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PDF file - 635K, Supplementary Figure S1. Genotypes included in the combinatorial genetic matrix. PTEN or RB1 were silenced by shRNA in isogenic KI cells.

XLSX file - 144K, Supplementary table S1. List of compounds employed in the present work. Supplementary Table S2. List of t-tests p values comparing the responses of the different mutant cell lines to a given drug concentration with the response of the WT Scramble control cells. Supplementary Table S3. List of the drugs included in the library and tested on HME-1 cell lines.

A critical step toward defining tailored therapy in patients with cancer is the identification of genetic interactions that may impair—or boost—the efficacy of selected therapeutic approaches. Cell models able to recapitulate combinations of genetic aberrations are important to find drug–genotype interactions poorly affected by the heterogeneous genetics of human tumors. In order to identify novel pharmacogenomic relationships, we employed an isogenic cell panel that reconstructs cancer genetic scenarios. We screened a library of 43 compounds in human hTERT-HME1 epithelial cells in which PTEN or RB1 were silenced in combination with the targeted knockin of cancer-associated mutations in EGFR, KRAS, BRAF, or PIK3CA oncogenes. Statistical analysis and clustering algorithms were applied to display similar drug response profiles and mutation-specific patterns of activity. From the screen, we discovered that proteasome inhibitors show selectivity toward BRAF V600E–mutant cells, irrespective of PTEN or RB1 expression. Preferential targeting of BRAF-mutant cells by proteasome inhibitors was corroborated in a second BRAF V600E isogenic model, as well as in a panel of colorectal cancer cell lines by the use of the proteasome inhibitor carfilzomib. Notably, carfilzomib also showed striking in vivo activity in a BRAF-mutant human colorectal cancer xenograft model. Vulnerability to proteasome inhibitors is dependent on persistent BRAF signaling, because BRAF V600E blockade by PLX4720 reversed sensitivity to carfilzomib in BRAF-mutant colorectal cancer cells. Our findings indicated that proteasome inhibition might represent a valuable targeting strategy in BRAF V600E–mutant colorectal tumors. Mol Cancer Ther; 12(12); 2950–61. ©2013 AACR.

BackgroundHuman African trypanosomiasis is a parasitic disease caused by trypanosomes among whichTrypanosoma brucei gambienseis responsible for a chronic form (gHAT) in West and Central Africa. Its elimination as a public health problem (EPHP) is being achieved. Côte d’Ivoire was one of the first countries to be validated by WHO in 2020 and this was particularly challenging as the country still reported around a hundred cases a year in the early 2000s. This article describes the strategies implemented including a mathematical model to evaluate the reporting results and infer progress towards sustainable elimination.MethodsThe control methods used combined both exhaustive and targeted medical surveillance strategies to diagnose and treat cases as well as vector control to reduce the risk of transmission in the most at risk areas. A mechanistic model was used to estimate the number of underlying infections and the probability of elimination of transmission (EoT) between 2000– 2021 in two endemic and two hypo-endemic health districts.ResultsBetween 2015 and 2019, nine gHAT cases were detected in two health districts in which the number of cases/10,000 inhabitants was far below 1, a necessary condition for validating the EPHP. Modelling estimated a slow but steady decline in transmission across the four health districts, bolstered in the two endemic health districts by the introduction of vector control. The decrease in underlying transmission in all health districts corresponds to a high probability that EoT has already occurred in Côte d’Ivoire.ConclusionThis success was achieved through a multi-stakeholder and multidisciplinary one health approach where research has played a major role in adapting tools and strategies to this large epidemiological transition to a very low prevalence. This integrated approach will need to continue to reach the verification of EoT in Côte d’Ivoire targeted by 2025.Author SummarySignificant efforts to controlTrypanosoma brucei gambiensehuman African trypanosomiasis (gHAT) have drastically reduced the prevalence of the disease and elimination of transmission (EoT) is targeted for 2030 by WHO. This reduction was particularly challenging in Côte d’Ivoire as it still faced epidemic episodes in the early 2000s. This large epidemiological transition to very low prevalence necessitated the adaptation and evolution of both medical and vector control strategies described in this article. A mathematical model was also used to retrospectively analyse case reporting results, indicating with high probability that local EoT has already been achieved in the four health districts analysed.With nine gHAT cases detected in two health districts between 2015 and 2019 and less than one case per 10,000 people per year in all health districts at national level over this five-year period, Côte d’Ivoire received validation by WHO of achievement of the elimination of the disease as a public health problem in 2020. These results combined with the modelling offer encouragement regarding reaching the verification of EoT targeted by 2025 in Côte d’Ivoire on condition of maintaining such multidisciplinary one health approach including research activities to continuously adapt it to the epidemiological transition to zero incidence.

