Shane A. Richards

Model selection and model averaging in behavioural ecology: the utility of the IT-AIC framework

Behavioural ecologists often study complex systems in which multiple hypotheses could be proposed to explain observed phenomena. For some systems, simple controlled experiments can be employed to reveal part of the complexity; often, however, observational studies that incorporate a multitude of causal factors may be the only (or preferred) avenue of study. We assess the value of recently advocated approaches to inference in both contexts. Specifically, we examine the use of information theoretic (IT) model selection using Akaike’s information criterion (AIC). We find that, for simple analyses, the advantages of switching to an IT-AIC approach are likely to be slight, especially given recent emphasis on biological rather than statistical significance. By contrast, the model selection approach embodied by IT approaches offers significant advantages when applied to problems of more complex causality. Model averaging is an intuitively appealing extension to model selection. However, we were unable to demonstrate consistent improvements in prediction accuracy when using model averaging with IT-AIC; our equivocal results suggest that more research is needed on its utility. We illustrate our arguments with worked examples from behavioural experiments.

The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine

Fibroblasts from patients with the severe laminopathy diseases, restrictive dermopathy (RD) and Hutchinson Gilford progeria syndrome (HGPS), are characterized by poor growth in culture, the presence of abnormally shaped nuclei and the accumulation of DNA double-strand breaks (DSB). Here we show that the accumulation of DSB and poor growth of the fibroblasts but not the presence of abnormally shaped nuclei are caused by elevated levels of reactive oxygen species (ROS) and greater sensitivity to oxidative stress. Basal levels of ROS and sensitivity to H(2)O(2) were compared in fibroblasts from normal, RD and HGPS individuals using fluorescence activated cell sorting-based assays. Basal levels of ROS and stimulated levels of ROS were both 5-fold higher in the progeria fibroblasts. Elevated levels of ROS were correlated with lower proliferation indices but not with the presence of abnormally shaped nuclei. DSB induced by etoposide were repaired efficiently in normal, RD and HGPS fibroblasts. In contrast, DSB induced by ROS were repaired efficiently in normal fibroblasts, but in RD and HGPS fibroblasts many ROS-induced DSB were un-repairable. The accumulation of ROS-induced DSB appeared to cause the poor growth of RD and HGPS fibroblasts, since culture in the presence of the ROS scavenger N-acetyl cysteine (NAC) reduced the basal levels of DSB, eliminated un-repairable ROS-induced DSB and greatly improved population-doubling times. Our findings suggest that un-repaired ROS-induced DSB contribute significantly to the RD and HGPS phenotypes and that inclusion of NAC in a combinatorial therapy might prove beneficial to HGPS patients.

Facilitated transport and diffusion take distinct spatial routes through the nuclear pore complex

Transport across the nuclear envelope is regulated by nuclear pore complexes (NPCs). Much is understood about the factors that shuttle and control the movement of cargos through the NPC, but less has been resolved about the translocation process itself. Various models predict how cargos move through the channel; however, direct observation of the process is missing. Therefore, we have developed methods to accurately determine cargo positions within the NPC. Cargos were instantly trapped in transit by high-pressure freezing, optimally preserved by low-temperature fixation and then localized by immunoelectron microscopy. A statistical modelling approach was used to identify cargo distribution. We found import cargos localized surprisingly close to the edge of the channel, whereas mRNA export factors were at the very centre of the NPC. On the other hand, diffusion of GFP was randomly distributed. Thus, we suggest that spatially distinguished pathways exist within the NPC. Deletion of specific FG domains of particular NPC proteins resulted in collapse of the peripheral localization and transport defects specific to a certain karyopherin pathway. This further confirms that constraints on the route of travel are biochemical rather than structural and that the peripheral route of travel is essential for facilitated import.

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

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

Modulation of global low-frequency motions underlies allosteric regulation: demonstration in CRP/FNR family transcription factors.

Allostery in bacterial transcription factors arises from changes in global low-frequency protein dynamics. Amino acids that regulate low-frequency dynamics are identified and seen to be evolutionarily conserved.

Prevalence, thresholds and the performance of presence–absence models

1.The use of species distribution models to understand and predict species’ distributions necessitates tests of fit to empirical data. Numerous performance metrics have been proposed, many of which require continuous occurrence probabilities to be converted to binary “present or absent” predictions using threshold transformations. It is widely accepted that both continuous and binary performance metrics should be independent of prevalence (the proportion of locations that are occupied). However, because these metrics have been mostly assessed on a case-specific basis, there are few general guidelines for measuring performance. 2.Here, we develop a conceptual framework for classifying performance metrics, based on whether they are sensitive to prevalence, and whether they require binary predictions. We use this framework to investigate how these performance metric properties influence the predictions made by the models they select. 3.A literature survey reveals that binary metrics are widely employed and that prevalence-independent metrics are used more frequently than prevalence-dependent metrics. However, we show that prevalence-dependent metrics are essential to assess the numerical accuracy of model predictions, and are more useful in applications that require occupancy estimates. Furthermore, we demonstrate that in comparison with continuous metrics, binary metrics often select models that have reduced ability to separate presences from absences, make predictions which over- or under-estimate occupancy, and give misleading estimates of uncertainty. Importantly, models selected using binary metrics will often be of reduced practical use even when applied to ecological problems that require binary decision-making. 4.We suggest that SDM performance should be assessed using prevalence-dependent performance metrics whenever the absolute values of occurrence predictions are important, and that continuous metrics should be used instead of binary metrics whenever possible. We thus recommend the wider application of prevalence-dependent continuous metrics, particularly likelihood-based metrics such as Akaikes information criterion (AIC), to assess the performance of presence-absence models.

