Isolation of an agent affecting the development of an internal parasitoid

The development of an internal braconid parasitoid, Glyptapanteles militaris, is adversely affected when its host, Pseudaletia unipuncta, is infected with the Hawaiian strain of granulosis virus. A plasma-derived agent, isolated from virus-infected hosts, was shown to elicit developmental aberrations in the parasitoid similar to those observed in virus-infected hosts. This agent was isolated by ammonium sulfate precipitation, gel filtration, and anion exchange chromatography, and its molecular weight, established by gel filtration and SDS-polyacrylamide gel electrophoresis, was determined to be about 64,000. The dilution end point of the agent and some stability properties were also established.     

Getting out of the habitus: an alternative model of dynamically embodied social action

Although Bourdieu's theory of practice has drawn widespread attention to the role of the body and space in social life, the concept of habitus is problematic as an explanatory account of dynamic embodiment because it lacks an adequate conception of the nature and location of human agency. An alternative model is presented which locates agency in the causal powers and capacities of embodied persons to engage in dialogic, signifying acts. Grounded in a non-Cartesian concept of person and 'new realist', post-positivist philosophy of science, vocal signs and action signs, not the dispositions of a habitus , become the means by which humans exercise agency in dynamically embodied practices. Ethnographic data from the communicative practices of the Nakota (Assiniboine) people of northern Montana (USA) support and illustrate the theoretical argument.     

Minimal model of self-replicating nanocells: a physically embodied information-free scenario

The building of minimal self-reproducing systems with a physical embodiment (generically called protocells) is a great challenge, with implications for both theory and applied sciences. Although the classical view of a living protocell assumes that it includes information-carrying molecules as an essential ingredient, a dividing cell-like structure can be built from a metabolism-container coupled system only. An example of such a system, modelled with dissipative particle dynamics, is presented here. This article demonstrates how a simple coupling between a precursor molecule and surfactant molecules forming micelles can experience a growth-division cycle in a predictable manner, and analyses the influence of crucial parameters on this replication cycle. Implications of these results for origins of cellular life and living technology are outlined.     

Filtration and digestion responses of an elementally homeostatic consumer to changes in food quality: a predictive model

In the study of the stoichiometric relationship between autotrophs and herbivores, attention has been largely focused on effects of the encountered mismatch between needs and supplies of an element on herbivore growth and ecosystem processes. Herbivore adaptation to poor food quality has rarely been investigated. This study presents a predictive model of feeding, assimilation, digestion and excretion of Daphnia facing a dietary deficiency in phosphorus. Biochemical compounds in the food were divided into phosphorous and non-phosphorus compounds. It was assumed that Daphnia is able to differently assimilate both types of compounds by regulation of target specific digestive enzymes. Feeding rate was regulated by optimal gut residence time of food particles, and assimilation efficiency by gut residence time and optimal secretion of both classes of gut enzymes. The model predicted the optimal strategy for a consumer facing an elementally imbalanced diet: (1) increase the ingestion rate, and (2) increase the secretion rate of both classes of gut enzymes. It resulted in decreased C and nutrient assimilation efficiencies, increased C feeding costs, and reduced growth rate. Sensitivity analysis showed that these predictions were qualitatively not influenced by parameter values. An alternative model was tested that includes an additive term allowing the direct excretion of C assimilated in excess. Results showed that this strategy is not optimal for the consumer growth rate. In conclusion, the model supports the hypothesis that carbon ingested in excess may generate energy that can be used to obtain more nutrients by increased feeding rate.     

