Cancer Cell Fitness Is Dynamic.

Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions. SIGNIFICANCE: Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug.

Reproductive site selection in a bromeliad breeding treefrog suggests complex evolutionary trade-offs.

Reproductive site selection is a key determinant of fitness in many taxa. However, if the site characteristics that enhance offspring survival are detrimental to the parent's survival or mating success, then complex evolutionary trade-offs occur. In the Brazilian Atlantic Forest, males of the treefrog species Aparasphenodon arapapa use the temporary water bodies in forest-floor bromeliads to court and mate. Males fit tightly into the plant with the head blocking the access and after mating, stay in the bromeliad with the offspring. Since evaporation of the temporary water body inside the bromeliad results in reproductive failure, we expected that males would simply choose the largest bromeliad tanks with the most water. We found that although this was generally true, males seemed to avoid both very large bromeliads and very high water volumes. Field observations suggested a trade-off mechanism for this pattern, whereby very large and water-filled tanks would reduce the male's ability to effectively seal the tank entrance, avoid predation, or call to mating females. Males also avoided bromeliads with leaf litter and preferred slightly inclined plants. Our results indicate that during reproductive site selection, this bromeliad-breeder needs to engage in complex trade-offs between selection pressures, balancing water requirements against the need for defense and potentially, the ability to attract a mate.

Fishery induces sperm depletion and reduction in male reproductive potential for crab species under male-biased harvest strategy.

Sperm depletion in males can occur when polygynous species are intensively exploited under a male-biased management strategy. In fisheries involving crabs species, the effects of this type of management on the reproductive potential is far from being understood. This study tests whether male-biased management of the principal Chilean crab fishery is able to affect the potential capacity of Metacarcinus edwardsii males to transfer sperm to females. Five localities in southern Chile, recording contrasting crab fishery landing, were selected to assess the potential of sperm depletion triggered by fishery. Seasonally, male crabs from each locality were obtained. Dry weight and histological condition of vasa deferentia and the Vaso-Somatic Index (VSI) were determined in order to use them as proxies for sperm depletion and male reproductive condition. A manipulative experiment was performed in the laboratory to estimate vasa deferentia weight and VSI from just-mated males in order to obtain a reference point for the potential effects of the fishery on sperm reserves. Sperm storage capacity is significantly affected by fisheries; during the mating season vasa deferentia from localities with low fishery intensity were heavier than those from high intensity fisheries, and these differences were even more evident in large males. Histological section showed that this disparity in vasa deferentia weight was explained principally by differences in the quantity of spermatophores rather than other seminal material. VSI was always higher in males from localities with low fishery intensity. Males from localities with high fishery intensity showed little capacity to recover sperm reserves and the VSI of these males remained below the values of the just-mated males. Detriment in the capacity of males to transfer sperm is the first step to sperm limitation in an exploited population, thus detection of sperm depletion can be an alert to introduce changes in the current management of crabs.

Organización de las redes cerebrales / Organization of brain networks

El procesamiento de información por el cerebro se basa en sistemas de redes (networks) que poseen propiedades estructurales y funcionales derivadas de su extrema complejidad. Al tratarse de sistemas complejos con propiedades dinámicos no lineares, las redes se auto organizan permanentemente para adecuarse tanto a los procesamientos rápidos, como en el caso de las funciones cognitivas o ejecutivas, como a las más lentas, derivadas de la capacidad de generar cambios plásticos para adaptarse a las situaciones cambiantes de los entornos externos e internos. El estudio de la conectividad en el SNC se ha sistematizado por teorías de gráficas, modelos simples de un sistema, basados en conjuntos de nodos y márgenes o bordes que poseen propiedades de pequeño mundo (ni azarística, ni regular) de modo tal que el conectoma se organiza en los pequeños volúmenes relativos del cerebro permietiendo una alta eficiencia a bajo costo dada la corta distancia ente nodos centrales que procesan gran cantidad de información. Las proyecciones largas entre regiones distantes del SNC si bien eficaces en las funciones integradoras son costosas en estructura y metabolismo, y por ello vulnerables tanto en el desarrollo como en patologías, como la enfermedad de Alzheimer, la esquizofreia, la epilepsia, el ADHD la esclerosis múltiple, etc. Se conceptualiza al conectoma como fenotipo intermedio o endofenotipo con características heredables modificables en las distintas etapas de la vida, desde el desarrollo pre y perinatal hasta el envejecimiento.

