Homology modelling of a sensor histidine kinase from Aeromonas hydrophila

Aeromonas hydrophila has been implicated in extra-intestinal infection and diarrhoea in humans. Targetting unique effectors of bacterial pathogens is considered a powerful strategy for drug design against bacterial variations to drug resistance. The two-component bacterial system involving sensor histidine kinase (SHK) and its response regulators is considered a lucrative target for drug design. This is the first report describing a three-dimensional (3D) structure for SHK of A. hydrophila. The model was constructed by homology modelling using the X-ray structure of PleD—a response regulator—in conjunction with cdiGMP (PDB code 1W25) and HemAT sensor domain (PDB code 1OR4)—a globin coupled sensor. A combination of homology modelling methodology and molecular dynamics (MD) simulations was applied to obtain a reasonable structure to understand the dynamic behaviour of SHK. Homology modelling was performed using MODELLER9v2 software. The structure was relaxed to eliminate bad atomic contacts. The final model obtained by molecular mechanics and dynamics methods was assessed using PROCHECK and VERIFY 3D graph, which confirmed that the final refined model is reliable. Until complete biochemical and structural data of SHK are determined by experimental means, this model can serve as a valuable reference for characterising the protein and could be explored for drug targetting by design of suitable inhibitors.     

On the Role of Ideas of Human Nature in Shaping Attitudes Towards Environmental Governance

Attitudes towards the management of the natural environment have been described mainly as building on individuals’ images of nature and the human–nature relationship. However, in previous qualitative research I found strong evidence that in order to understand public views on environmental policies we also need to understand individuals’ beliefs about their fellow humans. The present study tested the hypothesis that beliefs about human nature and preferences for certain governance approaches—such as regulations and collective action—are related to individuals’ attitudes towards concrete management measures. Survey results (n = 155), analysed by means of structural equation modelling, suggest that effects of beliefs about human nature are discernible, but not significant. I could, however, identify generic preferences for particular approaches to environmental governance. These significantly explained variation in attitudes towards environmental governance in an applied context, suggesting a strong need for further research in this politically highly relevant field.     

The series,the network,and the tree: changing metaphors of order in nature

The history of biological systematics documents a continuing tension between classifications in terms of nested hierarchies congruent with branching diagrams (the ‘Tree of Life’) versus reticulated relations. The recognition of conflicting character distribution led to the dissolution of the scala naturae into reticulated systems, which were then transformed into phylogenetic trees by the addition of a vertical axis. The cladistic revolution in systematics resulted in a representation of phylogeny as a strictly bifurcating pattern (cladogram). Due to the ubiquity of character conflict—at the genetic or morphological level, or at any level in between—some characters will necessarily have to be discarded (qua noise) in favor of others in support of a strictly bifurcating phylogenetic tree. Pattern analysts will seek maximal congruence in the distribution of characters (ultimately of any kind) relative to a branching tree-topology; process explainers will call such tree-topologies into question by reference to incompatible evolutionary processes. Pattern analysts will argue that process explanations must not be brought to bear on pattern reconstruction; process explainers will insist that the reconstructed pattern requires a process explanation to become scientifically relevant, i.e., relevant to evolutionary theory. The core question driving the current debate about the adequacy of the ‘Tree of Life’ metaphor seems to be whether the systematic dichotomization of the living world is an adequate representation of the complex evolutionary history of global biodiversity. In ‘Questioning the Tree of Life’, it seems beneficial to draw at least four conceptual distinctions: pattern reconstruction versus process explanation as different epistemological approaches to the study of phylogeny; open versus closed systems as expressions of different kinds of population (species) structures; phylogenetic trees versus cladograms as representations of evolutionary processes versus patterns of relationships; and genes versus species as expressions of different levels of causal integration and evolutionary transformation.     

The Social Impacts of Nanotechnology: an Ethical and Political Analysis

This paper attempts some predictions about the social consequences of nanotechnology and the ethical issues they raise. I set out four features of nanotechnology that are likely to be important in determining its impact and argue that nanotechnology will have significant social impacts in—at least—the areas of health and medicine, the balance of power between citizens and governments, and the balance of power between citizens and corporations. More importantly, responding to the challenge of nanotechnology will require confronting “philosophical” questions about the sort of society we wish to create and the role that technology might play in creating it. This in turn will require developing institutions and processes that allow the public to wield real power in relation to technological trajectories. My ultimate contention is that the immediate task established by the likely social impacts of nanotechnology is not so much to develop an ethics of nanotechnology as to facilitate an ethical conversation about nanotechnology.

