The reconstruction principle

The theory of epigenesis is the undisputed paradigm of embryology, and it is still based on the classical concept proposed by Aristotle: the idea that embryonic development is a generation of structures which takes place according to a design--today we say a set of instructions--already present in the fertilized egg. This is a doctrine which can be referred to as 'pre-information', since it claims the preexistence of information exactly as the old theory of preformation claimed the preexistence of form. Here, however, it is shown that a more general version of epigenesis can be held, because of a new principle which states that it is mathematically possible to obtain not only a convergent generation of form, or structure, but also a convergent generation of information.     

The New Haseman‐Elston Method and the Weighted Pairwise Correlation Statistic Are Variations on the Same Theme

Model free linkage analysis of quantitative traits has become increasingly popular in recent years. Its basic idea is to use the principle of similarity: Sib pairs that are genetically (dis)similar at a linked marker should be phenotypically (dis)similar and vice versa. The classical Haseman‐Elston method, the new Haseman‐Elston (nHE) method and the weighted pairwise correlation (WPC) method follow this principle. Similarities and differences between these approaches are discussed. It is proven that the nHE and the WPC statistic are identical under specific regularity conditions. It is furthermore demonstrated that the nHE and the WPC method are expected to yield similar results for a broad range of models. Finally, it is shown that it is impossible to a priori determine whether the nHE method or the WPC method has greater power to detect linkage under general genetic models.     

Intermediate Moral Respect and Proportionality Reasoning

In a recent article in this journal Jonathan Pugh critiques the idea of intermediate ‘moral respect’ which some say is owed to embryos. This concept is inherent within the ‘principle of proportionality’, the principle that destructive research on embryos is permissable only if the research serves an important purpose. Pugh poses two specific questions to proponents of the idea of intermediate moral respect. This article argues that while the questions posed by Pugh are certainly pertinent to the debate, the hypothetical responses he suggests to these questions do not quite get to the core of what is troublesome about the concept. The article suggests alternative responses to Pugh's questions in order to focus attention on more fundamental problems facing the idea of intermediate moral respect, while also pointing to how the intermediate moral respect proponent might best develop these responses. It goes on to argue that these hypothetical responses fail to answer convincingly the questions posed. More specifically, this article challenges two possible justifications for the distinct idea of intermediate moral respect, namely the argument from potentiality (the argument raised by Pugh) and an argument from the proportionality of fundamental moral status (not considered by Pugh). The article also raises a dilemma inherent in the application of the principle of proportionality to cases involving beings to which intermediate moral respect is owed even where it is allowed, ex hypothesi, that both the category of intermediate moral respect and the general proportionality reasoning underpinning the principle of proportionality are basically cogent. This article thus develops and adds to the challenge laid down by Pugh to proponents of the idea of intermediate moral respect.     

Production of lysophosphatidic acid by lysophospholipase D in incubated plasma of spontaneously hypertensive rats and Wistar Kyoto rats.

Lysophosphatidic acid has been identified as a vasopressor principle in incubated mammalian plasma and sera, and shown to be generated extracellulary by lysophospholipase D-like activity. In this study, we monitored the time course of changes in the major phospholipid fractions during incubation of plasma, and found that polyunsaturated lysophosphatidic acids accumulate more rapidly than saturated lysophosphatidic acids at expense of the corresponding lysophosphatidylcholines. We compared the phospholipase activities for producing bioactive LPA in age-matched spontaneously hypertensive rats and Wistar Kyoto rats. The lysophospholipase D activity in rat plasma was found to be independent of strain and age. We suggest that lysophospholipase D functions in rat for persistent production of bioactive LPA in the circulation throughout life. However, our finding that production of LPA in spontaneously hypertensive rats was not greater than that in Wistar Kyoto rats does not seem to support the idea that increased production of LPA is involved in the pathogenesis of hypertension.     

Morphogens in vertebrate development: How do they work?

The idea that concentration gradients of crucial substances might control the pattern of development, even in the embryos of complex organisms, has been around for a long time, but mostly in obscure forms. Twenty five years ago clear, experimentally testable ideas about how such gradients might work were enunciated, and more recently the morphogen gradient principle was shown to underlie the beginnings of patterning in Drosophila. Is it also central to vertebrate development? Four recent papers raise experimentation to a new level^(1–4), while showing how difficult it might be to pin down the precise form of the mechanism.     

Allelic variants of hereditary prions: The bimodularity principle

Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either “canonical” (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as “gene” and “allele” to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor.     

