Acidity, generated in hypoxia or hypermetabolic states, perturbs homeostasis and is a feature of solid tumors. That acid peripherally disperses lysosomes is a three‐decade‐old observation, yet one little understood or appreciated. However, recent work has recognized the inhibitory impact this spatial redistribution has on mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of metabolism. This finding argues for a paradigm shift in localization of mTORC1 activator Ras homolog enriched in brain (RHEB), a conclusion several others have now independently (...) reached. Thus, mTORC1, known to sense amino acids, mitogens, and energy to restrict biosynthesis to times of adequate resources, also senses pH and, via dampened mTOR‐governed synthesis of clock proteins, regulates the circadian clock to achieve concerted responses to metabolic stress. While this may allow cancer to endure metabolic deprivation, immune cell mTOR signaling likewise exhibits pH sensitivity, suggesting that suppression of antitumor immune function by solid tumor acidity may additionally fuel cancers, an obstacle potentially reversible through therapeutic pH manipulation. (shrink)

Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro‐environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin (...) complex 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. (shrink)

The Liver kinase B1 with its downstream target AMP activated protein kinase (LKB1‐AMPK), and the key nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) form two signaling systems that coordinate metabolic and cellular activity with changes in the environment in order to preserve homeostasis. For example, nutritional fluctuations rapidly feed back on these signaling systems and thereby affect cell‐specific functions. Recent studies have started to reveal important roles of these strategic metabolic regulators in Schwann cells for the (...) trophic support and myelination of axons. Because aberrant intermediate metabolism along with mitochondrial dysfunction in Schwann cells is mechanistically linked to nerve abnormalities found in acquired and inherited peripheral neuropathies, manipulation of the LKB1‐AMPK, and mTORC1 signaling hubs may be a worthwhile therapeutic target to mitigate nerve damage in disease. Here, recent advances in our understanding of LKB1‐AMPK and mTORC1 functions in Schwann cells are covered, and future research areas for this key metabolic signaling network are proposed. (shrink)

Dormancy or hibernation is a non‐proliferative state of cells with low metabolic activity and gene expression. Dormant cells sequester ribosomes in a translationally inactive state, called dormant/hibernating ribosomes. These dormant ribosomes are important for the preservation of ribosomes and translation shut‐off. While recent studies attempted to elucidate their modes of formation, the regulation and roles of the diverse dormant ribosomal populations are still largely understudied. The mechanistic details of the formation of dormant ribosomes in stress and especially their disassembly during (...) recovery remain elusive. In this review, we discuss the roles of dormant ribosomes and their potential regulatory mechanisms. Furthermore, we highlight the paradigms that need to be answered in the field of ribosomal dormancy. (shrink)

Recent studies support a model in which the progeny of SOX9+ epithelial progenitors at the distal tip of lung branches undergo cell allocation and differentiation sequentially along the distal‐to‐proximal axis. Concomitant with the elongation and ramification of lung branches, the descendants of the distal SOX9+ progenitors are distributed proximally, express SOX2, and differentiate into cell types in the conducting airways. Amid subsequent sacculation, the distal SOX9+ progenitors generate alveolar epithelial cells to form alveoli. Sequential cell allocation and differentiation are integrated (...) with the branching process to generate a functional branching organ. This review focuses on the roles of SOX9+ cells as precursors for new branches, as the source of various cell types in the conducting airways, and as progenitors of the alveolar epithelium. All of these processes are controlled by multiple signaling pathways. Many mouse mutants with defective lung branching contain underlying defects in one or more steps of cell allocation and differentiation of SOX9+ progenitors. This model provides a framework to understand the molecular basis of lung phenotypes and to elucidate the molecular mechanisms of lung patterning. It builds a foundation on which comparing and contrasting the mechanisms employed by different branching organs in diverse species can be made. (shrink)

