Arguments against non-programmed aging theories

Until recently, non-programmed theories of biological aging were popular because of the widespread perception that the evolution process could not support the development and retention of programmed aging in mammals. However, newer evolutionary mechanics theories including group selection, kin selection, and evolvability theory support mammal programmed aging, and multiple programmed aging theories have been published based on the new mechanics. Some proponents of non-programmed aging still contend that their non-programmed theories are superior despite the new mechanics concepts. However, as summarized here, programmed theories provide a vastly better fit to empirical evidence and do not suffer from multiple implausible assumptions that are required by non-programmed theories. This issue is important because programmed theories suggest very different mechanisms for the aging process and therefore different mechanisms behind highly age-related diseases and conditions such as cancer, heart disease, and stroke.     

Statistical theories of functions and the problem of epidemic disease

Several decades ago, Christopher Boorse formulated an influential statistical theory of normative biological functions but it has often been claimed that his theory suffers from insuperable problems such as an inability to handle cases of epidemic and universal diseases. This paper develops a new statistical theory of normative functions that is capable of dealing with the notorious problem of epidemic and universal diseases. The theory is also more detailed than its predecessors and offers other important advantages over them. It is argued here that statistical theories of biological functions should not be so quickly dismissed.     

Order without design

Experimental reality in molecular and cell biology, as revealed by advanced research technologies and methods, is manifestly inconsistent with the design perspective on the cell, thus creating an apparent paradox: where do order and reproducibility in living systems come from if not from design?I suggest that the very idea of biological design (whether evolutionary or intelligent) is a misconception rooted in the time-honored and thus understandably precious error of interpreting living systems/organizations in terms of classical mechanics and equilibrium thermodynamics. This error, introduced by the founders and perpetuated due to institutionalization of science, is responsible for the majority of inconsistencies, contradictions, and absurdities plaguing modern sciences, including one of the most startling paradoxes - although almost everyone agrees that any living organization is an open nonequilibrium system of continuous energy/matter flow, almost everyone interprets and models living systems/organizations in terms of classical mechanics, equilibrium thermodynamics, and engineering, i.e., in terms and concepts that are fundamentally incompatible with the physics of life.The reinterpretation of biomolecules, cells, organisms, ecosystems, and societies in terms of open nonequilibrium organizations of energy/matter flow suggests that, in the domain of life, order and reproducibility do not come from design. Instead, they are natural and inevitable outcomes of self-organizing activities of evolutionary successful, and thus persistent, organizations co-evolving on multiple spatiotemporal scales as biomolecules, cells, organisms, ecosystems, and societies. The process of self-organization on all scales is driven by economic competition, obeys empirical laws of nonequilibrium thermodynamics, and is facilitated and, thus, accelerated by memories of living experience persisting in the form of evolutionary successful living organizations and their constituents.     

Ecosystem engineering effects on species diversity across ecosystems: a meta‐analysis

Ecosystem engineering is increasingly recognized as a relevant ecological driver of diversity and community composition. Although engineering impacts on the biota can vary from negative to positive, and from trivial to enormous, patterns and causes of variation in the magnitude of engineering effects across ecosystems and engineer types remain largely unknown. To elucidate the above patterns, we conducted a meta‐analysis of 122 studies which explored effects of animal ecosystem engineers on species richness of other organisms in the community. The analysis revealed that the overall effect of ecosystem engineers on diversity is positive and corresponds to a 25% increase in species richness, indicating that ecosystem engineering is a facilitative process globally. Engineering effects were stronger in the tropics than at higher latitudes, likely because new or modified habitats provided by engineers in the tropics may help minimize competition and predation pressures on resident species. Within aquatic environments, engineering impacts were stronger in marine ecosystems (rocky shores) than in streams. In terrestrial ecosystems, engineers displayed stronger positive effects in arid environments (e.g. deserts). Ecosystem engineers that create new habitats or microhabitats had stronger effects than those that modify habitats or cause bioturbation. Invertebrate engineers and those with lower engineering persistence (<1 year) affected species richness more than vertebrate engineers which persisted for >1 year. Invertebrate species richness was particularly responsive to engineering impacts. This study is the first attempt to build an integrative framework of engineering effects on species diversity; it highlights the importance of considering latitude, habitat, engineering functional group, taxon and persistence of their effects in future theoretical and empirical studies.     

