Biomedical subjects

Norio Yamamura

Publications and source records attributed to Norio Yamamura.

12 recordsLinked to original sources

PubMed2006

How to compute the effective size of spatiotemporally structured populations using separation of time scales.

Calculations to derive effective population size become highly complicated when complex population structure is considered. We provide an easy method of computing the effective size of a subdivided population with overlapping generations (a spatiotemporally structured population) using an approximation based on separation of time scales. We also numerically compute the effective size to verify the accuracy of the derived formula. Various interesting quantities, including moments of coalescent time, are readily derived using this approach.

Age Factors↗

PubMed2006

Evolution of talking plants in a tritrophic context: conditions for uninfested plants to attract predators prior to herbivore attack.

Herbivory induces plants to emit volatile chemicals that attract enemies of the herbivores (bodyguards of plants). In this way, the plant acquires protection and the bodyguards gain food. These plant signals cause neighboring plants, not under attack, to release signals as well. We hypothesize that such "secondary" signals help to reduce damage from future herbivore attacks by the protection received from the bodyguards. By modeling we explore the conditions for such secondary signals to evolve. Three kinds of strategies are considered: plants of the first strategy always emit a signal, those of the second strategy emit a signal only when infested, and those of the third strategy emit a signal not only when infested, but also when a certain number of neighbors are infested (i.e. secondary signaling). When signaling is much less (much more) costly than damage from herbivory, the first (second) strategy will be favored by selection, whereas for intermediate costs the third strategy, i.e. secondary signaling, will evolve. However, secondary signaling will not evolve when the primary signals lure the bodyguards too effectively. This is because the undamaged plant gains associational defense when the infested individual is defending very well; therefore, the need for secondary signaling decreases.

Animals↗

PubMed2005

Persistence conditions of symmetric social hybridogenesis in haplo-diploid hymenoptera.

In eusocial Hymenoptera species, females variably develop into either alate females (queens) or workers, and in most cases, caste differentiation is determined environmentally. Recently, however, female castes in two harvester ant species, Pogonomyrmex rugosus and P. barbatus, were found to be determined genetically in hybrid zones of these two species. In the hybrid populations, homozygous females (e.g. AA or BB) and heterozygous females (AB) develop into alate females and workers, respectively. This genetic caste determination system is called symmetric social hybridogenesis (SSH). It is clear that populations with SSH can persist only if all four genotypes (AA and BB females, and A and B males) coexist simultaneously. However, it is not obvious that these populations are always persistent when the four genotypes simultaneously exist. Here, we examined the stability and persistence of an SSH population using a simple mathematical model. According to the analysis of the model, the SSH population persists only when some conditions are satisfied: (1) each female mates with more than two males, and (2) male production increases less steeply than linearly with increasing numbers of workers in a colony, and alate female production increases more steeply than linearly with increasing numbers of workers, or (2') male production increases more steeply than linearly with increasing numbers of workers in a colony, and alate female production increases much more steeply than male production. Therefore, it is not obvious that SSH populations are maintained and are stable for long periods. We discuss whether these conditions are satisfied in real SSH populations.

Animals↗

PubMed2005

Bidirectional cytoplasmic incompatibility and the stable coexistence of two Wolbachia strains in parapatric host populations.

Wolbachiaare intracellular bacteria which are very widely distributed among arthropods. In many insect species Wolbachiaare known to induce cytoplasmic mating incompatibility (CI). It has been suggested that Wolbachiacould promote speciation in their hosts if parapatric host populations are infected with two different Wolbachiastrains causing bidirectional mating incompatibilities. A necessary condition for this speciation scenario to work is that the two Wolbachiastrains can stably coexist. The following study investigates this problem analysing a mathematical model with two host populations and migration between them. We show that the stability of bidirectional CI can be fully described in terms of a critical migration rate which is defined as the highest migration below which a stable coexistence of two Wolbachiastrains is possible. For some special cases we could derive analytical solutions for the critical migration rate; for the general case estimations of the critical migration rate are given. Our main finding is that bidirectional CI can stably persist in the face of high migration and can be as high as over 15% per generation for CI levels observed in nature. These results have implications for the potential of Wolbachiato promote genetic divergence and speciation in their hosts.

Animals↗

PubMed2004

Evolution of mutualism through spatial effects.

Mutualism among species is ubiquitous in natural ecosystems but its evolution is not well understood. We provided a simple lattice model to clarify the importance of spatial structure for the evolution of mutualism. We assumed reproductive rates of two species are modified through interaction between species and examine conditions where mutualists of both species, that give some benefit to the other species with their own cost, invade non-mutualists populations. When dispersal of offspring is unlimited, we verified the evolution of mutualism is impossible under any condition. On the other hand, when the dispersal is limited to neighboring lattice sites, mutualists can invade if the ratio of cost to benefit is low and the intrinsic reproductive rate is low in case where the parameter values are symmetric between species. Under the same conditions, non-mutualists cannot invade mutualist populations, that is, the latter are evolutionarily stable. In case of asymmetric parameters, mutualists tend to invade if the average value of costs to two species is low or that of benefits is high, and if the intrinsic reproductive rate is low for one of the two species. A mechanistic explanation of why mutualists increase when the dispersal is limited is given by showing that mutualist pairs of the two species at the same lattice site rapidly increase at the initial phase of the invasion.

