Functional localization is a central aim of cognitive neuroscience. But the nature and extent of functional localization in the human brain have been subjects of fierce theoretical debate since the 19th Century. In this essay, I first examine how concepts of functional localization have changed over time. I then analyze contemporary challenges to functional localization drawing from research on neural reuse, neural degeneracy, and the context-dependence of neural functions. I explore the consequences (...) of these challenges for topics in philosophy of science and philosophy of mind including localizationist versus anti-localizationist approaches to cognitive neuroscience, multiple realizability, reverse inference in functional neuroimaging, and the modularity of mind. (shrink)

Functional localization has historically been one of the primary goals of neuroscience. There is still debate, however, about whether it is possible, and if so what kind of theories succeed at localization. I argue for a contextualist approach to localization. Most theorists assume that widespread contextual variability in function is fundamentally incompatible with functional decomposition in the brain, because contextualist accounts will fail to be generalizable and projectable. I argue that this assumption is misplaced. A (...) properly articulated contextualism can ground successful theories of localization even without positing completely generalizable accounts. Via a case study from perceptual neuroscience, I suggest that there is strong evidence for contextual variation in the function of perceptual brain areas. I then outline a version of contextualism that is empirically adequate with respect to this data, and claim that it can still distinguish brain areas from each other according to their functional properties. Finally, I claim that the view does not fail the norms for good theory in the way that anticontextualists suppose. It is true that, on a contextualist view, we will not have theories that are completely generalizable and predictive. We can, however, have successful partial generalizations that structure ongoing investigation and lead to novel functional insight, and this success is sufficient to ground the project of functional localization. (shrink)

This paper describes one style of functional analysis commonly used in the neurosciences called task-bound functional analysis. The concept of function invoked by this style of analysis is distinctive in virtue of the dependence relations it bears to transient environmental properties. It is argued that task-bound functional analysis cannot explain the presence of structural properties in nervous systems. An alternative concept of neural function is introduced that draws on the theoretical neuroscience literature, and an argument is given (...) to show that this alternative concept of may help to overcome the explanatory limitations of task-bound functional analysis. (shrink)

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task.Methods: Twenty-five patients with pharmaco-resistant epilepsy, (...) including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects.Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and pari... (shrink)

BackgroundThe neural activity and functional networks of emotion-based cognitive reappraisal have been widely investigated using electroencephalography and functional magnetic resonance imaging. However, single-mode neuroimaging techniques are limited in exploring the regulation process with high temporal and spatial resolution.ObjectivesWe proposed a source localization method with multimodal integration of EEG and fMRI and tested it in the source-level functional network analysis of emotion cognitive reappraisal.MethodsEEG and fMRI data were simultaneously recorded when 15 subjects were performing the emotional cognitive (...) reappraisal task. Fused priori weighted minimum norm estimation with sliding windows was proposed to trace the dynamics of EEG source activities, and the phase lag index was used to construct the functional brain network associated with the process of downregulating negative affect using the reappraisal strategy.ResultsThe functional networks were constructed with the measure of PLI, in which the important regions were indicated. In the gamma band source-level network analysis, the cuneus, the lateral orbitofrontal cortex, the superior parietal cortex, the postcentral gyrus, and the pars opercularis were identified as important regions in reappraisal with high betweenness centrality.ConclusionThe proposed multimodal integration method for source localization identified the key cortices involved in emotion regulation, and the network analysis demonstrated the important brain regions involved in the cognitive control of reappraisal. It shows promise in the utility in the clinical setting for affective disorders. (shrink)

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several dendritic (...) mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several dendritic (...) mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

