We give in this paper indications about the dynamical impact (as phenotypic changes) coming from the main sources of perturbation in biological regulatory networks. First, we define the boundary of the interaction graph expressing the regulations between the main elements of the network (genes, proteins, metabolites, ...). Then, we search what changes in the state values on the boundary could cause some changes of states in the core of the system (robustness to boundary conditions). After, we analyse the role of (...) the mode of updating (sequential, block sequential or parallel) on the asymptotics of the network, essentially on the occurrence of limit cycles (robustness to updating methods). Finally, we show the influence of some topological changes (e.g. suppression or addition of interactions) on the dynamical behaviour of the system (robustness to topology perturbations). (shrink)

The genetic code has evolved from its initial non-degenerate wobble version until reaching its present state of degeneracy. By using the stereochemical hypothesis, we revisit the problem of codon assignations to the synonymy classes of amino-acids. We obtain these classes with a simple classifier based on physico-chemical properties of nucleic bases, like hydrophobicity and molecular weight. Then we propose simple RNA (or more generally XNA, with X for D, P or R) ring structures that present, overlap included, one and only (...) one codon by synonymy class as solutions of a combinatory variational problem. We compare these solutions to sequences of present RNAs considered as relics, with a high interspecific invariance, like invariant parts of tRNAs and micro-RNAs. We conclude by emphasizing some optimal properties of the genetic code. (shrink)

A simple numerical procedure is presented for the problem of estimating the parameters of models for the distribution of eggs oviposited in a host. The modelling is extended to incorporate both host density and time dependence to produce a remarkably parsimonious structure with only seven parameters to describe a data set of over 3,000 observations. This is further refined using a mixed model to accommodate several large outliers. Both models show that the level of superparasitism declines with increasing host density, (...) and the rate declines over time. It is proposed that the differing behaviours represented by the mixed model may reflect a balance between behavioural strategies of different selective benefit. (shrink)

The formal definition of species as explanatory hypotheses presented by Fitzhugh (Marine Biol 26:155–165, 2005a , b ) is emended. A species is an explanatory account of the occurrences of the same character(s) among gonochoristic or cross-fertilizing hermaphroditic individuals by way of character origin and subsequent fixation during tokogeny. In addition to species, biological systematics also employs hypotheses that are ontogenetic, tokogenetic, intraspecific, and phylogenetic, each of which provides explanatory hypotheses for distinctly different classes of causal questions. It is suggested (...) that species hypotheses can not be applied to organisms with obligate asexual, parthenogenetic, and self-fertilizing modes of reproduction. Hypotheses explaining shared characters among such organisms are, instead, strictly phylogenetic. Several implications of this emended definition are examined, especially the relations between species, intraspecific, and phylogenetic hypotheses, as well as the limitations of species names to be applied to temporally different characters within populations. (shrink)

Morphogenesis is a key process in developmental biology. An important issue is the understanding of the generation of shape and cellular organisation in tissues. Despite of their great diversity, morphogenetic processes share common features. This work is an attempt to describe this diversity using the same formalism based on a cellular description. Tissue is seen as a multi-cellular system whose behaviour is the result of all constitutive cells dynamics. Morphogenesis is then considered as a spatiotemporal organization of cells activities. We (...) show how this formalism relies on Reaction–Diffusion/Positional Information approach and how it permits to generalize its modelling possibilities. Three quite different applications for concrete morphogenetic processes are presented. The first one is a model for epithelial invagination, the second is a model of cellular differentiation by local cell–cell signalling. The last example is the secondary radial growth of conifer trees. From the mathematical point of view, different modelling tools are used according to the specificity of each process. (shrink)

Dobzhansky argued that biology only makes sense if life on earth has a shared history. But his dictum is often reinterpreted to mean that biology only makes sense in the light of adaptation. Some philosophers of science have argued in this spirit that all work in ‘proximal’ biosciences such as anatomy, physiology and molecular biology must be framed, at least implicitly, by the selection histories of the organisms under study. Others have denied this and have proposed non-evolutionary ways in which (...) biologists can frame these investigations. This paper argues that an evolutionary perspective is indeed necessary, but that it must be a forward-looking perspective informed by a general understanding of the evolutionary process, not a backward-looking perspective informed by the specific evolutionary history of the species being studied. Interestingly, it turns out that there are aspects of proximal biology that even a creationist cannot study except in the light of a theory of their effect on future evolution. (shrink)

