bats, a globally distributed group of mammals with high ecological importance, are increasingly recognized as natural reservoir hosts for viral agents of significance to human and animal health. In the present study, we evaluated pools of blood samples obtained from two phylogenetically distant bat families, in particular from flying foxes (Pteropodidae), Eidolon helvum in West Africa, and from two species of New World leaf-nosed fruit bats (Phyllostomidae), Artibeus jamaicensis and Artibeus lituratus in Central America. A sequence-independent virus discovery technique (VIDISCA) was used in combination with high throughput sequencing to detect two novel parvoviruses: a PARV4-like virus named Eh-BtPV-1 in Eidolon helvum from Ghana and the first member of a putative new genus in Artibeus jamaicensis from Panama (Aj-BtPV-1). Those viruses were circulating in the corresponding bat colony at rates of 7–8%. Aj-BtPV-1 was also found in Artibeus lituratus (5.5%). Both viruses were detected in the blood of infected animals at high concentrations: up to 10E8 and to 10E10 copies/ml for Aj-BtPV-1 and Eh-BtPV-1 respectively. Eh-BtPV-1 was additionally detected in all organs collected from bats (brain, lungs, liver, spleen, kidneys and intestine) and spleen and kidneys were identified as the most likely sites where viral replication takes place. Our study shows that bat parvoviruses share common ancestors with known parvoviruses of humans and livestock. We also provide evidence that a variety of Parvovirinae are able to cause active infection in bats and that they are widely distributed in these animals with different geographic origin, ecologies and climatic ranges

Adaptive Evolution and the Birth of CTCF Binding Sites in the Drosophila Genome

Changes in the physical interaction between cis-regulatory DNA sequences and proteins drive the evolution of gene expression. However, it has proven difficult to accurately quantify evolutionary rates of such binding change or to estimate the relative effects of selection and drift in shaping the binding evolution. Here we examine the genome-wide binding of CTCF in four species of Drosophila separated by between ~2.5 and 25 million years. CTCF is a highly conserved protein known to be associated with insulator sequences in the genomes of human and Drosophila. Although the binding preference for CTCF is highly conserved, we find that CTCF binding itself is highly evolutionarily dynamic and has adaptively evolved. Between species, binding divergence increased linearly with evolutionary distance, and CTCF binding profiles are diverging rapidly at the rate of 2.22% per million years (Myr). At least 89 new CTCF binding sites have originated in the Drosophila melanogaster genome since the most recent common ancestor with Drosophila simulans. Comparing these data to genome sequence data from 37 different strains of Drosophila melanogaster, we detected signatures of selection in both newly gained and evolutionarily conserved binding sites. Newly evolved CTCF binding sites show a significantly stronger signature for positive selection than older sites. Comparative gene expression profiling revealed that expression divergence of genes adjacent to CTCF binding site is significantly associated with the gain and loss of CTCF binding. Further, the birth of new genes is associated with the birth of new CTCF binding sites. Our data indicate that binding of Drosophila CTCF protein has evolved under natural selection, and CTCF binding evolution has shaped both the evolution of gene expression and genome evolution during the birth of new genes

Echinococcus multilocularis and Echinococcus shiquicus in a small mammal community on the eastern Tibetan Plateau : host species composition, molecular prevalence, and epidemiological implications

Background The eastern part of the Tibetan Plateau is now recognized as an endemic region with the highest reported human infection rates in the world of human alveolar echinococcosis (AE) caused by Echinococcus multilocularis. Existing epidemiological studies on AE have mainly focused on the synanthropic environment, while basic parasitological and ecological aspects in wildlife host species remain largely unknown, especially for small mammal hosts. Therefore, we examined small mammal host species composition, occurrence, and the prevalence of both E. multilocularis and E. shiquicus in Shiqu County (Sichuan Province, China), eastern Tibetan Plateau. Results In total, 346 small mammals from five rodent and one pika species were trapped from four randomly set 0.25 ha square plots. Two vole species, Lasiopodomys fuscus (n = 144) and Microtus limnophilus (n = 44), and the plateau pika (Ochotona curzoniae) (n = 135), were the three most-dominant species trapped. Although protoscoleces of E. multilocularis and E. shiquicus were only observed in L. fuscus and O. curzoniae, respectively, cox1 and nad1 gene DNA of E. shiquicus was detected in all the small mammal species except for Neodon irene, whereas E. multilocularis was detected in the three most-dominant species. The overall molecular prevalence of Echinococcus species was 5.8 (95% CI: 3.3–8.2%) ~ 10.7% (95% CI: 7.4–14.0%) (the conservative prevalence to the maximum prevalence with 95% CI in parentheses), whereas for E. multilocularis it was 4.3 (95% CI: 2.2–6.5%) ~ 6.7% (95% CI: 4.0–9.3%), and 1.5 (95% CI: 0.2–2.7%) ~ 4.1% (95% CI: 2.0–6.1%) for E. shiquicus. The prevalence of both E. multilocularis and E. shiquicus, was significantly higher in rodents (mainly voles) than in pikas. Phylogenetic analyses revealed that Echinococcus haplotypes of cox1 from small mammal hosts were actively involved in the sylvatic and anthropogenic transmission cycles of E. multilocularis in the eastern Tibetan Plateau. Conclusions In contrast to previous studies, the current results indicated that rodent species, rather than pikas, are probably more important natural intermediate hosts of E. multilocularis and E. shiquicus in the eastern Tibetan Plateau. Thus, understanding interspecific dynamics between rodents and pikas is essential to studies of the echinococcosis transmission mechanism and human echinococcosis prevention in local communities. Keywords: Echinococcus multilocularis, E. shiquicus, Small mammal Prevalence, Tibetan Platea