The processing of information by the brain is based on systems of networks that have both structural and functional properties, given their extreme complexity. Because they consist in complex systems with nonlinear dynamic properties, the networks organize themselves permanently to adjust either to quick processings, as is the case with cognitive or executive functions and to the slowest processings which result from the capability of generating plastic changes to adapt to the changing contexts of the external and internal environments. The study of connectivity in the CNS has been systematized by graphics theories, which consist in simple models of a system based on sets of nodes and margins or borders that have properties of a small-world network (neither at random nor regular), so that the connectome is organized in the small relative volumes of the brain, enabling a high efficiency at a low cost, given the short distance between central nodes that process a large amount of information. Although the long projections between the regions that are far from the CNS are efficacious in the integrative functions, they are costly in structure and metabolism, and therefore, vulnerable both in development as well as in pathologies such as Alzheimer's Disease, schizophrenia, epilepsy and ADHD in multiple sclerosis, etc. The author conceptualizes the connectome as an intermediate phenotype or endophenotype with modifying inheritable characteristics in the different stages of life, from the pre- and perinatal development until ageing.

Fitness costs associated with field-evolved resistance to chlorantraniliprole in Plutella xylostella (Lepidoptera: Plutellidae).

Plutella xylostella (L.) is the most important pest of Brassicaceae worldwide, with a recent estimate of US$ 4-5 billion expenditure for the control of this insect. A case of very high resistance of this pest to chlorantraniliprole was recently associated with reduced efficacy in a Brazilian field of Brassica spp. Although diamide resistance has been characterized, the fitness of insects due to such resistance has yet to be examined. Therefore, in this study, biological parameters were assessed in both susceptible and resistant strains of P. xylostella subjected to sublethal chlorantraniliprole concentrations. The field strain showed high resistance to chlorantraniliprole (RR50=27,793-fold), although resistance rapidly decreased in the first generations, showing instability. The exposure of susceptible and resistant larvae to their respective LC1, LC10, and LC25 values led to an increased duration of the larval and pupae phases and reduced weight in both strains; however, no significant differences in pupal viability across the treatments were observed. The resistant insects presented significantly lower larval weight and fecundity and higher larval and pupal periods, hatchability, and male longevity when not exposed to chlorantraniliprole, suggesting a fitness cost associated with resistance. In addition, resistant females showed a significantly higher egg-laying period and longevity at LC25, whereas the males lived longer at LC1. Chlorantraniliprole negatively impacted the biological parameters of both strains tested, although these effects were more relevant to the resistant insects. Resistant P. xylostella showed negative and positive biological trade-offs when compared with the susceptible individuals in both the absence and presence of chlorantraniliprole. Despite the important role that these trade-offs may play in the evolution of resistance to chlorantraniliprole, practical applications still depend on such information as the dominance of fitness costs and resistance.

The effect of pollen source vs. flower type on progeny performance and seed predation under contrasting light environments in a cleistogamous herb.

Dimorphic cleistogamy is a specialized form of mixed mating system where a single plant produces both open, potentially outcrossed chasmogamous (CH) and closed, obligately self-pollinated cleistogamous (CL) flowers. Typically, CH flowers and seeds are bigger and energetically more costly than those of CL. Although the effects of inbreeding and floral dimorphism are critical to understanding the evolution and maintenance of cleistogamy, these effects have been repeatedly confounded. In an attempt to separate these effects, we compared the performance of progeny derived from the two floral morphs while controlling for the source of pollen. That is, flower type and pollen source effects were assessed by comparing the performance of progeny derived from selfed CH vs. CL and outcrossed CH vs. selfed CH flowers, respectively. The experiment was carried out with the herb Ruellia nudiflora under two contrasting light environments. Outcrossed progeny generally performed better than selfed progeny. However, inbreeding depression ranges from low (1%) to moderate (36%), with the greatest value detected under shaded conditions when cumulative fitness was used. Although flower type generally had less of an effect on progeny performance than pollen source did, the progeny derived from selfed CH flowers largely outperformed the progeny from CL flowers, but only under shaded conditions and when cumulative fitness was taken into account. On the other hand, the source of pollen and flower type influenced seed predation, with selfed CH progeny the most heavily attacked by predators. Therefore, the effects of pollen source and flower type are environment-dependant and seed predators may increase the genetic differences between progeny derived from CH and CL flowers. Inbreeding depression alone cannot account for the maintenance of a mixed mating system in R. nudiflora and other unidentified mechanisms must thus be involved.

