Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection

High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared with its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low, because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation.     

Asymptotic analysis of a TMDD model: when a reaction contributes to the destruction of its product

The multi-scale dynamics of a two-compartment with first order absorption Target-Mediated Drug Disposition (TMDD) pharmacokinetics model is analysed, using the Computational Singular Perturbation (CSP) algorithm. It is shown that the process evolves along two Slow Invariant Manifolds (SIMs), on which the most intense components of the model are equilibrated, so that the less intensive are the driving ones. The CSP tools allow for the identification of the components of the TMDD model that (i) constrain the evolution of the process on the SIMs, (ii) drive the system along the SIMs and (iii) generate the fast time scales. Among others, such diagnostics identify (i) the factors that determine the start and the duration of the period in which the ligand-receptor complex acts and (ii) the processes that determine its degradation rate. The counterintuitive influence of the process that transfers the ligand from the tissue to the main compartment, as it is manifested during the final stage of the process, is studied in detail.

     

A new model of reticulopodial motility and shape: evidence for a microtubule-based motor and an actin skeleton

Cytoskeletal inhibitors were used as probes to test the involvement of microtubules and actin microfilaments in the development, motility, and shape maintenance of the pseudopodial networks (i e, reticulopodia) of the foraminifers Allogromia sp strain NF and Allogromia laticollaris. Agents that disassemble cytoplasmic microtubules (cold, colchicine, and nocodazole) arrest all movement but have variable effects on reticulopodial shape. Electron microscopy reveals a granulofibrillar matrix but few, if any, microtubules in these motility-arrested reticulopods. Allogromiids treated with cytochalasin B or D lose substrate adhesion and undergo dramatic changes in shape and motile behavior, highlighted by the coalescence of reticulopodial cytoplasm into irregularly shaped bodies with chaotic motility. Serial semithick sections of such preparations, viewed by high-voltage electron microscopy, document a striking rearrangement of microtubules within these cytochalasin-induced bodies. All aspects of cytochalasin-altered motility are completely inhibited by colchicine. Actin is present in reticulopodia, as determined by staining with rhodamine-phalloidin; this staining is not observed in cytochalasin-treated organisms. These data provide compelling evidence that microtubules are required for reticulopodial motility. An actin-based cytoskeleton is thought to play a role in maintaining shape, mediating pseudopod/substrate adhesion, and coordinating the various microtubule-dependent processes.     

The folding and dimerization of HIV-1 protease: evidence for a stable monomer from simulations

HIV-1 protease (PR) is a major drug target in combating AIDS, as it plays a key role in maturation and replication of the virus. Six FDA-approved drugs are currently in clinical use, all designed to inhibit enzyme activity by blocking the active site, which exists only in the dimer. An alternative inhibition mode would be required to overcome the emergence of drug-resistance through the accumulation of mutations. This might involve inhibiting the formation of the dimer itself. Here, the folding of HIV-1 PR dimer is studied with several simulation models appropriate for folding mechanism studies. Simulations with an off-lattice Gō-model, which corresponds to a perfectly funneled energy landscape, indicate that the enzyme is formed by association of structured monomers. All-atom molecular dynamics simulations strongly support the stability of an isolated monomer. The conjunction of results from a model that focuses on the protein topology and a detailed all-atom force-field model suggests, in contradiction to some reported equilibrium denaturation experiments, that monomer folding and dimerization are decoupled. The simulation result is, however, in agreement with the recent NMR detection of folded monomers of HIV-1 PR mutants with a destabilized interface. Accordingly, the design of dimerization inhibitors should not focus only on the flexible N and C termini that constitute most of the dimer interface, but also on other structured regions of the monomer. In particular, the relatively high phi values for residues 23-35 and 79-87 in both the folding and binding transition states, together with their proximity to the interface, highlight them as good targets for inhibitor design.     

Nocturnal migratory songbirds adjust their travelling direction aloft: evidence from a radiotelemetry and radar study

In order to fully understand the orientation behaviour of migrating birds, it is important to understand when birds set their travel direction. Departure directions of migratory passerines leaving stopover sites are often assumed to reflect the birds'' intended travel directions, but this assumption has not been critically tested. We used data from an automated radiotelemetry system and a tracking radar at Falsterbo peninsula, Sweden, to compare the initial orientation of departing songbirds (recorded by radiotelemetry) with the orientation of songbird migrants in climbing and level flight (recorded by radar). We found that the track directions of birds at high altitudes and in level flight were more concentrated than the directions of departing birds and birds in climbing flight, which indicates that the birds adjust their travelling direction once aloft. This was further supported by a wide scatter of vanishing bearings in a subsample of radio-tracked birds that later passed an offshore radio receiver station 50 km southeast of Falsterbo. Track directions seemed to be more affected by winds in climbing compared with level flights, which may be explained by birds not starting to partially compensate for wind drift until they have reached cruising altitudes.     

