Defining vision: what homology thinking contributes

The specialization of visual function within biological function is reason for introducing “homology thinking” into explanations of the visual system. It is argued that such specialization arises when organisms evolve by differentiation from their predecessors. Thus, it is essentially historical, and visual function should be regarded as a lineage property. The colour vision of birds and mammals do not function the same way as one another, on this account, because each is an adaptation to special needs of the visual functions of predecessors—very different kinds of predecessors in each case. Thus, history underlies function. We also see how homology thinking figures in the hierarchical classification of visual systems, and how it supports the explanation of visual function by functional role analysis.

Prey specificity, comparative lethality and compositional differences of coral snake venoms

Toxicities of crude venoms from 49 coral snake (Micrurus sp.) populations, representing 15 nominal taxa, were examined in both laboratory mice and in native prey animals and compared with data gathered from two non-micrurine elapids and a crotalid, which served as outgroups. These venoms were further compared on the basis of 23 enzymatic activities. Both toxicities and enzymatic activities were analyzed with respect to natural prey preferences, as determined from stomach content analyses and literature reports. Venoms of nearly all Micrurus for which prey preferences are known, are more toxic to natural prey than to non-prey species. Except for amphisbaenians, prey are more susceptible to venoms of Micrurus that feed upon them, than to venoms of those that eat other organisms. All venoms were more toxic i.v.>i.p.>i.m. Route-specific differences in toxicity are generally greatest for preferred prey species. Cluster analyses of venom enzymatic activities resulted in five clusters, with the fish-eating M. surinamensis more distant from other Micrurus than even the crotalid, Bothrops moojeni. Ophiophagous and amphisbaenian-eating Micrurus formed two close subclusters, one allied to the outgroup species Naja naja and the other to the fossorial, ophiophagous Bungarus multicinctus. Prey preference is shown to be the most important determinant of venom composition in Micrurus.     

Improved scoring function for comparative modeling using the M4T method

Improvements in comparative protein structure modeling for the remote target-template sequence similarity cases are possible through the optimal combination of multiple template structures and by improving the quality of target-template alignment. Recently developed MMM and M4T methods were designed to address these problems. Here we describe new developments in both the alignment generation and the template selection parts of the modeling algorithms. We set up a new scoring function in MMM to deliver more accurate target-template alignments. This was achieved by developing and incorporating into the composite scoring function a novel statistical pairwise potential that combines local and non-local terms. The non-local term of the statistical potential utilizes a shuffled reference state definition that helped to eliminate most of the false positive signal from the background distribution of pairwise contacts. The accuracy of the scoring function was further increased by using BLOSUM mutation table scores.     

Proper names in twin worlds: Monophyly, paraphyly, and the world around us

This paper addresses the theoretical relevance of monophyletic, paraphyletic and polyphyletic groups under the paradigm of sophisticated scientific realism. The doctrine of metaphysical realism is introduced using the philosophy of Karl Popper as an example, which is then contrasted with scientific realism. A discussion of the nature of causal relations presents an account of counterfactual conditionals. The current state of art casts the theory of phylogenetic systematics in a stark contrast of classes (universals) and individuals (particulars). In practice, however, individuals piggyback on classes, or sets. Natural kinds are introduced in order to overcome this deep dichotomy. The theoretical relevance of natural kinds lies in their explanatory value, and that may change with changing context. It is for this reason that non-monophyletic groups can have explanatory value (their members can function as tokens of causally relevant kinds) within certain domains of evolutionary biology. Explanatory value is maximized by integration of the genealogical hierarchy of species and monophyletic taxa with other areas of evolutionary biology.     

Plural cities in comparative perspective

Adopting a comparative perspective, the article focuses on ethnically heterogeneous cities as sites shaped by political economy, and asks whether varieties of the plural city can be mapped against varieties of polity. Four ideotypical configurations of city, society and polity (preindustrial-patrimonial, colonial, modern-industrial-capitalist, neoliberal-postmodern-global) are discussed in terms of their modalities of ethnicity. In preindustrial-patrimonial cities, rulers were concerned less with the ethnicity of subordinate minority populations than their ability to render tribute, taxes and labour. The colonial city was grounded in the differentiation of the population in terms of supposed 'racial' distinctions. Modern-industrial-capitalist cities sought the cultural and linguistic homogeneity of their immigrant populations through assimilation, or, where certain groups ('races') were thought unassimilable, through exclusion. In the late twentieth century such cities have shifted towards postindustrial and postmodern forms of sociality in a globalized, transnational, world espousing neoliberal economic and social policies and contested forms of 'multiculturalism'.     