A new hypothesis for molecular behavior

In order to understand the living cell, biologists need workable explanations of molecular phenomena. From data in the literature, it is possible to construct a mathematical hypothesis: molecular behavior in the continuum can be represented by a set of simple, logarithmic functions. These functions apply not only to biology, but also to chemistry and to physics.Although empirical in its origins, this hypothesis satisfies criteria which are often associated with good theories. It is comprehensive in its application, and it is mathematically simple. It is easily tested; and it is accurate, when tested. Because it can be correlated with classical atomic and molecular theory, the hypothesis can be used to make strong predictions. The proposal also appears to be consistent with quantum mechanics.     

Biology Needs Information Theory

Communication is an important feature of the living world that mainstream biology fails to adequately deal with. Applying two main disciplines can be contemplated to fill in this gap: semiotics and information theory. Semiotics is a philosophical discipline mainly concerned with meaning; applying it to life already originated in biosemiotics. Information theory is a mathematical discipline coming from engineering which has literal communication as purpose. Biosemiotics and information theory are thus concerned with distinct and complementary possible meanings of the word ‘communication’. Since literal communication needs to be secured so as to enable semantics being communicated, information theory is a necessary prerequisite to biosemiotics. Moreover, heredity is a purely literal communication process of capital importance fully relevant to literal communication, hence to information theory. A short introduction to discrete information theory is proposed, which is centred on the concept of redundancy and its use in order to make sequences resilient to errors. Information theory has been an extremely active and fruitful domain of researches and the motor of the tremendous progress of communication engineering in the last decades. Its possible connections with semantics and linguistics are briefly considered. Its applications to biology are suggested especially as regards error-correcting codes which are mandatory for securing the conservation of genomes. Biology needs information theory so biologists and communication engineers should closely collaborate.     

Computational Models to Synthesize Human Walking

The synthesis of human walking is of great interest in biomechanics and biomimetic engineering due to its predictive capabilities and potential applications in clinical biomechanics, rehabilitation engineering and biomimetic robotics. In this paper, the various methods that have been used to synthesize humanwalking are reviewed from an engineering viewpoint. This involves a wide spectrum of approaches, from simple passive walking theories to large-scale computational models integrating the nervous, muscular and skeletal systems. These methods are roughly categorized under four headings： models inspired by the concept of a CPG （Central Pattern Generator）, methods based on the principles of control engineering, predictive gait simulation using optimisation, and models inspired by passive walking theory. The shortcomings and advantages of these methods are examined, and future directions are discussed in the context of providing insights into the neural control objectives driving gait and improving the stability of the predicted gaits. Future advancements are likely to be motivated by improved understanding of neural control strategies and the subtle complexities of the musculoskeletal system during human locomotion. It is only a matter of time before predictive gait models become a practical and valuable tool in clinical diagnosis, rehabilitation engineering and robotics.     

Means, Advantages and Limits of Merging Biology with Technology

The natural world spent billions of years in solution-finding during evolution, which could benefit Technology. How do we put that in a nutshell? Biological systems are more complex than the most complex current technology. Any given functiofi and effect are simultaneously coordinated and linked with others at many levels of biological organisation-from cell organelle to organism, to population and ecosystem. Technology does not have tools to deal with the complexity and “goalintendedness“ of living systems. But limits for interaction exist on both sides-Biological science itself is also too empirical and not mature enough to provide a solid base for correlating living with technical systems. Moving towards a synthesis, where engineers can utilize the vast amount of available biological data, we suggest using a tool called “Theory of Inventive Problem Solving“ (TRIZ) and clarifying some important methodological issues, which have not previously been recognised in bionic engineering: 1) Requirement for more appropriate definitions of “system“, “effect“, “function“, “law“ and “rule“. 2) Requirement for understanding or even measuring the degree of contradiction or analogy between functions in biological and artificial and/or non-living engineering system-there is no simple direct correlation between what engineers find useful and what biology does.     

Effect of certain professions on the structure of the cervical portion of the spine]

The roentgen-anatomical study of the cervical portion of the vertebral column (fluorography and roentgenography in 2 projections followed by morphometrical treatment) was performed in 603 representatives of different professions: turners, milling-machine operators, craftsmen, mechanicians, jugglers, engineers and constructors. The following facts were established: asymmetry of bodies CIV and CV of vertebra in turners and milling-machine operators; differently pronounced cervical lordosis in persons of different professions; specific features in the architectonics of the spongy substance of the cervical vertebra bodies.     

