Abstract Although noting the importance of organization in mechanisms, the new mechanistic philosophers of science have followed most biologists in focusing primarily on only the simplest mode of organization in which operations are envisaged as occurring sequentially. Increasingly, though, biologists are recognizing that the mechanisms they confront are non-sequential and the operations nonlinear. To understand how such mechanisms function through time, they are turning to computational models and tools of dynamical systems theory. Recent research on circadian rhythms (...) addressing both intracellular mechanisms and the intercellular networks in which these mechanisms are synchronized illuminates this point. This and other recent research in biology shows that the new mechanistic philosophers of science must expand their account of mechanistic explanation to incorporate computational modeling, yielding dynamical mechanistic explanations. Developing such explanations, however, is a challenge for both the scientists and the philosophers as there are serious tensions between mechanistic and dynamical approaches to science, and there are important opportunities for philosophers of science to contribute to surmounting these tensions. Content Type Journal Article Category Original paper in Philosophy of Science Pages 1-16 DOI 10.1007/s13194-012-0046-x Authors William Bechtel, Department of Philosophy, Center for Chronobiology, and Science Studies Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0119, USA Journal European Journal for Philosophy of Science Online ISSN 1879-4920 Print ISSN 1879-4912. (shrink)

We contrast reactive and endogenously active perspectives on brain activity. Both have been pursued continuously in neurophysiology laboratories since the early 20thcentury, but the endogenous perspective has received relatively little attention until recently. One of the many successes of the reactive perspective was the identification, in the second half of the 20th century, of the distinctive contributions of different brain regions involved in visual processing. The recent prominence of the endogenous perspective is due to new findings of ongoing (...) oscillatory activity in the brain at a wide range of time scales, exploiting such techniques as single-cell recording, EEG, and fMRI. We recount some of the evidence pointing to ways in which this endogenous activity is relevant to cognition and behavior. Our major objective is to consider certain implications of the contrast between the reactive and endogenous perspectives. In particular, we relate these perspectives to two different characterizations of explanation in the new mechanistic philosophy of science. In a basic mechanistic explanation, the operations of a mechanism are characterized qualitatively and as functioning sequentially until a terminating condition is realized. In contrast, a dynamic mechanistic explanation allows for non-sequential organization and emphasizes quantitative modeling of the mechanisms's behavior. For example, with appropriate parameter values a set of differential equations can be used to demonstrate ongoing oscillations in a system organized with feedback loops. We conclude that the basic conception of mechanistic explanation is adequate for reactive accounts of brain activity, but dynamical accounts are required to explain sustained, endogenous activity. (shrink)

Although a reactive framework has long been dominant in cognitive science and neuroscience, an alternative framework emphasizing dynamics and endogenous activity has recently gained prominence. We review some of the evidence for endogenous activity and consider the implications not only for understanding cognition but also for accounts of explanation offered by philosophers of science. Our recent characterization of dynamic mechanistic explanation emphasizes the coordination of accounts of mechanisms that identify parts and operations with computational models of their activity. These (...) can, and should, be extended to incorporate attention to mechanisms that are not only active, but endogenously active. (shrink)

Malignant cells are characterized by an increased content of endogenous formaldehyde formed as a by‐product of biosynthetic processes. Accumulation of formaldehyde in cancer cells is combined with activation of the processes of cellular formaldehyde clearance. These mechanisms include increased ALDH and suppressed ADH5/FDH activity, which oncologists consider poor and favorable prognostic markers, respectively. Here, the sources and regulation of formaldehyde metabolism in cancer cells are reviewed. The authors also analyze the participation of oncoproteins such as fibulins, FGFR1, HER2/neu, FBI‐1, (...) and MUC1‐C in the control of genes related to formaldehyde metabolism, suggesting the existence of two mutually exclusive processes in cancer cells: 1) production and 2) oxidation and elimination of formaldehyde from the cell. The authors hypothesize that the study of the anticancer properties of disulfiram and alpha lipoic acid – which affect the balance of formaldehyde in the body – may serve as the basis of future anticancer therapy. (shrink)

