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Search Results: 1 - 10 of 216912 matches for " Mark P. Zwart "
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One Is Enough: In Vivo Effective Population Size Is Dose-Dependent for a Plant RNA Virus
Mark P. Zwart ,José-Antonio Daròs,Santiago F. Elena
PLOS Pathogens , 2011, DOI: 10.1371/journal.ppat.1002122
Abstract: Effective population size (Ne) determines the strength of genetic drift and the frequency of co-infection by multiple genotypes, making it a key factor in viral evolution. Experimental estimates of Ne for different plant viruses have, however, rendered diverging results. The independent action hypothesis (IAH) states that each virion has a probability of infection, and that virions act independent of one another during the infection process. A corollary of IAH is that Ne must be dose dependent. A test of IAH for a plant virus has not been reported yet. Here we perform a test of an IAH infection model using a plant RNA virus, Tobacco etch virus (TEV) variants carrying GFP or mCherry fluorescent markers, in Nicotiana tabacum and Capsicum annuum plants. The number of primary infection foci increased linearly with dose, and was similar to a Poisson distribution. At high doses, primary infection foci containing both genotypes were found at a low frequency (<2%). The probability that a genotype that infected the inoculated leaf would systemically infect that plant was near 1, although in a few rare cases genotypes could be trapped in the inoculated leaf by being physically surrounded by the other genotype. The frequency of mixed-genotype infection could be predicted from the mean number of primary infection foci using the independent-action model. Independent action appears to hold for TEV, and Ne is therefore dose-dependent for this plant RNA virus. The mean number of virions causing systemic infection can be very small, and approaches 1 at low doses. Dose-dependency in TEV suggests that comparison of Ne estimates for different viruses are not very meaningful unless dose effects are taken into consideration.
Model-Selection-Based Approach for Calculating Cellular Multiplicity of Infection during Virus Colonization of Multi-Cellular Hosts
Mark P. Zwart, Nicolas Tromas, Santiago F. Elena
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064657
Abstract: The cellular multiplicity of infection (MOI) is a key parameter for describing the interactions between virions and cells, predicting the dynamics of mixed-genotype infections, and understanding virus evolution. Two recent studies have reported in vivo MOI estimates for Tobacco mosaic virus (TMV) and Cauliflower mosaic virus (CaMV), using sophisticated approaches to measure the distribution of two virus variants over host cells. Although the experimental approaches were similar, the studies employed different definitions of MOI and estimation methods. Here, new model-selection-based methods for calculating MOI were developed. Seven alternative models for predicting MOI were formulated that incorporate an increasing number of parameters. For both datasets the best-supported model included spatial segregation of virus variants over time, and to a lesser extent aggregation of virus-infected cells was also implicated. Three methods for MOI estimation were then compared: the two previously reported methods and the best-supported model. For CaMV data, all three methods gave comparable results. For TMV data, the previously reported methods both predicted low MOI values (range: 1.04–1.23) over time, whereas the best-supported model predicted a wider range of MOI values (range: 1.01–2.10) and an increase in MOI over time. Model selection can therefore identify suitable alternative MOI models and suggest key mechanisms affecting the frequency of coinfected cells. For the TMV data, this leads to appreciable differences in estimated MOI values.
Stability and Fitness Impact of the Visually Discernible Rosea1 Marker in the Tobacco etch virus Genome
Eszter Majer,José-Antonio Daròs,Mark P. Zwart
Viruses , 2013, DOI: 10.3390/v5092153
Abstract: Antirrhinum majus Rosea1 (Ros1) is an MYB-related transcription factor that induces anthocyanin biosynthesis in plant tissues, and has been shown to be suitable for visual tracking of virus infection in plants. However, activation of anthocyanin biosynthesis has far reaching effects on plant physiology and could consequently have negative effects on viral replication. Therefore, viruses carrying the Ros1 marker might have a low fitness and consequently rapidly lose the marker. To compare the stability of the Ros1 marker, we generated Tobacco etch virus (TEV) based constructs containing either Ros1 or the enhanced green fluorescent protein (eGFP) between the NIb and CP cistrons (TEV-Ros1 and TEV-eGFP, respectively). We measured the within-host competitive fitness of both viruses by direct competitions with a common competitor during infection of Nicotiana tabacum. The fitness of TEV-Ros1 was significantly lower than that of TEV-eGFP, and both recombinant viruses had a significantly lower fitness than the wild-type virus. Nevertheless, after seven weeks of infection in N. tabacum, similar levels of marker gene instability where found for both viruses. Despite lower fitness of the marked virus, Ros1 is therefore a viable alternative marker for tracking viral infection in plants.
