Binocular interaction: contrast matching and contrast discrimination are predicted by the same model

How do signals from the 2 eyes combine and interact? Our recent work has challenged earlier schemes in which monocular contrast signals are subject to square-law transduction followed by summation across eyes and binocular gain control. Much more successful was a new 'two-stage' model in which the initial transducer was almost linear and contrast gain control occurred both pre- and post-binocular summation. Here we extend that work by: (i) exploring the two-dimensional stimulus space (defined by left- and right-eye contrasts) more thoroughly, and (ii) performing contrast discrimination and contrast matching tasks for the same stimuli. Twenty-five base-stimuli made from 1 c/deg patches of horizontal grating, were defined by the factorial combination of 5 contrasts for the left eye (0.3-32%) with five contrasts for the right eye (0.3-32%). Other than in contrast, the gratings in the two eyes were identical. In a 2IFC discrimination task, the base-stimuli were masks (pedestals), where the contrast increment was presented to one eye only. In a matching task, the base-stimuli were standards to which observers matched the contrast of either a monocular or binocular test grating. In the model, discrimination depends on the local gradient of the observer's internal contrast-response function, while matching equates the magnitude (rather than gradient) of response to the test and standard. With all model parameters fixed by previous work, the two-stage model successfully predicted both the discrimination and the matching data and was much more successful than linear or quadratic binocular summation models. These results show that performance measures and perception (contrast discrimination and contrast matching) can be understood in the same theoretical framework for binocular contrast vision.     

Assessing formal teaching of ethics in physiology: an empirical survey, patterns, and recommendations

Ethics should be an important component of physiological education. In this report, we examined to what extent teaching of ethics is formally being incorporated into the physiology curriculum. We carried out an e-mail survey in which we asked the e-mail recipients whether their institution offered a course or lecture on ethics as part of the physiology teaching process at their institution, using the following query: "We are now doing an online survey in which we would like to know whether you offer a course or a lecture on ethics as part of your physiology teaching curriculum." The response rate was 53.3%: we received 104 responses of a total of 195 sent out. Our responses came from 45 countries. While all of our responders confirmed that there was a need for ethics during medical education and scientific training, the degree of inclusion of formal ethics in the physiology curriculum varied widely. Our survey showed that, in most cases (69%), including at our Medical University of Graz, ethics in physiology is not incorporated into the physiology curriculum. Given this result, we suggest specific topics related to ethics and ethical considerations that could be integrated into the physiology curriculum. We present here a template example of a lecture "Teaching Ethics in Physiology" (structure, content, examples, and references), which was based on guidelines and case reports provided by experts in this area (e.g., Benos DJ. Ethics revisited. Adv Physiol Educ 25: 189-190, 2001). This lecture, which we are presently using in Graz, could be used as a base that could lead to greater awareness of important ethical issues in students at an early point in the educational process.     

Sexually antagonistic co‐evolution: a model and an empirical test

Models reveal that sexually antagonistic co‐evolution exaggerates female resistance and male persistence traits. Here we adapt an established model by including directional sexual selection acting against persistence. We find similar equilibria to previous models showing that sexually antagonistic co‐evolution can be limited by counteracting sexual, as well as, natural selection. We tested the model using empirical data for the seaweed fly, Coelopa ursina, in which body size acts as a persistence and a resistance trait. Our model can generate continuous co‐evolutionary cycles and stable equilibria, however, all simulations using empirically derived parameter estimates reach stable equilibria. Thus, stable equilibria might be more common in nature than continuous co‐evolutionary cycles, suggesting that sexual conflict is unlikely to promote speciation. The model predicts male biased sexual size dimorphism for C. ursina, comparable with empirically observed values. Male persistence is shown to be more sensitive than female resistance to changes in model parameters.     

The power of two-dimensional dwell-time analysis for model discrimination, temporal resolution, multichannel analysis and level detection

Two-dimensional (2D) dwell-time analysis of time series of single-channel patch-clamp current was improved by employing a Hinkley detector for jump detection, introducing a genetic fit algorithm, replacing maximum likelihood by a least square criterion, averaging over a field of 9 or 25 bins in the 2D plane and normalizing per measuring time, not per events. Using simulated time series for the generation of the "theoretical" 2D histograms from assumed Markov models enabled the incorporation of the measured filter response and noise. The effects of these improvements were tested with respect to the temporal resolution, accuracy of the determination of the rate constants of the Markov model, sensitivity to noise and requirement of open time and length of the time series. The 2D fit was better than the classical hidden Markov model (HMM) fit in all tested fields. The temporal resolution of the two most efficient algorithms, the 2D fit and the subsequent HMM/beta fit, enabled the determination of rate constants 10 times faster than the corner frequency of the low-pass filter. The 2D fit was much less sensitive to noise. The requirement of computing time is a problem of the 2D fit (100 times that of the HMM fit) but can now be handled by personal computers. The studies revealed a fringe benefit of 2D analysis: it can reveal the "true" single-channel current when the filter has reduced the apparent current level by averaging over undetected fast gating.     

