Functional responses in the habitat selection of a generalist mega‐herbivore,the African savannah elephant

Resource selection function (RSF) models are commonly used to quantify species/habitat associations and predict species occurrence on the landscape. However, these models are sensitive to changes in resource availability and can result in a functional response to resource abundance, where preferences change as a function of availability. For generalist species, which utilize a wide range of habitats and resources, quantifying habitat selection is particularly challenging. Spatial and temporal changes in resource abundance can result in changes in selection preference affecting the robustness of habitat selection models. We examined selection preference across a wide range of ecological conditions for a generalist mega‐herbivore, the African savanna elephant Loxodonta africana, to quantify general patterns in selection and to illustrate the importance of functional responses in elephant habitat selection. We found a functional response in habitat selection across both space and time for tree cover, with tree cover being unimportant to habitat selection in the mesic, eastern populations during the wet season. A temporal functional response for water was also evident, with greater variability in selection during the wet season. Selection for low slopes, high tree cover, and far distance from people was consistent across populations; however, variability in selection coefficients changed as a function of the abundance of a given resource within the home range. This variability of selection coefficients could be used to improve confidence estimations for inferences drawn from habitat selection models. Quantifying functional responses in habitat selection is one way to better predict how wildlife will respond to an ever‐changing environment, and they provide promising insights into the habitat selection of generalist species.     

Virtual plants: modelling as a tool for the genomics of tolerance to water deficit

Modelling can simulate the responses of virtual plants carrying diverse combinations of alleles under different scenarios of abiotic stress. The main difficulty is mathematically expressing the genetic variability of responses to environmental conditions. Modelling via gene regulatory networks is not feasible for such complex systems, but plants can be modelled using response curves to environmental conditions that are 'meta mechanisms' at plant level. Each genotype is represented by a set of response parameters that are valid under a wide range of conditions. Transgenesis of one function experimentally affected one response parameter only. Transgenic plants or plants carrying any combination of quantitative trait loci might therefore be simulated and tested under different climatic scenarios, before genetic manipulations are performed.     

Sequence fingerprints in BRCA2 and RAD51: implications for DNA repair and cancer

In humans, the interactions between the breast cancer susceptibility protein, BRCA2, and the RAD51 recombinase are essential for DNA repair by homologous recombination (HR), failure of which can predispose to cancer. The interactions occur through conserved BRC repeat motifs, encoded in BRCA2, binding directly to RAD51. Here, we describe full and partial BRCA2 homologues from a wide range of eukaryotes, including Drosophila melanogaster and two Plasmodium species. The crystal structure of the human BRC4-RAD51 complex allows identification of residues that are important for protein-protein interaction, and defines interaction sequence fingerprints for the BRC repeat and for RAD51. These allow us to predict that most eukaryotic RAD51 and BRC repeat orthologues should be capable of mutual interactions. We find no evidence for the presence of BRC repeats in yeast, Archaea and bacteria, and their RAD51 orthologues do not fulfil the criteria for binding the BRC repeat. Similarly, human RAD51 paralogues, including RAD51B, RAD51C, RAD51D, XRCC2, XRCC3 and DMC1, are not predicted to bind the BRC repeat. Conservation of the BRC repeat and RAD51 sequence fingerprints across a wide range of eukaryotic species substantiates the functional significance of the BRCA2-RAD51 interactions. The idea of multiple BRC repeats with binding specificity towards RAD51 leads us to suggest a possible model for the participation of BRCA2 in RAD51 nucleoprotein filament formation.     

Inertia effects on characterization of dynamic response of brain tissue

Modeling and simulation of traumatic brain injury (TBI) resulted from collision or blast loading requires characterization of mechanical response over a wide range of loading rates under valid testing conditions. In this study, mechanical response of fresh bovine brain tissue was studied using the two modified Kolsky bar techniques. Radial deformation behavior of annular specimens, which are typically used to characterize the dynamic uniaxial compressive response of biological tissues, was examined using a modified Kolsky bar and a high speed camera to collect images while the specimen deforms at an axial strain rate of 2000s(-1). The high-speed images revealed inhomogeneous specimen deformation possibly brought about by radial inertia and causing a multi-axial stress state. To acquire valid stress-strain results that can be used to produce constitutive behavior of the soft materials, a novel torsion technique was developed to obtain pure shear response at dynamic loading rates. Experimental results show clear differences in the material response using the two methods. These results indicate that the previously demonstrated annular specimen geometry aimed at reducing inertia induced stress components for high rate soft materials uniaxial-compressive testing may still possess a significant component of radial inertia induced radial stress which consequently caused the observed inhomogeneous deformation in brain tissue test samples.     