The KCTD family includes tetramerization (T1) domain containing proteins with diverse biological effects. We identified a novel member of the KCTD family, BTBD10. A comprehensive analysis of protein‐protein interactions (PPIs) allowed us to put forth a number of testable hypotheses concerning the biological functions for individual KCTD proteins. In particular, we predict that KCTD20 participates in the AKT‐mTOR‐p70 S6k signaling cascade, KCTD5 plays a role in cytokinesis in a NEK6 and ch‐TOG‐dependent manner, KCTD10 regulates the RhoA/RhoB pathway. Developmental (...) regulator KCTD15 represses AP‐2α and contributes to energy homeostasis by suppressing early adipogenesis. TNFAIP1‐like KCTD proteins may participate in post‐replication DNA repair through PCNA ubiquitination. KCTD12 may suppress the proliferation of gastrointestinal cells through interference with GABAb signaling. KCTD9 deserves experimental attention as the only eukaryotic protein with a DNA‐like pentapeptide repeat domain. The value of manual curation of PPIs and analysis of existing high‐throughput data should not be underestimated. (shrink)

One might think that if the majority of virtue signallers judge that a proposition is true, then there is significant evidence for the truth of that proposition. Given the Condorcet Jury Theorem, individual virtue signallers need not be very reliable for the majority judgment to be very likely to be correct. Thus, even people who are skeptical of the judgments of individual virtue signallers should think that if a majority of them judge that a proposition is true, then that provides (...) significant evidence that the proposition is true. We argue that this is mistaken. Various empirical studies converge on the following point: humans are very conformist in the contexts in which virtue signalling occurs. And stereotypical virtue signallers are even more conformist in such contexts. So we should be skeptical of the claim that virtue signallers are sufficiently independent for the Condorcet Jury Theorem to apply. We do not seek to decisively rule out the relevant application of the Condorcet Jury Theorem. But we do show that careful consideration of the available evidence should make us very skeptical of that application. Consequently, a defense of virtue signalling would need to engage with these findings and show that despite our strong tendencies for conformism, our judgements are sufficiently independent for the Condorcet Jury Theorem to apply. This suggests new directions for the debate about the epistemology of virtue signalling. (shrink)

The accusation of virtue signalling is typically understood as a serious charge. Those accused usually respond by attempting to show that they are doing no such thing. In this paper, I argue that we ought to embrace the charge, rather than angrily reject it. I argue that this response can draw support from cognitive science, on the one hand, and from social epistemology on the other. I claim that we may appropriately concede that what we are doing is virtue signalling, (...) because virtue signalling is morally appropriate. It neither expresses vices, nor is hypocritical, nor does it degrade the quality of public moral discourse. Signalling our commitment to norms is a central and justifiable function of moral discourse, and the same signals provide evidence that is appropriately taken into account in forming moral beliefs. (shrink)

Why do well‐functioning psychological systems sometimes give rise to absurd beliefs that are radically misaligned with reality? Drawing on signalling theory, I develop and explore the hypothesis that groups often embrace beliefs that are viewed as absurd by outsiders as a means of signalling ingroup commitment. I clarify the game‐theoretic and psychological underpinnings of this hypothesis, I contrast it with similar proposals about the signalling functions of beliefs, and I motivate several psychological and sociological predictions that could be used to (...) distinguish it from alternative explanations of irrational group beliefs. (shrink)

In this paper I will discuss why (un) marked expressionstypically get an (un)marked interpretation: Horn''sdivision of pragmatic labor. It is argued that it is aconventional fact that we use language this way.This convention will be explained in terms ofthe equilibria of signalling games introduced byLewis (1969), but now in an evolutionary setting. Iwill also relate this signalling game analysis withParikh''s (1991, 2000, 2001) game-theoretical analysis ofsuccessful communication, which in turn is compared withBlutner''s: 2000) bi-directional optimality theory.