The DRAG test: an assay for detection of genotoxic damage

A high throughput assay (the DRAG test) is described, which could be a useful tool for the detection of repairable DNA adducts, and which is based on the inhibition of the growth of DNA repair-deficient Chinese hamster ovary (CHO) cells. The cytotoxicity of a test substance towards DNA repair-deficient CHO cell lines is compared with the corresponding cytotoxicity in the parental wild-type CHO cell line (AA8). A more pronounced toxicity toward a DNA repair-deficient cell line is interpreted as being the consequence of its inability to repair the DNA adduct induced by the compound. (+)-7beta,8alpha-Dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, camptothecin, ethyl methanesulphonate and mitomycin C were used as reference substances, and the overall results indicate that the DRAG test could be useful in the screening of compounds for the production of repairable DNA adducts. The main advantages with the DRAG test are that it provides a relevant endpoint, it is rapid, it requires small amounts of the test item, and it permits a large number of compounds to be tested.     

Energy model for contrast detection: spatiotemporal characteristics of threshold vision

A model for contrast detection of spatiotemporal stimuli is proposed which consists of a spatiotemporal linear filter, an energy device and a threshold device. Assuming the existence of independent intrinsic noise, the probability of stimulus detection was approximated by a Weibull function of the response energy. With this assumption, the stimulus energy is a constant at fixed detection probability. This energy model for contrast detection satisfactorily accounted for the elliptical threshold contours of line pairs at stimulus separations within the range 2–30 min and at stimulus onset asynchronies within the range 20–140 ms. The threshold contour at a large stimulus onset asynchrony (300 ms) was in the form of a rounded square. This finding was explained by assuming that the probability of seeing the line pair was determined by the joint probability that at least one stimulus had been detected. With the energy model, the temporal and spatial autocorrelation functions of the response to a flashed line were evaluated. The autocorrelation functions thus determined were used to predict the temporal contrast sensitivity function to a flickering line stimulus and the spatial contrast sensitivity function to flashed gratings, which were in agreement with the experimental data. The data obtained were fitted adequately by an impulse response approximated by a spatiotemporal Gabor-like function. Received: 08 December 1997 / Accepted in revised form: 26 January 1999     

Offspring size-number trade-offs in scorpions: an empirical test of the van Noordwijk and de Jong model

Abstract Life-history traits are expected to exhibit negative phenotypic trade-offs, but often do not. In a seminal paper, van Noordwijk and de Jong (1986) provided an answer to this seeming paradox. According to their model, trade-offs will be more difficult to detect if variation in resource acquisition (or investment) is high relative to variation in resource allocation to the traits under consideration. Despite its influence on subsequent life-history studies, this model has rarely been tested. I use data from 10 species of scorpion (a total of 30 datasets, including multiple populations or years for some species) to test the van Noordwijk-de Jong model as modified to examine the relationship between offspring size and number. For both the overall data and a subset, including only the species Centruroides vittatus , I found that the correlation between offspring size and number within a population was significantly negatively correlated with the ratio of allocation variance to investment variance. That is, strong trade-offs were found when the investment variance was low relative to the allocation variance. These results were robust to the particular measure of offspring size and to whether offspring data were adjusted for female size variation. My results therefore provide strong evidence in support of the van Noordwijk and de Jong model.     

