Transcription factor binding sites (TFBSs) on the DNA are generally accepted as the key nodes of gene control. However, the multitudes of TFBSs identified in genome‐wide studies, some of them seemingly unconstrained in evolution, have prompted the view that in many cases TF binding may serve no biological function. Yet, insights from transcriptional biochemistry, population genetics and functional genomics suggest that rather than segregating into ‘functional’ or ‘non‐functional’, TFBS inputs to their target genes may be generally cumulative, with (...) varying degrees of potency and redundancy. As TFBS redundancy can be diminished by mutations and environmental stress, some of the apparently ‘spurious’ sites may turn out to be important for maintaining adequate transcriptional regulation under these conditions. This has significant implications for interpreting the phenotypic effects of TFBS mutations, particularly in the context of genome‐wide association studies for complex traits. (shrink)

Graphical AbstractThe loosening of chromatin structures gives rise to unrestricted access to DNA and thus transcription factors (TFs) can bind to their otherwise masked target sequences. Regions bound by the same set of TFs tend to be located in close proximity and this might increase the probability of activating illegitimate genomic rearrangements.

Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome‐wide evidence for a “Hit‐and‐Run” model of transcription. In this model, a master TF “hits” a target promoter to initiate a rapid response to a signal. As the “hit” is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the “run”, the master TF “hits” other targets to propagate the response genome‐wide. As such, a TF may (...) act as a “catalyst” to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long‐term adaptive behavior in the whole organism. This “Hit‐and‐Run” model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF‐regulated and TF‐bound genes, implicating transient TF‐target binding. Here, we explore this “Hit‐and‐Run” model to suggest molecular mechanisms and its biological relevance. (shrink)

This volume brings together about 50 scientists and researchers from the four corners of the world to redefine and anticipate tomorrow's values, and reflect on ...

In his preface to Human, Too Human Nietzsche wrote: ‘My books have been labelled the school of suspicion … ‘ Predicted and desired by Nietzsche, the age of suspicion does seem to be one of the labels that best characterize the century that has just closed. And symptomatically it was used a few decades later in France to describe writers’ interrogations about the novel as a literary genre, its facilities and conventions, its easy determinisms, as well as the exorbitant power (...) of the novelist-demiurge. Is it necessary to recall that the forerunner to the nouveau roman, written by Nathalie Sarraute in the 1930s, was in fact entitled L’Ère du soupçon? It is impossible to emphasize enough this close concordance between philosophical questioning and aesthetic interrogations, particularly in the notion of avant-garde, which is indispensable for thinking about intellectual and political renewal. It is true that the 20th century was the century of the universal declaration of human rights, but also the century of rejection of norms inherited from philosophical, literary, cultural, religious or scientific traditions, which came to be suspected of providing only off-the-peg elements for thought and action at a time when the world was changing and required new forms of thinking. (shrink)

Résumé Le cheminement de la pensée occidentale, depuis plus d’un siècle, a vu : la mort de Dieu, la chute des idéologies politiques qui semblaient avoir pris le relais des valeurs « divines », la solitude de l’individu désorienté. Le malaise de l’individu serait le symptôme d’une remise en question de la notion même d’être humain. En reprenant la critiques de l’humanisme introduite par Nietzsche, Sloterdijk fait ressortir que l’homme aurait échappé à la bestialité par les moyens mêmes qu’il emploie (...) pour apprivoiser les animaux et les mettre à son service. Que dire de ce que la recherche permet actuellement de faire sur l’être humain? La manipulation du vivant a fait émerger la possibilité d’une fabrique de l’être humain. Les choix que nous avons à faire quant au devenir de l’humain restent éminemment politiques. Le terme d’humanisme est complexe : il est deux types d’humanisme. Celui qui conçoit l’humain comme une essence. La seconde forme considère qu’il n’y a pas de nature humaine, que l’on devient humain. Le monde humain est ouvert à la création, mais fragilisé parce que placé sous notre responsabilité. (shrink)

