Characterization and comparison of protein complexes initiated by the intracellular domain of individual Notch paralogs

The Notch signaling pathway is essential for embryonic development, organogenesis, and tissue homeostasis. Aberrant Notch signaling is associated with several types of cancers. The active form of Notch receptor is its intracellular domain (NICD), which is released from the cell membrane by serial proteolytic cleavages following ligand binding. Dose-dependent effects of NICD on cellular phenotypes have been observed under several conditions although the underlying mechanisms have not been well studied. Moreover, there are four mammalian Notch paralogs that have redundant as well as unique functions. The molecular basis for this variability is also not well understood. In this study, we used size exclusion chromatography to examine the overall distribution of NICD among NICD-containing protein complexes under conditions of increasing NICD abundance. We found that the assembly of NICD protein complexes was dose-dependent and that the abundance of the canonical complex was limited by, MAML, one of the proteins involved in the formation of canonical NICD transactivation complex, which became saturated with increasing NICD abundance. In addition, N4ICD showed a unique elution profile among the four NICDs. These results help to explain the dose-dependent and paralog-specific activities of NICD. These results are informative for the development of new reagents to block Notch signaling for therapeutic benefit.     

The species-area relation I. A model for discrete sampling

A simple mathematical model describing the species-area relation was developed. This paper dealt with the case that discrete random samples are combined. Modelling was made on the assumption that the occurrence probability of a species in a quadrat has a continuous density distribution. The model, given by the equation (6), holds only for a particular size of quadrat (i.e. the characteristic area). More general form applicable to the quadrats the size of which is near to the characteristic area was represented by the equation (9). Validity of the model was examined for the data of plant and insect communities, and it was concluded that the observation can be predicted by the model unless the size of sampling unit considerably differs from the characteristic area. The uniformity of specific density (i. e. the number of species per quadrat) and the size of characteristic area were discussed as being important in an understanding of community structure.     

A critique of the «increasing population density effect»

The «increasing population density effect» (IPDE) proposed by Macchiarelli and Bondioli (1986) represents one of the most recent attempts to account for dental reduction in modern human populations. Under the IPDE, the marked reduction in tooth size observed in post-Pleistocene human groups is seen as merely a side-effect of a more general reduction in body size, which resulted from an increase in population density. The model is dependent upon a strong correlation between tooth size and body size, which after numerous attempts has yet to be convincingly demonstrated in humans. This paper argues that the IPDE neglects the negative consequences on individual fitness of teeth which are too large to fit into diminishing jaws or are more susceptible to pathology, and that the worldwide reduction of tooth size is the result of selection for smaller teeth due to shifts to a softer and/or more cariogenic diet. Although increased population density may have intensified this selective effect by decreasing general fitness by lowering resistance to oral infections, it was not the primary cause of dental reduction. All proposed mechanisms of dental reduction, however, are in need of additional testing, and possible directions are offered for future studies of the phenomenon.     

Relationships between body size,reproductive traits,and food resource in three species of tropical flesh flies

Intra- and inter-specific comparisons in progeny size and clutch size were used to identify possible selection pressures acting on three sympatric species of ovoviviporous flesh flies. Both progeny and clutch sizes increased with body weight of the female parent in all species. There was no evidence for a simple trade-off between the two traits. In one species, the larger the female adult the smaller the relative biomass of larvae per clutch (total weight of larvae/body weight of female parent). Female flies produced similar progeny and clutch sizes over successive batches. Variation in progeny size did not influence either larval survival or duration of larval and pupal development. However, larger first instar larvae tended to form larger pupae in two of the species. The experiments testing the effect of progeny size on pupal weight under limited food conditions suggest a selective advantage for larger progeny size.     

Harvest-induced maturation evolution under different life-history trade-offs and harvesting regimes

The potential of harvesting to induce adaptive changes in exploited populations is now increasingly recognized. While early studies predicted that elevated mortalities among larger individuals select for reduced maturation size, recent theoretical studies have shown conditions under which other, more complex evolutionary responses to size-selective mortality are expected. These new predictions are based on the assumption that, owing to the trade-off between growth and reproduction, early maturation implies reduced growth. Here we extend these findings by analyzing a model of a harvested size-structured population in continuous time, and by systematically exploring maturation evolution under all three traditionally acknowledged costs of early maturation: reduced fecundity, reduced growth, and/or increased natural mortality. We further extend this analysis to the two main types of harvest selectivity, with an individual's chance of getting harvested depending on its size and/or maturity stage. Surprisingly, we find that harvesting mature individuals not only favors late maturation when the costs of early maturation are low, but promotes early maturation when the costs of early maturation are high. To our knowledge, this study therefore is the first to show that harvesting mature individuals can induce early maturation.     

