Molecular modeling and enzymatic studies of the interaction of a choline analogue and acetylcholinesterase

Pivaloyl-choline iodide 1 interactions with acetylcholinesterase (AChE) have been studied by theoretical and enzymatic methods. An integrated computational approach has clearly shown a substrate rather than inhibitory profile for 1. Enzymatic experiments have also supported the same theoretical conclusion indicating that AChE was able to hydrolyze 1 to choline.     

ASPMF: a new approach for identifying alternative splicing isoforms using peptide mass fingerprinting

Alternative splicing is generally accepted as a mechanism that explains the discrepancy between the number of genes and proteins. We used peptide mass fingerprinting with a theoretical database and scoring method to discover and identify alternative splicing isoforms. Our theoretical database was built using published alternative splicing databases such as ECgene, H-DBAS, and TISA. According to our theoretical database of 190,529 isoforms, 37% of human genes have multiple isoforms. The isoforms produced from a gene partially share common peptide fragments because they have common exons, making it difficult to distinguish isoforms. Therefore, we developed a new method that effectively distinguishes a true isoform among multiple isoforms in a gene. In order to evaluate our algorithm, we made test sets for 4226 protein isoforms extracted from our theoretical database randomly. Consequently, 94% of true isoforms were identified by our scoring algorithm.     

Theoretical and experimental yields for photoautotrophic, mixotrophic, and photoheterotrophic growth

Available electron methods are presented and used to estimate theoretical energetic growth yields for photoautotrophic, mixotrophic, and photoheterotrophic growth of algae and photosynthetic bacteria. The theoretical yields are compared to experimental values reported previously. For photoautotrophic and mixotrophic growth of algae experimental values that approach and even exceed the theoretical values have been reported in the literature. For photosynthetic bacteria experimental yields are much smaller than thetheoretical maximum values.     

A synopsis of calculations of the energy band structures for protein molecules

A review is given of the theoretical approaches that have been made to understand and describe the electronic energy band structures for protein molecules. In recent years significant progress has been made, and it is now clear that a theoretical basis does exist for the possibility that the electronic conduction properties of proteins are of biological relevance.     

Psychological categories as homologies: lessons from ethology

This article takes up the project of studying psychological categories as homologies. Ethologists have numerous theoretical ideas concerning the phylogeny and ontogeny of behavioral homologies. They also have well-developed operational methods for testing behavioral homologies. Many of these theoretical ideas and operational criteria can be applied to psychological homologies. This paper suggests that insights from ethology should be incorporated in adaptationist and functionalist approaches to psychology. Doing so would strengthen those approaches.     

The Evolution of Theoretically Useful Traits

The purely theoretical notion of fitness or optimality that is employed for instance in optimization theory has come under attack from those who think that only a more historically based notion of fitness could have a central role in evolutionary explanation. They argue that the key notion is proven usefulness rather than theoretical usefulness. This paper articulates a notion of theoretical usefulness and defends its role in functional evolutionary explanations.     

Complexity and evolution: What everybody knows

The consensus among evolutionists seems to be (and has been for at least a century) that the morphological complexity of organisms increases in evolution, although almost no empirical evidence for such a trend exists. Most studies of complexity have been theoretical, and the few empirical studies have not, with the exception of certain recent ones, been especially rigorous; reviews are presented of both the theoretical and empirical literature. The paucity of evidence raises the question of what sustains the consensus, and a number of suggestions are offered, including the possibility that certain cultural and/or perceptual biases are at work. In addition, a shift in emphasis from theoretical to empirical inquiry is recommended for the study of complexity, and guidelines for future empirical studies are proposed.     

Mixing ecology and epidemiology.

Mixing matrices can be used to describe subgroup interactions in mathematical models which have heterogeneity in population structure. A discussion is presented of two different approaches to the formulation of such mixing matrices. The relation between the two different methods is discussed, using examples based upon models of the transmission dynamics of HIV. There follows a discussion of the application of the mixing matrix approach to other areas in population biology, and a complementary overview of recent advances in theoretical ecology that may have applications in theoretical epidemiology.     

The role of ecological feedbacks in the evolution of host defence: what does theory tell us?