In his preface to Human, Too Human Nietzsche wrote: ‘My books have been labelled the school of suspicion … ‘ Predicted and desired by Nietzsche, the age of suspicion does seem to be one of the labels that best characterize the century that has just closed. And symptomatically it was used a few decades later in France to describe writers’ interrogations about the novel as a literary genre, its facilities and conventions, its easy determinisms, as well as the exorbitant power (...) of the novelist-demiurge. Is it necessary to recall that the forerunner to the nouveau roman, written by Nathalie Sarraute in the 1930s, was in fact entitled L’Ère du soupçon? It is impossible to emphasize enough this close concordance between philosophical questioning and aesthetic interrogations, particularly in the notion of avant-garde, which is indispensable for thinking about intellectual and political renewal. It is true that the 20th century was the century of the universal declaration of human rights, but also the century of rejection of norms inherited from philosophical, literary, cultural, religious or scientific traditions, which came to be suspected of providing only off-the-peg elements for thought and action at a time when the world was changing and required new forms of thinking. (shrink)

The basic elements of faceted thesauri are described, together with a review of their origins and some prominent examples. Their use in browsing and searching applications is discussed. Faceted thesauri are distinguished from faceted classification schemes, while acknowledging the close similarities. The paper concludes by comparing faceted thesauri and related knowledge organization systems to ontologies and discussing appropriate areas of use.

The generation of patterns and the diversity of cell types in a multicellular organism require differential gene regulation. At the heart of this process are enhancers or cis‐regulatory modules (CRMs), genomic regions that are bound by transcription factors (TFs) that control spatio‐temporal gene expression in developmental networks. To date, only a few CRMs have been studied in detail and the underlying cis‐regulatory code is not well understood. Here, we review recent progress on the genome‐wide identification of CRMs with chromatin immunoprecipitation (...) of TF‐DNA complexes followed by microarrays (ChIP‐on‐chip). We focus on two computational approaches that have succeeded in predicting the expression pattern driven by a CRM either based on TF binding site preferences and their expression levels, or quantitative analysis of CRM occupancy by key TFs. We also discuss the current limits of these methods and highlight some of the key problems that have to be solved to gain a more complete understanding of the structure and function of CRMs. (shrink)

Transcriptional silencing may not necessarily depend on the continuous residence of a sequence‐specific repressor at a control element and may act via a “hit and run” mechanism. Due to limitations in assays that detect transcription factor (TF) binding, such as chromatin immunoprecipitation followed by high‐throughput sequencing (ChIP‐seq), this phenomenon may be challenging to detect and therefore its prevalence may be underappreciated. To explore this possibility, erythroid gene promoters that are regulated directly by GATA1 in an inducible system are analyzed. (...) It is found that many regulated genes are bound immediately after induction of GATA1 but the residency of GATA1 decreases over time, particularly at repressed genes. Furthermore, it is shown that the repressive mark H3K27me3 is seldom associated with bound repressors, whereas, in contrast, the active (H3K4me3) histone mark is overwhelmingly associated with TF binding. It is hypothesized that during cellular differentiation and development, certain genes are silenced by repressive TFs that subsequently vacate the region. Catching such repressor TFs in the act of silencing via assays such as ChIP‐seq is thus a temporally challenging prospect. The use of inducible systems, epitope tags, and alternative techniques may provide opportunities for detecting elusive “hit and run” transcriptional silencing. Also see the video abstract here https://youtu.be/vgrsoP_HF3g. (shrink)

Transcription factors (TFs) have to find their binding sites, which are distributed throughout the genome. Facilitated diffusion is currently the most widely accepted model for this search process. Based on this model the TF alternates between one‐dimensional sliding along the DNA, and three‐dimensional bulk diffusion. In this view, the non‐specific associations between the proteins and the DNA play a major role in the search dynamics. However, little is known about how the DNA properties around the motif contribute to the (...) search. Accumulating evidence showing that TF binding sites are embedded within a unique environment, specific to each TF, leads to the hypothesis that the search process is facilitated by favorable DNA features that help to improve the search efficiency. Here, we review the field and present the hypothesis that TF‐DNA recognition is dictated not only by the motif, but is also influenced by the environment in which the motif resides. (shrink)