Use of the root contact concept,an empirical leaf conductance model and pressure-volume curves in simulating crop water relations

A simulation model “DanStress” was developed for studying the integrated effects of soil, crop and climatic conditions on water relations and water use of field grown cereal crops. The root zone was separated into 0.1 m deep layers of topsoil and subsoil. For each layer the water potential at the root surface was calculated by a single root model, and the uptake of water across the root was calculated by a root contact model. Crop transpiration was calculated by Monteith's combination equation for vapour flow. Crop conductance to water vapour transfer for use in Monteith's combination equation was scaled up from an empirical stomatal conductance model used on sunlit and shaded crop surfaces of different crop layers. In the model, transpirational water loss originates from root water uptake and changes in crop water storage. Crop water capacitance, used for describing the water storage, was derived from the slope of pressure-volume (PV) curves of the leaves. PV curves were also used for deriving crop water potential, osmotic potential, and turgor pressure. The model could simulate detailed diurnal soil-crop water relations during a 23-day-drying cycle with time steps of one hour. During the grain filling period in spring barley (Hordeum distichum L.), grown in a sandy soil in the field, measured and predicted values of leaf water and osmotic potential, RWC, and leaf stomatal conductance were compared. Good agreement was obtained between measured and predicted values at different soil water deficits and climatic conditions. In the field, measured and predicted volumetric soil water contents (θ) of topsoil and subsoil layers were also compared during a drying cycle. Predicted and measured θ-values as a function of soil water deficits were similar suggesting that the root contact model approach was valid. From the investigation we concluded: (I) a model, which takes the degree of contact between root surface and soil water into account, can be used in sandy soil for calculation of root water uptake, so that the root conductance during soil water depletion only varies by the degree of contact; (II) crop conductance, used for calculation of crop transpiration, can be scaled up from an empirical single leaf stomatal conductance model controlled by the level of leaf water potential and micrometeorological conditions; (III) PV curves are usable for describing crop water status including crop water storage.     

transition priors for protein hidden Markov models: an empirical study towards maximum discrimination.

Insertions and deletions in a profile hidden Markov model (HMM) are modeled by transition probabilities between insert, delete and match states. These are estimated by combining observed data and prior probabilities. The transition prior probabilities can be defined either ad hoc or by maximum likelihood (ML) estimation. We show that the choice of transition prior greatly affects the HMM's ability to discriminate between true and false hits. HMM discrimination was measured using the HMMER 2.2 package applied to 373 families from Pfam. We measured the discrimination between true members and noise sequences employing various ML transition priors and also systematically scanned the parameter space of ad hoc transition priors. Our results indicate that ML priors produce far from optimal discrimination, and we present an empirically derived prior that considerably decreases the number of misclassifications compared to ML. Most of the difference stems from the probabilities for exiting a delete state. The ML prior, which is unaware of noise sequences, estimates a delete-to-delete probability that is relatively high and does not penalize noise sequences enough for optimal discrimination.     

Song divergence at the edge of Amazonia: an empirical test of the peripatric speciation model

The evolutionary divergence of mating signals provides a powerful basis for animal speciation. Divergence in sympatry strengthens reproductive isolation, and divergence in allopatry can reduce or eliminate gene flow between populations on secondary contact. In birds, the first of these processes has empirical support, but the second remains largely hypothetical. This is perhaps because most studies have focused on oscine passerines, whose song learning ability may reduce the influence of vocalizations in reproductive isolation. In suboscine passerines, the role of learning in song development is thought to be minimal, and the resultant signals are relatively fixed. To investigate the role of song in the early stages of peripatric speciation, we therefore studied a suboscine, the chestnut‐tailed antbird Myrmeciza hemimelaena. We recorded male songs in a natural forest island (isolated for < 3000 years) at the southern fringe of Amazonia, and at two nearby sites in continuous forest. A previous study found the isolated population to be weakly differentiated genetically from the ancestral population suggesting that peripatric speciation was underway. In support of this, although we detected minor but significant differences in song structure between each site, the most divergent songs were those of island birds. On simulating secondary contact using playback, we found that pairs from the forest island responded more strongly to island (i.e. local) songs than to those from both non‐island sites, and vice versa. This pattern was not observed in pairs from one non‐island site, which responded with equal strength to local songs and songs from the other non‐island site. Island females were more likely to approach and sing after hearing local male songs, rather than songs from the non‐island populations, and vice versa; non‐island females did not appear to discriminate between local songs and those from the other non‐island site. These findings are consistent with the idea that vocal divergence arising in small populations at the edge of Amazonia may result in partial reproductive isolation when contact is resumed. They also suggest the possibility that song divergence in peripatry may, after much longer time‐frames, act as a barrier to gene flow in suboscines, perhaps because of an inability to learn or recognize divergent songs on secondary contact. © 2007 The Linnean Society of London, Biological Journal of the Linnean Society, 2007, 90 , 173–188.     