An analysis of two heuristic strategies for the development of mechanistic models, illustrated with historical examples from the life sciences. In Discovering Complexity, William Bechtel and Robert Richardson examine two heuristics that guided the development of mechanistic models in the life sciences: decomposition and localization. Drawing on historical cases from disciplines including cell biology, cognitive neuroscience, and genetics, they identify a number of "choice points" that life scientists confront in developing mechanistic explanations and show how different choices result in (...) divergent explanatory models. Describing decomposition as the attempt to differentiate functional and structural components of a system and localization as the assignment of responsibility for specific functions to specific structures, Bechtel and Richardson examine the usefulness of these heuristics as well as their fallibility—the sometimes false assumption underlying them that nature is significantly decomposable and hierarchically organized. When Discovering Complexity was originally published in 1993, few philosophers of science perceived the centrality of seeking mechanisms to explain phenomena in biology, relying instead on the model of nomological explanation advanced by the logical positivists (a model Bechtel and Richardson found to be utterly inapplicable to the examples from the life sciences in their study). Since then, mechanism and mechanistic explanation have become widely discussed. In a substantive new introduction to this MIT Press edition of their book, Bechtel and Richardson examine both philosophical and scientific developments in research on mechanistic models since 1993. (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)

This paper samples the large body of neuroscientific evidence suggesting that each mental function takes place within specific neural structures. For instance, vision appears to occur in the visual cortex, motor control in the motor cortex, spatial memory in the hippocampus, and cognitive control in the prefrontal cortex. Evidence comes from neuroanatomy, neurophysiology, neurochemistry, brain stimulation, neuroimaging, lesion studies, and behavioral genetics. If mental functions take place within neural structures, mental functions cannot survive brain death. Therefore, there is no mental (...) life after brain death. -/- 1. The Neural Localization of Mental Functions - 1.1 Perception and Motor Control - 1.2 Memory - 1.3 Emotion - 1.4 Language - 1.5 Thinking - 1.6 Attention and Consciousness - 1.7 Spirituality -- 2. Objections - 2.1 Linguistic Dualism - 2.2 Mere Correlation - 2.3 Neural Plasticity - 2.4 Intentionality - 2.5 Phenomenal Consciousness - 2.6 Subjectivity - 2.7 Self-Knowledge - 2.8 Free Will - 2.9 Are We Just Indulging in Physicalistic Wishful Thinking? -- 3. Conclusion -- Appendix: Physicalism and the Afterlife. (shrink)

A spate of recent anti-localizationist publications have re-ignited the old debate about the localization of function. Many of the recent attacks on localization, however, are directed at what I will argue to be a narrow and outmoded view of localization, and thus have little conceptual or empirical impact. What I hope to present here is an analysis of functional localization that more adequately reflects the sophistication and complexity of its use in neuroscientific research, both historically (...) and recently. Proceeding first by way of contrast, I examine theanti-localizationist positions of holism andequipotentiationism. Then, I present a four-fold analysis of localization according to physical scope, physical kind, functional scope, and functional kind. Next, I turn to a discussion of the heuristic value oflocalization in deciphering structure-functionrelationships. Finally, I hope to show that the overall view of functional localization that emerges from these considerations constitutes a much more elusive target than its critics assume. It serves to mitigate, and insome instances even defeat, some forms ofanti-localizationist criticisms. (shrink)

Spontaneous localization theory is a quantum theory proposed by GianCarlo Ghirardi, together with Alberto Rimini and Tullio Weber in 1986. However, soon it became clear to Ghirardi that his work was more than just one theory: he actually developed a framework, a family of theories in which the wavefunction jumps, but where the ontology of the theory is underdetermined. After acknowledging that the wavefunction did not provide a satisfactory ontology, he assumed that matter was described by a continuous matter (...) density field in three-dimensional space, whose evolution is governed by a stochastic wavefunction evolution. Alternatively, Bell assumed that the wavefunction would govern a spatiotemporal event ontology, dubbed ‘flashes.’ However, not much work has been done with the perhaps most obvious possibility, namely that physical objects are made of particles. This paper has two aims. First to explain the reason why people require spontaneous localization theory to be more than just a theory about the wavefunction. This is done by showing how the problem everyone in the foundation of quantum mechanics take to be the fundamental problem of quantum mechanics, namely the measurement problem, is a red herring. Then, the paper explores the possibility of spontaneous localization theories of particles. I argue that this discussion is not a mere exercise, as spontaneous localization theories of particles may be amenable to a relativistic extension which does not require a foliation, and because in general the peculiar type of indeterminism of spontaneous localization theories may help shedding new light on the nature of the tension between quantum theory and relativity. (shrink)