Chromosome imbalances in oligodendroglial tumors detected by comparative genomic hybridization

Seven well-differentiated oligodendrogliomas, 16 anaplastic oligodendrogliomas and two cases of oligoastrocytomas were investigated by comparative genomic hybridization (CGH) on frozen tissue samples. The most frequent losses found involved 1p and 19q in 32% of cases. Loss of 9p was observed during malignant progression in 25% of anaplastic oligodendrogliomas. In two anaplastic oligodendrogliomas gain of 1q was found. The frequent losses of chromosome 16 and 22 have not been reported previously. These results underscore that CGH is a powerful tool for the classification of gliomas complementing the traditional histopathological approach.     

Note on Confidence Regions in Multiple Assays

This note is in continuation of the author's results on ’classical‘ confidence regions for relative potencies in multiple assays (Bennett, 1987). It is shown by the use of a Bonferroni inequality (e.g. Miller, ch. 2, 1980) that approximate confidence regions for the relative potencies {M_i} i = 1, …, p may also be obtained directly. A comparison with the classical regions is made for the case: p = 2 using Finney's example (1978, ch. 2).     

Multiple forms of carboxylesterase activity in Acinetobacter calcoaceticus

A carboxylesterase activity (E.C.3.1.1) was found in all four strains of Acinetobacter calcoaceticus tested. The activity was present in both 2 X 10(4) gav h-1 supernatant and bacterial wall-membrane fractions. The activity in the supernatant was in two molecular weight forms, the predominant form with a Mr of about 10(3) K and a minor form Mr approximately 600 K. The activity was inhibited by phenylmethylsulfonyl fluoride. SDS-PAGE showed that in A. calcoaceticus NCIB 8250 the activity was composed of three components of Mr 43, 40 and 38 K. The individual components showed different activities with 1- or 2-naphthyl esters. Of the other strains used, one showed a nearly identical pattern of component activities, while the other two showed only two component activities.     

EST derived SSR markers for comparative mapping in wheat and rice

Structural and functional relationships between the genomes of hexaploid wheat (Triticum aestivum L.) (2n=6x=42) and rice (Oryza sativa L.) (2n=2x=24) were evaluated using linkage maps supplemented with simple sequence repeat (SSR) loci obtained from publicly available expressed sequence tags (ESTs). EST-SSR markers were developed using two main strategies to design primers for each gene: (1) primer design for multiple species based on supercluster analysis, and (2) species-specific primer design. Amplification was more consistent using the species-specific primer design for each gene. Forty-four percent of the primers designed specifically for wheat sequences were successful in amplifying DNA from both species. Existing genetic linkage maps were enhanced for the wheat and rice genomes using orthologous loci amplified with 58 EST-SSR markers obtained from both wheat and rice ESTs. The PCR-based anchor loci identified by these EST-SSR markers support previous patterns of conservation between wheat and rice genomes; however, there was a high frequency of interrupted colinearity. In addition, multiple loci amplified by these primers made the comparative analysis more difficult. Enhanced comparative maps of wheat and rice provide a useful tool for interpreting and transferring molecular, genetic, and breeding information between these two important species. These EST-SSR markers are particularly useful for constructing comparative framework maps for different species, because they amplify closely related genes to provide anchor points across species.Communicated by R. Hagemann     

A comparative psychophysical approach to visual perception in primates

Studies on the visual processing of primates, which have well developed visual systems, provide essential information about the perceptual bases of their higher-order cognitive abilities. Although the mechanisms underlying visual processing are largely shared between human and nonhuman primates, differences have also been reported. In this article, we review psychophysical investigations comparing the basic visual processing that operates in human and nonhuman species, and discuss the future contributions potentially deriving from such comparative psychophysical approaches to primate minds.     

