Sex determining mechanisms: An evolutionary perspective

Summary Theories on the evolution of sex determining mechanisms are reviewed for male and female heterogamety, environmental sex determination, and briefly, haplo-diploidy and hermaphroditism. Because of their discrete and well-defined nature, sex determining mechanisms lend themselves to three types of evolutionary questions:what variety occurs and might be expected but does not occur,how do changes occur from one mechanism to another, andwhy do certain changes occur? All three approaches were illustrated for these different sex determining mechanisms. A generality emerging from these studies is that, at the level of selection on the sex ratio, there are no intrinsic problems in evolving from one sex determining mechanism to another: straightforward transitions between different mechanisms exist under various conditions.     

In vitro amiodarone protein binding and its interaction with warfarin

The binding of amiodarone to human plasma protein and to bovine serum albumin was studied by three different methods, ultracentrifugation, equilibrium dialysis and fluorescence spectroscopy. The fraction of amiodarone bound to plasma protein amounted to 96.3%. The changes in the binding properties of 1-anilino-naphthalene-8-sulfonate for bovine serum albumin using warfarin and amiodarone as independent inhibitors were analyzed in terms of binding site specificity. The findings indicated that amiodarone and warfarin have two different binding sites on bovine serum albumin, so a noncompetitive inhibition mechanism was indicated. On the basis of our data we cannot exclude other mechanisms of interaction besides direct displacement of one drug by another; nevertheless, metabolite interference between amiodarone and coagulation cofactors may better explain the enhancement of warfarin's pharmacological action in association with amiodarone.     

In vitro amiodarone protein binding and its interaction with warfarin

Summary The binding of amiodarone to human plasma protein and to bovine serum, albumin was studied by three different methods, ultracentrifugation, equilibrium dialysis and fluorescence spectroscopy. The fraction of amiodarone bound to plasma protein amounted to 96.3%. The changes in the binding properties of 1-anilino-naphthalene-8-sulfonate for bovine serum albumin using warfarin and amiodarone as independent inhibitors were analyzed in terms of binding site specificity. The findings indicated that amiodarone and warfarin have two different binding sites on bovine serum albumin, so a noncompetitive inhibition mechanism was indicated. On the basis of our data we cannot exclude other mechanisms of interaction besides direct displacement of one drug by another; nevertheless, metabolite interference between amiodarone and coagulation cofactors may better explain the enhancement of warfarin's pharmacological action in association with amiodarone.This work was partially funded by the CNR (National Research Council, Rome, Italy), Program on Clinical Pharmacology and Rare Diseases. The authors would like to thanks Drs E. Marzi and E. riva for their help.     

Scepticism,relativism, and the structure of epistemic frameworks

This paper has four aims: first, to outline the role of the sceptical problem of the criterion in the principal argument for epistemic relativism; second, to establish that methodist and particularist responses to the problem of the criterion do not, by themselves, constitute successful strategies for resisting epistemic relativism; third, to argue that a more fruitful strategy is to attempt to evaluate epistemic frameworks on the basis of the epistemic resources that they have in common; and finally, to make the case that finding this common ground will necessarily involve determining how it is that a framework’s constituent epistemic methods depend on one another for not only their warrant, but for their application.     

Behaviour of intrinsically disordered proteins in protein–protein complexes with an emphasis on fuzziness

Intrinsically disordered proteins (IDPs) do not, by themselves, fold into a compact globular structure. They are extremely dynamic and flexible, and are typically involved in signalling and transduction of information through binding to other macromolecules. The reason for their existence may lie in their malleability, which enables them to bind several different partners with high specificity. In addition, their interactions with other macromolecules can be regulated by a variable amount of chemically diverse post-translational modifications. Four kinetically and energetically different types of complexes between an IDP and another macromolecule are reviewed: (1) simple two-state binding involving a single binding site, (2) avidity, (3) allovalency and (4) fuzzy binding; the last three involving more than one site. Finally, a qualitative definition of fuzzy binding is suggested, examples are provided, and its distinction to allovalency and avidity is highlighted and discussed.     

Reflections on the ambivalent helix

Summary The helix is nature's favourite shape. Because of its elementary geometry and distinctive appearance it is also the clearest instance of an enantiomorphic object-a helix and its mirror image are identical in all respects except their screw sense. This is a distinction that can be ignored from the points of view of pure geometry and pure group theory¹⁸ but any helical structure is actually available as either or both hands.Whether in nature helices do occur as just one hand, or both, is one of the best-perhaps the best-puzzles of the science of form. In this short review I look at a few examples of naturally occurring helices, some where only one hand is found, some where both are commonly found, and perhaps the most interesting examples in biological terms-those where both are found but one hand is very much rarer than the other. I review what mechanisms-physico-chemical, genetic, evolutionary-underlie the different manifestations of left- and right-handedness.     

