Substrate independence and mind-body functionalism claim that thinking does not depend on any particular kind of physical implementation. But real-world information processing depends on energy, and energy depends on material substrates. Biological evidence for these claims comes from ecology and neuroscience, while computational evidence comes from neuromorphic computing and deep learning. Attention to energy requirements undermines the use of substrate independence to support claims about the feasibility of artificial intelligence, the moral standing of robots, the possibility that we (...) may be living in a computer simulation, the plausibility of transferring minds into computers, and the autonomy of psychology from neuroscience. (shrink)

Interleukin 1β‐converting enzyme (ICE)‐like proteases (caspases) play an important role in programmed cell death (apoptosis), and elucidating the consequences of their proteolytic activity is central to our understanding of the molecular mechanisms of cell death. Diverse structural and regulatory proteins and enzymes, including protein kinase Cδ, the retinoblastoma protein (a protein involved in cell survival), the DNA repair enzyme DNA‐dependent protein kinase and the nuclear lamins, undergo specific and limited endoproteolytic cleavage by various caspases during apoptosis. Since individual caspases can (...) cleave multiple substrates, the consequences of cleavage of only a single substrate are still poorly understood. Nevertheless, proteolytic activation of protein kinase Cδ may be an important early step in the cell death pathway, and cleavage of the retinoblastoma protein could suppress its cell survival function, whereas proteolytic inactivation of DNA repair enzymes might compromise the ability of the cell to reverse DNA fragmentation. On the other hand, cleavages of nuclear and cytoplasmic structural proteins (e.g. the lamins and Gas2) appear to be required for or contribute to the dramatic rearrangements in cellular architecture that are necessary for the completion of the cell death process. An emerging theme is that parallel and sequential proteolytic activation and inactivation of key protein substrates occurs during the multiple steps of apoptosis. (shrink)

BackgroundExercise is primarily sustained by energy derived from lipids, and glucose. Substrate utilization is the pattern by which these fuel sources are used during activity. There are many factors that influence substrate utilization. We aim to delineate the effect of exercise intensity and body composition on substrate utilization.ObjectiveThe objective of our study was to discern the differences in substrate utilization profiles during a maximal and submaximal graded exercise test, and to determine the extent to which body (...) composition influences substrate utilization during the exercise tests.MethodsA total of 27 male athletes, 32.5 ± 11 years of age, were recruited for this study. Body composition was analyzed using a bioelectrical impedance analyzer. Maximal and submaximal exercise tests were performed on a treadmill. A novel graded submaximal treadmill protocol was used for the submaximal test.ResultsAverage percent body fat was 15.8 ± 5%. Average maximal oxygen consumption was 47.6 ± 9 mL/kg/min, while the average exercise intensity at which participants were shifting to glucose predominance for energy during the maximal and submaximal tests were 76 ± 8.3% and 58.4 ± 21.1%, respectively. A paired-samples t-test was conducted to compare percent VO2max at crossover point in maximal and submaximal graded exercise tests. There was a significant difference in percent VO2max at the crossover point for maximal and submaximal tests. A linear regression was performed to elucidate the interaction between exercise intensity at the crossover point and body composition during a maximal and submaximal graded exercise test. There was a significant effect of PBF on percent VO2max at crossover point during the maximal graded exercise test [F = 9.10, P = 0.006] with an R2 of 0.245. However, there was no significant effect of PBF on percent VO2max at crossover point during the submaximal graded exercise test.ConclusionSubstrate utilization, represented by the crossover point, is dependent on the rate of increase in exercise intensity. At maximal efforts, the crossover to carbohydrates from fats as the predominant fuel source occurs at a significantly later stage of percent VO2max than at submaximal efforts. Furthermore, body composition represented by PBF is a significant predictor of substrate utilization during maximal efforts. Athletes with a relatively higher PBF are more likely to have increased lipid oxidation during high intensity exercises than those with a lower body fat percentage. (shrink)

A central source of socially meaningful signals is the face, which can be visually analyzed to understand a person's emotions, intentions, beliefs, and desires, along with information about that person's social status, approachability, age, and gender. This article reviews the neural basis of the perception of such signals in humans, focusing on facial expression and gaze, and touching on lesser-studied signals such as pupil dilation and blushing. It discusses the involvement of structures such as the insula, orbitofrontal cortex, amygdala, and (...) superior temporal gyrus, which are studied in some detail with respect to how they process social stimuli. It reveals that social perception also involves information from other modalities and depends on the context in which signals occur. (shrink)

Over many centuries, the homing pigeon has been selectively bred for returning home from a distant location. As a result of this strong selective pressure, homing pigeons have developed an excellent spatial navigation system. This system passes through the hippocampal formation, which shares many striking similarities to the mammalian hippocampus; there are a host of shared neuropeptides, interconnections, and its role in the storage and manipulation of spatial maps. There are some notable differences as well: there are unique connectivity patterns (...) and spatial encoding strategies. This review summarizes the comparisons between the avian and mammalian hippocampal systems, and the responses of single neurons in several general categories: location and place cells responding in specific areas, path and goal cells responding between goal locations, context-dependent cells that respond before or during a task, and pattern, grid, and boundary cells that increase firing at stable intervals. Head-direction cells, responding to a specific compass direction, are found in mammals and other birds but not to date in pigeons. By studying an animal that evolved under significant adaptive pressure to quickly develop a complex and efficient spatial memory system, we may better understand the comparative neurology of neurospatial systems, and plot new and potentially fruitful avenues of comparative research in the future. (shrink)

We agree with Shors & Matzel's general hypothesis that the proposed link between NMDA-dependent LTP and memory is weak. They suggest that NMDA-dependent LTP is important to arousal or attentional processes which influence learning in an anterograde manner. However, current evidence is also consistent with the view that NMDA receptors modulate memory consolidation retroactively, as occurs in several other receptor classes.

Research only alluded to by Preston & de Waal (P&deW) indicates the disproportionate involvement of some brain regions in the perception and experience of certain emotions. This suggests that the neural substrate of primitive emotional contagion has some emotion-specific aspects, even if cognitively sophisticated forms of empathy do not. Goals for future research include determining the ways in which empathy is emotion-specific and dependent on overt or covert perception.