Altruism↗

PubMed2004

Herbivory promotes plant production and reproduction in nutrient-poor conditions: effects of plant adaptive phenology.

Many studies have demonstrated positive effects of herbivory on plant performance, and these encompass two categories of effects: enhancement of primary production and enhancement of reproductive success. These positive responses of plants to herbivory have been called "grazing optimization." One possible mechanism of these paradoxical phenomena is the nutrient cycling promoted by herbivory. This article models the nutrient cycling hypothesis and analyzes the evolution of plant production and reproduction enhanced by herbivores, using dynamic optimization of plant phenology. Especially when there is nutrient competition among plant individuals or nutrient transportation by herbivores, we can apply the concept of evolutionary stability for the dynamic optimization. Two types of plant responses, long-term and short-term, are examined. Long-term response is an adaptive response for a given level of herbivory pressure, while short-term response is a nonadaptive one to various levels of herbivory, different from the level to which the plant is adapted. The analysis shows that both long-term and short-term grazing optimizations in primary production can occur under poor nutrient conditions and high nutrient recycling rates. However, grazing optimization in reproduction occurs under the same conditions but requires further conditions. In particular, long-term reproductive grazing optimization occurs only when nutrient competition exists among plant individuals. Accordingly, the present analysis revealed the following points concerning grazing optimization: poor nutrient condition is necessary, nutrient competition between plant individuals can promote optimization, and the native condition of the plant is important in the short-term response.

Adaptation, Physiological↗

PubMed2004

Pharmacokinetic comparison of an angiotensin II receptor antagonist, telmisartan, in Japanese and western hypertensive patients using population pharmacokinetic method.

The objectives of this study were to develop a population pharmacokinetic (PPK) model for telmisartan based on the pooled data obtained from the different racial populations and then to identify the factors that affect the pharmacokinetics of telmisartan for the comparison between the regions. A PPK model was established based on the data of 1343 subjects in 12 clinical trials. The PK profiles of telmisartan were described with a 2-compartment model with first-order absorption. The obtained model could predict the observed plasma concentrations well. This PPK model suggested that CL/F was a function of age, dose, gender, race, alcohol consumption and liver function. A marked difference was observed in the plasma concentration profiles between Japanese and other countries' subjects. However, the effect of the factor "race" on CL/F was not large. In the present PPK model, "trial condition" affected all PK parameters except for V(2)/F. The condition differences were in food condition and formulation (Japanese: fed, capsule, US and EU: fasted, tablet). The extent of difference in the plasma concentration profiles simulated for Japanese and Caucasian using the PPK model under the same demographic condition was comparable with the results of the food effect study performed previously in Japan. The findings suggest that the difference in the plasma concentration profiles between Japanese and other countries' subjects was mainly due to the difference of food intake conditions under which the clinical trials were performed.

Adult↗

PubMed2004

Relationship between pharmacokinetic parameters and occurrence of adverse events in clinical trials performed in Europe and United States for an angiotensin II receptor antagonist, telmisartan.

The objective of this study was to clarify the relationship between the pharmacokinetic parameters of telmisartan and the occurrence of adverse events. In order to perform this study, a total of 1500 adverse events was collected from the eight clinical trials performed in Europe and the United States and the pharmacokinetic parameters (C(max) and AUC) were calculated with the parameters obtained from the population pharmacokinetic model which we have built. Using these data, the pharmacokinetic parameters (C(max) and AUC) were compared between subjects with or without the occurrence of adverse events. The Mann-Whitney test was performed to analyze ten adverse events selected based on the order of frequency. For eight of these ten adverse events, no significant between-group difference was observed in any pharmacokinetic parameter. For two adverse events, pain and sinusitis, the pharmacokinetic parameters, C(max) and AUC, were greater in subjects with adverse events as compared with those without adverse events, but the intersubject variability of pharmacokinetic parameters was large and there were many subjects in whom C(max) and AUC were high without any adverse event. These results suggest that there is no clear relationship between pharmacokinetic parameters of telmisartan and the occurrence of adverse events.

Angiotensin Receptor Antagonists↗

PubMed2003

Evolution of signal emission by non-infested plants growing near infested plants to avoid future risk.

