Interaction Parameters and the Demise of Paleo-Indian Craftsmanship

Abstract

Interaction plays a central role in archaeological interpretations, yet it has remained theoretically underdeveloped and has often been misused. A framework for dealing with interaction is presented, consisting of: 1) ultimate adaptive conditions for interaction; 2) specific reasons for various types of interaction; 3) modifications of interaction due to aspects of the social matrix; 4) interaction mechanisms; and 5) the artifact patterns resulting from all of these factors. It is clear that “interaction” cannot be treated as a monolithic phenomenon; rather there are many types of interaction with many different outcomes for artifact patterning. The transition from the Paleo-Indian to Archaic stages is analyzed within this framework, and it is suggested that in the simplified interaction context of generalized hunter/ gatherers the size of interaction networks is largely a function of resource reliability and the relative need to maintain subsistence-related alliances between bands.     

The use of regenerable, affinity ligand-based surfaces for immunosensor applications.

The regeneration of antibody-binding surfaces is of major importance for re-usable sensor formats such as required for direct 'real-time' biosensing technologies and is often difficult to achieve. Antibodies commonly bind the antigen with high avidity and may themselves be sensitive to regeneration conditions. The interaction of polyclonal anti-chlorpyriphos antibody with an immobilised chlorpyriphos-ovalbumin (chlor-oval) conjugate and the interaction of soluble recombinant CD4 with covalently immobilised anti-CD4 IgG are presented in order to highlight these difficulties. Affinity-capture is suggested as an alternative format as it facilitates surface regeneration, directed immobilisation and the attainment of interaction progress curves that conform to the ideal pseudo-first-order kinetic interaction model. Protein A, protein G and polyclonal anti-mouse Fe-coated surfaces were used to observe the interaction of captured anti-GST monoclonal antibody with glutathione-s-transferase (GST). It was shown that a protein A affinity-capture surface produced ideal interaction progress curves while both protein G and polyclonal anti-mouse Fe resulted in systemic deviations.     

Exploiting the co-evolution of interacting proteins to discover interaction specificity

Protein interactions are fundamental to the functioning of cells, and high throughput experimental and computational strategies are sought to map interactions. Predicting interaction specificity, such as matching members of a ligand family to specific members of a receptor family, is largely an unsolved problem. Here we show that by using evolutionary relationships within such families, it is possible to predict their physical interaction specificities. We introduce the computational method of matrix alignment for finding the optimal alignment between protein family similarity matrices. A second method, 3D embedding, allows visualization of interacting partners via spatial representation of the protein families. These methods essentially align phylogenetic trees of interacting protein families to define specific interaction partners. Prediction accuracy depends strongly on phylogenetic tree complexity, as measured with information theoretic methods. These results, along with simulations of protein evolution, suggest a model for the evolution of interacting protein families in which interaction partners are duplicated in coupled processes. Using these methods, it is possible to successfully find protein interaction specificities, as demonstrated for >18 protein families.     

Binding of IRBIT to the IP3 receptor: determinants and functional effects

IRBIT has previously been shown to interact with the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) in an IP3-sensitive way. So far it remained to be elucidated whether this interaction was direct or indirect, and whether it was functionally relevant. We now show that IRBIT can directly interact with the IP3R, and that both the suppressor domain and the IP3-binding core of the IP3R are essential for a strong interaction. Moreover, we identified a PEST motif and a PDZ-ligand on IRBIT which were critical for the interaction with the IP3R. Furthermore, we identified Asp-73 as a critical residue for this interaction. Finally, we demonstrated that this interaction functionally affects the IP3R: IRBIT inhibits both IP3 binding and IP3-induced Ca2+ release.     

Complexity and stability revisited

Since Robert May's work on random community matrices it has been known that stability tends to decrease with complexity. Recently, it was shown that this is not necessarily true in competitive ecosystems. We investigated the stability of random ecosystems and found that it can largely be predicted by simple matrix statistics such as the mean and the variance of the interaction coefficients. We use this to explain why stability can increase as well as decrease with complexity in ecological communities. We argue that the variance, and to a lesser extent the mean, of the interaction coefficients go a long way in explaining patterns in the stability of ecosystems.     

A theory of natural selection incorporating interaction among individuals. I. The modeling process

Short- and long-term consequences of natural selection, operating in accordance with the classical (non-interaction) model, are reviewed. This review provides the basis for comparisons of the optimum results of the classical model with the results from interaction models. Then as a first step, the simplest interaction modeling system (Model I) is developed subject to the following conditions: (i) The natural selection model is constructed so that it is compatible with the one that already exists for artificial selection theory. This condition ensures that an overall theory is formulated which embraces both natural and artificial selection with a single modeling system and a common notation. (ii) The interaction theory is developed so that it is an extension of the classical theory. This condition ensures that the generalized theory includes the classical results as a special case when interaction is absent.The short- and long-term consequences of selection operating with Model I are determined to be less than optimal when compared with the classical results. Future papers in this series will consider how the interaction model can be modified in order to produce results which tend toward optimality.     

