Hemagglutinin 1-specific immunoglobulin G and Fab molecules mediate postattachment neutralization of influenza A virus by inhibition of an early fusion event

In standard neutralization (STAN), virus and antibody are reacted together before inoculation of target cells, and inhibition of almost any of the processes concerned in the early interaction of virus and cell, including inhibition of virus attachment to cell receptors, can be the cause of neutralization by a particular monoclonal antibody (MAb). To simplify the interpretation of antibody action, we carried out a study of postattachment neutralization (PAN), where virus is allowed to attach to target cells before neutralizing antibody is introduced. We used influenza virus A/PR/8/34 (H1N1) and monoclonal immunoglobulin G (IgG) molecules and their Fabs specific to antigenic sites Sb (tip), Ca2 (loop), and Cb (hinge) of the hemagglutinin 1 (HA1) protein. All IgGs and Fabs gave PAN, although with reduced efficiency compared with STAN. Thus, bivalent binding of antibody was not essential for PAN. By definition, none of these MAbs gave PAN by inhibiting virus attachment, and they did not elute attached virus from the target cell or inhibit endocytosis of virus. However, virus-cell fusion, as demonstrated by R18 fluorescence dequenching or hemolysis of red blood cells, was inhibited in direct proportion to neutralization and in a dose-dependent manner and was thus likely to be responsible for the observed neutralization. However, to get PAN, it was necessary to inhibit the activation of the prefusion intermediate, the earliest known form on the fusion pathway that is created when virus is incubated at pH 5 and 4 degrees C. PAN antibodies may act by binding HA trimers in contact with the cell and/or trimers in the immediate vicinity of the virus-cell contact point and so inhibit the recruitment of additional receptor-HA complexes.     

Fast algorithms for large-scale genome alignment and comparison

We describe a suffix-tree algorithm that can align the entire genome sequences of eukaryotic and prokaryotic organisms with minimal use of computer time and memory. The new system, MUMmer 2, runs three times faster while using one-third as much memory as the original MUMmer system. It has been used successfully to align the entire human and mouse genomes to each other, and to align numerous smaller eukaryotic and prokaryotic genomes. A new module permits the alignment of multiple DNA sequence fragments, which has proven valuable in the comparison of incomplete genome sequences. We also describe a method to align more distantly related genomes by detecting protein sequence homology. This extension to MUMmer aligns two genomes after translating the sequence in all six reading frames, extracts all matching protein sequences and then clusters together matches. This method has been applied to both incomplete and complete genome sequences in order to detect regions of conserved synteny, in which multiple proteins from one organism are found in the same order and orientation in another. The system code is being made freely available by the authors.     

BpMatch: an efficient algorithm for a segmental analysis of genomic sequences

Here, we propose BpMatch: an algorithm that, working on a suitably modified suffix-tree data structure, is able to compute, in a fast and efficient way, the coverage of a source sequence S on a target sequence T, by taking into account direct and reverse segments, eventually overlapped. Using BpMatch, the operator should define a priori, the minimum length l of a segment and the minimum number of occurrences minRep, so that only segments longer than l and having a number of occurrences greater than minRep are considered to be significant. BpMatch outputs the significant segments found and the computed segment-based distance. On the worst case, assuming the alphabet dimension d is a constant, the time required by BpMatch to calculate the coverage is O(l2n). On the average, by setting l ≥ 2 log(d)(n), the time required to calculate the coverage is only O(n). BpMatch, thanks to the minRep parameter, can also be used to perform a self-covering: to cover a sequence using segments coming from itself, by avoiding the trivial solution of having a single segment coincident with the whole sequence. The result of the self-covering approach is a spectral representation of the repeats contained in the sequence. BpMatch is freely available on: www.sourceforge.net/projects/bpmatch.     