Metazoan genomes contain thousands of protein‐coding and non‐coding RNA genes, most of which are differentially expressed, i.e., at different locations, at different times during development, or in response to environmental signals. Differential gene expression is achieved through complex regulatory networks that are controlled in part by two types of trans‐regulators: transcription factors (TFs) and microRNAs (miRNAs). TFs bind to cis‐regulatory DNA elements that are often located in or near their target genes, while miRNAs hybridize to cis‐regulatory RNA elements mostly located (...) in the 3′ untranslated region of their target mRNAs. Here, we describe how these trans‐regulators interact with each other in the context of gene regulatory networks to coordinate gene expression at the genome‐scale level, and discuss future challenges of integrating these networks with other types of functional networks. (shrink)

Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co‐activators, co‐repressors, multiple TFs, histone‐modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a (...) pioneering role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP‐Seq, digital genomic footprinting, DHS‐Seq, live cell protein dynamics, and biochemical studies of ATP‐dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy‐dependent, non‐equilibrium steady states. (shrink)

High‐fidelity binding of transcription factors (TFs) to DNA target sites is fundamental for proper regulation of cellular processes, as well as for the maintenance of cell identity. Recognition of cognate binding motifs in the genome is attributed by and large to the DNA binding domains of TFs. As an additional mode of conferring binding specificity, noncoding RNAs (ncRNAs) have been proposed to assist associated TFs in finding their binding sites by interacting with either DNA or (...) RNA in the vicinity of their target loci. However, a well‐documented example of such a mechanism was lacking until we recently reported that a ncRNA made by Epstein‐Barr virus uses an RNA–RNA interaction with nascent transcripts generated from the viral genome to facilitate the recruitment of an interacting TF, PAX5, to viral DNA. This proof‐of‐principle finding suggests that cellular ncRNAs may likewise function in guiding interacting TFs to chromatin target sites. (shrink)

The role of membrane receptors is regarded as being to transduce the signal represented by ligand binding from the external cell surface across the membrane into the cell. Signals are subsequently conveyed from the cytoplasm to the nucleus through a combination of second-messenger molecules, kinase/phosphorylation cascades, and transcription factor (TF) translocation to effect changes in gene expression. Mounting evidence suggests that through direct targeting to the nucleus, polypeptide ligands and their receptors may have an important additional signaling role. Ligands (...) such as those of the platelet-derived and fibroblast growth factor classes, as well as cytokines such as interferon-γ and interleukins-1 and -5, have been found to localize in the nucleus through the action of nuclear localization sequences (NLSs). Where tested, these NLSs appear to be essential for full signaling activity and may be responsible for cotranslocating receptors to the nucleus in complexes with their ligands. The implication is that, subsequent to endocytosis at the membrane, particular polypeptide ligands or their receptors, or both, may translocate to the nucleus to participate directly in gene regulation. BioEssays 20:400–411, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Embryonic stem cells are derived from the preimplantation embryo and can differentiate into virtually any other cell type, which is governed by lineage specific transcriptions factors binding to cis regulatory elements to mediate changes in gene expression. The reliance on transcriptional regulation to maintain pluripotency makes ESCs a valuable model to study the role of distal CREs such as enhancers in modulating gene expression to affect cell fate decisions. This review will highlight recent advance on transcriptional enhancers, focusing on (...) studies performed in ESCs. In addition, we argue that the Nanog locus, which encodes for an ESC-critical TF, is particularly informative because it contains multiple co-regulated genes and enhancers in close proximity to one another. The unique landscape at Nanog permits the study of ongoing questions including whether multiple enhancers function additively versus synergistically, determinants of gene specificity, and cell-to-cell variability in gene expression. Nanog encodes a transcription factor required to maintain ESC pluripotency. The Nanog locus is an ideal model to study enhancers because it contains multiple highly potent super-enhancers within a small region. Nanog and three super-enhancers are in close physical proximity but only two SEs are required for Nanog expression. (shrink)