Th. W. Adorno’s aesthetics represents a comprehensive reflection on a number of important topics in aesthetic research. Among them is the issue of the aesthetic experience generated by the beauty of nature. In the perspective of Adorno’s theory, the experience of natural beauty is described as a quality that forms in an immanent relation to the historical and social reality of humans. In the first place, one can observe the fundamental dependence of natural beauty on the degree of social (...) domination of nature. By failing to reflect on this social mediation, the experience of natural beauty appears to be immediate and creates the deceptive fantasy of the primordial form of nature. At the same time, however, Adorno uncovers a positive potential in the experience of natural beauty – it lies in the ability to transcend a power-based subjectivity that reduces reality to the substrate of the domination. By means of the transcendence of subjectivity, the experience of natural beauty opens up the possibility to perceive and approach reality in the unreduced fullness of its qualities while also anticipating a reconciliation of man with nature in an allegorical way. The aim of my study is to describe the sketched aspects of the experience of natural beauty. (shrink)

A model for kinetics of circular substrate cleavage by restriction endonuclease was formulated. The aim of the analysis of the model was to extract kinetic constants for all target sites from time- dependence of fragment concentration in reaction products. That was proved to be possible for molecules with an odd number of fragments only. A symmetry of the molecules with an even number of fragment is the cause. A solution for molecules with an odd number of fragments was (...) found and methods for dealing with the other molecules were suggested. (shrink)

How might philosophers and art historians make the best use of one another's research? That, in nuce, is what this special issue considers with respect to questions concerning the nature of photography as an artistic medium; and that is what my essay addresses with respect to a specific case: the dialogue, or lack thereof, between the work of the philosopher Stanley Cavell and the art historian-critic Rosalind Krauss. It focuses on Krauss's late appeal to Cavell's notion of automatism to argue (...) that artists now have to invent their own medium, both to provide criteria against which to judge artistic success or failure and to insulate serious art from the vacuous generalization of the aesthetic in a media-saturated culture at large.1 Much in the spirit of ‘Avant-Garde and Kitsch’, paying attention to the medium is once again an artist's best line of defence against the encroachment of new media, the culture industry, and spectacle. That Krauss should appeal to Cavell at all, let alone in such a Greenbergian frame of mind, is surprising if one is familiar with the fraught history of debate about artistic media in art theory since Greenberg. Cavell's work in this domain has always been closely associated with that of Michael Fried, and the mutual estrangement of Fried and Krauss, who began their critical careers as two of Greenberg's leading followers, is legendary.2I have written about the close connection between Fried's and Cavell's conceptions of an artistic medium before.3 Whereas Fried's and Cavell's early conception of an artistic medium was in a sense collaborative, emerging from an ongoing exchange of ideas at Harvard in the latter half of the 1960s, Krauss's much later appeal to the ideas of automatism and the automatic underpinning Cavell's conception of the photographic substrate of film from the early 1970s is not. In what follows, I try to clarify both the grounds of this appeal and its upshot. Does Krauss's account shed new light on Cavell's, or is she trying to press his terms into service for which they are ill-served? Both could of course be true, the former as a consequence of the latter perhaps. Conversely, do the art historical and philosophical accounts pass one another by? Note that even if the latter were true, its explanation might still prove instructive in the context of an interdisciplinary volume seeking to bring art historians and philosophers into dialogue around the themes of agency and automatism, which is precisely what Krauss's appeal to Cavell turns on. (shrink)

Mitochondrial function and biogenesis depend on the transport of a large variety of proteins, ions, and metabolites across the two surrounding membranes. While several specific transporters are present in the inner membrane, transport processes across the outer membrane are less understood. Recent studies reveal that the number of outer membrane channels and their transport mechanisms are more diverse than originally thought. Four protein‐conducting channels promote transport of distinct sets of precursor proteins across and into the outer membrane. The voltage‐dependent anion (...) channel (VDAC) forms the major channel for small hydrophilic molecules. In addition, three channels with yet unknown substrate specificity exist in the outer membrane. In this review, we outline the emerging functional diversity, selectivity, and regulation of mitochondrial outer membrane channels. The presence of several channel‐forming proteins challenges the traditional view that the outer membrane forms an unspecific size‐exclusion filter for the flux of small hydrophilic molecules. (shrink)

Several types of amygdala-dependent learning can be blocked by local infusion of NMDA antagonists into the amygdala. This blockade shows anatomical, pharmacological, temporal, and behavioral specificity, providing a pattern of data more consistent with a role for NMDA receptors in learning than in arousal or attention, and supporting the contention that an “LTP-like” process is a neural substrate for memory formation.

The identification of neural substrates underlying the long lasting debilitating impact of drug cues is critical for developing novel therapeutic tools. Metabolic coupling has long been considered a key mechanism through which astrocytes and neurons actively interact in response of neuronal activity, but recent findings suggested that disrupting metabolic coupling may represent an innovative approach to prevent memory formation, in particular drug‐related memories. Here, we review converging evidence illustrating how memory and addiction share neural circuitry and molecular mechanisms implicating lactate‐mediated (...) metabolic coupling between astrocytes and neurons. With several aspects of addiction depending on mnemonic processes elicited by drug experience, disrupting lactate transport involved in the formation of a pathological learning, linking the incentive, and motivational effects of drugs with drug‐conditioned stimuli represent a promising approach to encourage abstinence. (shrink)

Philosophers have long debated ‘substrate’ and ‘bundle’ theories as to how properties hold together in objects ― but have neglected to consider that every chemical entity is defined by closure of relationships among components ― here designated ‘Closure Louis de Broglie.’ That type of closure underlies the coherence of spectroscopic and chemical properties of chemical substances, and is importantly implicated in the stability and definition of entities of many other types, including those usually involved in philosophic discourse ― such (...) as roses, statues, and tennis balls. Characteristics of composites are often presumed to ‘supervene on’ properties of components. This assumption does not apply when cooperative interactions among components are significant. Once correlations dominate, then adequate descriptions must involve different entities and relationships than those that are involved in ‘fundamental-level’ description of similar but uncorrelated systems. That is to say, descriptions must involve different semantics than would be appropriate if cooperative interactions were insignificant. This is termed ‘Closure Henri Poincaré. Networks of chemical reactions that have certain types of closure of processes display properties that make other more-complex coherences possible. This is termed ‘Closure Jacques Cauvin.’ Each of these three modes of closure provides a sufficient basis for warranted recognition of causal interaction, thus each of them has epistemological significance. Other modes of epistemologically-important closure probably exist. It is important to recognize that causal efficacy generally depends on closure of relationships of constituents. (shrink)

