Chemical machines, Maxwell's demon and living organisms

The problem considered in this paper is whether conventional chemical machines can be used in living organisms. I first point out that, due to their molecular nature, living systems pose unique thermodynamic problems, particularly in relation to Maxwell's demon. I then show that these problems may be solved by introducing time into the fundamental statement of the second law so that it becomes valid at the molecular level. This proposal, while clarifying certain logical anomalies in classical thermodynamics, makes no difference to that science in practice. However, I deduce from this statement that there are only two general ways of obtaining useful work from a chemical reaction: the first, a “constrained equilibrium” mechanism, is that employed by conventional chemical engines, but the second, a “molecular energy” mechanism, which depends upon the rapidity of resonant energy-transfer, may not have been suggested before. I then argue that because the former mechanism is essentially macroscopic in character it cannot, in fact, be used in those biological processes, like muscular contraction or active transport, in which useful molecular work is done and that only the latter may be so used. I also suggest reasons why this conclusion has been overlooked. Muscular contraction is used to illustrate these arguments and it is shown that all models of this process so far proposed fall into the first category. Although it is possible to eliminate such models a priori, several examples are finally criticized in detail to clarify the points raised. It is shown that in fact each of these models would have to be a Maxwell's demon machine.     

Simplification,Innateness, and the Absorption of Meaning from Context: How Novelty Arises from Gradual Network Evolution

How does new genetic information arise? Traditional thinking holds that mutation happens by accident and then spreads in the population by either natural selection or random genetic drift. There have been at least two fundamental conceptual problems with imagining an alternative. First, it seemed that the only alternative is a mutation that responds “smartly” to the immediate environment; but in complex multicellulars, it is hard to imagine how this could be implemented. Second, if there were mechanisms of mutation that “knew” what genetic changes would be favored in a given environment, this would have only begged the question of how they acquired that particular knowledge to begin with. This paper offers an alternative that avoids these problems. It holds that mutational mechanisms act on information that is in the genome, based on considerations of simplicity, parsimony, elegance, etc. (which are different than fitness considerations). This simplification process, under the performance pressure exerted by selection, not only leads to the improvement of adaptations but also creates elements that have the capacity to serve in new contexts they were not originally selected for. Novelty, then, arises at the system level from emergent interactions between such elements. Thus, mechanistically driven mutation neither requires Lamarckian transmission nor closes the door on novelty, because the changes it implements interact with one another globally in surprising and beneficial ways. Finally, I argue, for example, that genes used together are fused together; that simplification leads to complexity; and that evolution and learning are conceptually linked.     

Xenotransplantation: a problematic world behind a glamorous facade

The discussion about the ethics of xenotransplantation seems to focus upon the benefits for individual patients and the potential risks for human society, in general, to contract a newly emerging retrovirus. In these risk-benefit considerations, the moral concern for the research animals involved appears to be absent. This is remarkable, because the presumed successful xenograft is not expected very soon. A lot of basic problems in pig and primate xenotransplantations still need solving. These new experiments in our own biomedical laboratories raise questions regarding animal welfare and ethical justification in the light of possible alternative strategies. In this article, I discuss some of the moral issues related to preclinical, fundamental xenotransplantation research.     

Xenotransplantation: A Problematic World Behind a Glamorous Facade

The discussion about the ethics of xenotransplantation seems to focus upon the benefits for individual patients and the potential risks for human society, in general, to contract a newly emerging retrovirus. In these risk-benefit considerations, the moral concern for the research animals involved appears to be absent. This is remarkable, because the presumed successful xenograft is not expected very soon. A lot of basic problems in pig and primate xenotransplantations still need solving. These new experiments in our own biomedical laboratories raise questions regarding animal welfare and ethical justification in the light of possible alternative strategies. In this article, I discuss some of the moral issues related to preclinical, fundamental xenotransplantation research.     

A simple method for calculating the statistical power for detecting a QTL located in a marker interval

We developed a simple method for calculating the statistical power for detecting a QTL located in an interval flanked by two markers. The statistical method for QTL detection is assumed to be the Haley and Knott's simple regression method of interval mapping. This method allows us to answer one of the fundamental questions in designing a QTL mapping experiment: What is the minimum marker density required to detect a QTL explaining a certain heritable proportion of the phenotypic variance (denoted by h(2)) with a power gamma under a Type I error alpha in an F(2) or other mating designs with a sample size n? Computing the statistical power only requires the ability to evaluate a non-central F-distribution function and the inverse function of this distribution.     

