The beta thymosins are a highly conserved family of strongly polar 5 kDa polypeptides that are widely distributed among vertebrate classes; most are now known to bind to monomeric actin and inhibit its polymerization. One beta thymosin, beta four, (Tβ4) is the predominant form in mammalian cells, present at up to 0.5 mM. Many species are known to produce at least two beta thymosin isoforms, in some cases in the same cell. Their expression can be separately regulated. When present outside (...) the cell, the N‐terminal tetrapeptide of beta four appears to affect cell cycle regulation; beta thymosins or smaller fragments derived from them may have additional regulatory functions. We suggest that many developmental changes in beta thymosin levels within cells and tissues may be related to changes in G‐actin pool size. (shrink)

Electrical signaling by neurons depends on the precisely ordered distribution of a wide variety of ion channels on the neuronal surface. The mechanisms underlying the targeting of particular classes of ion channels to specific subcellular sites are poorly understood. Recent studies have identified a new class of protein‐protein interaction mediated by PDZ domains, protein binding modules that recognize specific sequences at the C terminus of membrane proteins. The PDZ domains of a family of synaptic cytoskeleton‐associated proteins, typified by PSD‐95, (...) bind to the intracellular C‐terminal tails of NMDA receptors and Shaker‐type K+ channels. This interaction appears to be important in the clustering and localization of these ion channels at synaptic sites. Recognition of specific C‐terminal peptide sequences by different PDZ domain‐containing proteins may be a general mechanism for differential targeting of proteins to a variety of subcellular locations. (shrink)

Many attempts have been made at supporting either one of the allegedly complementary divergence models Phyletic Gradualism and Punctuated Equilibria by patterns found in specific fossil sequences. However, assessing each model's connection with reality via such “individual case histories” appears not to constitute a relevant approach. Instead, in order to correctly establish the possible merits of both concepts, the claims of each have to be verified against general evolutionary theory. This is being pointed out herein by analyzing cladogenesis at (...) the specific level as an example. [Phyletic Gradualism; Punctuated Equilibria; evolutionary theory; divergence models; case histories; additive speciation.]. (shrink)

Many attempts have been made at supporting either one of the allegedly complementary divergence models Phyletic Gradualism and Punctuated Equilibria by patterns found in specific fossil sequences. However, assessing each model's connection with reality via such “individual case histories” appears not to constitute a relevant approach. Instead, in order to correctly establish the possible merits of both concepts, the claims of each have to be verified against general evolutionary theory. This is being pointed out herein by analyzing cladogenesis at (...) the specific level as an example. [Phyletic Gradualism; Punctuated Equilibria; evolutionary theory; divergence models; case histories; additive speciation.]. (shrink)

This paper summarizes the main features of the microgenetic account of consciousness, of the transition from self to image, act and object, the epochal nature of this transition, and its relation to introspection, imagination, and agency. The affinities of microgenetic theory to many aspects of process thought should be evident to readers of this journal, but the theory, which was developed in pathological case study, rests on a wealth of clinical detail that is beyond the scope of this article. In (...) brief, the micro-temporal transition from archaic to recent formations (distributed systems) in the phyletic history of forebrain constitutes the absolute mental state, with consciousness the relation of self to image and/or object. The discussion touches on the overlap of states, the continuity of the core over successive states, and subjective time experience. (shrink)

Bioactive peptides are a group of diverse intercellular signalling molecules. Almost half a century of research on this topic has resulted in an enormous amount of data. In this essay, a general perspective to interpret all these data will be given. In classical endocrinology, neuropeptides were thought of as simple signalling molecules that each elicit one response. However, the fact that the total bioactive peptide signal is far from simple puts this view under pressure. Cells and tissues express many (...) different bioactive peptides and they are also able to respond to many different bioactive peptides, indicating that multiple receptors and signal transduction pathways are present in a single cell. Therefore, the authors suggest that the bioactive peptide signalling system should be regarded in the context of network and systems biology. Bioactive peptides can best be viewed as an extension of the protein interaction network that allows regulating and fine‐tuning the metabolism of the different cells and tissues in the body. The cell thus responds to the ‘peptidome’ instead of to a single peptide. The intracellular part of this signalling network consists of the various signalling transduction cascades. Recently, new systems biology approaches have emerged for the modelling of cell signalling. The network and systems biology approach is also able to shed new light on the evolution of intercellular signalling. (shrink)

