Modelling collective cell behaviour

The classical mean-field approach to modelling biological systems makes a number of simplifying assumptions which typically lead to coupled systems of reaction-diffusion partial differential equations. While these models have been very useful in allowing us to gain important insights into the behaviour of many biological systems, recent experimental advances in our ability to track and quantify cell behaviour now allow us to build more realistic models which relax some of the assumptions previously made. This brief review aims to illustrate the type of models obtained using this approach

Moment Closure - A Brief Review

Moment closure methods appear in myriad scientific disciplines in the modelling of complex systems. The goal is to achieve a closed form of a large, usually even infinite, set of coupled differential (or difference) equations. Each equation describes the evolution of one "moment", a suitable coarse-grained quantity computable from the full state space. If the system is too large for analytical and/or numerical methods, then one aims to reduce it by finding a moment closure relation expressing "higher-order moments" in terms of "lower-order moments". In this brief review, we focus on highlighting how moment closure methods occur in different contexts. We also conjecture via a geometric explanation why it has been difficult to rigorously justify many moment closure approximations although they work very well in practice.Comment: short survey paper (max 20 pages) for a broad audience in mathematics, physics, chemistry and quantitative biolog

A Systematic Review of Mosquito Coils and Passive Emanators: Defining Recommendations for Spatial Repellency Testing Methodologies.

Mosquito coils, vaporizer mats and emanators confer protection against mosquito bites through the spatial action of emanated vapor or airborne pyrethroid particles. These products dominate the pest control market; therefore, it is vital to characterize mosquito responses elicited by the chemical actives and their potential for disease prevention. The aim of this review was to determine effects of mosquito coils and emanators on mosquito responses that reduce human-vector contact and to propose scientific consensus on terminologies and methodologies used for evaluation of product formats that could contain spatial chemical actives, including indoor residual spraying (IRS), long lasting insecticide treated nets (LLINs) and insecticide treated materials (ITMs). PubMed, (National Centre for Biotechnology Information (NCBI), U.S. National Library of Medicine, NIH), MEDLINE, LILAC, Cochrane library, IBECS and Armed Forces Pest Management Board Literature Retrieval System search engines were used to identify studies of pyrethroid based coils and emanators with key-words "Mosquito coils" "Mosquito emanators" and "Spatial repellents". It was concluded that there is need to improve statistical reporting of studies, and reach consensus in the methodologies and terminologies used through standardized testing guidelines. Despite differing evaluation methodologies, data showed that coils and emanators induce mortality, deterrence, repellency as well as reduce the ability of mosquitoes to feed on humans. Available data on efficacy outdoors, dose-response relationships and effective distance of coils and emanators is inadequate for developing a target product profile (TPP), which will be required for such chemicals before optimized implementation can occur for maximum benefits in disease control

Interacting effects of climate change and habitat fragmentation on drought-sensitive butterflies

Climate change is expected to increase the frequency of some climatic extremes. These may have drastic impacts on biodiversity, particularly if meteorological thresholds are crossed, leading to population collapses. Should this occur repeatedly, populations may be unable to recover, resulting in local extinctions. Comprehensive time series data on butterflies in Great Britain provide a rare opportunity to quantify population responses to both past severe drought and the interaction with habitat area and fragmentation. Here, we combine this knowledge with future projections from multiple climate models, for different Representative Concentration Pathways (RCPs), and for simultaneous modelled responses to different landscape characteristics. Under RCP8.5, which is associated with ‘business as usual’ emissions, widespread drought-sensitive butterfly population extinctions could occur as early as 2050. However, by managing landscapes and particularly reducing habitat fragmentation, the probability of persistence until mid-century improves from around zero to between 6 and 42% (95% confidence interval). Achieving persistence with a greater than 50% chance and right through to 2100 is possible only under both low climate change (RCP2.6) and semi-natural habitat restoration. Our data show that, for these drought-sensitive butterflies, persistence is achieved more effectively by restoring semi-natural landscapes to reduce fragmentation, rather than simply focusing on increasing habitat area, but this will only be successful in combination with substantial emission reductions

The General Transcriptional Repressor Tup1 Is Required for Dimorphism and Virulence in a Fungal Plant Pathogen