The evolution of life-history traits in parasitic and free-living platyhelminthes: a new perspective

Parasite life histories have been assumed to be shaped by their particular mode of existence. To test this hypothesis, we investigate the relationships between life-history traits of free-living and parasitic platyhelminthes. Using phylogenetically independent contrasts we examine patterns of interspecific covariation in adult size, progeny volume, daily fecundity, total reproductive capacity, age at first reproduction and longevity. The correlations obtained indicate a similar causal chain of life history variations for free-living and parasitic platyhelminthes. These results suggest that increased longevity favours delayed reproduction. Furthermore, growth pattern determines adult body size and age at maturity. For platyhelminthes, whether free-living or parasitic, the total reproductive capacity is found to be directly determined by the size of the worm. Within this group the parasitic way of life does not seem to influence the basic patterns of life history evolution. Received: 20 September 1997 / Accepted: 1 March 1998     

Mate fidelity and coloniality in waterbirds: a comparative analysis

Increased opportunities for information are one potential benefit of sociality. We apply this idea to the advantages of colonial breeding in bird species that are typically monogamous within a breeding season but often form new pair-bonds in subsequent seasons. Individuals may benefit from nesting in colonies at high density by identifying good-quality potential alternative mates among their neighbours. The opportunities for finding a better mating option are likely to increase with colony size and density. We tested this prediction with a comparative analysis of the association between mate fidelity and coloniality in waterbirds (wading birds and seabirds), where there is wide variation in both the degree of mate retention over consecutive breeding seasons and the degree of coloniality. We used two comparative statistical analyses, one based upon generalized least squares and the other based upon a continuous-time Markov model, to test whether the pattern of association between divorce rate and degree of coloniality was evidence for correlated evolutionary change in the two characters. We found a significant and positive association between divorce rate and the degree of coloniality in waterbirds. The probable ancestral state corresponds to a combination of a high degree of coloniality with no, or weak, mate fidelity. The reconstruction of the historical pattern of character origin and evolution indicates that the transition from a high to a low degree of coloniality occurred before the transition to higher mate fidelity. Received: 5 January 1998 / Accepted: 20 April 1998     

Mitochondrial dysfunction in fibroblasts of Multiple System Atrophy

Multiple System Atrophy is a severe neurodegenerative disorder which is characterized by a variable clinical presentation and a broad neuropathological spectrum. The pathogenic mechanisms are almost completely unknown. In the present study, we established a cellular model of MSA by using fibroblasts' primary cultures and performed several experiments to investigate the causative mechanisms of the disease, with a particular focus on mitochondrial functioning.Fibroblasts' analyses (7 MSA-P, 7 MSA-C and 6 healthy controls) displayed several anomalies in patients: an impairment of respiratory chain activity, in particular for succinate Coenzyme Q reductase (p?<?0.05), and a reduction of complex II steady-state level (p?<?0.01); a reduction of Coenzyme Q10 level (p?<?0.001) and an up-regulation of some CoQ10 biosynthesis enzymes, namely COQ5 and COQ7; an impairment of mitophagy, demonstrated by a decreased reduction of mitochondrial markers after mitochondrial inner membrane depolarization (p?<?0.05); a reduced basal autophagic activity, shown by a decreased level of LC3 II (p?<?0.05); an increased mitochondrial mass in MSA-C, demonstrated by higher TOMM20 levels (p?<?0.05) and suggested by a wide analysis of mitochondrial DNA content in blood of large cohorts of patients.The present study contributes to understand the causative mechanisms of Multiple System Atrophy. In particular, the observed impairment of respiratory chain activity, mitophagy and Coenzyme Q10 biosynthesis suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of the disease. Furthermore, these findings will hopefully contribute to identify novel therapeutic targets for this still incurable disorder.     

Progress in Multiple Sclerosis Genetics

A genetic component in the susceptibility to multiple sclerosis (MS) has long been known, and the first and major genetic risk factor, the HLA region, was identified in the 1970’s. However, only with the advent of genome-wide association studies in the past five years did the list of risk factors for MS grow from 1 to over 50. In this review, we summarize the search for MS risk genes and the latest results. Comparison with data from other autoimmune and neurological diseases and from animal models indicates parallels and differences between diseases. We discuss how these translate into an improved understanding of disease mechanisms, and address current challenges such as genotype-phenotype correlations, functional mechanisms of risk variants and the missing heritability.     

Inference on Multiple Endpoints in Clinical Trials with Adaptive Interim Analyses

Planned interim analyses which permit early stopping or sample size adaption of a trial are desirable for ethical and scientific reasons. Multiple test procedures allow inference about several hypotheses within a single clinical trial. In this paper, a method which combines multiple testing with adaptive interim analyses whilst controlling the experimentwise error rate is proposed. The general closed testing principle, the situation of a priori ordered hypotheses, and application of the Bonferroni-Holm method are considered. The practical application of the method is demonstrated by an example.     