Statistical inferences in phylogeography

In conventional phylogeographic studies, historical demographic processes are elucidated from the geographical distribution of individuals represented on an inferred gene tree. However, the interpretation of gene trees in this context can be difficult as the same demographic/geographical process can randomly lead to multiple different genealogies. Likewise, the same gene trees can arise under different demographic models. This problem has led to the emergence of many statistical methods for making phylogeographic inferences. A popular phylogeographic approach based on nested clade analysis is challenged by the fact that a certain amount of the interpretation of the data is left to the subjective choices of the user, and it has been argued that the method performs poorly in simulation studies. More rigorous statistical methods based on coalescence theory have been developed. However, these methods may also be challenged by computational problems or poor model choice. In this review, we will describe the development of statistical methods in phylogeographic analysis, and discuss some of the challenges facing these methods.     

A unifying framework for chaos and stochastic stability in discrete population models

 In this paper we propose a general framework for discrete time one-dimensional Markov population models which is based on two fundamental premises in population dynamics. We show that this framework incorporates both earlier population models, like the Ricker and Hassell models, and experimental observations concerning the structure of density dependence. The two fundamental premises of population dynamics are sufficient to guarantee that the model will exhibit chaotic behaviour for high values of the natural growth and the density-dependent feedback, and this observation is independent of the particular structure of the model. We also study these models when the environment of the population varies stochastically and address the question under what conditions we can find an invariant probability distribution for the population under consideration. The sufficient conditions for this stochastic stability that we derive are of some interest, since studying certain statistical characteristics of these stochastic population processes may only be possible if the process converges to such an invariant distribution. Received 15 May 1995; received in revised form 17 April 1996     

Matsigenka myth and morality: Notions of the social and the asocial

This paper explores Matsigenka notions of morality as evidenced in central mythological texts. The focus is on myth since, it is argued, myths provide a means whereby fundamental conditions of everyday life as conceptualized by their conventional audience can be understood and interpreted. Although myth does not provide a uniformly accepted cultural blueprint of social reality, a certain intersubjective consonance is to be expected. It is argued that to the Matsigenka morality is primarily a means to maintain conditions of conviviality. Matsigenka moral considerations are thus context‐dependent and can only be reflected upon casuistically.     

Cryonics for all?

In fascinating recent work, some philosophers have argued that it would be morally permissible and prudentially rational to sign up for cryonics—if you can afford the price tag of the procedure. In this paper I ask: why not share the elixir of extended life with everyone? Should governments financially support, positively encourage, or even require people to undergo cryonics? From a general principle of beneficence, I construct a formal argument for cryonics promotion policies. I consider the objection that a subset of these policies would violate autonomy, but I argue that—to the contrary—considerations of autonomy weigh in their favour. I then consider objections based on cost and population, but argue that neither is fatal. Finally, I raise the objection that I believe poses the most serious challenge: that those who revive the cryonically preserved might inflict suffering upon them.     