A method for planar biaxial mechanical testing that includes in-plane shear.

A limitation in virtually all planar biaxial studies of soft tissues has been the inability to include the effects of in-plane shear. This is due to the inability of current mechanical testing devices to induce a state of in-plane shear, due to the added cost and complexity. In the current study, a straightforward method is presented for planar biaxial testing that induces a combined state of in-plane shear and normal strains. The method relies on rotation of the test specimen's material axes with respect to the device axes and on rotating carriages to allow the specimen to undergo in-plane shear freely. To demonstrate the method, five glutaraldehyde treated bovine pericardium specimens were prepared with their preferred fiber directions (defining the material axes) oriented at 45 deg to the device axes to induce a maximum shear state. The test protocol included a wide range of biaxial strain states, and the resulting biaxial data re-expressed in material axes coordinate system. The resulting biaxial data was then fit to the following strain energy function W: [equation: see text] where E'ij is the Green's strain tensor in the material axes coordinate system and c and Ai are constants. While W was able to fit the data very well, the constants A5 and A6 were found not to contribute significantly to the fit and were considered unnecessary to model the shear strain response. In conclusion, while not able to control the amount of shear strain independently or induce a state of pure shear, the method presented readily produces a state of simultaneous in-plane shear and normal strains. Further, the method is very general and can be applied to any anisotropic planar tissue that has identifiable material axes.     

In vivo biomechanics of the fingerpad skin under local tangential traction

Small patches of fingerpad glabrous skin in human subjects were tested in vivo for their biomechanical properties under tangential loading and for large deformations. These conditions included stretching and shearing the skin at a length scale of 0.3mm using an apparatus comprising a pair of piezoelectric benders arranged to increase the stiffness/free deflection tradeoff when compared to ordinary cantilevered benders. It was then possible to test the skin with up to 80% of tangential strain. With feedback control, it was also possible to create isotonic and isometric testing conditions. The results showed much variability across subjects and it was seen that the glabrous skin exhibited nonlinear stiffening in tangential traction. The skin was consistently more elastic across the ridges than along the ridges regardless of the location of the sample on the fingerpad. The skin behaved visco-elastically but relaxed about twice as fast than it crept. Finally, it was found that under large deformation, there was consistently 80% of hysteretic loss for a wide range of loading conditions.     

Novel Approach to Simulate Sleep Apnea Patients for Evaluating Positive Pressure Therapy Devices

Bench testing is a useful method to characterize the response of different automatic positive airway pressure (APAP) devices under well-controlled conditions. However, previous models did not consider the diversity of obstructive sleep apnea (OSA) patients’ characteristics and phenotypes. The objective of this proof-of-concept study was to design a new bench test for realistically simulating an OSA patient’s night, and to implement a one-night example of a typical female phenotype for comparing responses to several currently-available APAP devices. We developed a novel approach aimed at replicating a typical night of sleep which includes different disturbed breathing events, disease severities, sleep/wake phases, body postures and respiratory artefacts. The simulated female OSA patient example that we implemented included periods of wake, light sleep and deep sleep with positional changes and was connected to ten different APAP devices. Flow and pressure readings were recorded; each device was tested twice. The new approach for simulating female OSA patients effectively combined a wide variety of disturbed breathing patterns to mimic the response of a predefined patient type. There were marked differences in response between devices; only three were able to overcome flow limitation to normalize breathing, and only five devices were associated with a residual apnea-hypopnea index of <5/h. In conclusion, bench tests can be designed to simulate specific patient characteristics, and typical stages of sleep, body position, and wake. Each APAP device behaved differently when exposed to this controlled model of a female OSA patient, and should lead to further understanding of OSA treatment.     