The matrix-tolerance hypothesis: an empirical test with frogs in the Atlantic Forest

The matrix-tolerance hypothesis suggests that the most abundant species in the inter-habitat matrix would be less vulnerable to their habitat fragmentation. This model was tested with leaf-litter frogs in the Atlantic Forest where the fragmentation process is older and more severe than in the Amazon, where the model was first developed. Frog abundance data from the agricultural matrix, forest fragments and continuous forest localities were used. We found an expected negative correlation between the abundance of frogs in the matrix and their vulnerability to fragmentation, however, results varied with fragment size and species traits. Smaller fragments exhibited stronger matrix-vulnerability correlation than intermediate fragments, while no significant relation was observed for large fragments. Moreover, some species that avoid the matrix were not sensitive to a decrease in the patch size, and the opposite was also true, indicating significant differences with that expected from the model. Most of the species that use the matrix were forest species with aquatic larvae development, but those species do not necessarily respond to fragmentation or fragment size, and thus affect more intensively the strengthen of the expected relationship. Therefore, the main relationship expected by the matrix-tolerance hypothesis was observed in the Atlantic Forest; however we noted that the prediction of this hypothesis can be substantially affected by the size of the fragments, and by species traits. We propose that matrix-tolerance model should be broadened to become a more effective model, including other patch characteristics, particularly fragment size, and individual species traits (e.g., reproductive mode and habitat preference).     

Single-locus species delimitation: a test of the mixed Yule-coalescent model, with an empirical application to Philippine round-leaf bats

Prospects for a comprehensive inventory of global biodiversity would be greatly improved by automating methods of species delimitation. The general mixed Yule-coalescent (GMYC) was recently proposed as a potential means of increasing the rate of biodiversity exploration. We tested this method with simulated data and applied it to a group of poorly known bats (Hipposideros) from the Philippines. We then used echolocation call characteristics to evaluate the plausibility of species boundaries suggested by GMYC. In our simulations, GMYC performed relatively well (errors in estimated species diversity less than 25%) when the product of the haploid effective population size (N(e)) and speciation rate (SR; per lineage per million years) was less than or equal to 10(5), while interspecific variation in N(e) was twofold or less. However, at higher but also biologically relevant values of N(e) × SR and when N(e) varied tenfold among species, performance was very poor. GMYC analyses of mitochondrial DNA sequences from Philippine Hipposideros suggest actual diversity may be approximately twice the current estimate, and available echolocation call data are mostly consistent with GMYC delimitations. In conclusion, we consider the GMYC model useful under some conditions, but additional information on N(e), SR and/or corroboration from independent character data are needed to allow meaningful interpretation of results.     

Performance of mice in an automated olfactometer: odor detection, discrimination and odor memory

Mice were trained on a variety of odor detection and discrimination tasks in 100- or 200-trial sessions using a go, no-go discrete trials operant conditioning procedure. Odors, presented for 1 s on each trial, were generated by an air dilution olfactometer (for threshold tests) and an easily constructed eight-channel liquid dilution unit (for two- and multiple-odor discrimination tasks). Mice rapidly acquired the operant task and demonstrated excellent stimulus control by odor vapors. Their absolute detection threshold for ethyl acetate was similar to that obtained with rats using similar methods. They readily acquired four separate two-odor discrimination tasks and continued to perform well when all eight odors were presented in random order in the same session and when reinforcement probability for correct responding was decreased from 1 to 0.5. Memory for these eight odors, assessed under extinction after a 32 day rest period, was essentially perfect. Time spent sampling the odor on S+ and S- trials was highly correlated with response accuracy. When accuracy was at chance levels (e.g. initial trials on a novel task), stimulus sampling time on both S+ and S- trials was approximately 0.5-0.7 s. As response accuracy increased, sampling time on S+ trials tended to increase and remain higher than sampling time on S- trials.     

Apoptosis and necrosis: detection, discrimination and phagocytosis.

