Identification and functional characterization of cis-regulatory elements in the apicomplexan parasite Toxoplasma gondii

Mining of genomic sequence data of the apicomplexan parasite Toxoplasma gondii identifies putative cis-regulatory elements using a de novo approach

A glycosylphosphatidylinositol-anchored carbonic anhydrase-related protein of Toxoplasma gondii is important for rhoptry biogenesis and virulence

Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites. The protein localizes throughout the rhoptry bulbs of mature tachyzoites and to the outer membrane of nascent rhoptries in dividing tachyzoites, as demonstrated by immunofluorescence and immunoelectron microscopy using specific antibodies. T. gondii mutant tachyzoites lacking TgCA_RP display a growth and invasion phenotype in vitro and have atypical rhoptry morphology. The mutants also exhibit reduced virulence in a mouse model. Our results show that TgCA_RP plays an important role in the biogenesis of rhoptries

Contact processes with long-range interactions

A class of non-local contact processes is introduced and studied using mean-field approximation and numerical simulations. In these processes particles are created at a rate which decays algebraically with the distance from the nearest particle. It is found that the transition into the absorbing state is continuous and is characterized by continuously varying critical exponents. This model differs from the previously studied non-local directed percolation model, where particles are created by unrestricted Levy flights. It is motivated by recent studies of non-equilibrium wetting indicating that this type of non-local processes play a role in the unbinding transition. Other non-local processes which have been suggested to exist within the context of wetting are considered as well.Comment: Accepted with minor revisions by Journal of Statistical Mechanics: Theory and experiment

A predominance of R5-like HIV genotypes in vaginal secretions is associated with elevated plasma HIV-1 RNA levels and the absence of anti-retroviral therapy

HIV expressed in genital secretions provides the inoculum from which transmitting variants are selected, both in sexual transmission and mother-to-infant transmission during partuition. Characterization of HIV levels and genotypes found in vaginal secretions and the impact of anti-retroviral therapy (ART) on this virus can provide valuable insight for the prevention of HIV transmission. Vaginal HIV was evaluated in a cohort of 43 women attending a New Orleans HIV outpatient clinic. Predominant vaginal genotypes were characterized as R5- or X4-like by heteroduplex tracking analyses of the envelope V3 region. Most women (67.4%) shed R5-like genotypes in vaginal secretions which was associated with elevated plasma HIV levels (≥ 10,000 copies HIV-RNA/mL) and absence of ART. Because R5-like genotypes are more frequently associated with transmission, these observations suggest that the majority of women shedding HIV in genital secretions present a transmission risk. The levels of vaginal virus were similar between both groups, but shedding of X4-like genotypes was associated with lower plasma viral loads and the use of ART, suggesting that ART use may impact the genotypes of virus found in the female genital compartment

Non-equilibrium Phase Transitions with Long-Range Interactions

This review article gives an overview of recent progress in the field of non-equilibrium phase transitions into absorbing states with long-range interactions. It focuses on two possible types of long-range interactions. The first one is to replace nearest-neighbor couplings by unrestricted Levy flights with a power-law distribution P(r) ~ r^(-d-sigma) controlled by an exponent sigma. Similarly, the temporal evolution can be modified by introducing waiting times Dt between subsequent moves which are distributed algebraically as P(Dt)~ (Dt)^(-1-kappa). It turns out that such systems with Levy-distributed long-range interactions still exhibit a continuous phase transition with critical exponents varying continuously with sigma and/or kappa in certain ranges of the parameter space. In a field-theoretical framework such algebraically distributed long-range interactions can be accounted for by replacing the differential operators nabla^2 and d/dt with fractional derivatives nabla^sigma and (d/dt)^kappa. As another possibility, one may introduce algebraically decaying long-range interactions which cannot exceed the actual distance to the nearest particle. Such interactions are motivated by studies of non-equilibrium growth processes and may be interpreted as Levy flights cut off at the actual distance to the nearest particle. In the continuum limit such truncated Levy flights can be described to leading order by terms involving fractional powers of the density field while the differential operators remain short-ranged.Comment: LaTeX, 39 pages, 13 figures, minor revision

ToxoDB: an integrated Toxoplasma gondii database resource

ToxoDB (http://ToxoDB.org) is a genome and functional genomic database for the protozoan parasite Toxoplasma gondii. It incorporates the sequence and annotation of the T. gondii ME49 strain, as well as genome sequences for the GT1, VEG and RH (Chr Ia, Chr Ib) strains. Sequence information is integrated with various other genomic-scale data, including community annotation, ESTs, gene expression and proteomics data. ToxoDB has matured significantly since its initial release. Here we outline the numerous updates with respect to the data and increased functionality available on the website