Delayed feedback control requires an internal forward model

Biological motor control provides highly effective solutions to difficult control problems in spite of the complexity of the plant and the significant delays in sensory feedback. Such delays are expected to lead to non trivial stability issues and lack of robustness of control solutions. However, such difficulties are not observed in biological systems under normal operating conditions. Based on early suggestions in the control literature, a possible solution to this conundrum has been the suggestion that the motor system contains within itself a forward model of the plant (e.g., the arm), which allows the system to ‘simulate’ and predict the effect of applying a control signal. In this work, we formally define the notion of a forward model for deterministic control problems, and provide simple conditions that imply its existence for tasks involving delayed feedback control. As opposed to previous work which dealt mostly with linear plants and quadratic cost functions, our results apply to rather generic control systems, showing that any controller (biological or otherwise) which solves a set of tasks, must contain within itself a forward plant model. We suggest that our results provide strong theoretical support for the necessity of forward models in many delayed control problems, implying that they are not only useful, but rather, mandatory, under general conditions.     

Density and distribution of Badgers in south-west England–a predictive model

This paper describes a predictive model for estimating the density and distribution of Badger social groups, in the south-west of England, based on habitat characteristics. Main sett density was used as an index of Badger social group density, and a preliminary study to define the different types of Badger sett observed in the field and to establish a relationship between main sett density and social group density is also described. The habitat characteristics that emerged as having the most influence on Badger social group density were the 'diggability' of the soils, the topography of the area, altitude, the length of hedgerows and the number of woodland units greater than 1 ha. The application of the model is briefly discussed.     

Survival of Campylobacter jejuni in foods and comparison with a predictive model

Campylobacter jejuni was inoculated into a range of raw and cooked foods and survival determined during storage at 20°, 10° and 20°C for up to 56 d. To facilitate easy enumeration, two antibiotic-resistant strains of Camp. jejuni , which had similar survival characteristics to the parent strain, were used. Campylobacter jejuni survived for longer at lower temperatures in all foods and inactivation was most rapid in pâté. There was generally good agreement between the survival data and predictions from a Camp. jejuni survival model (Food MicroModel).     

Rapid encoding of an internal model for imitative learning

As in human infant speech development, vocal imitation in songbirds involves sensory acquisition and memorization of adult-produced vocal signals, followed by a protracted phase of vocal motor practice. The internal model of adult tutor song in the juvenile male brain, termed ‘the template’, is central to the vocal imitation process. However, even the most fundamental aspects of the template, such as when, where and how it is encoded in the brain, remain poorly understood. A major impediment to progress is that current studies of songbird vocal learning use protracted tutoring over days, weeks or months, complicating dissection of the template encoding process. Here, we take the key step of tightly constraining the timing of template acquisition. We show that, in the zebra finch, template encoding can be time locked to, on average, a 2 h period of juvenile life and based on just 75 s of cumulative tutor song exposure. Crucially, we find that vocal changes occurring on the day of training correlate with eventual imitative success. This paradigm will lead to insights on how the template is instantiated in the songbird brain, with general implications for deciphering how internal models are formed to guide learning of complex social behaviours.     

Evolution of the cholera agent genome

"Mikrob" Russian Research Anti-Plague Institute, Saratov Studies of the genomic evolution of pathogenic bacteria became a priority research trend of modern molecular genetics. Vibrio cholerae, whose pathogenic properties are conditioned by the presence of virulence blocks of differing phylogenetic origins in 2 chromosomes, turned out to be a unique model object for studies of evolutionary transformations of genomes that are causative agents of extra dangerous infections. The molecular-and-genetic mechanisms underlying the change of biovariants and the emergence of a cholera agent of a new serogroup are in the focus of attention. Finally, the possibility that the new V. cholerae pathogenic clone originated due to horizontal genetic transfers and recombination phenomena is under discussion in the survey.     