The vertebrate immune system uses an impressive arsenal of mechanisms to combat harmful cellular states such as infection. One way is via cells delivering real‐time snapshots of their protein content to the cell surface in the form of short peptides. Specialized immune cells (T cells) sample these peptides and assess whether they are foreign, warranting an action such as destruction of the infected cell. The delivery of peptides to the cell surface is termed antigen processing and presentation, (...) and decades of research have provided unprecedented understanding of this process. However, predicting the capacity for a given peptide to be immunogenic—to elicit a T cell response—has remained both enigmatic and a long sought‐after goal. In the era of big data, a point is being approached where the steps of antigen processing and presentation can be quantified and assessed against peptide immunogenicity in order to build predictive models. This review presents new findings in this area and contemplates challenges ahead. (shrink)

Drosophila responds to a septic injury by the rapid synthesis of antimicrobial peptides. These molecules are predominantly produced by the fat body, a functional equivalent of mammalian liver, and are secreted into the hemolymph where their concentrations can reach up to 100 μM. Six distinct antibacterial peptides (plus isoforms) and one antifungal peptide have been characterized in Drosophila and their genes cloned. The induction of the gene encoding the antifungal peptide relies on the spätzle/Toll/cactus gene cassette, which is (...) involved in the control of dorsoventral patterning in the embryo, and shows interesting structural and functional similarities with cytokine‐induced activation of NF‐ϰB in mammalian cells. An additional pathway, dependent on the as yet unidentified imd (for immune‐deficiency) gene, is required for the full induction of the antibacterial peptide genes. Mutants deficient for the Toll and imd pathways exhibit a severely reduced survival to fungal and bacterial infections, respectively. Recent data on the molecular mechanisms underlying recognition of non‐self are also discussed in this review. (shrink)

Both W9 and OP3‐4 were known to bind the receptor activator of NF‐κB ligand (RANKL), inhibiting osteoclastogenesis. Recently, both peptides were shown to stimulate osteoblast differentiation; however, the mechanism underlying the activity of these peptides remains to be clarified. A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide‐induced alkaline phosphatase activity. Furthermore, both peptides promoted the phosphorylation of Akt and S6K1, (...) an upstream molecule of mTORC1 and the effector molecule of mTORC1, respectively. In the in vivo calvarial defect model, W9 and OP3‐4 accelerated BMP‐2‐induced bone formation to a similar extent, which was confirmed by histomorphometric analyses using fluorescence images of undecalcified sections. Our data suggest that these RANKL‐binding peptides could stimulate the mTORC1 activity, which might play a role in the acceleration of BMP‐2‐induced bone regeneration by the RANKL‐binding peptides. (shrink)

The allegedly alternative theories of Phyletic Gradualism and Punctuated Equilibria are examined as regards the nature of their differences. The explanatory value of both models is determined by establishing their actual connection with reality. It is concluded that they are to be considered complementary rather than mutually exclusive at all levels of infraspecific, specific, and supraspecific evolution. So, in order to be described comprehensively, the pathways of evolution require at least two distinct models, each based on a discrete range (...) of real phenomena. [Phyletic Gradualism; Punctuated Equilibria; evolutionary theories; divergence models; additive speciation; microevolution; macroevolution; anagenesis.]. (shrink)