Hedgehog is an important morphogenic signal that directs pattern formation during embryogenesis, but its activity also remains present through adult life. It is now becoming increasingly clear that during the reproductive phase of life and beyond it continues to direct cell renewal (which is essential to combat the chronic environmental stress to which the body is constantly exposed) and counteracts vascular, osteolytic and sometimes oncological insults to the body. Conversely, down‐regulation of hedgehog signalling is associated with ageing‐related diseases such as (...) type 2 diabetes, neurodegeneration, atherosclerosis and osteoporosis. Hence, in this essay we argue that hedgehog signalling is not only important at the start of life, but also constitutes an important anti‐geriatric influence, and that enhanced understanding of its properties may contribute to developing rational strategies for healthy ageing and prevention of ageing‐related diseases.Also watch the Video Abstract. (shrink)

Skyrms, building on the work of Dretske, has recently developed a novel information-theoretic account of propositional content in simple signalling systems. Information-theoretic accounts of content traditionally struggle to accommodate the possibility of misrepresentation, and I show that Skyrms’s account is no exception. I proceed to argue, however, that a modified version of Skyrms’s account can overcome this problem. On my proposed account, the propositional content of a signal is determined not by the information that it actually carries, but by the (...) information that it would carry at the nearest separating equilibrium of the underlying evolutionary dynamics. I show that this amended account yields reasonable ascriptions of false propositional content in a well-known formal model of the evolution of communication , and close with a discussion of the serious but perhaps not insuperable difficulties we face in applying the account to examples of signalling in the real world. (shrink)

ABSTRACT Justin Tosi and Brandon Warmke argue that virtue signalling – saying things in order to improve or protect your moral reputation – has a range of bad consequences and that as such there is a strong moral presumption against engaging in it. I argue that virtue signalling also has a range of good consequences, and that as such there is no default presumption either for or against engaging in it. Following from this, I argue that given that virtue signalling (...) is sometimes bad and sometimes good, we should avoid virtue signalling when we can be confident that the consequences will be bad, and we should press on with signalling when we can be confident that the consequences will be good. For the most part, I focus on three good consequences that are related to trusting dispositions: signalling trustworthiness, avoiding distrust, and scaffolding self-trust. I also highlight some additional positive consequences that are unrelated to trust. (shrink)

This paper discusses the evidence for the role of CREB in neural stem/progenitor cell (NSPC) function and oncogenesis and how these functions may be important for the development and growth of brain tumours. The cyclic‐AMP response element binding (CREB) protein has many roles in neurons, ranging from neuronal survival to higher order brain functions such as memory and drug addiction behaviours. Recent studies have revealed that CREB also has a role in NSPC survival, differentiation and proliferation. Recent work has shown (...) that over‐expression of CREB in transgenic animals can impart oncogenic properties on cells in various tissues and that aberrant CREB expression is associated with tumours in patients. It is the central position of CREB, downstream of key developmental and growth signalling pathways, which give CREB the ability to influence a spectrum of cell activities, such as cell survival, growth and differentiation in both normal and cancer cells. (shrink)

Communication involves a great deal of uncertainty. Prima facie, it is therefore surprising that biological communication systems—from cellular to human—exhibit a high degree of ambiguity and often leave its resolution to contextual cues. This puzzle deepens once we consider that contextual information may diverge between individuals. In the following we lay out a model of ambiguous communication in iterated interactions between subjectively rational agents lacking a common contextual prior. We argue ambiguity’s justification to lie in endowing interlocutors with means to (...) flexibly adapt language use to each other and the context of their interaction to serve their communicative preferences. Linguistic alignment is shown to play an important role in this process; it foments convergence of contextual expectations and thereby leads to agreeing use and interpretation of ambiguous messages. We conclude that ambiguity is ecologically rational when interlocutors’ contextual expectations are generally in line or they interact multiple times in an informative context, enabling for the alignment of their expectations. In light of these results meaning multiplicity can be understood as an opportunistic outcome enabled and shaped by linguistic adaptation and contextual information. 1Meaning Multiplicity in Communication 2Ambiguous Signalling through Pragmatic Inference 2.1Preliminaries 2.2Signalling behaviour 2.3Communicative success 2.4Iterated interactions 3Predictions for Single and Iterated Interactions 3.1Simulations 3.2Exploration and past experience 3.3Preemptive adaptation 4Discussion 5Conclusion Appendix. (shrink)