Interaction interface in the C-terminal parts of centriole proteins Sas6 and Ana2

The centriole is a ninefold symmetrical structure found at the core of centrosomes and, as a basal body, at the base of cilia, whose conserved duplication is regulated by Plk4 kinase. Plk4 phosphorylates a single serine residue at the N-terminus of Ana2 to promote Ana2''s loading to the site of procentriole formation. Four conserved serines in Ana2''s STAN motif are then phosphorylated by Plk4, enabling Sas6 recruitment. Crystallographic data indicate that the coiled–coil domain of Ana2 forms a tetramer but the structure of full-length Ana2 has not been solved. Here, we have employed hydrogen–deuterium exchange coupled with mass spectrometry (HDX-MS) to uncover the conformational dynamics of Ana2, revealing the high flexibility of this protein with one rigid region. To determine the elusive nature of the interaction surfaces between Ana2 and Sas6, we have confirmed complex formation between the phosphomimetic form of Ana2 (Ana2-4D) and Sas6 in vitro and in vivo. Analysis of this complex by HDX-MS identifies short critical regions required for this interaction, which lie in the C-terminal parts of both proteins. Mutational studies confirmed the relevance of these regions for the Ana2–Sas6 interaction. The Sas6 site required for Ana2 binding is distinct from the site required for Sas6 to bind Gorab and Sas6 is able to bind both these protein partners simultaneously.     

Denaturing gradient electrophoresis (DGE) and single-strand conformation polymorphism (SSCP) molecular fingerprintings revisited by simulation and used as a tool to measure microbial diversity

The exact extent of microbial diversity remains unknowable. Nevertheless, fingerprinting patterns [denaturing gradient electrophoresis (DGE), single-strand conformation polymorphism (SSCP)] provide an image of a microbial ecosystem and contain diversity data. We generated numerical simulation fingerprinting patterns based on three types of distribution (uniform, geometric and lognormal) with a range of units from 10 to 500,000. First, simulated patterns containing a diversity of around 1000 units or more gave patterns similar to those obtained in experiments. Second, the number of bands or peaks saturated quickly to about 35 and were unrelated to the degree of diversity. Finally, assuming lognormal distribution, we used an estimator of diversity on in silico and experimental fingerprinting patterns. Results on in silico patterns corresponded to the simulation inputs. Diversity results in experimental patterns were in the same range as those obtained from the same DNA sample in molecular inventories. Thus, fingerprinting patterns contain extractable data about diversity although not on the basis of a number of bands or peaks, as is generally assumed to be the case.     

Trait-based species richness: ecology and macroevolution

Understanding the origins of species richness patterns is a fundamental goal in ecology and evolutionary biology. Much research has focused on explaining two kinds of species richness patterns: (i) spatial species richness patterns (e.g. the latitudinal diversity gradient), and (ii) clade-based species richness patterns (e.g. the predominance of angiosperm species among plants). Here, I highlight a third kind of richness pattern: trait-based species richness (e.g. the number of species with each state of a character, such as diet or body size). Trait-based richness patterns are relevant to many topics in ecology and evolution, from ecosystem function to adaptive radiation to the paradox of sex. Although many studies have described particular trait-based richness patterns, the origins of these patterns remain far less understood, and trait-based richness has not been emphasised as a general category of richness patterns. Here, I describe a conceptual framework for how trait-based richness patterns arise compared to other richness patterns. A systematic review suggests that trait-based richness patterns are most often explained by when each state originates within a group (i.e. older states generally have higher richness), and not by differences in transition rates among states or faster diversification of species with certain states. This latter result contrasts with the widespread emphasis on diversification rates in species-richness research. I show that many recent studies of spatial richness patterns are actually studies of trait-based richness patterns, potentially confounding the causes of these patterns. Finally, I describe a plethora of unanswered questions related to trait-based richness patterns.     

Selective adhesion and mineral deposition by osteoblasts on carbon nanofiber patterns

In an effort to develop better orthopedic implants, osteoblast (bone-forming cells) adhesion was determined on microscale patterns (30 microm lines) of carbon nanofibers placed on polymer substrates. Patterns of carbon nanofibers (CNFs) on a model polymer (polycarbonate urethane [PCU]) were developed using an imprinting method that placed CNFs in selected regions. Results showed the selective adhesion and alignment of osteoblasts on CNF patterns placed on PCU. Results also showed greater attraction forces between fibronectin and CNF (compared with PCU) patterns using atomic force microscope force-displacement curves. Because fibronectin is a protein that mediates osteoblast adhesion, these results provide a mechanism of why osteoblast adhesion was directed towards CNF patterns. Lastly, this study showed that the directed osteoblast adhesion on CNF patterns translated to enhanced calcium phosphate mineral deposition along linear patterns of CNFs on PCU. Since CNFs are conductive materials, this study formulated substrates that through electrical stimulation could be used in future investigations to further promote osteoblasts to deposit anisotropic patterns of calcium-containing mineral similar to that observed in long bones.     