Explaining the complex dynamics exhibited in many biological mechanisms requires extending the recent philosophical treatment of mechanisms that emphasizes sequences of operations. To understand how nonsequentially organized mechanisms will behave, scientists often advance what we call dynamic mechanistic explanations. These begin with a decomposition of the mechanism into component parts and operations, using a variety of laboratory-based strategies. Crucially, the mechanism is then recomposed by means of computational models in which variables or terms in differential equations correspond (...) to properties of its parts and operations. We provide two illustrations drawn from research on circadian rhythms. Once biologists identified some of the components of the molecular mechanism thought to be responsible for circadian rhythms, computational models were used to determine whether the proposed mechanisms could generate sustained oscillations. Modeling has become even more important as researchers have recognized that the oscillations generated in individual neurons are synchronized within networks; we describe models being employed to assess how different possible network architectures could produce the observed synchronized activity. (shrink)

Angiogenesis is a complex morphogenetic process regulated by growth factors, but also by the force balance between endothelial cells traction stresses and extracellular matrix viscoelastic resistance. Studies conducted with in vitro angiogenesis assays demonstrated that decreasing ECM stiffness triggers an angiogenic switch that promotes organization of EC into tubular cords or pseudo-capillaries. Thus, mechano-sensitivity of EC with regard to proteases secretion, and notably matrix metalloproteinases, should likely play a pivotal role in this switching mechanism. While most studies analysing strain regulation (...) of MMPs used cell cultured on stretched membranes, this work focuses on MMP expression during self-assembly of EC into capillary-like structures within fibrin gels, i.e. on conditions that mimics more closely the in vivo cellular mechanical microenvironment. The activity of MMP-2 and MMP-9, two MMPs that have a pivotal role in capillaries formation, has been monitored in pace with the progressive elongation of EAhy926 cells that takes place during the emergence of cellular cords. We found an increase of the zymogen proMMP-2 that correlates with the initial stages of EC cords formation. However, MMP-2 was not detected. ProMMP-9 secretion decreased, with levels of MMP-9 kept at a rather low value. In order to analyse more precisely the observed differences of EAhy926 response on fibrin and plastic substrates, we proposed a theoretical model of the mechano-regulation of proMMP-2 activation in the presence of type 2 tissue inhibitor of MMPs. Using association/dissociation rates experimentally reported for this enzymatic network, the model adequately describes the synergism of proMMP-2 and TIMP-2 strain activation during pseudo-capillary morphogenesis. All together, these results provide a first step toward a systems biology approach of angiogenesis mechano-regulation by cell-generated extracellular stresses and strains. (shrink)