Two recent overviews of costly signalling theory—Maynard-Smith and Harper ( 2003 ) and Searcy and Nowicki ( 2005 )—both refuse to count signals kept honest by punishment of dishonesty, as costly signals, because (1) honest signals must be costly in cases of costly signalling, and (2) punishment of dishonesty itself requires explanation. I argue that both pairs of researchers are mistaken: (2) is not a reason to discount signals kept honest by punishment of dishonesty as cases of costly signalling, and (...) (1) betrays too narrow a focus on certain versions of costly signalling theory. In the course of so arguing, I propose a new schema for classifying signal costs, which suggests productive research questions for future conceptual and empirical work on costly signalling. (shrink)

A better understanding of how schistosomes exploit host nutrients, neuro‐endocrine hormones and signalling pathways for growth, development and maturation may provide new insights for improved interventions in the control of schistosomiasis. This paper describes recent advances in the identification and characterisation of schistosome tyrosine kinase and signalling pathways. It discusses the potential intervention value of insulin signalling, which may play an important role in glucose uptake and carbohydrate metabolism in schistosomes, providing the nutrients essential for parasite growth, development and, notably, (...) female fecundity. Significant progress has also been made in the characterisation of other schistosome growth factor receptors, such as transforming growth factor beta receptor and epidermal growth factor receptor, and in our understanding of their roles in the host‐parasite molecular dialogue and parasite development. The use of parasite signal transduction components as novel vaccine or drug targets may prove invaluable in prevention, treatment and control strategies to combat schistosomiasis. (shrink)

This paper develops a formal model of the subtle meaning differences that exist between grammatical alternatives in socially conditioned variation and how these variants can be used by speakers as resources for constructing personal linguistic styles. More specifically, this paper introduces a new formal system, called social meaning games, which allows for the unification of variationist sociolinguistics and game-theoretic pragmatics, two fields that have had very little interaction in the past. Although remarks have been made concerning the possible usefulness of (...) game-theoretic tools in the analysis of certain kinds of socially conditioned linguistic phenomena :645–668, 1977; Dror et al. in Lang Linguist Compass 7:561–579, 2013; in Lang Linguist Compass 8:230–242, 2014; Clark in Meaningful games: Exploring language with game theory, MIT Press, Cambridge, MA, 2014, among others), a general framework uniting game-theoretic pragmatics and quantitative sociolinguistics has yet to be developed. This paper constructs such a framework through giving a formalization of the Third Wave approach to the meaning of variation using signalling games and a probabilistic approach to speaker/listener beliefs of the kind commonly used in the Bayesian game-theoretic pragmatics framework :3–44, 2016, for recent overviews). (shrink)

Identification of the molecular mechanisms underlying axonal branching in vivo has begun in several neuronal systems, notably the projections formed by dorsal root ganglion (DRG) neurons or retinal ganglion cells (RGC). cGMP signalling is essential for sensory axon bifurcation at the spinal cord, whereas brain‐derived neurotrophic factor (BDNF) and ephrinA signalling establish position‐dependent branching of RGC axons. In the latter system, the degradation of specific signalling components, via the ubiquitin‐proteasome system, may provide an additional mechanism involved in axon branching of (...) RGC. The process of arborisation is essential for neurons to innervate multiple targets and to build topographic maps. The various forms of branching found in different types of neurons are regulated by distinct signalling pathways activated by multiple extracellular cues in addition to axonal guidance factors. These signalling cascades, together with transcriptional programs, most likely interact and trigger the polymerisation or depolymerisation of the actin and tubulin cytoskeleton to regulate branching. (shrink)

The importance of electrical signalling in bacteria is an emerging paradigm. Bacillus subtilis biofilms exhibit electrical communication that regulates metabolic activity and biofilm growth. Starving cells initiate oscillatory extracellular potassium signals that help even the distribution of nutrients within the biofilm and thus help regulate biofilm development. Quorum sensing also regulates biofilm growth and crucially there is convergence between electrical and quorum sensing signalling axes. This makes B. subtilis an interesting model for cell signalling research. SpoOF is predicted to act (...) as a logic gate for signalling pathway convergence, raising interesting questions about the functional nature of this gate and the relative importance of these disparate signals on biofilm behaviour. How is an oscillating signal integrated with a quorum signal? The model presented offers rich opportunities for future experimental and theoretical modelling research. The importance of direct cell‐to‐cell electrical signalling in prokaryotes, so characteristic of multicellular eukaryotes, is also discussed. (shrink)