Hypoxia hampers ATP production and threatens cell survival. Since cellular energetics tightly controls cell responses and fate, ATP levels and dynamics are of utmost importance. An integrated mathematical model of ATP synthesis by the mitochondrial oxidative phosphorylation/electron transfer chain system has been recently published (Beard, PLoS Comput Biol 1(4):e36, 2005). This model was validated under static conditions. To evaluate its performance under dynamical situations, we implemented and simulated it (Simulink®, The Mathworks). Inner membrane potential (ΔΨ) and [NADH] (feeding the electron (...) transfer chain) were used as indicators of mitochondrial function. Root mean squared error (rmse) was used to compare simulations and experiments (isolated cardiac mitochondria, Bose et al. J Biol Chem 278(40):39155–39165, 2003). Steady-state experimental data were reproduced within 2–6%. Model dynamics were evaluated under: (i) baseline, (ii) activation of NADH production, (iii) addition of ADP, (iv) addition of inorganic phosphate, (v) oxygen exhaustion. In all phases, except the last one, ΔΨ and [NADH] as well as oxygen consumption, were reproduced (within 10, 7 and 12%, respectively). Under anoxia, simulated ΔΨ markedly depolarized (no change in experiments). In conclusion, the model reproduces dynamic data as long as oxygen is present. Anticipated improvement by the inclusion of ATP consumption and explicit Krebs cycle are under evaluation. (shrink)

Deduction leads to causal explanation in phylogenetic inference when the evidence, the systematic character, is conceptualized as a transformation series. Also, the deductive entailment of modus tollens is satisfied when those kinds of events are operationalized as patristic difference. Arguments to the contrary are based largely on the premise that character-states are defined intensionally as objects, in terms of similarity relations. However, such relations leave biologists without epistemological access to the causal explanation and explanatory power of historical statements. Moreover, the (...) prediction-making to which those kinds of relations are limited in practice can lead to a category error—the mental conversion of an abstraction (the classes defined in terms of similarity relations) into a thing (such as an historical individual). The latter practices and problems characterize pattern cladistics, taxa being interpreted as homeostatic property cluster natural kinds, and other instrumentalist research programs. (shrink)

We consider a two-patch epidemiological system where individuals can move from one patch to another, and local interactions between the individuals within a patch are governed by the classical SIRS model. When the time-scale associated with migration is much smaller than the time-scale associated with infection, aggregation methods can be used to simplify the initial complete model formulated as a system of ordinary differential equations. Analysis of the aggregated model then shows that the two-patch basic reproduction rate is smaller than (...) the 1 patch one. We extend this result to a linear chain of P patches (P > 2). These results are illustrated by some examples for which numerical integration of the system of ordinary differential equations is performed. Simulations of an individual based model implemented with a multi-agent system are also carried out. (shrink)

In this work a mechanistic explanation of the classical algae growth model built by M. R. Droop in the late sixties is proposed. We first recall the history of the construction of the “predictive” variable yield Droop model as well as the meaning of the introduced cell quota. We then introduce some theoretical hypotheses on the biological phenomena involved in nutrient storage by the algae that lead us to a “conceptual” model. Though more complex than Droop’s one, our model remains (...) accessible to a complete mathematical study: its confrontation to the Droop model shows both have the same asymptotic behavior. However, while Droop’s cell quota comes from experimental bio-chemical measurements not related to intra-cellular biological phenomena, its analogous in our model directly follows our theoretical hypotheses. This new model should then be looked at as a re-interpretation of Droop’s work from a theoretical biologist’s point of view. (shrink)

We examine three critical aspects of Popper’s formulation of the ‘ Logic of Scientific Discovery ’—evidence, content and degree of corroboration—and place these concepts in the context of the Tree of Life (ToL) problem with particular reference to molecular systematics. Content, in the sense discussed by Popper, refers to the breadth and scope of existence that a hypothesis purports to explain. Content, in conjunction with the amount of available and relevant evidence, determines the testability, or potential degree of corroboration, of (...) a statement; content distinguishes scientific hypotheses from metaphysical assertions. Degree of corroboration refers to the relative and tentative confidence assigned to one hypothesis over another, based upon the performance of each under critical tests. Here we suggest that systematists attempt to maximize content and evidence to increase the potential degree of corroboration in all phylogenetic endeavors. Discussion of this “total evidence” approach leads to several interesting conclusions about generating ToL hypotheses. (shrink)

Apoptosis proteins play an essential role in regulating a balance between cell proliferation and death. The successful prediction of subcellular localization of apoptosis proteins directly from primary sequence is much benefited to understand programmed cell death and drug discovery. In this paper, by use of Chou’s pseudo amino acid composition (PseAAC), a total of 317 apoptosis proteins are predicted by support vector machine (SVM). The jackknife cross-validation is applied to test predictive capability of proposed method. The predictive results show that (...) overall prediction accuracy is 91.1% which is higher than previous methods. Furthermore, another dataset containing 98 apoptosis proteins is examined by proposed method. The overall predicted successful rate is 92.9%. (shrink)