Human African trypanosomiasis, caused by the gambiense subspecies of Trypanosoma brucei (gHAT), is a deadly parasitic disease transmitted by tsetse. Partners from around the world have stepped up efforts to eliminate the disease, and the Chadian government have had a particular focus on the previously high-prevalence setting of Mandoul. In this study, we evaluate the economic efficiency of the intensified strategies that were put in place from 2014 aimed at interrupting transmission of gHAT, and we make recommendations on the best way forward based on both epidemiological projections and cost-effectiveness. In our analysis we use a dynamic transmission model fit to epidemiological data from Mandoul to evaluate the cost-effectiveness of combinations of active screening, improved passive screening (defined as an expansion of the number of health posts capable of screening for gHAT), and vector control activities (the deployment of Tiny Targets). For cost-effectiveness analyses, our primary outcome is disease burden, denominated in disability-adjusted life-years (DALYs), and costs, denominated in 2020 US$. Although active and passive screening have enabled more rapid diagnosis and accessible treatment in Mandoul, the addition of vector control provided good value-for-money (at less than $750/DALY averted) and substantially increased the probability of reaching the 2030 elimination target for gHAT as set by the World Health Organization. Our transmission modelling and economic evaluations suggests that the gains have been made could be maintained by robust passive screening, and the inclusion of active screening and vector control strategies could be considered for other foci in the country with active transmission. Our analysis speaks to comparative efficiency, and it does not take into account all possible considerations; for instance, any cessation of on-going active screening should first consider that strong surveillance activities will be critical to verify elimination of transmission and to protect against the possible importation of infection from neighbouring endemic foci.Author summaryIn a drive to eliminate human African trypanosomiasis (gHAT or sleeping sickness) from Chad following a peak in 2002, the National Sleeping Sickness Control programme and their partners focused on making substantial changes to interventions within the high prevalence setting of Mandoul. These included the use of vector control starting in 2014 and improved screening in health facilities starting in 2015. To explore whether these interventions were an efficient use of resources we carried out a retrospective analysis using a dynamic transmission model fit to epidemiological data from Mandoul combined with a cost model. Our analysis indicated that active and passive screening have enabled more rapid diagnosis and accessible treatment in Mandoul compared to less ambitious interventions, and furthermore the addition of vector control provided good value-for-money and substantially increased the probability of reaching the 2030 elimination of transmission target for gHAT set by the World Health Organization. Looking forwards, our prospective analysis also considers the health economics of future strategies and, as part of this, concludes that the scaleback of vertical interventions appears cost-effective if passive screening remains robust in Mandoul. This could therefore enable shifting of resources to tackle other remaining foci in Chad.

Gambiense human African trypanosomiasis (gHAT) is a deadly vector-borne, neglected tropical disease found in West and Central Africa targeted for elimination of transmission (EoT) by 2030. The recent pandemic has illustrated how it can be important to quantify the impact that unplanned disruption to programme activities may have in achieving elimination of transmission. We used a previously developed model of gHAT fitted to data from the Democratic Republic of Congo, a country with the highest global case burden, to explore how interruptions to intervention activities, due to e.g. COVID-19, Ebola or political instability, could impact progress towards EoT and gHAT burden. We simulated transmission and reporting dynamics in 38 health zones under six interruption scenarios lasting for nine or twenty-one months. Included in the interruption scenarios are the cessation of active screening in all scenarios and a reduction in passive detection rates and a delay or suspension of vector control deployments in some scenarios. Our results indicate that, even under the most extreme 21-month interruption scenario, EoT is not predicted to be delayed by more than one additional year compared to the length of the interruption. If existing vector control deployments continue, we predict no delay in achieving EoT even when both active and passive screening activities are interrupted. If passive screening remains fully functional, we expect a marginal negative impact on transmission, however this depends on the strength of passive screening in each health zone. We predict a pronounced increase in additional gHAT disease burden (morbidity and mortality) in many health zones if both active and passive screening were interrupted compared to the interruption of active screening alone. The ability to continue existing vector control during medical activity interruption is also predicted to avert a moderate proportion of disease burden.Author SummaryWhilst the COVID-19 pandemic has produced wide-spread disruption for many disease programmes there are also a range of other factors that continue to risk programme interruptions including other disease outbreaks (e.g. Ebola, cholera, yellow fever, and measles) and the potential for political instability. In this study we examine the impact of interruptions by external factors to the gambiense human African trypanosomiasis (gHAT, sleeping sickness) elimination programme of the Democratic Republic of the Congo, a country which has the highest global case burden. We use our previously fitted gHAT model to simulate how transmission dynamics might be impacted by disruption to medical interventions and (where relevant) vector control activities in 38 health zones of the former Bandundu province. For each of the six interruption scenarios we use the model to forecast case numbers and disease burden as well as estimating the expected years and probabilities of elimination of transmission. This analysis provides invaluable insight into the impact that interruptions of any persuasion could have on burden, case reporting and time to achieve elimination of transmission of gHAT in the Democratic Republic of the Congo.

International audience; Species that have sex determined by environmental conditions during development (i.e., environmental sex determination [ESD]) are especially vulnerable to environmental change, including altered stress levels, habitat loss, and species translocations. These factors can produce multigenerational trends in population size and eco-evolutionary dynamics not captured by existing theory based on lifetime reproductive success (R0). Here, we extend ESD theory to use per capita growth rate r as a more appropriate measure of evolutionary success (fitness), and we demonstrate the importance of this change when males and females can differ in maturation times and when maturation times vary with local conditions (plasticity). In these cases, we show that primary and secondary sex ratios may be strongly biased; that optimal maturation times, when locally plastic, depend on the balance between mortality and growth effects; and that plasticity of maturation times can ameliorate fitness costs of increasing environmental stress

We initiated the use of a replicated, remote-video, artificial stream system to determine the effects of conspecific cue, refuge availability, and day/night conditions on movement, aggression, dominance, downstream preference, and refuge use by the crayfish Procambarus clarkii. In line with previous research, we found that walking on the gravel substrate was greatly increased and refuge use decreased in the dark. Conspecific cue (macerated crayfish filtrate) increased walking, contrary to our prediction but consistent with cue as a signal of food availability or of risk either from cannibalism or from visual predators. Exposure to conspecific cue in the streams resulted in a reduced degree of dominance in subsequent pairwise dominance trials. We developed and implemented a new and broadly applicable way of determining the extent of linearity (consistency of dominance ranks) for incomplete dominance; for our data, this method found a lack of evidence for linear hierarchies in these stream systems. Our results suggest that streams may tend to feature weaker dominance and reduced linearity of social hierarchies, relative to standing-water systems, a hypothesis that requires further testing.

