Unifying Time to Contact Estimation and Collision Avoidance across Species

The [Formula: see text]-function and the [Formula: see text]-function are phenomenological models that are widely used in the context of timing interceptive actions and collision avoidance, respectively. Both models were previously considered to be unrelated to each other: [Formula: see text] is a decreasing function that provides an estimation of time-to-contact (ttc) in the early phase of an object approach; in contrast, [Formula: see text] has a maximum before ttc. Furthermore, it is not clear how both functions could be implemented at the neuronal level in a biophysically plausible fashion. Here we propose a new framework - the corrected modified Tau function - capable of predicting both [Formula: see text]-type ("[Formula: see text]") and [Formula: see text]-type ("[Formula: see text]") responses. The outstanding property of our new framework is its resilience to noise. We show that [Formula: see text] can be derived from a firing rate equation, and, as [Formula: see text], serves to describe the response curves of collision sensitive neurons. Furthermore, we show that [Formula: see text] predicts the psychophysical performance of subjects determining ttc. Our new framework is thus validated successfully against published and novel experimental data. Within the framework, links between [Formula: see text]-type and [Formula: see text]-type neurons are established. Therefore, it could possibly serve as a model for explaining the co-occurrence of such neurons in the brain.     

(13)C NMR Reveals No Evidence of n-π* Interactions in Proteins

An [Formula: see text] interaction between neighboring carbonyl groups has been postulated to stabilize protein structures. Such an interaction would affect the [Formula: see text]C chemical shielding of the carbonyl groups, whose paramagnetic component is dominated by [Formula: see text] and [Formula: see text] excitations. Model compound calculations indicate that both the interaction energetics and the chemical shielding of the carbonyl group are instead dominated by a classical dipole-dipole interaction. A set of high-resolution protein structures with associated carbonyl [Formula: see text]C chemical shift assignments verifies this correlation and provides no evidence for an inter-carbonyl [Formula: see text] interaction.     

Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using Raman microspectroscopy

This paper presents a nonivasive approach to study redox state of reduced cytochromes [Formula: see text], [Formula: see text] and [Formula: see text] of complexes II and III in mitochondria of live cardiomyocytes by means of Raman microspectroscopy. For the first time with the proposed approach we perform studies of rod- and round-shaped cardiomyocytes, representing different morphological and functional states. Raman mapping and cluster analysis reveal that these cardiomyocytes differ in the amounts of reduced cytochromes [Formula: see text], [Formula: see text] and [Formula: see text]. The rod-shaped cardiomyocytes possess uneven distribution of reduced cytochromes [Formula: see text], [Formula: see text] and [Formula: see text] in cell center and periphery. Moreover, by means of Raman spectroscopy we demonstrated the decrease in the relative amounts of reduced cytochromes [Formula: see text], [Formula: see text] and [Formula: see text] in the rod-shaped cardiomyocytes caused by H(2)O(2)-induced oxidative stress before any visible changes. Results of Raman mapping and time-dependent study of reduced cytochromes of complexes II and III and cytochrome [Formula: see text] in cardiomyocytes are in a good agreement with our fluorescence indicator studies and other published data.     

Limits to the rate of adaptive substitution in sexual populations

In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, [Formula: see text], that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is [Formula: see text], where [Formula: see text] is the population size, [Formula: see text] is the rate of beneficial mutations per genome, and [Formula: see text] is their mean selective advantage. Heritable variance [Formula: see text] in log fitness due to unlinked loci reduces [Formula: see text] by [Formula: see text] under polygamy and [Formula: see text] under monogamy. With a linear genetic map of length [Formula: see text] Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] only through the baseline density: [Formula: see text]. Under the approximation that the interference due to different sweeps adds up, we show that [Formula: see text], implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for [Formula: see text]; for higher [Formula: see text], the rate of adaptation grows above [Formula: see text], but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common-diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection.     