Redesigning metabolic networks using mathematical programming

The design of new generation bioprocessing plants is increasingly dependent on the design of process-compatible microorganisms. The latter, whether through genetic or physiological manipulations, can be greatly assisted by metabolic engineering. An emerging powerful tool in metabolic engineering research is computer-assisted cell design using mathematical programming. In this work, the problem of optimizing cellular metabolic networks has been formulated as a Mixed Integer Nonlinear Programming (MINLP) model. The model can assist genetic engineers to identify which cellular enzymes should be modified, and the new levels of activity required to produce an optimal network. Results are presented from the tricarboxylic acid cycle in Dictyostelium discoideum. Copyright 1998 John Wiley & Sons, Inc.     

Human leg model predicts ankle muscle-tendon morphology, state, roles and energetics in walking

A common feature in biological neuromuscular systems is the redundancy in joint actuation. Understanding how these redundancies are resolved in typical joint movements has been a long-standing problem in biomechanics, neuroscience and prosthetics. Many empirical studies have uncovered neural, mechanical and energetic aspects of how humans resolve these degrees of freedom to actuate leg joints for common tasks like walking. However, a unifying theoretical framework that explains the many independent empirical observations and predicts individual muscle and tendon contributions to joint actuation is yet to be established. Here we develop a computational framework to address how the ankle joint actuation problem is resolved by the neuromuscular system in walking. Our framework is founded upon the proposal that a consideration of both neural control and leg muscle-tendon morphology is critical to obtain predictive, mechanistic insight into individual muscle and tendon contributions to joint actuation. We examine kinetic, kinematic and electromyographic data from healthy walking subjects to find that human leg muscle-tendon morphology and neural activations enable a metabolically optimal realization of biological ankle mechanics in walking. This optimal realization (a) corresponds to independent empirical observations of operation and performance of the soleus and gastrocnemius muscles, (b) gives rise to an efficient load-sharing amongst ankle muscle-tendon units and (c) causes soleus and gastrocnemius muscle fibers to take on distinct mechanical roles of force generation and power production at the end of stance phase in walking. The framework outlined here suggests that the dynamical interplay between leg structure and neural control may be key to the high walking economy of humans, and has implications as a means to obtain insight into empirically inaccessible features of individual muscle and tendons in biomechanical tasks.     

On tensegrity in cell mechanics

All models are wrong, but some are useful. This famous saying mirrors the situation in cell mechanics as well. It looks like no particular model of the cell deformability can be unconditionally preferred over others and different models reveal different aspects of the mechanical behavior of living cells. The purpose of the present work is to discuss the so-called tensegrity models of the cell cytoskeleton. It seems that the role of the cytoskeleton in the overall mechanical response of the cell was not appreciated until Donald Ingber put a strong emphasis on it. It was fortunate that Ingber linked the cytoskeletal structure to the fascinating art of tensegrity architecture. This link sparked interest and argument among biologists, physicists, mathematicians, and engineers. At some point the enthusiasm regarding tensegrity perhaps became overwhelming and as a reaction to that some skepticism built up. To demystify Ingber's ideas the present work aims at pinpointing the meaning of tensegrity and its role in our understanding of the importance of the cytoskeleton for the cell deformability and motility. It should be noted also that this paper emphasizes basic ideas rather than carefully follows the chronology of the development of tensegrity models. The latter can be found in the comprehensive review by Dimitrije Stamenovic (2006) to which the present work is complementary.     

Cell-substrate interaction with cell-membrane-stress dependent adhesion

Cell-substrate interaction is examined in a two-dimensional mechanics model. The cell and substrate are treated as a shell and an elastic solid, respectively. Their interaction through adhesion is treated using nonlinear springs. Compared to previous cell mechanics models, the present model introduces a cohesive force law that is dependent not only on cell-substrate distance but also on internal cell-membrane stress. It is postulated that a living cell would establish focal adhesion sites with density dependent on the cell-membrane stress. The formulated mechanics problem is numerically solved using coupled finite elements and boundary elements for the cell and the substrate, respectively. The nodes in the adhesion zone from either side are linked by the cohesive springs. The specific cases of a cell adhering to a homogeneous substrate and a heterogeneous bimaterial substrate are examined. The analyses show that the substrate stiffness affects the adhesion behavior significantly and regulates the direction of cell adhesion, in good agreement with the experimental results in the literature. By introducing a reactive parameter (i.e., cell-membrane stress) linking biological responses of a living cell to a mechanical environment, the present model offers a unified mechanistic vehicle for characterization and prediction of living cell responses to various kinds of mechanical stimuli including local extracellular matrix and neighboring cells.     