Spatial attention and eye-movements are tightly coupled, but the precise nature of this coupling is controversial. The influential but controversial Premotor theory of attention makes four specific predictions about the relationship between motor preparation and spatial attention. Firstly, spatial attention and motor preparation use the same neural substrates. Secondly, spatial attention is functionally equivalent to planning goal directed actions such as eye-movements (i.e. planning an action is both necessary and sufficient for a shift of spatial attention). Thirdly, planning a goal (...) directed action with any effector system is sufficient to trigger a shift of spatial attention. Fourthly, the eye-movement system has a privileged role in orienting visual spatial attention. This article reviews empirical studies that have tested these predictions. Contrary to predictions one and two there is evidence of anatomical and functional dissociations between endogenous spatial attention and motor preparation. However, there is compelling evidence that exogenous attention is reliant on activation of the oculomotor system. With respect to the third prediction, there is correlational evidence that spatial attention is directed to the endpoint of goal-directed actions but no direct evidence that this attention shift is dependent on motor preparation. The few studies to have directly tested the fourth prediction have produced conflicting results, so the extent to which the oculomotor system has a privileged role in spatial attention remains unclear. Overall, the evidence is not consistent with the view that spatial attention is functionally equivalent to motor preparation so the Premotor theory should be rejected, although a limited version of the Premotor theory in which only exogenous attention is dependent on motor preparation may still be tenable. A plausible alternative account is that activity in the motor system contributes to biased competition between different sensory representations with the winner of the competition becoming the attended item. (shrink)

Integrated Information Theory (IIT) stands out as one of the most promising theories for dealing with the hard problem of consciousness. Founded on five axioms derived from phenomenology, IIT seeks for the physical substrate of consciousness that complies with such axioms according to the criterion of maximally integrated information (Φ). Eventually, IIT identifies phenomenal consciousness with maximal Φ or, what is the same thing, with the strongest cause-effect power in the system. Among the scholars critical of this theory, some (...) point to the so-called Intrinsicality Problem (IP), namely that consciousness cannot be an intrinsic property of the system because maximal Φ crucially depends on the possible existence of bigger values of Φ if the initial system is appropriately linked to or embedded in larger systems. Although proposals in the recent literature aim to solve the IP by going beyond reductionism and physicalism, none of them tackle the real issue, i.e., the insufficiency of IIT’s causal-metaphysical structure. This papers endeavors to provide a solution to the IP in IIT within a hylomorphist ontology that includes formal causation. Complementing IIT with formal causation provides the theory with a criterion of individuation that solves the IP and, by relaxing identification between maximal Φ and consciousness, it lends a more robust metaphysical structure. To wit, maximal Φ is a necessary but not sufficient condition for the existence of consciousness. (shrink)

The present study examined the neural substrate of two classes of quantifiers: numerical quantifiers like ” at least three” which require magnitude processing, and logical quantifiers like ” some” which can be understood using a simple form of perceptual logic. We assessed these distinct classes of quantifiers with converging observations from two sources: functional imaging data from healthy adults, and behavioral and structural data from patients with corticobasal degeneration who have acalculia. Our findings are consistent with the claim that (...) numerical quantifier comprehension depends on a lateral parietal-dorsolateral prefrontal network, but logical quantifier comprehension depends instead on a rostral medial prefrontal-posterior cingulate network. These observations emphasize the important contribution of abstract number knowledge to the meaning of numerical quantifiers in semantic memory and the potential role of a logic-based evaluation in the service of non-numerical quantifiers. (shrink)

Aus bekannten Versuchsergebnissen und Naturbeobachtungen lÄsst sich ein Mechanismus der ontogenetischen Evolution und Involution ableiten, der mit den unten stehenden vier GrundsÄtzen gekennzeichnet werden kann. Es wird dabei als anerkannt vorausgesetzt, dass die Entwicklung der Lebewesen auf genotypischen Potenzen beruht, die nach Einwirkung bestimmter Umweltreize bestimmte phÄnotypische Effekte bewirken. Es wird als “phylogenetischer Auslesefaktor” einer genotypischen Potenz derjenige Faktor der Äusseren oder inneren Umwelt bezeichnet, an den in der Phylogenese die Anpassung erfolgt ist. Der phylogenetische Auslesefaktor einer genotypischen Potenz wird (...) in der Ontogenese als genaktivierender Manifestationsreiz für den entsprechenden phÄnotypischen Effekt rekapituliert. Nach dem Ende des genaktivierenden Manifestationsreizes nimmt der von diesem Reiz abhÄngige Aktivierungszustand der genotypischen Potenz in charakteristischer Weise ab, und entsprechend bildet sich der von diesem Genaktivierungszustand abhÄngige phÄnotypische Effekt zurück; infolgedessen wird der phÄnotypische Effekt je nach der verschiedenen ReizabhÄngigkeit des Genaktivierungszustandes manifest als reizabhÄngige Modifikation, als vorübergehend reizunabhÄngige Dauermodifikation oder als fortgepflanzte vorübergehend reizunabhÄngige Dauermodifikation. Bei der ontogenetischen Evolution ist im Bereich der inneren Umwelt der phÄnotypische Effekt einer Entwicklungsstufe als rekapitulierter phylogenetischer Auslesefaktor der genotypischen Potenz der nÄchsten Entwicklungsstufe auch der genaktivierende Manifestationsreiz für den phÄnotypischen Effekt der nÄchsten Entwicklungsstufe . Bei Beendigung der ontogenetischen Evolution mit PhÄn x ist im Bereich der inneren Umwelt PhÄn x−1 der phylogenetische Auslesefaktor für Gen x−1 und wird als der genaktivierende Manifestationsreiz für PhÄn x rekapituliert. Mit der Manifestation von PhÄn x verschwindet PhÄn x−1 und damit auch der von ihm ausgehende genaktivierende Manifestationsreiz für PhÄn x ; infolgedessen beginnt die ontogenetische Involution von PhÄn x nach Massgabe der StabilitÄt des Aktivierungsgrades von Gen x−1.The development of living individuals is due to genotypical potencies, which lead to certain phenotypical effects after the influence of certain stimuli of the environment. The factor of the exogenous or endogenous environment to which adaptation has occurred during the phylogenesis is defined as the phylogenetical selectionfactor.A mechanism of ontogenetical evolution and involution is deduced from known experimental results and observations. This mechanism can be characterized by the following four main principles. The phylogenetical selectionfactor of a genotypical potency is recapitulated during ontogenesis as the gene-activating stimulus for the manifestation of the corresponding phenotypical effect. After the cessation of the gene-activating stimulus the activation of the genotypical potency declines in a characteristic manner. And according to it the phenotypical effect being dependent on this condition of gene-activation is involuted. This means that a phenotypical effect is manifest as stimulus dependent modification, as a temporary stimulus independent modification or as a temporary stimulus independent modification which is transmitted from generation to generation. During the ontogenetical evolution the phenotypical effect in a certain step of the development in the sphere of the endogenous environment is the manifestation stimulus activating the gene for the phenotypical effect of the following developmental step , since Phene n or Substrate n is the recapitulated selectionfactor for the genotypical potency of this step . When the ontogenetical evolution ends with the appearance of Phene n , Phene x−1 is the phylogenetical selectionfactor for Gene x−1 in the endogenous environment and is recapitulated as the gene-activating stimulus for the manifestation of Phene x . By the manifestation of Phene x Phene x−1 vanishes and thus the manifestationstimulus for Phene x . Consequently the ontogenetical involution of Phene x begins according to the degree of instability of the activated condition of Gene x−1. (shrink)