Variation in Pollination: Causes and Consequences for Plant Reproduction

Pollen dispersal by animals varies extensively because of differences in pollinator visitation rates among plants, dissimilar pollination by the various pollinators that visit individual plants, and stochastic variation in deposition as an individual pollinator disperses a plant’s pollen to subsequently visited recipient flowers. Such variation reduces expected female and male success if seed production decelerates with increasing pollen receipt, because less than average receipt diminishes mean seed production more than copious pollination increases it (Jensen’s inequality). We report empirical studies of the nature and magnitude of pollen dispersal variance, which provide the basis for a numerical model of the consequences of dispersal for expected seed production. Model fitting revealed that dispersal of Brassica napus pollen by bumblebees and especially butterflies exhibited much more variation than is expected of a binomial process and was best modeled as a beta‐binomial process with a constant mean. Overdispersion arose primarily during pollen dispersal by individual insects, since differences between individuals of the same pollinator type were limited. Our model revealed variance limitation as a previously unrecognized, substantial, and ubiquitous component of pollen limitation of seed production. Variance limitation should select for floral traits that increase pollinator visitation, reduce dispersal variance, or reduce the postpollination nonlinearities that cause Jensen’s inequality.

Assessing the future threat from vivax malaria in the United Kingdom using two markedly different modelling approaches.

BackgroundThe world is facing an increased threat from new and emerging diseases, and there is concern that climate change will expand areas suitable for transmission of vector borne diseases. The likelihood of vivax malaria returning to the UK was explored using two markedly different modelling approaches. First, a simple temperature-dependent, process-based model of malaria growth transmitted by Anopheles atroparvus, the historical vector of malaria in the UK. Second, a statistical model using logistic-regression was used to predict historical malaria incidence between 1917 and 1918 in the UK, based on environmental and demographic data. Using findings from these models and saltmarsh distributions, future risk maps for malaria in the UK were produced based on UKCIP02 climate change scenarios.ResultsThe process-based model of climate suitability showed good correspondence with historical records of malaria cases. An analysis of the statistical models showed that mean temperature of the warmest month of the year was the major factor explaining the distribution of malaria, further supporting the use of the temperature-driven processed-based model. The risk maps indicate that large areas of central and southern England could support malaria transmission today and could increase in extent in the future. Confidence in these predictions is increased by the concordance between the processed-based and statistical models.ConclusionAlthough the future climate in the UK is favourable for the transmission of vivax malaria, the future risk of locally transmitted malaria is considered low because of low vector biting rates and the low probability of vectors feeding on a malaria-infected person.

Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis

Summary Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging.

OsSFR6 is a functional rice orthologue of SENSITIVE TO FREEZING-6 and can act as a regulator of COR gene expression, osmotic stress and freezing tolerance in Arabidopsis.

The Arabidopsis protein SENSITIVE TO FREEZING-6 (AtSFR6) is required for cold- and drought-inducible expression of COLD-ON REGULATED (COR) genes and, as a consequence, AtSFR6 is essential for osmotic stress and freezing tolerance in Arabidopsis. Therefore, orthologues of AtSFR6 in crop species represent important candidate targets for future manipulation of stress tolerance. We identified and cloned a homologue of AtSFR6 from rice (Oryza sativa), OsSFR6, and confirmed its orthology in Arabidopsis. OsSFR6 was identified by homology searches, and a full-length coding region isolated using reverse transcription polymerase chain reaction (RT-PCR) from Oryza sativa cDNA. To test for orthology, OsSFR6 was expressed in an Arabidopsis sfr6 loss-of-function mutant background, and restoration of wild-type phenotypes was assessed. Searching the rice genome revealed a single homologue of AtSFR6. Cloning and sequencing the OsSFR6 coding region showed OsSFR6 to have 61.7% identity and 71.1% similarity to AtSFR6 at the predicted protein sequence level. Expression of OsSFR6 in the atsfr6 mutant background restored the wild-type visible phenotype, as well as restoring wild-type levels of COR gene expression and tolerance of osmotic and freezing stresses. OsSFR6 is an orthologue of AtSFR6, and thus a target for future manipulation to improve tolerance to osmotic and other abiotic stresses.