Peptides serve as important signalling molecules in development and differentiation in the simple metazoan Hydra. A systematic approach (The Hydra Peptide Project) has revealed that Hydra contains several hundreds of peptide signalling molecules, some of which are neuropeptides and others emanate from epithelial cells. These peptides control biological processes as diverse as muscle contraction, neuron differentiation, and the positional value gradient. Signal peptides cause changes in cell behaviour by controlling target genes such as matrix metalloproteases. The abundance (...) of peptides in Hydra raises the question of whether, in early metazoan evolution, cell–cell communication was based mainly on these small molecules rather than on the growth‐factor‐like cytokines that control differentiation and development in higher animals. BioEssays 23:420–427, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Mastering how to convey meanings using language is perhaps the main challenge facing any language learner. However, satisfactory accounts of how this is achieved, and even of what it is for a linguistic item to have meaning, are hard to come by. Nick Chater was one of the pioneers involved in the early development of one of the most successful methodologies within the cognitive science of language for discovering meaning: distributional semantics. In this article, we review this approach and discuss (...) its successes and shortcomings in capturing semantic phenomena. In particular, we discuss what we dub the “distributional paradox:” how can models that do not implement essential dimensions of human semantic processing, such as sensorimotor grounding, capture so many meaning-related phenomena? We conclude by providing a preliminary answer, arguing that distributional models capture the statistical scaffolding of human language acquisition that allows for communication, which, in line with Nick Chater's more recent ideas, has been shaped by the features of human cognition on the timescale of cultural evolution. (shrink)

It is commonly presumed that abiotic membranes were colonized by proteins later on. Yet, hydrophobic peptides could have formed primordial protein‐dominated membranes on their own. In a metabolism‐first context, “autocatalytically closed” sets of statistical peptides could organize a self‐maintaining protometabolism, assisted by an unfolding set of ribotide‐related cofactors. Pairwise complementary ribotide cofactors may have formed docking guides for stochastic peptide formation, before replicating RNA emerged from this subset. Tidally recurring wet‐drying cycles and an early onset of photosynthetic activities (...) are considered most likely to meet the thermodynamic requirements. Conceivably, the earliest peptide‐dominated vesicles were engaged in light harvesting, together with isoprenoid‐tethered pigments, rather than providing an external boundary. Early on, the bulk of prebiotic organic matter can have formed a contiguous layer covering the mineral sediment, held in place by colloidal coherence of a hydrogel matrix. This unconventional scenario assumes a late onset of cellular individualization – perhaps from within, resembling endosporogenesis. (shrink)

Atrial natriuretic peptides appear to elicit their actions in some target tissues by binding to a novel cell‐surface transmembrane protein which possesses both peptide binding and guanylate cyclase activities. Ligand binding stimulates enzyme activity to produce increased intracellular concentrations of cyclic GMP which, in turn, mediates the cell's physiological response.

A decision maker has to choose one of several random variables whose distributions are not known. As a Bayesian, she behaves as if she knew the distributions. In this paper we suggest an axiomatic derivation of these (subjective) distributions, which is more economical than the derivations by de Finetti or Savage. Whereas the latter derive the whole joint distribution of all the available random variables, our approach derives only the marginal distributions. Correspondingly, the preference questionnaire needed in our case (...) is less smaller. (shrink)

This paper considers the relationship between distributive justice and vocational education. It examines both the way that the very notion of a vocational education carries implications for distributive justice and how the meaning of justice itself might be shifting towards one of inclusion. The argument, which is based on the recent work of Bernard Williams (2002), may have some general explanatory and predictive power particularly relevant to the educational uses of certain terms. 'Vocational' is used in the paper as an (...) exemplar. It is argued that consideration of what is just in any liberal society involves weighting the application of principles in ways that respect the shared values of that society. These values are communicated partly through hopeful myths that enable social cohesion. One such set of myths currently serves to sustain some degree of hope that emphasis on the vocational in education will enable distributive justice. Increasingly however experience of and research within vocational education reveals some truths that challenge these myths. Neither myth nor truth floats free of structure, however, and the paper also includes discussion of the ways that structure, truth and myth are related. (shrink)

Unsupervised grammar induction systems commonly judge potential constituents on the basis of their effects on the likelihood of the data. Linguistic justifications of constituency, on the other hand, rely on notions such as substitutability and varying external contexts. We describe two systems for distributional grammar induction which operate on such principles, using part-of-speech tags as the contextual features. The advantages and disadvantages of these systems are examined, including precision/recall trade-offs, error analysis, and extensibility.