ON THE PLAUSIBILITY OF HOMEOPATHIC ‘SIMILITUDE’

The homeopathic principle of similitude is not based on the principle of vaccination but on the more general principle of inversion of effects, a widespread medical phenomenon. Based on the systemic networks which play an important role in response to stress, this principle concerns the reorganization of regulation systems, through a coherent response to the medicine. This model is backed by a large number of published studies from our laboratory and others, by toxicological evidence such as the emerging fields of ‘hormesis’, of neuropharmacology, and of systems biology. The immune system is just one example of the possible application of this law of similitude, which constitutes the true ‘heart’ of the homeopathic idea, and again ethically justifies the attempt to apply it to experimental pharmacology.     

Generation of purpura-producing principle from pneumococcal cell walls.

The in vitro kinetics of muramic acid-alanine bond hydrolysis and pneumococcal purpura-producing principle generation by incubation of Streptococcus pneumoniae cell wall preparations with the bacterial autolysin N-acetylmuramyl-L-alanine amidase were similar. The generated purpura-producing principle preparation had a weight-average molecular weight of ca. 2.6 X 10(7) and possessed the glycan and teichoic acid constituents of the pneumococcal cell wall. The results support the idea that the pneumococcal purpura-producing principle is a high-molecular-weight, glycan-teichoic acid fragment released by hydrolysis of the muramic acid-alanine bonds in the bacterial cell wall.     

Are there effective resistance management strategies for vectors of human disease?*

The rotation of insecticides used by the Onchocerciasis Control Programme in West Africa is reviewed and the motives for this rotation are shown to be not only management of temephos resistance in the Simulium vectors but also constraints on what compounds are usable at particular seasons. A computer model indicates that without these seasonal constraints there is unlikely to be an advantage in a pre-planned rotation of insecticides, as compared with the prompt switching of compounds as dictated by detection of build up of resistance and switching back to the original compound if the regression of resistance is found to give the opportunity to do so. The latter sequence of events can hardly be called a ‘strategy’ for resistance management, but is what any well-managed pest control programme would be expected to do. The use of an insecticide mixture is different in principle from the use of rotation and depends on the idea that if the mixture is used from the outset, when resistance to both components of the mixture is likely to be rare, the double resistance combination would be so rare as to be dwarfed in numbers by those insects which avoid exposure altogether. The prospects for successful use of a mixture depend on each component killing a very high percentage of the exposed insects which are genetically susceptible to it. Whether this condition is met could be tested, for example, in the case of exposure of mosquitoes to insecticide-treated bednets.     

The template principle: Paradigm of modern genetics

The idea of continuity in living systems, which was initially developed in mid-19th century, reached its peak in 1928 thanks to N.K. Kol’tsov, who proposed the template principle in chromosome reproduction. The determination of genetic functions of nucleic acids and the advent of molecular genetics led to F. Crick’s statement of the central dogma of molecular biology in 1958. This dogma became a contemporary version of the template principle (templates of the first order). The discovery of “protein inheritance” underlay the notion of steric or conformational templates (second order) for reproducing conformation in a number of proteins. The template principle supplemented by this notion claims to be the main paradigm of modern genetics.     

An Improved Estimator of the Variance of the Regression Estimator

In this paper, the problem of estimation of variance of the general linear regression estimator has been considered. It has been shown that the first order calibration approach is a special case of the class of estimators proposed by Deng and Wu (1987). A second order calibration approach is suggested. Some new estimators are shown to be the special case of the proposed calibration approach. The efficiency of the proposed strategy is shown to improve on the original strategy. An idea to find a non-negative estimate of variance has been suggested.     

The equivalence of neo-Darwinism and Walrasian equilibrium: in defense of <Emphasis Type="Italic">Organismus economicus</Emphasis>

Neo-Darwinism is based on the same principles as the Walrasian analysis of equilibrium. This may be surprising for evolutionary economists who resort to neo-Darwinism as a result of their dissatisfaction with Walrasian economics. As it is well-known, the principle of rationality does not play a role in neo-Darwinism. In fact, the whole (neo-)Darwinian agenda became popular exactly because it expunged the idea of rationality from nature, and hence, from equilibrium. It is less known, however, that the rationality principle is also not central in Walrasian equilibrium analysis. Therefore, if we find that the rationality principle must be central to the analysis of decision making of human and nonhuman organisms, we must advance organomics. Organomics is bioeconomics understood as the use of rational choice to the study of the behavior of human and nonhuman organisms. Organomics offers a different starting point than the one offered by neo-Darwinism.     

A biological relativity view of the relationships between genomes and phenotypes

This article explores the relativistic principle that there is no privileged scale of causality in biology to clarify the relationships between genomes and phenotypes. The idea that genetic causes are primary views the genome as a program. Initially, that view was vindicated by the discovery of mutations and knockouts that have large and specific effects on the phenotype. But we now know that these form the minority of cases. Many changes at the genome level are buffered by robust networks of interactions in cells, tissues and organs. The ‘differential’ view of genetics therefore fails because it is too restrictive. An ‘integral’ view, using reverse engineering from systems biological models to quantify contributions to function, can solve this problem. The article concludes by showing that far from breaking the supervenience principle, downward causation requires that it should be obeyed.     