An entirely different mechanism and localization were recently proposed for the COPII coat complex, challenging its well‐accepted function to select and concentrate cargo into small COPII‐coated spherical transport vesicles. Instead, the COPII complex is suggested to form a dynamic yet stationary collar that forms a boundary between the ER and the ER export membrane domain. This membrane domain, the ER exit site (ERES), is the site of COPII‐mediated sorting and concentration of transport competent proteins. Subsequently, the ERES is implicated (...) to mature and bud to form a sizeable pleiomorphic transport carrier that translocate on microtubules to fuse with the Golgi apparatus. Despite this drastic mechanistic dogma shift, most of the underlying protein‐protein and protein‐membrane interactions remain unchanged. Here, we attempt to provide a detailed description of the newly proposed model of how ER to Golgi transport works by describing the role of several essential proteins of the transport machinery. (shrink)

In the late 19th century, physiologists such as David Ferrier, Eduard Hitzig, and Hermann Munk argued that cerebral brain functions are localized in discrete structures. By the early 20th century, this became the dominant position. However, another prominent physiologist, Friedrich Goltz, rejected theories of cerebral localization and argued against these physiologists until his death in 1902. I argue in this paper that previous historical accounts have failed to comprehend why Goltz rejected cerebral localization. I show that Goltz adhered (...) to a falsificationist methodology, and I reconstruct how he designed his experiments and weighted different kinds of evidence. I then draw on the exploratory experimentation literature from recent philosophy of science to trace one root of the debate to differences in how the German localizers designed their experiments and reasoned about evidence. While Goltz designed his experiments to test hypotheses about the functions of predetermined cerebral structures, the localizers explored new functions and structures in the process of constructing new theories. I argue that the localizers relied on untested background conjectures to justify their inferences about functional organization. These background conjectures collapsed a distinction between phenomena they produced direct evidence for (localized symptoms) and what they reached conclusions about (localized functions). (shrink)

Although many aspects of the physiological and pathophysiological mechanisms remain unknown, recent advances in our knowledge suggest that the CREC proteins are promising disease biomarkers or targets for therapeutic intervention in a variety of diseases. The CREC family of low affinity, Ca2+‐binding, multiple EF‐hand proteins are encoded by five genes,RCN1,RCN2,RCN3,SDF4, andCALU, resulting in reticulocalbin, ER Ca2+‐binding protein of 55 kDa (ERC‐55), reticulocalbin‐3, Ca2+‐binding protein of 45 kDa (Cab45), and calumenin. Alternative splicing increases the number of gene products. The proteins are (...) localized in the cytosol, in various parts of the secretory pathway, secreted to the extracellular space or localized on the cell surface. The emerging functions appear to be highly diverse. The proteins interact with several different ligands. Rather well‐described functions are attached to calumenin with the inhibition of several proteins in the endoplasmic or sarcoplasmic reticulum membrane, the vitamin K12,3‐epoxide reductase, the γ‐carboxylase, the ryanodine receptor, and the Ca2+‐transporting ATPase. Other functions concern participation in the secretory process, chaperone activity, signal transduction as well as participation in a large variety of disease processes. (shrink)

The problem of finding a covariant expression for the distribution and conservation of gravitational energy-momentum dates to the 1910s. A suitably covariant infinite-component localization is displayed, reflecting Bergmann's realization that there are infinitely many gravitational energy-momenta. Initially use is made of a flat background metric (or rather, all of them) or connection, because the desired gauge invariance properties are obvious. Partial gauge-fixing then yields an appropriate covariant quantity without any background metric or connection; one version is the collection of (...) pseudotensors of a given type, such as the Einstein pseudotensor, in _every_ coordinate system. This solution to the gauge covariance problem is easily adapted to any pseudotensorial expression (Landau-Lifshitz, Goldberg, Papapetrou or the like) or to any tensorial expression built with a background metric or connection. Thus the specific functional form can be chosen on technical grounds such as relating to Noether's theorem and yielding expected values of conserved quantities in certain contexts and then rendered covariant using the procedure described here. The application to angular momentum localization is straightforward. Traditional objections to pseudotensors are based largely on the false assumption that there is only one gravitational energy rather than infinitely many. (shrink)