Metabolism, growth, and the energetic definition of fitness: a quantitative genetic study in the land snail Cornu aspersum.

Life-history evolution-the way organisms allocate time and energy to reproduction, survival, and growth-is a central question in evolutionary biology. One of its main tenets, the allocation principle, predicts that selection will reduce energy costs of maintenance in order to divert energy to survival and reproduction. The empirical support for this principle is the existence of a negative relationship between fitness and metabolic rate, which has been observed in some ectotherms. In juvenile animals, a key function affecting fitness is growth rate, since fast growers will reproduce sooner and maximize survival. In principle, design constraints dictate that growth rate cannot be reduced without affecting maintenance costs. Hence, it is predicted that juveniles will show a positive relationship between fitness (growth rate) and metabolic rate, contrarily to what has been observed in adults. Here we explored this problem using land snails (Cornu aspersum). We estimated the additive genetic variance-covariance matrix for growth and standard metabolic rate (SMR; rate of CO2 production) using 34 half-sibling families. We measured eggs, hatchlings, and juveniles in 208 offspring that were isolated right after egg laying (i.e., minimizing maternal and common environmental variance). Surprisingly, our results showed that additive genetic effects (narrow-sense heritabilities, h(2)) and additive genetic correlations (rG) were small and nonsignificant. However, the nonadditive proportion of phenotypic variances and correlations (rC) were unexpectedly large and significant. In fact, nonadditive genetic effects were positive for growth rate and SMR ([Formula: see text]; [Formula: see text]), supporting the idea that fitness (growth rate) cannot be maximized without incurring maintenance costs. Large nonadditive genetic variances could result as a consequence of selection eroding the additive genetic component, which suggests that past selection could have produced nonadditive genetic correlation. It is predicted that this correlation is reduced when adulthood is attained and selection starts to promote the reduction in metabolic rate.

Size and asymmetry: are there costs to winning the royalty race?

Body size and morphology are key fitness-determining traits that can vary genotypically. They are likely to be important in social insect queens, which mate in swarms and found colonies independently, but genetic influences on queen morphology have been little investigated. Here, we show that the body size and morphology of queens are influenced by their genotype in the leaf-cutting ant Acromyrmex echinatior, a species in which certain lineages (patrilines) bias their development towards reproductive queens rather than sterile workers. We found no relationship between the queen-worker skew of patrilines and the size or morphology of queens, but there was a significant relationship with fluctuating asymmetry, which was greater in more queen-biased patrilines. Our results suggest that queen-biased patrilines do not incur a fitness cost in terms of body size, but may face more subtle costs in developmental stability. Such costs may constrain the evolution of royal cheating in social insects.

The mean and variance of environmental temperature interact to determine physiological tolerance and fitness.

Global climate change poses one of the greatest threats to biodiversity. Most analyses of the potential biological impacts have focused on changes in mean temperature, but changes in thermal variance will also impact organisms and populations. We assessed the combined effects of the mean and variance of temperature on thermal tolerances, organismal survival, and population growth in Drosophila melanogaster. Because the performance of ectotherms relates nonlinearly to temperature, we predicted that responses to thermal variation (±0° or ±5°C) would depend on the mean temperature (17° or 24°C). Consistent with our prediction, thermal variation enhanced the rate of population growth (r(max)) at a low mean temperature but depressed this rate at a high mean temperature. The interactive effect on fitness occurred despite the fact that flies improved their heat and cold tolerances through acclimation to thermal conditions. Flies exposed to a high mean and a high variance of temperature recovered from heat coma faster and survived heat exposure better than did flies that developed at other conditions. Relatively high survival following heat exposure was associated with low survival following cold exposure. Recovery from chill coma was affected primarily by the mean temperature; flies acclimated to a low mean temperature recovered much faster than did flies acclimated to a high mean temperature. To develop more realistic predictions about the biological impacts of climate change, one must consider the interactions between the mean environmental temperature and the variance of environmental temperature.

