Functional dissociation of mu opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction.

Opiate analgesia, tolerance, and addiction are mediated by drug-induced activation of the mu opioid receptor. A fundamental question in addiction biology is why exogenous opiate drugs have a high liability for inducing tolerance and addiction while native ligands do not. Studies indicate that highly addictive opiate drugs such as morphine are deficient in their ability to induce the desensitization and endocytosis of receptors. Here, we demonstrate that this regulatory mechanism reveals an independent functional property of opiate drugs that can be distinguished from previously established agonist properties. Moreover, this property correlates with agonist propensity to promote physiological tolerance, suggesting a fundamental revision of our understanding of the role of receptor endocytosis in the biology of opiate drug action and addiction.     

Knee-clicks and visual traits indicate fighting ability in eland antelopes: multiple messages and back-up signals

Background  

Given the costs of signalling, why do males often advertise their fighting ability to rivals using several signals rather than just one? Multiple signalling theories have developed largely in studies of sexual signals, and less is known about their applicability to intra-sexual communication. We here investigate the evolutionary basis for the intricate agonistic signalling system in eland antelopes, paying particular attention to the evolutionary phenomenon of loud knee-clicking.     

Why is the world green? The interactions of top–down and bottom–up processes in terrestrial vegetation ecology

A classic question in plant ecology is “why is the world green?” That is, if plants are food for animals why do not animals eat all the available food – changing a ‘green world’ into a ‘brown world’. We first reviewed this question in 2009 and now revisit our arguments in the light of new data and new thinking. Here we argue that (1) the top–down bottom–up dichotomy is probably too simple for understanding a complex system – such as vegetation – rich in feedback processes. (2) Nevertheless it appears that bottom–up processes are generally more important for maintaining the presence of some sort of vegetation while top–down control process are generally more important in determining the type of vegetation at a site. (3) Although this review mainly takes a qualitative and experimental approach to the question, we also argue that simple well-known mathematical models from population ecology can be very informative in thinking about the types of explanations for the green world phenomenon, and demonstrating that it is rarely a simple choice between one form of control or another.     

Beyond "the State" and Failed Schemes

In this article, I propose five ways to move beyond the analytical scheme of James Scott's Seeing Like a State (1998). I question the spatial optic that posits an "up there," all-seeing state operating as a preformed repository of power, spread progressively outward to "nonstate" spaces beyond its reach. I highlight the role of parties beyond "the state" that attempt to govern—social reformers, scientists, and the so-called nongovernmental agencies, among others. I look beyond authoritarian high modernism to the more general problematic of "improvement" emerging from a governmental rationality focused on the welfare of populations. I explore the recourse to mētis (contextualized, local knowledge and practice) situated beyond the purview of planning. Finally, I reframe the question posed by Scott—why have certain schemes designed to improve the human condition failed?—to examine the question posed so provocatively by James Ferguson: What do these schemes do? What are their messy, contradictory, conjunctural effects?     

Plant Morphogenesis 123: a renaissance in modern botany?

Plants are a group of multicellular organisms crucial for the biosphere on the Earth. In the 17th century, the founding fathers of modern botany viewed the bud as the basic unit undergoing the plant life cycle. However, for many understandable reasons, the dominant conceptual framework evolved away from the “bud-centered” viewpoint to a “plant-centered” viewpoint that treated the whole plant, consisting of numerous buds, as a unit and considered the entire plant to be the functional equivalent of an animal individual. While this “plant-centered” viewpoint is convenient and great progress has been made using this conceptual framework, some fundamental problems remain logically unsolvable. Previously, I have proposed a new conceptual framework for interpretation of plant morphogenesis, called Plant Morphogenesis 123, which revives a “bud-centered” viewpoint. The perspective of Plant Morphogenesis 123 allows us to address new questions regarding to the mechanisms of plant morphogenesis that are important, and technically accessible, but previously neglected under the “plant-centered” conceptual framework. In addition to describing these questions, I address a more fundamental question for further discussion: why do people study plants?

     

Variation in developmental time affects mating success and Allee effects

A fundamental question in biological conservation and invasion biology is why do some populations go extinct? Allee effects, notably those caused by mate location failure, are potentially key factors leading to the extinction of sparse populations. Several previous studies have focused on the inability of males and females to locate each other in space when populations are at low densities but here we investigate the effects of differences in the timing of male and female maturation on mating success. We develop a generalized model to clarify the role of protandry (the appearance of males before female emergence) and variability in adult maturation times. We show that temporal asynchrony can substantially reduce the probability of successful mating. We then apply this generalized model to estimate mating success in invading populations of the gypsy moth in North America in relation to local climate and its associated seasonality. Considerable geographic heterogeneity was observed in simulated mating success and this variability was not correlated with previous evaluations of bioclimatic requirements and habitat suitability. Furthermore, we found that the generalized model of temporal asynchrony provided reliable predictions and that detailed modeling of gypsy moth development was not necessary.     

The visual system as a constraint on the survival and success of specific artworks

Why should vision science turn its gaze towards artworks? One possibility is that understanding visual processing might yield some fundamental insight into the nature of art. However, there are many examples of phenomena that can be seen - such as automobiles, clouds or leaves - but which are not explained in any deep sense by the properties of human visual perception. We examine one art historical question that might benefit from knowledge about the visual system: why do some artworks 'survive' historically while others fade into the dustbin of time? One possible reason, suggested by studies of rapid visual categorization, is that some objects are recognized more quickly and easily than others and thus are less culturally specific in terms of pictorial representation. A second, related, explanation is that many artistic techniques use the eyes as a channel to evoke other senses, cognition, emotions and the motor system. 'Art' is a social and historical construct - after all, the concept of 'fine art' was invented in the 18th century - and thus many aspects of artistic appreciation are specific to particular cultural and historical contexts. Some great works, however, may be adopted by successive generations because of an ability to appeal to a shared perceptual system.     

What makes us human? Answers from evolutionary anthropology

Today, scholars from numerous and highly diverse fields are not only addressing the question of what makes us human, but also seeking input from other disciplines to inform their answers to this fundamental issue. However, for the most part, evolutionary anthropologists are not particularly prominent in this discussion, or at least not acknowledged to be. Why is this the case? One reason may be that although evolutionary anthropologists are uniquely positioned to provide valuable insight on this subject, the responses from any one of us are likely to be as different as the research specializations and intellectual experiences that we bring to the table. Indeed, one would anticipate that a paleoanthropologist would not only have different views than a primatologist, geneticist, or behavioral ecologist, but from other paleoanthropologists as well. Yet if asked by a theologian, psychologist, or political scientist, and perhaps most importantly, by any curious person outside the walls of academia, do we have a response that most evolutionary anthropologists could agree on as reflecting our contributions to the understanding of being and becoming human? Our introductory textbooks usually begin with this fundamental question, yet seldom produce a concise answer. © 2012 Wiley Periodicals, Inc.     

How MAP kinase modules function as robust,yet adaptable,circuits

Genetic and biochemical studies have revealed that the diversity of cell types and developmental patterns evident within the animal kingdom is generated by a handful of conserved, core modules. Core biological modules must be robust, able to maintain functionality despite perturbations, and yet sufficiently adaptable for random mutations to generate phenotypic variation during evolution. Understanding how robust, adaptable modules have influenced the evolution of eukaryotes will inform both evolutionary and synthetic biology. One such system is the MAP kinase module, which consists of a 3-tiered kinase circuit configuration that has been evolutionarily conserved from yeast to man. MAP kinase signal transduction pathways are used across eukaryotic phyla to drive biological functions that are crucial for life. Here we ask the fundamental question, why do MAPK modules follow a conserved 3-tiered topology rather than some other number? Using computational simulations, we identify a fundamental 2-tiered circuit topology that can be readily reconfigured by feedback loops and scaffolds to generate diverse signal outputs. When this 2-kinase circuit is connected to proximal input kinases, a 3-tiered modular configuration is created that is both robust and adaptable, providing a biological circuit that can regulate multiple phenotypes and maintain functionality in an uncertain world. We propose that the 3-tiered signal transduction module has been conserved through positive selection, because it facilitated the generation of phenotypic variation during eukaryotic evolution.     

The ageing surgeon

Why do some surgeons retire (or not), and perhaps more importantly, when should some surgeons retire? Interviews were conducted with 21 senior plastic surgeons to determine why plastic surgeons choose not to retire. In an effort to answer the second question (When should surgeons retire?), an analogy is constructed between surgeons and commercial airline pilots.     

Cracking the folding code. Why do some proteins adopt partially folded conformations, whereas other don't?

Many, but not all, globular proteins have been shown to have compact intermediate state(s) under equilibrium conditions in vitro, giving rise to the question: why do some proteins adopt partially folded conformations, whereas other do not? Here we show that charge to hydrophobicity ratio of a polypeptide chain may represent a key determinant in this respect, as proteins known to form equilibrium partially folded intermediates are specifically localized within a unique region of charge-hydrophobicity space. Thus, the competence of a protein to form equilibrium intermediate(s) may be determined by the bulk content of hydrophobic and charged amino acid residues rather than by the positioning of amino acids within the sequence.     

Behavioral Epiphenomena Revisited: Reply to Skok and Škorjanc

In a recent article in this journal, Ethology, 2014 present arguments as to why fighting in piglets during suckling may not be an epiphenomenon as we had previously suggested Ethology, 119, 2013, 353 and provide several alternative explanations. Although the new information Skok and ?korjanc bring to this debate is carefully considered and important, I argue here that it is not sufficient to counter our original claim that fighting among piglets (and kittens) during suckling may be an epiphenomenon, a largely inconsequential by‐product, of developmental processes anticipating the use of these behaviors and associated anatomical structures in later functional contexts. However, the points Skok and ?korjanc raise contribute importantly to identifying areas where further information and experimental work are needed to resolve this and related behavioral issues. I therefore conclude that this debate, independent of any particular final outcome, constructively points to the general difficulty and need for caution in interpreting behavior in seemingly ‘obvious’ functional terms, and particularly during development.     

"Unpredictablity of the quantum world" and logical catastrophe

The fundamental gnoseological question that is always present in a basic science is: Can this science adequately predict the future? In classical mechanics, we deal in many cases with dynamic chaos; therefore, this prediction is most often impossible. In the quantum theory, the dynamic chaos associated with the disturbances of initial conditions is formally absent. Nevertheless, as it was shown in this work, there are other reasons that directly relate to what is called the paradoxes of formal logic, which, in the case of quantum theory, too, do not enable one to precisely determine what will happen in the future.     

Bacteria as a new model system for aging studies: investigations using light microscopy

Aging-the decline in an individual's condition over time-is at the center of an active research field in medicine and biology. Some very basic questions have, however, remained unresolved, the most fundamental being: do all organisms age? Or are there organisms that would continue to live forever if not killed by external forces? For a long time it was believed that aging only affected organisms such as animals, plants, and fungi. Bacteria, in contrast, were assumed to be potentially immortal and until recently this assertion remained untested. We used phase-contrast microscopy (on an Olympus BX61) to follow individual bacterial cells over many divisions to prove that some bacteria show a distinction between an aging mother cell and a rejuvenated daughter, and that these bacteria thus age. This indicates that aging is a more fundamental property of organisms than was previously assumed. Bacteria can now be used as very simple model system for investigating why and how organisms age.     

On the Explanatory Roles of Natural Selection

Can selection explain why individuals have the traits they do? This question has generated significant controversy. I will argue that the debate encompasses two separable aspects, to detrimental effect: (1) the role of selection in explaining the origin and evolution of biological traits and (2) the implications this may have for explaining why individuals have the traits they do. (1) can be settled on the basis of evolutionary theory while (2) requires additional, extra-scientific assumptions. By making a distinction between traits affected by a single factor and traits affected by multiple factors I show that selection can, under certain conditions, help explain the origin of traits. Resolving the first aspect enables us to critically assess the various incompatible and independent philosophical commitments made within the second aspect of the debate.     