Specificity of Hpa II and Hae III DNA methylases

The methylases M.HaeIII and M.HpaII recognize the tetranucleotide sequences [Formula: see text] and [Formula: see text] respectively, in DNA, and transfer a methyl group from S-adenosylmethionine to the 5-position of cytosine on each strand as indicated by the asterisks. Restriction endonuclease R.HaeIII does not cleave the methylated sequence [Formula: see text] but can cleave [Formula: see text] in which methylation is introduced on the unnatural external cytosine positions. Similarly, R.HpaII does not cleave [Formula: see text] but can cleave [Formula: see text].Images     

Critical motor number for fractional steps of cytoskeletal filaments in gliding assays

In gliding assays, filaments are pulled by molecular motors that are immobilized on a solid surface. By varying the motor density on the surface, one can control the number [Formula: see text] of motors that pull simultaneously on a single filament. Here, such gliding assays are studied theoretically using Brownian (or Langevin) dynamics simulations and taking the local force balance between motors and filaments as well as the force-dependent velocity of the motors into account. We focus on the filament stepping dynamics and investigate how single motor properties such as stalk elasticity and step size determine the presence or absence of fractional steps of the filaments. We show that each gliding assay can be characterized by a critical motor number, [Formula: see text]. Because of thermal fluctuations, fractional filament steps are only detectable as long as [Formula: see text]. The corresponding fractional filament step size is [Formula: see text] where [Formula: see text] is the step size of a single motor. We first apply our computational approach to microtubules pulled by kinesin-1 motors. For elastic motor stalks that behave as linear springs with a zero rest length, the critical motor number is found to be [Formula: see text], and the corresponding distributions of the filament step sizes are in good agreement with the available experimental data. In general, the critical motor number [Formula: see text] depends on the elastic stalk properties and is reduced to [Formula: see text] for linear springs with a nonzero rest length. Furthermore, [Formula: see text] is shown to depend quadratically on the motor step size [Formula: see text]. Therefore, gliding assays consisting of actin filaments and myosin-V are predicted to exhibit fractional filament steps up to motor number [Formula: see text]. Finally, we show that fractional filament steps are also detectable for a fixed average motor number [Formula: see text] as determined by the surface density (or coverage) of the motors on the substrate surface.     

Robustness and information propagation in attractors of random boolean networks

Attractors represent the long-term behaviors of Random Boolean Networks. We study how the amount of information propagated between the nodes when on an attractor, as quantified by the average pairwise mutual information ([Formula: see text]), relates to the robustness of the attractor to perturbations ([Formula: see text]). We find that the dynamical regime of the network affects the relationship between [Formula: see text] and [Formula: see text]. In the ordered and chaotic regimes, [Formula: see text] is anti-correlated with [Formula: see text], implying that attractors that are highly robust to perturbations have necessarily limited information propagation. Between order and chaos (for so-called "critical" networks) these quantities are uncorrelated. Finite size effects cause this behavior to be visible for a range of networks, from having a sensitivity of 1 to the point where [Formula: see text] is maximized. In this region, the two quantities are weakly correlated and attractors can be almost arbitrarily robust to perturbations without restricting the propagation of information in the network.     

The dynamics, causes and possible prevention of hepatitis e outbreaks

Rapidly spreading infectious diseases are a serious risk to public health. The dynamics and the factors causing outbreaks of these diseases can be better understood using mathematical models, which are fit to data. Here we investigate the dynamics of a Hepatitis E outbreak in the Kitgum region of northern Uganda during 2007 to 2009. First, we use the data to determine that [Formula: see text] is approximately 2.25 for the outbreak. Secondly, we use a model to estimate that the critical level of latrine and bore hole coverages needed to eradicate the epidemic is at least [Formula: see text] and [Formula: see text] respectively. Lastly, we further investigate the relationship between the co-infection factor for malaria and Hepatitis E on the value of [Formula: see text] for Hepatitis E. Taken together, these results provide us with a better understanding of the dynamics and possible causes of Hepatitis E outbreaks.     