Evolution of longevity through optimal resource allocation

Models of life history evolution predict optimal traits of a simplified organism under various environmental conditions, but they at most acknowledge the existence of ageing. On the other hand, genetic models of ageing do not consider the effects of ageing on life histroy traits other than fecundity and longevity. This paper reports the results of a dynamic programming model which optimizes resource allocation to growth, reproduction and somatic repair. A low extrinsic (environmentally caused) mortality rate and high repair efficiency promote allocation to repair, especially early in life, resulting in delayed ageing and low growth rates, delayed maturity, large body size and dramatic enhancement of survival and maximum lifespan. The results are generally consistent with field, comprative and experimental data. They also suggest that the relationships between maximum lifespan and age at maturity and body size observed in nature may be by-products of optimal allocation strategies.     

On the (dis) advantages of cannibalism

Cannibalism is an interaction between individuals that can produce counter- intuitive effects at the population level. A striking effect is that a population may persist under food conditions such that the non-cannibalistic variant is doomed to go extinct. This so-called life boat mechanism has received considerable attention. Implicitly, such studies sometimes suggest, that the life boat mechanism procures an evolutionary advantage to the cannibalistic trait. Here we compare, in the context of a size structured population model, the conditions under which the life boat mechanism works, with those that guarantee, that a cannibalistic mutant can invade successfully under the steady environmental conditions as set by a non-cannibalistic resident. We find qualitative agreement and quantitative difference. In particular, we find that a prerequisite for the life boat mechanism is, that cannibalistic mutants are successful invaders. Roughly speaking, our results show that cannibalism brings advantages to both the individuals and the population when adult food is limiting.     

Numerical solution of structured population models

Numerical methods are presented for a general mass-structured population model with demographic rates that depend on individual mass, time, and total population mass. Several types of numerical methods are described, Eulerian methods, implicit methods, and the method of characteristics. These methods are compared for a sample problem with an exact solution. The preferred numerical technique combines the method of characteristics with an adaptive grid. Numerical solution of model equations developed for mosquitofish illustrates this method and demonstrates how seasons can play a dominant role in shaping population development.     

Dental reduction in post-pleistocene Nubia

Tooth size changes among Nubian archaeological populations dating from the Mesolithic through the Christian era, a period of approximately 12,000 years, are analyzed. Standard length and breadth dimensions of all permanent teeth from several cultural horizons are combined to form three large samples: Mesolithic, 10000-70000 B.C.; Agriculturalist, 3300-1100 B.C. (A-group, C-group, Pharaonic); and Intensive Agriculturalist, A.D. 0-1400 (Meroitic, X-Group, Christian). Such information not only fills a void in the knowledge of Nubian skeletal biology, but also provides a much needed African reference point for the comparison of tooth size data among anatomically modern Homo sapiens from various regions of the world. Changes in mean tooth size and associated t-tests reveal strong and significant reduction in dental size between the Mesolithic and Agriculturalist samples, followed by a continued although diminished trend of reduction for only the molar teeth between the two Agriculturalist groups. These patterns are best observed by examining tooth breadths, which are considered as the most reliable indicator of tooth size. Previously published odontometrics of the Nubian Mesolithic are briefly compared to the findings of this diachronic analysis of Nubian dental change.     

Of mice and wrens: the relation between abundance and geographic range size in British mammals and birds

We examine the relation between population size and geographic range size for British breeding birds and mammals. As for most other assemblages studied, a strong positive interspecific correlation is found in both taxa. The relation is also recovered once the phylogenetic relatedness of species has been controlled for using an evolutionary comparative method. The slope of the relation is steeper for birds than for mammals, but this is due in large part to two species of mammals that have much higher population sizes than expected from their small geographic ranges. These outlying mammal species are the only ones in Britain to be found only on small offshore islands, and so may be exhibiting density compensation effects. With them excluded, the slope of the abundance–range size relation for mammals is not significantly different to that for birds. However, the elevation of the relation is higher for mammals than for birds, indicating that mammals are approximately 30 times more abundant than birds of equivalent geographic range size. An earlier study of these assemblages showed that, for a given body mass, bats had abundances more similar to birds than to non-volant mammals, suggesting that the difference in abundance between mammals and birds might be due to constraints of flight. Our analyses show that the abundance–range size relation for bats is not different for that from other mammals, and that the anomalously low abundance of bats for their body mass may result because they have smaller than expected geographic extents for their size. Other reasons why birds and mammals might have different elevations for the relation between population size and geographic range size are discussed, together with possible reasons for why the slopes of these relations might be similar.     