Unrelated males sometimes share their nests and their mates, an example of male-male cooperation that calls for an evolutionary explanation. We developed a game-theoretic model of this situation under the assumption that males could be either "aggressors," attempting to drive off any other arriving male, or "tolerators," willing to share a nest and mates with another tolerator male. We modeled nest dynamics by changing the frequency of the two types in the population and determined how this affected their fitness. We use the sea lamprey as a case study to generate a plausible array of behavioral traits and ecological conditions for the model. Under these conditions, only aggressors or only tolerators could persist, not both, but we also show how exceptions can arise. Aggressors predominated for the standard conditions we chose, but tolerators could take over when females favored them through nest choice or increased mating rate. High nesting densities and high fighting costs also tended to favor tolerators. At moderate to low densities of individuals in the nesting area, female behavior, based on their own costs and benefits, should determine the outcome.

International audience; Besides egg fertilization, females of many taxa obtain direct fitness benefits from male mates, such as food, protection or paternal care. But males often increase their own fitness by mating with several females, among which they distribute sperm along with the above-mentioned benefits, reducing the benefits to individual females. These diverging interests lead to a conflict in which each female may try to ensure male fidelity and get exclusive access to male-provided benefits. Here, we use a theoretical model to show how a female of an externally fertilizing species may achieve mate fidelity by soliciting copulations at such a rate that the male has insufficient sperm left to increase his fitness with additional females. We show that three alternative condition-dependent evolutionarily stable mating relationships emerge in this scenario, based on whether one mate’s preference for mating rate dominates, or the conflict is resolved by what amounts to negotiation. We demonstrate how these outcomes depend on some features of physiology, ecology, and behavior. In particular, a greater reproductive benefit to a female from exclusive access to a male partner—or the occasional tendency of females to withhold eggs during mating—can increase male fidelity; and continuous sperm regeneration rather than an initially-set stock of sperm allows for multiple within-pair mating across all three mating pattern

BackgroundIn recent years, an integrated programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections has led to a rapid decline in cases in the Mandoul disease focus of Chad. In this study, we assess whether elimination of transmission has already been achieved in the region despite low-level case reporting, quantify the role of intensified interventions in transmission reduction, and predict the trajectory of gHAT in Mandoul for the next decade under a range of control scenarios.MethodWe utilise human case data (2000–2019) to update a previous model of transmission of gHAT in Mandoul. We also test the updated model, which now has refined assumptions on diagnostic specificity of the current algorithm and an improved fitting method, via a data censoring approach.ResultsWe conclude that passive detection rates have increased due to improvements in diagnostic availability in fixed health facilities since 2015, by 2.1-fold for stage 1 detection, and by 1.5-fold for stage 2. We find that whilst the diagnostic algorithm for active screening is estimated to be highly specific (99.93%, 95% CI: 99.91–99.95%), the high screening level and limited remaining infection means that some recently reported cases might be false positives, especially the ones that were not parasitologically confirmed. We also find that the focus-wide tsetse vector reduction estimated through model fitting (99.1%, 95% CI: 96.1–99.6%) is comparable to the very high reduction previously measured by the decline in catches of tsetse from monitoring traps. In line with previous results, the model suggests that transmission was likely interrupted in 2015 as a result of intensified interventions.ConclusionsWe recommend that additional confirmatory testing is performed in Mandoul in order that the endgame can be carefully monitored now that infection levels are so low. More specific measurement of cases would better inform when it is safe to stop active screening and vector control.

Decisions made while searching for settlement sites (e.g., nesting, oviposition) often have major fitness implications. Despite numerous case studies, we lack theory to explain why some species are thriving while others are making poor habitat choices after environmental change. We develop a model to predict (1) which kinds of environmental change have larger, negative effects on fitness, (2) how evolutionary history affects susceptibility to environmental change, and (3) how much lost fitness can be recovered via readjustment after environmental change. We model the common scenario where animals search an otherwise inhospitable matrix, encountering habitats of varying quality and settling when finding a habitat better than a threshold quality level. We consider decisions and fitness before environmental change, immediately following change (assuming that animals continue to use their previously adaptive decision rules), and after optimal readjustment (e.g., via learning or evolution). We find that decreases in survival per time step searching and declines in habitat quality or availability generally have stronger negative effects than reduced season duration. Animals that were adapted to good conditions remained choosy after conditions declined and thus suffered more from environmental change than those adapted to poor conditions. Readjustment recovered much of the fitness lost through a reduction in average habitat quality but recovered much less following reductions in habitat availability or survival while searching. Our model offers novel predictions for empiricists to test as well as suggestions for prioritizing alternative mitigation steps.

While a large body of research has focused on the physiological effects of multiple environmental stressors, behavioral effects remain far less studied. However, behavioural plasticity can not only directly drive responses to stressors but can also mediate physiological responses. Here, we provide a conceptual framework incorporating four fundamental tradeoffs explicitly linking animal behaviour to life history-based pathways for energy allocation, shaping the impact of multiple stressors on fitness. We first address how small-scale behavioural changes can drive conflicts between the effects of multiple stressors and alternative physiological responses. We then discuss how animal behaviour gives rise to three additional understudied and interrelated trade-offs: balancing the benefits and risks of obtaining the energy needed to cope with stressors, allocation of energy between life-history traits and stressor responses, and larger-scale escape from stressors in space or time via dispersal or dormancy. Finally, we outline how these trade-offs interactively affect fitness and qualitative ecological outcomes resulting from multiple stressors. Our framework suggests that animal behavior could underlie the extensive context dependence in results from stressor research, highlighting promising avenues for future empirical and theoretical research.