Plasticity in Dendroclimatic Response across the Distribution Range of Aleppo Pine (Pinus halepensis)

We investigated the variability of the climate-growth relationship of Aleppo pine across its distribution range in the Mediterranean Basin. We constructed a network of tree-ring index chronologies from 63 sites across the region. Correlation function analysis identified the relationships of tree-ring index to climate factors for each site. We also estimated the dominant climatic gradients of the region using principal component analysis of monthly, seasonal, and annual mean temperature and total precipitation from 1,068 climatic gridpoints. Variation in ring width index was primarily related to precipitation and secondarily to temperature. However, we found that the dendroclimatic relationship depended on the position of the site along the climatic gradient. In the southern part of the distribution range, where temperature was generally higher and precipitation lower than the regional average, reduced growth was also associated with warm and dry conditions. In the northern part, where the average temperature was lower and the precipitation more abundant than the regional average, reduced growth was associated with cool conditions. Thus, our study highlights the substantial plasticity of Aleppo pine in response to different climatic conditions. These results do not resolve the source of response variability as being due to either genetic variation in provenance, to phenotypic plasticity, or a combination of factors. However, as current growth responses to inter-annual climate variability vary spatially across existing climate gradients, future climate-growth relationships will also likely be determined by differential adaptation and/or acclimation responses to spatial climatic variation. The contribution of local adaptation and/or phenotypic plasticity across populations to the persistence of species under global warming could be decisive for prediction of climate change impacts across populations. In this sense, a more complex forest dynamics modeling approach that includes the contribution of genetic variation and phenotypic plasticity can improve the reliability of the ecological inferences derived from the climate-growth relationships.     

Dynamic Sensorimotor Planning during Long-Term Sequence Learning: The Role of Variability,Response Chunking and Planning Errors

Many everyday skills are learned by binding otherwise independent actions into a unified sequence of responses across days or weeks of practice. Here we looked at how the dynamics of action planning and response binding change across such long timescales. Subjects (N = 23) were trained on a bimanual version of the serial reaction time task (32-item sequence) for two weeks (10 days total). Response times and accuracy both showed improvement with time, but appeared to be learned at different rates. Changes in response speed across training were associated with dynamic changes in response time variability, with faster learners expanding their variability during the early training days and then contracting response variability late in training. Using a novel measure of response chunking, we found that individual responses became temporally correlated across trials and asymptoted to set sizes of approximately 7 bound responses at the end of the first week of training. Finally, we used a state-space model of the response planning process to look at how predictive (i.e., response anticipation) and error-corrective (i.e., post-error slowing) processes correlated with learning rates for speed, accuracy and chunking. This analysis yielded non-monotonic association patterns between the state-space model parameters and learning rates, suggesting that different parts of the response planning process are relevant at different stages of long-term learning. These findings highlight the dynamic modulation of response speed, variability, accuracy and chunking as multiple movements become bound together into a larger set of responses during sequence learning.     

The biomechanics of human femurs in axial and torsional loading: comparison of finite element analysis, human cadaveric femurs, and synthetic femurs

To assess the performance of femoral orthopedic implants, they are often attached to cadaveric femurs, and biomechanical testing is performed. To identify areas of high stress, stress shielding, and to facilitate implant redesign, these tests are often accompanied by finite element (FE) models of the bone/implant system. However, cadaveric bone suffers from wide specimen to specimen variability both in terms of bone geometry and mechanical properties, making it virtually impossible for experimental results to be reproduced. An alternative approach is to utilize synthetic femurs of standardized geometry, having material behavior approximating that of human bone, but with very small specimen to specimen variability. This approach allows for repeatable experimental results and a standard geometry for use in accompanying FE models. While the synthetic bones appear to be of appropriate geometry to simulate bone mechanical behavior, it has not, however, been established what bone quality they most resemble, i.e., osteoporotic or osteopenic versus healthy bone. Furthermore, it is also of interest to determine whether FE models of synthetic bones, with appropriate adjustments in input material properties or geometric size, could be used to simulate the mechanical behavior of a wider range of bone quality and size. To shed light on these questions, the axial and torsional stiffness of cadaveric femurs were compared to those measured on synthetic femurs. A FE model, previously validated by the authors to represent the geometry of a synthetic femur, was then used with a range of input material properties and change in geometric size, to establish whether cadaveric results could be simulated. Axial and torsional stiffnesses and rigidities were measured for 25 human cadaveric femurs (simulating poor bone stock) and three synthetic "third generation composite" femurs (3GCF) (simulating normal healthy bone stock) in the midstance orientation. The measured results were compared, under identical loading conditions, to those predicted by a previously validated three-dimensional finite element model of the 3GCF at a variety of Young's modulus values. A smaller FE model of the 3GCF was also created to examine the effects of a simple change in bone size. The 3GCF was found to be significantly stiffer (2.3 times in torsional loading, 1.7 times in axial loading) than the presently utilized cadaveric samples. Nevertheless, the FE model was able to successfully simulate both the behavior of the 3GCF, and a wide range of cadaveric bone data scatter by an appropriate adjustment of Young's modulus or geometric size. The synthetic femur had a significantly higher stiffness than the cadaveric bone samples. The finite element model provided a good estimate of upper and lower bounds for the axial and torsional stiffness of human femurs because it was effective at reproducing the geometric properties of a femur. Cadaveric bone experiments can be used to calibrate FE models' input material properties so that bones of varying quality can be simulated.     