The study of combined action of agents using differential geometry of dose-effect surfaces

Although graphic surfaces have been used routinely in the study of combined action of agents, they are mainly used for display purposes. In this paper, it is shown that useful mechanistic information can be obtained from an analytical study of these surfaces using the tools of differential geometry. From the analysis of some simple dose-effect surfaces, it is proposed that the intrinsic curvature, referred to in differential geometry as the Gaussian curvature, of a dose-effect surface can be used as a general criterion for the classification of interaction between different agents. This is analogous to the interpretation of the line curvature of a dose-effect curve as an indication of self-interaction between doses for an agent. In this framework, the dose-effect surface would have basic uniform fabric with zero curvature in the absence of interaction, tentatively referred to as null-interaction. Pictorially speaking, this fabric is distorted locally or globally like the stretching and shrinking of a rubber sheet by the presence of interaction mechanisms between different agents. Since self-interaction with dilution dummies does not generate intrinsic curvature, this criterion of null-interaction would describe the interaction between two trulydifferent agents. It is shown that many of the published interaction mechanisms give rise to dose-effect surfaces with characteristic curvatures. This possible correlation between the intrinsic geometric curvature of dose-effect surfaces and the biophysical mechanism of interaction presents an interesting philosophical viewpoint for the study of combined action of agents.     

Chiral interaction in protein structures

A new mode of interaction, to be termed chiral interaction, is proposed between chiral molecules such as proteins and polar solvents (H₂O). Such a mode of interaction is well-recognized for macroscopic chiral devices, such as windmills or electric cells, and various media, such as wind or electrolyte. This mode of interaction requires several structural ingredients, all possessed by proteins, and its source is in ionic motion in the solvent. Such an interaction exists only for chiral objects or molecules and therefore possesses several peculiar and uncommon features, which may be of special biological significance. From a thermodynamical viewpoint this phenomenon is non-ergodic and time-irreversible, and therefore does not obey the principle of detailed balance. The energy content of this interaction is rather small and therefore it is to be regarded as a subthermal organization. Chiral interaction appears in the form of an intrinsic flow of perturbation or currents throughout the molecule and hence it is not easily observable. Two experiments are proposed for its observation. One is direct and the other is based on an assumption that couples chiral interaction with enzymatic activity. A model is proposed that links this interaction with the natural selection of the L-enantiomer of amino acids via the magnetic field of the earth. Several structural and other properties may obtain biological significance via the concept of chiral interaction. It is conjectured that chiral interaction may play a significant role in the control of protein activity.     

Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold

SHARPIN (SHANK-associated RH domain interacting protein) is part of a large multi-protein E3 ubiquitin ligase complex called LUBAC (linear ubiquitin chain assembly complex), which catalyzes the formation of linear ubiquitin chains and regulates immune and apoptopic signaling pathways. The C-terminal half of SHARPIN contains ubiquitin-like domain and Npl4-zinc finger domains that mediate the interaction with the LUBAC subunit HOIP and ubiquitin, respectively. In contrast, the N-terminal region does not show any homology with known protein interaction domains but has been suggested to be responsible for self-association of SHARPIN, presumably via a coiled-coil region. We have determined the crystal structure of the N-terminal portion of SHARPIN, which adopts the highly conserved pleckstrin homology superfold that is often used as a scaffold to create protein interaction modules. We show that in SHARPIN, this domain does not appear to be used as a ligand recognition domain because it lacks many of the surface properties that are present in other pleckstrin homology fold-based interaction modules. Instead, it acts as a dimerization module extending the functional applications of this superfold.     

Analysis of a case of mutagen specificity in Neurospora crassa

Summary When ultraviolet irradiation of doubly auxotrophic conidia was preceded or followed by weakly mutagenic doses of DEB, the frequency of adenine-reversions was increased above additivity, while that of inositol-reversions was additive or—usually—was decreased below additivity. These interactions did not affect completed revertants nor were they due to plating interactions between potential revertants and the non-mutant background cells. The interaction was stronger when DEB was given as pretreatment than when it was given as post-treatment. During the DEB-treatment, sensitivity to interaction increased from the low effect observed with post-treatment to the higher one typical for pretreatment. Irradiation towards the end of the treatment period gave the same interaction as irradiation of treated and washed cells. In post-treatment experiments, the irradiated cells retained their capacity for interaction with DEB undiminished for at least on hour. In pretreatment experiments, the washed cells retained their capacity for interaction with UV over at least 16 minutes. After 2 hours, interaction was diminished; after 4 hours, it had disappeared.These results suggest a number of conclusions. (a) Interaction is mainly or wholly due to the effect of DEB on UV-induced mutations. (b) Interaction does not occur at the level of the primary lesions in DNA but at some later step in mutagenesis. (c) The mechanism of interaction is not the same for the two types of reversion. (d) The enhanced frequency of adenine-reversions is possibly due to inhibition of a repair enzyme by DEB. (e) The decreased frequency of inositol-reversions does not appear to be due to inositol-less death, but does seem connected with some specific phenotypic feature of inositol-reversions.     