Hosts have evolved a diverse range of defence mechanisms in response to challenge by infectious organisms (parasites and pathogens). Whether defence is through avoidance of infection, control of the growth of the parasite once infected, clearance of the infection, tolerance to the disease caused by infection or innate and/or acquired immunity, it will have important implications for the population ecology (epidemiology) of the host-parasite interaction. As a consequence, it is important to understand the evolutionary dynamics of defence in the light of the ecological feedbacks that are intrinsic to the interaction. Here, we review the theoretical models that examine how these feedbacks influence the nature and extent of the defence that will evolve. We begin by briefly comparing different evolutionary modelling approaches and discuss in detail the modern game theoretical approach (adaptive dynamics) that allows ecological feedbacks to be taken into account. Next, we discuss a number of models of host defence in detail and, in particular, make a distinction between 'resistance' and 'tolerance'. Finally, we discuss coevolutionary models and the potential use of models that include genetic and game theoretical approaches. Our aim is to review theoretical approaches that investigate the evolution of defence and to explain how the type of defence and the costs associated with its acquisition are important in determining the level of defence that evolves.     

Ecology and evolution of long-lived semelparous plants

One of the more dramatic life histories in the natural world is that characterized by a single, massive, fatal reproductive episode ('semelparity'). A wealth of increasingly sophisticated theoretical models on differential life history evolution have been produced over the last two decades. In recent years, empirical studies of the ecology of semelparous plants (and their iteroparous relatives) have begun to address many aspects of the biology of these species, and to test the assumptions and predictions of theoretical models. Semelparity in long-lived plants is one of the few natural phenomena that has yielded specific quantitative tests of mathematical evolutionary theory.     

Theoretical morphology of developmental asymmetries

Morphospaces are theoretical tools to explore the morphological organization of living and fossil organisms. They have been used mostly by the paleontological community in an effort to get the most out of one of the only pieces of evidence that fossil material usually provide: the morphology of hard parts. The expectation with the establishment of theoretical morphospaces is that, by abstracting and modeling the fundamental parts of form, the multiple processes that generate the phenotypes of embryonic and adult structures will be better understood. In this essay, we suggest that ontogenetic trajectories can be used as the generative functions that build morphospaces, and propose approaches to build theoretical models for the establishment of left-right asymmetries during vertebrate heart embryogenesis.     

Exponential pattern of cell age distribution in dividing cells of plant meristems

In order to determine the pattern of cell age distribution in proliferating cells of Allium cepa roots we have measured by cytophotometry two cell size parameters, protein content and surface area projection, in cells that correspond to the entire proliferating population or only to the ana-telophase subpopulation. The size values of ana-telophase cells have been employed to construct theoretical size distributions for the entire proliferating cell population of the root meristem by assuming either a uniform or an exponential cell age distribution. Statistical comparison of theoretical distributions with the experimental one rules out a uniform cell age distribution and strongly favours an exponential age distribution similar to that found in bacteria.     

酚类抗氧化剂清除自由基活性的理论表征与应用

筛选高效、低毒、价廉的抗氧化剂一直是自由基生物学的核心课题之一。由于筛选工作的复杂性与艰巨性,近来开始用理论方法加快这一过程。已发现许多理论参数与抗氧化剂清除自由基速率常数的对数有良好的相关性,其中尤以有征Ｏ－Ｈ解离能的△ＨＯＦ值研究得最深入。借助这一理论指标可解释酚类抗氧化剂的构效关系。对复杂抗氧化体系中抗氧化剂的活性差异也能给予较好的预测,而且还可指导新型抗氧化剂的理论构建,至此这一理论的有效     

Theoretical frameworks for human behavioral endocrinology

How can we best discover the ultimate, evolved functions of endocrine signals within the field of human behavioral endocrinology? Two related premises will guide my proposed answer. First, hormones typically have multiple, simultaneous effects distributed throughout the brain and body, such that in an abstract sense their prototypical function is the coordination of diverse outcomes. Second, coordinated output effects are often evolved, functional responses to specific eliciting conditions that cause increases or decreases in the relevant hormones. If we accept these premises, then a natural way to study hormones is to hypothesize and test how multiple eliciting conditions are mapped into coordinated output effects via hormonal signals. I will call these input–output mappings “theoretical frameworks.” As examples, partial theoretical frameworks for gonadal hormones will be proposed, focusing on the signaling roles of testosterone in men and on estradiol and progesterone in women. Recent research on oxytocin in humans will also be considered as an example in which application of the theoretical framework approach could be especially helpful in making functional sense of the diverse array of findings associated with this hormone. The theoretical framework approach is not especially common in the current literature, with many theories having eschewed explicit consideration of input–output mappings in favor of parsimony-based arguments that attempt to find the one main thing that a hormone does with respect to psychology or behavior. I will argue that these parsimony-based models have many shortcomings, and conclude that the construction and testing of theoretical frameworks provides a better means of discovering the evolved functions of human endocrine signals.     

