736 research outputs found

    Defining species specific genome differences in malaria parasites

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    <p>Abstract</p> <p>Background</p> <p>In recent years a number of genome sequences for different <it>plasmodium </it>species have become available. This has allowed the identification of numerous conserved genes across the different species and has significantly enhanced our understanding of parasite biology. In contrast little is known about species specific differences between the different genomes partly due to the lower sequence coverage and therefore relatively poor annotation of some of the draft genomes particularly the rodent malarias parasite species.</p> <p>Results</p> <p>To improve the current annotation and gene identification status of the draft genomes of <it>P. berghei</it>, <it>P. chabaudi </it>and <it>P. yoelii</it>, we performed genome-wide comparisons between these three species. Through analyses via comparative genome hybridizations using a newly designed pan-rodent array as well as in depth bioinformatics analysis, we were able to improve on the coverage of the draft rodent parasite genomes by detecting orthologous genes between these related rodent parasite species. More than 1,000 orthologs for <it>P. yoelii </it>were now newly associated with a <it>P. falciparum </it>gene. In addition to extending the current core gene set for all plasmodium species this analysis also for the first time identifies a relatively small number of genes that are unique to the primate malaria parasites while a larger gene set is uniquely conserved amongst the rodent malaria parasites.</p> <p>Conclusions</p> <p>These findings allow a more thorough investigation of the genes that are important for host specificity in malaria.</p

    Quantitative protein expression profiling reveals extensive post-transcriptional regulation and post-translational modifications in schizont-stage malaria parasites

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    A quantitative time-course analysis of protein abundance for Plasmodium falciparum schizonts using two-dimensional differential gel electrophoresis reveals significant post-transcriptional regulation

    Characterization of the repertoire diversity of the Plasmodium falciparum stevor multigene family in laboratory and field isolates

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    BACKGROUND: The evasion of host immune response by the human malaria parasite Plasmodium falciparum has been linked to expression of a range of variable antigens on the infected erythrocyte surface. Several genes are potentially involved in this process with the var, rif and stevor multigene families being the most likely candidates and coding for rapidly evolving proteins. The high sequence diversity of proteins encoded by these gene families may have evolved as an immune evasion strategy that enables the parasite to establish long lasting chronic infections. Previous findings have shown that the hypervariable region (HVR) of STEVOR has significant sequence diversity both within as well as across different P. falciparum lines. However, these studies did not address whether or not there are ancestral stevor that can be found in different parasites. METHODS: DNA and RNA sequences analysis as well as phylogenetic approaches were used to analyse the stevor sequence repertoire and diversity in laboratory lines and Kilifi (Kenya) fresh isolates. RESULTS: Conserved stevor genes were identified in different P. falciparum isolates from different global locations. Consistent with previous studies, the HVR of the stevor gene family was found to be highly divergent both within and between isolates. Importantly phylogenetic analysis shows some clustering of stevor sequences both within a single parasite clone as well as across different parasite isolates. CONCLUSION: This indicates that the ancestral P. falciparum parasite genome already contained multiple stevor genes that have subsequently diversified further within the different P. falciparum populations. It also confirms that STEVOR is under strong selection pressure

    Dynamics of a hyperbolic system that applies at the onset of the oscillatory instability

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    A real hyperbolic system is considered that applies near the onset of the oscillatory instability in large spatial domains. The validity of that system requires that some intermediate scales (large compared with the basic wavelength of the unstable modes but small compared with the size of the system) remain inhibited; that condition is analysed in some detail. The dynamics associated with the hyperbolic system is fully analysed to conclude that it is very simple if the coefficient of the cross-nonlinearity is such that , while the system exhibits increasing complexity (including period-doubling sequences, quasiperiodic transitions, crises) as the bifurcation parameter grows if ; if then the system behaves subcritically. Our results are seen to compare well, both qualitatively and quantitatively, with the experimentally obtained ones for the oscillatory instability of straight rolls in pure Rayleigh - Bénard convection

    De Novo Generated Human Red Blood Cells in Humanized Mice Support Plasmodium falciparum Infection

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    Immunodeficient mouse–human chimeras provide a powerful approach to study host specific pathogens like Plasmodium (P.) falciparum that causes human malaria. Existing mouse models of P. falciparum infection require repeated injections of human red blood cells (RBCs). In addition, clodronate lipsomes and anti-neutrophil antibodies are injected to suppress the clearance of human RBCs by the residual immune system of the immunodeficient mice. Engraftment of NOD-scid Il2rg[superscript -/-] mice with human hematopoietic stem cells leads to reconstitution of human immune cells. Although human B cell reconstitution is robust and T cell reconstitution is reasonable in the recipient mice, human RBC reconstitution is generally poor or undetectable. The poor reconstitution is mainly the result of a deficiency of appropriate human cytokines that are necessary for the development and maintenance of these cell lineages. Delivery of plasmid DNA encoding human erythropoietin and interleukin-3 into humanized mice by hydrodynamic tail-vein injection resulted in significantly enhanced reconstitution of erythrocytes. With this improved humanized mouse, here we show that P. falciparum infects de novo generated human RBCs, develops into schizonts and causes successive reinvasion. We also show that different parasite strains exhibit variation in their ability to infect these humanized mice. Parasites could be detected by nested PCR in the blood samples of humanized mice infected with P. falciparum K1 and HB3 strains for 3 cycles, whereas in other strains such as 3D7, DD2, 7G8, FCR3 and W2mef parasites could only be detected for 1 cycle. In vivo adaptation of K1 strain further improves the infection efficiency and parasites can be detected by microscopy for 3 cycles. The parasitemia ranges between 0.13 and 0.25% at the first cycle of infection, falls between 0.08 and 0.15% at the second cycle, and drops to barely detectable levels at the third cycle of infection. Compared to existing mouse models, our model generates human RBCs de novo and does not require the treatment of mice with immunomodulators.Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology

    The Houses of Parliament and Reid's Inquiries into User Perception

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    This paper provides a brief overview of the role of user perception in the development of Reid ventilation system for the Palace of Westminster. User-perception was used as a performance indicator in the day-to-day management of the ventilation, but also it was also a major design factor underlying the development of the ventilation system for the Permanent Houses of Commons

    Glycaemic variability, infections and mortality in a medical-surgical intensive care unit.

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    In critically ill patients, glycaemic variability (GV) was reported as a better predictor of mortality than mean blood glucose level (BGL). We compared the ability of different GV indices and mean BGLs to predict mortality and intensive care unit-acquired infections in a population of ICU patients.Retrospective study on adult ICU patients with ≥ three BGL measurements. GV was assessed by SD, coefficient of variation (CV) and mean amplitude of glycaemic excursion (MAGE), and by one timeweighted index, the glycaemic lability index (GLI), and compared with mean BGL. We studied 2782 patients admitted to the 12-bed medical-surgical ICU of a teaching hospital from January 2004 until December 2010.Logistic regression analyses were performed to assess the association between GV and ICU mortality and ICU-acquired infections. The areas under receiver operating characteristic curves were calculated to compare the discriminatory ability of GV and mean BGL for infections and mortality.Mortality was 16.6%, and 30% of patients had at least one infection. Patients with infections or diabetes or who were treated with insulin had a higher mean BGL and GV than other patients. GLI, SD, CV and MAGE were significantly associated with infections and mortality; mean BGL was not. Quartiles of increasing GLI were independently associated with higher mortality and an increased infection rate. Patients in the upper quartile of mean BGL and GLI had the strongest association with infections (odds ratio, 5.044 [95% CI, 1.695-15.007]; P = 0.004).High GV is associated with higher risk of ICUCrit acquired infection and mortality
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