William Uttal's The new phrenology is a broad attack on localization in cognitive neuroscience. He argues that even though the brain is a highly differentiated organ, "high level cognitive functions" should not be localized in specific brain regions. First, he argues that psychological processes are not well-defined. Second, he criticizes the methods used to localize psychological processes, including imaging technology: he argues that variation among individuals compromises localization, and that the statistical methods used to construct activation maps are (...) flawed. Neither criticism is compelling. First, as we illustrate, there are behavioral measures which offer at least weak constraints on psychological attribution. Second, though imaging does face methodological difficulties associated with variation among individuals, these are broadly acknowledged; moreover, his specific criticisms of the imaging work, and in particular of fMRI, misrepresent the methodology. In concluding, we suggest a way of framing the issues that might allow us to resolve differences between localizationist models and more distributed models empirically. (shrink)

This essay introduces the massive redeployment hypothesis, an account of the functional organization of the brain that centrally features the fact that brain areas are typically employed to support numerous functions. The central contribution of the essay is to outline a middle course between strict localization on the one hand, and holism on the other, in such a way as to account for the supporting data on both sides of the argument. The massive redeployment hypothesis is supported by (...) case studies of redeployment, and compared and contrasted with other theories of the localization of function. (shrink)

A simple geometry utilizing a laser-excited atomic beam as light source, and a nearby oscillating mirror, would permit the observation of a two-channel optical interference effect involving photons which can be localized predominantly in one channel by coincidence observations of the recoiling source atom. A sacrifice of the optimum conditions for photon interference is necessary even when photon localization in one channel is accomplished by an observation of the recoil atom. This necessity arises because the width of the slit (...) defining the atomic beam, and with it the important optical source dimension, must be comparable to the optical wavelength to obtain the small uncertainty in initial total momentum needed for significant localization. Quantum mechanical calculations of the coincidence intensity and singles intensity as a function of mirror position are made for a source width of five quarter wavelengths and are compared to a classical optics calculation of the singles intensity. The coincidence intensity calculation, as expected, predicts a smaller interference effect than classical optics due to the photon localization. The singles intensity calculation also predicts the same reduction in the classical interference effect, as a consequence of the orthoganality of the final atom states. (shrink)

It has been shown earlier that while strict localization of the free Dirac particle is not describable within the usual mathematical formalism, it is possible to describe sequences of positive-energy states whose spread Δ x =〈(x−x 0)2〉 about any given point x 0 approaches zero, where x is Dirac's position operator. The concept of a generalized function is extended here to allow for the succinct description of localized states in terms of “Asymptotic Localizing Functions.” Localization of both the (...) nonrelativistic particle and the Dirac particle can be adequately represented in this new formalism. (shrink)

In this paper I criticize a view of functional localization in neuroscience, which I call “computational absolutism”. “Absolutism” in general is the view that each part of the brain should be given a single, univocal function ascription. Traditional varieties of absolutism posit that each part of the brain processes a particular type of information and/or performs a specific task. These function attributions are currently beset by physiological evidence which seems to suggest that brain areas are multifunctional—that they process (...) distinct information and perform different tasks depending on context. Many theorists take this contextual variation as inimical to successful localization, and claim that we can avoid it by changing our functional descriptions to computational descriptions. The idea is that we can have highly generalizable and predictive functional theories if we can discover a single computation performed by each area regardless of the specific context in which it operates. I argue, drawing on computational models of perceptual area MT, that this computational version of absolutism fails to come through on its promises. In MT, the modeling field has not produced a univocal computational description, but instead a plurality of models analyzing different aspects of MT function. Moreover, CA cannot appeal to theoretical unification to solve this problem, since highly general models, on their own, neither explain nor predict what MT does in any particular context. I close by offering a perspective on neural modeling inspired by Nancy Cartwright’s and Margaret Morrison’s views of modeling in the physical sciences. (shrink)