On beginning with justice: Bioethics,advocacy and the rights of asylum seekers

The situation around the seeking of refuge, both in Australia and abroad, has become a core human rights issue of our time, engendering protest and activism from the public, researchers, healthcare professionals and academics. The question remains: do bioethicists have duties to advocate on behalf of such populations, and if so, why? I argue that if our work is founded upon the principle of justice, then we do have such duties, and that our research, in itself, can become a form of advocacy.     

Homeostasis of eye growth and the question of myopia

As with other organs, the eye's growth is regulated by homeostatic control mechanisms. Unlike other organs, the eye relies on vision as a principal input to guide growth. In this review, we consider several implications of this visual guidance. First, we compare the regulation of eye growth to that of other organs. Second, we ask how the visual system derives signals that distinguish the blur of an eye too large from one too small. Third, we ask what cascade of chemical signals constitutes this growth control system. Finally, if the match between the length and optics of the eye is under homeostatic control, why do children so commonly develop myopia, and why does the myopia not limit itself? Long-neglected studies may provide an answer to this last question.     

Implications of clonality for ageing research

Senescence, an organismal performance decline with age, has historically been considered a universal phenomenon by evolutionary biologists and zoologist. Yet, increasing fertility and survival with age are nothing new to plant ecologists, among whom it is common knowledge that senescence is not universal. Recently, these two realities have come into a confrontation, begging for the rephrasing of the classical question that has led ageing research for decades: “why do we senesce?” to a more practical “what are the mechanisms by which some organisms escape from senescence?” Plants are amenable to examining this question because of their rich repertoire of life history strategies. These include the existence of permanent seed banks, vegetative dormancy and ability to produce clones, among others. Here, I use a large number of high resolution demographic models from 181 species that reflect life history strategies and their trade-offs among herbaceous perennials, succulents and shrubs measured under field conditions worldwide to examine whether senescence rates of ramets from clonal plants differ from those of whole plants reproducing either strictly sexually, or with a combination of sexual and clonal mechanisms. Contrary to the initial expectation from the mutation accumulation theory of senescence, ramets of clonal plants were more likely to exhibit senescence than those species employing sexual reproduction. I discuss why these comparisons between ramets and genets are useful, as well as its implications and future directions for ageing research.     

Infinite populations and counterfactual frequencies in evolutionary theory

One finds intertwined with ideas at the core of evolutionary theory claims about frequencies in counterfactual and infinitely large populations of organisms, as well as in sets of populations of organisms. One also finds claims about frequencies in counterfactual and infinitely large populations--of events--at the core of an answer to a question concerning the foundations of evolutionary theory. The question is this: to what do the numerical probabilities found throughout evolutionary theory correspond? The answer in question says that evolutionary probabilities are 'hypothetical frequencies' (including what are sometimes called 'long-run frequencies' and 'long-run propensities'). In this paper, I review two arguments against hypothetical frequencies. The arguments have implications for the interpretation of evolutionary probabilities, but more importantly, they seem to raise problems for biologists' claims about frequencies in counterfactual or infinite populations of organisms and sets of populations of organisms. I argue that when properly understood, claims about frequencies in large and infinite populations of organisms and sets of populations are not threatened by the arguments. Seeing why gives us a clearer understanding of the nature of counterfactual and infinite population claims and probability in evolutionary theory.     

Lipid imbalance in the neurological disorder, Niemann-Pick C disease

Niemann-Pick C (NPC) disease is a progressive neurological disorder in which cholesterol, gangliosides and bis-monoacylglycerol phosphate accumulate in late endosomes/lysosomes. This disease is caused by mutations in either the NPC1 or NPC2 gene. NPC1 and NPC2 are involved in egress of lipids, particularly cholesterol, from late endosomes/lysosomes but the precise functions of these proteins are not clear. An important question regarding the function of NPC proteins is: why do mutations in these ubiquitously expressed proteins have such dire consequences in the brain? This review summarizes the roles of NPC proteins in lipid homeostasis particularly in the central nervous system.