The goal of this paper is to encourage a reconfiguration of the discussion about typology in biology away from the metaphysics of essentialism and toward the epistemology of classifying natural phenomena for the purposes of empirical inquiry. First, I briefly review arguments concerning ‘typological thinking’, essentialism, species, and natural kinds, highlighting their predominantly metaphysical nature. Second, I use a distinction between the aims, strategies, and tactics of science to suggest how a shift from metaphysics to epistemology might be accomplished. Typological (...) thinking can be understood as a scientific tactic that involves representing natural phenomena using idealizations and approximations, which facilitates explanation, investigation, and theorizing via abstraction and generalization. Third, a variety of typologies from different areas of biology are introduced to emphasize the diversity of this representational reasoning. One particular example is used to examine how there can be epistemological conflict between typology and evolutionary analysis. This demonstrates that alternative strategies of typological thinking arise due to the divergent explanatory goals of researchers working in different disciplines with disparate methodologies. I conclude with several research questions that emerge from an epistemological reconfiguration of typology. (shrink)

This paper addresses the general problem of how to rationally choose an algorithm for phylogenetic inference. Specifically, the controversy between maximum likelihood (ML) and maximum parsimony (MP) perspectives is reframed within the philosophical issue of theory choice. A Kuhnian approach in which rationality is bounded and value-laden is offered and construed through the notion of a Style of Modeling. A Style is divided into four stages: collecting remnant models, constructing models of taxonomical identity, implementing modeling algorithms, and finally inferring and (...) confirming evolutionary trees or cladograms. The identification and investigation of styles is useful for exploring sociological and epistemological issues such as individuating scientific communities and assessing the rationality of algorithm choice. Regarding the last point, this paper suggests that the values motivating ML and MP perspectives are justified but only contextually; these algorithms also have normative force because they can be therapeutic by allowing us to rationally choose among several competing trees, nonetheless this force is limited and cannot be used in order to decide the controversy tout court. (shrink)

Sickle cell haemoglobin (HbS) polymerization reduces erythrocyte deformability, causing deleterous vaso-occlusions. The double-nucleation model states that polymers grow from HbS aggregates, the nuclei, (i) in solution (homogeneous nucleation), (ii) onto existing polymers (heterogeneous nucleation). When linearized at initial HbS concentration, this model predicts early polymerization and its characteristic delay-time (Ferrone et al. J Mol Biol 183(4):591–610, 611–631, 1985). Addressing its relevance for describing complete polymerization, we constructed the full, non-linearized model (Simulink®, The MathWorks). Here, we compare the simulated outputs to experimental (...) progress curves (n = 6–8 different [HbS], 3–6 mM range, from Ferrone’s group). Within 10% from start, average root mean square (rms) deviation between simulated and experimental curves is 0.04 ± 0.01 (25°C, n = 8; mean ± standard error). Conversely, for complete progress curves, averaged rms is 0.48 ± 0.04. This figure is improved to 0.13 ± 0.01 by adjusting heterogeneous pathway parameters (p 2 μ cc : + 40%), and the fraction of polymer surface available for nucleation (ϕ), from 5e−7, (3 mM) to 13 (6 mM). Similar results are obtained at 37°C. We conclude that the physico-chemical description of heterogeneous nucleation warrants refinements in order to capture the whole HbS polymerization process. (shrink)

The influence of sediment oxygen heterogeneity, due to bioturbation, on diffusive oxygen flux was investigated. Laboratory experiments were carried out with 3 macrobenthic species presenting different bioturbation behaviour patterns: the polychaetes Nereis diversicolor and Nereis virens, both constructing ventilated galleries in the sediment column, and the gastropod Cyclope neritea, a burrowing species which does not build any structure. Oxygen two-dimensional distribution in sediments was quantified by means of the optical planar optode technique. Diffusive oxygen fluxes (mean and integrated) and a (...) variability index were calculated on the captured oxygen images. All species increased sediment oxygen heterogeneity compared to the controls without animals. This was particularly noticeable with the polychaetes because of the construction of more or less complex burrows. Integrated diffusive oxygen flux increased with oxygen heterogeneity due to the production of interface available for solute exchanges between overlying water and sediments. This work shows that sediment heterogeneity is an important feature of the control of oxygen exchanges at the sediment–water interface. (shrink)

Species are generally considered to be the basic units of evolution, and hence to constitute spatio-temporally bounded entities. In addition, it has been argued that species also instantiate a natural kind. Evolution is fundamentally about change. The question then is how species can remain the same through evolutionary change. Proponents of the species qua individuals thesis individuate species through their unique evolutionary origin. Individuals, or spatio-temporally located particulars in general, can be bodies, objects, events, or processes, or a combination of (...) these. It is here argued that species are best understood as open or closed, causally integrated processual systems that also instantiate an historically conditioned homeostatic property cluster natural kind. (shrink)

I attempt to raise questions regarding elements of systematics—primarily in the realm of phylogenetic reconstruction—in order to provoke discussion on the current state of affairs in this discipline, and also evolutionary biology in general: e.g., conceptions of homology and homoplasy, hypothesis testing, the nature of and objections to Hennigian “phylogenetic systematics”, and the schism between (neo)Darwinian descendants of the “modern evolutionary synthesis” and their supposed antagonists, cladists and punctuationalists.

