On a logical paradox implicit in the notion of a self-reproducing automation

The notion of automaton as used by J. von Neumann is formalized according to methods previously described (Rosen, 1958,Bull. Math. Biophysics 20, 245–60; 317–41). It is observed that a logical paradox arises when one attempts to describe the notion of self-reproducing automaton in this formalism. This paradox is discussed, together with some of the recent attempts to construct automata which exhibit self-reproduction. The relation of these results to biological problems is then investigated.     

Are all genes regulatory genes?

Although much has been learned about hereditary mechanisms since Gregor Mendel’s famous experiments, gene concepts have always remained vague, notwithstanding their central role in biology. During over hundred years of genetic research, gene concepts have often and dynamically changed to accommodate novel experimental findings, without ever providing a generally accepted definition of the ‘gene.’ Yet, the distinction between ‘regulatory genes’ and ‘structural genes’ has remained a common theme in modern gene concepts since the definition of the operon-model. This distinction is now challenged by recent findings which suggest that, at least in eukaryotes, structural genes may in many situations have a regulatory function that is independent of the function of the gene product (protein or non-coding RNA molecule). This brief paper discusses these new findings and some possible implications for the notion of the ‘regulatory gene.’     

Self-reproduction and serial message transfer: Two related problems

For a certain class of physical machines, termed “structure-determined,” the problem of self-reproduction can be reduced to the problem of serial message reproduction. Serial message reproduction however presupposes a sort of “open system” constraint. This leads to the principle of pseudo, or exogenously standardized, respectively, self-reproduction. It seems to be consistent with both chemical and biological self-reproduction. It thus may reflect a general principle of biological design. The proposed principle is a physico chemical analog to Robert Rosen's abstract relational self-reproduction constraint.     

Suggestion for a possible approach to molecular biology

A hypothetical “self-reproducing living molecule” has been recently frequently discussed in the literature. A physical theory of such a molecule is tentatively outlined. The relational, rather than the quantitative, aspects of the process are emphasized. The process of synthesis of such a molecule from its components is considered as a transition of a complex system between two quantum-mechanical states. The requirement that a “living molecule” should be able to multiply only by self-reproduction but not by a formationde novo leads to the conclusion that the above mentioned transition is a forbidden one. A constellation of conditions under which the forbiddenness is lifted by the presence of an already existing “living molecule” is suggested. The outlined mechanism leads to the conclusion that the property of self-reproduction does not so much reside in the self-reproducing molecule itself as in its relations to other molecules of a system.     

Modularity and the units of evolution

Summary While many developmental processes (e. g., gene networks or signaling pathways) are astonishingly conserved during evolution, they may be employed differently in different metazoan taxa or may be used multiply in different contexts of development. This suggests that these processes belong to building blocks or modules, viz., highly integrated parts of the organism, which develop and/or function relatively independent from other parts. Such modules may be relatively easy to dissociate from other modules and, therefore, could also serve as units of evolution. However, in order to further explore the implications of modularity for evolution, the vague notion of “modularity” as well as its relation to concepts like “unit of evolution” need to be more precisely specified. Here, a module is characterized as a certain type of dynamic pattern of couplings among the constituents of a process. It may or may not form a spatially contiguous unit. A unit of selection is defined as a unit of those constituents of a reproducing process/system, which exists in different variants and acts as a non-decomposable unit of fitness and variant reproduction during a particular selection process. The more general notion of a unit of evolution is characterized as a nondecomposable unit of constituents with reciprocal fitness dependence, be it due to fitness epistasis or due to the lack of independent variability. Because such fitness dependence may only be observed for some combinations of variants, several constituents may act as a unit of evolution only with a certain probability (coevolution probability). It is argued, that under certain conditions modules are likely to act as units of evolution with high coevolution probabilities, because there is likely to be a close tie between the pattern of couplings of the constituents of a reproducing system and their interdependent fitness contributions. Moreover and contrary to the traditional dichotomy of genes versus organisms as units of selection, modules tend to be more important in delimiting actual units of selection than either organisms or genes, because they are less easily disrupted by recombination than organisms, while having less contextsensitive fitness values than genes. Finally, it is suggested that the evolution of modularity is self-reinforcing, because the flexibility of intermodular connections facilitates the recombination among modules and their multiple employment in new contexts.     

Ecosystem and Ecotomo: A Nature or Society-Nature Relationship?

The notion of entorno is discussed and its mutual dependence upon the organism is emphasised. Both the etymology and meaning of ethos, oikos, entorno and ecotomo are discussed. The intimate relation between Ethology and Ecology is also shown. A reference background is given to explain how the commonly considered isolated components organism/society and entorno/nature articulate in the form of a relation. It is argued that the integrated concepts that originated the notion of ecosystem have been set aside. The term ecotomo is proposed, which refers to any territorial unit that, considered at a local, regional or global level, emerges from the society-nature relationship.     