A critical step in the life cycle of many fungal pathogens is the transition between yeast-like growth and the formation of filamentous structures, a process known as dimorphism. This morphological shift, typically triggered by multiple environmental signals, is tightly controlled by complex genetic pathways to ensure successful pathogenic development. In animal pathogenic fungi, one of the best known regulators of dimorphism is the general transcriptional repressor, Tup1. However, the role of Tup1 in fungal dimorphism is completely unknown in plant pathogens. Here we show that Tup1 plays a key role in orchestrating the yeast to hypha transition in the maize pathogen Ustilago maydis. Deletion of the tup1 gene causes a drastic reduction in the mating and filamentation capacity of the fungus, in turn leading to a reduced virulence phenotype. In U. maydis, these processes are controlled by the a and b mating-type loci, whose expression depends on the Prf1 transcription factor. Interestingly, Δtup1 strains show a critical reduction in the expression of prf1 and that of Prf1 target genes at both loci. Moreover, we observed that Tup1 appears to regulate Prf1 activity by controlling the expression of the prf1 transcriptional activators, rop1 and hap2. Additionally, we describe a putative novel prf1 repressor, named Pac2, which seems to be an important target of Tup1 in the control of dimorphism and virulence. Furthermore, we show that Tup1 is required for full pathogenic development since tup1 deletion mutants are unable to complete the sexual cycle. Our findings establish Tup1 as a key factor coordinating dimorphism in the phytopathogen U. maydis and support a conserved role for Tup1 in the control of hypha-specific genes among animal and plant fungal pathogens

Identification and characterization of secreted and pathogenesis-related proteins in Ustilago maydis

Interactions between plants and fungal pathogens require a complex interplay at the plant–fungus interface. Extracellular effector proteins are thought to play a crucial role in establishing a successful infection. To identify pathogenesis-related proteins in Ustilago maydis we combined the isolation of secreted proteins using a signal sequence trap approach with bioinformatic analyses and the subsequent characterization of knock-out mutants. We identified 29 secreted proteins including hydrophobins and proteins with a repetitive structure similar to the repellent protein Rep1. Hum3, a protein containing both, a hydrophobin domain and a repetitive Rep1-like region, is shown to be processed during passage through the secretory pathway. While single knock-outs of hydrophobin or repellent-like genes did not affect pathogenicity, we found a strong effect of a double knock-out of hum3 and the repetitive rsp1. Yeast-like growth, mating, aerial hyphae formation and surface hydrophobicity were unaffected in this double mutant. However, pathogenic development in planta stops early after penetration leading to a complete loss of pathogenicity. This indicates that Hum3 and Rsp1 are pathogenicity proteins that share an essential function in early stages of the infection. Our results demonstrate that focusing on secreted proteins is a promising way to discover novel pathogenicity proteins that might be broadly applied to a variety of fungal pathogens

Strategies to Control a Common Carp Population by Pulsed Commercial Harvest

Commercial fisheries are commonly used to manage nuisance fishes in freshwater systems, but such efforts are often unsuccessful. Strategies for successfully controlling a nuisance population of common carpCyprinus carpio by pulsed commercial harvest were evaluated with a combination of (1) field sampling, (2) population estimation and CPUE indexing, and (3) simulation using an exponential semidiscrete biomass dynamics model (SDBDM). The range of annual fishing mortalities (F) that resulted in successful control (F= 0.244–0.265) was narrow. Common carp biomass dynamics were sensitive to unintentional underharvest due to high rates of surplus production and a biomass doubling time of 2.7 years. Simulations indicated that biomanipulation never achieved successful control unless supplemental fishing mortality was imposed. Harvest of a majority of annual production was required to achieve successful control, as indicated by the ecotrophic coefficient (EC). Readily available biomass data and tools such as SDBDMs and ECs can be used in an adaptive management framework to successfully control common carp and other nuisance fishes by pulsed commercial fishing

The spatial resolution of epidemic peaks

The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible

Sex‐skewed trophic impacts in ephemeral wetlands

Predation can have marked impacts on ecosystem structure, function, and stability. However, quantifications of biotic interactions frequently overlook demographic variabilities within populations, which can modulate interaction strengths, such as sex and reproductive status. Compositional population ratios between males and females, alongside reproductive status, are highly variable temporally in ephemeral aquatic systems, and may profoundly mediate levels of ecological impact and thus stability of trophic groups. In the present study, we apply functional responses (resource intake as a function of resource density) to quantify predatory impacts of adult males, non‐gravid females, and gravid females of the calanoid copepod Lovenula raynerae (Diaptomidae), an abundant ephemeral pond specialist, on larvae of the Culex pipiens (Culicidae) mosquito complex. We then develop a novel metric to forecast population‐level impacts across different population sex ratio scenarios. Lovenula raynerae demonstrated prey population destabilising Type II functional responses irrespective of sex and reproductive status, yet variable functional response magnitudes were found. While male and non‐gravid female copepods exhibited similar functional response maximum feeding rates, gravid female feeding rates were substantially higher, implying higher resource demands for progeny development. Ecological impacts of L. raynerae on lower trophic groups increased markedly where their abundances increased but, crucially, also as population sex ratios became more biased towards gravid female copepods. We demonstrate that population‐level impacts do not only correlate tightly with abundance but may be further modulated by reproductive status variations. Thus, the development of sex‐skewed ratios in favour of gravid females during the hydroperiod probably heightens ecological impacts on lower trophic groups. The implications of these results for prey population stability are discussed in the context of freshwater ecosystems

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals