Modelling and the fall and rise of the handicap principle

The story of the fall and rise of Zahavi??s handicap principle is one of a battle between models. Early attempts at formal modeling produced negative results and, unsurprisingly, scepticism about the principle. A major change came in 1990 with Grafen??s production of coherent models of a handicap mechanism of honest signalling. This paper??s first claim is that acceptance of the principle, and its dissemination into other disciplines, has been driven principally by that, and subsequent modeling, rather than by empirical results. Secondly, there is a vast literature on biological signalling but few studies that make all of the observations necessary to diagnose the handicap mechanism. My final claim is that many of the applications of ??costly signalling theory?? in other disciplines are conceptually confused. Misinterpretations of what is meant by ??costly signalling?? are common. Demonstrating that a signal is costly is insufficient and is not always necessary in order to prove that, and explain why, a signal is honest. In addition to the biological modelling of signals, there is an economic literature on the same subject. The two run in parallel in the sense that they have had little mutual interaction. Additionally, it is the biological modelling that has been picked up, and often misapplied, by other disciplines.     

Qualitative and quantitative aspects of the biosynthesis of ribonucleic acid and of protein in the liver and the lung of the Syrian golden hamster

1. The incorporation of orotic acid and of uridine into total RNA was measured in vivo in liver and lung of the Syrian golden hamster. Specific activities of total acid-soluble UMP were measured in both organs. An estimation of the rate of RNA biosynthesis showed that hamster lung synthesizes RNA at about one-half of the rate of that of hamster liver. 2. The apparent K(m) and V(max.) values of a few enzymes involved in pyrimidine biosynthesis were measured in the 100000g supernatants of liver and lung. The apparent K(m) values were very similar in both organs. From the estimated V(max.,) it was concluded that hamster lung cells have less capacity to metabolize orotic acid than have liver cells. 3. A time-response and a dose-response study showed that actinomycin D inhibits pulmonary RNA synthesis as efficiently as hepatic RNA synthesis. 4. Protein synthesis, measured as the incorporation of leucine, was inhibited in both organs 30min after a dose of 2mg of cycloheximide/kg. The dose-response patterns were similar in both liver and lung 3h after cycloheximide. 5. It is concluded that RNA and protein synthesis in vivo in hamster lung are very similar to the corresponding reactions in liver. Alterations of RNA and protein synthesis by toxic agents can therefore be evaluated in lung with a similar approach to that used to study the pathological biochemistry of liver.     

Metamorphosis in the Cirripedia Rhizocephala and the homology of the kentrogon and trichogon

The Rhizocephala are considered to be monophyletic due to several synapomorphies in the ontogeny of the cndoparasitic phase. The various types of metamorphosis described in the Rhizocephala are discussed and compared to metamorphosis in the Cirripedia Thoracica and Acrothoracica. In males and females of the suborder Kentrogonida. the cyprid settles and metamorphoses into a new instar, in males the trichogen and in females the infective kentrogon. The kentrogon goes through yet another. incomplete moult associated with the development of the stylet. Within the three kentrogonidan families. the Iernaeodiscid-peltogastrid type of kentrogon differs from the sacculinid type in the mode of attachment to the host. in the complexity of internal anatomy. in the position and penetration of the stylet, and in whether or not the cyprid carapace must be shed prior to penetration of the stylet. In the Akentrogonida metamorphosis never results in a new instar. Where observed (Clistosaccidae and Thompsoniidae). both male and female cyprids settle and penetrate into their substrate (female parasite or new host) with one of the antennules. Using the antennule as a syringe. male cyprids inject spermatogonia while female cyprids injects embryonic cells developing into an endoparasite. By comparison with metamorphosis in the Cirripedia Thoracica and Acrothoracica it is concluded that the presence of a metamorphic moult leading to a post-cyprid instar is plesiomorphic and that the trichogon and kentrogon are homologous with the first metamorphosed juvenile in these outgroups. The abbreviated ontogeny in the Akentrogonida without metamorphic moult and post-cyprid larval instars is considered apomorphic. This contradicts the long-held supposition that the Akentrogonida are the most‘primitive’Rhizocephala and dovetails with new information that this suborder contains many advanced traits. Within the Kentrogonida. the lernacodiseid-peltogastrid type of kentrogon is considered more plesiomorphic than the sacculinid type, which resembles the clistosaccidthompsoniid type in having the antennules involved in the penetration process. The homologization of the kentrogon with a juvenile barnacle indicates that presence of a kentrogon is plesiomorphic within the Rhizocephala and that the Kentrogonida is paraphyletic.     

The septomaxilla of fossil and recent synapsids and the problem of the septomaxilla of monotremes and armadillos

The septomaxilla is a paired intramembranous ossification in the external nares that occurs in Lepidosauria among Recent Sauropsida and is purported to be present in Monotremata and Dasypodidae (armadillos) among Recent Mammalia. A review of neontological and palaeontological evidence regarding this element in mammals supports the following conclusions: (1) monotremes have a true septomaxilla resembling that known for non-mammalian therapsids and some Mesozoic mammals; (2) the element in dasypodids is a neomorph; it neither resembles the septomaxilla of other synapsids nor does it exhibit the same relationship to the developing nasal-floor cartilage as the septomaxilla of lepidosaurs and monotremes; (3) a septomaxilla is lacking in all Recent therians, and there is no evidence that this bone is fused to the premaxilla in Recent therians, as has been suggested by previous authors.     

Effect of stress and the antioxidant ionol on the biosynthesis of catecholamines and the content of dopamine in the heart and adrenal glands

The effects of a synthetic antioxidant ionol (dibunol) on the biosynthesis and content of catecholamines in the heart and adrenal glands were studied. It was shown that in stress a mobilization of catecholamine reserve is combined with a considerable increase in dopamine concentration. In conditions of physiological rest, ionol did not affect the studied indices of adrenal catecholamine biosynthesis, while in the heart it enhanced the dopamine synthesis and content. With ionol administration, stress did not suppress but, on the contrary, increased the neuronal uptake and noradrenaline biosynthesis, catecholamine concentration remaining practically unchanged. Simultaneously, a manyfold increase in the biosynthesis along with a considerable increase in the concentration of dopamine developed in both organs. The data obtained suggest that ionol realizes its stress-defensive effect to a great extent due to the activation of catecholamine biosynthesis and to a concomitant increase in dopamine accumulation.     

Probing the importance of the amino-terminal sequence of the beta- and gamma-chains to the properties of normal adult and fetal hemoglobins

A recombinant mutant of human fetal hemoglobin (Hb F), named rHb Oscar, has been constructed to explore the importance of the sequence of the amino-terminal region of the gamma-chain to the structural and functional properties of Hb F as compared to human normal adult hemoglobin (Hb A). Substitutions in the N-terminal region of Hb A have shown this region to be important to its structural and functional properties. Recent studies of recombinant mutants of Hb A with gamma-chain mutations have been used to probe the significance of the N-terminal sequence to the properties of Hb F. One of these mutants of Hb A, called rHb Felix, contains eight substitutions in the N-terminal region of the beta-chain corresponding to the sequence of the gamma-chain in that region [Dumoulin et al. (1998) J. Biol. Chem. 273, 35032-35038]. rHb Felix exhibits a 2,3-bisphosphoglycerate (2,3-BPG) response like that of Hb A, but its tetramer-dimer dissociation constant is similar to that of Hb F. In contrast, rHb Oscar contains a gamma-chain with eight mutations at the N-terminal end corresponding to the sequence of the beta-chain of Hb A in that region. (1)H NMR studies of rHb Oscar indicate a global structure like that of Hb F. rHb Oscar is not as stable against alkaline denaturation as Hb F but is more stable than Hb A, and it exhibits a stronger response to 2,3-BPG and inositol hexaphosphate as compared to Hb F. The 2,3-BPG effect in rHb Oscar also appears to be slightly enhanced compared to that in Hb A. Subzero isoelectric focusing experiments suggest that rHb Oscar does not have dissociation properties like those of Hb A. These results along with those of rHb Felix illustrate that the effects of the N-terminal region on structure and function of the Hb molecule are complicated by interactions with the rest of the molecule that are not yet well defined. However, studies of complementary mutations of Hb A and Hb F may eventually help to define such interactions and lead to a better understanding of the relationship between the amino acid sequence and the properties of the Hb molecule.     