Over the past decade, high‐throughput studies have identified many novel transcripts. While their existence is undisputed, their coding potential and functionality have remained controversial. Recent computational approaches guided by ribosome profiling have indicated that translation is far more pervasive than anticipated and takes place on many transcripts previously assumed to be non‐coding. Some of these newly discovered translated transcripts encode short, functional proteins that had been missed in prior screens. Other transcripts are translated, but it might be the process of (...) translation rather than the resulting peptides that serves a function. Here, we review annotation studies in zebrafish to discuss the challenges of placing RNAs onto the continuum that ranges from functional protein‐encoding mRNAs to potentially non‐functional peptide‐producing RNAs to non‐coding RNAs. As highlighted by the discovery of the novel signaling peptide Apela/ELABELA/Toddler, accurate annotations can give rise to exciting opportunities to identify the functions of previously uncharacterized transcripts. (shrink)

Synthesizing the domains of investigation highlighted in current research in distributed cognition and related fields, this paper offers an initial taxonomy of the overlapping types of resources which typically contribute to distributed or extended cognitive systems. It then outlines a number of key dimensions on which to analyse both the resulting integrated systems and the components which coalesce into more or less tightly coupled interaction over the course of their formation and renegotiation.

Childress and colleagues conclude that arguments from distributive justice do not justify discontinuing ECMO over a capacitated patient’s objections (Childress et al. 2023). However, this conclusio...

The phenomenon of distributed knowledge is well-known in epistemic logic. In this paper, a similar phenomenon in ethics, somewhat neglected so far, is investigated, namely distributed morality. The article explains the nature of distributed morality, as a feature of moral agency, and explores the implications of its occurrence in advanced information societies. In the course of the analysis, the concept of infraethics is introduced, in order to refer to the ensemble of moral enablers, which, although morally neutral per se, can (...) significantly facilitate or hinder both positive and negative moral behaviours. (shrink)

Richard Heersmink argues that self‐narratives are distributed across embodied organisms and their environment, given that their building blocks, autobiographical memories, are distributed. This argument faces two problems. First, it commits a fallacy of composition. Second, it relies on Marya Schechtman's narrative self‐constitution view, which is incompatible with the distributed cognition framework. To solve these problems, this article develops an alternative account of self‐narratives. On this account, we actively connect distributed autobiographical memories through distributed conversational and textual self‐narrative practices. This account (...) enhances our understanding of the memory–narrative nexus and has implications for philosophical conceptions of self. (shrink)

The allegedly alternative theories of Phyletic Gradualism and Punctuated Equilibria are examined as regards the nature of their differences. The explanatory value of both models is determined by establishing their actual connection with reality. It is concluded that they are to be considered complementary rather than mutually exclusive at all levels of infraspecific, specific, and supraspecific evolution. So, in order to be described comprehensively, the pathways of evolution require at least two distinct models, each based on a discrete range (...) of real phenomena. [Phyletic Gradualism; Punctuated Equilibria; evolutionary theories; divergence models; additive speciation; microevolution; macroevolution; anagenesis.]. (shrink)

There are various philosophical approaches and theories describing the intimate relation people have to artifacts. In this paper, I explore the relation between two such theories, namely distributed cognition and distributed morality theory. I point out a number of similarities and differences in these views regarding the ontological status they attribute to artifacts and the larger systems they are part of. Having evaluated and compared these views, I continue by focussing on the way cognitive artifacts are used in moral practice. (...) I specifically conceptualise how such artifacts (a) scaffold and extend moral reasoning and decision-making processes, (b) have a certain moral status which is contingent on their cognitive status, and (c) whether responsibility can be attributed to distributed systems. This paper is primarily written for those interested in the intersection of cognitive and moral theory as it relates to artifacts, but also for those independently interested in philosophical debates in extended and distributed cognition and ethics of (cognitive) technology. (shrink)