Calpain (Cp) is a calcium (Ca2+)‐dependent cysteine protease. Activation of the major isoforms of Cp, CpI and CpII, are required for a number of important cellular processes including adherence, shape change and migration. The current concept that cytoplasmic Cp locates and associates with its regulatory subunit (Rs) and substrates as well as translocates throughout the cell via random diffusion is not compatible with the spatial and temporal constraints of cellular metabolism. The novel finding that Cp and Rs function relies upon (...) tenacious hydrophobic interactions with organelle membranes offers a unifying explanation for the paradoxical and puzzling features of Cp activation and regulation such as how nM concentrations of intracellular Ca2+ can activate Cp molecules requiring μM to mM concentrations of Ca2+ for in vitro activation, and how this protease can spatially and temporally locate specific substrates and translocate throughout the cell. We hypothesize that Cp and its regulatory moieties associate with organelles to facilitate the activation of this protease resulting in the cleavage of substrates and aid in its translocation throughout the cell. BioEssays 28: 850–859, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The process of protein folding in the cell is now known to depend on the action of other proteins. These proteins include molecular chaperones, Which interact non‐covalently with proteins as they fold and improve the final yields of active protein in the cell. The precise mechanism by which molecular chaperones act is obscure. Experiments reported recently(1) show that for one molecular chaperone (Cpn60, typified by the E. coli protein GroEL), the folding reaction is driven by cycles of binding and release (...) of the co‐chaperone Cpn10 (known as GroES in E. coli). These alternate with binding and release of the unfolded protein substrate. These cycles come about because of the opposite effects of Cpn10 and unfolded protein on the Cpn60 complex: the former stabilises the ADP‐bound state of Cpn60, whereas the latter stimulates ADP‐ATP exchange. This model proposes that the substrate protein goes through multiple cycles of binding and release, and is released into the cavity of the Cpn60 complex where it can undergo folding without interacting with other nearby folding intermediates. This is consistent with the ability of Cpn60 proteins to enhance folding by blocking pathways to aggregation. (shrink)

In eukaryotic cells terminally misfolded proteins of the secretory pathway are retarded in the endoplasmic reticulum (ER) and subsequently degraded in a ubiquitin‐proteasome‐dependent manner. This highly conserved process termed ER‐associated protein degradation (ERAD) ensures homeostasis in the secretory pathway by disposing faulty polypeptides and preventing their deleterious accumulation and eventual aggregation in the cell. The focus of this paper is the functional description of membrane‐bound ubiquitin ligases, which are involved in all critical steps of ERAD. In the end we want (...) to speculate on how the modular architecture of these entities ensures the specificity of substrate selection and possibly accomplishes the transport of misfolded polypeptides from the ER into the cytoplasm. (shrink)

The “Slicing Problem” is a thought experiment that raises questions for substrate-neutral computational theories of consciousness, including those that specify a certain causal structure for the computation like Integrated Information Theory. The thought experiment uses water-based logic gates to construct a computer in a way that permits cleanly slicing each gate and connection in half, creating two identical computers each instantiating the same computation. The slicing can be reversed and repeated via an on/off switch, without changing the amount of (...) matter in the system. The question is what do different computational theories of consciousness believe is happening to the number and nature of individual conscious units as this switch is toggled. Under a token interpretation, there are now two discrete conscious entities; under a type interpretation, there may remain only one. Both interpretations lead to different implications depending on the adopted theoretical stance. Any route taken either allows mechanisms for “consciousness-multiplying exploits” or requires ambiguous boundaries between conscious entities, raising philosophical and ethical questions for theorists to consider. We discuss resolutions under different theories of consciousness for those unwilling to accept consciousness-multiplying exploits. In particular, we specify three features that may help promising physicalist theories to navigate such thought experiments. (shrink)

Objects come in three kinds: physical objects that exist in space and in time, and are independent from subjects knowing them, even though they may have built them, as for artifacts ; ideal objects that exist outside of space and time, and are independent from the subjects knowing them, but which, after having been discovered, can be socialized; social objects, that do not exist as such in space, since their physical presence is limited to the inscription, but last in time, (...) and whose existence depends on the subjects who know, or at least can use, them and who, in certain cases, have constituted them. This latter circumstance display us the fact that social objects, for which construction is necessary, depends on social acts, whose inscription constitutes the object. As I show through the law Object = Inscribed Act, social objects consist in the recording of acts that encompass at least two people, and are characterized by being inscribed, on a physical substrate what so ever, from marble to neurons, passing through paper and computers. If all this is true, then a theory of social objects develops naturally into a theory of the document, understood as an inquire centered on the definition of what I call “documentality”, namely the properties that constitute, in each case, the necessary and sufficient conditions to be a social object. At last, there is no society if there are no documents, and documents are records with a particular social value. (shrink)

Shape and locomotion of tissue cells depend on the interaction of elements of the cytoskeleton, adhesion to the substrate and an intracellular hydrostatic pressure. The existence of this pressure becomes obvious from increase in cell volume on cessation of contractile forces and from observations with ultrasound acoustic microscopy. Wherever such an internal pressure is established, it is involved in generation of shape and driving force of cell locomotion. Therefore each hypothesis on cell shape and locomotion must consider this property (...) of a living cell. Apparently different types of locomotion depend on differences in substrate adhesion and/or cytoskeleton organisation. (shrink)

Human language is a salient example of a neurocognitive system that is specialized to process complex dependencies between sensory events distributed in time, yet how this system evolved and specialized remains unclear. Artificial Grammar Learning (AGL) studies have generated a wealth of insights into how human adults and infants process different types of sequencing dependencies of varying complexity. The AGL paradigm has also been adopted to examine the sequence processing abilities of nonhuman animals. We critically evaluate this growing literature in (...) species ranging from mammals (primates and rats) to birds (pigeons, songbirds, and parrots) considering also cross‐species comparisons. The findings are contrasted with seminal studies in human infants that motivated the work in nonhuman animals. This synopsis identifies advances in knowledge and where uncertainty remains regarding the various strategies that nonhuman animals can adopt for processing sequencing dependencies. The paucity of evidence in the few species studied to date and the need for follow‐up experiments indicate that we do not yet understand the limits of animal sequence processing capacities and thereby the evolutionary pattern. This vibrant, yet still budding, field of research carries substantial promise for advancing knowledge on animal abilities, cognitive substrates, and language evolution. (shrink)