Does K-selection imply prudent predation?

Competition models are derived from predator-prey models. The population parameters r and K are thus expressed as composites of quantities measuring properties of the individual. This enables us to show that the idea that K-selection maximizes K is not valid as a general principle and is equivalent to asserting that selection on predators leads to prudent predation. Models of density-dependent selection, which predict maximization of K, implicitly assume no evolution of hunting efficiency. A valid general principle instead states that K-selection minimizes the equilibrium density of prey or food resource. It is then shown that the phenotypic profiles of r- and K-selected organisms are often identical. They diverge only if there are genetic constraints of a particular kind between the various evolving traits. Furthermore, divergence is in opposite direction to that which is commonly expected.     

Sexual selection in hermaphrodites: where did our ideas come from?

Interpretations of hermaphroditism have been influenced by theold idea that organisms can be arranged in a series from lowerto higher, with human beings at the top, leading toward theangels and God (the scala naturae). The consequent notion thathermaphroditism is a primitive condition is still with us. Suchissues need to be addressed empirically, in a phylogenetic context.Darwin's theory of sexual selection provided the key to understandingsex switches, but it was not invoked until 1969 when it wasconjoined with ideas about relative size influenced by the workof Bernhard Rensch. In principle the problem could have beensolved a century earlier, and genetics was misleading ratherthan helpful. What really helped was an appreciation of Darwin'snonteleological way of thinking.     

Naturalising purpose: from comparative anatomy to the 'adventure of reason'

Kant's analysis of the concept of natural purpose in the Critique of judgment captured several features of organisms that he argued warranted making them the objects of a special field of study, in need of a special regulative teleological principle. By showing that organisms have to be conceived as self-organizing wholes, epigenetically built according to the idea of a whole that we must presuppose, Kant accounted for three features of organisms conflated in the biological sciences of the period: adaptation, functionality and conservation of forms. Kant's unitary concept of natural purpose was subsequently split in two directions: first by Cuvier's comparative anatomy, that would draw on the idea of adaptative functions as a regulative principle for understanding in reconstituting and classifying organisms; and then by Goethe's and Geoffroy's morphology, a science of the general transformations of living forms. However, such general transformations in nature, objects of an alleged 'archaeology of nature', were thought impossible by Kant in section paragraph 80 of the Critique of judgment. Goethe made this 'adventure of reason' possible by changing the sense of 'explanation': scientific explanation was shifted from the investigation of the mechanical processes of generation of individual organisms to the unveiling of some ideal transformations of types instantiated by those organisms.     

Haldane’s view of natural selection

Among many things, J. B. S. Haldane is known for demonstrating how the principle of natural selection can be used to build a mathematical, and in particular quantitative, theory of evolution. However, to the end, he remained open to the idea of other evolutionary mechanisms. In his late writings, he repeatedly drew attention to situations in which natural selection did not operate, was hemmed in by constraints, or worked in a surprising manner. In this respect Haldane stands out among the architects of the Modern Synthesis.     

Clone selection and the mutation rate

A statistical model for mutation and selection is formulated for organisms that reproduce by division. The mutation rate that optimizes the probability of clone survival is approximated using the theory of branching processes. However, it is shown by example that this optimizing mutation rate need not be the most advantageous mutation rate. The principle that selection favors those modifying features that optimize the probability of clone survival is thereby shown to be of limited applicability.     

Inference of Structure Ensembles of Flexible Biomolecules from Sparse,Averaged Data

We present the theoretical foundations of a general principle to infer structure ensembles of flexible biomolecules from spatially and temporally averaged data obtained in biophysical experiments. The central idea is to compute the Kullback-Leibler optimal modification of a given prior distribution with respect to the experimental data and its uncertainty. This principle generalizes the successful inferential structure determination method and recently proposed maximum entropy methods. Tractability of the protocol is demonstrated through the analysis of simulated nuclear magnetic resonance spectroscopy data of a small peptide.     

Kinematics of metachronous walking. III. Invariants]

The concept of a kinematic space for a locomotor system is introduced and regime of locomotion is defined as a continued one-dimensional manifold of this space. The problem of describing of locomotion is set (settled) by kinematic invariants. It is shown that metachrony of such millipedes as Scolopendra and Julus can be considered as a special case of some "relativity principle", on the basis of which the expression of metachrony invariant has come out. The attempt is made to use this principle for the determination of step's invariants of each individual leg too.