A key challenge for understanding transcriptional regulation is being able to measure transcription factor (TF)‐DNA binding events with sufficient spatial and temporal resolution; that is, when and where TFs occupy their cognate sites. A recent study by Para et al. has highlighted the dynamics underlying the activation of gene expression by a master regulator TF. This study provides concrete evidence for a long‐standing hypothesis in biology, the “hit‐and‐run” mechanism, which was first proposed decades ago. That is, gene expression is (...) dynamically controlled by a TF that transiently binds and activates a target gene, which might stay in a transcriptionally active state after the initial binding event has ended. Importantly, the experimental procedure introduced, TARGET, provides a useful way for identifying multiple target genes transiently bound by their regulators, which can be used in conjunction with other well‐established methods to improve our understanding of transcriptional regulatory dynamics. (shrink)

The role of membrane receptors is regarded as being to transduce the signal represented by ligand binding from the external cell surface across the membrane into the cell. Signals are subsequently conveyed from the cytoplasm to the nucleus through a combination of second-messenger molecules, kinase/phosphorylation cascades, and transcription factor (TF) translocation to effect changes in gene expression. Mounting evidence suggests that through direct targeting to the nucleus, polypeptide ligands and their receptors may have an important additional signaling role. Ligands (...) such as those of the platelet-derived and fibroblast growth factor classes, as well as cytokines such as interferon-γ and interleukins-1 and -5, have been found to localize in the nucleus through the action of nuclear localization sequences (NLSs). Where tested, these NLSs appear to be essential for full signaling activity and may be responsible for cotranslocating receptors to the nucleus in complexes with their ligands. The implication is that, subsequent to endocytosis at the membrane, particular polypeptide ligands or their receptors, or both, may translocate to the nucleus to participate directly in gene regulation. BioEssays 20:400–411, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Despite ever‐increasing accumulation of genomic data, the fundamental question of how individual genes are switched on during development, lineage‐specification and differentiation is not fully answered. It is widely accepted that this involves the interaction between at least three fundamental regulatory elements: enhancers, promoters and insulators. Enhancers contain transcription factor binding sites which are bound by transcription factors (TFs) and co‐factors expressed during cell fate decisions and maintain imposed patterns of activation, at least in part, via their epigenetic modification. This (...) information is transferred from enhancers to their cognate promoters often by coming into close physical proximity to form a ‘transcriptional hub’ containing a high concentration of TFs and co‐factors. The mechanisms underlying these stages of transcriptional activation are not fully explained. This review focuses on how enhancers and promoters are activated during differentiation and how multiple enhancers work together to regulate gene expression. We illustrate the currently understood principles of how mammalian enhancers work and how they may be perturbed in enhanceropathies using expression of the α‐globin gene cluster during erythropoiesis, as a model. (shrink)

DNA–protein interactions are fundamental to many biological processes, including the regulation of gene expression. Determining the binding affinities of transcription factors (TFs) to different DNA sequences allows the quantitative modeling of transcriptional regulatory networks and has been a significant technical challenge in molecular biology for many years. A recent paper by Maerkl and Quake1 demonstrated the use of microfluidic technology for the analysis of DNA–protein interactions. An array of short DNA sequences was spotted onto a glass slide, which was (...) then covered with a microfluidic device allowing each spot to be within a chamber into which the flow of materials was controlled by valves. By trapping the DNA–protein complexes on the surface and measuring their concentrations microscopically, they could determine the binding affinity to a large number of DNA sequences that were varied systematically. They studied four TFs from the basic helix–loop–helix family of proteins, all of which bind to E‐box sites with the consensus CAnnTG (where “n” can be any base), and showed that variations in affinity for different sites allows each TF to regulate different genes. BioEssays 29:717–721, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Plant‐specific NAC transcription factors (TFs) evolve during the transition from aquatic to terrestrial plant life and are amplified to become one of the biggest TF families. This is because they regulate genes involved in water conductance and cell support. They also control flower and fruit formation. The review presented here focuses on various properties, regulatory intricacies, and developmental roles of NAC family members. Processes controlled by NACs depend majorly on their transcriptional properties. NACs can function as both activators and/or repressors. (...) Additionally, their homo/hetero dimerization abilities can also affect DNA binding and activation properties. The active protein levels are dependent on the regulatory cascades. Because NACs regulate both development and stress responses in plants, in‐depth knowledge about them has the potential to help guide future crop improvement studies. (shrink)