Replication in abstract and natural systems

Real reproducing systems are contrasted with cellular automata-based models of self-reproduction. It is argued that the reproduction described by the latter is trivial compared to its biological counterpart. The paper explores a few reasons and consequences of this situation, along with a discussion on different forms of the basic reproduction (and construction) process.     

Theory of biological similarities,nondimensional parameters and invariant numbers

In previous papers (1955–1957) a theory of biological similarity was established, assuming that the limits are the mechanical and the electrodynamical similarity criteria. The range of this theory lies between the coefficient of the time exponent (γ) for mechanical (0.5γ) and electrodynamical (1.0γ) similarities, being the mode 0.93γ. Moreover, for certain functions this restricted theoretical range should be extended to the hydrodynamical similarity criterion (2γ), so that the dimensionless numbers commonly used in Physics (Reynolds, Froude, Weber, etc.) can be included within the total range (0.5–2γ) of biological similarities. From dimensional analysis of physiological, functions it was possible to obtain, by means of dimensional and solution matrices, a group of “nondimensional numbers” by applying Buckingham's Pi-theorem. Nevertheless, only if a single similarity criterion was applied, the residual weight exponent was exactly zero; in all other instances the weight exponent was not zero, due to the existence of a range for biological similarities and to the statistical meaning of exponent (b) of the allometric equations. From the similarity criteria “invariant numbers” can be obtained, by means of which it is possible to establish correlations between numerous morphological and physiological characteristics of a particular system (circulation, respiration, metabolism, etc.).     

“Force-Talk” in Evolutionary Explanation: Metaphors and Misconceptions

The notion of “pressure” as an evolutionary “force” that “causes” evolution is a pervasive linguistic feature of biology textbooks, journal articles, and student explanatory discourse. We investigated the consequences of using a textbook and curriculum that incorporate so-called force-talk. We examined the frequency with which biology majors spontaneously used notions of evolutionary “pressures” in their explanations, students’ definitions and explanations of what they meant when they used pressures, and the structure of explanatory models that incorporated evolutionary pressures and forces. We found that 12–20 percent of undergraduates spontaneously used “pressures” and/or “forces” as explanatory factors but significantly more often in trait gain scenarios than in trait loss scenarios. The majority of explanations using “force-talk” were characterized by faulty evolutionary reasoning. We discuss the conceptual similarity between faulty notions of evolutionary pressures and linguists’ force-dynamic models of everyday reasoning and ultimately question the appropriateness of force-talk in evolution education.     

Systematics, similarity and Acanthaceae pollen morphology

SCOTLAND, R. W., 1992. Systematics, similarity and Acanthaceae pollen morphology. A brief discussion of the history of Acanthaceae classifications is provided. It is argued that several approaches utilizing pollen morphological data for the classification of the family can be identified. The Lindau pollen types are shown to have an indirect relationship to Lindau's own classification. Pollen morphological similarity is explored within the context of cladistic methodology. It is shown that some of the Lindau pollen types are analogous. It is demonstrated that shared similarities can be of three types: conflicting (homoplasious), plesiomorphic and apomorphic.     

A novel approach to local similarity of protein binding sites substantially improves computational drug design results

We present a novel notion of binding site local similarity based on the analysis of complete protein environments of ligand fragments. Comparison of a query protein binding site (target) against the 3D structure of another protein (analog) in complex with a ligand enables ligand fragments from the analog complex to be transferred to positions in the target site, so that the complete protein environments of the fragment and its image are similar. The revealed environments are similarity regions and the fragments transferred to the target site are considered as binding patterns. The set of such binding patterns derived from a database of analog complexes forms a cloud-like structure (fragment cloud), which is a powerful tool for computational drug design. It has been shown on independent test sets that the combined use of a traditional energy-based score together with the cloud-based score responsible for the quality of embedding of a ligand into the fragment cloud improves the self-docking and screening results dramatically. The usage of a fragment cloud as a source of positioned molecular fragments fitting the binding protein environment has been validated by reproduction of experimental ligand optimization results.     

Existence of a limiting pattern for a system of nonlinear equations describing interpopulation competition

A system of arbitrarily many nonlinear ordinary differential equations which can be interpreted as describing competition between populations is studied here. It is found that limits exist for the system given specified constraints on the “signal function” which describes input-output relations at the level of single populations. Existence of limits is shown by means of a function which records which variable in the system is growing fastest at a given time i.e. who is winning the competition. Generalizations are discussed to sigmoid signal functions which appear in models of pattern discrimination by neuron populations.     

Nucleotide sequence and analysis of conjugative plasmid pVT745

The complete nucleotide sequence and genetic map of pVT745 are presented. The 25-kb plasmid was isolated from Actinobacillus actinomycetemcomitans, a periodontal pathogen. Two-thirds of the plasmid encode functions related to conjugation, replication, and replicon stability. Among potential gene products with a high degree of similarity to known proteins are those associated with plasmid conjugation. It was shown that pVT745 derivatives not only mobilized a coresident nontransmissible plasmid, pMMB67, but also mediated their own conjugative transfer to different A. actinomycetemcomitans strains. However, transfer of pVT745 derivatives from A. actinomycetemcomitans to Escherichia coli JM109 by conjugation was successful only when an E. coli origin of replication was present on the pVT745 construct. Surprisingly, 16 open reading frames encode products of unknown function. The plasmid contains a conserved replication region which belongs to the HAP (Haemophilus-Actinobacillus-Pasteurella) theta replicon family. However, its host range appears to be rather narrow compared to other members of this family. Sequences homologous to pVT745 have previously been detected in the chromosomes of numerous A. actinomycetemcomitans strains. The nature and origin of these homologs are discussed based on information derived from the nucleotide sequence.     