One of the reasons why the Neural Correlates of Consciousness Program could appear attractive in the 1990s was that it seemed to disentangle theoretical and empirical problems. Theoretical disagreements could thus be sidestepped in order to focus on empirical research regarding the neural substrate of consciousness. One of the further consequences of this dissociation of empirical and theoretical questions was that fundamental questions regarding the Mind Body Problem or the “Hard Problem of Consciousness” could remain unresolved even if the (...) search for the neural correlates had been successful.Drawing on historical examples, a widely held consensus in the philosophy of science, and actual NCC research we argue that there is no such independence. Moreover, as the dependence between the theoretical and the empirical level is mutual, empirical progress will go hand in hand with theoretical development. Thus, contrary to what the original NCC program suggested, we conclude that NCC research may significantly take advantage from and contribute to theoretical progress in our explanation and understanding of consciousness. Eventually, this might even contribute to a solution of the Hard Problem of Consciousness. (shrink)

Prism Adaptation is a useful method to study the mechanisms of sensorimotor adaptation. After-effects following adaptation to the prismatic deviation constitute the probe that adaptive mechanisms occurred, and current evidence suggests an involvement of the cerebellum at this level. Whether after-effects are transferable to another task is of great interest both for understanding the nature of sensorimotor transformations and for clinical purposes. However, the processes of transfer and their underlying neural substrates remain poorly understood. Transfer from throwing to pointing is (...) known to occur only in individuals who had previously reached a good level of expertise in throwing, not in novices. The aim of this study was to ascertain whether anodal stimulation of the cerebellum could boost after-effects transfer from throwing to pointing in novice participants. Healthy participants received anodal or sham transcranial direction current stimulation of the right cerebellum during a PA procedure involving a throwing task and were tested for transfer on a pointing task. Terminal errors and kinematic parameters were in the dependent variables for statistical analyses. Results showed that active stimulation had no significant beneficial effects on error reduction or throwing after-effects. Moreover, the overall magnitude of transfer to pointing did not change. Interestingly, we found a significant effect of the stimulation on the longitudinal evolution of pointing errors and on pointing kinematic parameters during transfer assessment. These results provide new insights on the implication of the cerebellum in transfer and on the possibility to use anodal tDCS to enhance cerebellar contribution during PA in further investigations. From a network approach, we suggest that cerebellum is part of a more complex circuitry responsible for the development of transfer which is likely embracing the primary motor cortex due to its role in motor memories consolidation. This paves the way for further work entailing multiple-sites stimulation to explore the role of M1-cerebellum dynamic interplay in transfer. (shrink)

Dicer is a key player in microRNA (miRNA) and RNA interference (RNAi) pathways, processing miRNA precursors and doublestranded RNA into ~21-nt-long products ultimately triggering sequence-dependent gene silencing. Although processing of substrates in vertebrate cells occurs in the cytoplasm, there is growing evidence suggesting Dicer is also present and functional in the nucleus. To address this possibility, we searched for a nuclear localization signal (NLS) in human Dicer and identified its C-terminal double-stranded RNA binding domain (dsRBD) as harboring NLS activity. We (...) show that the dsRBD-NLS can mediate nuclear import of a reporter protein via interaction with importins β, 7, and 8. In the context of full-length Dicer, the dsRBD-NLS is masked. However, duplication of the dsRBD localizes the full-length protein to the nucleus. Furthermore, deletion of the N-terminal helicase domain results in partial accumulation of Dicer in the nucleus upon leptomycin B treatment, indicating that CRM1 contributes to nuclear export of Dicer. Finally, we demonstrate that human Dicer has the ability to shuttle between the nucleus and the cytoplasm. We conclude that Dicer is a shuttling protein whose steady-state localization is cytoplasmic. (shrink)

Integrated information theory (IIT) starts from the essential properties of experience and translates them into requirements that any physical system must satisfy to be conscious. It argues that the physical substrate of consciousness (PSC) must constitute a maximum of irreducible, internal cause‐effect power of a specific form, and provides a calculus to determine, in principle, both the quality and the quantity of an experience. Applied to the brain, IIT predicts that the spatio‐temporal grain of the neural units constituting the (...) PSC, and the relevant neural states, are those that maximize cause‐effect power. Moreover, the PSC can shrink, move, split and disintegrate depending on various anatomical and physiological parameters. These predictions are testable with brain stimulation and recording experiments. The theory can explain parsimoniously many known facts about the relationship between consciousness and the brain, including its association with certain cortical structures, its breakdown in deep sleep, anesthesia and seizures, and its return in dreams. (shrink)

The development of new approaches is critical to gain further insights into biological processes that cannot be obtained by existing methods or technologies. The detection of protein–protein interaction is often challenging, especially for weak and transient interactions or for membrane proteins. Over the last decade, several proximity‐tagging methodologies have been developed to explore protein interactions in living cells. Among those, the most efficient are based on protein partner modification, such as biotinylation or pupylation. Such technologies are based on engineered variants (...) of enzymes like peroxidases or ligases that release reactive molecules, in the presence of specific substrates, that bind surrounding proteins. Fusing a protein of interest (POI) to these enzymes allows the definition of an unbiased “proxisome,” that is, all of the proteins in interaction or in close vicinity of the POI. Here, the different proximity‐labeling tools available are described and comprehensive comparison to discuss advantages and limitations is provided. (shrink)