Proteolytic cleavage of extracellular matrix (ECM) is a critical regulator of many physiological and pathological events. It affects fundamental processes such as cell growth, differentiation, apoptosis and migration. Most proteases are produced as inactive proenzymes that undergo proteolytic cleavage for activation. Proteolytic activity is additionally modified by endogenous inhibitors. Mechanisms that localize and concentrate protease activity in the pericellular microenvironment of cells are prerequisites for processes like angiogenesis, bone development, inflammation and tumor cell invasion. Methods that enable real‐time, high‐resolution (...) imaging and precise quantification of local proteolytic activity in vitro and in vivo remain major challenges. These methods will play an important role in the understanding of basic principles e.g. in cancer cell invasion, the identification of new therapeutical targets and hence drug design. This review highlights mechanisms and functions of local proteolytic activity with special emphasis on tumor cell invasion and metastasis, and focuses on techniques for the investigation of this process. BioEssays 27:1181–1191, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Whether active and passive, top-down and bottom-up, or endogenous and exogenous, attention is typically divided into two types. To show the relationship between attention and other functions (sleep, memory, learning), one needs to show whether the type of attention in question is of the active or passive variety. However, the division between active and passive is not sharp in any area of consciousness research. In phenomenology, the experience of voluntariness is taken to indicate activity, but this experience (...) is often confused with others. In psychology, task-dependent behavior is taken to indicate activity, but is often conflated with complex automatic behavior. In neuroscience, top-down processes are taken to exclusively indicate activity despite the fact that both top-down and bottom-up activations are always present in the brain. Moreover, work in attention has shown that the results of so-called passive and active processes are sometimes inseparable. Carrasco, et al. (2004), for example, show that active attention results in the same change in perceptual contrast that is enacted by bottom-up mechanisms. Likewise, Reynolds and Desimone (2003) show that top-down and bottom-up attention effect neural contrast in the same way. Thus, the passive-active distinction does not seem to neatly separate two types of attention. Perhaps a more convincing model of attention combines active and passive processing into a single mechanism of control. One such potential model is what we call the Unitary Saliency Map Model, first suggested by Koch and Ullman (1985) and developed by Treue (2003). In such a model, top-down and bottom-up processes each feed into the same saliency map, from which attention is controlled. We argue that this makes sense of the phenomenological, psychological, and neuroscientific data. Finally, the acceptance of such a model will force us to review some of our previous findings on attention and its relation to consciousness. (shrink)

dickenson briefly mentions that peripheral opioid receptors somehow become active following inflammation and that the appearance of endogenous opioid peptides at the injury site may be related to immune cell proliferation. Recent findings elucidate the underlying mechanisms in more detail and provide an incentive for the development of a novel generation of analgesics devoid of typical central opioid side effects.

La plupart des projets d’architectures cognitives dans les sciences cognitives et des explications des processus cérébraux dans les neurosciences interprètent l’esprit/cerveau comme réactif : le processus est déclenché par un stimulus et se termine par une réponse. Mais il y a de plus en plus de données laissant penser que le cerveau est endogéniquement actif : des oscillations de l’activité électrochimique à de multiples fréquences ont lieu dans le cerveau même en l’absence de stimuli et ceux-ci servent plutôt à moduler (...) ces oscillations qu’à déclencher l’activité. De plus, des données montrent que cette activité endogène est utilisée dans diverses activités de traitement de l’information. Je m’appuie sur les données issues des enregistrements cellulaires unitaires, de l’EEG et de l’IRMf en situation passive, afin de soutenir la thèse d’un comportement oscillatoire continu dans le cerveau et d’identifier plusieurs manières dont ce comportement peut contribuer à la cognition. Si les sciences cognitives ont pour but de comprendre comment nous effectuons des tâches cognitives, elles ont besoin de développer des architectures cognitives qui intègrent le type d’activité endogène dynamique présentée par le cerveau. (shrink)

La plupart des projets d’architectures cognitives dans les sciences cognitives et des explications des processus cérébraux dans les neurosciences interprètent l’esprit/cerveau comme réactif : le processus est déclenché par un stimulus et se termine par une réponse. Mais il y a de plus en plus de données laissant penser que le cerveau est endogéniquement actif : des oscillations de l’activité électrochimique à de multiples fréquences ont lieu dans le cerveau même en l’absence de stimuli et ceux-ci servent plutôt à moduler (...) ces oscillations qu’à déclencher l’activité. De plus, des données montrent que cette activité endogène est utilisée dans diverses activités de traitement de l’information. Je m’appuie sur les données issues des enregistrements cellulaires unitaires, de l’EEG et de l’IRMf en situation passive, afin de soutenir la thèse d’un comportement oscillatoire continu dans le cerveau et d’identifier plusieurs manières dont ce comportement peut contribuer à la cognition. Si les sciences cognitives ont pour but de comprendre comment nous effectuons des tâches cognitives, elles ont besoin de développer des architectures cognitives qui intègrent le type d’activité endogène dynamique présentée par le cerveau. (shrink)

