3,621 research outputs found
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Plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria.
Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi - macaque model systems and summarizing exciting new progress in this area of research
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PacBio assembly of a Plasmodium knowlesi genome sequence with Hi-C correction and manual annotation of the SICAvar gene family.
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features. Today, long-read PacBio and chromatin conformation technologies are overcoming such obstacles. Here, based on the use of these technologies, we present a highly refined de novo P. knowlesi genome sequence of the Pk1(A+) clone. This sequence and annotation, referred to as the 'MaHPIC Pk genome sequence', includes manual annotation of the SICAvar gene family with 136 full-length members categorized as type I or II. This sequence provides a framework that will permit a better understanding of the SICAvar repertoire, selective pressures acting on this gene family and mechanisms of antigenic variation in this species and other pathogens
Comparing two approaches for parsimonious vegetation modelling in semiarid regions using satellite data
[EN] Large portions of Earth's terrestrial surface are arid or semiarid. As in these regions, the hydrological cycle and the vegetation dynamics are tightly interconnected, a coupled modelling of these two systems is needed to fully reproduce the ecosystem behaviour. In this paper, the performance of two parsimonious dynamic vegetation models, suitable for the inclusion in operational ecohydrological models and based on well-established but different approaches, is compared in a semiarid Aleppo Pine region. The first model [water use efficiency (WUE) model] links growth to transpiration through WUE; the second model [light use efficiency (LUE) model] simulates biomass increase in relation to absorbed photosynthetically active radiation and LUE. Furthermore, an analysis of the information contained in MODIS products is presented to indicate the best vegetation indices to be used as observational verification for the models. Enhanced Vegetation Index is reported in literature to be highly correlated with leaf area index, so it is compared with modelled LAI(mod) (rWUE model = 0.45; rLUE model = 0.57). In contrast, Normalized Difference Vegetation Index appears highly linked to soil moisture, through the control exerted by this variable on chlorophyll production, and is therefore used to analyze LAI*(mod), models' output corrected by plant water stress (rWUE model = 0.62; rLUE model = 0.59). Moderate-resolution imaging spectroradiometer Leaf Area Index and evapotranspiration are found to be unrealistic in the studied area. The performance of both models in this semiarid region is found to be reasonable. However, the LUE model presents the advantages of a better performance, the possibility to be used in a wider range of climates and to have been extensively tested in literature. (C) Copyright 2014 John Wiley & Sons, Ltd.The research leading to these results has received funding from the Spanish Ministry of Economy and Competitiveness through the research projects FLOOD-MED (ref. CGL2008-06474-C02-02), SCARCE-CONSOLIDER (ref. CSD2009-00065) and ECO-TETIS (ref. CGL2011-28776-C02-01), and from the European Community's Seventh Framework Programme (FP7 2007-2013) under grant agreement no. 238366. The MODIS data were obtained through the online Data Pool at the NASA Land Processes Distributed Active Archive Centre (LP DAAC), USGS/Earth Resources Observation and Science (EROS) Centre, Sioux Falls, South Dakota (https://lpdaac.usgs.gov/get_data). The meteorological data were provided by the Spanish National Weather Agency (AEMET). The authors thank Antonio Del Campo Garcia and Maria Gonzalez Sanchis at the Universitat Politecnica de Valencia for their support and valuable comments.Pasquato, M.; Medici, C.; Friend, A.; Francés, F. (2015). Comparing two approaches for parsimonious vegetation modelling in semiarid regions using satellite data. Ecohydrology. 8(6):1024-1036. https://doi.org/10.1002/eco.1559S102410368
Interplay of quantum and classical fluctuations near quantum critical points
For a system near a quantum critical point (QCP), above its lower critical
dimension , there is in general a critical line of second order phase
transitions that separates the broken symmetry phase at finite temperatures
from the disordered phase. The phase transitions along this line are governed
by thermal critical exponents that are different from those associated with the
quantum critical point. We point out that, if the effective dimension of the
QCP, ( is the Euclidean dimension of the system and the
dynamic quantum critical exponent) is above its upper critical dimension ,
there is an intermingle of classical (thermal) and quantum critical
fluctuations near the QCP. This is due to the breakdown of the generalized
scaling relation between the shift exponent of the critical
line and the crossover exponent , for by a \textit{dangerous
irrelevant interaction}. This phenomenon has clear experimental consequences,
like the suppression of the amplitude of classical critical fluctuations near
the line of finite temperature phase transitions as the critical temperature is
reduced approaching the QCP.Comment: 10 pages, 6 figures, to be published in Brazilian Journal of Physic
Chiral corrections to the Gell-Mann-Oakes-Renner relation
The next to leading order chiral corrections to the
Gell-Mann-Oakes-Renner (GMOR) relation are obtained using the pseudoscalar
correlator to five-loop order in perturbative QCD, together with new finite
energy sum rules (FESR) incorporating polynomial, Legendre type, integration
kernels. The purpose of these kernels is to suppress hadronic contributions in
the region where they are least known. This reduces considerably the systematic
uncertainties arising from the lack of direct experimental information on the
hadronic resonance spectral function. Three different methods are used to
compute the FESR contour integral in the complex energy (squared) s-plane, i.e.