ECOLOGICAL ASPECTS OF ADAPTIVE RADIATION IN BIRDS

1. Relatively few birds feed heavily upon green-plant materials, though a number may take substantial numbers of buds. Birds appear not to possess adequate gut biota to break down cellulose efficiently, and even it they did, this system would not be compatible with efficient flight, on account of the long processing times required. 2. Birds have stronger adaptations toward feeding upon seeds and make a particularly heavy impact upon seeds in trees and on those in widely scattered or unpredictable crops. 3. Several families, mostly of tropical distribution, feed primarily upon fruit. Again, they are most successful in exploiting resources reached only with difficulty by other groups. A similar pattern holds for nectar stores. In the case of fruit and nectar, evolutionary complications result because the plants compete for seed dispersers and pollinators. 4. Most primarily herbivorous species feed their young partially or totally upon insects or other animal foods. Only a few species are able to fledge upon an entirely herbivorous diet, and those that do so often have extremely long fledging periods, which subject their young to high rates of predation unless the parents nest in places inaccessible to predators. 5. In general, herbivorous birds make a heavy impact relative to other animals only when they exploit resources that the other groups have difficulty in obtaining (hard to reach, or widely scattered in space and/or time). 6. Insects are exploited by more families of birds than any other food category. Birds are of greatest relative importance in capturing insects on the wing and in arboreal locations. Other terrestrial invertebrates are probably taken by techniques similar to those used for insects. 7. A variety of species take invertebrate prey along the water's edge or in shallow water. 8. Almost without exception, vertebrate prey is of small size, in part a function of the size of birds. Occasionally predation upon small terrestrial vertebrates may be relatively heavy, generally in outbreak situations. 9. Several families feed exclusively upon fish, crustacea, squid, and other aquatic prey. Some indirect evidence suggests that exploitation of these resources may sometimes be heavy, though there is little evidence that these groups often make an appreciable impact upon this food source. 10. Birds appear to be among the most important scavengers of animal remains. 11. Like the herbivorous birds, carnivorous birds appear to exert their greatest impact upon resources that are hard to reach or are widely scattered in space and/or time. 12. One-third of the avian families feed regularly on a variety of resources, as recognized in Table I. Most of these families specialize upon resources located in certain areas (ground, water's edge, trees, etc.). Only 13% of these families regularly use such a wide range of foods that they transcend both of these considerations (food type, segment of the habitat). In very few cases (5 %) does this designation result from some species of a family specializing upon one category of food and others using a different category. 13. There have been few large (> 20 kg), primarily herbivorous birds, though there have been several large omnivorous species. Large carnivorous species have been even rarer. All of these large species have been flightless, and in most cases they have occurred when or where large mammals were scarce or absent. 14. Birds have made extremely limited use of subterranean areas, caves, or deep water, and adaptations facilitating other types of life appear to be virtually incompatible with success in these situations. All these areas are characterized by a rapidly decreasing food gradient. 15. Bats exploit certain, but not all, of the food resources regularly exploited by birds. The resources not used by bats that are exploited by birds are those that are available over a full 24 h period; thus, bats' nocturnal habits do not provide them with an advantage in exploiting them. 16. Insects also use some of the resources exploited by birds. With few exceptions, insects are smaller than birds or bats. Considerable indirect evidence is consistent with the argument that the segregation in time, resource type, and size of flying animals is at least in part caused by competition. 17. While selection for anti-predatory mechanisms can be surmised, the reciprocal density relationships frequently noticed between birds and other organisms suggest that they arise from competition, rather than predation. 18. Most information suggests that interactions between birds and other animals of the same trophic level are usually, though not invariably, over food. 19. The types of relationship existing between birds and other organisms described above are repeated in a variety of other animal groups, though they clearly are not ubiquitous in the animal kingdom.     

INFOLDED BASAL PLASMA MEMBRANES FOUND IN EPITHELIA NOTED FOR THEIR WATER TRANSPORT

Epithelia noted for their water transport have been studied by electron microscopy with particular emphasis upon basal specializations. Epithelia of the submaxillary gland, choroid plexus, and ciliary body are described in this article, and compared with previous observations on the kidney. The basal surface of all these epithelia is tremendously expanded by folds which penetrate deeply into the cytoplasm. In the submaxillary gland this is particularly notable in cells of the serous alveoli and in the secretory ducts. In these instances the folds have a fairly regular distribution and have a marked tendency to turn back upon themselves and so form repeating S-shaped patterns. In the choroid plexus the penetrating basal folds are limited to the lateral regions of each ependymal cell where they blend with the intercellular membranes that are also folded. In the epithelium of the ciliary body it is the inner layer that is specialized. The surface adjacent to the cavity of the eye penetrates irregularly, nearly through the full depth of the cell layer. The exposed surface is, in a fundamental sense, the basal surface of this epithelial layer. It is apparent that the pattern of folding is quite distinctive in the different epithelia. Therefore, the specializations should be regarded as analogous rather than homologous. Topographic considerations presumably limit the manner in which basal cell surfaces might be expanded. Penetrating folds would seem to represent almost the only possible solution.     

Experimental design and analysis to investigate predator preferences for prey

Experimental design and statistical analysis of data for predator preferences towards different types of prey have been problematic for several reasons. In addition to fundamental issues concerning the definition of preference, traditional statistical issues such as the appropriateness of statistical distributions such as the Binomial distribution, pseudo-replication, and the appropriate conditioning of probabilities have hindered progress on this important topic in ecology. This paper discusses these issues in the context of the methodology proposed by Underwood and Clarke [Underwood, A.J., Clarke, K.R., 2005. Solving some statistical problems in analyses of experiments on choices of food and on associations with habitat. J. Exp. Mar. Biol. Ecol. 318, 227-237.] in order to provide further clarity concerning the assumptions of this approach and therefore its applicability. In light of the difficulty justifying the validity of these assumptions in practice, an alternative approach is presented which has simpler statistical assumptions.     

Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen.

Type I collagen is the most abundant protein in humans, and it helps to maintain the integrity of many tissues via its interactions with cell surfaces, other extracellular matrix molecules, and growth and differentiation factors. Nearly 50 molecules have been found to interact with type I collagen, and for about half of them, binding sites on this collagen have been elucidated. In addition, over 300 mutations in type I collagen associated with human connective tissue disorders have been described. However, the spatial relationships between the known ligand-binding sites and mutation positions have not been examined. To this end, here we have created a map of type I collagen that includes all of its ligand-binding sites and mutations. The map reveals the existence of several hot spots for ligand interactions on type I collagen and that most of the binding sites locate to its C-terminal half. Moreover, on the collagen fibril some potentially relevant relationships between binding sites were observed including the following: fibronectin- and certain integrin-binding regions are near neighbors, which may mechanistically relate to fibronectin-dependent cell-collagen attachment; proteoglycan binding may potentially impact upon collagen fibrillogenesis, cell-collagen attachment, and collagen glycation seen in diabetes and aging; and mutations associated with osteogenesis imperfecta and other disorders show apparently nonrandom distribution patterns within both the monomer and fibril, implying that mutation positions correlate with disease phenotype. These and other observations presented here may provide novel insights into evaluating type I collagen functions and the relationships between its binding partners and mutations.     

The quest for a null model for macroecological patterns: geometry of species distributions at multiple spatial scales

There have been several attempts to build a unified framework for macroecological patterns. However, these have mostly been based either on questionable assumptions or have had to be parameterized to obtain realistic predictions. Here, we propose a new model explicitly considering patterns of aggregated species distributions on multiple spatial scales, the property which lies behind all spatial macroecological patterns, using the idea we term 'generalized fractals'. Species' spatial distributions were modelled by a random hierarchical process in which the original 'habitat' patches were randomly replaced by sets of smaller patches nested within them, and the statistical properties of modelled species assemblages were compared with macroecological patterns in observed bird data. Without parameterization based on observed patterns, this simple model predicts realistic patterns of species abundance, distribution and diversity, including fractal-like spatial distributions, the frequency distribution of species occupancies/abundances and the species–area relationship. Although observed macroecological patterns may differ in some quantitative properties, our concept of random hierarchical aggregation can be considered as an appropriate null model of fundamental macroecological patterns which can potentially be modified to accommodate ecologically important variables.     

Plant movements caused by differential growth--unity or diversity of mechanisms?

A very wide range of plant organ movements have been described and yet it is not clear how each of them is related to the others. This uncertainty has had two undesirable consequences. Firstly, some workers have accepted the idea of a vague unity in the area and have subsequently been misled by information obtained in one system and applied without adequate justification to a study of a quite different system. Secondly, some researchers have evoked a possible diversity to explain why a particular mechanistic explanation may continue to be valid even when the model fails to explain events of a very similar nature in a slightly different system. We argue that this confusion has resulted from a classification of organ movements which has been based on functional rather than on mechanistic considerations. Mechanistic unity is to be expected on evolutionary grounds. This unity, however, may apply only to certain elements of the stimulus-response chain, at certain levels of organization. It follows from this that in seeking this unity, comparisons should be made between equivalent elements of the stimulus-response chain at the same level of organization in different systems. Only when this is done will theories built around the concept of unity provoke meaningful discussion.     

Mapping mutations on phylogenies

Mapping of mutations on a phylogeny has been a commonly used analytical tool in phylogenetics and molecular evolution. However, the common approaches for mapping mutations based on parsimony have lacked a solid statistical foundation. Here, I present a Bayesian method for mapping mutations on a phylogeny. I illustrate some of the common problems associated with using parsimony and suggest instead that inferences in molecular evolution can be made on the basis of the posterior distribution of the mappings of mutations. A method for simulating a mapping from the posterior distribution of mappings is also presented, and the utility of the method is illustrated on two previously published data sets. Applications include a method for testing for variation in the substitution rate along the sequence and a method for testing whether the d(N)/d(S) ratio varies among lineages in the phylogeny.     