Evolution of circulating wild poliovirus and of vaccine-derived poliovirus in an immunodeficient patient: a unifying model

We determined nucleotide sequences of the VP1 and 2AB genes and portions of the 2C and 3D genes of two evolving poliovirus lineages: circulating wild viruses of T geotype and Sabin vaccine-derived isolates from an immunodeficient patient. Different regions of the viral RNA were found to evolve nonsynchronously, and the rate of evolution of the 2AB region in the vaccine-derived population was not constant throughout its history. Synonymous replacements occurred not completely randomly, suggesting the need for conservation of certain rare codons (possibly to control translation elongation) and the existence of unidentified constraints in the viral RNA structure. Nevertheless the major contribution to the evolution of the two lineages came from linear accumulation of synonymous substitutions. Therefore, in agreement with current theories of viral evolution, we suggest that the majority of the mutations in both lineages were fixed as a result of successive sampling, from the heterogeneous populations, of random portions containing predominantly neutral and possibly adverse mutations. As a result of such a mode of evolution, the virus fitness may be maintained at a more or less constant level or may decrease unless more-fit variants are stochastically generated. The proposed unifying model of natural poliovirus evolution has important implications for the epidemiology of poliomyelitis.     

Evolution of cell motility in an individual-based model of tumour growth

Tumour invasion is driven by proliferation and importantly migration into the surrounding tissue. Cancer cell motility is also critical in the formation of metastases and is therefore a fundamental issue in cancer research. In this paper we investigate the emergence of cancer cell motility in an evolving tumour population using an individual-based modelling approach. In this model of tumour growth each cell is equipped with a micro-environment response network that determines the behaviour or phenotype of the cell based on the local environment. The response network is modelled using a feed-forward neural network, which is subject to mutations when the cells divide. With this model we have investigated the impact of the micro-environment on the emergence of a motile invasive phenotype. The results show that when a motile phenotype emerges the dynamics of the model are radically changed and we observe faster growing tumours exhibiting diffuse morphologies. Further we observe that the emergence of a motile subclone can occur in a wide range of micro-environmental growth conditions. Iterated simulations showed that in identical growth conditions the evolutionary dynamics either converge to a proliferating or migratory phenotype, which suggests that the introduction of cell motility into the model changes the shape of fitness landscape on which the cancer cell population evolves and that it now contains several local maxima. This could have important implications for cancer treatments which focus on the gene level, as our results show that several distinct genotypes and critically distinct phenotypes can emerge and become dominant in the same micro-environment.     

Use of caryophyllene oxide as an antifungal agent in an in vitro experimental model of onychomycosis

Caryophyllene oxide, an oxygenated terpenoid, well known as preservative in food, drugs and cosmetics, has been tested in vitro as an antifungal against dermatophytes. Its antifungal activity has been compared to ciclopiroxolamine and sulconazole, commonly used in onychomycosis treatment and chosen because of their very different chemical structures. So, a new model has been tested, utilizing sheep hoof plates in order to simulate human nails, which are almost unobtainable for in vitro tests. Three protocols were utilized: pre-treatment. simultaneous treatment and post-treatment. Among these, the post-treatment method was the best to simulate antifungal therapy. as it permitted testing and comparing the efficiency of different antifungal drugs.This revised version was published online in October 2005 with corrections to the Cover Date.     

Streptomyces plicatus as a model biocontrol agent

Three hundred and seventy two isolates belonging to the genusStreptomyces were isolated and screened for chitinase production.Streptomyces plicatus was found to be the best producer. The highest chitinase production were incubated for 3 d at 30 °C on buffered culture medium (pH 8.0) containing chitin plus sucrose and calcium nitrate as carbon and nitrogen sources.S. plicatus chitinase had a highly significant inhibitory effect on spore germination, germ tube elongation and radial growth ofFusarium oxysporum f.sp.lycopersict., Altrernaria alternata andVerticillium albo-atrum, the causal organisms ofFusarium wilt, stem canker andVerticillium wilt diseases of tomato. Application ofS. plicatus to the root system of tomato plants before transplantation markedly protected tomato plants against the tested phytopathogenic fungiin vivo.     