Conflict can profoundly affect individuals and their groups. Oftentimes, conflict involves a clash between one side seeking change and increased gains through victory and the other side defending the status quo and protecting against loss and defeat. However, theory and empirical research largely neglected these conflicts between attackers and defenders, and the strategic, social, and psychological consequences of attack and defense remain poorly understood. To fill this void, we model (1) the clashing of attack and defense as games of strategy (...) and reveal that (2) attack benefits from mismatching its target's level of defense, whereas defense benefits from matching the attacker's competitiveness. This suggests that (3) attack recruits neuroendocrine pathways underlying behavioral activation and overconfidence, whereas defense invokes neural networks for behavioral inhibition, vigilant scanning, and hostile attributions; and that (4) people invest less in attack than defense, and attack often fails. Finally, we propose that (5) in intergroup conflict, out-group attack needs institutional arrangements that motivate and coordinate collective action, whereas in-group defense benefits from endogenously emerging in-group identification. We discuss how games of attack and defense may have shaped human capacities for prosociality and aggression, and how third parties can regulate such conflicts and reduce their waste. (shrink)

The mammalian Zc3h12a/MCPIP1/Regnase-1, an extensively studied regulator of inflammatory response, is the founding member of a ribonuclease family, which includes proteins related by the presence of the so-called Zc3h12a-like NYN domain. Recently, several related proteins have been described in Caenorhabditis elegans, allowing comparative evaluation of molecular functions and biological roles of these ribonucleases. We discuss the structural features of these proteins, which endow some members with ribonuclease activity while others with auxiliary or RNA-independent functions. We also consider their RNA specificity (...) and highlight a common role for these proteins in cellular defense, which is remarkable considering the evolutionary distance and fundamental differences in cellular defense mechanisms between mammals and nematodes. Regnase-1-related RNases have evolutionary conserved roles connected to cellular defense, targeting exogenous and endogenous pathogenic agents. (shrink)

Aversive experiences have been thought to provoke or exacerbate clinical depression. The present review provides a brief survey of the stress-depression literature and suggests that the effects of stressful experiences on affective state may be related to depletion of several neurotransmitters, including norepinephrine, dopamine, and serotonin. A major element in determining the neurochemical changes is the organism's ability to cope with the aversive stimuli through behavioral means. Aversive experiences give rise to behavioral attempts to cope with the stressor, coupled with (...) increased utilization and synthesis of brain amines to contend with environmental demands. When behavioral coping is possible, neurochemical systems are not overly taxed, and behavioral pathology will not ensue. However, when there can be no behavioral control over the stressful stimuli, or when the aversive experience is perceived as uncontrollable, increased emphasis is placed on coping through endogenous neurochemical mechanisms. Amine utilization increases appreciably and may exceed synthesis, resulting in a net reduction of amine stores, which in turn promotes or exacerbates affective disorder. The processes governing the depletions may be subject to sensitization or conditioning, such that exposure to traumatic experiences may have long-term repercussions when the organism subsequently encounters related stressful stimuli. With continued uncontrollable stimulation, adaptation occurs in the form of increased activity of synthetic enzymes, and levels of amines approach basal values. It is suggested that either the initial amine depletion provoked by aversive experiences or a dysfunction of the adaptive processes, resulting in persistent amine depletion, contributes to behavioral depression. Aside from the contribution of behavioral coping, several organismic, experiential, and environmental variables will influence the effects of aversive experiences on neurochemical activity, and may thus influence vulnerability to depression. (shrink)

Does the desirability of social institutions for public goods provision depend on the extent to which they include mechanisms for endogenous enforcement of cooperative behavior? We consider alternative institutions that vary the use of direct punishments to promote social cooperation. In one institution, subjects participate in a public goods experiment in which an initial stage of voluntary contribution is followed by a second stage of voluntary, costly sanctioning. Another institution consists of the voluntary contribution stage only, with no subsequent (...) opportunity to sanction. In a third stage subjects vote for which institution they prefer for future interactions: do they prefer one that does allow sanctions or one that does not allow sanctions? Our results show that even though sanctions are frequently used when available, the clear majority of individuals vote for the institution that does not allow sanctions. Thus, a distinction is required between the principles that guide the choice of institutions and the principles that apply to actions guided by institutions. Our results indicate that it is the wealth generated by the institution that determines its desirability. (shrink)