Concealed fecundity and extended female sexual receptivity have evolved in some primates, including humans, conferring advantages both within primarily monogamous relationships (e.g., benefits from paternity assurance) and from extrapair liaisons (e.g., better access to good genes). As humans evolved the intellectual capacity for decision-making, women became capable of altering their own fertility. In some circumstances, they may choose to ameliorate risks and responsibilities associated with pregnancy by reducing sexual motivation near the perceived most fecund time of their menstrual cycle. But three findings-a general inability of women to accurately recognize their own intervals of fecundity, high variability in ovulation timing, and unconscious transmission and reception of cues associated with fecundity-constitute a physiological and behavioral syndrome that can be considered self-deception. In this study, I develop a descriptive model to determine implications of the hypothesis that these features of female and male physiology and behavior have been shaped by natural selection in response to female decision-making. My analysis shows that consensus motivation for coitus between partners influences both the importance of variable ovulation date and the probability of conception, under the influence of self-deception. It also identifies priorities for future empirical work.

© 2020 by the authors., Behaviors may enhance fitness in some situations while being detrimental in others. Linked behaviors (behavioral syndromes) may be central to understanding the maintenance of behavioral variability in natural populations. The spillover hypothesis of premating sexual cannibalism by females explains genetically determined female aggression towards both prey and males: growth to a larger size translates into higher fecundity, but at the risk of insufficient sperm acquisition. Here, we use an individual-based model to determine the ecological scenarios under which this spillover strategy is more likely to evolve over a strategy in which females attack approaching males only once the female has previously secured sperm. We found that a classic spillover strategy could never prevail. However, a more realistic early-spillover strategy, in which females become adults earlier in addition to reaching a larger size, could be maintained in some ecological scenarios and even invade a population of females following the other strategy. We also found under some ecological scenarios that both behavioral types coexist through frequency-dependent selection. Additionally, using data from the spider Lycosa hispanica, we provide strong support for the prediction that the two strategies may coexist in the wild. Our results clarify how animal personalities evolve and are maintained in nature., This work was partially funded by te Spanish Ministry of Science and Innovation grant CGL2004-03153 to J.M.-L.

Most flowering plants are simultaneous hermaphrodites. Within species and even within local populations, sex allocation is usually highly plastic. Here, we link pollen sufficiency to the size of pollen-exchanging groups (i.e., pollen neighborhoods) and to pollen transfer efficiency, using an individual-based game-theoretic framework to determine the stable distribution of sex allocation that does not require the unrealistic assumption of infinitely large, panmictic populations. In the absence of selfing, we obtain the novel result that pollen limitation destabilizes hermaphroditism and favors separate sexes, whereas hermaphroditism remains stable without pollen limitation. With mixed mating, hermaphroditism is stable except when the fitness value of selfed offspring is less than half that of outcrossed offspring (i.e., strong inbreeding depression). In that case, the size of pollen neighborhoods, pollen transfer efficiencies, and the relative fitness of selfed offspring determine whether separate sexes or hermaphroditism is the stable outcome. The model thus predicts that separate sexes can derive from either of two ancestral states: obligate outcrossing under pollen limitation, or mixed mating (competing self-fertilization) under severe inbreeding depression. It also predicts conditions under which variance in sex-allocation among hermaphrodites within pollen exchanging groups along a gradient of pollen limitation can range from high (dioecy) to near zero (equal proportions of male and female investment).

Eastern gamagrass (Tripsacum dactyloides L.) belongs to the same tribe of the Poaceae family as maize (Zea mays L.) and grows naturally in the same region where maize is commercially produced in the USA. Although no evidence exists of gene flow from maize to eastern gamagrass in nature, experimental crosses between the two species were produced using specific techniques. As part of environmental risk assessment, the possibility of transgene flow from maize to eastern gamagrass populations in nature was evaluated with the objectives: (1) to assess the seeds of eastern gamagrass populations naturally growing near commercial maize fields for the presence of a transgenic glyphosate-tolerance gene (cp4 epsps) that would indicate cross-pollination between the two species, and (2) to evaluate the possibility of interspecific hybridization between transgenic maize used as male parent and eastern gamagrass used as female parent. A total of 46,643 seeds from 54 eastern gamagrass populations collected in proximity of maize fields in Illinois, USA were planted in a field in 2014 and 2015. Emerged seedlings were treated with glyphosate herbicide and assessed for survival. An additional 48,000 seeds from the same 54 eastern gamagrass populations were tested for the presence of the cp4 epsps transgene markers using TaqMan® PCR method. The results from these trials showed that no seedlings survived the herbicide treatment and no seed indicated presence of the herbicide tolerant cp4 epsps transgene, even though these eastern gamagrass populations were exposed to glyphosate-tolerant maize pollen for years. Furthermore, no interspecific hybrid seeds were produced from 135 hand-pollination attempts involving 1529 eastern gamagrass spikelets exposed to maize pollen. Together, these results indicate that there is no evidence of gene flow from maize to eastern gamagrass in natural habitats. The outcome of this study should be taken in consideration when assessing for environmental risks regarding the consequence of gene flow from transgenic maize to its wild relatives. Electronic supplementary material The online version of this article (doi:10.1007/s11248-017-0020-7) contains supplementary material, which is available to authorized users.