The biochemistry of natural fasting at its limits.

There are several groups of animals that are adapted for extremely long duration fasting as part of their reproductive cycle. Penguins, bears and seals routinely fast without food or water for months at time. However, they do not 'starve', as the biochemical implications of starving are very different from those of successful fasting. There are distinct biochemical adaptations in lipid, carbohydrate and especially protein metabolism that allow these animals to survive. It appears, at least for penguins and seals, that the duration of the fast may be limited by changes that occur in biochemical regulation near the ned of the fast. In all of these species, the biochemistry of fasting and the ecological and behavioral demands of their breeding cycles are closely interrelated.     

Sex chromosomes and sex-determining genes: insights from marsupials and monotremes

Comparative studies of the genes involved in sex determination in the three extant classes of mammals, and other vertebrates, has allowed us to identify genes that are highly conserved in vertebrate sex determination and those that have recently evolved roles in one lineage. Analysis of the conservation and function of candidate genes in different vertebrate groups has been crucial to our understanding of their function and positioning in a conserved vertebrate sex-determining pathway. Here we review comparisons between genes in the sex-determining pathway in different vertebrates, and ask how these comparisons affect our views on the role of each gene in vertebrate sex determination.     

Tracking migration during human T cell development

Specialized microenvironments within the thymus are comprised of unique cell types with distinct roles in directing the development of a diverse, functional, and self-tolerant T cell repertoire. As they differentiate, thymocytes transit through a number of developmental intermediates that are associated with unique localization and migration patterns. For example, during one particular developmental transition, immature thymocytes more than double in speed as they become mature T cells that are among the fastest cells in the body. This transition is associated with dramatic changes in the expression of chemokine receptors and their antagonists, cell adhesion molecules, and cytoskeletal components to direct the maturing thymocyte population from the cortex to medulla. Here we discuss the dynamic changes in behavior that occur throughout thymocyte development, and provide an overview of the cell-intrinsic and extrinsic mechanisms that regulate human thymocyte migration.     

Mental processes and disorders: a neurobehavioral perspective in human biometeorology

Research concerning the complex relation between weather and psychological processes has emphasized three important issues: methodological problems, the determination of the major behavioral factors, and the isolation of neurobiological mechanisms. This paper reviews the current status of each issue. Weather changes are most frequently associated with behaviors that are the endpoints of inferred psychological processes that include mood, subclinical pain, anxiety, and the correlates of schedule shifts. Learning and conditioning appear to mediate a powerful influence over weather-related responses. This may explain the large individual variability in these behaviors. The most well-known group effects associated with weather changes involve psychiatric populations. Clinical subpopulations may respond in different ways to different aspects of the same weather system as well as to different types of air masses. Likely neurobiological mechanisms through which meteorogenic stimuli may mediate whole organismic effects include the locus coeruleal and limbic systems. Expected psychobiological consequences are examined in detail. The magnitude and temporal-spatial characteristics of weather effects indicate they are the subject matter of behavioral epidemiology.     

Mental processes and disorders: A neurobehavioral perspective in human biometeorology

Summary Research concerning the complex relation between weather and psychological processes has emphasized three important issues: methodological problems, the determination of the major behavioral factors, and the isolation of neurobiological mechanisms. This paper reviews the current status of each issue. Weather changes are most frequently associated with behaviors that are the endpoints of inferred psychological processes that include mood, subclinical pain, anxiety, and the correlates of schedule shifts. Learning and conditioning appear to mediate a powerful influence over weather-related responses. This may explain the large individual variability in these behaviors. The most well-known group effects associated with weather changes involve psychiatric populations. Clinical subpopulations may respond in different ways to different aspects of the same weather system as well as to different types of air masses. Likely neurobiological mechanisms through which meteorogenic stimuli may mediate whole organismic effects include the locus coeruleal and limbic systems. Expected psychobiological consequences are examined in detail. The magnitude and temporal-spatial characteristics of weather effects indicate they are the subject matter of behavioral epidemiology.     