The confirmation rate of primary hits: a predictive model

HTS data from primary screening are usually analyzed by setting a cutoff for activity, in order to minimize both false-negative and false-positive rates. An alternative approach, based on a calculated probability of being active, is presented here. Given the predicted confirmation rate derived from this probability, the number of primary positives selected for follow-up can be optimized to maximize the number of true positives without picking too many false positives. Typical cutoff-determining methods are more serendipitous in their nature and not easily optimized in an effort to optimize screening efforts. An additional advantage of calculating a probability of being active for each compound screened is that orthogonal mixtures can be deconvoluted without presetting a deconvolution threshold. An important consequence of using the probability of being active with orthogonal mixtures is that individual compound screening results can be recorded irrespective of whether the assays were performed on single compounds or on cocktails.     

Gyrfalcon nest distribution in Alaska based on a predictive GIS model

The gyrfalcon (Falco rusticolus) is an uncommon, little studied circumpolar Arctic bird that faces conservation concerns. We used 455 historical nest locations, 12 environmental abiotic predictor layers, Geographic Information System (ArcGIS), and TreeNet modeling software to create a spatially explicit model predicting gyrfalcon breeding distribution and population size across Alaska. The model predicted that 75% of the state had a relative gyrfalcon nest occurrence index value of <20% (where essentially no nests are expected to occur) and 7% of the state had a value of >60%. Areas of high predicted occurrence were in northern and western Alaska. The most important predictor variable was soil type, followed by sub-surface geology and vegetation type. Nine environmental factors were useful in predicting nest occurrence, indicating complex multivariate habitat relationships exist. We estimated the breeding gyrfalcon population in Alaska is 546 ± 180 pairs. The model was 67% accurate at predicting nest occurrence with an area under the curve score of 0.76 when assessed with independent data; this is a good result when considering its application to the entire state of Alaska. Prediction accuracy estimates were as high as 97% using 10-fold cross validation of the training data. The model helps guide science-based management efforts in times of increasing and global pressures for this species and Arctic landscapes.     

Survival model predictive accuracy and ROC curves

The predictive accuracy of a survival model can be summarized using extensions of the proportion of variation explained by the model, or R2, commonly used for continuous response models, or using extensions of sensitivity and specificity, which are commonly used for binary response models. In this article we propose new time-dependent accuracy summaries based on time-specific versions of sensitivity and specificity calculated over risk sets. We connect the accuracy summaries to a previously proposed global concordance measure, which is a variant of Kendall's tau. In addition, we show how standard Cox regression output can be used to obtain estimates of time-dependent sensitivity and specificity, and time-dependent receiver operating characteristic (ROC) curves. Semiparametric estimation methods appropriate for both proportional and nonproportional hazards data are introduced, evaluated in simulations, and illustrated using two familiar survival data sets.     

Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis

The side effects of cancer chemotherapeutic agents such as mitoxantrone (MIT) in multiple sclerosis (MS) patients justify the search for less toxic drugs. Ethonafide is an anthracene-based antineoplastic drug similar to MIT. With reference to MIT, we examined the effect of ethonafide on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, an animal model of human MS. We demonstrated that ethonafide is effective in preventing development of EAE as well as in ameliorating the severity of EAE when disease is ongoing. In relatively higher dosages, the effects of ethonafide and MIT on EAE were identical, whereas in lower dosages, MIT seemed more effective. Therapeutic effects of ethonafide were associated with the initial reduction in cellular counts of CD3(+), CD4(+), CD8(+), B220(+), CD11b(+), NK cells, and NKT cells, followed by recovery of these cells from the bone marrow. Interestingly, the recovered autoreactive T cells in ethonafide-treated animals have reduced capacity to expand and produce cytokines in response to myelin Ag stimulation. Furthermore, CD4(+)CD25(+) regulatory T cells were relatively resistant to depletion and/or recovered faster than T effector cells. The ability of regulatory T cells to resist depletion and replenish quickly during cell ablation therapy may provide an opportunity to reprogram the immune system. Moreover, we provided evidences that ethonafide has less cardiac toxicity compared with MIT. The effectiveness and the low cardiotoxicity of ethonafide might make it a promising immunosuppressive agent for clinical use in treating MS patients.