Fixed Order Perturbation Theory, Contour Improved Perturbation Theory, and a
fixed renormalization scale scheme. We obtain for the corrections to the GMOR
relation, , the value . This result
is substantially more accurate than previous determinations based on QCD sum
rules; it is also more reliable as it is basically free of systematic
uncertainties. It implies a light quark condensate . As a byproduct, the chiral perturbation theory (unphysical) low energy
constant is predicted to be , or .Comment: A comment about the value of the strong coupling has been added at
the end of Section 4. No change in results or conslusion
A four phase development model for integrated care services in the Netherlands
Background. Multidisciplinary and interorganizational arrangements for the delivery of coherent integrated care are being developed in a large number of countries. Although there are many integrated care programs worldwide, the process of developing these programs and interorganizational collaboration is described in the literature only to a limited extent. The purpose of this study is to explore how local integrated care services are developed in the Netherlands, and to conceptualize and operationalize a development model of integrated care. Methods. The research is based on an expert panel study followed by a two-part questionnaire, designed to identify the development process of integrated care. Essential elements of integrated care, which were developed in a previous Delphi and Concept Mapping Study, were analyzed in relation to development process of integrated care. Results. Integrated care development can be characterized by four developmental phases: the initiative and design phase; the experimental and execution phase; the expansion and monitoring phase; and the consolidation and transformation phase. Different elements of integrated care have been identified in the various developmental phases. Conclusion. The findings provide a descriptive model of the development process that integrated care services can undergo in the Netherlands. The findings have important implications for integrated care services, which can use the model as an instrument to reflect on their current practices. The model can be used to help to identify improvement areas in practice. The model provides a framework for developing evaluation designs for integrated care arrangements. Further research is recommended to test the developed model in practice and to add international experiences
The Plasmodium falciparum, Nima-related kinase Pfnek-4: a marker for asexual parasites committed to sexual differentiation
<b>Background</b>
Malaria parasites undergo, in the vertebrate host, a developmental switch from asexual replication to sexual differentiation leading to the formation of gametocytes, the only form able to survive in the mosquito vector. Regulation of the onset of the sexual phase remains largely unknown and represents an important gap in the understanding of the parasite's complex biology.
<b>Methods:</b>
The expression and function of the Nima-related kinase Pfnek-4 during the early sexual development of the human malaria parasite Plasmodium falciparum were investigated, using three types of transgenic Plasmodium falciparum 3D7 lines: (i) episomally expressing a Pfnek-4-GFP fusion protein under the control of its cognate pfnek-4 promoter; (ii) episomally expressing negative or positive selectable markers, yeast cytosine deaminase-uridyl phosphoribosyl transferase, or human dihydrofolate reductase, under the control of the pfnek-4 promoter; and (iii) lacking a functional pfnek-4 gene. Parasite transfectants were analysed by fluorescence microscopy and flow cytometry. In vitro growth rate and gametocyte formation were determined by Giemsa-stained blood smears.