Ecogeographical rules: elements of a synthesis

The development of a more synthetic approach to understanding spatial patterns in biogeography, particularly of the way in which these patterns interact, constitutes a major challenge for the field. Here we propose some key elements of such a synthesis for what can broadly be termed 'ecogeographical rules', that is spatial patterns in biological traits. These include understanding: (1) the different kinds of patterns (intraspecific, interspecific and assemblage), and the distinctions between them; (2) the unifying role that geographical ranges play in linking the patterns together; (3) that this unification can be obscured by the methodological assumptions made in documenting some patterns (e.g. assuming that intraspecific variation does not significantly influence interspecific and assemblage patterns in traits); (4) the implications of other methodological issues for the nature of observed patterns (e.g. how ranges are located on positional or environmental axes for interspecific patterns); (5) the need for further development of models linking different types of traits; (6) the nature of the generality of documented patterns at all levels, and particularly the difference between the frequency with which patterns are documented in the literature and the variety of extant species; and (7) the constraints that the form of intraspecific patterns place on interspecific and assemblage patterns, and that interspecific patterns place on assemblage patterns.     

An equilibrium-point model of electromyographic patterns during single-joint movements based on experimentally reconstructed control signals

The purpose of this work has been to develop a model of electromyographic (EMG) patterns during single-joint movements based on a version of the equilibrium-point hypothesis, a method for experimental reconstruction of the joint compliant characteristics, the dual-strategy hypothesis, and a kinematic model of movement trajectory. EMG patterns are considered emergent properties of hypothetical control patterns that are equally affected by the control signals and peripheral feedback reflecting actual movement trajectory. A computer model generated the EMG patterns based on simulated movement kinematics and hypothetical control signals derived from the reconstructed joint compliant characteristics. The model predictions have been compared to published recordings of movement kinematics and EMG patterns in a variety of movement conditions, including movements over different distances, at different speeds, against different-known inertial loads, and in conditions of possible unexpected decrease in the inertial load. Changes in task parameters within the model led to simulated EMG patterns qualitatively similar to the experimentally recorded EMG patterns. The model's predictive power compares it favourably to the existing models of the EMG patterns.     

Discover 1: a new program to search for unusually represented DNA motifs.

DISCOVER1 (DIStribution COunter VERsion 1) is a new program that can identify DNA motifs occurring with a high deviation from the expected frequency. The program generates families of patterns, each family having a common set of defined bases. Undefined bases are inserted amongst the defined bases in different ways, thus generating the diverse patterns of each family. The occurrences of the different patterns are then compared and analysed within each family, assuming that all patterns should have the same probability of occurrence. An extensive use of computer memory, combined with the immediate sorting of counts by address calculation allow a complete counting of all DNA motifs on a single pass on the DNA sequence. This approach offers a very fast way to search for unusually distributed patterns and can identify inexact patterns as well as exact patterns.     

The quest for a null model for macroecological patterns: geometry of species distributions at multiple spatial scales

There have been several attempts to build a unified framework for macroecological patterns. However, these have mostly been based either on questionable assumptions or have had to be parameterized to obtain realistic predictions. Here, we propose a new model explicitly considering patterns of aggregated species distributions on multiple spatial scales, the property which lies behind all spatial macroecological patterns, using the idea we term 'generalized fractals'. Species' spatial distributions were modelled by a random hierarchical process in which the original 'habitat' patches were randomly replaced by sets of smaller patches nested within them, and the statistical properties of modelled species assemblages were compared with macroecological patterns in observed bird data. Without parameterization based on observed patterns, this simple model predicts realistic patterns of species abundance, distribution and diversity, including fractal-like spatial distributions, the frequency distribution of species occupancies/abundances and the species–area relationship. Although observed macroecological patterns may differ in some quantitative properties, our concept of random hierarchical aggregation can be considered as an appropriate null model of fundamental macroecological patterns which can potentially be modified to accommodate ecologically important variables.     