Three major morphologies of cell death have been described: apoptosis (type I), cell death associated with autophagy (type II) and necrosis (type III). Apoptosis and cell death associated with autophagy can be distinguished by certain biochemical events. However, necrosis is characterized mostly in negative terms by the absence of caspase activation, cytochrome c release and DNA oligonucleosomal fragmentation. A particular difficulty in defining necrosis is that in the absence of phagocytosis apoptotic cells become secondary necrotic cells with many morphological features of primary necrosis. In this review, we present a selection of techniques that can be used to identify necrosis and to discriminate it from apoptosis. These techniques rely on the following cell death parameters: (1) morphology (time-lapse and transmission electron microscopy and flow fluorocytometry); (2) cell surface markers (phosphatidylserine exposure versus membrane permeability by flow fluorocytometry); (3) intracellular markers (oligonucleosomal DNA fragmentation by flow fluorocytometry, caspase activation, Bid cleavage and cytochrome c release by western blotting); (4) release of extracellular markers in the supernatant (caspases, HMGB-1 and cytokeratin 18). Finally, we report on methods that can be used to examine interactions between dying cells and phagocytes. We illustrate a quantitative method for detecting phagocytosis of dying cells by flow fluorocytometry. We also describe a recently developed approach based on the use of fluid phase tracers and different kind of microscopy, transmission electron and fluorescence microscopy, to characterize the mechanisms used by phagocytes to internalize dying cells.     

The Saanen goat as an animal model for post-laryngectomy research: practical implications

A modern way of voice rehabilitation after total laryngectomy includes the use of shunt valves and tracheostoma valves. Problems of fixation to the surrounding tissue are a major drawback in the use of the shunt valve, heat and moisture exchange (HME) filters and, especially, the tracheostoma valve. To solve these problems different tissue connectors were developed. The main objective was to test the feasibility of these prototypes in a new animal model. Here we discuss the results, problems and complications of the selected Saanen goat model. In this prospective laboratory study, 19 healthy adult female Saanen goats (Capra hircus) were used and observed post-surgically for 12 weeks. Selection criteria such as comparable anatomy to humans and easy handling were used for animal model development. Also a literature search using the Medline and the ISI Web of Science databases was performed. The anatomy of the Saanen goat was investigated in a separate postmortem study. Surgery consisted of a laryngotracheal separation and implantation of a tracheo-oesophageal and tracheostoma tissue connector with fibrin tissue glue. Postoperative care consisted of frequent stoma care, monitoring appetite, weight, vital signs and administration of antibiotics, analgesics and mucolytic agents. All animals survived the surgical procedure. However, postoperative care was extensive, labour intensive and was accompanied by several complications. Eleven animals died spontaneously before the end of the experiment. The tracheostoma tissue connector caused signs of local infection in all cases. There was no evidence of infection around the tracheo-oesophageal tissue connector in 18 cases. It was concluded that the use of goats in this tracheostoma model was associated with major complications and should, therefore, only be used for short-term experiments with intensive care. Additional research is needed to see if clinical application of the tissue connectors is possible in the future.     

The geography of speciation in butterflies (Lepidoptera,Papilionoidea): an empirical test of theoretical models

Despite the fundamental role of speciation in formation of biodiversity, the genetic and ecological mechanisms related to this process, as well as the geography of speciation are still poorly known. In our research we have used methods of molecular phylogenetics and phylogeography to reconstruct the stages of speciation in two model groups of butterflies. Phylogeographic analysis showed that speciation in Agrodiaetus blues started in allopatry. An additional age-range correlation test also revealed a pattern consistent with allopatric speciation. However, the formation of new wing colors, the characters most important for maintenance of pre-zygotic reproductive isolation, was shown to occur after transition from allopatry to sympatry. Analysis of karyotypes, mitochondrial and nuclear molecular markers in the Wood White butterfly Leptidea sinapis L. showed that clinal speciation may have occurred in this case; this process is theoretically possible but difficult to document.     

Reconciling neutral community models and environmental filtering: theory and an empirical test

It is widely believed that the neutral theory of biodiversity cannot be used for parameter inference if the assumption of neutrality is not met. The goal of this work is to extend this neutral framework to quantify the intensity of recruitment limitation (limited dispersal plus environmental filtering) in natural species assemblages. We model several local communities as part of a larger metacommunity, and we assume that neutrality holds in each local community, but not in the metacommunity. The immigration rate m does not only reflect dispersal limitation into a given local community, but also the intensity of environmental filtering. We develop a novel statistical method to infer the immigration parameter m in each local community. Using simulated datasets, we show that m indeed depends on both dispersal limitation and on the intensity of environmental filtering. We then apply this method to a network of tropical tree plots in central Panama. Inferred recruitment rates m were positively correlated with the fraction of trees dispersed by mammals, and with annual rainfall, possibly due to a weaker environmental filtering as rainfall increases. Finally, m, as estimated from trees greater than 1 cm trunk diameter, were significantly larger than an estimation based on trees greater than 10 cm trunk diameter. This suggests a cumulative effect of environmental filtering upon trees throughout their ontogeny.