True handedness in the cotton-top tamarin (Saguinus oedipus)?

Hand use for 8 activities was studied in 20 captive cotton-top tamarins (Saguinus oedipus). The purpose of the study was to discover if hand preferences existed across tasks and across subjects, and, if so, whether these followed the patterns of preference inMacNeilage et al.'s (1987) “postural origins” theory of the evolution of hand preference and hemispheric specialization in primates. This theory suggests that, for haplorines, the right hand is used preferentially for manipulative acts while the left hand is used preferentially for visually guided acts. The study showed statistically significant right hand preferences for six of the seven actions which produced sufficient data to be tested. The strength and consistency of this preference makes this study the first to suggest true handedness in a non-human primate species. Deviations from the pattern were seen in scratching and other actions when performed in a vertical posture, but these deviations took the form of a weakening of the right hand preference rather than a reversal. The findings of the study may be seen as supportingMacNeilage et al.'s (1987) theoryonly if the actions studied are all considered to be manipulative, which can be argued to be the case, though some of the actions were also visually guided.     

Sphingosine-1-phosphate as a mediator involved in development of fibrotic diseases

Fibrosis is a pathological process characterized by massive deposition of extracellular matrix (ECM) such as type I/III collagens and fibronectin that are secreted by an expanded pool of myofibroblasts, which are phenotypically altered fibroblasts with more contractile, proliferative, migratory and secretory activities. Fibrosis occurs in various organs including the lung, heart, liver and kidney, resulting in loss of normal tissue architecture and functions. Myofibroblasts could originate from multiple sources including tissue-resident fibroblasts, epithelial and endothelial cells through mechanisms of epithelial/endothelial-mesenchymal transition (EMT/EndMT), and bone marrow-derived circulating progenitors called fibrocytes. Emerging evidence in recent years shows that sphingosine-1-phosphate (S1P) acts on several types of target cells and is engaged in pro-fibrotic inflammatory process and fibrogenic process through multiple mechanisms, which include vascular permeability change, leukocyte infiltration, and migration, proliferation and myofibroblast differentiation of fibroblasts. Many of these S1P actions are receptor subtype-specific. In these actions, S1P has multiple cross-talks with other cytokines, particularly transforming growth factor-β (TGFβ), which plays a major role in fibrosis. The cross-talks include the regulation of S1P production through altered expression and activity of sphingosine kinases in fibrotic lesions, altered expression of S1P receptors, and S1P receptor-mediated transactivation of TGFβ signaling pathway. These cross-talks may give rise to a feed-forward, amplifying loop between S1P and TGFβ, and possibly with other cytokines in stimulating fibrogenesis. Another lysophospholipid mediator lysophosphatidic acid has also been recently implicated in fibrosis. The lysophospholipid signaling pathways represent novel, promising therapeutic targets for treating refractory fibrotic diseases. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.     

Non-opioid actions of opioid peptides

Beside the well known actions of opioid peptides on mu-, delta- and kappa-opioid receptors, increasing amount of pharmacological and biochemical evidence has recently been published about non-opioid actions of various opioid peptides. These effects are not abolished by naloxone treatments. Such non-opioid effects are observed both in nervous tissues and in the cellular elements of the immune system. Peptides exhibiting non-opioid effects include beta-endorphin, dynorphin A, nociceptin/OFQ, endomorphins, hemorphins and a number of Proenkephalin A derived peptides, such as Met-enkephalin, Met-enkephalin-Arg-Phe (MERF) and bovine adrenal medullary peptide (BAM22). Non-opioid actions are exerted through different neuronal receptors, e.g., dynorphin hyperalgesia through NMDA receptor, Met-enkephalin induced regulation of cell growth through zeta receptors, pain modulation by nociceptin through ORL-1 or NOP receptors, while BAM22 acts through sensory neuron specific G protein-coupled receptors (SNSR). We have investigated Met-enkephalin-Arg-Phe (MERF) and its analogues by the means of direct and indirect radioligand binding assays. It has been found that in addition to kappa(2) and delta-opioid receptors, MERF can act also through sigma(2)- or probably via FMRF-NH(2) receptors in rat cerebellum. A role of functionally assembling heterodimer receptors in mediating the non-conventional actions of these peptide ligands can not be excluded as well.     

Neurotrophic factors and neurologic disease.