Regular heartbeat dynamics are associated with cardiac health

The human heartbeat series is more variable and, hence, more complex in healthy subjects than in congestive heart failure (CHF) patients. However, little is known about the complexity of the heart rate variations on a beat-to-beat basis. We present an analysis based on symbolic dynamics that focuses on the dynamic features of such beat-to-beat variations on a small time scale. The sequence of acceleration and deceleration of eight successive heartbeats is represented by a binary sequence consisting of ones and zeros. The regularity of such binary patterns is quantified using approximate entropy (ApEn). Holter electrocardiograms from 30 healthy subjects, 15 patients with CHF, and their surrogate data were analyzed with respect to the regularity of such binary sequences. The results are compared with spectral analysis and ApEn of heart rate variability. Counterintuitively, healthy subjects show a large amount of regular beat-to-beat patterns in addition to a considerable amount of irregular patterns. CHF patients show a predominance of one regular beat-to-beat pattern (alternation of acceleration and deceleration), as well as some irregular patterns similar to the patterns observed in the surrogate data. In healthy subjects, regular beat-to-beat patterns reflect the physiological adaptation to different activities, i.e., sympathetic modulation, whereas irregular patterns may arise from parasympathetic modulation. The patterns observed in CHF patients indicate a largely reduced influence of the autonomic nervous system. In conclusion, analysis of short beat-to-beat patterns with respect to regularity leads to a considerable increase of information compared with spectral analysis or ApEn of heart-rate variations.     

Inferring a District-Based Hierarchical Structure of Social Contacts from Census Data

Researchers have recently paid attention to social contact patterns among individuals due to their useful applications in such areas as epidemic evaluation and control, public health decisions, chronic disease research and social network research. Although some studies have estimated social contact patterns from social networks and surveys, few have considered how to infer the hierarchical structure of social contacts directly from census data. In this paper, we focus on inferring an individual’s social contact patterns from detailed census data, and generate various types of social contact patterns such as hierarchical-district-structure-based, cross-district and age-district-based patterns. We evaluate newly generated contact patterns derived from detailed 2011 Hong Kong census data by incorporating them into a model and simulation of the 2009 Hong Kong H1N1 epidemic. We then compare the newly generated social contact patterns with the mixing patterns that are often used in the literature, and draw the following conclusions. First, the generation of social contact patterns based on a hierarchical district structure allows for simulations at different district levels. Second, the newly generated social contact patterns reflect individuals social contacts. Third, the newly generated social contact patterns improve the accuracy of the SEIR-based epidemic model.     

The Concept of Taxon Invariance in Ecology: Do Diversity Patterns Vary with Changes in Taxonomic Resolution?

Diversity patterns cannot be properly interpreted without a theory providing criteria for their evaluation. We propose a concept to prevent artifictions caused by improper consideration of changes in observed patterns due to variation in taxon delimitation. Most biodiversity patterns concern assemblages of species of given higher taxon (e.g. class). Some patterns seem to be universal, e.g., body size distribution, species-abundance distribution, species-area relationship, or the relationship between diversity and energy availability. However, truly universal patterns should not change when we change taxonomic scope by focusing on subtaxa or when we merge several sister taxa together and analyze patterns in resulting higher taxon. Similarly, some patterns may not change when changing the basic unit of the study e.g., when replacing species by genera or families (or any monophyletic clades), although other patterns may not be invariant against the variation of the basic unit. In fact, there are only two possibilities: biodiversity patterns are either taxon-invariant or they vary systematically with taxonomic resolution, which would indicate some fundamental taxonomic level with interesting implications for biological processes behind those patterns. Here we develop the concept of taxon invariance of diversity patterns and apply it on the abovementioned patterns. We show that simple theoretical considerations markedly constrain the set of possible patterns, as some of them cannot be simultaneously valid for both a taxon and its subtaxa – frequency distributions of abundances cannot be simultaneously lognormal for a given taxon and all its subtaxa, the taxa-area relationship cannot follow a power-law for all levels of taxonomic resolution, and energy availability cannot affect diversity of all taxonomic units in the same way. Analyses of the variation in the form of biodiversity patterns with changing taxonomic resolution thus provide an extremely useful tool for revealing properties of respective patterns, their universality and logical consistency.     