Hormonal control of gene expression: interactions between two trans-acting regulators in Drosophila

The steroid hormone 20-hydroxyecdysone (20HE) and the Broad-Complex locus (BRC) are involved in regulating developmental changes in gene expression around the time of metamorphosis in Drosophila. We have investigated the regulatory interactions between 20HE, BRC, and a set of genes expressed in the fat body of third-instar Drosophila larvae. RNA levels for two hormone-inducible genes, Larval Serum Protein-2 and P1, accumulate to normal levels in BRC-mutant larvae. In contrast, RNA levels for the P6 gene were affected by mutations at BRC. On the basis of the results of experiments in which hormone concentrations were varied in BRC-mutant or wild-type larvae, we conclude that 20HE can both increase and decrease P6 RNA levels in the absence of BRC product(s). BRC appears to be a trans-acting modulator of the response of P6 to the hormone. We propose that BRC attenuates the repressive effect of the hormone, expanding the range of hormone concentrations that induce the gene, thus allowing P6 RNA to reach high levels during the third larval instar. The results are discussed in relation to other genes that are regulated by the same two trans-acting factors. A model is presented that refines the model of Ashburner et al. (1974, Cold Spring Harbor Symp. Quant. Biol. 38: 655-662) for the hormonal regulation of gene activity.     

Choice of selection environment for improving crop yields in saline areas

Spatial variability in salt-affected fields is normally very high. Thus, most salinity affected lands are actually comprised of many micro-environments, ranging from low to high salinity in the same field. The evidence on testing genotypes across a broad range of salinity levels shows that the genotype-by-salinity level interaction is commonly large. Thus, breeding for saline areas can be compared to what has been known as breeding for wide adaptation. The target environments both for breeding for saline soils or for wide adaptation are actually a population of many possible environments, for which there exists a significant component of genotype-by-environment(G x E) interaction. Thus it is possible to study the merit of potential strategies for breeding for salinity tolerance using the tools that have been developed for the study of breeding for wide adaptation. The evidence from selection and breeding experiments for wide adaptation seems to favour testing on a representative subset of environments, including stress and non-stress locations; but the choice of these locations is complicated by the multidimensional nature of G x E. However, in the case of salt stress, the crop-yield response functions to salinity are well known. This paper presents an attempt to systematise the choice of the optimum environment(s) to select for improved yield under saline soil conditions, based on the three-piece linear equation presented by Maas and Hoffman (1977) and the theory of direct and indirect responses to selection. It is proposed that three saline levels should be enough to make a valid estimation of the suitability of a number of selection strategies. A worked example with data from a set of grain sorghum inbred lines tested on ten saline levels shows that the same selection strategies would be chosen using the information from the ten saline levels as that obtained using the two extremes and one intermediate level.     