The degradation of the majority of cellular proteins is mediated by the proteasomes. Ubiquitin‐dependent proteasomal protein degradation is executed by a number of enzymes that interact to modify the substrates prior to their engagement with the 26S proteasomes. Alternatively, certain proteins are inherently unstable and undergo “default” degradation by the 20S proteasomes. Puzzlingly, proteins are by large subjected to both degradation pathways. Proteins with unstructured regions have been found to be substrates of the 20S proteasomes in vitro and, therefore, unstructured (...) regions may serve as signals for protein degradation “by default” in the cell. The literature is loaded with examples where engagement of a protein into larger complexes increases protein stability, possibly by escaping degradation “by default”. Our model suggests that formation of protein complexes masks the unstructured regions, making them inaccessible to the 20S proteasomes. This model not only provides molecular explanations for a recent theoretical “cooperative stability” principle, but also provokes new predictions and explanations in the field of protein regulation and functionality. BioEssays 28: 844–849, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Underplayed Ethics and the Dilemmas of Psychiatric CareChong Siow Ann and Tamra LysaghtThe practice of psychiatry is fraught with uncertainty. The exact causes and the biological substrates underlying mental disorders remain to be elucidated; even the diagnosis of these disorders is descriptive and not based on an etiological understanding and no biological diagnostic markers have been validated. The manifestation of almost all mental disorders results from a complex interaction (...) of biological and environmental factors which encompasses the patient’s unique life history, experiences and relationship with others and the community. In the face of such uncertainties — at times extending to the types of treatment (psychiatry is generally acknowledged not be an exact science) — it has been argued that adopting a pragmatic approach is necessary.1 Accordingly, this approach necessitates high ethical standards among mental health practitioners.Some mental illnesses are associated with varying degrees and types of cognitive impairments. Others have certain symptoms like auditory hallucinations and delusions that might severely compromise the patients’ autonomy, distort their sense of reality, increase the risk of harm to themselves or others and render them incapable of making informed decisions in their treatment and participation in research.Consequently, there are issues that are particular to the provision of mental healthcare. These include the need for enforced involuntary treatment with the corollary of depriving a patient of his personal liberty even [End Page 173] though it is often justified on the grounds that it is in the patient’s best interests. However, at times, it is the legal and societal obligation of mental health practitioners to protect those who might be harmed from the patient’s action that might seem to be more pressing. In this situation of double agency, lies the tension of providing confidential care for patients and acting as “an agent of the state” where that patient’s confidentiality might be breached and his liberty infringed upon. This situation is further aggravated by the stigma that clings ever so tenaciously to those who suffer from mental disorders and where it is the norm to stereotype them as dangerous and unpredictable.Consideration of a patient’s autonomy is also challenged by characteristics that are unique to the practice of psychiatry. The prescription of certain psychotropic medications can alter how people think and feel, while psychotherapy works towards changing the patient’s views and values. The philosopher, Jennifer Radden, describes this process as “re-forming the patient’s whole self or character … akin to the responsibilities of raising children”.2 The psychotherapeutic relationship is thus particularly personal and intimate because patients are asked to provide information that often reveals their innermost feelings, fears and fantasies. This information is provided on the basis of trust and assurance of confidentiality, and with expectation of being helped.Jeremy Holmes and Gwen Adshead have elaborated on the vulnerability of patients seeking psychotherapy: they might be particularly susceptible to exploitation because their past experiences of being exploited have led to their distress and help seeking — their dependency and the extreme privacy of the therapeutic relationship make any transgression difficult to be uncovered.3 There is a calamitous combination of the “unconscious wish in the patient to be used” with the complicity of an unethical therapist seeking to fulfil his own interests.4As in any other doctor-patient relationship, the relationship between the mental healthcare practitioner and the patient is one of unequal power where the former is ascendant. While that power should be exercised to heal and to relieve suffering, it also gives the practitioner tremendous power “to harm, reject, misunderstand, or exploit patients who struggle with the experience of mental illness, which itself may generate helplessness, despair, distress, and exceptional dependence on the clinician”.5 Given the potential of doing good and harm coupled with the likelihood of being so significant in the life of the patient,6 providing care for those with mental disorders and distress is necessarily ethically exacting — arguably more so than in other medical practice settings. [End Page 174]This precariousness has led to the suggestion that ethics in psychiatry should have a special status and that the more general principles of biomedical ethics are too limited in scope to... (shrink)

Several lines of evidence have underscored the remarkable neuroplasticity of the primate sensorimotor cortex, characterizing these cortical areas as dynamic constructs that are modelled in a use-dependent manner by behaviourally significant experiences. Their plasticity likely provides a neural substrate that may contribute to the dynamic systems paradigm argued by Shanker & King (S&K) as crucial for development of communication skills.

ON A GENERAL READING of the Metaphysics and the treatises of the so-called Organon, the types of assertion which Aristotle would allow as genuine predications seem relatively straightforward. According to the Categories, for instance, a species is characteristically predicated of the individuals falling under it, while genera and differentiae are predicated both of the relevant species and their associated individuals. The predicates are, in these instances, universals in a familiar Aristotelian sense. Furthermore, these intra-categorial predications, such as "Socrates is a (...) man" and "white is a color," are not the only instances of categorial acts. Aristotle also admits certain cross-categorial predications as logically well-formed; for example, "Socrates is white" and "Socrates is in the marketplace". These latter predications are at first glance also intelligible enough, though there are in both cases questions yet to be faced about the logical structure and ontological commitments of such ways of speaking. For Aristotle, one metaphysical theme presented even on the face of these linguistic appearances is the possibility that being a substrate for predication counts as a criterion for ontological primacy or, more generally, that being an ultimate substrate for meaningful discourse is grounds for being primarily real. An obvious corollary to this line of thought is the thesis that whatever might be said of or predicated of such primary substrata is ontologically dependent upon them. Just such a criterion seems to be at work in disqualifying universals from their claim to be substance in a significant sense. Therefore, it would be somewhat surprising to find primary substance appearing anywhere as a predicate. (shrink)

Nanotechnologies are technologies applied to a molecular level, which can be embedded in materials including human cells and atoms of mineral, chemical, or physical substrates. Nanotechnologies have been used in attempts to foster interactions between a multitude of products, production processes, and social actors. Just like bio, info, and cognitive science, nanotechnologies belong to the so-called converging technologies, which are expected to change main societal paths toward a more functional and coarser mesh. However, research, development, and di fusion of converging (...) technologies depends on the adaptability of existing economic structures and on the social acceptance of products and services augmented by nanotechnologies. Because of these characteristics, externalities and the risk of systemic divergences caused by potentially noncontrollable or unwanted interactions between sectors, actors, and environments may arise and disturb the e ficiency of the innovation process. Converging institutions, however, aim to manage these market imperfections and social risks in the long run. (shrink)

This article deploys Peircean approach to bodily skills, foregrounding motricity as a semiotically mediated and a “suprasubjective” process. By examining two contrasting skills – javelin and martial arts – I draw out the relevance of dynamic movement to the semiotics of sport and embodiment. These contrasting movements expose different epistemological assumptions since they emerge in distinct cultural traditions. To attend to the cultural dimension of movement practices – including the mediation of signs making certain movement forms seem reasonable or desirable (...) in the first place – I highlight ecological dimensions of each somatic tradition. This ecological focus aligns with Peirce’s project of tracking how semiotic signs are positioned and mediated. To make ecological factors of motricity more recognizable, I contrast somatic engagements that take place on synthetic, predictable substrates and somatic engagements that take place on variable, unpredictable ground. In a similar way to the classic gestalt figure-ground relations, where perception of a figure depends on the particulars of the ground, I suggest that the ground upon which somatic action occurs shapes the way we make sense of it epistemologically. These different grounds – both literally and figuratively – operate representationally via thirdness: they lead us to conceptualize movement in culturally and historically particular ways. (shrink)

