Agent-based modeling of malaria vectors: The importance of spatial simulation

Background: The modeling of malaria vector mosquito populations yields great insight into drivers of malaria transmission at the village scale. Simulation of individual mosquitoes as agents in a distributed, dynamic model domain may be greatly beneficial for simulation of spatial relationships of vectors and hosts. Methods. In this study, an agent-based model is used to simulate the life cycle and movement of individual malaria vector mosquitoes in a Niger Sahel village, with individual simulated mosquitoes interacting with their physical environment as well as humans. Various processes that are known to be epidemiologically important, such as the dependence of parity on flight distance between developmental habitat and blood meal hosts and therefore spatial relationships of pools and houses, are readily simulated using this modeling paradigm. Impacts of perturbations can be evaluated on the basis of vectorial capacity, because the interactions between individuals that make up the population- scale metric vectorial capacity can be easily tracked for simulated mosquitoes and human blood meal hosts, without the need to estimate vectorial capacity parameters. Results: As expected, model results show pronounced impacts of pool source reduction from larvicide application and draining, but with varying degrees of impact depending on the spatial relationship between pools and human habitation. Results highlight the importance of spatially-explicit simulation that can model individuals such as in an agent-based model. Conclusions: The impacts of perturbations on village scale malaria transmission depend on spatial locations of individual mosquitoes, as well as the tracking of relevant life cycle events and characteristics of individual mosquitoes. This study demonstrates advantages of using an agent-based approach for village-scale mosquito simulation to address questions in which spatial relationships are known to be important. © 2014 Bomblies; licensee BioMed Central Ltd

The changing risk of extreme event impacts on Vermont transportation infrastructure

Vermont is seeing significant increases in extreme precipitation, total precipitation, and precipitation persistence. These changes can affect the behavior of stream flows, resulting in changing magnitude of extreme flows such as the 100-year discharge. For hydraulic design of culverts and bridges, design flows are traditionally used based on assumptions of stationarity, resulting in a design that does not incorporate ongoing changes in streamflow behavior. This report describes a modeling study in the Mad River and the Missisquoi River that derives change factors for Vermont that can be applied to the magnitude of a design discharge (100- year, 50-year flow and 25-year discharge). The methodology is based on a stochastic Monte Carlo Markov Chain model that simulates the changing precipitation statistics and a hydrology model that translates climate inputs into stream discharge for the two test rivers based on climate-sensitive snowpack and soil moisture. The change factors for 100-year flows in 2050 for the Mad River (more flashy) and the Missisquoi River (less flashy) are 1.6 and 1.4, respectively. These results are based on the assumption that changes in the extreme value distributions continue in the same manner as during the observed period. The derived change factors can be applied based on a spatial map of changes of extreme precipitation. The differences in design flows from the nonstationary model, the stationary model, and downscaled climate model output are very large. This sensitivity of outcome to methodology presents a design challenge, and the results of this study can be applied to make conservative estimates of future extreme discharges

Cheaters divide and conquer

Three ‘killer genes’ in one species of fission yeast act selfishly and keep it reproductively isolated from a closely related species

Genetics of adaptation

The rediscovery of Mendel’s work showing that the heredity of phenotypes is controlled by discrete genes was followed by the reconciliation of Mendelian genetics with evolution by natural selection in the middle of the last century with the Modern Synthesis. In the past two decades, dramatic advances in genomic methods have facilitated the identification of the loci, genes, and even individual mutations that underlie phenotypic variants that are the putative targets of natural selection. Moreover, these methods have also changed how we can study adaptation by flipping the problem around, allowing us to first examine what loci show evidence of having been under selection, and then connecting these genetic variants to phenotypic variation. As a result, we now have an expanding list of actual genetic changes that underlie potentially adaptive phenotypic variation. Here, we synthesize how considering the effects of these adaptive loci in the context of cellular environments, genomes, organisms, and populations has provided new insights to the genetic architecture of adaptation

Speciation due to hybrid necrosis in plant-pathogen models

We develop a model for speciation due to postzygotic incompatibility generated by autoimmune reactions. The model is based on predator-prey interactions between a host plants and their pathogens. Such interactions are often frequency-dependent, so that pathogen attack is focused on the most abundant plant phenotype, while rare plant types may escape pathogen attack. Thus, frequency dependence can generate disruptive selection, which can give rise to speciation if distant phenotypes become reproductively isolated. Based on recent experimental evidence from {\it Arabidopsis}, we assume that at the molecular level, incompatibility between strains is caused by epistatic interactions between two proteins in the plant immune system, the guard and the guardee. Within each plant strain, immune reactions occur when the guardee protein is modified by a pathogen effector, and the guard subsequently binds to the guardee, thus precipitating an immune response. However, when guard and guardee proteins come from phenotypically distant parents, a hybrid's immune system can be triggered by erroneous interactions between these proteins even in the absence of pathogen attack, leading to severe autoimmune reactions in hybrids. Our model shows how phenotypic variation generated by frequency-dependent host-pathogen interactions can lead to postzygotic incompatibility between extremal types, and hence to speciation.Comment: 21 page, 3 figure