Abalone I: Analyzing Mark-Recapture-Recovery Data Incorporating Growth and Delayed Recovery

Abalone are semimobile marine gastropods that form the basis of Australia's second most valuable fishery. A site off the coast of Port Arthur, Tasmania, was visited on six occasions. On each occasion, any unmarked live abalone found were marked with a unique identification number and were recorded. Any previously marked abalone found had its identification number and whether or not it was still alive recorded. This results in integrated mark-recapture-recovery data, as in Catchpole et al. (1998, Biometrics 54, 33-46). During the study period, abalone grew in size, and we model the survival of individuals as a function of their size, estimated from a fitted growth curve. The shells of dead animals are long lasting, and we extend existing methodology to allow for the possibility that an animal found dead may have been dead but overlooked for several visits.     

Some beneficial effects of aggregation in young larvae ofPryeria sinica moore (Lepidoptera: Zygaenidae)

The effects of group size on the survival and development of young larvae of Pryeria sinicaMoore were investigated by laboratory and field experiments. Under laboratory conditions, about 20% of isolated larvae died of unsuccessful feeding in the first instar, however, larvae survived successfully in aggregations of four or more individuals. In the field, larvae emerge in early spring and wait for new leaves to open before feeding. In this period, the larger the group size of hatchlings the survival rate became higher. The nest-web spun by hatchlings was considered to play an important role in protecting them from desiccation. In the period that larvae began to feed on leaves, more than 36 larvae are necessary to aggregate for the successful establishment of feeding groups. The nest-web played an important role also in the establishment of feeding group. However, the natural group size of the first instar larvae was larger than the minimum group size to spin a sound nest-web in the field experiment. On the other hand, in later stage, larvae in a large group did not have an excess advantage in survival or developmental rate over larvae in a small group. It was found that the experiments on survival and developmental rates could not explain the reason that this species maintain large compact groups in the most part of larval period.     

Periodicity in an epidemic model with a generalized non-linear incidence

We develop and analyze a simple SIV epidemic model including susceptible, infected and perfectly vaccinated classes, with a generalized non-linear incidence rate subject only to a few general conditions. These conditions are satisfied by many models appearing in the literature. The detailed dynamics analysis of the model, using the Poincaré index theory, shows that non-linearity of the incidence rate leads to vital dynamics, such as bistability and periodicity, without seasonal forcing or being cyclic. Furthermore, it is shown that the basic reproductive number is independent of the functional form of the non-linear incidence rate. Under certain, well-defined conditions, the model undergoes a Hopf bifurcation. Using the normal form of the model, the first Lyapunov coefficient is computed to determine the various types of Hopf bifurcation the model undergoes. These general results are applied to two examples: unbounded and saturated contact rates; in both cases, forward or backward Hopf bifurcations occur for two distinct values of the contact parameter. It is also shown that the model may undergo a subcritical Hopf bifurcation leading to the appearance of two concentric limit cycles. The results are illustrated by numerical simulations with realistic model parameters estimated for some infectious diseases of childhood.     

Size-structured demographic models of coral populations

The demographic processes of growth, mortality, and the recruitment of young individuals, are the major organizing forces regulating communities in open systems. Here we present a size-structured (rather than age-structured) population model to examine the role of these different processes in space-limited open systems, taking coral reefs as an example. In this flux-diffusion model the growth rate of corals depends both on the available free-space (i.e. density-dependence) and on the particular size of the coral. In our analysis we progressively study several different forms of growth rate functions to disentangle the effects of free space and size-dependence on the model's stability. Unlike Roughgarden et al. [1985. Demographic theory for an open marine population space-limited recruitment. Ecology 66(1), 54-67], whose principal result is that the growth of settled organisms is destabilizing, we find that size-dependent growth rate often has the potential to endow stability. This is particularly true, if the growth rate is dependent on available free space (i.e. density dependent), but examples are given for growth rates that even lack this property. Further insights into reef system fragility are found through studying the sensitivity of the model steady state to changes in recruitment.     