Eco-evolutionary dynamics

Evolutionary ecologists and population biologists have recently considered that ecological and evolutionary changes are intimately linked and can occur on the same time-scale. Recent theoretical developments have shown how the feedback between ecological and evolutionary dynamics can be linked, and there are now empirical demonstrations showing that ecological change can lead to rapid evolutionary change. We also have evidence that microevolutionary change can leave an ecological signature. We are at a stage where the integration of ecology and evolution is a necessary step towards major advances in our understanding of the processes that shape and maintain biodiversity. This special feature about ‘eco-evolutionary dynamics’ brings together biologists from empirical and theoretical backgrounds to bridge the gap between ecology and evolution and provide a series of contributions aimed at quantifying the interactions between these fundamental processes.     

Theoretical and experimental approaches to understand morphogen gradients

Morphogen gradients, which specify different fates for cells in a direct concentration‐dependent manner, are a highly influential framework in which pattern formation processes in developmental biology can be characterized. A common analysis approach is combining experimental and theoretical strategies, thereby fostering relevant data on the dynamics and transduction of gradients. The mechanisms of morphogen transport and conversion from graded information to binary responses are some of the topics on which these combined strategies have shed light. Herein, we review these data, emphasizing, on the one hand, how theoretical approaches have been helpful and, on the other hand, how these have been combined with experimental strategies. In addition, we discuss those cases in which gradient formation and gradient interpretation at the molecular and/or cellular level may influence each other within a mutual feedback loop. To understand this interplay and the features it yields, it becomes essential to take system‐level approaches that combine experimental and theoretical strategies.     

Theoretical calculation of pKa reveals an important role of Arg205 in the activity and stability of Streptomyces sp. N174 chitosanase

Based on the crystal structure of chitosanase from Streptomyces sp. N174, we have calculated theoretical pK(a) values of the ionizable groups of this protein using a combination of the boundary element method and continuum electrostatics. The pK(a) value obtained for Arg(205), which is located in the catalytic cleft, was abnormally high (>20.0), indicating that the guanidyl group may interact strongly with nearby charges. Chitosanases possessing mutations in this position (R205A, R205H, and R205Y), produced by Streptomyces lividans expression system, were found to have less than 0.3% of the activity of the wild type enzyme and to possess thermal stabilities 4-5 kcal/mol lower than that of the wild type protein. In the crystal structure, the Arg(205) side chain is in close proximity to the Asp(145) side chain (theoretical pK(a), -1.6), which is in turn close to the Arg(190) side chain (theoretical pK(a), 17.7). These theoretical pK(a) values are abnormal, suggesting that both of these residues may participate in the Arg(205) interaction network. Activity and stability experiments using Asp(145)- and Arg(190)-mutated chitosanases (D145A and R190A) provide experimental data supporting the hypothesis derived from the theoretical pK(a) data and prompt the conclusion that Arg(205) forms a strong interaction network with Asp(145) and Arg(190) that stabilizes the catalytic cleft.     

What can mathematical modeling tell us about hybrid invasions?

Compared to the vast theoretical literature on the dynamics of single species invasions, relatively few models have dealt with the emergence of invasive hybrids. Here, we review the variety of modeling approaches that have been used to study the dynamics of hybridization, outlining the underlying assumptions and highlighting their advantages and disadvantages. We summarize the predicted outcomes for the persistence for the native species and the resulting genetic composition of the native–exotic–hybrid complex under a variety of model scenarios. We highlight promising future directions for theoretical investigation and its integration with experimental studies.     

Nucleosome organization on Kluyveromyces lactis centromeric DNAs

The preferential assembly of specialized nucleosomes on budding yeast centromeres can be due either to the higher stability of specialized centromeric nucleosomes and/or to the lower stability of canonical centromeric nucleosomes with respect to bulk nucleosomes. We have evaluated the thermodynamic stability of canonical nucleosomes, assembled on Kluyveromyces lactis centromeric DNAs, with a competitive reconstitution assay and a theoretical method recently developed by us. The results, obtained by both methods, show that all five known centromeric DNAs from K. lactis are able to organize canonical nucleosomes, characterized by higher stability with respect those of bulk DNA. With 'footprinting' and theoretical prediction, based on sequence-dependent DNA elasticity, we have found that centromeric canonical nucleosomes are characterized by nucleosome dyad axis multiple positioning, rotationally phased. The isoenergetic nucleosome multiple positions are relevant in understanding the transition from canonical to specialized nucleosomes in interacting with centromere protein complexes. The satisfactory agreement between the results obtained from theoretical and experimental methods shows that sequence-dependent centromeric DNA elasticity has a main role in nucleosome thermodynamic stability and positioning.