The role of environment and core‐margin effects on range‐wide phenotypic variation in a montane grasshopper

The integration of genetic information with ecological and phenotypic data constitutes an effective approach to gain insight into the mechanisms determining interpopulation variability and the evolutionary processes underlying local adaptation and incipient speciation. Here, we use the Pyrenean Morales grasshopper (Chorthippus saulcyi moralesi) as study system to (i) analyse the relative role of genetic drift and selection in range‐wide patterns of phenotypic differentiation and (ii) identify the potential selective agents (environment, elevation) responsible for variation. We also test the hypothesis that (iii) the development of dispersal‐related traits is associated with different parameters related to population persistence/turnover, including habitat suitability stability over the last 120 000 years, distance to the species distribution core and population genetic variability. Our results indicate that selection shaped phenotypic differentiation across all the studied morphological traits (body size, forewing length and shape). Subsequent analyses revealed that among‐population differentiation in forewing length was significantly explained by a temperature gradient, suggesting an adaptive response to thermoregulation or flight performance under contrasting temperature regimes. We found support for our hypothesis predicting a positive association between the distance to the species distribution core and the development of dispersal‐related morphology, which suggests an increased dispersal capability in populations located at range edges that, in turn, exhibit lower levels of genetic variability. Overall, our results indicate that range‐wide patterns of phenotypic variation are partially explained by adaptation in response to local environmental conditions and differences in habitat persistence between core and peripheral populations.     

Variance in Bacillus anthracis virulence assessed through Bayesian hierarchical dose-response modelling

Aims: To develop a predictive dose–response model for describing the survival of animals exposed to Bacillus anthracis to support risk management options. Methods and Results: Dose–response curves were generated from a large dose–mortality data set (>11 000 data points) consisting of guinea pigs exposed via the inhalation route to 76 different product preparations of B. anthracis. Because of the predictive nature of the Bayesian hierarchical approach (BHA), this method was used. The utility of this method in planning for a variety of scenarios from best case to worst case was demonstrated. Conclusions: A wide range of expected virulence was observed across products. Median estimates of virulence match well with previously published statistical estimates, but upper bound values of virulence are much greater than previous statistical estimates. Significance and Impact of the Study: This study is the first meta‐analysis in open literature to estimate the dose–response relationship for B. anthracis from a very large data set, generally a rare occurrence for highly infectious pathogens. The results are also the first to suggest the extent of variability, which is contributed by product preparation and/or dissemination methods, information needed for health‐based risk management decisions in response to a deliberate release. A set of possible benchmark values produced through this analysis can be tied to the risk tolerance of the decision‐maker or available intelligence. Further, the substantial size of the data set led to the ability to assess the appropriateness of the assumed distributional form of the prior, a common limitation in Bayesian analysis.     

Environmental and genetic influences on the germination of Arabidopsis thaliana in the field

Seasonal germination timing strongly influences lifetime fitness and can affect the ability of plant populations to colonize and persist in new environments. To quantify the influence of seasonal environmental factors on germination and to test whether pleiotropy or close linkage are significant constraints on the evolution of germination in different seasonal conditions, we dispersed novel recombinant genotypes of Arabidopsis thaliana into two geographic locations. To decouple the photoperiod during seed maturation from the postdispersal season that maternal photoperiod predicts, replicates of recombinant inbred lines were grown under short days and long days under controlled conditions, and their seeds were dispersed during June in Kentucky (KY) and during June and November in Rhode Island (RI). We found that postdispersal seasonal conditions influenced germination more strongly than did the photoperiod during seed maturation. Genetic variation was detected for germination responses to all environmental factors. Transgressive segregation created novel germination phenotypes, revealing a potential contribution of hybridization of ecotypes to the evolution of germination. A genetic trade-off in germination percentage across sites indicated that determinants of fitness at or before the germination stage may constrain the geographic range that a given genotype can inhabit. However, germination timing exhibited only weak pleiotropy across treatments, suggesting that different sets of genes contribute to variation in germination behavior in different seasonal conditions and geographic locations. Thus, the genetic potential exists for rapid evolution of appropriate germination responses in novel environments, facilitating colonization across a broad geographic range.     

Quantitation of ibogaine and 12-hydroxyibogamine in human plasma by liquid chromatography with fluorimetric detection

A high-performance liquid chromatographic (HPLC) method with fluorimetric detection was developed for the simultaneous determination of ibogaine and noribogaine in human plasma using fluorescein as internal standard. This method involved a solid phase extraction of the compounds from plasma using N-vinylpyrrolidone-divinybenzene copolymer cartridges. Separation of the three analytes was performed on a reversed-phase Supelcosil C18 analytical column (75 mm x 4.6mm i.d., 3 microm particle size). The excitation wavelength was set at 230 nm for the first 15.8min and then at 440 nm for the following 14.2 min; the emission wavelength was set at 336 nm for the first 15.8 min and then at 514 nm for the following 14.2 min. Obtained from the method validation, inter-assay precision was 6.0-12.5% and accuracy was 95.4-104%. The extraction efficiencies of the assay were higher than 94% and were constant across the calibration range. The lower limits of quantitation were 0.89 ng/ml for ibogaine and 1 ng/ml for noribogaine; at these levels, precision was < or =17% and accuracy was 95-105%. In this paper, extensive stability testing was undertaken using a wide range of storage conditions. Special attention must be paid to sample handling to avoid light degradation of the compounds.     