Sociality, glucocorticoids and direct fitness in the communally rearing rodent, Octodon degus.

While ecological causes of sociality (or group living) have been identified, proximate mechanisms remain less clear. Recently, close connections between sociality, glucocorticoid hormones (cort) and fitness have been hypothesized. In particular, cort levels would reflect a balance between fitness benefits and costs of group living, and therefore baseline cort levels would vary with sociality in a way opposite to the covariation between sociality and fitness. However, since reproductive effort may become a major determinant of stress responses (i.e., the cort-adaptation hypothesis), cort levels might also be expected to vary with sociality in a way similar to the covariation between sociality and fitness. We tested these expectations during three years in a natural population of the communally rearing degu, Octodon degus. During each year we quantified group membership, measured fecal cortisol metabolites (a proxy of baseline cort levels under natural conditions), and estimated direct fitness. We recorded that direct fitness decreases with group size in these animals. Secondly, neither group size nor the number of females (two proxies of sociality) influenced mean (or coefficient of variation, CV) baseline cortisol levels of adult females. In contrast, cortisol increased with per capita number of offspring produced and offspring surviving to breeding age during two out of three years examined. Together, our results imply that variation in glucocorticoid hormones is more linked to reproductive challenge than to the costs of group living. Most generally, our study provided independent support to the cort-adaptation hypothesis, according to which reproductive effort is a major determinant, yet temporally variable, influence on cort-fitness covariation.

Emergent neutrality drives phytoplankton species coexistence.

The mechanisms that drive species coexistence and community dynamics have long puzzled ecologists. Here, we explain species coexistence, size structure and diversity patterns in a phytoplankton community using a combination of four fundamental factors: organism traits, size-based constraints, hydrology and species competition. Using a 'microscopic' Lotka-Volterra competition (MLVC) model (i.e. with explicit recipes to compute its parameters), we provide a mechanistic explanation of species coexistence along a niche axis (i.e. organismic volume). We based our model on empirically measured quantities, minimal ecological assumptions and stochastic processes. In nature, we found aggregated patterns of species biovolume (i.e. clumps) along the volume axis and a peak in species richness. Both patterns were reproduced by the MLVC model. Observed clumps corresponded to niche zones (volumes) where species fitness was highest, or where fitness was equal among competing species. The latter implies the action of equalizing processes, which would suggest emergent neutrality as a plausible mechanism to explain community patterns.

Early fitness consequences and hormonal correlates of parental behaviour in the social rodent, Octodon degus.

Males are expected to assist their mates whenever this behaviour raises survival of offspring with little expense in terms of mating opportunities. At a more proximate level, cortisol and testosterone hormones seem involved in the expression of parental care in mammals. We examined the consequences to postnatal offspring development and survival of the males' presence in the social rodent, Octodon degus. Offspring quality and quantity, and maternal condition of females were contrasted among females rearing their litters in the presence of the sire, females breeding in the presence of a non-breeding female, and females breeding solitarily. We related these differences to variation in parental behaviour and plasma levels of testosterone and cortisol. Twenty two females and their litters were studied under constant conditions of adult density, nest availability, food availability, and breeding experience. Males huddled over and groomed offspring. However, neither the number nor the mass of pups from dams that nested with the sire differed from those recorded to breeding females that nested with a non-breeding female and females that nested solitarily. Body weight loss and associated levels of plasma cortisol in dams nesting with the sire were similar to those of solitary females, but higher than mothers nesting with a non-breeding female. Thus, male care had no consequences to offspring, and seemed detrimental to breeding females. Circulating levels of cortisol and total testosterone were either poor (mothers) or no (fathers, non-breeding females) predictors of parental care.

Evolution of bacterial genes: evidences of positive Darwinian selection and fixation of base substitutions in virulence genes of Helicobacter pylori.