Biofeedback mechanisms (a) between individuals, (b) between the individual and the society structures which shape individual cognitions, and (c) within the individual genetic biochemical circulation, may explain the diversity of trustworthiness potential and the option of mutual trust for every individual in any given society.

This article deals with mechanisms conceived as composed of entities and activities. In response to many perplexities about the nature of activities, a number of arguments are developed concerning their epistemic and ontological status. Some questions concerning the relations between cause and causal explanation and mechanisms are also addressed.

Unless one embraces activities as foundational, understanding activities in mechanisms requires an account of the means by which entities in biological mechanisms engage in their activities—an account that does not merely explain activities in terms of more basic entities and activities. Recent biological research on molecular motors exemplifies such an account, one that explains activities in terms of free energy and constraints. After describing the characteristic “stepping” activities of these molecules and mapping the stages of those steps onto (...) the stages of the motors’ hydrolytic cycles, researchers pieced together from images of the molecules in different hydrolyzation states accounts of how the chemical energy in ATP is transformed in the constrained environments of the motors into the characteristic activities of the motors. We argue that New Mechanism’s standard set of analytic categories—entities, activities, and organization—should be expanded to include constraints and energetics. Not only is such an expansion required descriptively to capture research on molecular motors but, more importantly from a philosophical point of view, it enables a non-regressive account of activities in mechanisms. In other words, this expansion enables a philosophical account of mechanistic explanation that avoids a regress of entities and activities “all the way down.” Rather, mechanistic explanation bottoms out in constraints and energetics. (shrink)

Aversive experiences have been thought to provoke or exacerbate clinical depression. The present review provides a brief survey of the stress-depression literature and suggests that the effects of stressful experiences on affective state may be related to depletion of several neurotransmitters, including norepinephrine, dopamine, and serotonin. A major element in determining the neurochemical changes is the organism's ability to cope with the aversive stimuli through behavioral means. Aversive experiences give rise to behavioral attempts to cope with the stressor, coupled with (...) increased utilization and synthesis of brain amines to contend with environmental demands. When behavioral coping is possible, neurochemical systems are not overly taxed, and behavioral pathology will not ensue. However, when there can be no behavioral control over the stressful stimuli, or when the aversive experience is perceived as uncontrollable, increased emphasis is placed on coping through endogenous neurochemical mechanisms. Amine utilization increases appreciably and may exceed synthesis, resulting in a net reduction of amine stores, which in turn promotes or exacerbates affective disorder. The processes governing the depletions may be subject to sensitization or conditioning, such that exposure to traumatic experiences may have long-term repercussions when the organism subsequently encounters related stressful stimuli. With continued uncontrollable stimulation, adaptation occurs in the form of increased activity of synthetic enzymes, and levels of amines approach basal values. It is suggested that either the initial amine depletion provoked by aversive experiences or a dysfunction of the adaptive processes, resulting in persistent amine depletion, contributes to behavioral depression. Aside from the contribution of behavioral coping, several organismic, experiential, and environmental variables will influence the effects of aversive experiences on neurochemical activity, and may thus influence vulnerability to depression. (shrink)

