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Kershenbaum A.,Haifa University | Kershenbaum A.,National Institute for Mathematical and Biological Synthesis NIMBioS | Blank L.,Haifa University | Sinai I.,Haifa University | And 4 more authors.
Oecologia | Year: 2014

When populations reside within a heterogeneous landscape, isolation by distance may not be a good predictor of genetic divergence if dispersal behaviour and therefore gene flow depend on landscape features. Commonly used approaches linking landscape features to gene flow include the least cost path (LCP), random walk (RW), and isolation by resistance (IBR) models. However, none of these models is likely to be the most appropriate for all species and in all environments. We compared the performance of LCP, RW and IBR models of dispersal with the aid of simulations conducted on artificially generated landscapes. We also applied each model to empirical data on the landscape genetics of the endangered fire salamander, Salamandra infraimmaculata, in northern Israel, where conservation planning requires an understanding of the dispersal corridors. Our simulations demonstrate that wide dispersal corridors of the low-cost environment facilitate dispersal in the IBR model, but inhibit dispersal in the RW model. In our empirical study, IBR explained the genetic divergence better than the LCP and RW models (partial Mantel correlation 0.413 for IBR, compared to 0.212 for LCP, and 0.340 for RW). Overall dispersal cost in salamanders was also well predicted by landscape feature slope steepness (76 %), and elevation (24 %). We conclude that fire salamander dispersal is well characterised by IBR predictions. Together with our simulation findings, these results indicate that wide dispersal corridors facilitate, rather than hinder, salamander dispersal. Comparison of genetic data to dispersal model outputs can be a useful technique in inferring dispersal behaviour from population genetic data. © 2014 Springer-Verlag Berlin Heidelberg.


Nikitina I.Y.,Central Tuberculosis Research Institute | Kondratuk N.A.,Central Tuberculosis Research Institute | Kosmiadi G.A.,Central Tuberculosis Research Institute | Amansahedov R.B.,Central Tuberculosis Research Institute | And 4 more authors.
PLoS ONE | Year: 2012

Background: Effector CD4 T cells represent a key component of the host's anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of Mtb-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection. Methodology/Principal Findings: The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27 low cells within a population of Mtb- specific CD4 T lymphocytes ("CD27 lowIFN-γ +" cells). The percentages of CD27 lowIFN-γ+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p<0.0005). Within the group of patients, the percentages of CD27 lowIFN-γ + cells were uniformly high in the lungs (>76%), but varied in blood (12-92%). The major correlate for the accumulation of CD27 lowIFN-γ + cells in blood was lung destruction (r = 0.65, p = 2.7×10 -7). A cutoff of 47% of CD27 lowIFN-γ + cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27 lowIFN-γ +cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01). Conclusions: Highly differentiated CD27 low Mtb-specific (CD27 lowIFN-γ +) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27 lowIFN-γ + cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell differentiation during TB; evaluation of CD27 lowIFN-γ + cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy. © 2012 Nikitina et al.


Ngonghala C.N.,Harvard University | Ngonghala C.N.,National Institute for Mathematical and Biological Synthesis NIMBioS | Teboh-Ewungkem M.I.,Lehigh University | Ngwa G.A.,University of Buea
Journal of Mathematical Biology | Year: 2015

We derive and study a deterministic compartmental model for malaria transmission with varying human and mosquito populations. Our model considers disease-related deaths, asymptomatic immune humans who are also infectious, as well as mosquito demography, reproduction and feeding habits. Analysis of the model reveals the existence of a backward bifurcation and persistent limit cycles whose period and size is determined by two threshold parameters: the vectorial basic reproduction number $$\fancyscript{R}_{m}$$Rm, and the disease basic reproduction number $$\fancyscript{R}_0$$R0, whose size can be reduced by reducing $$\fancyscript{R}_{m}$$Rm. We conclude that malaria dynamics are indeed oscillatory when the methodology of explicitly incorporating the mosquito’s demography, feeding and reproductive patterns is considered in modeling the mosquito population dynamics. A sensitivity analysis reveals important control parameters that can affect the magnitudes of $$\fancyscript{R}_{m}$$Rm and $$\fancyscript{R}_0$$R0, threshold quantities to be taken into consideration when designing control strategies. Both $$\fancyscript{R}_{m}$$Rm and the intrinsic period of oscillation are shown to be highly sensitive to the mosquito’s birth constant $$\lambda _{m}$$λm and the mosquito’s feeding success probability $$p_{w}$$pw. Control of $$\lambda _{m}$$λm can be achieved by spraying, eliminating breeding sites or moving them away from human habitats, while $$p_{w}$$pw can be controlled via the use of mosquito repellant and insecticide-treated bed-nets. The disease threshold parameter $$\fancyscript{R}_0$$R0 is shown to be highly sensitive to $$p_{w}$$pw, and the intrinsic period of oscillation is also sensitive to the rate at which reproducing mosquitoes return to breeding sites. A global sensitivity and uncertainty analysis reveals that the ability of the mosquito to reproduce and uncertainties in the estimations of the rates at which exposed humans become infectious and infectious humans recover from malaria are critical in generating uncertainties in the disease classes. © 2014, Springer-Verlag Berlin Heidelberg.


Akcay E.,National Institute for Mathematical and Biological Synthesis NIMBioS | Roughgarden J.,Stanford University
Proceedings of the Royal Society B: Biological Sciences | Year: 2011

Most of the work in evolutionary game theory starts with a model of a social situation that gives rise to a particular payoff matrix and analyses how behaviour evolves through natural selection. Here, we invert this approach and ask, given a model of how individuals behave, how the payoff matrix will evolve through natural selection. In particular, we ask whether a prisoner's dilemma game is stable against invasions by mutant genotypes that alter the payoffs. To answer this question, we develop a two-tiered framework with goal-oriented dynamics at the behavioural time scale and a diploid population genetic model at the evolutionary time scale. Our results are two-fold: first, we show that the prisoner's dilemma is subject to invasions by mutants that provide incentives for cooperation to their partners, and that the resulting game is a coordination game similar to the hawk-dove game. Second, we find that for a large class of mutants and symmetric games, a stable genetic polymorphism will exist in the locus determining the payoff matrix, resulting in a complex pattern of behaviour al diversity in the population. Our results highlight the importance of considering the evolution of payoff matrices to understand the evolution of animal social systems. © 2010 The Royal Society.


Gonzalez-Forero M.,University of Tennessee at Knoxville | Gonzalez-Forero M.,National Institute for Mathematical and Biological Synthesis NIMBioS
Evolution | Year: 2014

Individuals can manipulate the behavior of social partners. However, manipulation may conflict with the fitness interests of the manipulated individuals. Manipulated individuals can then be favored to resist manipulation, possibly reducing or eliminating the manipulated behavior in the long run. I use a mathematical model to show that conflicts where manipulation and resistance coevolve can disappear as a result of the coevolutionary process. I find that while manipulated individuals are selected to resist, they can simultaneously be favored to express the manipulated behavior at higher efficiency (i.e., providing increasing fitness effects to recipients of the manipulated behavior). Efficiency can increase to a point at which selection for resistance disappears. This process yields an efficient social behavior that is induced by social partners, and over which the inducing and induced individuals are no longer in conflict. A necessary factor is costly inefficiency. I develop the model to address the evolution of advanced eusociality via maternal manipulation (AEMM). The model predicts AEMM to be particularly likely in taxa with ancestrally imperfect resistance to maternal manipulation. Costly inefficiency occurs if the cost of delayed dispersal is larger than the benefit of exploiting the maternal patch. I discuss broader implications of the process. © 2014 The Society for the Study of Evolution.

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