Gene diversity in Helicobacter pylori from different origins results in a phylogeographic differentiation, and this genetic variation among populations might be driven by random drift or by selective forces. However, only the selective forces would contribute to adaptation of the bacteria to the physiology and environment of its local host and to its association with gastroduodenal diseases. We studied evolutionary forces acting on variable regions of virulence genes cagA, babA and oipA, which present geographic differences among H. pylori strains from different human groups. Gene sequences in H. pylori strains from Asia, Europe and America were analysed using state of the art analytical methods like the Maximum Likelihood method. The rate and nature of polymorphisms in these virulence genes were also compared among populations using the AMOVA and McDonald-Kreitman tests. We found strong and significant positive selection acting on variable regions of cagA, babA and oipA. We found in cagA from Asian strains regions under positive selection, which localised in amino acid sites defining the Asian fingerprint for this gene and in sites with important biological activity. Different evolutionary forces are acting on the variable region of virulence genes; they partly explain the source of genetic diversity and the differences in risk for gastroduodenal diseases among different human populations.

Modified alpha-amylase activity among insecticide-resistant and -susceptible strains of the maize weevil, Sitophilus zeamais.

Fitness cost is usually associated with insecticide resistance and may be mitigated by increased energy accumulation and mobilization. Preliminary evidence in the maize weevil (Coleoptera: Curculionidae) suggested possible involvement of amylases in such phenomenon. Therefore, alpha-amylases were purified from an insecticide-susceptible and two insecticide-resistant strains (one with fitness cost [resistant cost strain], and the other without it [resistant no-cost strain]). The main alpha-amylase of each strain was purified by glycogen precipitation and ion-exchange chromatography (>or=70-fold purification,

Physiological approach to explain the ecological success of 'superclones' in aphids: interplay between detoxification enzymes, metabolism and fitness.

'Superclones' are predominant and time-persistent genotypes, exhibiting constant fitness across different environments. However, causes of this ecological success are still unknown. Therefore, we studied the physiological mechanisms that could explain this success, evaluating the effects of wheat chemical defences on detoxification enzymes [cytochrome P450 monooxygenases (P450), glutathione S-transferases (GST), esterases (EST)], standard metabolic rate (SMR), and fitness-related traits [adult body mass and intrinsic rate of increase (r(m))] of two 'superclones' (Sa1 and Sa2) of the grain aphid, Sitobion avenae. Additionally, we compared 'superclones' with a less-frequent genotype (Sa46). Genotypes were reared on three wheat cultivars with different levels of hydroxamic acids (Hx; wheat chemical defences). Detoxification enzymes and SMR did not differ between wheat hosts. However, GST and EST were different between 'superclones' and Sa46, while Sa1 showed a higher SMR than Sa2 or Sa46 (p=0.03). Differences between genotypes were found for r(m), which was higher for Sa1 than for Sa2 or Sa46. For all cases, genotype-host interactions were non-significant, except for aphid body mass. In conclusion, 'superclones' exhibit a broad host range, flat energetic costs for non-induced detoxification enzymes, and low variation in their reproductive performance on different defended hosts. However, physiological specialization of 'superclones' that could explain their ecological success was not evident in this study.

How ecology shapes caste evolution: linking resource use, morphology, performance and fitness in a superorganism.

Caste evolution is a central process in the adaptive diversification of insect superorganisms. Nevertheless, how ecology shapes adaptive caste evolution remains poorly understood. Recent work with the ant genus Cephalotes has provided new comparative evidence that ecological specialization may drive adaptive caste specialization. Here, three key predictions of this adaptive hypothesis are supported, using a representative of the highest level of ecological specialization and the most specialized soldier phenotype. First, soldier defensive performance was maximal for the specific nesting resource used most often in nature. Second, colonies only used a specialized subset of available nesting resources and preferred the specific resource that maximizes soldier performance. Third, soldier performance and its limitations on resource use were found to have both direct and indirect consequences for colony reproduction. These findings suggest that the most specialized soldier phenotype in Cephalotes is indeed an adaptation to ecological specialization on a narrowly defined subset of available nesting resources.