Size distribution dependence of prion aggregates infectivity

We consider a model for the polymerization (fragmentation) process involved in infectious prion self-replication and study both its dynamics and non-zero steady state. We address several issues. Firstly, we extend a previous study of the nucleated polymerization model [M.L. Greer, L. Pujo-Menjouet, G.F. Webb, A mathematical analysis of the dynamics of prion proliferation, J. Theoret. Biol. 242 (2006) 598; H. Engler, J. Pruss, G.F. Webb, Analysis of a model for the dynamics of prions II, J. Math. Anal. Appl. 324 (2006) 98] to take into account size dependent replicative properties of prion aggregates. This is achieved by a choice of coefficients in the model that are not constant. Secondly, we show stability results for this steady state for general coefficients where reduction to a system of differential equations is not possible. We use a duality method based on recent ideas developed for population models. These results confirm the potential influence of the amyloid precursor production rate in promoting amyloidogenic diseases. Finally, we investigate how the converting factor may depend upon the aggregate size. Besides the confirmation that size-independent parameters are unlikely to occur, the present study suggests that the PrPsc aggregate size repartition is amongst the most relevant experimental data in order to investigate this dependence. In terms of prion strain, our results indicate that the PrPsc aggregate repartition could be a constraint during the adaptation mechanism of the species barrier overcoming, that opens experimental perspectives for prion amyloid polymerization and prion strain investigation.     

The Temperature–Size Rule in Lecane inermis (Rotifera) is adaptive and driven by nuclei size adjustment to temperature and oxygen combinations

The evolutionary implications of the Temperature–Size Rule (TSR) in ectotherms is debatable; it is uncertain whether size decrease with temperature increase is an adaptation or a non-adaptive by-product of some temperature-dependent processes. We tested whether (i) the size of the rotifer Lecane inermis affects fecundity in a way that depends on the combination of low or high temperature and oxygen content and (ii) the proximate mechanism underlying TSR in this species is associated with nuclei size adjustment (a proxy of cell size).Small-type and large-type rotifers were obtained by culturing at different temperatures prior to the experiment and then exposed to combinations of two temperature and two oxygen conditions. Fecundity was estimated and used as a measure of fitness. Nuclei and body sizes were measured to examine the response to both environmental factors tested.The results show the following for L. inermis. (i) Body size affects fecundity in response to both temperature and oxygen, supporting a hypothesis regarding the contribution of oxygen in TSR. (ii) Large individuals are generally more fecund than small ones; however, under a combination of high temperature and poor oxygen conditions, small individuals are more fecund than large ones, in accordance with a hypothesis of the adaptive significance of TSR. (iii) The body size response to temperature is realised by nuclei size adjustment. (iv) Nuclei size changes in response to temperature and oxygen conditions, in agreement with hypotheses on the cellular mechanism underlying TSR and on a contribution of oxygen availability in TSR. These results serve as empirical evidence for the adaptive significance of TSR and validation of the cellular mechanism for the observed response.     

Darwinian selection leads to Gaia

The Gaia hypothesis, in its strongest form, states that the Earth's atmosphere, oceans, and biota form a tightly coupled system that maintains environmental conditions close to optimal for life. According to Gaia theory, optimal conditions are intrinsic, immutable properties of living organisms. It is assumed that the role of Darwinian selection is to favor organisms that act to stabilize environmental conditions at these optimal levels. In this paper, an alternative form of Gaia theory based on more traditional Darwinian principles is proposed. In the new approach, environmental regulation is a consequence of population dynamics, not Darwinian selection. The role of selection is to favor organisms that are best adapted to prevailing environmental conditions. However, the environment is not a static backdrop for evolution, but is heavily influenced by the presence of living organisms. The resulting co-evolving dynamical process eventually leads to the convergence of equilibrium and optimal conditions. A simple Daisyworld model is used to illustrate this convergence phenomenon. Sensitivity analysis of the Daisyworld model suggests that in stable ecosystems, the convergence of equilibrium and optimal conditions is inevitable, provided there are no externally driven shocks to the system. The end result may appear to be the product of a cooperative venture, but is in fact the outcome of Darwinian selection acting upon "selfish" organisms.