This paper explores the implications of extended and distributed cognition theory for our notions of personal identity. On an extended and distributed approach to cognition, external information is under certain conditions constitutive of memory. On a narrative approach to personal identity, autobiographical memory is constitutive of our diachronic self. In this paper, I bring these two approaches together and argue that external information can be constitutive of one’s autobiographical memory and thus also of one’s diachronic self. To develop this claim, (...) I draw on recent empirical work in human-computer interaction, looking at lifelogging technologies in both healthcare and everyday contexts. I argue that personal identity can neither be reduced to psychological structures instantiated by the brain nor by biological structures instantiated by the organism, but should be seen as an environmentally-distributed and relational construct. In other words, the complex web of cognitive relations we develop and maintain with other people and technological artifacts partly determines our self. This view has conceptual, methodological, and normative implications: we should broaden our concepts of the self as to include social and artifactual structures, focus on external memory systems in the (empirical) study of personal identity, and not interfere with people’s distributed minds and selves. (shrink)

Introducing the main theories of distributional justice the book covers utilitarianism and welfare economics, moving on to Rawls's social contract and the Sen/Nussbaum capability approach with a refreshingly readable style. There is a chapter covering the position of mothers and children in theories of justice. The book then studies empirical methods used in analysing the distribution of economic goods, covering Lorenz curves and inequality measures. The concepts of income, wealth and economic goods are comprehensively discussed, with a particular view (...) to their role in theories of justice. This book is an important read for economists and other social scientists, as well as philosophers who want to quantify social and economic justice. (shrink)

Signal transduction via receptors for N‐formylmethionyl peptide chemoattractants (FPR) on human neutrophils is a highly regulated process which involves participation of cytoskeletal elements. Evidence exists suggesting that the cytoskeleton and/or the membrane skeleton controls the distribution of FPR in the plane of the plasma membrane, thus controlling the accessibility of FPR to different proteins in functionally distinct domains. In desensitized cells, FPR are restricted to domains which are depleted of G proteins but enriched in cytoskeletal proteins such as actin (...) and fodrin. Thus, the G protein signal transduction partners of FPR become inaccessible to the agonist‐occupied receptor, preventing cell activation. The mechanism of interaction of FPR with the membrane skeleton is poorly understood but evidence is accumulating that suggests a direct binding of FPR (and other receptors) to cytoskeletal proteins such as actin. (shrink)

Contributors to this book include key theorists and practitioners from media theory, Native Science, bio-media and sound art, philosophy, art history and design informatics. Collectively, they examine the becoming-technique of animal-human- machinic perceptibilities; and micro-perceptions that lie beneath the threshold of known perceptions yet create energetic vibrations. Who, what, and where perceives, and how? What are the sedimentations, inscriptions and axiologies of animal, human and machinic perceptions? What are their perceptibilities? Deleuze uses the word 'visibilities' to indicate that visual perception (...) isn't just a physiological given but cues operations productive of new assemblages. Perceptibilities are, by analogy, spatio- temporal, geolocative, kinaesthetic, audio-visual, and haptic operations that are always already memory. In the case of strong inscriptions, they are also epigenetic events. The contributors show distributed perception to be a key notion in addressing the emergence and persistence of plant, animal, human and machine relations. An invaluable reference for students and scholars in a range of areas including Media Theory, Sociology, Philosophy, Art and Design. (shrink)