Signaling by the Epidermal Growth Factor Receptor (EGFR) and related ErbB family receptor tyrosine kinases can be deregulated in human malignancies as the result of mutations in the genes that encode these receptors. The recent identification of EGFR mutations that correlate with sensitivity and resistance to EGFR tyrosine kinase inhibitors in lung and colon tumors has renewed interest in such activating mutations. Here we review current models for ligand stimulation of receptor dimerization and for activation of receptor signaling by receptor (...) dimerization. In the context of these models, we discuss ErbB receptor mutations that affect ligand binding and those that cause constitutive receptor phosphorylation and signaling as a result of constitutive receptor dimerization. We discuss mutations in the cytoplasmic regions that affect enzymatic activity, substrate specificity and coupling to effectors and downstream signaling pathways. Finally, we discuss how emergent mechanisms of ErbB receptor mutational activation could impact the search for clinically relevant ErbB receptor mutations. BioEssays 29:558–565, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The developmental programs of eukaryotic organisms involve the programmed transcription of genes. A characteristic gene expression pattern is established and preserved in each different cell type. Therefore, gene activation at a particular time and its maintenance during cell division are significant for cellular differentiation and individual development. Although many studies have sought to explain the molecular mechanisms of gene expression regulation, the mechanism through which gene expression states are inherited during cell division has not been fully elucidated yet. This (...) review illustrates the general principles and the complexities involved in the establishment and maintenance of active transcription through cell cycles. It focuses on the most‐recent findings about the ways in which molecular memory marks for active transcription are coordinated with cell cycle events, such as replication, mitosis and nuclear organization, to mediate transcription memory across cell division events, which may establish a unifying memory process of active transcription. BioEssays 27:1239–1245, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

In this article I examine whether an influential theory of mechanisms proposed by Peter Machamer, Lindley Darden and Carl Craver can accommodate polygenic effects. This theory is both interesting and problematic, I will argue, because it ascribes a central role to activities. In it, activities are needed not only to constitute mechanisms but also to perform their causal role. These putative functions of activities become problematic in certain situations where several causes or elements of a mechanism contribute simultaneously, (...) i.e. with certain forms of polygenic causation. The problematic form of polygeny, polygeny 2, occurs when the polygenic contribution concerns one and the same property or aspect of the affected object. When the result of such causation is that nothing happens, the theory suggested by Machamer and his colleagues cannot be applied. More generally, it seems that, whenever polygeny 2 is involved, the Machamer approach leads to an impoverished conception of mechanism. (shrink)

The central question facing sleep and dream science today seems to be: What is the physiological basis of the subset of NREM dreams that are qualitatively indistinguishable from REM dreams (“apex dreams”)? Two competing answers have emerged: (1) all apex dreams are generated by REM sleep control mechanisms, albeit sometimes covertly; and (2) all such dreams are generated by forebrain mechanisms, independently of classical pontine sleep-cycle control mechanisms. The principal objection to the first answer is that it (...) lacks evidential support. The principal objection to the second answer (which is articulated in my target article) is that it takes inadequate account of interactions that surely exist between the putative forebrain mechanisms and the well established brainstem mechanisms of conscious state control. My main response to this objection (elaborated below) is that it conflates nonspecific brainstem modulation – which supports consciousness in general – with a specific pontine mechanism that is supposed to generate apex dreaming in particular. The latter mechanism is in fact neither necessary nor sufficient for apex dreaming. The putative forebrain mechanisms, by contrast, are necessary for apex dreaming (although they are nor sufficient, in the limited sense that all conscious states of the forebrain are modulated by the brainstem). (shrink)

ObjectivesThe aims of this research were to compare the levels of physical activity of eHealth users and non-users, to determine the effects of these technologies on motivations, and to establish the relationship that could exist between psychological constructs and physical activity behaviors.MethodsThis cross-sectional study involved 569 adults who responded to an online questionnaire during confinement in France. The questions assessed demographics, usage of eHealth for exercise and physical activity, and behavioral levels. The questionnaire also measured the constructs of Social Cognitive (...) Theory, the Theory of Planned Behavior, and automaticity facets toward eHealth for exercise and physical activity.ResultsParticipants who were users of eHealth for exercise and physical activity presented significantly higher levels of vigorous physical activity and total physical activity per week than non-users. The chi-square test showed significant interactions between psychological constructs toward eHealth and physical activity levels. Self-efficacy was significantly and negatively correlated with walking time per week. Concerning the automaticity facets, efficiency was positive and significantly correlated with vigorous physical activity levels per week. Then, regressions analyses showed that self-efficacy and automaticity efficiency explained 5% of the variance of walking minutes per week and vigorous physical activity per week, respectively.ConclusionThis study has shown that people during confinement looked for ways to stay active through eHealth. However, we must put any technological solution into perspective. The eHealth offers possibilities to stay active, however its benefits and the psychological mechanisms affected by it remains to be demonstrated: eHealth could be adapted to each person and context. (shrink)