The septomaxilla of fossil and recent synapsids and the problem of the septomaxilla of monotremes and armadillos

The septomaxilla is a paired intramembranous ossification in the external nares that occurs in Lepidosauria among Recent Sauropsida and is purported to be present in Monotremata and Dasypodidae (armadillos) among Recent Mammalia. A review of neontological and palaeontological evidence regarding this element in mammals supports the following conclusions: (1) monotremes have a true septomaxilla resembling that known for non-mammalian therapsids and some Mesozoic mammals; (2) the element in dasypodids is a neomorph; it neither resembles the septomaxilla of other synapsids nor does it exhibit the same relationship to the developing nasal-floor cartilage as the septomaxilla of lepidosaurs and monotremes; (3) a septomaxilla is lacking in all Recent therians, and there is no evidence that this bone is fused to the premaxilla in Recent therians, as has been suggested by previous authors.     

Referral of Touch and Ownership between the Hands and the Role of the Somatosensory Cortices

Recent studies have shown that the feeling of body ownership can be fooled by simple visuo-tactile manipulations. Perceptual illusions have been reported in which participants sense phantom touch seen on a rubber hand (rubber hand illusion). While previous studies used homologous limbs for those experiments, we here examined an illusion where people feel phantom touch on a left rubber hand when they see it brushed simultaneously with brushes applied to their right hand. Thus, we investigated a referral of touch from the right to the left hand (across the body midline). Since it is known from animal studies that tactile illusions may alter early sensory processing, we expected a modulation of the primary somatosensory cortex (SI) corresponding to this illusion. Neuromagnetic source imaging of the functional topographic organization in SI showed a shift in left SI, associated with the strength of the referral of touch. Hence, we argue that SI seems to be closely associated with this perceptual illusion. The results suggest that the transfer of tactile information across the body midline could be mediated by neurons with bilateral tactile receptive fields (most likely BA2).     

Inositol lipids and phosphates in the regulation of the growth and differentiation of haemopoietic and other cells

Stimulation of phosphatidylinositol 4,5-bisphosphate hydrolysis is an important signalling reaction involved in the responses of cells to some, but not all, stimuli that promote cell proliferation. Active agents in this regard include antigens activating T and B lymphocytes, angiotensin (employing a receptor encoded by the mas oncogene), bombesin and platelet-derived growth factor PDGF). However, accumulating evidence suggests that inositol lipids and phosphates also have other roles in the regulation of cell growth and differentiation. Growth factor receptors that encode tyrosine kinases (such as that for PDGF) activate a kinase that synthesises phosphatidylinositol 3-phosphate, a novel lipid, and loss of this kinase-activating function abolishes growth-promoting activity. Human interleukin-4, a lymphokine that activates B lymphocytes, appears to employ phosphatidylinositol 4,5-bisphosphate hydrolysis as a brief initial signal that is followed by a sustained rise in cyclic adenosine monophosphate (cAMP): both signals are needed for the successful induction of the surface antigen CD23. Moreover, the same inositol lipid signalling pathway as is employed by antigen-stimulated mature T lymphocytes to provoke proliferation may be redeployed in immature T cells to trigger their elimination when they encounter self-antigens. Finally, studies of HL60 promyelocytic cells have shown that these cells contain high concentrations of inositol 3,4,5,6-tetrakisphosphate, 1,3,4,5,6-pentakisphosphate and hexakisphosphate, three inositol polyphosphates that are probably formed independently of inositol lipid metabolism. When these cells are induced to differentiate either towards neutrophils (in the presence of dimethylsulphoxide) or macrophages (in phorbol myristate acetate), cessation of growth and acquisition of differentiated characteristics are accompanied by large and different changes in the concentrations of these inositol phosphates that may be characteristic of these two pathways of differentiation.     