Genetic evidence for long-term population decline in a savannah-dwelling primate: inferences from a hierarchical bayesian model

The purpose of this study was to test for evidence that savannah baboons (Papio cynocephalus) underwent a population expansion in concert with a hypothesized expansion of African human and chimpanzee populations during the late Pleistocene. The rationale is that any type of environmental event sufficient to cause simultaneous population expansions in African humans and chimpanzees would also be expected to affect other codistributed mammals. To test for genetic evidence of population expansion or contraction, we performed a coalescent analysis of multilocus microsatellite data using a hierarchical Bayesian model. Markov chain Monte Carlo (MCMC) simulations were used to estimate the posterior probability density of demographic and genealogical parameters. The model was designed to allow interlocus variation in mutational and demographic parameters, which made it possible to detect aberrant patterns of variation at individual loci that could result from heterogeneity in mutational dynamics or from the effects of selection at linked sites. Results of the MCMC simulations were consistent with zero variance in demographic parameters among loci, but there was evidence for a 10- to 20-fold difference in mutation rate between the most slowly and most rapidly evolving loci. Results of the model provided strong evidence that savannah baboons have undergone a long-term historical decline in population size. The mode of the highest posterior density for the joint distribution of current and ancestral population size indicated a roughly eightfold contraction over the past 1,000 to 250,000 years. These results indicate that savannah baboons apparently did not share a common demographic history with other codistributed primate species.     

Heterarchy in biological systems: a logic-based dynamical model of abstract biological network derived from time-state-scale re-entrant form

Heterarchical structure is important for understanding robustness and evolvability in a wide variety of levels of biological systems. Although many studies emphasize the heterarchical nature of biological systems, only a few computational representations of heterarchy have been created thus far. We propose here the time-state-scale re-entrant form to address the self-referential property derived from setting heterarchical structure. In this paper, we apply the time-state-scale re-entrant form to abstract self-referential modeling for a functional manifestation of biological network presented by [Tsuda, I., Tadaki, K., 1997. A logic-based dynamical theory for a genesis of biological threshold. BioSystems 42, 45-64]. The numerical results of this system show different intermittent phase transitions and power-law distribution of time spent in activating functional manifestation. The Hierarchically separated time-scales obtained from spectrum analysis imply that the reactions at different levels simultaneously appear in a dynamical system. The results verify the mutual inter-relationship between heterarchical structure in biological systems and the self-referential property of computational heterarchical systems.     

Properties of a new form of DNA from whole calf thymus nuclei: evidence for reactive, special sites in DNA

A new method for DNA preparation from whole calf thymus nuclei, which was designed to minimize enzymatic activity throughout to the greatest possible extent, is presented. The isolated DNA shows a number of interesting properties differing from those of DNA prepared by standard literature methods. The most important property is that the DNA prepared from our whole, purified nuclei, having originally a high molecular weight of 20.5 million, cleaved on EDTA treatment into a number of relatively homogeneous DNA fractions with a mean molecular weight of 2.3 million. In contrast, the standard DNA did not cleave on EDTA treatment. On the basis of this finding it was concluded that in the DNA backbone special sites exist at which cleavage can occur. These sites were further shown to occur in one of two possible forms: (1) fully covalent and (2) noncovalent. The proportion of the sites in form 1 increases with increasing ATP level. In standard DNA all special sites are most likely in the covalent form. It was also shown that for the conversion from one form to the other enzymes of the nucleus are necessary. The ATP level very probably controls this enzymatic activity in vivo.     