We propose protein localization dependent signal activation (PLDSA) as a model to describe pre‐existing protein partitioning between the cytosol, and membrane surface, as a means to modulate signal activation, specificity, and robustness. We apply PLDSA to explain possible molecular links between type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) by describing Ca+2‐mediated interactions between the Src non‐receptor tyrosine kinase and p52Shc adaptor protein. We suggest that these interactions may serve as a contributing factor to disease development and progression. (...) In particular, we propose that signaling response is regulated, in part, by Ca+2‐mediated partitioning of lipid‐bound and soluble forms of Src and p52shc. Thus, protein‐protein interactions that drive signaling in response to extracellular ligand binding are also mediated by partitioning of signaling proteins between membrane‐bound and soluble populations. We propose that PLDSA effects may explain, in part, the evolutionary basis of promiscuous protein interaction domains and their importance in cellular function. (shrink)

Most binaural speech source localization models perform poorly in unprecedentedly noisy and reverberant situations. Here, this issue is approached by modelling a multiscale dilated convolutional neural network. The time-related crosscorrelation function and energy-related interaural level differences are preprocessed in separate branches of dilated convolutional network. The multiscale dilated CNN can encode discriminative representations for CCF and ILD, respectively. After encoding, the individual interaural representations are fused to map source direction. Furthermore, in order to improve the parameter adaptation, a novel (...) semiadaptive entropy is proposed to train the network under directional constraints. Experimental results show the proposed method can adaptively locate speech sources in simulated noisy and reverberant environments. (shrink)

Functional human brain mapping is commonly performed during invasive monitoring with intracranial electroencephalographic electrodes prior to resective surgery for drug­ resistant epilepsy. The current gold standard, electrocortical stimulation mapping, is time ­consuming, sometimes elicits pain, and often induces after discharges or seizures. Moreover, there is a risk of overestimating eloquent areas due to propagation of the effects of stimulation to a broader network of language cortex. Passive iEEG spatial-temporal functional mapping has recently emerged as a potential alternative to (...) ESM. However, investigators have observed less correspondence between STFM and ESM maps of language than between their maps of motor function. We hypothesized that incongruities between ESM and STFM of language function may arise due to propagation of the effects of ESM to cortical areas having strong effective connectivity with the site of stimulation. We evaluated five patients who underwent invasive monitoring for seizure localization, whose language areas were identified using ESM. All patients performed a battery of language tasks during passive iEEG recordings. To estimate the effective connectivity of stimulation sites with a broader network of task-activated cortical sites, we measured cortico-cortical evoked potentials elicited across all recording sites by single-pulse electrical stimulation at sites where ESM was performed at other times. With the combination of high gamma power as well as CCEPs results, we trained a logistic regression model to predict ESM results at individual electrode pairs. The average accuracy of the classifier using both STFM and CCEPs results combined was 87.7%, significantly higher than the one using STFM alone, indicating that the correspondence between STFM and ESM results is greater when effective connectivity between ESM stimulation sites and task-activated sites is taken into consideration. These findings, though based on a small number of subjects to date, provide preliminary support for the hypothesis that incongruities between ESM and STFM may arise in part from propagation of stimulation effects to a broader network of cortical language sites activated by language tasks, and suggest that more studies, with larger numbers of patients, are needed to understand the utility of both mapping techniques in clinical practice. (shrink)

Since the use of systems of satellite positioning such as the global positioning system, applications have tried to locate vehicles on maps representing the environment with their attributes. For one decade, this has led to both localization and navigation services for users. Recently, new researches have begun in order to extend the functionalities of the existing systems and thus to develop new applications using these technologies in the design of driver assistance systems. These new systems will indeed allow us (...) to anticipate road departures or prevent overspeed turn approaches. Nevertheless, to deploy such new functionalities, it is imperative to ensure the association of vehicle position with one of the roadmap segments. In this article, we propose a new approach based on the belief theory taking into account the imperfections of available data in order to ensure the positioning and tracking of a vehicle on a roadmap and to manage conflicts and ambiguities using a multi-hypotheses decision. (shrink)