Cardiovascular Magnetic Resonance Characterization of Mitral Valve Prolapse

ObjectivesThis study sought to develop cardiovascular magnetic resonance (CMR) diagnostic criteria for mitral valve prolapse (MVP) using echocardiography as the gold standard and to characterize MVP using cine CMR and late gadolinium enhancement (LGE)-CMR.BackgroundMitral valve prolapse is a common valvular heart disease with significant complications. Cardiovascular magnetic resonance is a valuable imaging tool for assessing ventricular function, quantifying regurgitant lesions, and identifying fibrosis, but its potential role in evaluating MVP has not been defined.MethodsTo develop CMR diagnostic criteria for MVP, characterize mitral valve morphology, we analyzed transthoracic echocardiography and cine CMR images from 25 MVP patients and 25 control subjects. Leaflet thickness, length, mitral annular diameters, and prolapsed distance were measured. Two- and three-dimensional LGE-CMR images were obtained in 16 MVP and 10 control patients to identify myocardial regions of fibrosis in MVP.ResultsWe found that a 2-mm threshold for leaflet excursion into the left atrium in the left ventricular outflow tract long-axis view yielded 100% sensitivity and 100% specificity for CMR using transthoracic echocardiography as the clinical gold standard. Compared with control subjects, CMR identified MVP patients as having thicker (3.2 ± 0.1 mm vs. 2.3 ± 0.1 mm) and longer (10.5 ± 0.5 mm/m2 vs. 7.1 ± 0.3 mm/m2) indexed posterior leaflets and larger indexed mitral annular diameters (27.8 ± 0.7 mm/m2 vs. 21.5 ± 0.5 mm/m2 for long axis and 22.9 ±0.7 mm/m2 vs. 17.8 ± 0.6 mm/m2 for short axis). In addition, we identified focal regions of LGE in the papillary muscles suggestive of fibrosis in 10 (63%) of 16 MVP patients and in 0 of 10 control subjects. Papillary muscle LGE was associated with the presence of complex ventricular arrhythmias in MVP patients.ConclusionsCardiovascular magnetic resonance image can identify MVP by the same echocardiographic criteria and can identify myocardial fibrosis involving the papillary muscle in MVP patients. Hyperenhancement of papillary muscles on LGE is often present in a subgroup of patients with complex ventricular arrhythmias

The Alveolate Perkinsus marinus: Biological Insights from EST Gene Discovery

<p>Abstract</p> <p>Background</p> <p><it>Perkinsus marinus</it>, a protozoan parasite of the eastern oyster <it>Crassostrea virginica</it>, has devastated natural and farmed oyster populations along the Atlantic and Gulf coasts of the United States. It is classified as a member of the Perkinsozoa, a recently established phylum considered close to the ancestor of ciliates, dinoflagellates, and apicomplexans, and a key taxon for understanding unique adaptations (<it>e.g</it>. parasitism) within the Alveolata. Despite intense parasite pressure, no disease-resistant oysters have been identified and no effective therapies have been developed to date.</p> <p>Results</p> <p>To gain insight into the biological basis of the parasite's virulence and pathogenesis mechanisms, and to identify genes encoding potential targets for intervention, we generated >31,000 5' expressed sequence tags (ESTs) derived from four trophozoite libraries generated from two <it>P. marinus </it>strains. Trimming and clustering of the sequence tags yielded 7,863 unique sequences, some of which carry a spliced leader. Similarity searches revealed that 55% of these had hits in protein sequence databases, of which 1,729 had their best hit with proteins from the chromalveolates (E-value ≤ 1e-5). Some sequences are similar to those proven to be targets for effective intervention in other protozoan parasites, and include not only proteases, antioxidant enzymes, and heat shock proteins, but also those associated with relict plastids, such as acetyl-CoA carboxylase and methyl erythrithol phosphate pathway components, and those involved in glycan assembly, protein folding/secretion, and parasite-host interactions.</p> <p>Conclusions</p> <p>Our transcriptome analysis of <it>P. marinus</it>, the first for any member of the Perkinsozoa, contributes new insight into its biology and taxonomic position. It provides a very informative, albeit preliminary, glimpse into the expression of genes encoding functionally relevant proteins as potential targets for chemotherapy, and evidence for the presence of a relict plastid. Further, although <it>P. marinus </it>sequences display significant similarity to those from both apicomplexans and dinoflagellates, the presence of trans-spliced transcripts confirms the previously established affinities with the latter. The EST analysis reported herein, together with the recently completed sequence of the <it>P. marinus </it>genome and the development of transfection methodology, should result in improved intervention strategies against dermo disease.</p

Different facets of the raise and peel model

The raise and peel model is a one-dimensional stochastic model of a fluctuating interface with nonlocal interactions. This is an interesting physical model. It's phase diagram has a massive phase and a gapless phase with varying critical exponents. At the phase transition point, the model exhibits conformal invariance which is a space-time symmetry. Also at this point the model has several other facets which are the connections to associative algebras, two-dimensional fully packed loop models and combinatorics.Comment: 29 pages 17 figure

The strategies WDK: a graphical search interface and web development kit for functional genomics databases

Web sites associated with the Eukaryotic Pathogen Bioinformatics Resource Center (EuPathDB.org) have recently introduced a graphical user interface, the Strategies WDK, intended to make advanced searching and set and interval operations easy and accessible to all users. With a design guided by usability studies, the system helps motivate researchers to perform dynamic computational experiments and explore relationships across data sets. For example, PlasmoDB users seeking novel therapeutic targets may wish to locate putative enzymes that distinguish pathogens from their hosts, and that are expressed during appropriate developmental stages. When a researcher runs one of the approximately 100 searches available on the site, the search is presented as a first step in a strategy. The strategy is extended by running additional searches, which are combined with set operators (union, intersect or minus), or genomic interval operators (overlap, contains). A graphical display uses Venn diagrams to make the strategy’s flow obvious. The interface facilitates interactive adjustment of the component searches with changes propagating forward through the strategy. Users may save their strategies, creating protocols that can be shared with colleagues. The strategy system has now been deployed on all EuPathDB databases, and successfully deployed by other projects. The Strategies WDK uses a configurable MVC architecture that is compatible with most genomics and biological warehouse databases, and is available for download at code.google.com/p/strategies-wdk