T‐bet and Eomes are two related transcription factors (TFs) that regulate the differentiation of cytotoxic lymphocytes such as Natural Killer (NK) cells and CD8 T cells. Recent genome‐wide analyses suggest they have complementary roles in instructing the transcriptional program of NK cells, although their DNA binding sites appear to be very similar. In this essay, we discuss the mechanisms that could specify their action, addressing their expression profile, the cofactors they interact with, as well as their roles in the (...) epigenetic regulation of chromatin accessibility. Based on the recent literature on these TFs, we propose different models to describe how they regulate gene expression in NK cells at steady state, or in the context of activation or exhaustion. We also discuss recent findings in the field of CD8 T cell differentiation and residency, where Eomes and T‐bet appear to be major regulators, and the parallels that can be drawn between mechanisms of NK and CD8 T cell differentiation and trafficking. (shrink)

In “Bayesianism, Infinite Decisions, and Binding”, Arntzenius et al. (Mind 113:251–283, 2004 ) present cases in which agents who cannot bind themselves are driven by standard decision theory to choose sequences of actions with disastrous consequences. They defend standard decision theory by arguing that if a decision rule leads agents to disaster only when they cannot bind themselves, this should not be taken to be a mark against the decision rule. I show that this claim has surprising implications for (...) a number of other debates in decision theory. I then assess the plausibility of this claim, and suggest that it should be rejected. (shrink)

In temporal binding, the temporal interval between one event and another, occurring some time later, is subjectively compressed. We discuss two ways in which temporal binding has been conceptualized. In studies showing temporal binding between a voluntary action and its causal consequences, such binding is typically interpreted as providing a measure of an implicit or pre-reflective “sense of agency”. However, temporal binding has also been observed in contexts not involving voluntary action, but only the passive (...) observation of a cause-effect sequence. In those contexts, it has been interpreted as a top-down effect on perception reflecting a belief in causality. These two views need not be in conflict with one another, if one thinks of them as concerning two separate mechanisms through which temporal binding can occur. In this paper, we explore an alternative possibility: that there is a unitary way of explaining temporal binding both within and outside the context of voluntary action as a top-down effect on perception reflecting a belief in causality. Any such explanation needs to account for ways in which agency, and factors connected with agency, have been shown to affect the strength of temporal binding. We show that principles of causal inference and causal selection already familiar from the literature on causal learning have the potential to explain why the strength of people’s causal beliefs can be affected by the extent to which they are themselves actively involved in bringing about events, thus in turn affecting binding. (shrink)

ABSTRACT Quine insisted that the satisfaction of an open modalised formula by an object depends on how that object is described. Kripke's ‘objectual’ interpretation of quantified modal logic, whereby variables are rigid, is commonly thought to avoid these Quinean worries. Yet there remain residual Quinean worries for epistemic modality. Theorists have recently been toying with assignment-shifting treatments of epistemic contexts. On such views an epistemic operator ends up binding all the variables in its scope. One might worry that this (...) yields the undesirable result that any attempt to ‘quantify in’ to an epistemic environment is blocked. If quantifying into the relevant constructions is vacuous, then such views would seem hopelessly misguided and empirically inadequate. But a famous alternative to Kripke's semantics, namely Lewis' counterpart semantics, also faces this worry since it also treats the boxes and diamonds as assignment-shifting devices. As I'll demonstrate, the mere fact that a variable is bound is no obstacle to binding it. This provides a helpful lesson for those modelling de re epistemic contexts with assignment sensitivity, and perhaps leads the way toward the proper treatment of binding in both metaphysical and epistemic contexts: Kripke for metaphysical modality, Lewis for epistemic modality. (shrink)