Discovered only 40 years ago, nerve growth factor is the prototypic neurotrophic factor. By binding to specific receptors on certain neurons in the peripheral nervous system and brain, nerve growth factor acts to enhance their survival, differentiation, and maintenance. In recent years, many additional neurotrophic factors have been discovered; some are structurally related to nerve growth factor while others are distinct from it. The robust actions of neurotrophic factors have suggested their use in preventing or lessening the dysfunction and death of neurons in neurologic disorders. We review the progress in defining neurotrophic factors and their receptors and in characterizing their actions. We also discuss some of the uses of neurotrophic factors in animal models of disease. Finally, we discuss how neurotrophic factors could be implicated in the pathogenesis of neurologic disorders.     

GLP-1 and extra-islet effects.

The main target of action of glucagon-like peptide-1 (GLP-1) is the islet, where the hormone stimulates insulin secretion, promotes beta cell proliferation and neogenesis, and inhibits glucagon secretion. However, GLP-1 receptors are also expressed outside the islets, increasing the likelihood that GLP-1 also plays a role in other organs. These functions are mainly the inhibition of gastric emptying, gastric acid secretion and exocrine pancreatic secretion, indicating that the hormone acts as an enterogastrone--a hormone released from the distal portion of the small intestine that inhibits proximal gastrointestinal events. Another important action of GLP-1 is to induce satiety. Other effects of the hormone include cardioprotection, neuroprotection, induction of learning and memory, stimulation of afferent, sensory nerves, stimulation of surfactant production in the lung, dilatation of pulmonary vessels, induction of diuresis, and also under some conditions, induction of antidiabetic actions unrelated to islet function. Thus, GLP-1 clearly has several manifestations of activity. The physiological relevance of these actions and their contribution to the overall antidiabetic action of GLP-1 when used in treatment of type 2 diabetes remains to be established.     

Developmental effects of ghrelin

Ghrelin is a pleiotropic hormone that was originally described as promoting feeding and stimulating growth hormone release in adults. A growing body of evidence suggests that ghrelin may also exert developmental and organizational effects during perinatal life. The perinatal actions of ghrelin include the regulation of early developmental events such as blastocyst development and perinatal growth. Moreover, alterations in perinatal ghrelin levels result in structural differences in various peripheral organs, such as the pancreas and gastrointestinal tract. Recent data have also suggested that ghrelin acts on appetite-related brain centers in early life. Together, these observations indicate that exposure to factors that alter how ghrelin impacts development may induce lasting effects on physiological regulation.     

The evolution of costly displays,cooperation and religion: credibility enhancing displays and their implications for cultural evolution

This paper lays out an evolutionary theory for the cognitive foundations and cultural emergence of the extravagant displays (e.g., ritual mutilation, animal sacrifice and martyrdom) that have so tantalized social scientists, as well as more mundane actions that influence cultural learning and historical processes. In Part I, I use the logic of natural selection to build a theory for how and why seemingly costly displays influence the cognitive processes associated with cultural learning — why do “actions speak louder than words?” The core idea is that cultural learners can both avoid being manipulated by their models (those they are inclined to learn from) and more accurately assess their belief commitment by attending to displays or actions by the model that would seem costly to the model if he held beliefs different from those he expresses verbally. Part II examines the implications for cultural evolution of this learning bias in a simple evolutionary model. The model reveals the conditions under which this evolved bias can create stable sets of interlocking beliefs and practices, including quite costly practices. Part III explores how cultural evolution, driven by competition among groups or institutions stabilized at alternative sets of these interlocking belief-practice combinations, has led to the association of costly acts, often in the form of rituals, with deeper commitments to group beneficial ideologies, higher levels of cooperation within groups, and greater success in competition with other groups or institutions. I close by discussing the broader implications of these ideas for understanding various aspects of religious phenomena.     

A continuous-time neural model for sequential action

Action selection, planning and execution are continuous processes that evolve over time, responding to perceptual feedback as well as evolving top-down constraints. Existing models of routine sequential action (e.g. coffee- or pancake-making) generally fall into one of two classes: hierarchical models that include hand-built task representations, or heterarchical models that must learn to represent hierarchy via temporal context, but thus far lack goal-orientedness. We present a biologically motivated model of the latter class that, because it is situated in the Leabra neural architecture, affords an opportunity to include both unsupervised and goal-directed learning mechanisms. Moreover, we embed this neurocomputational model in the theoretical framework of the theory of event coding (TEC), which posits that actions and perceptions share a common representation with bidirectional associations between the two. Thus, in this view, not only does perception select actions (along with task context), but actions are also used to generate perceptions (i.e. intended effects). We propose a neural model that implements TEC to carry out sequential action control in hierarchically structured tasks such as coffee-making. Unlike traditional feedforward discrete-time neural network models, which use static percepts to generate static outputs, our biological model accepts continuous-time inputs and likewise generates non-stationary outputs, making short-timescale dynamic predictions.     