From computational quantum chemistry to computational biology: experiments and computations are (full) partners

Computations are being integrated into biological research at an increasingly fast pace. This has not only changed the way in which biological information is managed; it has also changed the way in which experiments are planned in order to obtain information from nature. Can experiments and computations be full partners? Computational chemistry has expanded over the years, proceeding from computations of a hydrogen molecule toward the challenging goal of systems biology, which attempts to handle the entire living cell. Applying theories from ab initio quantum mechanics to simplified models, the virtual worlds explored by computations provide replicas of real-world phenomena. At the same time, the virtual worlds can affect our perception of the real world. Computational biology targets a world of complex organization, for which a unified theory is unlikely to exist. A computational biology model, even if it has a clear physical or chemical basis, may not reduce to physics and chemistry. At the molecular level, computational biology and experimental biology have already been partners, mutually benefiting from each other. For the perception to become reality, computation and experiment should be united as full partners in biological research.     

Grand challenges for biological engineering

Biological engineering will play a significant role in solving many of the world's problems in medicine, agriculture, and the environment. Recently the U.S. National Academy of Engineering (NAE) released a document "Grand Challenges in Engineering," covering broad realms of human concern from sustainability, health, vulnerability and the joy of living. Biological engineers, having tools and techniques at the interface between living and non-living entities, will play a prominent role in forging a better future. The 2010 Institute of Biological Engineering (IBE) conference in Cambridge, MA, USA will address, in part, the roles of biological engineering in solving the challenges presented by the NAE. This letter presents a brief outline of how biological engineers are working to solve these large scale and integrated problems of our society.     

Mammal aging: Active and passive mechanisms and their medical implications

This article compares two hypotheses regarding the mechanisms responsible for aging in humans and other mammals. In the passive mechanism, aging is the result of inadequacies in maintenance and repair functions that act to prevent or repair damage from fundamental deteriorative processes. In the active mechanism, a life span management system purposely limits life span by deactivating maintenance and repair processes beyond a species-specific age.As described here, the active mechanism provides a much better fit to observational evidence while the passive mechanism provides a much better fit to traditional evolutionary mechanics theory. However, there are many other observations that conflict with traditional theory and consequently a number of alternative evolutionary mechanics theories have been developed since 1962. Several of these alternatives support active life span management and aging theories providing a rationale for active life span management have been developed based on each of those alternatives.This issue is very important to our ability to treat age-related diseases and conditions. If indeed the passive mechanism is correct, then efforts should continue to be exerted to find treatments for each different manifestation of aging, independently of the others. If the active concept is valid it is clear that there are, in addition, substantial opportunities for finding agents that generally delay aging and simultaneously ameliorate multiple manifestations of aging.In the past, the evolutionary issues have been used as essentially the entire justification for summarily rejecting active theories. Given the public health considerations and the increasing number of issues surrounding evolutionary mechanics theory, this is no longer a reasonable or responsible path.     

A bridge-builder: Wolf-Ernst Reif and the Darwinisation of German paleontology

Wolf-Ernst Reif was an outstanding German paleontologist, who, along with his empirical studies (biomechanics, functional and constructional morphology, etc.), paid significant attention to theoretical issues and the history of his discipline. Reif was a bridge-builder, skillfully synthesising history, theory and empirical studies within German-language paleontology. This paper briefly discusses sophisticated relationships between German paleontology and Darwinism based on the historical studies of Wolf-Ernst Reif. German paleontology did not fully embrace Darwinism until the 1970s. There are several reasons for this. First, alternative evolutionary theories (saltationism, neo-Lamarckism, orthogenesis) occupied a significant segment of the theoretical landscape in the German life sciences. Second, typological thinking persisted in German paleontology after the Second World War. Third, German paleontologists were relatively uninterested in discussing mechanisms of evolution, concentrating instead on reconstructing phylogenetic history.     

Bioinspiration: applying mechanical design to experimental biology

The production of bioinspired and biomimetic constructs has fostered much collaboration between biologists and engineers, although the extent of biological accuracy employed in the designs produced has not always been a priority. Even the exact definitions of "bioinspired" and "biomimetic" differ among biologists, engineers, and industrial designers, leading to confusion regarding the level of integration and replication of biological principles and physiology. By any name, biologically-inspired mechanical constructs have become an increasingly important research tool in experimental biology, offering the opportunity to focus research by creating model organisms that can be easily manipulated to fill a desired parameter space of structural and functional repertoires. Innovative researchers with both biological and engineering backgrounds have found ways to use bioinspired models to explore the biomechanics of organisms from all kingdoms to answer a variety of different questions. Bringing together these biologists and engineers will hopefully result in an open discourse of techniques and fruitful collaborations for experimental and industrial endeavors.