Binding can be described at three different levels: In neuroscience it refers to the integration of single-cell activities to form functional neural assemblies, especially in response to global stimulus properties; in cognitive science it refers to the integration of distributed modular input processing to form unified representations for memory and action, and in consciousness studies it refers to the unity of phenomenal consciousness . To describe and explain the unity of consciousness, detailed phenomenological descriptions of binding at the (...) phenomenal level and clarification of the underlying cognitive and neural mechanisms are required. The disunity of consciousness during dreaming is a fruitful avenue to study phenomenal binding and its mechanisms. The notion of the 'bizarreness' of dreams is closely related to the concept of 'binding': bizarreness can be reconceptualized as referring to different types of unusual combinations of features in the binding of dream images coherently together. The present study concentrates on the representation of human characters and the bizarreness found in these representations. We developed a rating scale that distinguishes different types of bizarreness on the basis of the unusual combinations of elements that are manifested in dream images. The data consisted of 592 dream reports in the home-based dream diaries of 52 students. The results indicate that about half of the human characters appearing in our dreams contain bizarre elements, and that certain types of bizarreness are more frequent than others. Phenomenal features intrinsic to the representation of a person are less frequently bizarre than is the external relation between the person and the context . Thus, binding the local features of a representation coherently together appears to be less prone to errors than binding several different information streams together into a coherent phenomenal model of the world. (shrink)

The “binding problem” has been a central question in vision science for some 30 years: When encoding multiple objects or maintaining them in working memory, how are we able to represent the correspondence between a specific feature and its corresponding object correctly? In this letter we argue that the boundaries of this research program in fact extend far beyond vision, and we call for coordinated pursuit across the broader cognitive science community of this central question for cognition, which we (...) dub “Binding Problem 2.0”. (shrink)

The capacity for feature binding is typically explained in terms of the attribution model: a perceptual state selects an individual and attributes properties to it (Kahneman & Treisman 1984; Clark 2004; Burge 2010). Thus features are bound together in virtue of being attributed to the same individual. While the attribution model successfully explains some cases of binding in perception, not all binding need be understood as property attribution. This chapter argues that some forms of binding—those involving (...) holistic iconic representations, which bind features outside the limits of attention and object files—don’t fit the attribution model. The chapter then sketches an alternative coordination model of binding that construes icons as complex analog representations. (shrink)

It is nearly 10 years since Patrick Haggard and colleagues first reported the ‘intentional binding’ effect . The intentional binding effect refers to the subjective compression of the temporal interval between a voluntary action and its external sensory consequence. Since the first report, considerable interest has been generated and a fascinating array of studies has accumulated. Much of the interest in intentional binding comes from the promise to shed light on human agency. In this review we survey (...) studies on intentional binding, focusing, in particular, on the link between intentional binding and the sense of agency . We suggest that, whilst it is yet to be fully explicated, the link between intentional binding and the sense of agency is compelling. We conclude by considering outstanding questions and future directions for research on intentional binding. (shrink)

In this paper, we defend a traditional approach to semantics, that holds that the outputs of compositional semantics are propositional, i.e. truth conditions. Though traditional, this view has been challenged on a number of fronts over the years. Since classic work of Lewis, arguments have been offered which purport to show that semantic composition requires values that are relativized, e.g. to times, or other parameters that render them no longer propositional. Focusing in recent variants of these arguments involving quantification and (...) binding, we argue that a correct understanding of how composition works gives no reason to relativize semantic values, and that propositional semantic values are in fact the preferred option. We take our argument to be mainly empirical, but along the way, we defend some more general theses. Simple propositional semantic values are viable in composition, we maintain, because composition is itself a complex phenomenon, involving multiple modes of composition. Furthermore, some composition principles make adjustments to the meanings of constituents in the course of composition. These adjustments are by triggered syntactic environments. We argue such small contributions of meaning from syntactic structure are acceptable. (shrink)

A more extensive discussion of certain of the more technical notions appears in my paper "On Binding" (Chomsky,; henceforth, OB). ...