Quercus (oak) regeneration failure threatens many forest and savanna communities worldwide, where preservation of vegetation structure and composition depends on acorns germinating and surviving into adulthood. However, predation on the acorns and browsing of seedlings limits oak regeneration. To better understand the effects of these 2 mechanisms on oak recruitment in the endangered Bluegrass savanna—woodland of Kentucky, we compared seed predation and herbivory on Quercus muehlenbergii (Chinquapin Oak) with Carya laciniosa (Shellbark Hickory), a successfully regenerating tree species. Compared to hickory nuts, acorns were predated more, cached less, and dispersed shorter distances. Neither the distribution of the seedlings under the parent canopy nor browse damage differed between the 2 species. Our results suggest that seed-predation prevents regeneration of oaks in this endangered community.

We addressed the implications of limb loss and regeneration for multispecies interactions and their impacts on ecosystem engineering in freshwater stream environments.We included regenerative and nonregenerative crayfish as well as fish predators in a 2 × 2 factorial design to assess the effects on water turbidity of interactions between crayfish ecosystem engineers differing in regenerative status and their fish predators.We demonstrated that crayfish limb loss and predation risks lead to more turbidity in field and mesocosm conditions. Moreover, ongoing regeneration of crayfish increased turbidity, while fish presence seemed to hinder crayfish turbidity‐inducing behaviors (such as tail‐flipping and burrowing) in the mesocosm experiment.We confirmed that greater numbers of crayfish produce a greater amount of turbidity in situ in streams.Although mechanical burrowing crayfish capacities may depend on crayfish burrowing classification (primary, secondary, or tertiary), our work emphasizes the implication for turbidity levels of crayfish autotomy in freshwater streams., We addressed the implications of limb loss and regeneration for multispecies interactions and their impacts on ecosystem engineering in freshwater stream environments. We demonstrated that crayfish limb loss and predation risks lead to more turbidity in field and mesocosm conditions. Although mechanical burrowing crayfish capacities may depend on crayfish burrowing classification (primary, secondary, or tertiary), our work emphasizes the implication for turbidity levels of crayfish autotomy in freshwater streams.

Clonal organisms persist at a range of population sex ratios, from equal numbers of males and females to single-sex systems. When intersexual competition is strong enough to drive one sex locally extinct, the maintenance of the sexes is facilitated by the semi-independent dynamics of populations within a metapopulation. These semi-independent dynamics are influenced by dispersal and recolonization rates, which are affected by the spatial arrangement of populations. To establish the quantitative relationship between spatially complex metapopulations and the maintenance of the sexes, we used a mathematical model of the liverwort Marchantia inflexa. This clonal organism is found in discrete patches on rocks and along the banks of streams, which form single-sex and two-sex metapopulations. In this system, asexual propagules mainly disperse short distances. Long-distance between-patch dispersal and recolonization mainly occurs via sexual propagules, which require both sexes to be present. Dispersal of these two types of propagules could interact with the spatial arrangement of populations to affect the maintenance of the sexes. With our mathematical model, we found that at intermediate distances between populations, metapopulations maintained both sexes, and the spatial arrangement of populations changed the threshold at which one sex was lost. On the other hand, when populations were close to one another, one sex was lost and the single-sex metapopulation persisted through dispersal of asexual propagules. When populations were far apart, one sex was lost, and the metapopulation either went extinct due to lack of recolonization by asexual propagules or persisted because clumped populations facilitated recolonization. These idealized spatial arrangements help clarify the effects of the spatial arrangement on the maintenance of the sexes and the persistence of metapopulations of clonal organisms, which can help explain geographic parthenogenesis and the distribution of asexual populations, the persistence of asexual species, and inform the conservation of clonal organisms.

Simultaneous hermaphrodites that exchange gametes within pairs allow us to test whether equity of resource exchange is positively associated with duration of cooperative partnerships. The chalk bass (Serranus tortugarum) provides an excellent model system for such research because they spawn daily, trading sex roles with the same mating partners in repeated spawning bouts (a tactic called "egg parceling"). Even so, they live in site-attached aggregations with opportunities for extra-pair matings. We asked whether individuals spawn preferentially with 1 long-term partner and whether partner fidelity was associated with matching in the number of eggs produced in a single day by individuals within pairs. In addition, we observed random focal individuals during spawning to determine whether egg parceling was coordinated within pairs: we asked whether parcel number (per day) was well matched within pairs and whether parcels were exchanged in nonrandom sequences. We did not witness any "break-ups" in our long-term pairs; during each monthly census, all identified pairs were found spawning and courting with their "primary" mating partner until one or both of them disappeared. Daily egg production and the number of egg parcels exchanged within primary partnerships were coordinated. The sequence of parcel exchange was fairly regular, although ca. 20% of focal individuals fertilized or exchanged a few egg parcels with another partner(s); parceling allows individuals the option to exchange eggs outside of the primary pair. Our study provides novel empirical evidence of strong pair bonds and resource matching even in relatively large social groups with extra-pair trading opportunities.

Parental management of early offspring development is a complex but essential contribution to reproductive success for oviparous species. Mothers faced with incubating eggs in a variable environment maximize reproductive success by adaptively adjusting offspring number in a clutch and incubation schedules to facilitate egg development while meeting their own energetic demands. However, the optimal resolution of these trade-offs varies with physiological and ecological factors and is thus hard to determine using empirical data from natural systems. To untangle the complex factors driving optimal maternal decisions, we developed an ecophysiological model that identifies optimal maternal strategies and their implications for offspring, comparing results for example altricial and precocial species. We showed how plastic maternal strategies can ameliorate effects of food scarcity, offspring mortality risk, variable levels of biparental care, and constraints on producing multiple clutches within a season. In the altricial case in particular, we identified important downstream fitness effects from decisions made in the incubation stage. Additionally, we showed that seasonal decreases in clutch size may result from cumulative fecundity costs for the altricial case and from a seasonal decline in female quality for precocial species. Many of the novel results in this study are testable in future empirical work.