Heterogeneous Host Susceptibility Enhances Prevalence of Mixed-Genotype Micro-Parasite Infections
Wopke van der Werf ,Lia Hemerik ,Just M. Vlak,Mark P. Zwart
PLOS Computational Biology , 2011, DOI: 10.1371/journal.pcbi.1002097
Abstract: Dose response in micro-parasite infections is usually shallower than predicted by the independent action model, which assumes that each infectious unit has a probability of infection that is independent of the presence of other infectious units. Moreover, the prevalence of mixed-genotype infections was greater than predicted by this model. No probabilistic infection model has been proposed to account for the higher prevalence of mixed-genotype infections. We use model selection within a set of four alternative models to explain high prevalence of mixed-genotype infections in combination with a shallow dose response. These models contrast dependent versus independent action of micro-parasite infectious units, and homogeneous versus heterogeneous host susceptibility. We specifically consider a situation in which genome differences between genotypes are minimal, and highly unlikely to result in genotype-genotype interactions. Data on dose response and mixed-genotype infection prevalence were collected by challenging fifth instar Spodoptera exigua larvae with two genotypes of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), differing only in a 100 bp PCR marker sequence. We show that an independent action model that includes heterogeneity in host susceptibility can explain both the shallow dose response and the high prevalence of mixed-genotype infections. Theoretical results indicate that variation in host susceptibility is inextricably linked to increased prevalence of mixed-genotype infections. We have shown, to our knowledge for the first time, how heterogeneity in host susceptibility affects mixed-genotype infection prevalence. No evidence was found that virions operate dependently. While it has been recognized that heterogeneity in host susceptibility must be included in models of micro-parasite transmission and epidemiology to account for dose response, here we show that heterogeneity in susceptibility is also a fundamental principle explaining patterns of pathogen genetic diversity among hosts in a population. This principle has potentially wide implications for the monitoring, modeling and management of infectious diseases.
Evolutionary Trajectory of White Spot Syndrome Virus (WSSV) Genome Shrinkage during Spread in Asia
Mark P. Zwart,Bui Thi Minh Dieu,Lia Hemerik,Just M. Vlak
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013400
Abstract: White spot syndrome virus (WSSV) is the sole member of the novel Nimaviridae family, and the source of major economic problems in shrimp aquaculture. WSSV appears to have rapidly spread worldwide after the first reported outbreak in the early 1990s. Genomic deletions of various sizes occur at two loci in the WSSV genome, the ORF14/15 and ORF23/24 variable regions, and these have been used as molecular markers to study patterns of viral spread over space and time. We describe the dynamics underlying the process of WSSV genome shrinkage using empirical data and a simple mathematical model.
Within-Host Spatiotemporal Dynamics of Plant Virus Infection at the Cellular Level
Nicolas Tromas equal contributor,Mark P. Zwart equal contributor ,Guillaume Lafforgue,Santiago F. Elena
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004186
Abstract: A multicellular organism is not a monolayer of cells in a flask; it is a complex, spatially structured environment, offering both challenges and opportunities for viruses to thrive. Whereas virus infection dynamics at the host and within-cell levels have been documented, the intermediate between-cell level remains poorly understood. Here, we used flow cytometry to measure the infection status of thousands of individual cells in virus-infected plants. This approach allowed us to determine accurately the number of cells infected by two virus variants in the same host, over space and time as the virus colonizes the host. We found a low overall frequency of cellular infection (<0.3), and few cells were coinfected by both virus variants (<0.1). We then estimated the cellular contagion rate (R), the number of secondary infections per infected cell per day. R ranged from 2.43 to values not significantly different from zero, and generally decreased over time. Estimates of the cellular multiplicity of infection (MOI), the number of virions infecting a cell, were low (<1.5). Variance of virus-genotype frequencies increased strongly from leaf to cell levels, in agreement with a low MOI. Finally, there were leaf-dependent differences in the ease with which a leaf could be colonized, and the number of virions effectively colonizing a leaf. The modeling of infection patterns suggests that the aggregation of virus-infected cells plays a key role in limiting spread; matching the observation that cell-to-cell movement of plant viruses can result in patches of infection. Our results show that virus expansion at the between-cell level is restricted, probably due to the host environment and virus infection itself.