Several plant species indirectly defend themselves against herbivory by attracting natural enemies of herbivores by releasing signal chemicals when infested. Previous empirical research suggested that the chemical signals also reflexively induce signal emission by neighboring undamaged plants. We hypothesize that such a reflexively induced signal is a defensive strategy used by undamaged plants to avoid possible future risk. Using a mathematical model, we show that this defense against future risk can evolve if the following conditions are met: (1) the cost of the signal is small relative to the cost of damage by infestation, (2) the attractiveness of the signal to natural enemies is positively correlated with the local density of the signal chemical, (3) plants with infested neighbors are at greater risk than those without infested neighbors, and (4) the lifespan of plants is long compared with that of herbivores. We also discuss the relationship between our model and recent models of the evolution of cooperation.

Animals↗

PubMed2003

Population pharmacokinetics of an angiotensin II receptor antagonist, telmisartan, in healthy volunteers and hypertensive patients.

OBJECTIVE: To describe the factors affecting pharmacokinetics of telmisartan, an angiotensin II receptor antagonist, a population pharmacokinetic (PPK) model has been developed based upon the data collected from healthy volunteers and hypertensive patients. METHODS: A total of 1566 plasma samples were collected from 20 healthy volunteers and 129 hypertensive patients, together with the demographic background. The data were analyzed by the NONMEM program using two-compartment model with first-order absorption. The robustness of the obtained PPK model was validated by the bootstrapping resampling method. RESULTS: The oral clearance (CL/F) was found to be associated with age, dose and alcohol consumption, but neither related to serum creatinine nor smoking history. The volume of distribution for the central compartment was related to age and dose, and the volume of distribution for the peripheral compartment was related to body weight and gender. The absorption rate constant (Ka) and the absorption lag time were described as function of dose. The CL/F decreased with advanced age. The CL/F decreased and Ka increased with higher dose, reflecting the super-proportional increase in the plasma levels of telmisartan. The AUC and C(max) values predicted by the present PPK model were well consistent with the observed values. The means of parameter estimates obtained with 200 bootstrap replicates were within 95-111% of the final parameter estimates from the original data set. CONCLUSION: A PPK model for telmisartan developed here well described the individual variability and exposure, and robustness of the model has been validated by the bootstrapping method.

Journal Article↗

PubMed2002

Soldier production strategy in lower termites: from young instars or old instars?

We constructed a mathematical model to explain from which instars soldiers should be produced to maximize the growth rate of a termite colony. The model is based on the demography of the lower termite's colony: many of them feed inside the nest. The model predicts the following: (1) When the colony is young (it still has enough food and needs a high ratio of soldiers to workers) it will produce soldiers from young instars. (2) When the colony is old (it does not have enough food any more and needs a lower ratio of soldiers to workers) it will produce soldiers from old instars. This prediction fits well with the fact investigated by past empirical researches. With the samples of colonies of Neotermes koshunensis, we measured the antennal joint number of soldiers of each colony. We plotted the antennal joint number (1) of the average and (2) of the maximum one for each colony, against the total number of colony members. For both in each colony, we confirmed the consistency between the model and the samples: as the colony matures, it produces soldiers from older instars. The model also explains why higher termites produce soldiers from fixed instars. Their life style, in which they go outside to collect food, does not require a change in their soldier production strategy.

Aging↗

PubMedDate not supplied

A Tc-99m-labeled long chain fatty acid derivative for myocardial imaging.

C-11- and I-123-labeled long chain fatty acid derivatives have been reported as useful radiopharmaceuticals for the estimation of myocardial fatty acid metabolism. We have reported that Tc-99m-labeled N-[[[(2-mercaptoethyl)amino]carbonyl]methyl]-N-(2-mercaptoethyl)-6-aminohexanoic acid ([(99m)Tc]MAMA-HA), a medium chain fatty acid derivative, is metabolized by beta-oxidation in the liver and that the MAMA ligand is useful for attaching to the omega-position of fatty acid derivatives as a chelating group for Tc-99m. On the basis of these findings, we focused on developing a Tc-99m-labeled long chain fatty acid derivative that reflected fatty acid metabolism in the myocardium. In this study, we synthesized a dodecanoic acid derivative, MAMA-DA, and a hexadecanoic acid derivative, MAMA-HDA, and performed radiolabeling and biodistribution studies. [(99m)Tc]MAMA-DA and [(99m)Tc]MAMA-HDA were prepared using a ligand-exchange reaction. Biodistribution studies were carried out in normal mice and rats. Then, a high initial uptake of Tc-99m was observed, followed by a rapid clearance from the heart. The maximum heart/blood ratio was 3.6 at 2 min postinjection of [(99m)Tc]MAMA-HDA. These kinetics were similar to those with postinjection of p-[(125)I]iodophenylpentadecanoic acid. Metabolite analysis showed [(99m)Tc]MAMA-HDA was metabolized by beta-oxidation in the body. In conclusion, [(99m)Tc]MAMA-HDA is a promising compound as a long chain fatty acid analogue for estimating beta-oxidation of fatty acid in the heart.

Animals↗