Hastening death and the boundaries of the self

When applying moral principles to concrete cases, we assume a background shared understanding of the boundaries of the persons to whom the principles apply. In most contexts, this assumption is unproblematic. However, in end-of-life contexts, when patients are receiving 'artificial' life-support, judgments about where a person's self begins and ends can become controversial. To illustrate this possibility, this paper presents a case in which a decision must be made whether to deactivate a patient's pacemaker as a means to hasten his death. After discussing some common moral principles that are often applied to resolve ethical problems at the end of life and after explaining why they are of no help here, the paper argues that the correct analysis of this case, and of cases of this sort, turns on considerations that relate to the constitution of the self. These considerations, the paper further argues, sometimes resist resolution. The constitution of the self is fixed in large measure by our concepts and social conventions, and these do not always provide determinate grounds for delimiting the boundaries of the self.     

Genetic matches and the logic of the law

In a recent article Levine and Kobilinsky (1997) point out that current methods in forensic DNA 'identification' are inadequate because the commercial kits commonly used in forensic practice do not detect the true genotype, but rather a genotype based on convenient categorization. For this reason, Levine and Kobilinsky argue that statistics attached to such categorizations are invalid. The authors believe that the arguments of Levine and Kobilinsky are logically flawed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Mitosis in the formation and function of the primary hypoblast of the chick

Summary The present work demonstrates that a normal stage-XIII hypoblast, if submitted to an X-ray dose of 6,000 rads (sufficient to stop cell division), retains the capacity to induce axis formation on the chick epiblast. Examination of the process of hypoblast formation indicates, in agreement with previous findings, that a hypoblastic layer can form in the absence of cell division from an irradiated stage-X blastoderm. Furthermore, it is observed that this hypoblastic layer, formed in the absence of cell division, can induce the development of an embryonic axis when combined with a normal stage-XIII epiblast.     

Art and the Re-Presentation of the Past

This article considers conceptual links between producing installation art works in the present and interpreting prehistoric lifeworlds. We consider connections between the work of contemporary 'landscape', 'environmental' or 'ecological' artists and an on-going landscape archaeology project centred on Leskernick Hill, Bodmin Moor in the south-west of Britain. We argue that the production of art works in the present can be a powerful means of interpreting the past in the present. Both the practices of interpreting the past and producing art result in the production of something new that transforms our understanding of place and space resulting in the creation of new meaning. Art and archaeology can act together dialectically to produce a novel conceptualization of the past and produce a means of relating to the past that is considerably more than the sum of its parts.     

Androgens and the development of the vagina

Today it is generally held that the vagina develops from sinovaginal bulbs and that the lower third of the definitive vagina is derived from the urogenital sinus. Here we show that the entire vagina arises by downward growth of Wolffian and Müllerian ducts, that the sinovaginal bulbs are in fact the caudal ends of the Wolffian ducts, and that vaginal development is under negative control of androgens. We designed a genetic experiment in which the androgen receptor defect in the Tfm mouse was used to examine the effects of androgens. Vaginal development was studied by 3D reconstruction in androgen-treated female embryos and in complete androgen-insensitive littermates. In androgen-treated females, descent of the genital ducts was inhibited, and a vagina formed in androgen-insensitive Tfm embryos as it does in normal females. By immmunohistochemical localization of the androgen receptor in normal mouse embryos, we demonstrated that the androgen receptor was expressed in Wolffian duct and urogenital sinus-derived structures, and was entirely absent in the Müllerian duct derivatives. We conclude that the Wolffian ducts are instrumental in conveying the negative control by androgens on vaginal development. The results are discussed under evolutionary aspects at the transition from marsupial to eutherian mammals.     

Symerythrin structures at atomic resolution and the origins of rubrerythrins and the ferritin-like superfamily

Rubrerythrins are diiron-containing peroxidases that belong to the ferritin-like superfamily (FLSF). Here, we describe the structures of symerythrin, a novel rubrerythrin variant from the oxygenic phototroph Cyanophora paradoxa, at 1.20-1.40 Å resolution in three different states: diferric, azide-bound diferric and chemically reduced. The symerythrin metallocenter has a unique eighth ligating residue compared to rubrerythrin—an additional glutamate inserted into helix A of the four-helix bundle that resides on a π-helical segment. Otherwise, the diferric metallocenter structure is highly similar to that of characterized rubrerythrins. Azide binds the diferric center in a μ-1,1 orientation similar to how peroxide binds to diferric rubrerythrin. The structure of the diferrous metallocenter shows heterogeneity that we ascribe to the acidic pH of the crystals. In what we consider the neutral pH conformation, reduction causes a 2.0-Å shift in Fe1 and the toggling of a Glu to a His ligand, as seen with rubrerythrins. The function of symerythrin remains unknown, but preliminary tests showing oxidase and peroxidase activities and the similarities of its metallocenter to other rubrerythrins suggest similar functionalities between the two despite the additional ligating glutamate in symerythrin. Of particular interest is the high internal symmetry of symerythrin, which supports the notion that its core four-helix bundle was formed by the gene duplication and fusion of a two-helix peptide. Sequence comparisons with another family in the FLSF that also has notable internal symmetry provide compelling evidence that, contrary to previous assumptions, there have been multiple gene fusion events that have generated the single-chain FLSF fold.     