Our understanding of communication and its evolution has advanced significantly through the study of simple models involving interacting senders and receivers of signals. Many theorists have thought that the resources of mathematical information theory are all that are needed to capture the meaning or content that is being communicated in these systems. However, the way theorists routinely talk about the models implicitly draws on a conception of content that is richer than bare informational content, especially in contexts where false content (...) is important. This article shows that this concept can be made precise by defining a notion of functional content that captures the degree to which different states of the world are involved in stabilizing senders’ and receivers’ use of a signal at equilibrium. A series of case studies is used to contrast functional content with informational content, and to illustrate the explanatory role and limitations of this definition of functional content. _1_ Introduction _2_ Modelling Framework _3_ Two Kinds of Content _3.1_ Informational content _3.2_ Functional content _4_ Cases _4.1_ Case 1: Simplest case _4.2_ Case 2: Partial pooling _4.3_ Case 3: Bottleneck _4.4_ Case 4: Partial common interest _4.5_ Case 5: Deception _4.6_ Case 6: A further problem arising from divergent interests _5_ Discussion Appendix. (shrink)

The Wnt signalling cascade is a highly conserved signalling pathway throughout the animal kingdom. In Xenopus, Wnt signalling functions in mesodermal dorsoventral patterning. Earlier work on deciphering the components of the wnt signalling cascade left a gap between cytosolic β‐catenin, the final member of the cascade, and the nuclear target genes. Several recent papers now reveal how the Wnt signal is transmitted into the nucleus. Surprisingly, β‐catenin directly interacts with the transcription factor LEF‐1/XTCF‐3, and thereby is not only translocated into (...) the nucleus but also modulates the properties of LEF‐1/XTCF‐3 as a transcription factor(1–5). (shrink)

Lewis signalling games are often used to explain how it is possible for simple agents to develop systems of conventional semantic meaning. In these games, all players obtain identical payoffs in every outcome. This is an unrealistic payoff structure, but it is often employed because it is thought that semantic meaning will not emerge if interests conflict. Here it is shown that not only is conventional meaning possible when interests conflict, but it is the most likely outcome in a finite (...) population model of learning known as the Moran process. On the basis of this result it is suggested that evolutionary game theory’s standard models may yield results that are systematically distorted for a class of signalling games that have the abstract structure of social dilemmas. 1 Introduction2 The Seduction Game3 Imitation Dynamics with Small Mutations4 Dynamics with Unverifiable Message5 Analysis of a Related Three-Strategy Game6 Conclusion. (shrink)

The Evolution of Animal Communication is a detailed examination of a wide variety of animal signalling systems. The main focus of the book is explaining how such signalling systems remain reliable when there is apparent evolutionary pressure to deceive. The principle strategy is to appeal to signal costs: signals remain reliable because the potential benefits of deceit are outweighed by the costs of producing the deceptive signal. In this review I show just how difficult this idea is to test, even (...) in the simplest cases. (shrink)

Wnt proteins are involved in a large number of events during development and disease. The crucial element in the transduction of the signal elicited by Wnt is the state and activity of β-catenin. There are two pools of β-catenin, one associated with cadherins at the cell surface and a soluble one in the cytolasm, whose state and concentration are critical for Wnt signalling. In the absence of Wnt, the cytoplasmic pool is low due to targetted degradation of β-catenin. Upon Wnt (...) signalling, β-catenin is stabilized. As a consequence, it can access the nucleus where it interacts with members of the Tcf family of transcription factors to modulate the expression of defined targets. Recent reports indicate that, in addition to Tcfs, β-catenin can interact with other nuclear proteins raising the possibility that Wnt signalling has a wider modulatory effect on transcription than is mediated by its interactions with Tcfs. BioEssays 23:311–318, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Our commentary summarises the current understanding of how testosterone can be used as a mechanism to link quality to external traits potentially used in sexual signalling, particularly female choice. Testosterone-dependent traits may reveal male's status to rivals and immunocompetence to females. We highlight some interesting unanswered questions and suggest that cross-disciplinary collaboration would help solve them.