<b>Results:</b>
The Pfnek-4-GFP protein was found to be expressed in stage II to V gametocytes and, unexpectedly, in a subset of asexual-stage parasites undergoing schizogony. Culture conditions stimulating gametocyte formation resulted in significant increase of this schizont subpopulation. Moreover, sorted asexual parasites expressing the Pfnek-4-GFP protein displayed elevated gametocyte formation when returned to in vitro culture in presence of fresh red blood cells, when compared to GFP- parasites from the same initial population. Negative selection of asexual parasites expressing pfnek-4 showed a marginal reduction in growth rate, whereas positive selection caused a marked reduction in parasitaemia, but was not sufficient to completely abolish proliferation. Pfnek-4- clones are not affected in their asexual growth and produced normal numbers of stage V gametocytes.
<b>Conclusions:</b>
The results indicate that Pfnek-4 is not strictly gametocyte-specific, and is expressed in a small subset of asexual parasites displaying high rate conversion to sexual development. Pfnek-4 is not required for erythrocytic schizogony and gametocytogenesis. This is the first study to report the use of a molecular marker for the sorting of sexually-committed schizont stage P. falciparum parasites, which opens the way to molecular characterization of this pre-differentiated subpopulation
Current Status of a Model System: The Gene Gp-9 and Its Association with Social Organization in Fire Ants
The Gp-9 gene in fire ants represents an important model system for studying the evolution of social organization in insects as well as a rich source of information relevant to other major evolutionary topics. An important feature of this system is that polymorphism in social organization is completely associated with allelic variation at Gp-9, such that single-queen colonies (monogyne form) include only inhabitants bearing B-like alleles while multiple-queen colonies (polygyne form) additionally include inhabitants bearing b-like alleles. A recent study of this system by Leal and Ishida (2008) made two major claims, the validity and significance of which we examine here. After reviewing existing literature, analyzing the methods and results of Leal and Ishida (2008), and generating new data from one of their study sites, we conclude that their claim that polygyny can occur in Solenopsis invicta in the U.S.A. in the absence of expression of the b-like allele Gp-9b is unfounded. Moreover, we argue that available information on insect OBPs (the family of proteins to which GP-9 belongs), on the evolutionary/population genetics of Gp-9, and on pheromonal/behavioral control of fire ant colony queen number fails to support their view that GP-9 plays no role in the chemosensory-mediated communication that underpins regulation of social organization. Our analyses lead us to conclude that there are no new reasons to question the existing consensus view of the Gp-9 system outlined in Gotzek and Ross (2007)
Uracil moieties in Plasmodium falciparum genomic DNA
Plasmodium falciparum parasites undergo multiple genome duplication events during their development. Within the intraerythrocytic stages, parasites encounter an oxidative environment and DNA synthesis necessarily proceeds under these circumstances. In addition to these conditions, the extreme AT bias of the P. falciparum genome poses further constraints for DNA synthesis. Taken together, these circumstances may allow appearance of damaged bases in the PlasmodiumDNA. Here, we focus on uracil that may arise in DNA either via oxidative deamination or thymine-replacing incorporation. We determine the level of uracil at the ring, trophozoite, and schizont intraerythrocytic stages and evaluate the base-excision repair potential of P. falciparum to deal with uracil-DNA repair. We find approximately 7–10 uracil per million bases in the different parasite stages. This level is considerably higher than found in other wild-type organisms from bacteria to mammalian species. Based on a systematic assessment of P. falciparum genome and transcriptome databases, we conclude that uracil-DNA repair relies on one single uracil-DNA glycosylase and proceeds through the long-patch base-excision repair route. Although potentially efficient, the repair route still leaves considerable level of uracils in parasite DNA, which may contribute to mutation rates in P. falciparum. © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd
A model of decay
We suggest a parameterization of the matrix element for decay using kinematic variables convenient for experimental
analysis. The contributions of intermediate - and -states up
to spin 3 have been taken into account. The angular distributions for each
discussed hypothesis have been obtained and analysed using Monte-Carlo
simulation.Comment: 24 pages, 9 figures, 1 table; V2: text in some places improved and
acknowledgments adde
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