Morphine intake and the effects of naltrexone and buprenorphine on the acquisition of methamphetamine intake

Some common genetic factors appear to influence risk for drug dependence across multiple drugs of abuse. In previous research, mice that were selectively bred for higher amounts of methamphetamine consumption, using a two‐bottle choice methamphetamine drinking procedure, were found to be less sensitive to the locomotor stimulant effects of morphine and of the more selective μ‐opioid receptor agonist fentanyl, compared to mice that were bred for low methamphetamine consumption. This suggested that μ‐opioid receptor‐mediated pathways may influence genetic risk for methamphetamine consumption. We hypothesized that these differences in opioid sensitivity would impact opioid intake in the methamphetamine drinking lines and that drugs with μ‐opioid receptor activity would impact methamphetamine intake. Consumption of morphine was examined in 2, two‐bottle choice studies, one that compared morphine to quinine consumption and another that used a saccharin fading procedure. Next, naltrexone (0, 0.5, 1, 2, 5, 10 and 20 mg/kg), a μ‐opioid receptor antagonist, and buprenorphine (0, 1, 2 or 4 mg/kg), a μ‐opioid receptor partial agonist, were each examined for their effects on the acquisition of methamphetamine consumption. Low methamphetamine drinking mice consumed more morphine compared to high methamphetamine drinking mice. Naltrexone did not alter methamphetamine consumption in either selected line; however, buprenorphine reduced methamphetamine intake in the high methamphetamine drinking line. These data show that greater sensitivity to opioids is associated with greater opioid intake and warrant further investigation of drugs with μ‐opioid receptor‐specific agonist activity in genetically determined differences in methamphetamine consumption.     

Rock-scissors-paper and the survival of the weakest.

In the children's game of rock-scissors-paper, players each choose one of three strategies. A rock beats a pair of scissors, scissors beat a sheet of paper and paper beats a rock, so the strategies form a competitive cycle. Although cycles in competitive ability appear to be reasonably rare among terrestrial plants, they are common among marine sessile organisms and have been reported in other contexts. Here we consider a system with three species in a competitive loop and show that this simple ecology exhibits two counter-intuitive phenomena. First, the species that is least competitive is expected to have the largest population and, where there are oscillations in a finite population, to be the least likely to die out. As a consequence an apparent weakening of a species leads to an increase in its population. Second, evolution favours the most competitive individuals within a species, which leads to a decline in its population. This is analogous to the tragedy of the commons, but here, rather than leading to a collapse, the 'tragedy' acts to maintain diversity.     

Isolation and characterization of the alpha and beta subunits of the platelet-activating glycoprotein from the venom of Crotalus durissus cascavella

It was concluded in a previous paper that the high Mr platelet-activating glycoprotein isolated earlier from the venom of Crotalus durissus cascavella has an hexameric structure of the alpha 3 beta 3 type involving two distinct subunits. Data reported here demonstrate that these two subunits are separable from each other by ion exchange chromatography under denaturating conditions, have similar Mrs (alpha = 12,540 et beta = 13,770) and exist in a one to one ratio within the native molecule. Carbohydrate analysis indicated that they are both similarly glycosylated to a small extent. They have slightly different amino-acid compositions, a common N-terminal sequence up to the fifth residue and similar extinction coefficients at 280 nm. The native molecule has a calculated Mr of 78,930. Additional data demonstrated that convulxin from the venom of Crotalus durissus terrificus is the same platelet-activating agent as the presently described platelet-activating glycoprotein (PAG) from the venom of Crotalus durissus cascavella.