Specificity in Computational Protein Design

A long-standing goal of computational protein design is to create proteins similar to those found in Nature. One motivation is to harness the exquisite functional capabilities of proteins for our own purposes. The extent of similarity between designed and natural proteins also reports on how faithfully our models represent the selective pressures that determine protein sequences. As the field of protein design shifts emphasis from reproducing native-like protein structure to function, it has become important that these models treat the notion of specificity in molecular interactions. Although specificity may, in some cases, be achieved by optimization of a desired protein in isolation, methods have been developed to address directly the desire for proteins that exhibit specific functions and interactions.     

Statistical distance between texts and filtration methods in sequence comparison

Upon searching local similarities in long sequences, the necessityof a ‘rapid’ similarity search becomes acute. Quadraticcomplexity of dynamic programming algorithms forces the employmentof filtration methods that allow elimination of the sequenceswith a low similarity level. The paper is devoted to the theoreticalsubstantiations of the filtration method based on the statisticaldistance between texts. The notion of the filtration efficiencyis introduced and the efficiency of several filters is estimated.It is shown that the efficiency of the statistical l-tuple filtrationupon DNA database search is associated with a potential extensionof the original four–letter alphabet and grows exponentiallywith increasing l. The formula that allows one to estimate thefiltration parameters is presented.     

Fragmentomics of natural peptide structures

Natural fragmentation of peptide and other chemical structures is well known. They are a significant object of biochemical investigations. In this connection, the bases and determination are given for the notion of the “fragmentome” as a set of all fragments of a single substance, as well as for global fragmentome of all chemical components of living organisms. It is described how protein-peptide fragments are formed in nature, what experimental and theoretical methods are used for their investigation, as well as mathematical characteristics of fragmentomes. Individual fragmentomes of all subunits and of complete casein fragmentome are considered in detail. Structural and functional variety of its possible fragments was revealed by computer analysis. Formation in an organism of an exogenous-endogenous pool of oligopeptides and correlation of these data with concepts of structure-functional continuum of regulatory molecules is shown on an example of food protein fragments. Possible practical importance of the use of natural fragments in dietology, therapy, as well as in sanitary hygiene and cosmetics is noted.     

The effect of birthplace on heat tolerance and mortality in Milan, Italy, 1980–1989

The temperature–mortality relationship follows a well-known J-V shaped pattern with mortality excesses recorded at cold and hot temperatures, and minimum at some optimal value, referred as Minimum Mortality Temperature (MMT). As the MMT, which is used to measure the population heat-tolerance, is higher for people living in warmer places, it has been argued that populations will adapt to temperature changes. We tested this notion by taking advantage of a huge migratory flow that occurred in Italy during the 1950s, when a large number of unemployed people moved from the southern to the industrializing north-western regions. We have analyzed mortality–temperature relationships in Milan residents, split by groups identified by area of birth. In order to obtain estimates of the temperature-related risks, log-linear models have been used to fit daily death count data as a function of different explanatory variables. Results suggest that mortality risks differ by birthplace, regardless of the place of residence, namely heat tolerance in adult life could be modulated by outdoor temperature experienced early in life. This indicates that no complete adaptation might occur with rising external environmental temperatures.     

Question 7: New Aspects of Interactions Among Vesicles

In this short article I discuss the relevance of two aspects of vesicle reactivity that are germane to understand the role of compartments in the origin of early cells. Studies of vesicle self-reproduction indicate that simple vesicles can grow and divide, maintaining inside most of their content and giving rise to a simple autopoietic system. New aspects of vesicle reactivity are also introduced, such as selection and competition processes within vesicle populations, emphasizing the concepts of vesicle diversity, inter-vesicles and vesicles–environment interactions, intended as synthetic analogs of primitive ‘ecological’ processes. Presented at: International School of Complexity – 4th Course: Basic Questions on the Origins of Life; “Ettore Majorana” Foundation and Centre for Scientific Culture, Erice, Italy, 1–6 October 2006.     

Intrinsic time scaling in survival analysis: Application to biological populations

A method of dimensionless time-scaling based on extrinsic expectation of life at birth but intrinsic to a system generating a survival distribution is introduced. Such scaling allows the survival fraction function and its associated mortality function to serve as Green's functions for their generalized equivalents. i.e. a “population” function and a “death” function. The analytical mechanics of utilizing these concepts are formulated, applied to the classical Gompertz and Weibull survival models, and discussed with respect to biological relevance.