Identification and characterization of intramolecular γ-halo interaction in d<Superscript>0</Superscript> complexes: a theoretical approach

A mechanistic investigation to detect intramolecular M?X–C type interactions in d⁰ neutral and cationic complexes was carried out through a benchmark study employing different density functional methods. As γ-halogen is involved in M?X–C type interactions, it is denoted as a γ-halo interaction and the respective conformers are designated as halo-conformers. By analyzing the geometrical parameters of halo-conformers, it was observed that, irrespective of the nature of the metal and the halogen, the C_γ–X bond distance increases compared to the usual C–X bond, which brings the M and X centers close enough to generate a weak interaction. Generation of the M?X–C interaction was confirmed by performing NBO, AIM and Wiberg bond index analyses, from which the persistence of γ-halo interaction was seen to be prominent. Moreover, for each neutral and cationic complex, the values of Wiberg bond order are in good agreement with the AIM results. The effect of the metal center, as well as γ-halogen substitution, on γ-halo interaction was also studied in the present work. To justify the practical subsistence of the halo-conformers, we checked the stability of the conformers with respect to their β-conformers by comparing the zero-point-corrected electronic energies. Therefore, the entire study was designed in such a way that it can provide evidence in support of intramolecular M?X–C interactions, where, instead of the C–H bond, the C_γ–X bond will interact with the central transition metal.     

Measuring Information-Transfer Delays

In complex networks such as gene networks, traffic systems or brain circuits it is important to understand how long it takes for the different parts of the network to effectively influence one another. In the brain, for example, axonal delays between brain areas can amount to several tens of milliseconds, adding an intrinsic component to any timing-based processing of information. Inferring neural interaction delays is thus needed to interpret the information transfer revealed by any analysis of directed interactions across brain structures. However, a robust estimation of interaction delays from neural activity faces several challenges if modeling assumptions on interaction mechanisms are wrong or cannot be made. Here, we propose a robust estimator for neuronal interaction delays rooted in an information-theoretic framework, which allows a model-free exploration of interactions. In particular, we extend transfer entropy to account for delayed source-target interactions, while crucially retaining the conditioning on the embedded target state at the immediately previous time step. We prove that this particular extension is indeed guaranteed to identify interaction delays between two coupled systems and is the only relevant option in keeping with Wiener’s principle of causality. We demonstrate the performance of our approach in detecting interaction delays on finite data by numerical simulations of stochastic and deterministic processes, as well as on local field potential recordings. We also show the ability of the extended transfer entropy to detect the presence of multiple delays, as well as feedback loops. While evaluated on neuroscience data, we expect the estimator to be useful in other fields dealing with network dynamics.     

Cellular localisation of a water-soluble fullerene derivative

Fullerenes are a new class of compounds with potential uses in biology and medicine and many insights were made in the knowledge of their interaction with various biological systems. However, their interaction with organised living systems as well as the site of their potential action remains unclear. In this work, we have demonstrated that a fullerene derivative could cross the external cellular membrane and it localises preferentially to the mitochondria. We propose that our finding supports the potential use of fullerenes as drug delivery agents as their structure mimics that of clathrin known to mediate endocytosis.     

Select host cell proteins coelute with monoclonal antibodies in protein A chromatography

The most significant factor contributing to the presence of host cell protein (HCP) impurities in Protein A chromatography eluates is their association with the product monoclonal antibodies (mAbs) has been reported previously, and it has been suggested that more efficacious column washes may be developed by targeting the disruption of the mAbs-HCP interaction. However, characterization of this interaction is not straight forward as it is likely to involve multiple proteins and/or types of interaction. This work is an attempt to begin to understand the contribution of HCP subpopulations and/or mAb interaction propensity to the variability in HCP levels in the Protein A eluate. We performed a flowthrough (FT) recycling study with product respiking using two antibody molecules of apparently different HCP interaction propensities. In each case, the ELISA assay showed depletion of select subpopulations of HCP in Protein A eluates in subsequent column runs, while the feedstock HCP in the FTs remained unchanged from its native harvested cell culture fluid (HCCF) levels. In a separate study, the final FT from each molecule's recycling study was cross-spiked with various mAbs. In this case, Protein A eluate levels remained low for all but two molecules which were known as having high apparent HCP interaction propensity. The results of these studies suggest that mAbs may preferentially bind to select subsets of HCPs, and the degree of interaction and/or identity of the associated HCPs may vary depending on the mAb.     

