Over 300 years ago the father of microscopy, Antonie van Leeuwenhoek, observed dried rotifers “coming back to life” upon rehydration. Since then, scientists have been fascinated by the enduring mystery of how certain organisms survive losing essentially drying out completely. Historically sugars, such as the disaccharide trehalose, have been viewed as major functional mediators of desiccation tolerance. However, some desiccation tolerant organisms do not produce this sugar, hinting that additional mediators, and potentially novel mechanisms exist. It has become apparent that (...) a common theme among such organisms is the production and use of intrinsically disordered proteins to mediate survival in this dry state. However, the basic biology of these proteins – which unlike globular proteins lack persistent three-dimensional structure – is poorly understood, as are the functional mechanisms utilized by these enigmatic proteins that allow them to mediate desiccation tolerance. We purpose that probing the biochemical and biophysical nature of stress-related IDPs will provide mechanistic insights into these fascinating proteins. Remarkably, organisms from every kingdom of life can survive losing nearly all their intracellular water. A hallmark of desiccation tolerance is the use of intrinsically disordered proteins, but how IDPs contribute to tolerance is poorly understood. Here, we discuss possible mechanisms and avenues for studying these enigmatic proteins. (shrink)

Science and philosophy still lack an overarching theory of consciousness. We suggest that a further step toward it requires going beyond the view of the brain as input-output machine and focusing on its intrinsic activity, which may express itself in two distinct modalities, i.e. aware and unaware. We specifically investigate the predisposition of the brain to evaluate and to model the world. These intrinsic activities of the brain retain a deep relation with consciousness. In fact the ability of (...) the brain to evaluate and model the world can develop in two modalities, implicit or explicit, that correspond to what we usually refer to as the unconscious and consciousness, and both are multilevel configurations of the brain along a continuous and dynamic line. Starting from an empirical understanding of the brain as intrinsically active and plastic, we here distinguish between higher cognitive functions and basic phenomenal consciousness, suggesting that the latter might characterize the brain’s intrinsic activity as such, even if at a very basic level. We proceed to explore possible impacts of the notion of intrinsic cerebral phenomenality on our understanding of consciousness and its disorders, particularly on the diagnosis and management of patients with disorders of consciousness. (shrink)

Objectives: Autism spectrum disorder (ASD) is a juvenile onset neurodevelopmental disorder with social impairment and stereotyped behavior as the main symptoms. Unaffected relatives may also exhibit similar ASD features due to genetic factors. Although previous studies have demonstrated atypical brain morphological features as well as task-state brain function abnormalities in unaffected parents with ASD children, it remains unclear the pattern of brain function in the resting state.Methods: A total of 42 unaffected parents of ASD children (pASD) and 39 (...) age-, sex-, and handedness-matched controls were enrolled. Multiple resting-state fMRI (rsfMRI) analyzing methods were applied, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC), to reveal the functional abnormalities of unaffected parents in ASD-related brain regions. Spearman Rho correlation analysis between imaging metric values and the severity of ASD traits were evaluated as well.Results: ALFF, ReHo, and DC methods all revealed abnormal brain regions in the pASD group, such as the left medial orbitofrontal cortex (mOFC) and rectal gyrus (ROI-1), bilateral supplementary motor area (ROI-2), right caudate nucleus head and right amygdala/para-hippocampal gyrus (ROI-3). FC decreasing was observed between ROI-1 and right anterior cingulate cortex (ACC), ROI-2, and bilateral precuneus. FC enhancing was observed between ROI-3 and right anterior cerebellar lobe, left medial temporal gyrus, left superior temporal gyrus, left medial frontal gyrus, left precentral gyrus, right postcentral gyrus in pASD. In addition, ALFF values in ROI-1, DC values in ROI-3 were positively correlated with AQ scores in pASD (ρ1 = 0.298, P1 = 0.007; ρ2 = 0.220, P2 = 0.040), while FC values between ROI-1 and right ACC were negatively correlated with AQ scores (ρ3 = −0.334, P3 = 0.002).Conclusion: rsfMRI metrics could be used as biomarkers to reveal the underlying neurobiological feature of ASD for unaffected parents. (shrink)

Protein–protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein–protein recognition mechanism, mediated by disordered regions longer than 20–30 residues. Bioinformatics predictions and well‐characterized examples, such as the kinase‐inhibitory domain of Cdk inhibitors and the Wiskott–Aldrich syndrome protein (WASP)‐homology domain 2 (...) of actin‐binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains. (shrink)

Protein–protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein–protein recognition mechanism, mediated by disordered regions longer than 20–30 residues. Bioinformatics predictions and well‐characterized examples, such as the kinase‐inhibitory domain of Cdk inhibitors and the Wiskott–Aldrich syndrome protein (WASP)‐homology domain 2 (...) of actin‐binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains. (shrink)

N‐type inactivation of potassium channels is controlled by cytosolic loops that are intrinsically disordered. Recent experiments have shown that the mechanism of N‐type inactivation through disordered regions can be stereospecific and vary depending on the channel type. Variations in mechanism occur despite shared coarse grain features such as the length and amino acid compositions of the cytosolic disordered regions. We have adapted a phenomenological model designed to explain how specificity in molecular recognition is achieved through disordered regions. We propose that (...) the channel‐specific observations for N‐type inactivation represent distinct mechanistic choices for achieving function through conformational selection versus induced fit. It follows that the dominant mechanism for binding and specificity can be modulated through subtle changes in the amino acid sequences of disordered regions, which is interesting given that specificity in function is realized in the absence of autonomous folding. (shrink)