We formulate and analyze the dynamics of an influenza pandemic model with vaccination and treatment using two preventive scenarios: increase and decrease in vaccine uptake. Due to the seasonality of the influenza pandemic, the dynamics is studied in a finite time interval. We focus primarily on controlling the disease with a possible minimal cost and side effects using control theory which is therefore applied via the Pontryagin’s maximum principle, and it is observed that full treatment effort should be given while (...) increasing vaccination at the onset of the outbreak. Next, sensitivity analysis and simulations (using the fourth order Runge-Kutta scheme) are carried out in order to determine the relative importance of different factors responsible for disease transmission and prevalence. The most sensitive parameter of the various reproductive numbers apart from the death rate is the inflow rate, while the proportion of new recruits and the vaccine efficacy are the most sensitive parameters for the endemic equilibrium point. (shrink)

Despite the amount of work that has been produced on the subject over the years, the ‘transformation of cladistics’ is still a misunderstood episode in the history of comparative biology. Here, I analyze two outstanding, highly contrasting historiographic accounts on the matter, under the perspective of an influential dichotomy in the philosophy of science: the opposition between Scientific Realism and Empiricism. Placing special emphasis on the notion of ‘causal grounding’ of morphological characters ( sensu Olivier Rieppel) in modern developmental biology’s (...) (mechanistic) theories, I arrive at the conclusion that a ‘new transformation of cladistics’ is philosophically plausible. This ‘reformed’ understanding of ‘pattern cladistics’ entails retaining the interpretation of cladograms as ‘schemes of synapomorphies’, but in association to construing cladogram nodes as ‘developmental-genetic taxic homologies’, instead of ‘standard Darwinian ancestors’. The reinterpretation of pattern cladistics presented here additionally proposes to take Bas Van Fraassen’s ‘constructive empiricism’ as a philosophical stance that could properly support such analysis of developmental-genetic data for systematic purposes. The latter suggestion is justified through a reappraisal of previous ideas developed by prominent pattern cladists (mainly, Colin Patterson), which concerned a scientifically efficient ‘observable/non-observable distinction’ linked to the conceptual pair ‘ontogeny and phylogeny’. Finally, I argue that a robust articulation of Antirealist alternatives in systematics may provide a rational basis for its disciplinary separation from evolutionary biology, as well as for a critical reconsideration of the proper role of certain Scientific Realist positions, currently popular in comparative biology. (shrink)

The development of comparative biology (systematics) has been of interest to philosophers and historians. Particular attention has been placed on the ‘war’ of the 1970s and 1980s, the apparent dispute among those who preferred this or that methodology. In this contribution we examine the history of comparative biology from the perspective of fundamentals rather than methodologies. Our examination is framed within the artificial—natural classification dichotomy, a viewpoint currently lost from view but worth resurrecting.

The dangers of character reification for cladistic inference are explored. The identification and analysis of characters always involves theory-laden abstraction—there is no theory-free “view from nowhere.” Given theory-ladenness, and given a real world with actual objects and processes, how can we separate robustly real biological characters from uncritically reified characters? One way to avoid reification is through the employment of objectivity criteria that give us good methods for identifying robust primary homology statements. I identify six such criteria and explore each (...) with examples. Ultimately, it is important to minimize character reification, because poor character analysis leads to dismal cladograms, even when proper phylogenetic analysis is employed. Given the deep and systemic problems associated with character reification, it is ironic that philosophers have focused almost entirely on phylogenetic analysis and neglected character analysis. (shrink)

Matrix models are widely used in biology to predict the temporal evolution of stage-structured populations. One issue related to matrix models that is often disregarded is the sampling variability. As the sample used to estimate the vital rates of the models are of finite size, a sampling error is attached to parameter estimation, which has in turn repercussions on all the predictions of the model. In this study, we address the question of building confidence bounds around the predictions of matrix (...) models due to sampling variability. We focus on a density-dependent Usher model, the maximum likelihood estimator of parameters, and the predicted stationary stage vector. The asymptotic distribution of the stationary stage vector is specified, assuming that the parameters of the model remain in a set of the parameter space where the model admits one unique equilibrium point. Tests for density-dependence are also incidentally provided. The model is applied to a tropical rain forest in French Guiana. (shrink)