Redundant Enhancers Mediate Transcriptional Repression of AGAMOUS by APETALA2

AbstractThe floral homeotic gene AGAMOUS specifies stamen and carpel fate in the central whorls of Arabidopsis flowers. Transcription of AGAMOUS RNA is restricted to the center of developing flowers by several, partially redundant negative regulators, one of which is the homeotic gene APETALA2. We have identified regulatory elements that mediate transcriptional repression of AGAMOUS by APETALA2 and found that several redundant elements respond independently to loss of APETALA2 activity. Thus, redundancy at the level of cis-regulatory sequences is independent of redundancy at the level of trans-regulators. We have also found that only the early, but not the late, effects of APETALA2 on AGAMOUS require the meristem-identity protein LEAFY, a positive regulator of AGAMOUS

Modeling the impacts of changing climatic extremes on streamflow and sediment yield in a northeastern US watershed

Study region: We investigate the impacts of local temperature and precipitation trends on discharge and sediment loading by applying the model to a watershed in the northeastern US, where trends in increasing precipitation exceed those of other regions in North America. Study focus: In this study we simulate the response of watershed sediment loading to changing frequencies and magnitudes of extreme precipitation events using a coupled model that explicitly simulates streambank erosion and failure within a distributed watershed model. To drive the model, we use meteorological inputs from general circulation models (GCMs) as well as from a statistical weather generator (WG). New hydrological insights for the region: Changes in the timing and magnitude of snow melt and spring flows, as well as associated sediment mobilization, resulted from increases in temperature. Increases in discharge and sediment load resulted from increases in precipitation events exceeding the 95th percentile. In runs driven by WG weather data, positive trends were evident in peak (as well as annual) discharge and suspended sediment yields over the years modeled. No clear trends were seen in GCM-driven runs, which do not capture historically-observed trends in extreme precipitation. This work is consistent with other studies in that it shows important changes in discharge and sediment yields from a watershed resulting from ongoing changes in climate

Extending Coalescent Theory to Autotetraploids

We develop coalescent models for autotetraploid species with tetrasomic inheritance. We show that the ancestral genetic process in a large population without recombination may be approximated using Kingman’s standard coalescent, with a coalescent effective population size 4N. Numerical results suggest that this approximation is accurate for population sizes on the order of hundreds of individuals. Therefore, existing coalescent simulation programs can be adapted to study population history in autotetraploids simply by interpreting the timescale in units of 4N generations. We also consider the possibility of double reduction, a phenomenon unique to polysomic inheritance, and show that its effects on gene genealogies are similar to partial self-fertilization.Organismic and Evolutionary Biolog

Complex Evolutionary Events at a Tandem Cluster of Arabidopsis thaliana Genes Resulting in a Single-Locus Genetic Incompatibility

Non-additive interactions between genomes have important implications, not only for practical applications such as breeding, but also for understanding evolution. In extreme cases, genes from different genomic backgrounds may be incompatible and compromise normal development or physiology. Of particular interest are non-additive interactions of alleles at the same locus. For example, overdominant behavior of alleles, with respect to plant fitness, has been proposed as an important component of hybrid vigor, while underdominance may lead to reproductive isolation. Despite their importance, only a few cases of genetic over- or underdominance affecting plant growth or fitness are understood at the level of individual genes. Moreover, the relationship between biochemical and fitness effects may be complex: genetic overdominance, that is, increased or novel activity of a gene may lead to evolutionary underdominance expressed as hybrid weakness. Here, we describe a non-additive interaction between alleles at the Arabidopsis thaliana OAK (OUTGROWTH-ASSOCIATED PROTEIN KINASE) gene. OAK alleles from two different accessions interact in F1 hybrids to cause a variety of aberrant growth phenotypes that depend on a recently acquired promoter with a novel expression pattern. The OAK gene, which is located in a highly variable tandem array encoding closely related receptor-like kinases, is found in one third of A. thaliana accessions, but not in the reference accession Col-0. Besides recruitment of exons from nearby genes as promoter sequences, key events in OAK evolution include gene duplication and divergence of a potential ligand-binding domain. OAK kinase activity is required for the aberrant phenotypes, indicating it is not recognition of an aberrant protein, but rather a true gain of function, or overdominance for gene activity, that leads to this underdominance for fitness. Our work provides insights into how tandem arrays, which are particularly prone to frequent, complex rearrangements, can produce genetic novelty