Mechanical reductionism, which deals entirely with homogeneous variables, will constrain and enable the activities of richly heterogeneous living systems, but it cannot determine their outcomes. Such indeterminism owes to problems with dimensionality, dynamical logic, intractability, and insufficiency. The order in any living structure arises via an historical series of contingencies that were selected endogenously by stable autocatalytic processes in tandem with, and usually in opposition to, conventional external influences (natural selection). The development of living communities thereby resembles a Heraclitean (...) dialectic between processes that build up and those that tear down. Investigating this unconventional dynamic requires metaphysical assumptions that are complementary to those that have guided science over the past three centuries. The new dynamics can be represented in terms of weighted networks of interacting processes, which facilitate the statement of testable hypotheses. Network analysis thereby implements and tests ideas that heretofore could only be addressed as verbal propositions. (shrink)

This paper develops a mechanistic account of basic mental agency by identifying similarities between two of its major exemplars: endogenous attention and imagination. Five key similarities are identified: i) that both capacities are driven by currently prioritised goals that are either person-level or apt to become person-level. ii) that both deliver their outputs to the working memory iii) that both range across all and only conceptual contents; iv) that both proceed under the guidance of norms and/or habits; and v) that (...) both directly activate rather than inhibit content. These five features are consolidated by proposing that basic mental agency is essentially the power to call for conceptual content and hold it within our working memories. (shrink)

This chapter present a glimpse of medieval academic discussions concerning sense perception, which had by the end of the Middle Ages gained a prominent position as a major element of Aristotelian psychology.

Convincing narratives are not confabulations. Presumably they “feel right” to decision-making agents because the probabilities they assign intuitively (i.e., implicitly) to potential outcomes are plausible. Can we render explicit the calculations that would be performed by a decision-making agent to evaluate the plausibility of competing narratives? And if we can, what, exactly, makes a narrative “feel right” to an agent?

The phenomenon of consciousness has received through the centuries a profusion of interpretations, engaging researchers across many disciplines. Nevertheless, consensus still floats at large. The aim of the present work is therefore twofold. Through the review of a selected number of existing proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network will consequently be introduced which, besides being able to accommodate the main (...) tenets of the reviewed theories, appears able to compensate for the explanatory gaps they leave behind. The EFN proposes consciousness as the phenomenon emerging from a distinct neural network broadcasting the changes associated to mental activations across the brain. It additionally argues for the need to include a 5th element to Ned Block’s taxonomy that is, non-cognitive consciousness. (shrink)

In the most inclusive sense, psychological mechanisms offer a type of causal explanation of mental states and behavior, often with reference to underlying processes, systems, activities, or entities. By postulating and investigating such mechanisms, researchers have sought explanations of a wide range of psychological phenomena. However, the concept has been deployed in dramatically different ways, with very different meanings, depending upon the particular school or tradition of psychology (and specific research program therein). In fact, usage has been so (...) diverse as to defy easy categorization or definition. But a historical perspective, even if rather selective, can trace the broad outlines of the significance of psychological mechanisms for the study of the mind. Perhaps most notable is the role they have played in the psychoanalytic tradition; research efforts within behaviorism and cognitive science have also made liberal use of versions of the concept in their explanatory frameworks (for discussion of evolutionary psychology, see the entry “evolved psychological mechanisms”). Cutting across all of these traditions are several key themes relating to psychological mechanisms, including questions concerning the scope of the relevant causal claims, debates about causal determinism and regularity, and the unresolved relation between mind and body. (shrink)