Maize plants with mutations at brachytic 2 (br2) reduce plant height through internode shortening while maintaining the rest of the plant's relative size. The gene product of Br2 encodes an ATP binding cassette type B (ABCB) auxin transporter. Several br2 mutations have been previously reported, notably independent characterizations of 8 bp and 241 bp deletions (br2-23 and br2-qpa1, respectively), a single missense mutation (br2-qph1), and a MITE transposon insertion (br2-NC238). Two new br2 mutations (designated br2-7081 and br2-7861) have now been characterized with different genetic mechanisms than prior reports providing further examples of functional genetic variation in maize. A gene edited br2 allele (designated br2-1005) has also been generated through use of CRISPR-Cas9 technology. Both novel br2 transposon mutants in this report (br2-7081, br2-7861) arose spontaneously, independently and were identified in proprietary maize germplasm; both contain insertions that result in frameshifts with presence of premature stop codons. The br2-7081 allele contains a 4.7 kb insertion in exon 5, which is identified as a Ty1-copia family long terminal repeat (LTR) retrotransposon. The br2-7861 allele contains a 579 bp insertion in intron 4, which is identified as a partial Sirevirus LTR retrotransposon, and encodes a transcribed exon of 190 bp. A gene edit in br2 (br2-1005) was generated when a CRISPR-Cas9-induced double strand break was repaired by the plant via non-homologous end joining, causing a 1 bp frameshift resulting in a premature stop codon in exon 5. Also, of note in this study is the 8 bp deletion reportedly characterizing the br2-23 mutant allele was unexpectedly found in wild-type Br2 (non-brachytic) germplasm indicating the 8 bp deletion by itself likely does not result in a brachytic phenotype. The novel mutant alleles reported here provide further examples of functional genetic variation in maize br2, either through inherent genetic variation mechanisms or generated using site-directed nuclease technology. The br2-1005 allele highlights the utility of gene editing to phenocopy naturally occurring mutations, and all three alleles in this report provide additional opportunities to research the brachytic semi-dwarf phenotype in maize.

Equation 3 of the original published version of this article was incorrect. Correct presentation is given below.

Correlations between behavioral, physiological, and morphological traits linked to life history have been given the label “pace-of-life syndrome” (POLS), hypothesized to arise through variation in the resolution of a trade-off between present and future reproduction. However, other trade-offs over energy allocation may also have effects and influence the present-future trade-off. We analyzed an optimality model of basal metabolic rate (BMR) across variation in food availability and two types of mortality. The model contained three major features: (1) feedback between activity and energy acquisition, (2) links between BMR and the use of energy for other traits, and (3) allocation trade-offs between BMR and all other traits, between activity and defense, and between defense against activity-related risk and activity-independent risk. The model produced an intermediate optimal BMR that was usually highest at an intermediate level of food availability. Food availability and both types of mortality risk interacted to influence the exact value of optimal BMR. Trait correlations expected in the POLS existed under some environmental conditions, but these correlations flipped sign under different conditions and were not always strong. Our model reproduces trait correlations consistent with the POLS, but also generated a “sloppy” syndrome with considerable non-POLS-like variation. In addition, among-individual, non-adaptive variation in BMR produced adjustments of the other traits. These fit a best-of-a-bad job strategy, and the adjustments further weakened trait correlations. The results emphasize that variation in resources and mortality risk creates a diversity of correlation structures. This complexity means the POLS is likely to be a variable construct. Many attributes important for reproduction and survival are associated. Such associations may arise through common physiological processes and correlated selection. We modeled metabolic rate within a system in which foraging behavior both depended on and mediated the acquisition of resources necessary for metabolism, while energy was allocated among multiple attributes. Variation in several environmental variables (food availability and two types of mortality risk) influenced basal metabolic rate, activity, and defenses against mortality risk. This variation affected the correlations between the traits in complex ways. When basal metabolic rate was non-optimal, evolution of the allocation of energy to other traits partially compensated, but this further eroded consistent trait correlations. Our results indicate that complexity in how energy is acquired and used can potentially disrupt trait correlations normally associated with the pace-of-life syndrome.

When females choose mates, males may respond in several ways: by allowing an evaluation by the female and investing substantially in subsequent reproduction (here, type 1), by allowing evaluation but withholding investment following mating (type 2), or by preventing evaluation and attempting to coerce the female to mate (type 3). In this modeling analysis, we examine the conditions under which these strategies, individually or in combination, are expected to persist in the population primarily using the criterion of evolutionary stability. We also consider the roles of female resistance, social policing, and extra-pair paternity in influencing these outcomes. Using six focal systems taken from primates, fish, birds, and insects, we derived parameters for a game-theoretical model to determine the expected evolutionary stable frequencies or unstable combinations of the male strategies based on system-specific parameter magnitudes. In chimpanzees, guppies, Japanese water striders, and scorpionflies, males making the highest investment in each reproductive event were the sole persisting type; in mallard ducks, an evolutionarily stable mixture of types 1 and 3 prevailed; and in humans, a stable mixture of types 1 and 2 persisted. In accord with the infrequency of consistent coercion across taxa, our results suggest that coercion may often be evolutionarily unstable and available only opportunistically as the strategy of last resort. Our game theory model examined mate choice in six species of primates, fish birds, and insects to identify patterns predicted to persist from an evolutionary perspective. We found that differences in ecological, physiological, and behavioral characteristics resulted in the persistence of individual or multiple male mating strategies generally consistent with observations in nature. In particular, coercive males could persist in a population when fertilization rates and reproductive outcomes were similar to those of less forceful males.