Expectation of others’ cooperative behavior plays a core role in economic cooperation. However, the dynamic neural substrates of expectation of cooperation are little understood. To fully understand EOC behavior in more natural social interactions, the present study employed functional near-infrared spectroscopy hyperscanning to simultaneously measure pairs of participants’ brain activations in a modified prisoner’s dilemma game. The data analysis revealed the following results. Firstly, under the high incentive condition, team EOC behavior elicited higher interbrain synchrony in the right inferior frontal (...) gyrus than individual EOC behavior. Meanwhile, the IBS in the IFG could predict the relationship between empathy/agreeableness and EOC behavior, and this prediction role was modulated by social environmental cues. These results indicate the involvement of the human mirror neuron system in the EOC behavior and the different neural substrates between team EOC and individual EOC, which also conform with theory that social behavior was affected by internal and external factors. Secondly, female dyads exhibited a higher IBS value of cooperative expectation than male dyads in the team EOC than the individual EOC in the dorsal medial prefrontal cortex, while in the individual EOC stage, the coherence value of female dyads was significantly higher than that of male dyads under the low incentive reward condition in the rIFG. These sex effects thus provide presumptive evidence that females are more sensitive to environmental cues and also suggest that during economic social interaction, females’ EOC behavior depends on more social cognitive abilities. Overall, these results raise intriguing questions for future research on human cooperative behaviors. (shrink)

Lysine acetylation has been shown to occur in many protein targets, including core histones, about 40 transcription factors and over 30 other proteins. This modification is reversible in vivo, with its specificity and level being largely controlled by signal‐dependent association of substrates with acetyltransferases and deacetylases. Like other covalent modifications, lysine acetylation exerts its effects through “loss‐of‐function” and “gain‐of‐function” mechanisms. Among the latter, lysine acetylation generates specific docking sites for bromodomain proteins. For example, bromodomains of Gcn5, PCAF, TAF1 and CBP (...) are able to recognize acetyllysine residues in histones, HIV Tat, p53, c‐Myb or MyoD. In addition to the acetyllysine moiety, the flanking sequences also contribute to efficient recognition. The relationship between acetyllysine and bromodomains is reminiscent of the specific recognition of phosphorylated residues by phospho‐specific binding modules such as SH2 domains and 14‐3‐3 proteins. Therefore, lysine acetylation forges a novel signaling partnership with bromodomains to govern the temporal and spatial regulation of protein functions in vivo. BioEssays 26:1076–1087, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Humans are a part of the complex system including both natural and cultural-technological environment. Evolution of this system included self-amplifying feedbacks that lead to the appearance of human conscious mind. We describe the current state of the understanding of human brain evolution that stresses neurohormonal and biochemical changes rather than simple increase of anatomical substrate for the mind. It follows that human brain is strongly influenced by the state of the body and may operate at various levels of consciousness (...) depending on its biochemical environment created by ingestion of various substances and by specific physical activities. Through the study of the widespread phenomenon of shamanism that uses mind-altering practices we argue that altered states of consciousness and non-local minds are not only real phenomena, but that they are products of natural evolution, valuable for human survival and development. Consideration of altered states of consciousness and broadening of the framework for understanding brain function beyond mechanistic interpretations is necessary to further develop human adaptations and provide a better way of fitting humans as parts of the interconnected system into the global and universal patterns. (shrink)

Contemporary textbooks often define evolution in terms of the replication, mutation, and selective retention of DNA sequences, ignoring the contribution of the physical processes involved. In the closing line of The Origin of Species, however, Darwin recognized that natural selection depends on prior more basic living functions, which he merely described as life’s “several powers.” For Darwin these involved the organism’s capacity to maintain itself and to reproduce offspring that preserve its critical functional organization. In modern terms we have come (...) to recognize that this involves the continual generation of complex organic molecules in complex configurations accomplished with the aid of persistent far-from-equilibrium chemical self-organizing and self-assembling processes. But reliable persistence and replication of these processes also requires constantly available constraints and boundary conditions. Organism autonomy further requires that these constraints and co-dependent dynamics are reciprocally produced, each by the other. In this paper I argue that the different constraint-amplifying dynamics of two or more self-organizing processes can be coupled so that they reciprocally generate each other’s critical supportive boundary conditions. This coupling is a higher-order constraint that effectively constitutes a sign vehicle “interpreted” by the synergistic dynamics of these co-dependent self-organizing process so that they reconstitute this same semiotic-dynamic relationship and its self-reconstituting potential in new substrates. This dynamical co-dependence constitutes Darwin’s “several powers” and is the basis of the biosemiosis that enables evolution. (shrink)

The mechanistic significance of a kinetic isotope effect on a cytochrome P‐450catalyzed reaction depends, fundamentally, on the nature of the interaction of the substrate with the active site of the enzyme as well as on the nature of the chemistry of the reaction catalyzed. Consequently, kinetic isotope effects can be used to extract information on the topology of the enzyme and the mechanism of substrate oxidation. Kinetic isotope effect studies are sometimes accompanied by ‘metabolic switching’ or a change (...) in metabolic pathway, catalyzed either by the same enzyme or by a different enzyme. For the specific case where ‘metabolic switching’ gives rise to a change in regional specificity for the cytochrome P‐450 catalyzed metabolism of a compound, this change can be explained in terms of the topological constraints on substrate binding imposed by the active site of the enzyme. (shrink)

Some 20 years ago Todd and colleagues proposed that rhythm perception is mediated by the conjunction of a sensory representation of the auditory input and a motor representation of the body (Todd, 1994a, 1995 ), and that a sense of motion from sound is mediated by the vestibular system (Todd, 1992a, 1993b ). These ideas were developed into a sensory-motor theory of rhythm and beat induction (Todd et al., 1999 ). A neurological substrate was proposed which might form the (...) biological basis of the theory (Todd et al., 2002 ). The theory was implemented as a computational model and a number of experiments conducted to test it. In the following time there have been several key developments. One is the demonstration that the vestibular system is primal to rhythm perception, and in related work several experiments have provided further evidence that rhythm perception is body dependent. Another is independent advances in imaging, which have revealed the brain areas associated with both vestibular processing and rhythm perception. A third is the finding that vestibular receptors contribute to auditory evoked potentials (Todd et al., 2014a, b ). These behavioral and neurobiological developments demand a theoretical overview which could provide a new synthesis over the domain of rhythm perception. In this paper we suggest four propositions as the basis for such a synthesis. (1) Rhythm perception is a form of vestibular perception; (2) Rhythm perception evokes both external and internal guidance of somatotopic representations; (3) A link from the limbic system to the internal guidance pathway mediates the “dance habit”; (4) The vestibular reward mechanism is innate. The new synthesis provides an explanation for a number of phenomena not often considered by rhythm researchers. We discuss these along with possible computational implementations and alternative models and propose a number of new directions for future research. (shrink)

