病毒感染的动态模型

以SARS病毒为例,从病毒在宿主细胞内的复制和在细胞间的传播两个方面建立了数学模型,对模型平衡点的稳定性和分岔类型做出了初步分析,同时讨论了不同个体的免疫力和病毒感染能力之间的关系.由此可定性地认识病毒在宿主体内的动态特征,以了解病毒的致病机理.本文还对模型提出进一步研究的方向.     

Dynamic dissociating homo-oligomers and the control of protein function

Homo-oligomeric protein assemblies are known to participate in dynamic association/disassociation equilibria under native conditions, thus creating an equilibrium of assembly states. Such quaternary structure equilibria may be influenced in a physiologically significant manner either by covalent modification or by the non-covalent binding of ligands. This review follows the evolution of ideas about homo-oligomeric equilibria through the 20th and into the 21st centuries and the relationship of these equilibria to allosteric regulation by the non-covalent binding of ligands. A dynamic quaternary structure equilibria is described where the dissociated state can have alternate conformations that cannot reassociate to the original multimer; the alternate conformations dictate assembly to functionally distinct alternate multimers of finite stoichiometry. The functional distinction between different assemblies provides a mechanism for allostery. The requirement for dissociation distinguishes this morpheein model of allosteric regulation from the classical MWC concerted and KNF sequential models. These models are described alongside earlier dissociating allosteric models. The identification of proteins that exist as an equilibrium of diverse native quaternary structure assemblies has the potential to define new targets for allosteric modulation with significant consequences for further understanding and/or controlling protein structure and function. Thus, a rationale for identifying proteins that may use the morpheein model of allostery is presented and a selection of proteins for which published data suggests this mechanism may be operative are listed.     

An SIS epidemiology game with two subpopulations

There is significant current interest in the application of game theory to problems in epidemiology. Most mathematical analyses of epidemiology games have studied populations where all individuals have the same risks and interests. This paper analyses the rational-expectation equilibria in an epidemiology game with two interacting subpopulations of equal size where decisions change the prevalence and transmission patterns of an infectious disease. The transmission dynamics are described by an SIS model and individuals are only allowed to invest in daily prevention measures like hygiene. The analysis shows that disassortative mixing may lead to multiple Nash equilibria when there are two interacting subpopulations affecting disease prevalence. The dynamic stability of these equilibria is analysed under the assumption that strategies change slowly in the direction of self-interest. When mixing is disassortative, interior Nash equilibria are always unstable. When mixing is positively assortative, there is a unique Nash equilibrium that is globally stable.     

An SIS epidemiology game with two subpopulations

There is significant current interest in the application of game theory to problems in epidemiology. Most mathematical analyses of epidemiology games have studied populations where all individuals have the same risks and interests. This paper analyses the rational-expectation equilibria in an epidemiology game with two interacting subpopulations of equal size where decisions change the prevalence and transmission patterns of an infectious disease. The transmission dynamics are described by an SIS model and individuals are only allowed to invest in daily prevention measures like hygiene. The analysis shows that disassortative mixing may lead to multiple Nash equilibria when there are two interacting subpopulations affecting disease prevalence. The dynamic stability of these equilibria is analysed under the assumption that strategies change slowly in the direction of self-interest. When mixing is disassortative, interior Nash equilibria are always unstable. When mixing is positively assortative, there is a unique Nash equilibrium that is globally stable.     

Global dispersal reduces local diversity

Metapopulation models and stepping-stone models in genetics are based on very different underlying dispersal structures, yet it can be difficult to distinguish the behaviour of the two kinds of models. We demonstrate a striking qualitative difference in the equilibrium behaviour possible with these two kinds of dispersal. If, in a local patch, there are multiple stable equilibria (and consequently an unstable equilibrium), we demonstrate that, for the spatial system with a metapopulation structure, at equilibrium every patch has to be near one of the stable equilibria. This contrasts with the clinal structure possible with a stepping-stone or continuous space model; thus the result can be used to deduce qualitative information about the form of dispersal from observations of allele frequencies.     

Grazers and Diggers: Exploitation Competition and Coexistence among Foragers with Different Feeding Strategies on a Single Resource

A mathematical model is presented that describes a system where two consumer species compete exploitatively for a single renewable resource. The resource is distributed in a patchy but homogeneous environment; that is, all patches are intrinsically identical. The two consumer species are referred to as diggers and grazers, where diggers deplete the resource within a patch to lower densities than grazers. We show that the two distinct feeding strategies can produce a heterogeneous resource distribution that enables their coexistence. Coexistence requires that grazers must either move faster than diggers between patches or convert the resources to population growth much more efficiently than diggers. The model shows that the functional form of resource renewal within a patch is also important for coexistence. These results contrast with theory that considers exploitation competition for a single resource when the resource is assumed to be well mixed throughout the system.     