Building on previous work, we derive an optimization model for a two-state stochastic environment and evaluate the fitnesses of five reproductive strategies across generations. To do this, we characterize spatiotemporal variation and define grain (=patch) size as the scale of fitness autocorrelation. Fitness functions of environmental condition are Gaussian. The strategies include two specialists on each of the environmental conditions; two generalists that each fare equally well under both conditions, but one (a conservative bet hedger) optimizes the shape of the fitness function; and a diversified bet hedger producing an optimal mix of the two specialists within individual broods. When the environment is primarily in one of the two states, the specialist on that state achieves the highest fitness. In the more interesting situation where the two environments are equally prevalent in the long term, with low-moderate environmental variation, a generalist strategy (that copes with both states well) does best. Higher variation favors diversified bet hedgers, or surprisingly, specialists, depending mainly on whether spatial or temporal variation predominates. These strategies reduce variance in fitness and optimize the distribution of offspring among patches differently: specialists by spreading offspring among many independently varying patches, while diversified bet hedgers put all offspring into a few patches or a single patch. We distinguish features consistent with strategies like diversified bet hedgers that spread risk in time from features linked to strategies like specialists that spread risk in space. Finally, we present testable hypotheses arising from this study and suggest directions for future work.

The seasonal availability of food resources is an important factor shaping the life-history strategies of organisms. During times of nutritional restriction, physiological trade-offs can induce periods of immune suppression, thereby increasing susceptibility to infectious disease. Our goal was to provide a conceptual framework describing how the endemic level bovine brucellosis (Brucella abortus) may be maintained in Yellowstone bison based on the seasonality of food resources and the life-history strategies of the host and pathogen. Our analysis was based on active B. abortus infection (measured via bacterial culture), nutritional indicators (measured as metabolites and hormones in plasma), and carcass measurements of 402 slaughtered bison. Data from Yellowstone bison were used to investigate (1) whether seasonal changes in diet quality affect nutritional condition and coincide with the reproductive needs of female bison; (2) whether active B. abortus infection and infection intensities vary with host nutrition and nutritional condition; and (3) the evidence for seasonal changes in immune responses, which may offer protection against B. abortus, in relation to nutritional condition. Female bison experienced a decline in nutritional condition during winter as reproductive demands of late gestation increased while forage quality and availability declined. Active B. abortus infection was negatively associated with bison age and nutritional condition, with the intensity of infection negatively associated with indicators of nutrition (e.g., dietary protein and energy) and body weight. Data suggest that protective cell-mediated immune responses may be reduced during the B. abortus transmission period, which coincides with nutritional insufficiencies and elevated reproductive demands during spring. Our results illustrate how seasonal food restriction can drive physiological trade-offs that suppress immune function and create infection and transmission opportunities for pathogens.

Understanding the role of adaptive plasticity under random environmental variation is a central challenge of contemporary life history analysis. An important class of plastic responses is “cohort splitting” ( Sunderland et al., 1976 ), in which groups of organisms beginning development at nearly the same time follow discrete developmental pathways or tracks differing in duration. We identify published studies on the topic and focus on three mechanisms predominant in those studies; we refer to the mechanisms as initiation asynchrony , in which differences in start-up timing can cause a split; mid-point cueing , a bifurcation at some seasonal time and intermediate developmental stage; and diversified tracking , in which individuals are assigned to developmental tracks probabilistically at the outset of development. We use optimization models to evaluate production of cohort splits by these mechanisms. We show that initiation asynchrony is generally a possible explanation but is highly sensitive to environmental conditions. Initiation asynchrony may result either from random variation in development or environment, with subsequent adaptive choices of life-cycle pathway—or from adjustments in developmental onset via diversified bet hedging. Mid-point cueing requires sufficiently high random variation in developmental rates. The adaptive response for Mid-point cueing results from matching the fitness-maximizing pathway to the stage of development at the bifurcation point. Diversified tracking can result from diversified bet hedging, but in this case, high random variation between pathways in reproductive success is essential for diversified tracking to prove adaptive. When diversified tracking results instead from frequency dependence of survival or reproductive success, this mechanism is potentially independent of environmental variation, but frequency dependence is challenging to demonstrate. Additional empirical analyses, especially experimental and comparative approaches, are high priorities for future work.

Invasive species are often able to establish and spread with the help of diseases they bring that can infect native competitors. But sometimes, seemingly successful invasions, in which the invasive species may reach high densities, suddenly collapse, with abrupt decline and extinction of the invader. Diseases have been implicated in invasion collapses, though the underlying mechanism accounting for the entire invasion arc is unresolved. In this study, we simulated a disease-mediated invasion (DMI) by constructing a susceptible-infected-susceptible model for infection and population dynamics of a native and an invasive species. We found that when a competitively dominant native species became an inferior competitor due to infection with the invader’s disease, the native population could often withstand replacement and could sometimes reverse the invasion by evolving an effective disease defense—a resistance-driven evolutionary rebound leading to invasion collapse. The collapse pattern depended on a lag between the disease advance and the invader advance, creating a region of time and space in which the native populations contended only with the disease, evolving disease resistance before confronting the competing invader. We determined the biological conditions and spatial scale in which a DMI may end in evolutionary rebound and collapse, and we present testable predictions for DMI community dynamics.