Changes to airborne pollen counts across Europe

A progressive global increase in the burden of allergic diseases has affected the industrialized world over the last half century and has been reported in the literature. The clinical evidence reveals a general increase in both incidence and prevalence of respiratory diseases, such as allergic rhinitis (common hay fever) and asthma. Such phenomena may be related not only to air pollution and changes in lifestyle, but also to an actual increase in airborne quantities of allergenic pollen. Experimental enhancements of carbon dioxide (CO[Formula: see text]) have demonstrated changes in pollen amount and allergenicity, but this has rarely been shown in the wider environment. The present analysis of a continental-scale pollen data set reveals an increasing trend in the yearly amount of airborne pollen for many taxa in Europe, which is more pronounced in urban than semi-rural/rural areas. Climate change may contribute to these changes, however increased temperatures do not appear to be a major influencing factor. Instead, we suggest the anthropogenic rise of atmospheric CO[Formula: see text] levels may be influential.     

Fracture Faces in the Cell Envelope of Escherichia coli

Freeze-fracturing of Escherichia coli cells in the presence of 30% (v/v) glycerol resulted in a double cleavage of the cell envelope exposing two convex and two concave fracture faces ([Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text]) with characteristic patterns. Complementary replicas revealed the relationship of the fracture faces to their corresponding fracture planes. The inner fracture plane splits the plasma membrane at one particular level. Apparently the outer fracture plane was located in the outer part of the wall, as it was separated by a layer ([Formula: see text]) from the fractured profile (CW1) presumably corresponding to the murein layer. The outer fracture plane did alternate toward the cell periphery, exposing complementary smooth areas ([Formula: see text] and [Formula: see text]). When cells were freeze-fractured in the absence of glycerol, the outer cell surface appeared as an etching face rather than a fracture face. A schematic representation of the relative location of the different fracture faces in the E. coli cell envelope is given.     

A Mathematical Model of Rift Valley Fever with Human Host

Rift Valley Fever is a vector-borne disease mainly transmitted by mosquito. To gain some quantitative insights into its dynamics, a deterministic model with mosquito, livestock, and human host is formulated as a system of nonlinear ordinary differential equations and analyzed. The disease threshold [Formula: see text] is computed and used to investigate the local stability of the equilibria. A sensitivity analysis is performed and the most sensitive model parameters to the measure of initial disease transmission [Formula: see text] and the endemic equilibrium are determined. Both [Formula: see text] and the disease prevalence in mosquitoes are more sensitive to the natural mosquito death rate, d(m). The disease prevalence in livestock and humans are more sensitive to livestock and human recruitment rates, [Formula: see text] and [Formula: see text], respectively, suggesting isolation of livestock from humans is a viable preventive strategy during an outbreak. Numerical simulations support the analytical results in further exploring theoretically the long-term dynamics of the disease at the population level.     

Testing a simple rule for dominance in resource competition

Competition for limiting resources long has been considered an important factor generating community structure. A minimal model of resource competition predicts that the species that reduces the limiting resource R to the lowest level ([Formula: see text]) will exclude its competitors. Whether this "[Formula: see text] rule" is robust to violations of model assumptions remains largely unknown. I conducted a competition experiment with four species of bacterivorous protists in laboratory microcosms and predicted the outcome from each species' [Formula: see text] value. I also examined how the outcome of competition, species abundances, and the effect of protists on bacterial density varied with productivity. Microcosms were unstirred batch cultures containing a variety of bacteria, challenging the robustness of the simplest competition models. Protists with low [Formula: see text] values were less affected by competition, although competing protists often coexisted. The values of [Formula: see text] can predict competitive dominance, even in the absence of competitive exclusion. Other model predictions were less robust. Contrary to expectation, densities of grazed bacteria increased with productivity, and the effect of some protists on bacterial density did not vary with productivity. Bacterial heterogeneity may account for deviations from model predictions. Further experiments should examine the conditions under which simple rules can be expected to identify dominant species.     