This paper discusses two distinct questions of distributive justice raised by climate change. Stated very roughly, one question concerns how much protection is owed to the potential victims of climate change (the Just Target Question), and the second concerns how the burdens (and benefits) involved in preventing dangerous climate change should be distributed (the Just Burden Question). In Section II, I focus on the first of these questions, the Just Target Question. The rest of the paper examines the second question, (...) the Just Burden Question. To answer this question, I argue, it is necessary to address two important methodological questions (one concerning the choice between what I term Integrationism and Isolationism and the other concerning the choice between what I term Holism and Atomism). Sections III-V, thus, set out and explore these two methodological issues. Having done so, the paper then turns from methodological issues to substantive analysis, and in Section VI it examines three principles of distributive justice that, it has been suggested, should determine how the burden of addressing dangerous climatic changes should be distributed (the Polluter Pays Principle, the Ability to Pay Principle and the Beneficiary Pays Principle). (shrink)

Affective disorders arise in stressful situations from aberrant sensory information integration that affects energetic nutrient (i.e., glucose) utilization to the cognitive centers of the brain. Because energy flow is mediated by molecular signals and receptors that evolved before the first complex brains, the phylogenetically oldest signaling systems are essential in the etiology of affective disorders. The corticotropin‐releasing factor (CRF) peptide subfamily is a phylogenetically old metazoan peptide family and is pivotal for regulating organismal energy response associated with stress. Highly conserved, (...) both the CRF peptide family and its receptors possess a structural relationship to the teneurins, and their receptors, latrophilins, respectively. The CRF homologous region of teneurin is defined as the “teneurin C‐terminal associated peptide” (TCAP) and antagonizes CRF action, regulates mitochondrial energy production, and is anxiolytic in vivo. Here, it is postulated that TCAP represents an ancient peptide that mediates intercellular information transfer of stressful and noxious events by regulating energy utilization among neurons. (shrink)

This dissertation offers and defends a phenomenological account of personal identity. It does so critically in conversation with Anglo-analytical traditions and varieties of other philosophical traditions from around the world, especially Zen Buddhism. Chapter One brings together three areas of philosophy: the multiple realizability thesis from philosophy of science, the logical pluralist position from philosophical logic, and the various conceptions of personhood from metaphysics. I argue that even though the divide in the literature on the metaphysics of personal identity is (...) unresolved, there is a core notion, “person,” that is understood to be the target of explanation in each of the traditions. The multiple-realizability of personhood entails the multiple realizability of identity. Because "person" is an unsettled term, "personal identity" is also unsettled. Chapter Two examines those metaphysics traditions in more detail. After outlining the claims of body continuity theorists, psychological continuity theorists, and narrative continuity theorists, I raise objections to each of the theories. In Chapter Three, I propose that all three categories of metaphysics approaches to identity face a unified objection: they presume a level of objectivity that belies the negotiation of our identities. This chapter examines the limits of methodological naturalism and examines the work of two Indigenous scholars from North and South America who present theories of identity that embrace contradictory beliefs and goals. Chapter Four proposes that phenomenology offers a new and more promising approach to studying personal identity. In this chapter, I point out that there is a disciplinary divide over whether identity is a thing (something of substance) or a way of understanding. By shifting the approach to identity from metaphysics to epistemology, I demonstrate that phenomenology avoids the objections that the metaphysics theories face. In this chapter, I also raise objections that arise in Buddhist traditions. The chapter concludes with close readings of Keiji Nishitani's critique of Western philosophy from Religion and Nothingness and Jean-Paul Sartre's defense of phenomenology, which appears in Being and Nothingness. Chapter Five defends the phenomenological analysis of identity against Nishitani’s critique. I show that the phenomenological approach to identity entails that identities are distributed within contexts. I adopt a deflationary account of identity grounded in the term existence—all that can be said about one's identity is that it is whatever makes them stand out against a background. No amount of precision that is added to the various accounts will settle whether the metaphysics or epistemic approach to identity is better. Therefore, the deflationary understanding of identity allows us to continue talking about the core notion even if the term remains unsettled. In the end, I offer an account of personal identity that suggests that identity is a distributed phenomenon. If one’s identity is intelligible only in the context of the world, then my circumstances are part of my identity. (shrink)