Mechanisms for cardiac arrhythmias

Possible cellular electrophysiological mechanisms for arrhythmias have been investigated through studies of isolated cardiac tissues. Records through extracellular and intracellular electrodes indicate that arrhythmias may result from either focal or non-focal mechanisms. Focal mechanisms include abnormal impulse initiation (normal or abnormal automaticity), triggering from either early or delayed afterdepolarizations and reflection, whereas the non-focal mechanisms are various forms of reentry due to circus movement. It is reasonable to assume that these mechanisms also occur in vivo. Although it is safe to identify macro-re-entry as the cause of some atrial and ventricular arrhythmias, for the most part direct proof of mechanism usually is lacking for the focal arrhythmias. If 'on line' activation sequence mapping techniques can be developed to quickly and specifically locate arrhythmogenic foci in the in situ heart, it may be possible to use unipolar extracellular recording techniques to identify the exact cellular electrophysiological mechanisms operating within them.     

Discrete Euler processes and their applications

This paper introduces discrete Euler processes and shows their application in detecting and forecasting cycles in non‐stationary data where periodic behavior changes approximately linearly in time. A discrete Euler process becomes a classical stationary process if ‘time’ is transformed properly. By moving from one time domain to another, one may deform certain time‐varying data to non‐time‐varying data. With these non‐time‐varying data on the deformed timescale, one may use traditional tools to do parameter estimation and forecasts. The obtained results then can be transformed back to the original timescale. For datasets with an underlying discrete Euler process, the sample M‐spectrum and the spectra estimator of a Euler model (i.e., EAR spectral) are used to detect cycles of a Euler process. Beam response and whale data are used to demonstrate the usefulness of a Euler model. Copyright © 2008 John Wiley & Sons, Ltd.     

Pineal melatonin rhythms and the timing of puberty in mammals

The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknown. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.     

Pineal melatonin rhythms and the timing of puberty in mammals

Summary The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknow. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.     

Unification and mechanistic detail as drivers of model construction: Models of networks in economics and sociology

We examine the diversity of strategies of modelling networks in (micro) economics and (analytical) sociology. Field-specific conceptions of what explaining (with) networks amounts to or systematic preference for certain kinds of explanatory factors are not sufficient to account for differences in modelling methodologies. We argue that network models in both sociology and economics are abstract models of network mechanisms and that differences in their modelling strategies derive to a large extent from field-specific conceptions of the way in which a good model should be a general one. Whereas the economics models aim at unification, the sociological models aim at a set of mechanism schemas that are extrapolatable to the extent that the underlying psychological mechanisms are general. These conceptions of generality induce specific biases in mechanistic explanation and are related to different views of when knowledge from different fields should be seen as relevant.     

Oenocytes of poultry liceLipeurus lawrensis tropicalis Peters (Phthiraptera: Ischnocera)

Summary Oenocytes ofLipeurus lawrensis tropicalis Peters, an ischnoceran Mallophaga (Sens. Lat. Phthiraptera) occur either singly or in clusters of 2–6, and do not exhibit any changes in the different stages of nymphs and adults of the 2 sexes.Acknowledgment. Thanks are due to Head of the Zoology Department Banaras Hindu University, for laboratory facilities and to State Council of Science and Technology, U.P. for financial assistance under the grant No.SCST/4779/BHU (43)/77     

Lipid transport pathways in mammalian cells

Summary A major deficit in our understanding of membrane biogenesis in eukaryotes is the definition of mechanisms by which the lipid constituents of cell membranes are transported from their sites of intracellular synthesis to the multiplicity of membranes that constitute a typical cell. A variety of approaches have been used to examine the transport of lipids to different organelles. In many cases the development of new methods has been necessary to study the problem. These methods include cytological examination of cells labeled with fluorescent lipid analogs, improved methods of subcellular fractionation, in situ enzymology that demonstrates lipid translocation by changes in lipid structure, and cell-free reconstitution with isolated organelles. Several general patterns of lipid transport have emerged but there does not appear to be a unifying mechanism by which lipids move among different organelles. Significant evidence now exists for vesicular and metabolic energy-dependent mechanisms as well as mechanisms that are clearly independent of cellular ATP content.     

Zur Frage des Angriffspunktes des Thiouracil

Summary The mechanism of action of thiouracil and thiourea was investigated on Xenopus tadpoles. Both substances are able to stop metamorphotic changes if administered early enough. Characteristic disturbances occur in the epithelium of the thyroid follicles after only 24 hours. The action of these substances over a period of several weeks may lead to goitre. In the pituitary anterior lobe, on the other hand, the same characteristic changes take place in the basophilic cells as after thyroidectomy. The thyroid structure of hypophysectomised tadpoles corresponds to that of untreated hypophysectomised animals. Thiourea and thiouracil do not inhibit the thyroxine effect on thyroidectomised and hypophysectomised tadpoles. These findings indicate that the point of attack of thiouracil and thiourea lies in the follicular epithelium of the thyroid, and thus supportAstwood's hypothesis.