Research in Medical Education: Some Methodological Considerations

The complexities of describing human characteristics with sufficient accuracy to enable successful selection of candidates for medical school demand precise and penetrating analysis. An important tool is statistical analysis; however, current methods have not been sufficient. Methods of multivariate analysis which have been extended only recently to problems in the social sciences have great diversity and power. These methods have been outlined and their application in medical education indicated. The appropriateness of a particular method depends upon four factors: the subjects under study, nature of the data, conditions under which data were obtained, and the purpose of the analysis. A critical consideration of these factors should enable the choice of a method capable of providing meaningful conclusions concerning medical school selection to be made.     

Grinnellian and Eltonian niches and geographic distributions of species

In the recent past, availability of large data sets of species presences has increased by orders of magnitude. This, together with developments in geographical information systems and statistical methods, has enabled scientists to calculate, for thousands of species, the environmental conditions of their distributional areas. The profiles thus obtained are obviously related to niche concepts in the Grinnell tradition, and separated from those in Elton's tradition. I argue that it is useful to define Grinnellian and Eltonian niches on the basis of the types of variables used to calculate them, the natural spatial scale at which they can be measured, and the dispersal of the individuals over the environment. I use set theory notation and analogies derived from population ecology theory to obtain formal definitions of areas of distribution and several types of niches. This brings clarity to several practical and fundamental questions in macroecology and biogeography.     

PHYLOGENETIC ANALYSES OF THE CORRELATED EVOLUTION OF CONTINUOUS CHARACTERS: A SIMULATION STUDY

We use computer simulation to compare the statistical properties of several methods that have been proposed for estimating the evolutionary correlation between two continuous traits, and define alternative evolutionary correlations that may be of interest. We focus on Felsenstein's (1985) method and some variations of it and on several “minimum evolution” methods (of which the procedure of Huey and Bennett [1987] is a special case), as compared with a nonphylogenetic correlation. The last, a simple correlation of trait values across the tips of a phylogeny, virtually always yields inflated Type I error rates, relatively low power, and relatively poor estimates of evolutionary correlations. We therefore cannot recommend its use. In contrast, Felsenstein's (1985) method yields acceptable significance tests, high power, and good estimates of what we term the input correlation and the standardized realized evolutionary correlation, given complete phylogenetic information and knowledge of the rate and mode of character change (e.g., gradual and proportional to time [“Brownian motion”] or punctuational, with change only at speciation events). Inaccurate branch length information may affect any method adversely, but only rarely does it cause Felsenstein's (1985) method to perform worse than do the others tested. Other proposed methods generally yield inflated Type I error rates and have lower power. However, certain minimum evolution methods (although not the specific procedure used by Huey and Bennett [1987]) often provide more accurate estimates of what we term the unstandardized realized evolutionary correlation, and their use is recommended when estimation of this correlation is desired. We also demonstrate how correct Type I error rates can be obtained for any method by reference to an empirical null distribution derived from computer simulations, and provide practical suggestions on choosing an analytical method, based both on the evolutionary correlation of interest and on the availability of branch lengths and knowledge of the model of evolutionary change appropriate for the characters being analyzed. Computer programs that implement the various methods and that will simulate (correlated) character evolution along a known phylogeny are available from the authors on request. These programs can be used to test the effectiveness of any new methods that might be proposed, and to check the generality of our conclusions with regard to other phylogenies.     

The distribution of fitness effects among beneficial mutations in Fisher's geometric model of adaptation

Recent models of adaptation at the DNA sequence level assume that the fitness effects of new mutations show certain statistical properties. In particular, these models assume that the distribution of fitness effects among new mutations is in the domain of attraction of the so-called Gumbel-type extreme value distribution. This assumption has not, however, been justified on any biological or theoretical grounds. In this note, I study random mutation in one of the simplest models of mutation and adaptation-Fisher's geometric model. I show that random mutation in this model yields a distribution of mutational effects that belongs to the Gumbel type. I also show that the distribution of fitness effects among rare beneficial mutations in Fisher's model is asymptotically exponential. I confirm these analytic findings with exact computer simulations. These results provide some support for the use of Gumbel-type extreme value theory in studies of adaptation and point to a surprising connection between recent phenotypic- and sequence-based models of adaptation: in both, the distribution of fitness effects among rare beneficial mutations is approximately exponential.