In eukaryotes, double‐stranded RNAs (dsRNAs) or short, interfering dsRNAs (siRNAs) can reduce the accumulation of a sequence‐related mRNA, often resulting in a loss‐of‐function phenotype—a process termed RNA interference (RNAi). Unfortunately, some mRNAs are resistant to the effects of dsRNA. Experiments designed to unravel RNAi mechanisms in Caenorhabditis elegans have led to the identification of two worm proteins, RRF‐31,2 and, now, ERI‐1,3 that can inhibit RNAi responses. Animals defective in either protein can display enhanced RNAi phenotypes for mRNAs that were (...) previously resistant to dsRNA. Since ERI‐1 is a conserved protein, development of procedures to enhance RNAi effectiveness in other systems may be possible. BioEssays 26:715–718, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Quantum mechanical and molecular dynamics methods were used to analyze the structure and stability of neutral and zwitterionic configurations of the extracted active site sequence from a Burkholderia cepacia lipase, histidyl-seryl-glutamin (His86-Ser87-Gln88) and its mutated form, histidyl-cysteyl-glutamin (His86-Cys87-Gln88) in vacuum and different solvents. The effects of solvent dielectric constant, explicit and implicit water molecules and side chain mutation on the structure and stability of this sequence in both neutral and zwitterionic forms are represented. The quantum mechanics computations represent that (...) the relative stability of zwitterionic and neutral configurations depends on the solvent structure and its dielectric constant. Therefore, in vacuum and the considered non-polar solvents, the neutral form of the interested sequences is more stable than the zwitterionic form, while their zwitterionic form is more stable than the neutral form in the aqueous solution and the investigated polar solvents in most cases. However, on the potential energy surfaces calculated, there is a barrier to proton transfer from the positively charged ammonium group to the negatively charged carboxylat group or from the ammonium group to the adjacent carbonyl oxygen and or from side chain oxygen and sulfur to negatively charged carboxylat group. Molecular dynamics simulations (MD) were also performed by using periodic boundary conditions for the zwitterionic configuration of the hydrated molecules in a box of water molecules. The obtained results demonstrated that the presence of explicit water molecules provides the more compact structures of the studied molecules. These simulations also indicated that side chain mutation and replacement of sulfur with oxygen leads to reduction of molecular flexibility and packing. (shrink)

his monograph examines the metaphysical commitments of the new mechanistic philosophy, a way of thinking that has returned to center stage. It challenges a variant of reductionism with regard to higher-level phenomena, which has crystallized as a default position among these so-called New Mechanists. Furthermore, it opposes those philosophers who reject the possibility of interlevel causation. Contemporary philosophers believe that the explanation of scientific phenomena requires the discovery of relevant mechanisms. As a result, new mechanists are, in the main, (...) concerned solely with epistemological questions. But, the author argues, their most central claims rely on metaphysical assumptions. Thus, they must also take into account metaphysics, a system of thought concerned with explaining the fundamental nature of being and the world around it. This branch of philosophy does indeed matter to the empirical sciences. The chapters investigate the nature of mechanisms, their components, and the ways in which they can bring about different phenomena. In addition, the author develops a novel account of causation in terms of activities. The analysis provides the basis for many further research projects on mechanisms and their relations to, for example, the mind-body problem, realization, multiple realization, natural kinds, causation, laws of nature, counterfactuals, and scientific levels. (shrink)

I support the music and social bonding framework, but submit that the authors' predictions lack discriminative power, and that they do not engage sufficiently with the emotion mechanisms that mediate between musical features and social bonding. I elaborate on how various mechanisms may contribute, in unique ways, to social bonding at various levels to help account for the socio-emotional effects of music.