The structure of the brain and the nature of evolution suggest that, despite its uniqueness, language likely depends on brain systems that also subserve other functions. The declarative / procedural model claims that the mental lexicon of memorized word- specific knowledge depends on the largely temporal-lobe substrates of declarative memory, which underlies the storage and use of knowledge of facts and events. The mental grammar, which subserves the rule-governed combination of lexical items into complex representations, depends on a distinct neural (...) system. This system, which is composed of a network of specific frontal, basal - ganglia, parietal and cerebellar structures, underlies procedural memory, which supports the learning and execution of motor and cognitive skills, especially those involving sequences. The functions of the two brain systems, together with their anatomical, physiological and biochemical substrates, lead to specific claims and predictions regarding their roles in language. These predictions are compared with those of other neurocognitive models of language. Empirical evidence is presented from neuroimaging studies of normal language processing, and from developmental and adult- onset disorders. It is argued that this evidence supports the DP model. It is additionally proposed that “ language ” disorders, such as specific language impairment and non-fluent and fluent aphasia, may be profitably viewed as impairments primarily affecting one or the other brain system. Overall, the data suggest a new neurocognitive framework for the study of lexicon and grammar. (shrink)

The study of imitation and other mechanisms of social learning is an exciting area of research for all those interested in understanding the origin and the nature of animal learning in a social context. Moreover, imitation is an increasingly important research topic in Artificial Intelligence and social robotics which opens up the possibility of individualized social intelligence in robots that are part of a community, and allows us to harness not only individual learning by the single robot, but also the (...) acquisition of new skills by observing other members of the community. After an introduction to the main research issues in research on imitation in various fields, we motivate the particular focus of this work, namely the correspondence problem. We describe Action Learning for Imitation via Correspondences between Embodiments, an implemented generic framework for solving the correspondence problem between differently embodied robots. Alice enables a robotic agent to learn a behavioral repertoire suitable to performing a task by observing a model agent. Importantly, the model agent could possibly possess a different type of body, e.g. a different number of limbs or joints, a different height, different sensors, a different basic action repertoire, etc. Previously, in a test-bed where the agents differed according to their possible movement patterns, we demonstrated that the character of imitation achieved will depend on the granularity of subgoal matching, and on the metrics used to evaluate success. In our current work, we implemented Alice in a new test-bed called Rabit where simple simulated robotic arm agents use various metrics for evaluating success according to actions, states, effects, or weighted combinations. We examine the roles of synchronization, looseness of perceptual matching, and of proprioceptive matching by a series of experiments. Also, we study how Alice copes with changes in the embodiment of the imitator during learning. Our simulation results suggest that synchronization and loose perceptual matching allow for faster acquisition of behavioral compentencies at low error rates. Social learning plays a role as a replication mechanism for behaviors and results in variability when the transmitted behavior differs from the model’s behavior, thus providing the evolutionary substrate for culture and its pre-cursors. Social learning in robotics could therefore serve as the basis for culture in societies whose members include artificial agents. We address the use of imitative social learning mechanisms like Alice for transmission of skills between robots, and give first examples of transmission of a skill despite differences in embodiment of agents involved. In the particular setup, transmission occurs through a chain, as well as emerging in cyclic arrangements of robots. These simple examples demonstrate that by using social learning and imitation, cultural transmission is possible among robots, even in heterogeneous groups of robots. (shrink)

Working memory is the system responsible for maintaining and manipulating information, in the face of ongoing distraction. In turn, WM span is perceived to be an individual-differences construct reflecting the limited capacity of this system. Recently, however, there has been some evidence to suggest that WM capacity can increase through training, raising the possibility that training can functionally alter the neural structures supporting WM. To address the hypothesis that the neural substrates underlying WM are targeted by training, we conducted a (...) meta-analysis of functional magnetic resonance imaging studies of WM training using Activation Likelihood Estimation. Our results demonstrate that WM training is associated exclusively with decreases in blood oxygenation level-dependent responses in clusters within the fronto-parietal system that underlie WM, including the bilateral inferior parietal lobule, middle and superior frontal gyri, and medial frontal gyrus bordering on the cingulate gyrus. We discuss the various psychological and physiological mechanisms that could be responsible for the observed reductions in the BOLD signal in relation to WM training, and consider their implications for the construct of WM span as a limited resource. (shrink)

This article explores the notion of the Web-extended mind, which is the idea that the technological and informational elements of the Web can sometimes serve as part of the mechanistic substrate that realizes human mental states and processes. It is argued that while current forms of the Web may not be particularly suited to the realization of Web-extended minds, new forms of user interaction technology as well as new approaches to information representation do provide promising new opportunities for Web-based (...) forms of cognitive extension. In addition, it is suggested that extended cognitive systems often rely on the emergence of social practices and conventions that shape how a technology is used. Web-extended minds may thus depend on forms of socio-technical co-evolution in which social forces and factors play just as important a role as do the processes of technology design and development. (shrink)

Imprinted genes are monoallelically expressed in a parent‐of‐origin‐dependent manner and can affect brain and behavioural phenotypes. The X chromosome is enriched for genes affecting neurodevelopment and is donated asymmetrically to male and female progeny. Hence, X‐linked imprinted genes could potentially influence sexually dimorphic neurobiology. Consequently, investigations into such loci may provide new insights into the biological basis of behavioural differences between the sexes and into why men and women show different vulnerabilities to certain mental disorders. In this review, we summarise (...) recent advances in our knowledge of X‐linked imprinted genes and the brain substrates that they may act upon. In addition, we suggest strategies for identifying novel X‐linked imprinted genes and their downstream effects and discuss evolutionary theories regarding the origin and maintenance of X‐linked imprinting. BioEssays 28:35–44, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

Currently, a central question in biology is how signals from the cell surface modulate intracellular processes. In recent years phosphoinositides have been shown to play a key role in signal transduction. Two phosphoinositide pathways have been characterized, to date. In the canonical phosphoinositide turnover pathway, activation of phosphatidylinositol‐specific phospholipase C results in the hydrolysis of phosphatidylinositol 4,5‐bisphospate and the generation of two second messengers, inositol 1,4,5‐trisphosphate and diacylglycerol. The 3‐phosphoinositide pathway involves protein‐tyrosine kinase‐mediated recruitment and activation of phosphatidylinositol 3‐kinase, resulting (...) in the production of phosphatidylinositol 3,4‐bisphosphate and phosphatidylinositol 3,4,5‐trisphosphate. The 3‐phosphoinositides are not substrates of any known phospholipase C, are not components of the canonical phosphoinositide turnover pathway, and may themselves act as intracellular mediators. The 3‐phosphoinositide pathway has been implicated in growth factor‐dependent mitogenesis, membrane ruffling and glucose uptake. Furthermore the homology of the yeast vps34 with the mammalian phosphatidylinositol 3‐kinase has suggested a role for this pathway in vesicular trafficking.In this review the different mechanisms employed by protein‐tyrosine kinases to activate phosphatidylinositol 3‐kinase, and its involvement in the signaling cascade initiated by tyrosine phosphorylation, are examined. (shrink)