Effect of Spatial Dispersion on Evolutionary Stability: A Two-Phenotype and Two-Patch Model

In this paper, we investigate a simple two-phenotype and two-patch model that incorporates both spatial dispersion and density effects in the evolutionary game dynamics. The migration rates from one patch to another are considered to be patch-dependent but independent of individual’s phenotype. Our main goal is to reveal the dynamical properties of the evolutionary game in a heterogeneous patchy environment. By analyzing the equilibria and their stabilities, we find that the dynamical behavior of the evolutionary game dynamics could be very complicated. Numerical analysis shows that the simple model can have twelve equilibria where four of them are stable. This implies that spatial dispersion can significantly complicate the evolutionary game, and the evolutionary outcome in a patchy environment should depend sensitively on the initial state of the patches.     

Blocking HTLV-1/2 silent transmission in Brazil: Current public health policies and proposal for additional strategies

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.     

Expression of human telomerase (hTERT) does not prevent stress-induced senescence in normal human fibroblasts but protects the cells from stress-induced apoptosis and necrosis

Cells subjected to sub-lethal doses of stress such as irradiation or oxidative damage enter a state that closely resembles replicative senescence. What triggers stress-induced premature senescence (SIPS) and how similar this mechanism is to replicative senescence are not well understood. It has been suggested that stress-induced senescence is caused by rapid telomere shortening resulting from DNA damage. In order to test this hypothesis directly, we examined whether overexpression of the catalytic subunit of human telomerase (hTERT) can protect cells from SIPS. We therefore analyzed the response of four different lines of normal human fibroblasts with and without hTERT to stress induced by UV, gamma-irradiation, and H(2)O(2). SIPS was induced with the same efficiency in normal and hTERT-immortalized cells. This suggests that SIPS is not triggered by telomere shortening and that nonspecific DNA damage serves as a signal for induction of SIPS. Although telomerase did not protect cells from SIPS, fibroblasts expressing hTERT were more resistant to stress-induced apoptosis and necrosis. We hypothesize that healing of DNA breaks by telomerase inhibits the induction of cell death, but because healing does not provide legitimate DNA repair, it does not protect cells from SIPS.     

Consequences of cyclic vegetation management for arthropod survival: Simulation experiments

Many rare arthropod species occupy open grasslands. Mowing or grazing is needed to preserve the habitat for these species. Alternatively the vegetation cover in parts of the managed area can be periodically destroyed by ploughing or rototilling. Such treatment results in a dynamic mosaic of habitat patches in different stages of succession. This mosaic may serve as a habitat for many species. However, the interplay between the frequency of rototilling, the spatial structure of the landscape and life history attributes of the animal species will determine the success of such cyclic management strategies. We used a spatially implicit individual-based metapopulation model to examine optimal spatio-temporal management strategies. The model explicitly incorporates succession, population dynamics and dispersal between habitat patches.Optimal management patterns strongly depend on the species’ properties. Our simulation experiments show that in general the more fertile species with strong intraspecific competition are most robust against the large fluctuations of habitat quality resulting from cyclic management. However, the best management strategies found in our experiments cover the requirements of up to 70% of the species tested. Frequent management of relatively small sub-areas minimizes local fluctiations of patch capacity. Though reducing effective patch capacity by more than 50% these strategies may support the survival of the majority of species.     

Malaria Drug Resistance: The Impact of Human Movement and Spatial Heterogeneity

Human habitat connectivity, movement rates, and spatial heterogeneity have tremendous impact on malaria transmission. In this paper, a deterministic system of differential equations for malaria transmission incorporating human movements and the development of drug resistance malaria in an \(n\) patch system is presented. The disease-free equilibrium of the model is globally asymptotically stable when the associated reproduction number is less than unity. For a two patch case, the boundary equilibria (drug sensitive-only and drug resistance-only boundary equilibria) when there is no movement between the patches are shown to be locally asymptotically stable when they exist; the co-existence equilibrium is locally asymptotically stable whenever the reproduction number for the drug sensitive malaria is greater than the reproduction number for the resistance malaria. Furthermore, numerical simulations of the connected two patch model (when there is movement between the patches) suggest that co-existence or competitive exclusion of the two strains can occur when the respective reproduction numbers of the two strains exceed unity. With slow movement (or low migration) between the patches, the drug sensitive strain dominates the drug resistance strain. However, with fast movement (or high migration) between the patches, the drug resistance strain dominates the drug sensitive strain.     