The mirror mechanism: recent findings and perspectives

Mirror neurons are a specific type of visuomotor neuron that discharge both when a monkey executes a motor act and when it observes a similar motor act performed by another individual. In this article, we review first the basic properties of these neurons. We then describe visual features recently investigated which indicate that, besides encoding the goal of motor acts, mirror neurons are modulated by location in space of the observed motor acts, by the perspective from which the others’ motor acts are seen, and by the value associated with the object on which others’ motor acts are performed. In the last part of this article, we discuss the role of the mirror mechanism in planning actions and in understanding the intention underlying the others’ motor acts. We also review some human studies suggesting that motor intention in humans may rely, as in the monkey, on the mirror mechanism.     

Mathematical models in genetics

In this study, we present some of the basic ideas of population genetics. The founders of population genetics are R.A. Fisher, S. Wright, and J. B.S. Haldane. They, not only developed almost all the basic theory associated with genetics, but they also initiated multiple experiments in support of their theories. One of the first significant insights, which are a result of the Hardy–Weinberg law, is Mendelian inheritance preserves genetic variation on which the natural selection acts. We will limit to simple models formulated in terms of differential equations. Some of those differential equations are nonlinear and thus emphasize issues such as the stability of the fixed points and time scales on which those equations operate. First, we consider the classic case when selection acts on diploid locus at which wу can get arbitrary number of alleles. Then, we consider summaries that include recombination and selection at multiple loci. Also, we discuss the evolution of quantitative traits. In this case, the theory is formulated in respect of directly measurable quantities. Special cases of this theory have been successfully used for many decades in plants and animals breeding.     

Polycomb complexes and silencing mechanisms

Advances in the past couple of years have brought important new knowledge on the mechanisms by which Polycomb-group proteins regulate gene expression and on the consequences of their actions. The discovery of histone methylation imprints specific for Polycomb and Trithorax complexes has provided mechanistic insight on how this ancient epigenetic memory system acts to repress and indicates that it may share mechanistic aspects with other silencing and genome-protective processes, such as RNA interference.     

The biology of interferon actions

The interferons comprise a group of proteins which were first identified by their ability to protect cells against virus infections. They are synthesized and secreted by a variety of cell types in response to various inducers and exert their effects in vivo by interaction with specific cellular receptors. In this sense the interferons are analogous to polypeptide hormones. In recent years it has become clear that the interferons are capable of influencing cellular physiology and behavior in a number of ways. Their effects include antiviral actions, inhibition of cell growth and proliferation, regulation of the expression of specific genes, modulation of cell differentiation and activation of various cell types in the immune system. This review aims to summarize the current state of biology of interferon actions with special emphasis on the hemopoetic system.     

Getting back to the rough ground: deception and 'social living'

At the heart of the social intelligence hypothesis is the central role of 'social living'. But living is messy and psychologists generally seek to avoid this mess in the interests of getting clean data and cleaner logical explanations. The study of deception as intelligent action is a good example of the dangers of such avoidance. We still do not have a full picture of the development of deceptive actions in human infants and toddlers or an explanation of why it emerges. This paper applies Byrne & Whiten's functional taxonomy of tactical deception to the social behaviour of human infants and toddlers using data from three previous studies. The data include a variety of acts, such as teasing, pretending, distracting and concealing, which are not typically considered in relation to human deception. This functional analysis shows the onset of non-verbal deceptive acts to be surprisingly early. Infants and toddlers seem to be able to communicate false information (about themselves, about shared meanings and about events) as early as true information. It is argued that the development of deception must be a fundamentally social and communicative process and that if we are to understand why deception emerges at all, the scientist needs to get 'back to the rough ground' as Wittgenstein called it and explore the messy social lives in which it develops.     

Human Sensorimotor Communication: A Theory of Signaling in Online Social Interactions

Although the importance of communication is recognized in several disciplines, it is rarely studied in the context of online social interactions and joint actions. During online joint actions, language and gesture are often insufficient and humans typically use non-verbal, sensorimotor forms of communication to send coordination signals. For example, when playing volleyball, an athlete can exaggerate her movements to signal her intentions to her teammates (say, a pass to the right) or to feint an adversary. Similarly, a person who is transporting a table together with a co-actor can push the table in a certain direction to signal where and when he intends to place it. Other examples of “signaling” are over-articulating in noisy environments and over-emphasizing vowels in child-directed speech. In all these examples, humans intentionally modify their action kinematics to make their goals easier to disambiguate. At the moment no formal theory exists of these forms of sensorimotor communication and signaling. We present one such theory that describes signaling as a combination of a pragmatic and a communicative action, and explains how it simplifies coordination in online social interactions. We cast signaling within a “joint action optimization” framework in which co-actors optimize the success of their interaction and joint goals rather than only their part of the joint action. The decision of whether and how much to signal requires solving a trade-off between the costs of modifying one’s behavior and the benefits in terms of interaction success. Signaling is thus an intentional strategy that supports social interactions; it acts in concert with automatic mechanisms of resonance, prediction, and imitation, especially when the context makes actions and intentions ambiguous and difficult to read. Our theory suggests that communication dynamics should be studied within theories of coordination and interaction rather than only in terms of the maximization of information transmission.     