Complexity-entropy causality plane as a complexity measure for two-dimensional patterns

Complexity measures are essential to understand complex systems and there are numerous definitions to analyze one-dimensional data. However, extensions of these approaches to two or higher-dimensional data, such as images, are much less common. Here, we reduce this gap by applying the ideas of the permutation entropy combined with a relative entropic index. We build up a numerical procedure that can be easily implemented to evaluate the complexity of two or higher-dimensional patterns. We work out this method in different scenarios where numerical experiments and empirical data were taken into account. Specifically, we have applied the method to [Formula: see text] fractal landscapes generated numerically where we compare our measures with the Hurst exponent; [Formula: see text] liquid crystal textures where nematic-isotropic-nematic phase transitions were properly identified; [Formula: see text] 12 characteristic textures of liquid crystals where the different values show that the method can distinguish different phases; [Formula: see text] and Ising surfaces where our method identified the critical temperature and also proved to be stable.     

The IspA protease's involvement in the regulation of the sporulation process of Bacillus thuringiensis is revealed by proteomic analysis

We have observed that the process of sporulation of the ispA-deficient mutant was delayed under phase-contrast microscopy. The protein profiles of the ispA-deficient mutant have been analyzed using two-dimensional gel electrophoresis. The results of a proteomic analysis using MALDI-TOF MS indicated that a sporulation-associated protein, pro- [Formula: see text], was upregulated, while two other sporulation-associated proteins, SpoVD and SpoVR, were downregulated in the ispA-deficient mutant. It has been known that pro- [Formula: see text] is a precursor of [Formula: see text] and is required for gene expression related to the late stage of sporulation. Moreover, SpoVD and SpoVR are known to be involved in the formation of the spore cortex. Based on these observations, we propose that the delay in the sporulation process observed in the ispA-deficient mutant may be due to a failure of [Formula: see text] to signal sporulation. This phenomenon may be further enhanced by insufficient amount of SpoVD and SpoVR for cortex formation. In this study, we have revealed for the first time a possible pathway for the regulation of sporulation-associated proteins via IspA.     

Morphology and Viscoelasticity of Actin Networks Formed with the Mutually Interacting Crosslinkers: Palladin and Alpha-actinin

Actin filaments and associated actin binding proteins play an essential role in governing the mechanical properties of eukaryotic cells. Even though cells have multiple actin binding proteins (ABPs) that exist simultaneously to maintain the structural and mechanical integrity of the cellular cytoskeleton, how these proteins work together to determine the properties of actin networks is not clearly understood. The ABP, palladin, is essential for the maintenance of cell morphology and the regulation of cell movement. Palladin coexists with [Formula: see text]-actinin in stress fibers and focal adhesions and binds to both actin and [Formula: see text]-actinin. To obtain insight into how mutually interacting actin crosslinking proteins modulate the properties of actin networks, we characterized the micro-structure and mechanics of actin networks crosslinked with palladin and [Formula: see text]-actinin. We first showed that palladin crosslinks actin filaments into bundled networks which are viscoelastic in nature. Our studies also showed that composite networks of [Formula: see text]-actinin/palladin/actin behave very similar to pure palladin or pure [Formula: see text]-actinin networks. However, we found evidence that palladin and [Formula: see text]-actinin synergistically modify network viscoelasticity. To our knowledge, this is the first quantitative characterization of the physical properties of actin networks crosslinked with two mutually interacting crosslinkers.     