Mating strategies in primates: a game theoretical approach to infanticide

Infanticide by newly immigrated or newly dominant males is reported among a variety of taxa, such as birds, rodents, carnivores and primates. Here we present a game theoretical model to explain the presence and prevalence of infanticide in primate groups. We have formulated a three-player game involving two males and one female and show that the strategies of infanticide on the males' part and polyandrous mating on the females' part emerge as Nash equilibria that are stable under certain conditions. Moreover, we have identified all the Nash equilibria of the game and arranged them in a novel hierarchical scheme. Only in the subspace spanned by the males are the Nash equilibria found to be strict, and hence evolutionarily stable. We have therefore proposed a selection mechanism informed by adaptive dynamics to permit the females to transition to, and remain in, optimal equilibria after successive generations. Our model concludes that polyandrous mating by females is an optimal strategy for the females that minimizes infanticide and that infanticide confers advantage to the males only in certain regions of parameter space. We have shown that infanticide occurs during turbulent changes accompanying male immigration into the group. For changes in the dominance hierarchy within the group, we have shown that infanticide occurs only in primate groups where the chance for the killer to sire the next infant is high. These conclusions are confirmed by observations in the wild. This model thus has enabled us to pinpoint the fundamental processes behind the reproductive decisions of the players involved, which was not possible using earlier theoretical studies.     

On the global stability of an epidemic model of computer viruses

In this paper, we study the global properties of a computer virus propagation model. It is, interesting to note that the classical method of Lyapunov functions combined with the Volterra–Lyapunov matrix properties, can lead to the proof of the endemic global stability of the dynamical model characterizing the spread of computer viruses over the Internet. The analysis and results presented in this paper make building blocks towards a comprehensive study and deeper understanding of the fundamental mechanism in computer virus propagation model. A numerical study of the model is also carried out to investigate the analytical results.     

Psychometric Properties of Prodromal Questionnaire-Brief Version among Chinese Help-Seeking Individuals

Prodromal Questionnaire (PQ) and Structured Interview for Prodromal Syndromes (SIPS) have been used as a two-stage process for identifying subjects at clinical high risk (CHR) of psychosis. The Prodromal Questionnaire-Brief version (PQ-B) contains 21 items derived from the PQ. The present study aimed to examine the psychometric properties of PQ-B in a Chinese help-seeking outpatient sample and to explore which items can better predict CHR diagnosis by SIPS and future transition to psychosis. In our preliminary epidemiological study, 1461 patients from a pool of 2101 individuals (15–45 years of age) completed the two-stage process. In the present study, 239 (20%) people were randomly selected among the sample who met the initial PQ-B screening criteria but had no positive diagnosis on SIPS, as well as 72 individuals with negative results on both PQ-B and SIPS, 89 prodromal and 105 psychotic subjects, yielding a total of 505 participants. The internal consistency coefficient for the PQ-B was good, with a Cronbach’s alpha of 0.897. The concordant validity of PQ-B with SIPS dichotomized diagnosis of prodrome/psychosis versus no psychosis was 0.54. To ensure 80% or a higher sensitivity and a certain specificity, 7 and 24 were respectively set as the cutoff points for the PQ-B total score and distress score for Chinese help-seeking outpatients. A logistic regression model based on six PQ-B items could allow predicting the psychotic diagnosis on SIPS, with an accuracy of 65.8%. Prodromal individuals who scored higher on the 12^th item of PQ-B (Do you worry at times that something may be wrong with your mind?) were less likely to convert to psychosis. PQ-B is a useful instrument for screening CHR subjects, but the cutoff score may be higher than that recommended by the author scores for help-seeking individuals in outpatient clinics. Some specific PQ-B items may have significant predictive power on dichotomized SIPS diagnoses and deserve special attention from researchers in future studies.     

高盐环境可培养细菌噬菌体的研究进展

病毒广泛存在于各类环境中并担负着重要的生态功能,其中包括高盐环境。对高盐环境病毒的研究已成为极端环境微生物研究领域的新热点,目前已被报道的100多株盐病毒中,90多株感染古菌,仅有14株感染细菌。本文综述了目前已知的14株高盐环境细菌噬菌体的形态特征、盐度响应及基因组学的研究进展,并分析了高盐噬菌体的形态多样性、生存策略以及包含在基因组中的进化和起源信息,分析结果表明:高盐噬菌体以有尾噬菌体为主;它们具有广盐性(Euryhaline)的特征,盐度极大地影响其吸附和增殖;它们与非高盐环境噬菌体可能具有共同的起源。高盐噬菌体虽然历经近30年的研究历程,但仅有14株被分离与培养,所以其分离纯化是今后重要工作之一,且结合免培养技术揭示高盐噬菌体的多样性与生态功能是其研究的发展方向。     