Some views on the role of noise in “self”-organizing systems

This paper deals with information transfer from the environment and “self”-organization in open, nonlinear systems far from thermodynamic equilibrium — in the presence of either non-stationary phase jitter noise, or amplitude stationary noise. By “self”-organization we mean here the progressive formation within the system of sequential, ordered (coherent) relationships between appropriate dynamical variables-like for example, the phase differences between the oscillating components of the system. We take up (in Section II) the classical Laser as a specific example and examine in detail the influence of phase jitter noise in the mode (phase) locking process. We find—as expected—that phase fluctuations in the cavity cause degradation of the coherent behaviour (i.e. increase the entropy) of the system — which, however, levels off, or saturates with time. Further (in Section III) we examine systems where the number of self-sustained oscillating components may vary with time in such a way that the maximum entropy of the system increases faster than the overall instantaneous entropy. We put forth the hypothesis that in such cases — because of the increase of the redundancy — the system gets organized not just in spite of, but merely because of the presence of Noise. Possible applications in biological systems (especially concerning a model of cerebral organization) are briefly discussed. It is understood here, that the system has to display some preliminary dynamical structure before the organizing procedure takes over. What happens afterwards is the subject of this paper.     

The Role of Teleological Thinking in Learning the Darwinian Model of Evolution

Human beings are predisposed to think of evolution as teleological—i.e., having a purpose or directive principle—and the ways scientists talk about natural selection can feed this predisposition. This work examines the suggestion that students’ teleological thinking operates as an obstacle when the natural selection evolution model is taught. What we mean by obstacle is an established way of thinking that resists change due to its explanatory power. In light of this approach, the challenges of teaching evolution in biology education have been revised, and improved methodological strategies aimed at a better comprehension of the Darwinian evolution model are suggested.     

Retrofitting Autonomic Capabilities onto Legacy Systems

sec:abstractnak Autonomic computing—self-configuring, self-healing, self-managing applications, systems and networks—is a promising solution to ever-increasing system complexity and the spiraling costs of human management as systems scale to global proportions. Most results to date, however, suggest ways to architect new software designed from the ground up as autonomic systems, whereas in the real world organizations continue to use stovepipe legacy systems and/or build “systems of systems” that draw from a gamut of disparate technologies from numerous vendors. Our goal is to retrofit autonomic computing onto such systems, externally, without any need to understand, modify or even recompile the target system's code. We present an autonomic infrastructure that operates similarly to active middleware, to explicitly add autonomic services to pre-existing systems via continual monitoring and a feedback loop that performs reconfiguration and/or repair as needed. Our lightweight design and separation of concerns enables easy adoption of individual components for use with a variety of target systems, independent of the rest of the full infrastructure. This work has been validated by several case studies spanning multiple real-world application domains.     

Tuning the cochlea: wave-mediated positive feedback between cells

Frequency analysis by the mammalian cochlea is traditionally thought to occur via a hydrodynamically coupled ‘travelling wave’ along the basilar membrane. A persistent difficulty with this picture is how sharp tuning can emerge. This paper proposes, and models, a supplementary or alternative mechanism: it supposes that the cochlea analyses sound by setting up standing waves between parallel rows of outer hair cells. In this scheme, multiple cells mutually interact through positive feedback of wave-borne energy. Analytical modelling and numerical evaluation presented here demonstrate that this can provide narrow-band frequency analysis. Graded cochlear tuning will then rely on the distance between rows becoming greater as distance from the base increases (as exhibited by the actual cochlea) and on the wave’s phase velocity becoming slower. In effect, tuning is now a case of varying the feedback delay between the rows, and a prime candidate for a wave exhibiting suitably graded phase velocity—a short-wavelength ‘squirting wave’—is identified and used in the modelling. In this way, resonance between rows could supply both amplification and high Q, characteristics underlying the ‘cochlear amplifier’—the device whose action has long been evident to auditory science but whose anatomical basis and mode of operation are still obscure.     

Responses of blowfly motion-sensitive neurons to reconstructed optic flow along outdoor flight paths

The retinal image flow a blowfly experiences in its daily life on the wing is determined by both the structure of the environment and the animal’s own movements. To understand the design of visual processing mechanisms, there is thus a need to analyse the performance of neurons under natural operating conditions. To this end, we recorded flight paths of flies outdoors and reconstructed what they had seen, by moving a panoramic camera along exactly the same paths. The reconstructed image sequences were later replayed on a fast, panoramic flight simulator to identified, motion sensitive neurons of the so-called horizontal system (HS) in the lobula plate of the blowfly, which are assumed to extract self-motion parameters from optic flow. We show that under real life conditions HS-cells not only encode information about self-rotation, but are also sensitive to translational optic flow and, thus, indirectly signal information about the depth structure of the environment. These properties do not require an elaboration of the known model of these neurons, because the natural optic flow sequences generate—at least qualitatively—the same depth-related response properties when used as input to a computational HS-cell model and to real neurons.     