Architecture of the Outer Membrane of Escherichia coli III. Protein-Lipopolysaccharide Complexes in Intramembraneous Particles

In a previous paper (A. Verkleij, L. van Alphen, J. Bijvelt, and B. Lugtenberg, Biochim. Biophys. Acta 466:269-282, 1977) we have hypothesized that particles on the outer fracture face of the outer membrane ([Formula: see text]), with corresponding pits on the inner fracture face of the outer membrane ([Formula: see text]), consist of lipopolysaccharide (LPS) aggregates stabilized by divalent cations and that they might contain protein and/or phospholipid. In the present paper the roles of LPS, cations, and proteins in these [Formula: see text] particles are described more extensively, using a strain that lacks the major outer membrane proteins, b, c, and d (b(-) c(-) d(-)), and has a reduction in the number of [Formula: see text] particles of 75%. To study the role of divalent cations in the formation of [Formula: see text] particles, these b(-) c(-) d(-) cells were grown or incubated with Ca(2+), Mg(2+), or putrescine. The presence of Ca(2+) resulted in the appearance of many [Formula: see text] particles and [Formula: see text] pits. Mg(2+) and putrescine were less effective than Ca(2+). Introduction of these particles was not accompanied by alterations in the relative amounts of LPS and cell envelope proteins. Ca(2+) treatment of a heptoseless derivative of a b(-) c(-) d(-) strain did not result in morphological changes. Incubation of Ca(2+)-treated cells with ethylenediaminetetraacetate caused the disappearance of the introduced particles as well as the release of more than 60% of the cellular LPS. These results strongly support the hypothesis that LPS is involved in the formation of [Formula: see text] particles and [Formula: see text] pits. The roles of various outer membrane proteins in the formation of [Formula: see text] particles were studied by comparing the freeze-fracture morphology of b(-) c(-) d(-) cells with that of cells which contain one of the outer membrane proteins b, c, d, and e or the receptor protein for bacteriophage lambda. The results showed that the presence of any of these five proteins in a b(-) c(-) d(-) background resulted in a large increase in the number of [Formula: see text] particles and [Formula: see text] pits, indicating that these proteins are, independent of each other, involved in the formation of [Formula: see text] particles and [Formula: see text] pits. The simplest explanation for the results is that in wild-type cells each particle consists of LPS complexed with some molecules of a single protein species, stabilized by either divalent cations or polyamines. It is hypothesized that the outer membrane of the wild-type cell contains a heterogeneous population of particles, of which 75% consists of protein b-LPS, protein c-LPS, and protein d-LPS particles. A function of these particles as aqueous pores is proposed.     

Trans-Theta Logistics: A New Family of Population Growth Sigmoid Functions

Sigmoid functions have been applied in many areas to model self limited population growth. The most popular functions; General Logistic (GL), General von Bertalanffy (GV), and Gompertz (G), comprise a family of functions called Theta Logistic ([Formula: see text] L). Previously, we introduced a simple model of tumor cell population dynamics which provided a unifying foundation for these functions. In the model the total population (N) is divided into reproducing (P) and non-reproducing/quiescent (Q) sub-populations. The modes of the rate of change of ratio P/N was shown to produce GL, GV or G growth. We now generalize the population dynamics model and extend the possible modes of the P/N rate of change. We produce a new family of sigmoid growth functions, Trans-General Logistic (TGL), Trans-General von Bertalanffy (TGV) and Trans-Gompertz (TG)), which as a group we have named Trans-Theta Logistic (T [Formula: see text] L) since they exist when the [Formula: see text] L are translated from a two parameter into a three parameter phase space. Additionally, the model produces a new trigonometric based sigmoid (TS). The [Formula: see text] L sigmoids have an inflection point size fixed by a single parameter and an inflection age fixed by both of the defining parameters. T [Formula: see text] L and TS sigmoids have an inflection point size defined by two parameters in bounding relationships and inflection point age defined by three parameters (two bounded). While the Theta Logistic sigmoids provided flexibility in defining the inflection point size, the Trans-Theta Logistic sigmoids provide flexibility in defining the inflection point size and age. By matching the slopes at the inflection points we compare the range of values of inflection point age for T [Formula: see text] L versus [Formula: see text] L for model growth curves.     