Characterization of ovarian surface epithelial cells from the hen: a unique model for ovarian cancer

To further develop the hen as a model of ovarian adenocarcinoma, we have studied normal and neoplastic ovaries as well as cultured cells from the ovarian surface epithelium (OSE). We characterized the OSE layer of the hen for specific histologic markers and evaluated these markers on tumor tissue. We also isolated and characterized the epithelial cells that are the likely source of the ovarian tumors of the hen. The surface epithelium of normal ovaries demonstrated positive staining for cytokeratin, proliferating cell nuclear antigen (PCNA), progesterone receptor (PR), and negative staining for vimentin. Ovarian tumors demonstrated positive cytokeratin, PCNA, PR, and weak vimentin staining in the gland-like areas. Epithelial cell cultures were obtained by an explant method utilizing small and large yellow follicles. These cells were positive for cytokeratin and negative for vimentin on Days 1 and 3. By Day 10, cytokeratin protein expression was less for some cells, and vimentin expression was weakly present in some cells. Expression of PCNA was observed at Days 1 and 3, but was rarely seen in cells cultured for 10 days. Expression of PR was observed on Day 10 after 24-hr estrogen treatment. Epithelial cells grew slowly in culture, and were susceptible to trypsin or other dissociation treatments.     

Coral reef ecosystems as a source of atmospheric CO2: evidence from PCO2 measurements of surface waters

 Precise measurements of the partial pressure of CO₂ (PCO₂) in oceanic and lagoonal surface waters from Palau Barrier Reef and Majuro Atoll were taken to ascertain the net effect of these coral reef systems on air-sea CO₂ exchange. PCO₂ in the surface water in the lagoon of Palau Barrier Reef and Majuro Atoll was 48 and 14 μatm higher than in the surrounding oceanic water, respectively. A total carbon dioxide vs. total alkalinity diagram indicates that calcification is mainly responsible for CO₂ evasion in these coral reef systems. Accepted: 31 March 1997     

Herbivore–vegetation feedbacks can expand the range of savanna persistence: insights from a simple theoretical model

Theoretical models of tree–grass coexistence in savannas have focused primarily on the role of resource availability and fire. It is clear that herbivores heavily impact vegetation structure in many savannas, but their role in driving tree–grass coexistence and the stability of the savanna state has received less attention. Theoretical models of tree–grass dynamics tend to treat herbivory as a constant rather than a dynamic variable, yet herbivores respond dynamically to changes in vegetation structure in addition to modifying it. In particular, many savannas host two distinct herbivore guilds, grazers and browsers, both of which have the potential to exert profound effects on tree/grass balance. For example, grazers may indirectly favor tree recruitment by suppressing the destructive effects of fire, and browsers may facilitate the expansion of grassland by reducing the competitive dominance of trees. We use a simple theoretical model to explore the role of grazer and browser dynamics on savanna vegetation structure and stability across fire and resource availability gradients. Our model suggests that herbivores may expand the range of conditions under which trees and grasses are able to stably coexist, as well as having positive reciprocal effects on their own niche spaces. In addition, we suggest that given reasonable assumptions, indirect mutualisms can arise in savannas between functional groups of herbivores because of the interplay of consumption and ecosystem feedbacks.     

Effects of temperature, potassium concentration, and sugar on human spermatozoa motility: a cell preservation model from reproductive medicine.

Two experiments were performed in vitro with human sperm from a panel of 11 donors. In both experiments, washed sperm from each donor were divided into four equivolume samples, three of which were resuspended in various formulations of Tyrode's solution and the fourth was resuspended in its own seminal plasma. Each of the four samples was then stored at 37 or 3 degrees C for fixed intervals of 0, 2, 6, 12, and 24 h. Motility was assessed at 37 degrees C for all samples at the end of each interval. The results indicate that sperm survival in vitro at 3 degrees C was significantly enhanced by 20 mM K+ in Tyrode's solution relative to Tyrode's with less K+. A metabolizable sugar such as glucose was essential to maintaining sperm viability in K(+)-free media. The addition of raffinose to media containing glucose improved motility of sperm stored at 3 degrees C for 6 h.     

The effect of heterogeneity on invasion in spatial epidemics: from theory to experimental evidence in a model system

Heterogeneity in host populations is an important factor affecting the ability of a pathogen to invade, yet the quantitative investigation of its effects on epidemic spread is still an open problem. In this paper, we test recent theoretical results, which extend the established "percolation paradigm" to the spread of a pathogen in discrete heterogeneous host populations. In particular, we test the hypothesis that the probability of epidemic invasion decreases when host heterogeneity is increased. We use replicated experimental microcosms, in which the ubiquitous pathogenic fungus Rhizoctonia solani grows through a population of discrete nutrient sites on a lattice, with nutrient sites representing hosts. The degree of host heterogeneity within different populations is adjusted by changing the proportion and the nutrient concentration of nutrient sites. The experimental data are analysed via Bayesian inference methods, estimating pathogen transmission parameters for each individual population. We find a significant, negative correlation between heterogeneity and the probability of pathogen invasion, thereby validating the theory. The value of the correlation is also in remarkably good agreement with the theoretical predictions. We briefly discuss how our results can be exploited in the design and implementation of disease control strategies.     