The Vibrio cholerae porins OmpU and OmpT have distinct channel properties

Numerous environmental signals regulate the production of virulence factors and the composition of the outer membrane of Vibrio cholerae. In particular, bile promotes the ToxR-dependent expression of the porin OmpU. Strains expressing solely OmpU are more resistant to bile, are better able to colonize the intestine, and produce more cholera toxin than strains expressing solely the OmpT porin. To gain some understanding in the physiological relevance and the molecular mechanism underlying these porin-dependent phenotypes, we have undertaken a thorough electrophysiological characterization of the channel properties of the two porins. Purified OmpU or OmpT was reconstituted in liposomes suitable for patch clamp and in planar lipid bilayers. The high resolution of the patch clamp technique allowed us to analyze in detail the behavior of single OmpU and OmpT channels. Both channels exhibit closing transitions to various conductance states. OmpT is a much more dynamic channel than OmpU, displaying frequent and prolonged closures, even at low transmembrane potentials. With a critical voltage for closure V(c) of approximately +/-90 mV, OmpT is much more voltage-sensitive than OmpU (with a V(c) of approximately +/-160 mV), a feature that is also readily apparent in the voltage dependence of closing probability observed in patch clamp in the +/-100 mV range. OmpT has low ionic selectivity (P(K)/P(Cl) = approximately 4), whereas OmpU is more cation-selective (P(K)/P(Cl) = approximately 14). The distinct functional properties of the two porins are likely to play an integrated role with environmental regulation of their expression. For example, the higher selectivity of OmpU for cations provides a possible explanation for the protective role played by this porin in a bile-containing environment, because this type of selectivity would restrict the flux of anionic bile salts through the outer membrane and thus would reduce the exposure of the cytoplasmic membrane to this natural detergent.     

Global analysis of a two-allele mating system

The global analysis of a two-allele mating system is provided. One allele is dominant to the other. Mating is random, but mating between unlike phenotypes has a lower fertility than that between like phenotypes. The generations are discrete and non-overlapping. The population is considered to be infinite, and the model is deterministic. There are three equilibria of the difference equations. Two of the equilibria are the (two) homozygous states, and these are asymptotically stable. The third equilibrium is polymorphic but is unstable. It is proven that almost all populations converge to one of the two homozygous states. The remaining populations converge to the unstable equilibrium, and lie on a curve that separates the basins of attraction for the other two equilibria. This curve is shown to satisfy some simple properties.     

Steric effects on multivalent ligand-receptor binding: exclusion of ligand sites by bound cell surface receptors.

Steric effects can influence the binding of a cell surface receptor to a multivalent ligand. To account for steric effects arising from the size of a receptor and from the spacing of binding sites on a ligand, we extend a standard mathematical model for ligand-receptor interactions by introducing a steric hindrance factor. This factor gives the fraction of unbound ligand sites that are accessible to receptors, and thus available for binding, as a function of ligand site occupancy. We derive expressions for the steric hindrance factor for various cases in which the receptor covers a compact region on the ligand surface and the ligand expresses sites that are distributed regularly or randomly in one or two dimensions. These expressions are relevant for ligands such as linear polymers, proteins, and viruses. We also present numerical algorithms that can be used to calculate steric hindrance factors for other cases. These theoretical results allow us to quantify the effects of steric hindrance on ligand-receptor kinetics and equilibria.     

Association of Paramecium bursaria Chlorella viruses with Paramecium bursaria cells: ultrastructural studies

Paramecium bursaria Chlorella viruses were observed by applying transmission electron microscopy in the native symbiotic system Paramecium bursaria (Ciliophora, Oligohymenophorea) and the green algae Chlorella (Chlorellaceae, Trebouxiophyceae). Virus particles were abundant and localized in the ciliary pits of the cortex and in the buccal cavity of P. bursaria. This was shown for two types of the symbiotic systems associated with two types of Chlorella viruses - Pbi or NC64A. A novel quantitative stereological approach was applied to test whether virus particles were distributed randomly on the Paramecium surface or preferentially occupied certain zones. The ability of the virus to form an association with the ciliate was investigated experimentally; virus particles were mixed with P. bursaria or with symbiont-free species P. caudatum. Our results confirmed that in the freshwater ecosystems two types of P. bursaria -Chlorella symbiotic systems exist, those without Chlorella viruses and those associated with a large amount of the viruses. The fate of Chlorella virus particles at the Paramecium surface was determined based on obtained statistical data and taking into account ciliate feeding currents and cortical reorganization during cell division. A life cycle of the viruses in the complete symbiotic system is proposed.     

Pairwise competition and the replicator equation

Spite in Hamilton’s sense is defined as the willingness to harm oneself in order to harm another more. The standard replicator dynamic predicts that evolutionarily stable strategies are payoff-maximizing equilibria of the underlying game, and hence rules out the evolution of spiteful behavior. We propose a modified replicator dynamic, where selection is based on local outcomes, rather than on the population ’state’, as in standard models. We show that under this new model spite can evolve readily. The new dynamic suggests conditions under which spite in animals might be found.