Spatially explicit modeling of metapopulation dynamics of broadcast spawners and stabilizing/destabilizing effects of heterogeneity of quality across local habitats.

Many coastal invertebrate species are broadcast spawners. These species have a highly sedentary adult stage and disperse by oceanic transport of planktonic larvae. One commercially important group of broadcast spawners is abalones, which live in suitable habitat patches of rock reefs that are discretely distributed. Because of these life-history and habitat characteristics, abalones tend to exhibit a metapopulation structure. Despite fisheries management and the release of juveniles, wild populations of broadcast spawners have undergone dramatic reductions in density due to overexploitation, which has been partly attributed to a failure to account for spatial structure. To clarify the relationship between the persistence of a metapopulation and the bottleneck that occurs during reproduction and dispersal processes caused by spatial structure, we developed a spatially explicit metapopulation model accounting for the effects of both life history and fishery pressure. By analyzing the model, we derived a metric to evaluate metapopulation quality as the leading eigenvalue of a non-negative matrix (the landscape matrix). Using this measure, we clarified that the effect of spatial structure on metapopulation stability is explained well by the mean and variance of parameter values across patches under the condition in which the heterogeneity of the metapopulation network is weak. In particular, the presence of both a higher average and higher variance of quality in the landscape could indicate stable fishery stocks under certain conditions. For example, when the decline in the mean longevity of local patch due to the fishery pressures gradually diminishes, the rescue effects by good patches would work more effectively than the negative effect of bad patches and then the stabilizing effect of spatial heterogeneity could be observed in a metapopulation. Furthermore, optimal patch characteristics for the improvement of quality strongly depend on specific parameter values. For example, when adult fertility is improved, a patch with higher "source" ability is more suitable. In contrast, when the settlement success of planktonic larvae is improved or fishery pressure is reduced, a patch with higher "buffer" ability is more suitable for the improvement of fishery management.

Epidemic dynamics of a vector-borne disease on a villages-and-city star network with commuters.

We develop a star-network of connections between a central city and peripheral villages and analyze the epidemic dynamics of a vector-borne disease as influenced by daily commuters. We obtain an analytical solution for the global basic reproductive number R0 and investigate its dependence on key parameters for disease control. We find that in a star-network topology the central hub is not always the best place to focus disease intervention strategies. Disease control decisions are sensitive to the number of commuters from villages to the city as well as the relative densities of mosquitoes between villages and city. With more commuters it becomes important to focus on the surrounding villages. Commuting to the city paradoxically reduces the disease burden even when the bulk of infections are in the city because of the resulting diluting effects of transmissions with more commuters. This effect decreases with heterogeneity in host and vector population sizes in the villages due to the formation of peripheral epicenters of infection. We suggest that to ensure effective control of vector-borne diseases in star networks of villages and cities it is also important to focus on the commuters and where they come from.

Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia.

A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (CGC-type) has significantly reduced promoter activity. A newly developed method for detecting ongoing positive selection was applied to the ST8SIA2 genomic region with the identification of an unambiguous sweep signal in a rather restricted region of 18 kb length surrounding the promoter. We also found that while the CGC-type emerged in anatomically modern humans in Africa over 100 thousand years ago, it has increased its frequency in Asia only during the past 20-30 thousand years. These findings support that the positive selection is driven by psychosocial stress due to changing social environments since around the last glacial maximum, and raise a possibility that schizophrenia extensively emerged during the Upper Paleolithic and Neolithic era.

Spotting Epidemic Keystones by R0 Sensitivity Analysis: High-Risk Stations in the Tokyo Metropolitan Area.

How can we identify the epidemiologically high-risk communities in a metapopulation network? The network centrality measure, which quantifies the relative importance of each location, is commonly utilized for this purpose. As the disease invasion condition is given from the basic reproductive ratio R0, we have introduced a novel centrality measure based on the sensitivity analysis of this R0 and shown its capability of revealing the characteristics that has been overlooked by the conventional centrality measures. The epidemic dynamics over the commute network of the Tokyo metropolitan area is theoretically analyzed by using this centrality measure. We found that, the impact of countermeasures at the largest station is more than 1,000 times stronger compare to that at the second largest station, even though the population sizes are only around 1.5 times larger. Furthermore, the effect of countermeasures at every station is strongly dependent on the existence and the number of commuters to this largest station. It is well known that the hubs are the most influential nodes, however, our analysis shows that only the largest among the network plays an extraordinary role. Lastly, we also found that, the location that is important for the prevention of disease invasion does not necessarily match the location that is important for reducing the number of infected.

Epidemic process over the commute network in a metropolitan area.

An understanding of epidemiological dynamics is important for prevention and control of epidemic outbreaks. However, previous studies tend to focus only on specific areas, indicating that application to another area or intervention strategy requires a similar time-consuming simulation. Here, we study the epidemic dynamics of the disease-spread over a commute network, using the Tokyo metropolitan area as an example, in an attempt to elucidate the general properties of epidemic spread over a commute network that could be used for a prediction in any metropolitan area. The model is formulated on the basis of a metapopulation network in which local populations are interconnected by actual commuter flows in the Tokyo metropolitan area and the spread of infection is simulated by an individual-based model. We find that the probability of a global epidemic as well as the final epidemic sizes in both global and local populations, the timing of the epidemic peak, and the time at which the epidemic reaches a local population are mainly determined by the joint distribution of the local population sizes connected by the commuter flows, but are insensitive to geographical or topological structure of the network. Moreover, there is a strong relation between the population size and the time that the epidemic reaches this local population and we are able to determine the reason for this relation as well as its dependence on the commute network structure and epidemic parameters. This study shows that the model based on the connection between the population size classes is sufficient to predict both global and local epidemic dynamics in metropolitan area. Moreover, the clear relation of the time taken by the epidemic to reach each local population can be used as a novel measure for intervention; this enables efficient intervention strategies in each local population prior to the actual arrival.

In vivo imaging of hierarchical spatiotemporal activation of caspase-8 during apoptosis.

BACKGROUND: Activation of caspases is crucial for the execution of apoptosis. Although the caspase cascade associated with activation of the initiator caspase-8 (CASP8) has been investigated in molecular and biochemical detail, the dynamics of CASP8 activation are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We have established a biosensor based on fluorescence resonance energy transfer (FRET) for visualizing apoptotic signals associated with CASP8 activation at the single-cell level. Our dual FRET (dual-FRET) system, comprising a triple fusion fluorescent protein, enabled us to simultaneously monitor the activation of CASP8 and its downstream effector, caspase-3 (CASP3) in single live cells. With the dual-FRET-based biosensor, we detected distinct activation patterns of CASP8 and CASP3 in response to various apoptotic stimuli in mammalian cells, resulting in the positive feedback amplification of CASP8 activation. We reproduced these observations by in vitro reconstitution of the cascade, with a recombinant protein mixture that included procaspases. Furthermore, using a plasma membrane-bound FRET-based biosensor, we captured the spatiotemporal dynamics of CASP8 activation by the diffusion process, suggesting the focal activation of CASP8 is sufficient to propagate apoptotic signals through death receptors. CONCLUSIONS: Our new FRET-based system visualized the activation process of both initiator and effector caspases in a single apoptotic cell and also elucidated the necessity of an amplification loop for full activation of CASP8.