Biotic interactions as a structuring force in soil communities: evidence from the micro-arthropods of an Antarctic moss model system

Current meta-community theories postulate that the structure of local communities depends on dispersal, environmental filtering, and biotic interactions. However, disentangling the relative effects of these factors in the field and for diverse assemblages is a major challenge. A solution is to address natural but simple communities (i.e. with low numbers of species in few trophic levels), wherein one of these factors is predominant. Here, we analyse the micro-arthropod community of a moss-turf habitat typical of the Antarctic Peninsula region, and test the widely accepted hypothesis that this system is abiotically driven. In the austral summers 2006/7 and 2007/8, we sampled nearly 80 units of moss from four islands in the Argentine Islands. Using variance partitioning, we quantified the relative contribution of: (1) multiple scale spatio-temporal autocorrelation; (2) environmental effects; (3) the island effect. Little variance (1 %) was accounted for by sources 1 (1 %, significant) and 2 (<1 %, not significant). The island effect significantly accounted for the largest amount of variation (8 %). There was a relatively large effect of spatially structured environmental variation (7 %). Null models demonstrated that species co-occurred less frequently than expected by chance, suggesting the prevalence of negative interactions. Our data support the novel hypothesis that negative biotic interactions are the most important structuring force of this micro-arthropod community. The analysed system is a good proxy for more complex communities in terms of taxonomic composition and the functional groups present. Thus, biotic interaction might be a predominant factor in soil meta-community dynamics.     

Bivalent ligand dissociation kinetics from receptor-bound immunoglobulin E: evidence for a time-dependent increase in ligand rebinding at the cell surface.

The bivalent ligand N,N'-bis[[epsilon-[(2,4- dinitrophenyl)amino]caproyl]-L-tyrosyl]cystine [(DCT)2-Cys] binds and cross-links anti-dinitrophenyl (DNP) immunoglobulin E (IgE)-receptor complexes on the cell surface of rat basophilic leukemia cells. The rate of dissociation of this bound ligand was monitored by using a fluorescence method under two different conditions. In one case the monovalent ligand DCT was added in large excess to prevent the dissociating ligand from rebinding to unoccupied antibody combining sites. Under these conditions, dissociation of the bivalent ligand from IgE-sensitized cells proceeds to completion with kinetics that are well described by two rate constants that are independent of the time of preincubation of the bivalent ligand with the cells. In the second case, dissociation of (DCT)2-Cys from cell-bound anti-DNP IgE was monitored in the presence of a large excess of anti-DNP IgE in solution that acts as a sink to absorb the dissociated ligand. Under these conditions, the bivalent ligand becomes more resistant to dissociation as the preincubation time of the bivalent ligand with the cells is increased. An increasing fraction of the bound ligand does not dissociate on a measurable time scale in the presence of this sink. The results indicate that cell-associated IgE-receptor complexes undergo a time-dependent change that facilitates the reformation of the cross-linked state when one end of the ligand dissociates to break up the existing cross-link. The possible physical basis and functional implications of these results are discussed.     

Uridine insertion into preedited mRNA by a mitochondrial extract from Leishmania tarentolae: stereochemical evidence for the enzyme cascade model.

An RNA editing-like internal uridine (U) incorporation activity (G. C. Frech, N. Bakalara, L Simpson, and A. M. Simpson, EMBO J. 14:178-187, 1995) and a 3'-terminal U addition activity (N. Bakalara, A. M. Simpson, and L. Simpson, J. Biol. Chem. 264:18679-18686, 1989) have been previously described by using a mitochondrial extract from Leishmania tarentolae. Chiral phosphorothioates were used to investigate the stereoconfiguration requirements and the stereochemical course of these nucleotidyl transfer reactions. The extract utilizes (SP)-alpha-S-UTP for both 3' and internal U incorporation into substrate RNA. The internal as well as the 3' incorporation of (SP)-alpha-S-UTP proceeds via inversion of the stereoconfiguration. Furthermore, internal U incorporation does not occur at sites containing thiophosphodiesters of the RP configuration. Our results are compatible with an enzyme cascade model for this in vitro U insertion activity involving sequential endonuclease and uridylyl transferase directly from UTP and RNA ligase steps and are incompatible with models involving the transfer of U residues from the 3' ends of guide RNAs.