The activity of Wnt and Notch signalling is central to many cell fate decisions during development and to the maintenance and differentiation of stem cell populations in homeostasis. While classical views refer to these pathways as independent signal transduction devices that co‐operate in different systems, recent work has revealed intricate connections between their components. These observations suggest that rather than operating as two separate pathways, elements of Wnt and Notch signalling configure an integrated molecular device whose main function is to (...) regulate transitions between cell states in development and homeostasis. Here, we propose a general framework for the structure and function of the interactions between these signalling systems that is focused on the notion of ‘transition states’, i.e. intermediates that arise during cell fate decision processes. These intermediates act as checkpoints in cell fate decision processes and are characterised by the mixed molecular identities of the states involved in these processes.Editor's suggested further reading in BioEssays: Notch: Implications of endogenous inhibitors for therapy Abstract. (shrink)

Bone morphogenetic proteins (BMPs) are typically members of the transforming growth factor β (TGF-β) family with diverse roles in embryonic development. At least five genes with homology to BMPs are expressed during Xenopus development, along with their receptors and intracellular signalling pathways. The evidence suggests that BMPs have roles to play in both mesoderm induction and dorsoventral patterning. Studies in Xenopus have also identified a number of inhibitory binding proteins for the classical BMPs, encoded by genes such as chordin and (...) noggin. These proteins appear to be responsible for establishing a morphogen gradient of BMP4 activity, which specifies different dorsoventral fates in early gastrulae. An emerging theme is that inhibition of BMP signalling is an important mechanism regulating cell fate decisions in early development. BioEssays 21:751–760, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Special relativity is said to prohibit faster-than-light (superluminal) signalling, yet controversy regularly arises as to whether this or that physical phenomenon violates the prohibition. I argue that the controversy is a result of a lack of clarity as to what it means to `signal', and I propose a criterion. I show that although we have no reason to think that one can send signals faster than light, this is not prohibited by special relativity.

The orderly sequence of events that constitutes the cell cycle is carefully regulated. A part of this regulation depends upon the ubiquitous calcium signalling system. Many growth factors utilize the messenger inositol trisphosphate (InsP3) to set up prolonged calcium signals, often organized in an oscillatory pattern. These repetitive calcium spikes require both the entry of external calcium and its release from internal stores. One function of this calcium signal is to activate the immediate early genes responsible for inducing resting cells (...) (G0) to re‐enter the cell cycle. It may also promote the initiation of DNA synthesis at the G1/S transition. Finally, calcium contributes to the completion of the cell cycle by stimulating events at mitosis. The role of calcium in cell proliferation is highlighted by the increasing number of anticancer therapies and immunosuppressant drugs directed towards this calcium signalling pathway. (shrink)

Recent work combining cognitive neuroscience with computational modelling suggests that distributed patterns of neural firing may represent probability distributions. This paper asks: what makes it the case that distributed patterns of firing, as well as carrying information about (correlating with) probability distributions over worldly parameters, represent such distributions? In examples of probabilistic population coding, it is the way information is used in downstream processing so as to lead to successful behaviour. In these cases content depends on factors beyond bare information, (...) contra Brian Skyrms’ (2010) view that representational content can be fully characterised in information-theoretic terms. (shrink)

Adenosine 5′-triphosphate (ATP) was identified in 1970 as the transmitter responsible for non-adrenergic, non-cholinergic neurotransmission in the gut and bladder and the term ‘purinergic’ was coined. Purinergic cotransmission was proposed in 1976 and ATP is now recognized as a cotransmitter in all nerves in the peripheral and central nervous systems. P1 (adenosine) and P2 (ATP) receptors were distinguished in 1978. Cloning of these receptors in the early 1990s was a turning point in the acceptance of the purinergic signalling hypothesis. There (...) are both short-term purinergic signalling in neurotransmission, neuromodulation and secretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation and death in development and regeneration. Much is known about the mechanisms of ATP release and its breakdown by ectonucleotidases. Recently, there has been emphasis on purinergic pathophysiology, including neurodegenerative and neuropsychiatric disorders. Purinergic therapeutic strategies are being developed for treatment of gut, kidney, bladder, lung, skeletal and reproductive system disorders, pain and cancer. (shrink)