The distinction between star clusters and associations
Mark Gieles,Simon Portegies Zwart
Physics , 2010, DOI: 10.1111/j.1745-3933.2010.00967.x
Abstract: In Galactic studies a distinction is made between (open) star clusters and associations. For barely resolved objects at a distance of several Mpc this distinction is not trivial to make. Here we provide an objective definition by comparing the age of the stars to the crossing time of nearby stellar agglomerates. We find that a satisfactory separation can be made where this ratio equals unity. Stellar agglomerates for which the age of the stars exceeds the crossing time are bound, and are referred to as star clusters. Alternatively, those for which the crossing time exceeds the stellar age are unbound and are referred to as associations. This definition is useful whenever reliable measurements for the mass, radius and age are available.
Young massive star clusters
Simon Portegies Zwart,Steve McMillan,Mark Gieles
Physics , 2010, DOI: 10.1146/annurev-astro-081309-130834
Abstract: Young massive clusters are dense aggregates of young stars that form the fundamental building blocks of galaxies. Several examples exist in the Milky Way Galaxy and the Local Group, but they are particularly abundant in starburst and interacting galaxies. The few young massive clusters that are close enough to resolve are of prime interest for studying the stellar mass function and the ecological interplay between stellar evolution and stellar dynamics. The distant unresolved clusters may be effectively used to study the star-cluster mass function, and they provide excellent constraints on the formation mechanisms of young cluster populations. Young massive clusters are expected to be the nurseries for many unusual objects, including a wide range of exotic stars and binaries. So far only a few such objects have been found in young massive clusters, although their older cousins, the globular clusters, are unusually rich in stellar exotica. In this review we focus on star clusters younger than $\sim100$ Myr, more than a few current crossing times old, and more massive than $\sim10^4$ \Msun, irrespective of cluster size or environment. We describe the global properties of the currently known young massive star clusters in the Local Group and beyond, and discuss the state of the art in observations and dynamical modeling of these systems. In order to make this review readable by observers, theorists, and computational astrophysicists, we also review the cross-disciplinary terminology.
Defining prediabetes in polycystic ovarian syndrome  [PDF]
Mark P. Trolice
Open Journal of Obstetrics and Gynecology (OJOG) , 2011, DOI: 10.4236/ojog.2011.12008
Abstract: Objective: The article will review the associations between Prediabetes (PD) and Polycystic Ovarian Syndrome (PCOS) and present factors that decrease the progression of PD into type 2 diabetes mellitus (T2DM).Metformin will also be examined for its role in ovulation induction, pregnancy and ameliorating the metabolic syndrome. Study Design: Medline search. Methods of study: Keyword search: Prediabetes (PD), Polycystic Ovarian Syndrome (PCOS), Metformin, Glucose Tolerance Test (GTT), Type 2 Diabetes Mellitus. Results: As the most common endocrinopathy during the reproductive years, PCOS has a genetic multifactorial inheritance and is associated with a high risk of insulin resistance. The use of metformin has shown mixed results in this patient population as a therapy to improve ovulation function and the metabolic syndrome and showed no definitive reduction in the rate of miscarriage. PCOS patients are significantly predisposed to PD and T2DM. Conclusion: Lifestyle changes such as weight loss and physical activity reduce the progression of PD into T2DM in PCOS patients. The new AACE and ADA guidelines establish simplified methods of screening and treating PD. The role of metformin remains undefined in the infertile PCOS patient.
How well do STARLAB and NBODY4 compare? I: Simple models
P. Anders,H. Baumgardt,N. Bissantz,S. Portegies Zwart
Physics , 2009, DOI: 10.1111/j.1365-2966.2009.14695.x
Abstract: N-body simulations are widely used to simulate the dynamical evolution of a variety of systems, among them star clusters. Much of our understanding of their evolution rests on the results of such direct N-body simulations. They provide insight in the structural evolution of star clusters, as well as into the occurrence of stellar exotica. Although the major pure N-body codes STARLAB/KIRA and NBODY4 are widely used for a range of applications, there is no thorough comparison study yet. Here we thoroughly compare basic quantities as derived from simulations performed either with STARLAB/KIRA or NBODY4. We construct a large number of star cluster models for various stellar mass function settings (but without stellar/binary evolution, primordial binaries, external tidal fields etc), evolve them in parallel with STARLAB/KIRA and NBODY4, analyse them in a consistent way and compare the averaged results quantitatively. For this quantitative comparison we develop a bootstrap algorithm for functional dependencies. We find an overall excellent agreement between the codes, both for the clusters' structural and energy parameters as well as for the properties of the dynamically created binaries. However, we identify small differences, like in the energy conservation before core collapse and the energies of escaping stars, which deserve further studies. Our results reassure the comparability and the possibility to combine results from these two major N-body codes, at least for the purely dynamical models (i.e. without stellar/binary evolution) we performed. (abridged)
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