Three-dimensional architectures grown by simple 'stigmergic' agents

A simple model of multi-agent three-dimensional construction is presented. The properties of this model are investigated. Based on these properties, a fitness function is defined to characterize the structured patterns that can be generated by the model. The fitness function assigns a value to each pattern. The choice of the fitness function is validated by the fact that human observers tend to view patterns with high (resp. low) fitness as structured (resp. unstructured). A genetic algorithm based on this fitness function is used to explore the space of possible patterns. The genetic algorithm is able to make use of sub-modules of existing patterns and recombine them to produce novel patterns, but strong epistatic interactions among genes make the fitness landscape rugged and prevent more complex patterns from being produced.     

Formation of banded vegetation patterns resulted from interactions between sediment deposition and vegetation growth

This research investigates the formation of banded vegetation patterns on hillslopes affected by interactions between sediment deposition and vegetation growth. The following two perspectives in the formation of these patterns are taken into consideration: (a) increased sediment deposition from plant interception, and (b) reduced plant biomass caused by sediment accumulation. A spatial model is proposed to describe how the interactions between sediment deposition and vegetation growth promote self-organization of banded vegetation patterns. Based on theoretical and numerical analyses of the proposed spatial model, vegetation bands can result from a Turing instability mechanism. The banded vegetation patterns obtained in this research resemble patterns reported in the literature. Moreover, measured by sediment dynamics, the variation of hillslope landform can be described. The model predicts how treads on hillslopes evolve with the banded patterns. Thus, we provide a quantitative interpretation for coevolution of vegetation patterns and landforms under effects of sediment redistribution.     

Sequences of symmetry-breaking in phyllotactic transitions

This paper studies the transition of phyllotactic patterns by a group-theoretic approach. Typical phyllotactic patterns are represented here as dotted patterns on a cylinder, where the cylinder is regarded as the stem of a plant and the dots are points where leaves branch from the stem. We can then classify the symmetries of the alternate and opposite phyllotaxis into four types of groups, and clarify sequences of symmetry-breaking among these groups. The sequences turn out to correspond to transition paths of phyllotactic patterns found in the wild. This result shows the usefulness of classification of phyllotactic patterns based on their group symmetries. Moreover, the breaking of reflection symmetry is found to be an important rule for real phyllotactic transitions.     

Pattern discrimination by the honeybee (Apis mellifera): training on two pairs of patterns alternately

Pattern discrimination in the honeybee was studied by training alternately with two different pairs of patterns. Individually marked bees made a forced choice from a fixed distance in a standard Y-choice maze for a reward of sugar solution. Bees were trained, first on one pair of patterns for 10min then on a second pair, and so on, alternately between the two pairs. The pairs of patterns were selected to test the hypothesis that bees have a limited number of parallel mechanisms for the detection and discrimination of certain generalized global features. If this is so, it might be expected that each channel could process one pair of patterns simultaneously, but two pairs of patterns that are processed by the same channel would interfere with each other during the learning process. Features tested were: average orientation of edges, radial and tangential edges based on a symmetry of three or six, the position of a black spot, and the exchange of black and white. The bees fail to learn when the two alternated pairs of patterns offer the same feature, and they discriminate when the pairs offer two different features.     

Four levels of patterns in tree-rings: an archaeological approach to dendroecology

This paper introduces a method detailing how tree-ring data from subfossil and archaeological wood can be interpreted in palaeoecological terms. On the basis of a literature review concerning the effects of known impacts on tree growth, an attempt is undertaken to provide a general theoretical framework for structuring and interpreting non-recent data where the ecological context is usually missing. The most important tools are dendrotypology and the systematic analysis of tree-ring patterns on four levels. These levels are: (1) ring-anatomical patterns; (2) impact patterns in ring width series at the single-tree level; (3) stand-dynamic patterns, i.e. patterns in ring width series on a stand-wide level; (4) complex patterns that are made up of consistent combinations of the other three pattern levels with each other or additional information. The distinction of these patterns allows the disentangling of different sources of influence on tree growth, which can also potentially be applied to archaeological wood. Several types of reaction to different categories of impact are defined. On a stand-wide scale, the phases of stand development can be reconstructed by identifying characteristic combinations of events. Thus, the range of possible interpretations can be narrowed down to a few possibilities, and sometimes only one. While the general concept is thought to be applicable to a wider range of regions and ecological settings, the presented discussion focuses on gap-phase dominated lowland forests and anthropogenic stands derived from such, which form the focus of central European dendroarchaeological research.