The origins of human social cooperation confound simple evolutionary explanation. But from Darwin and Durkheim onward, theorists (anthropologists and sociologists especially) have posited a potential link with another curious and distinctively human social trait that cries out for explanation: religion. This dissertation explores one contemporary theory of the co-evolution of religion and human social cooperation: the signalling theory of religion, or religious signalling theory (RST). According to the signalling theory, participation in social religion (and its associated rituals and sanctions) acts (...) as an honest signal of one’s commitment to a religiously demarcated community and its way of doing things. This signal would allow prosocial individuals to positively assort with one another for mutual advantage, to the exclusion of more exploitative individuals. In effect, the theory offers a way that religion and cooperation might explain one another, but which that stays within an individualist adaptive paradigm. My approach is not to assess the empirical adequacy of the religious signalling explanation or contrast it with other explanations, but rather to deal with the theory in its own terms – isolating and fleshing out its core commitments, explanatory potential, and limitations. The key to this is acknowledging the internal complexities of signalling theory, with respect to the available models of honest signalling and the extent of their fit (or otherwise) with religion as a target system. The method is to take seriously the findings of formal modelling in animal signalling and other disciplines, and to apply these (and methods from the philosophy of biology more generally) to progressively build up a comprehensive picture of the theory, its inherent strengths and weaknesses. The first two chapters outline the dual explanatory problems that cooperation and religion present for evolutionary human science, and surveys contemporary approaches toward explaining them. Chapter three articulates an evolutionary conception of the signalling theory, and chapters four to six make the case for a series of requirements, limitations, and principles of application. Chapters seven and eight argue for the value of formal modelling to further flesh out the theory’s commitments and potential and describe some simple simulation results which make progress in this regard. Though the inquiry often problematizes the signalling theory, it also shows that it should not be dismissed outright, and that it makes predictions which are apt for empirical testing. (shrink)

Communication involves a great deal of uncertainty. Prima facie, it is therefore surprising that biological communication systems—from cellular to human—exhibit a high degree of ambiguity and often leave its resolution to contextual cues. This puzzle deepens once we consider that contextual information may diverge between individuals. In the following we lay out a model of ambiguous communication in iterated interactions between subjectively rational agents lacking a common contextual prior. We argue ambiguity’s justification to lie in endowing interlocutors with means to (...) flexibly adapt language use to each other and the context of their interaction to serve their communicative preferences. Linguistic alignment is shown to play an important role in this process; it foments convergence of contextual expectations and thereby leads to agreeing use and interpretation of ambiguous messages. We conclude that ambiguity is ecologically rational when interlocutors’ contextual expectations are generally in line or they interact multiple times in an informative context, enabling for the alignment of their expectations. In light of these results meaning multiplicity can be understood as an opportunistic outcome enabled and shaped by linguistic adaptation and contextual information. (shrink)

Mehr et al. seek to explain music's evolution in terms of a unitary proper function – signalling cooperative intent – which they cash out in two guises, coalition signalling and parental attention signalling. Although we recognize the role signalling almost certainly played in the evolution of music, we reject “ultimate” causal explanations which focus on a unidirectional, narrow range of causal factors.

This paper is a short survey of different languageswith imperfect information introduced in (Hintikka and Sandu 1989).The imperfect information concerns both quantifiers and connectives.At the end, I will sketch a connection between these languages and linearlogic.

The purinergic signalling system, which utilises ATP, related nucleotides and adenosine as transmitter molecules, appeared very early in evolution: release mechanisms and ATP‐degrading enzymes are operative in bacteria, and the first specific receptors are present in single cell eukaryotic protozoa and algae. Further evolution of the purinergic signalling system resulted in the development of multiple classes of purinoceptors, several pathways for release of nucleotides and adenosine, and a system of ectonucleotidases controlling extracellular levels of purinergic transmitters. The purinergic signalling system (...) is expressed in virtually all types of tissues and cells, where it mediates numerous physiological reactions and contributes to pathological responses in a variety of diseases. (shrink)

The hypotheses in both target articles rely implicitly on much the same logic. For a “social-bonding” device to make sense, there must be an underlying reason why an otherwise-arbitrary behaviour sustains alliances – namely, credible signals of one's value to partners. To illustrate our points, we draw on the parallels with supposed bonding behaviours in nonhuman animals.