The effects of personal interaction on triglyceride and uric acid levels, and coronary risk in a managerial population: a longitudinal study

This two year longitudinal study of managers investigated whether the level of interaction with other individuals was a job stressor that influences coronary risk factors. The results presented here show that increased levels of interaction were associated with increased serum triglyceride and increased serum uric acid levels. It is suggested that past research positing stress effects from responsibility for people may be due to interaction levels rather than responsibility per se. It was also found that Type A behavior and physical activity levels moderated these effects. While it is difficult to say that personal interaction, as a job stressor, contributes very significantly to either coronary risk factors or coronary heart disease the evidence supports the hypothesis that the amount of interaction has some specific stress effects.     

The influence of protein-lipid interactions on the order-disorder conformational transitions of the hydrocarbon chain.

The phases of simple systems involving one type of protein (lysozyme or cytochrome c) and one type of lipid (phosphatidic acid) have been characterized by X-ray crystallography, chemical analysis and spin-labeling technique as a function of temperature. They are of the lamellar type with alternative protein monolayers and lipid bilayers. According to the pH, two types of lamellar phases are obtained, one where the lipid-protein interactions are mainly hydrophobic, the other where they are electrostatic. In both cases, a phase transition occurs as temperature is lowered, between a high temperature phase, where all the lipids are in the liquid-like state, and another phase where some lipid chains are rigid. In the case of the phases with electrostatic interaction, it is shown that the onset of the order-disorder transition is shifted towards low temperature as compared with the homologous lipid-water phase and that the protein content of the phase decreases as the ratio of the liquid to rigid hydrocarbon chains decreases. This leads us to suggest that in the systems studied in this work the proteins interact only with lipid in the liquid-like state. In the case of the phases with hydrophobic interaction, it is shown that the extent of hydrophobic interaction between protein and lipid increases as the unsaturation of the hydrocarbon chains increases. The onset of the order-disorder transition shows a greater shift towards low temperature than the one observed in the case of the phase with electrostatic interaction.     

Rheological investigation on hyaluronan-fibrinogen interaction

This paper concerns the interaction between hyaluronan and fibrinogen as model for protein-polysaccharide interaction. From rheological investigation, it is shown that a 3D physical network is promoted by mixing the two components; the mechanism is attributed to electrostatic interactions. The influences of the molecular weight and of the hyaluronan concentration are examined; the loose interaction obtained for addition of small amount of soluble protein induces a non-Newtonian behaviour which may be in direct relation with the behaviour observed previously on synovial fluids.     

Protein-protein ratchets: stochastic simulation and application to processive enzymes

Interaction between a protein and a series of binding sites on a cytoskeletal substrate can create a resistance, or "protein friction," as the protein is moved along the substrate. If attachment and detachment rates are specified asymmetrically, this resistance can depend on the direction of movement, and the binding interaction acts as a ratchet. Stochastic computer simulations have been used to examine this type of protein-protein interaction. The performance of a protein-protein ratchet in the piconewton and nanometer range is significantly limited by thermal fluctuations, which in experimental measurements with single molecules are evident as Brownian motion. Simulations with a two-component model combining a conventional motor enzyme model with a protein-protein ratchet confirm previous suggestions that the processive movement of a single motor enzyme molecule against a load, as seen in experiments with inner arm dynein molecules, might be made possible by an accessory protein interaction that prevents backward slippage. When this accessory protein interaction is defined so that it acts as a ratchet, backward slippage can be prevented with minimal interference with forward progression.     

A fast layout algorithm for protein interaction networks

MOTIVATION: Graph drawing algorithms are often used for visualizing relational information, but a naive implementation of a graph drawing algorithm encounters real difficulties when drawing large-scale graphs such as protein interaction networks. RESULTS: We have developed a new, extremely fast layout algorithm for visualizing large-scale protein interaction networks in the three-dimensional space. The algorithm (1) first finds a layout of connected components of an entire network, (2) finds a global layout of nodes with respect to pivot nodes within a connected component and (3) refines the local layout of each connected component by first relocating midnodes with respect to their cutvertices and direct neighbors of the cutvertices and then by relocating all nodes with respect to their neighbors within distance 2. Advantages of this algorithm over classical graph drawing methods include: (1) it is an order of magnitude faster, (2) it can directly visualize data from protein interaction databases and (3) it provides several abstraction and comparison operations for effectively analyzing large-scale protein interaction networks. AVAILABILITY: http://wilab.inha.ac.kr/interviewer/