The binding problem is frequently discussed in consciousness research. However, it is by no means clear what the problem is supposed to be and how exactly it relates to consciousness. In the present paper the nature of the binding problem is clarified by distinguishing between different formulations of the problem. Some of them make no mention of consciousness, whereas others are directly related to aspects of phenomenal experience. Certain formulations of the binding problem are closely connected to (...) the classical philosophical problem of the unity of consciousness and the currently fashionable search for the neural correlates of consciousness. Nonetheless, only a part of the current empirical research on binding is directly relevant to the study of consciousness. The main message of the present paper is that the science of consciousness needs to establish a clear theoretical view of the relation between binding and consciousness and to encourage further empirical work that builds on such a theoretical foundation. (shrink)

It is tempting to hold that perceptual experience amounts to a co-conscious collection of visual, auditory, tactual, gustatory, and olfactory episodes. If so, each aspect of perceptual experience on each occasion is associated with a specific modality. This paper, however, concerns a core variety of multimodal perceptual experience. It argues that there is perceptually apparent intermodal feature binding. I present the case for this claim, explain its consequences for theorizing about perceptual experience, and defend it against objections. I maintain (...) that just as one thing may perceptually appear at once to jointly bear several features associated with the same sense modality, one thing also may perceptually appear at once to jointly bear features associated with different sense modalities. For instance, just as something may visually appear at once to be both red and round, or to have a red part and a green part, something may multimodally perceptually appear at once to be both bright and loud, or to have a red part and a rough part. The main lesson, I argue, is that perceiving is not just co-consciously seeing, hearing, feeling, tasting, and smelling at the same time. And perceptual phenomenal character is not on each occasion exhausted by that which is distinctive to or associated with a given modality, along with that which accrues thanks to simple co-consciousness. Not all ways of perceiving are modality specific. I defend this account against three main objections: that singular content theorists avoid my conclusions; that apparent infusion of perceptible features is required for perceptually apparent binding but does not occur intermodally; and that the diversity of objects across modalities makes perceptually apparent intermodal binding rare. (shrink)

o (2000), 243). In particular, the idea is that binding interactions between the relevant expressions and natural lan- guage quantifiers are best explained by the hypothesis that those expressions harbor hidden but bindable variables. Recently, however, Herman Cappelen and Ernie Lepore have rejected such binding arguments for the presence of hid- den variables on the grounds that they overgeneralize — that, if sound, such arguments would establish the presence of hidden variables in all sorts of ex- pressions where (...) it is implausible that they exist (Cappelen and Lepore (2005), Cappelen and Lepore (2002)).1 In what follows we respond to Cappelen’s and Lepore’s attempted reductio by bringing out crucial disanalogies between cases where the binding argument is successful and cases where it is not. But we have a deeper purpose than merely to respond to Cappelen and Lepore: we think the attempted reductio goes wrong by not taking sufficiently seriously the nature of the binding relation that holds between quantifiers and arguments/variables, and that our criticism will serve to highlight the nature and importance of this relation. (shrink)

Theories of binding have recently come into the focus of the consciousness debate. In this review, we discuss the potential relevance of temporal binding mechanisms for sensory awareness. Specifically, we suggest that neural synchrony with a precision in the millisecond range may be crucial for conscious processing, and may be involved in arousal, perceptual integration, attentional selection and working memory. Recent evidence from both animal and human studies demonstrates that specific changes in neuronal synchrony occur during all of (...) these processes and that they are distinguished by the emergence of fast oscillations with frequencies in the gamma-range. (shrink)

Binding specificity is a centrally important concept in molecular biology, yet it has received little philosophical attention. Here I aim to remedy this by analyzing binding specificity as a causal property. I focus on the concept’s role in drug design, where it is highly prized and hence directly studied. From a causal perspective, understanding why binding specificity is a valuable property of drugs contributes to an understanding of causal selection—of how and why scientists distinguish between causes, not (...) just causes from noncauses. In particular, the specificity of drugs is precisely what underwrites their value as experimental interventions on biological processes. (shrink)