Addicts may simply deny that they are addicted; or they may use self-signalling to try to provide evidence that giving up is not worthwhile. I provide an account that shows how easy it is to provide apparent evidence either that the addiction is so bad that it cannot be escaped; or that there is no real addiction, and hence nothing to escape. I suggest that the most effective way of avoiding this is to avoid self-signalling altogether.

It is a frequent assumption that—via superluminal information transfers—superluminal signals capable of enabling communication are necessarily exchanged in any quantum theory that posits hidden superluminal influences. However, does the presence of hidden superluminal influences automatically imply superluminal signalling and communication? The non-signalling theorem mediates the apparent conflict between quantum mechanics and the theory of special relativity. However, as a ‘no-go’ theorem there exist two opposing interpretations of the non-signalling constraint: foundational and operational. Concerning Bell’s theorem, we argue that Bell employed (...) both interpretations, and that he finally adopted the operational position which is associated often with ontological quantum theory, e.g., de Broglie–Bohm theory. This position we refer to as “effective non-signalling”. By contrast, associated with orthodox quantum mechanics is the foundational position referred to here as “axiomatic non-signalling”. In search of a decisive communication-theoretic criterion for differentiating between “axiomatic” and “effective” non-signalling, we employ the operational framework offered by Shannon’s mathematical theory of communication, whereby we distinguish between Shannon signals and non-Shannon signals. We find that an effective non-signalling theorem represents two sub-theorems: Non-transfer-control theorem, and Non-signification-control theorem. Employing NTC and NSC theorems, we report that effective, instead of axiomatic, non-signalling is entirely sufficient for prohibiting nonlocal communication. Effective non-signalling prevents the instantaneous, i.e., superluminal, transfer of message-encoded information through the controlled use—by a sender-receiver pair —of informationally-correlated detection events, e.g., in EPR-type experiments. An effective non-signalling theorem allows for nonlocal quantum information transfer yet—at the same time—effectively denies superluminal signalling and communication. (shrink)

Various writers have attempted to use the sender-receiver formalism to account for the representational capacities of biological systems. This paper has two goals. First, I argue that the sender-receiver approach to representation cannot be complete. The mammalian circadian system represents the time of day, yet it does not control circadian behaviours by producing signals with time of day content. Informative signalling need not be the basis of our most basic representational capacities. Second, I argue that representational capacities are primarily about (...) control, and only when specific conditions obtain does this control require informative signalling. (shrink)

This article is an inquiry into the discourse phenomenon of grounding, viz. the foreground-background structure. It explains the place of the phenomenon in the structure of discourse and provides evidence of grounding from short news items. Focusing on the surface structure level of discourse organization, the article examines variant marking of the FG-BG articulation at sentence-initial position. Using English and Arabic news data, the article explicates the grounding-signalling function of entities that appear in that position and shows that Arabic news (...) texts rely on certain prefatory expressions to signal the grounding values of underlying propositions. The study underscores the influence of the cognitive level of information on grounding and its marking in the hierarchical structure of discourse. (shrink)

Cell proliferation in response to growth factors is mediated by specific high affinity receptors. Ligand‐binding by receptors of the protein tyrosine kinase family results in the stimulation of several intracellular signal transduction pathways. Key signalling enzymes are recruited to the plasma membrane through the formation of stable complexes with activated receptors. These interactions are mediated by the conserved, non‐catalytic SH2 domains present in the signalling molecules, which bind with high affinity and specificity to tyrosine‐phosphorylated sequences on the receptors. The assembly (...) of enzyme complexes is emerging as a major mechanism of signal transduction and may regulate the pleiotropic effects of growth factors. (shrink)