A comparison of approaches for modelling the occurrence of marine animals

Approaches for modelling the distribution of animals in relation to their environment can be divided into two basic types, those which use records of absence as well as records of presence and those which use only presence records. For terrestrial species, presence–absence approaches have been found to produce models with greater predictive ability than presence-only approaches. This study compared the predictive ability of both approaches for a marine animal, the harbour porpoise (Phoceoena phocoena). Using data on the occurrence of harbour porpoises in the Sea of Hebrides, Scotland, the predictive abilities of one presence–absence approach (generalised linear modelling—GLM) and three presence-only approaches (Principal component analysis—PCA, ecological niche factor analysis—ENFA and genetic algorithm for rule-set prediction—GARP) were compared. When the predictive ability of the models was assessed using receiver operating characteristic (ROC) plots, the presence–absence approach (GLM) was found to have the greatest predictive ability. However, all approaches were found to produce models that predicted occurrence significantly better than a random model and the GLM model did not perform significantly better than ENFA and GARP. The PCA had a significantly lower predictive ability than GLM but not the other approaches. In addition, all models predicted a similar spatial distribution. Therefore, while models constructed using presence–absence approaches are likely to provide the best understanding of species distribution within a surveyed area, presence-only models can perform almost as well. However, careful consideration of the potential limitations and biases in the data, especially with regards to representativeness, is needed if the results of presence-only models are to be used for conservation and/or management purposes. Guest editor: V. D. Valavanis Essential Habitat Mapping in the Mediterranean     

Genetic foundations of human intelligence

Individual differences in intelligence (cognitive abilities) are a prominent aspect of human psychology, and play a substantial role in influencing important life outcomes. Their phenotypic structure—as described by the science of psychometrics—is well understood and well replicated. Approximately half of the variance in a broad range of cognitive abilities is accounted by a general cognitive factor (g), small proportions of cognitive variance are caused by separable broad domains of mental function, and the substantial remainder is caused by variance that is unique to highly specific cognitive skills. The heritability of g is substantial. It increases from a low value in early childhood of about 30%, to well over 50% in adulthood, which continues into old age. Despite this, there is still almost no replicated evidence concerning the individual genes, which have variants that contribute to intelligence differences. Here, we describe the human intelligence phenotype, summarise the evidence for its heritability, provide an overview of and comment on molecular genetic studies, and comment on future progress in the field.     

Sociability leads to instability

We present a general stochastic model showing that colonial breeding can lead to complex multi-colony population dynamics when combined with nothing more than (inevitably) imperfect decision-making by individuals. In particular, frequent “switching cascades”—mass movement of individuals between locations from one breeding season to the next—arise naturally from our model, bringing into question the need to invoke a separate, fitness-based explanation for this commonly observed real-world phenomenon. A key component of the model is the development, at the beginning of each breeding season, of a set of colonies, based on sequential choices by individuals about where to breed. Individuals favor the colony they bred in previously, but are also attracted to colonies that are rapidly establishing, and may switch locations. This provides a positive feedback that leads to switching cascades. We examine the effect on the dynamics of individuals’ access to (and ability to act on) information, as well as the overall size of the colony system and of individual colonies. We compare the model’s dynamics to the observed population dynamics of a set of heron and egret breeding colonies in New York Harbor.     

Learning with incomplete information and the mathematical structure behind it

We investigate the problem of learning with incomplete information as exemplified by learning with delayed reinforcement. We study a two phase learning scenario in which a phase of Hebbian associative learning based on momentary internal representations is supplemented by an ‘unlearning’ phase depending on a graded reinforcement signal. The reinforcement signal quantifies the success-rate globally for a number of learning steps in phase one, and ‘unlearning’ is indiscriminate with respect to associations learnt in that phase. Learning according to this model is studied via simulations and analytically within a student–teacher scenario for both single layer networks and, for a committee machine. Success and speed of learning depend on the ratio λ of the learning rates used for the associative Hebbian learning phase and for the unlearning-correction in response to the reinforcement signal, respectively. Asymptotically perfect generalization is possible only, if this ratio exceeds a critical value λ _c , in which case the generalization error exhibits a power law decay with the number of examples seen by the student, with an exponent that depends in a non-universal manner on the parameter λ. We find these features to be robust against a wide spectrum of modifications of microscopic modelling details. Two illustrative applications—one of a robot learning to navigate a field containing obstacles, and the problem of identifying a specific component in a collection of stimuli—are also provided.     