Field observations and mechanistic modeling of the malaria transmission response to environmental climatic variability

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2009.Includes bibliographical references (leaves 205-222).A coupled HYDrology, Entomology and MAlaria Transmission Simulator (HYDREMATS) has been developed. The model simulates the hydrological and climatological determinants of malaria transmission mechanistically and at high spatialand temporal resolution, and is valid for semi-arid, desert fringe environments where the mosquito Anopheles gambiae s.l. is the dominant malaria vector. This includes much of the most malarious parts of Africa such as the Sahel. The model is validated with several years of field data collected from Banizoumbou village in southwestern Niger. Simulations of the 2005 and 2006 rain seasons in Banizoumbou using measured meteorological data successfully reproduce the observed interannual variability in malaria vector mosquito abundance. The distributed hydrology model operates at high spatial and temporal resolution, and incorporates remotely-sensed data for land cover and topography to simulate the formation and persistence of the small, temporary pools that constitute the breeding habitat of Anopheles gambiae s.l. mosquitoes. An agent-based mosquito population model is coupled to the distributed hydrology model, with aquatic stage and adult stage components. Aquatic stage mosquitoes are allowed to breed in any surface water, but the developing eggs, larvae and pupae die if the pool dries. The model structure maintains the spatial relationships of breeding pools, mosquitoes, and human habitation. For each individual adult mosquito, the model tracks the attributes relevant to population dynamics and malaria transmission, which are updated as mosquitoes interact with their environment, humans, and animals.(cont.) The model reproduces mosquito population variability at seasonal and interannual time scales, and highlights individual pool persistence as a dominant control of mosquito population dynamics. HYDREMATS is applied to study the impact of village-scale spatial variability in hydrologic conditions on malaria transmission. Zindarou is a village located only 30 km from Banizoumbou, but hydrologically it is very different from Banizoumbou. The groundwater table around Banizoumbou is about 25 meters below the surface, while the groundwater table around Zindarou is a few meters below the surface. HYDREMATS reproduces the much higher mosquito populations observed in Zindarou arising from the lush, wet conditions compared to drier Banizoumbou. This result exposes small scale spatial variability in surface and subsurface hydrology as a principal control of villagescale malaria transmission. Further experiments simulate the effect of climate shifts on Sahel malaria-transmitting mosquito abundance using HYDREMATS. Climate variability and climate change in West Africa often occur in the form of a shift from a wet regime to a dry regime or vice versa. Such a climate shift in the West African Sahel can greatly impact the intensity of regional malaria transmission. To investigate possible outcomes of such shifts, meteorological data from two different Sahel stations are used as alternate climatic forcings for the Banizoumbou model domain. The stations are located north and south of Banizoumbou in Agoufou, Mali, and in Djougou, Benin at 200 km and 400 km in the north-south direction from Banizoumbou, respectively.(cont.) These data series represent possible climate shift scenarios, based on the observation that a northward or southward translation of Sahelian climate conditions along the north-south gradient has accompanied past climate shifts. A series of simulations investigate individually the effects of precipitation frequency and ambient temperature on anopheles mosquito populations and vectorial capacity. The vectorial capacity with Djougou, Benin conditions exhibited a 25% increase compared to baseline Banizoumbou conditions, whereas the vectorial capacity decreased by 26% with the Agoufou, Mali meteorological conditions. Isolation of temperature contributions to these differences show that in a cooling scenario (to resemble Benin), elasticity of mosquito abundance is 1.3, compared to -8.9 for the shift to hotter conditions found in Agoufou, Mali. Mosquito mortality ultimately limits malaria transmission in shifts to warmer conditions, and parasite extrinsic incubation period (sporogony) becomes limiting at low temperatures. In all cases, changes in precipitation frequency can limit mosquito breeding due to small-scale hydrological processes influencing breeding pool persistence. Finally, a simple model of human immune response to malaria transmission is built into HYDREMATS. The HYDREMATS representation of acquired immunity acting in opposition to-yet depending on-malaria parasite in the bloodstream explains field observations of very similar malaria prevalence in Zindarou and Banizoumbou despite pronounced difference in vectorial capacity.(cont.) The results are consistent with various paradoxical observations in the literature of unexpectedly low prevalence with higher biting pressure. HYDREMATS represents acquired immunity as dependent on repeated inoculations of malaria, with a slow loss of immunity in the absence of infectious bites. Because climate variability determines variability in vectorial capacity, in an endemic environment acquired immunity level in a human population has a memory of past climate variability. Model experiments in Banizoumbou evaluating the impacts of climate shifts confirm this.by Arne Bomblies.Ph.D