Contrasting growth forecasts across the geographical range of Scots pine due to altitudinal and latitudinal differences in climatic sensitivity

Ongoing changes in global climate are altering ecological conditions for many species. The consequences of such changes are typically most evident at the edge of a species’ geographical distribution, where differences in growth or population dynamics may result in range expansions or contractions. Understanding population responses to different climatic drivers along wide latitudinal and altitudinal gradients is necessary in order to gain a better understanding of plant responses to ongoing increases in global temperature and drought severity. We selected Scots pine (Pinus sylvestris L.) as a model species to explore growth responses to climatic variability (seasonal temperature and precipitation) over the last century through dendrochronological methods. We developed linear models based on age, climate and previous growth to forecast growth trends up to year 2100 using climatic predictions. Populations were located at the treeline across a latitudinal gradient covering the northern, central and southernmost populations and across an altitudinal gradient at the southern edge of the distribution (treeline, medium and lower elevations). Radial growth was maximal at medium altitude and treeline of the southernmost populations. Temperature was the main factor controlling growth variability along the gradients, although the timing and strength of climatic variables affecting growth shifted with latitude and altitude. Predictive models forecast a general increase in Scots pine growth at treeline across the latitudinal distribution, with southern populations increasing growth up to year 2050, when it stabilizes. The highest responsiveness appeared at central latitude, and moderate growth increase is projected at the northern limit. Contrastingly, the model forecasted growth declines at lowland‐southern populations, suggesting an upslope range displacement over the coming decades. Our results give insight into the geographical responses of tree species to climate change and demonstrate the importance of incorporating biogeographical variability into predictive models for an accurate prediction of species dynamics as climate changes.     

Measuring the transverse Young’s modulus of maize rind and pith tissues

Wind-induced bending loads frequently cause failure of maize (corn) stalks. When failure occurs, it usually manifests as transverse buckling. Because this failure mode is closely related to transverse tissue stiffness, the purpose of this study was to develop a method for measuring the transverse Young’s modulus of maize stalk rind and pith tissues. Short, disc-shaped stalk segments were used for this purpose. X-ray computed tomography was used to obtain the geometry of each specimen prior to testing. Each specimen was tested in two different configurations. Computed tomography data was used to create a specimen-specific finite element model of each test specimen. Data from the first testing configuration was used in conjunction with the finite element model to determine the Young’s Modulus values for each specimen. The specimen-specific finite element models provided estimates of the stress states in the stem under transverse loading, and these stress states accurately predicted the location of failure in transverse test specimens. The entire testing method was validated using data from one test configuration to predict the structural response of each specimen during the second test configuration.     

New motion analysis system for characterization of the chemosensory response kinetics of Rhodobacter sphaeroides under different growth conditions

We developed a new set of software tools that enable the speed and response kinetics of large numbers of tethered bacterial cells to be rapidly measured and analyzed. The software provides precision, accuracy, and a good signal-to-noise ratio combined with ease of data handling and processing. The software was tested on the single-cell chemosensory response kinetics of large numbers of Rhodobacter sphaeroides cells grown under either aerobic or photoheterotrophic conditions and either in chemostats or in batch cultures, allowing the effects of growth conditions on responses to be accurately measured. Aerobically and photoheterotrophically grown R. sphaeroides exhibited significantly different chemosensory response kinetics and cell-to-cell variability in their responses to 100 μM propionate. A greater proportion of the population of aerobically grown cells responded to a 100 μM step decrease in propionate; they adapted faster and showed less cell-to-cell variability than photosynthetic populations. Growth in chemostats did not significantly reduce the measured cell to cell variability but did change the adaptation kinetics for photoheterotrophically grown cells.