Dispersal and biogeography of silica-scaled chrysophytes

The silica-scaled chrysophytes—here mainly represented by the freshwater genera Mallomonas and Synura—have special problems in dispersal from one habitat to another because they cannot tolerate desiccation. Their dispersal is limited by the fragile construction and aquatic habit. Dispersal from one water body to another involves dangerous changes of the environment, and the ability to avoid desiccation during transport is crucial. So, air-borne and ectozoic dispersal by birds or mammals can only work at short distances. This danger may be avoided by endozoic dispersal of thick-walled cysts; as far as they can tolerate the digestion fluids in the intestine. In spite of these difficulties, Chrysophytes have been dispersed worldwide, but they display various distinct distribution patterns, e.g., cosmopolitan, arctic-northern temperate, bipolar, and tropical. Quite a large proportion may be considered endemic, occurring only within a restricted area. Even if the exact dispersal methods are elusive, the distribution of chrysophytes around the world proves their ability for dispersal. On the other hand, the different degree of distribution shows the varying success of the individual species. The distribution of a species at a given time depends on several factors: dispersal capacity—available vectors—suitable available habitats—and most important: sufficient time for dispersal. It is remarkable that the chrysophytes—in spite of their fragile cell construction and apparently low dispersal capacity—show distribution types comparable to those found in, e.g., blue–greens and desmids, whose cell construction appears much better adapted for dispersal. Special Issue: Protist diversity and geographic distribution. Guest editor: W. Foissner     

Isolation of Plant Gene Space-Related Sequence Elements by High C+G Patch (HCGP) Filtration: Model Study on Rice

For the isolation of gene space representative sequence elements, a new methodology—high C+G patch (HCGP) filtration—has been developed using rice as a model. The method is based on the fragmentation of the genomic DNA by methylation-sensitive HpaII and MspI restriction endonucleases having exclusively G/C base pair-containing recognition sites. These enzymes fragment the genome at high C+G content and hypomethylated regions. Cloning fragments spanning such regions in close vicinity (200–2,000 bp) revealed that about 60% of the clones represented gene space sequences resulting in twofold enrichment of these sequences, which is close to the theoretical maximum in rice. The sequence information of clones used in the present study was deposited in the NCBI database under the accession numbers EI 365676–EI 366364.     

Correction factors used for estimating prey biomass in the diet of American minkMustela vison

Feeding experiment on nine feral minkMustela vison Schreber, 1777 was carried out to find differences in digestibility of particular prey types. The values of correction factors (CF), which show the ratio between consumed prey biomass and undigested remains, were calculated for seven food types. The experiment revealed that results obtained by commonly used percentage of occurrence methods differed from the real intake of food. Food types which were intensively digested were underestimated by percentage of occurrence methods and prey which had hardly digestive elements of their body were overestimated. The calculated values of CF are as follows: crayfish — 14.8, fish — 30.8, frog — 61.3, small passerine bird — 17.2, chicken — 41.3, rodent — 17.3, egg — 687.5. The variability in CF values did not depend on mink individuals but could be explained by the mean weight of prey items eaten by mink. The positive correlation between the prey size and its digestibility was recorded for crayfish, fish and chicken. The biomass of frog, passerine and rodent remains was not related to the body mass of eaten prey. The use of evaluated correction factors enables more accurate estimates of the food composition of wild living mustelids.     

On the mathematical modelling of pain

In this review a case is presented for the use of mathematical modelling in the study of pain. The philosophy of mathematical modelling is outlined and a recommendation is made for the use of modern nonlinear techniques and computational neuroscience in the modelling of pain. Classic and more recent examples of modelling in neurobiology in general and pain in particular, at three different levels—molecular, cellular and neural networks—are described and evaluated. Directions for further progress are indicated, particularly in plasticity and in modelling brain mechanisms. Major advantages of mathematical modelling are that it can handle extremely complex theories and it is non-invasive, and so is particularly valuable in the investigation of chronic pain. Special issue dedicated to Dr. Herman Bachelard     

Morphological studies on the Sulawesi macaques I: Phyletic analysis of body color

The body color of Sulawesi macaques was measured quantitatively and compared among the different monkeys. As a result, divergence models for extant Sulawesi macaques, withtonkeana as the starting point and fading as the sole direction of color change, were inferred as follows: (1) fading slightly on the upper half of the body—nigra, fading more on the proximal part of the body—nigrescens; (2) fading over the whole body—maura; (3) fading greatly on the legs—hecki; and (4) fading on the distal part of the body—ochreata, fading more over the whole body, including the proximal part of the body—brunnescens. The color changed progressively in the order of (1) through (4). The divergence model, excluding the position ofhecki (3), supports the speciation model ofFooden (1969). If the proto-Sulawesi macaques had a body color pattern similar to the livingnemestrina, darkening would have been necessary for the evolution of the Sulawesi macaques after their immigration, and it may have been acquired as an adaptation to the ground (forest floor) living nature of the Sulawesi macaques, together with influences deriving from the insularity and/or from the absence of predators.