The "cryptic" mechanism of action of glucagon-like peptide-2

Glucagon-like peptide-2 (GLP-2) is a peptide hormone with multiple beneficial effects on the intestine, including expansion of the mucosal surface area through stimulation of crypt cell proliferation, as well as enhancement of nutrient digestion and absorption. Recent advances in clinical trials involving GLP-2 necessitate elucidation of the exact signaling pathways by which GLP-2 acts. In particular, the GLP-2 receptor has been localized to several intestinal cell types that do not include the proliferating crypt cells, and the actions of GLP-2 have thus been linked to a complex network of indirect mediators that induce diverse signaling pathways. The intestinotropic actions of GLP-2 on the colon have been shown to be mediated through the actions of keratinocyte growth factor and insulin-like growth factor (IGF)-2, whereas small intestinal growth has been linked to IGF-1, IGF-2, and ErbB ligands, as well as the IGF-1 receptor and ErbB. The cellular source of these mediators remains unclear, but it likely includes the intestinal subepithelial myofibroblasts. Conversely, the anti-inflammatory and blood flow effects of GLP-2 are dependent on vasoactive intestinal polypeptide released from submucosal enteric neurons and nitric oxide, respectively. Finally, recent studies have suggested that GLP-2 not only modulates intestinal stem cell behavior but may also promote carcinogenesis in models of sporadic colon cancer. Further consideration of the molecular cross-talk and downstream signaling pathways mediating the intestinotropic effects of GLP-2 is clearly warranted.     

What are you doing? How active and observational experience shape infants' action understanding

From early in life, infants watch other people''s actions. How do young infants come to make sense of actions they observe? Here, we review empirical findings on the development of action understanding in infancy. Based on this review, we argue that active action experience is crucial for infants'' developing action understanding. When infants execute actions, they form associations between motor acts and the sensory consequences of these acts. When infants subsequently observe these actions in others, they can use their motor system to predict the outcome of the ongoing actions. Also, infants come to an understanding of others’ actions through the repeated observation of actions and the effects associated with them. In their daily lives, infants have plenty of opportunities to form associations between observed events and learn about statistical regularities of others’ behaviours. We argue that based on these two forms of experience—active action experience and observational experience—infants gradually develop more complex action understanding capabilities.     

Is Chordin a morphogen?

Models employing gradients of diffusible morphogens are often invoked to explain regional specification in the early embryo. In these models, a concentration gradient of a secreted factor generates distinct cell fates, based on the differential response of cells to local concentrations of this morphogen. In recent years, there has been a great deal of focus on the factors involved in the dorsoventral patterning of the vertebrate mesoderm and ectoderm. Dorsoventral specification during amphibian gastrulation is regulated by the antagonistic actions of the Bone Morphogenetic Proteins (BMPs) and a number of dorsally expressed inhibitors, including the secreted factor, Chordin. In a recent paper, Blitz and colleagues explore the possibility that Chordin acts as a long-range factor in the amphibian gastrula embryo, to establish a functional gradient of BMP activity.     

The action of FMRFamide (Phe-Met-Arg-Phe-NH2) and related peptides on mammals

First purified 11 years ago from clam ganglia, FMRFamide (Phe-Met-Arg-Phe-NH2) was quickly demonstrated to be cardioactive in several molluscan species. Subsequent discovery that FMRFamide, or FMRFamide-related peptides (FaRPs), were present in mammalian central nervous system and gastrointestinal tract prompted investigations into the effect of FMRFamide on mammals. FMRFamide has now been shown to be cardioexcitatory in mammals, to inhibit morphine-induced antinociception, and to block morphine-, defeat-, and deprivation-induced feeding. It also inhibits colonic propulsive motility, induces behavioral effects when administered intrathecally, and has been reported to have amnesic effects in rodents. A proposal has arisen that a FMRFamide-like substance is an endogenous opioid antagonist and has stimulated a search for such a substance. However, FMRFamide has only weak affinity for opioid receptors and not all the actions of FMRFamide appear to be explained by actions at opioid receptors. Alternative mechanisms have been proposed which suggest that FMRFamide acts as a neuromodulator.