Tradeoffs – negative reciprocal causal relationships in net benefits between trait magnitudes – have not always been studied in depth appropriate to their central role in life-history analysis. Here we focus on allocation tradeoffs, in which acquisition of a limiting resource requires allocation of resource to alternative traits. We identify the components of this allocation process and emphasize the importance of quantifying them. We then propose categorizing allocation tradeoffs into linear, concave and convex relationships based on the way that resource allocation yields trait magnitudes under the tradeoff. Linear relationships are over-represented in the literature because of typically small data sets over restricted ranges of trait magnitudes, an emphasis on simple correlation analysis, and a failure to remove variation associated with acquisition of the limiting resource in characterizing the tradeoff. (We provide methods for controlling these acquisition effects.) Non-linear relationships have been documented and are expected under plausible conditions that we summarize. We note ways that shifting environments and biological features yield plasticity of tradeoff graphs. Finally, we illustrate these points using case studies and close with priorities for future work.

Body size can strongly influence the components of fitness. We investigated the role of body mass in the reproductive success of the parasitoid Copidosoma bakeri (Howard) (Hymenoptera: Encyrtidae). Copidosoma bakeri develops polyembryonically, producing thousands of genetically identical individuals from one egg. In this species, the brood size and body mass of clonal individuals developing within a host are in a trade-off relationship, which flexibly responds to the environment while maintaining female-biased sexual size dimorphism. We addressed the following questions regarding several possible effects of body mass on male and female reproductive success. (1) Is longevity positively related to body size in both sexes? (2) Is potential fecundity positively related to female body size? (3) Is mating competitiveness positively correlated with male body size? We found that body size increased with longevity of females, but not of males. Copidosoma bakeri was weakly synovigenic; a few eggs were produced after female maturation. Also, egg volume increased with age of the females. We did not detect a relationship between body size and potential fecundity, but mated females produced more eggs than unmated females. Thus, larger females may increase their opportunities to mate, find hosts, and oviposit primarily by living longer. Male mating competitiveness was not related to body mass. Mating reduced male longevity, suggesting a cost of mating that was independent of body mass. Differences between males and females in the effects of body mass on longevity suggest sex-specific selection pressures on body mass that may explain female-biased sexual size dimorphism.

Recent releases of mosquitoes infected with different Wolbachia types into Australia have led to conditions that have not been observed naturally and that have not been considered theoretically. In an ongoing public health campaign, two Wolbachia infection types have been introduced, and the infections differ in their fitness cost imposed on the host mosquito. The dynamics of each infection type as it interacts with the indigenous uninfected host population have been previously examined via models and empirical tests. Here we conduct a modeling analysis to predict the dynamics when the two infection types do not remain geographically isolated. The results demonstrate the potential replacement and loss of the more costly infection type, which may not be the desired public health outcome.

Many temperate bat species deal with harsh winter conditions by hibernating. Brief periods of arousal from torpor occur at regular intervals throughout hibernation, although energetically costly. Factors that increase arousal frequency, such as the recently discovered white-nose syndrome (WNS), can thereby greatly decrease survival rates of overwintering bats. Evidence increasingly suggests that evaporative water loss (EWL) may be an important driver of arousal behavior in infected bats. We examined the role that EWL could play in torpor arousals and energy expenditures by developing an individual-based energetics model using EWL as the stimulus for arousal in populations of healthy and WNS-affected little brown myotis (Myotis lucifugus). Our model also examined how EWL could affect spatial distributions of healthy and infected bats within a cave throughout winter. We calculated mean torpor bout duration and survival of populations that inhabited 2 modeled caves typical of both northern and midrange hibernacula. In a northern cave, the mean torpor bout duration was 19.97 days 6 5.49 SD between arousals for healthy bats and 8.60 6 2.11 days for WNS-affected bats, accompanied by survival rates of 0.80 6 0.07 SD (healthy) and 0.04 6 0.02 (infected). In a midrange cave, the mean torpor bout duration was 20.88 6 6.22 days for healthy bats and 8.88 6 2.47 for infected bats, and survival rates were 0.98 6 0.02 (healthy) and 0.55 6 0.05 (infected). When bats clustered, survival rates increased in both healthy and diseased populations; however, slight changes in relative humidity or the rate of EWL from infected skin counteracted these advantages. We show that, by causing an increase in arousal rates, EWL could play an important role in the pathology of WNS. Additionally, populations experiencing shorter southern winters could persist longer than their northern counterparts when faced with WNS, a fact that could be critical in maintaining viable populations for WNS-vulnerable species.

Ambient temperature can influence development through effects on metabolic rate and by inducing physiological stress. In this study, we assessed temperature effects on a host–parasitoid interaction and on the body size and brood size of emerging wasps. By examining the development at two different temperatures of the koinobiont parasitoid, Copidosoma bakeri, and its host, Agrotis ipsilon, we asked: (1) Does the growth response to temperature by A. ipsilon depend on whether the moth caterpillar is parasitized? (2) Does the allocation pattern of body size and brood size in C. bakeri change with temperature? To answer these questions, we exposed A. ipsilon larvae parasitized by C. bakeri to high or low non-lethal temperatures when A. ipsilon was in early or late larval stages and measured their development time and body mass for all four treatment combinations. We also examined the brood size and body mass of emerging wasps. Whether parasitized or not, A. ipsilon larvae decreased development time, but generally did not decrease final body mass, at the higher temperature. When parasitized A. ipsilon was exposed to the higher temperature only late in their development, enlargement of the host by the parasitoid was reduced. C. bakeri brood size significantly increased when the higher temperature was applied early in host development. We did not detect a shift with temperature in the allocation pattern of the size–number trade-off for wasp offspring, suggesting that this trade-off relationship may be under selection strong enough to yield insensitivity to temperature.