The biosynthesis of 4-hydroxycoumarin and dicoumarol by Aspergillus fumigatus Fresenius

A strain of Aspergillus fumigatus Fresenius, isolated from spoiled hay, converts melilotic acid (o-hydroxyphenylpropionic acid) and o-coumaric acid into 4-hydroxycoumarin and dicoumarol. The sequence is shown to be melilotic acid (I) [Formula: see text] coumaric acid (IV) [Formula: see text] beta-hydroxymelilotic acid (II) [Formula: see text] beta-oxomelilotic acid (III) [Formula: see text] 4-hydroxycoumarin (VI), on the basis of (1) studies on the formation of postulated intermediates, (2) experiments with isotopically labelled materials and (3) sequential enzyme induction. In the presence of semicarbazide, o-coumaraldehyde is formed from o-coumaric acid: there is no evidence, however, that this lies on the normal metabolic pathway.     

Copper(I)-alkyl sulfide and -cysteine tri-nuclear clusters as models for metallo proteins: a structural density functional analysis

After having set up the computational methodology for Cu(I)-sulfur systems as models for copper proteins, namely using the simple ligands H(2)S, HS(-), CH(3)SH, and CH(3)S(-), the Cu(I)-Cysteine systems have been investigated: [Cu(I)( S -H(2)Cys) (n) ](+) (H(2)Cys, cysteine, NH(2),SH,COOH) [Cu(I)( S -HCys) (n) ](1-) (n) (NH(2),S(-),COOH). Finally, the structures for bi-nuclear [Formula: see text] (Et, CH(2)CH(3)), [Formula: see text] and tri-nuclear [Cu(I)( S -SH)](3), [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] (NH(2),SH,COOH), [Formula: see text] (NH(2),S(-),COOH, and NH(2),SH,COO(-)), as well as [Formula: see text] (NH(2),S(-),COO(-)), were also optimized to mimic the active center for a metallo-chaperone copper transport protein (CopZ). The X-ray structures for the biomolecules were matched fairly well as regards the Cu-S bond distances and Cu…Cu contact distances in the case the model cysteine S atom is deprotonated. Upon protonation of ligand S atoms, the conformation of clusters is altered and might bring about the di- and tri-nuclear core breakage. These findings suggest that subtle protonation/deprotonation steps, i.e. small and/or local pH changes play a significant role for copper transport processes.     

Ocean acidification leads to counterproductive intestinal base loss in the gulf toadfish (opsanus Beta)

Abstract Oceanic CO(2) has increased from 280 to 380 μatm since preindustrial times and is expected to reach 1,900 μatm by 2300. In addition, regional upwelling zones exhibit levels up to 2,300 μatm, making exploration at future global projected CO(2) levels ecologically relevant today. Recent work has demonstrated that CO(2) exposure as low as 1,000 μatm induces acidosis in toadfish (Opansus beta), leading to metabolic compensation by retention of blood [Formula: see text] in an effort to defend pH. Since increased serosal [Formula: see text] translates to increased [Formula: see text] secretion rates in isolated intestinal tissue, we predicted that blood elevation of [Formula: see text] and Pco(2) during exposure to 1,900 μatm CO(2) would increase in vivo base secretion rates. Rectal fluid and CaCO(3) excretions were collected from toadfish exposed to 380 (control) and 1,900 μatm CO(2) for 72 h. Fluids were analyzed for pH, osmolality, ionic composition, and total CO(2). Precipitated CaCO(3) was analyzed for titratable alkalinity, Mg(2+), and Ca(2+) content. Fish exposed to 1,900 μatm CO(2) exhibited higher rectal base excretion rates, higher rectal fluid [Formula: see text] (mmol L(-1)), and lower fluid Cl(-) (mmol L(-1)) than controls, suggesting increased intestinal anion exchange as a result of the compensated respiratory acidosis. This study verifies that imminent projected CO(2) levels expected by the year 2300 lead to greater intestinal [Formula: see text] loss, a process that acts against compensation for a CO(2)-induced acidosis.