Studies have shown that in the mammalian neuromuscular system stretch reflexes are localized within individual muscles. Neuromuscular compartmentalization, the partitioning of sensory output from muscles, and the partitioning of segmental pathways to motor nuclei have also been demonstrated. This evidence indicates that individual motor nuclei and the muscles they innervate are not homogeneous functional units. An analysis of the functional significance of reflex localization and partitioning suggests that segmental control mechanisms are based on subdivisions of motor nuclei–muscle (...) complexes. A partitioned organization of segmental control mechanisms could utilize (1) the potential functional diversity of muscle fiber types, (2) the variety of mechanical actions of individual muscles arising from their distributed origins and insertions, and (3) diverse architectural features such as intramuscular variations in pinnation and complex in-series and in-parallel arrangements of muscle fibers. The differentiated activity observed in some muscles during natural movements also calls for localized segmental control mechanisms. Partitioning may also play a role in mechanical interactions between contracting motor units and in increasing the stability of neuromuscular systems. The functional advantages of reflex localization and partitioning suggest they are probably common features of segmental systems, whose organization reflects the structure and function of their associated neuromuscular systems. (shrink)

Müller misconstrues autonomy to mean strict locality of brain function, something quite different from the functional autonomy that linguists claim. Similarly, he misperceives the interaction of learned and innate components hypothesized in current generative models. Evidence from sign languages, Creole languages, and neurological studies of rare forms of aphasia also argues against his conclusions.

Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular medium (...) where it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular medium (...) where it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Specification of the anterior‐posterior axis of the Drosophila embryo is brought about by the asymmetric localization of specific maternally expressed RNAs and proteins within the oocyte. While many of these localized molecules have been identified and progress has been made towards understanding their functions, how the localization process is instigated remains unclear. A recent paper reports that protein kinase A (PKA) activity is essential for many of these RNA localizations and for the correct polarization of the microtubule cytoskeleton(1). (...) These and other results support a model for anterior‐posterior axis establishment which involves intercellular signalling between the oocyte and certain neighbouring somatic cells. (shrink)

The apoptosis protein has a central role in the development and the homeostasis of an organism. Obtaining information about the subcellular localization of apoptosis protein is very helpful to understand the apoptosis mechanism and the function of this protein. Prediction of apoptosis protein’s subcellular localization is a challenging task, and currently the existing feature extraction methods mainly rely on the protein’s primary sequence. In this paper we develop a feature extraction model based on two different descriptors of evolutionary (...) information, which contains the 192 frequencies of triplet codons (FTC) in the RNA sequence derived from the protein’s primary sequence and the 190 features from a detrended forward moving-average cross-correlation analysis (DFMCA) based on a position-specific scoring matrix (PSSM) generated by the PSI-BLAST program. Hence, this model is called FTC-DFMCA-PSSM. A 382-dimensional (382D) feature vector is constructed on the ZD98, ZW225 and CL317 datasets. Then a support vector machine is adopted as classifier, and the jackknife cross-validation test method is used for evaluating the accuracy. The overall prediction accuracies are further improved by an objective and rigorous jackknife test. Our model not only broadens the source of the feature information, but also provides a more accurate and reliable automated calculation method for the prediction of apoptosis protein’s subcellular localization. (shrink)

Does consciousness collapse the quantum wave function? This idea was taken seriously by John von Neumann and Eugene Wigner but is now widely dismissed. We develop the idea by combining a mathematical theory of consciousness (integrated information theory) with an account of quantum collapse dynamics (continuous spontaneous localization). Simple versions of the theory are falsified by the quantum Zeno effect, but more complex versions remain compatible with empirical evidence. In principle, versions of the theory can be tested by experiments (...) with quantum computers. The upshot is not that consciousness-collapse interpretations are clearly correct, but that there is a research program here worth exploring. (shrink)

Book to honor the work of GianCarlo Ghirardi.