A species assemblage approach to comparative phylogeography of birds in southern Australia

We present a novel approach to investigating the divergence history of biomes and their component species using single-locus data prior to investing in multilocus data. We use coalescent-based hierarchical approximate Bayesian computation (HABC) methods (MsBayes) to estimate the number and timing of discrete divergences across a putative barrier and to assign species to their appropriate period of co-divergence. We then apply a coalescent-based full Bayesian model of divergence (IMa) to suites of species shown to have simultaneously diverged. The full Bayesian model results in reduced credibility intervals around divergence times and allows other parameters associated with divergence to be summarized across species assemblages. We apply this approach to 10 bird species that are wholly or patchily discontinuous in semi-arid habitats between Australia's southwest (SW) and southeast (SE) mesic zones. There was substantial support for up to three discrete periods of divergence. HABC indicates that two species wholly restricted to more mesic habitats diverged earliest, between 594,382 and 3,417,699 years ago, three species from semi-arid habitats diverged between 0 and 1,508,049 years ago, and four diverged more recently, between 0 and 396,843 years ago. Eight species were assigned to three periods of co-divergence with confidence. For full Bayesian analyses, we accounted for uncertainty in the two remaining species by analyzing all possible suites of species. Estimates of divergence times from full Bayesian divergence models ranged between 429,105 and 2,006,355; 67,172 and 663,837; and 24,607 and 171,085 for the earliest, middle, and most recent periods of co-divergence, respectively. This single-locus approach uses the power of multitaxa coalescent analyses as an efficient means of generating a foundation for further, targeted research using multilocus and genomic tools applied to an understudied biome.     

Evidence for balancing selection acting on KIR2DL4 genotypes in rhesus macaques of Indian origin

The interaction of killer-cell immunoglobulin-like receptors (KIR) and their respective major histocompatibility complex (MHC) ligands can alter the activation state of the natural killer (NK) cell. In both humans and rhesus macaques, particular types of non-classical MHC class I molecules are predominantly expressed on the trophoblast. In humans, human leukocyte antigen G has been demonstrated to act as a ligand for KIR2DL4, present on all NK cells, whereas Mamu-AG may execute a similar function in rhesus macaques. During primate evolution, orthologues of KIR2DL4 appear to have been highly conserved, suggesting strong purifying selection. A cohort of 112 related and unrelated rhesus macaques of mostly Indian origin were selected to study their KIR2DL4 genes for the occurrence of polymorphism. Comparison of the proximal region provided evidence for strong conservative selection acting on the exons encoding the Ig domains. As is found in humans, in the Indian rhesus macaque population, two different KIR2DL4 entities are encountered, which differ for their intra-cellular signalling motifs. One genotype contains a complex mutation in the distal region of exon 9, which negates a serine/threonine kinase site. Furthermore, both allelic entities are present in a distribution, which suggests that balancing selection is operating on these two distinct forms of KIR2DL4. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

On Confidence Regions in Multiple Assays

In multiple assays a ‘Standard’ preparation is compared in a single assay with two or more ‘Test’ preparations (Finney, 1978, ch. 11). In addition to the estimation of the relative potency of the ‘Test’ preparations the question arises as to simultaneous confidence limits, or else a joint confidence region for these relative potencies. This paper compares a joint confidence region using a LR statistic with separate limits based on Fieller's theorem. These results are presented in an Example on a multiple assay of two tuberculin preparations A, B compared with a Standard one (data of Wadley, Finney, 1978, Table 11.1).     

There May be Strict Empirical Laws in Biology, after All

This paper consists of four parts. Part 1 is an introduction. Part 2 evaluates arguments for the claim that there are no strict empirical laws in biology. I argue that there are two types of arguments for this claim and they are as follows: (1) Biological properties are multiply realized and they require complex processes. For this reason, it is almost impossible to formulate strict empirical laws in biology. (2) Generalizations in biology hold contingently but laws go beyond describing contingencies, so there cannot be strict laws in biology. I argue that both types of arguments fail. Part 3 considers some examples of biological laws in recent biological research and argues that they exemplify strict laws in biology. Part 4 considers the objection that the examples in part 3 may be strict laws but they are not distinctively biological laws. I argue that given a plausible account of what distinctively biological means, such laws are distinctively biological.