Just fifteen years ago, the common non-religious consensus was that homosexual acts were immoral. Within one decade, however, this consensus waned. The secular majority no longer held, as they previously did, that such actions are morally bad. What explains this sudden change? One explanation is that many conservatives lacked adequate philosophical tools to explain the foundations of the earlier historical consensus. Another is that modern research has shown that there never existed any solid philosophical grounds for calling such actions immoral (...) in the first place. This book questions the latter narrative; for prior to this book no exhaustive historical treatment of philosophical thought on the moral question of homosexual acts existed. Both liberals and conservatives failed to research adequately the long history of thought on this issue. The current author not only argues that the earlier non-religious philosophical consensus has largely been ignored, but that the proliferation of arguments in favor of acting on homosexual inclinations reveal a strong desire to justify what isn't possible to justify morally. The non-religious arguments of the great philosopher Thomas Aquinas are then examined; they reveal that his reasoning can soundly show that acting on homosexual inclinations is morally wrong, and also that the same argument rightly entails that every untruthful assertive speech act is morally problematic. If conservatives wish to be consistent, they ought to reject lying too. And if liberals expect conservatives to believe that what they preach is true, then they ought to stand with Aquinas and reject all lying as intrinsically evil. (shrink)

This chapter highlights the complexity of the relationship between enhancement of mood and cognition on the one hand and the improvement of people's well‐being on the other. To do so, two psychiatric conditions, Asperger's syndrome and bipolar disorder, are presented in the chapter. Even though there are both negative and positive aspects to Asperger's syndrome or to bipolar disorders, taking away even these negative aspects would not necessarily promote well‐being. It might also be impossible to isolate the positive aspects (...) of these disorders. An increase in specific forms of cognition might be intrinsically connected to a decrease in specific aspects of mood. A decrease in specific aspects of mood might be intrinsically connected to an increase in creativity. Neither is necessarily linked to any changes in some general form of “well‐being.”. (shrink)

The rare phenomenon in which a person desires amputation of a healthy limb, now often termed body integrity identity disorder, raises central questions for biomedical ethics. Standard bioethical discussions of surgical intervention in such cases fail to address the meaning of bodily integrity, which is intrinsic to a theological understanding of the goodness of the body. However, moral theological responses are liable to assume that such interventions necessarily represent an implicitly docetic manipulation of the body. Through detailed attention (...) to the ethics of mutilation and of surgery for psychiatric disorders, this article explores the theological and ethical significance of the body for human identity. (shrink)

Disorders of consciousness (DOC) raise profound scientific, clinical, ethical, and philosophical issues. Growing knowledge on fundamental principles of brain organization in healthy individuals offers new opportunities for a better understanding of residual brain function in DOCs. We here discuss new perspectives derived from a recently proposed scheme of brain organization underlying consciousness in healthy individuals. In this scheme, thalamo-cortical networks can be divided into two, often antagonistic, global systems: (i) a system of externally oriented, sensory-motor networks (the ‘‘extrinsic’’ system); and (...) (ii) a system of inward-oriented networks (the ‘‘intrinsic’’ or default system). According to this framework, four distinct mental states would be possible that could be relevant for understanding DOCs. In normal healthy volunteers and locked-in syndrome patients, a state of high functionality of both the extrinsic and intrinsic or default systems is expected — associated with full awareness of environment and self. In this case, mental imagery tasks combined with fMRI can be used to detect covert awareness in patients that are unable to communicate. According to the framework, two complementary states of system imbalance are also possible, in which one system is in a hyperfunctional state, while the other is hypoactive. Extrinsic system hyperfunction is expected to lead to a state of total sensory-motor ‘‘absorption’’ or ‘‘lost self.’’ In contrast, intrinsic or default system hyperfunction is expected to lead to a state of complete detachment from the external world. A state where both extrinsic and intrinsic systems are hypofunctional is predicted to lead to markedly impaired consciousness as seen in DOCs. Finally, we review the potential use of ultra-slow fluctuations in BOLD signal as a tool for assessing the functional integrity of extrinsic and intrinsic systems during ‘‘resting state’’ fMRI acquisitions.. (shrink)

Protein misfolding is a topic that is of primary interest both in biology and medicine because of its impact on fundamental processes and disease. In this review, we revisit the concept of protein misfolding and discuss how the field has evolved from the study of globular folded proteins to focusing mainly on intrinsically unstructured and often disordered regions. We argue that this shift of paradigm reflects the more recent realisation that misfolding may not only be an adverse event, as originally (...) considered, but also may fulfil a basic biological need to compartmentalise the cell with transient reversible granules. We nevertheless provide examples in which structure is an important component of a much more complex aggregation behaviour that involves both structured and unstructured regions of a protein. We thus suggest that a more comprehensive evaluation of the mechanisms that lead to aggregation might be necessary. (shrink)

Membership in a protein domain database does not a domain make; a feature we realized when generating a consensus view of protein fold space with our consensus domain dictionary (CDD). This dictionary was used to select representative structures for characterization of the protein dynameome: the Dynameomics initiative. Through this endeavor we rejected a surprising 40% of the 1,695 folds in the CDD as being non‐autonomous folding units. Although some of this was due to the challenges of grouping similar fold topologies, (...) the dissonance between the cataloguing and structural qualification of protein domains remains surprising. Another potential factor is previously overlooked intrinsic disorder; predictions suggest that 40% of proteins have either local or global disorder. One thing is clear, filtering a structural database and ensuring a consistent definition for protein domains is crucial, and caution is prescribed when generalizations of globular domains are drawn from unfiltered protein domain datasets. (shrink)

Membership in a protein domain database does not a domain make; a feature we realized when generating a consensus view of protein fold space with our consensus domain dictionary (CDD). This dictionary was used to select representative structures for characterization of the protein dynameome: the Dynameomics initiative. Through this endeavor we rejected a surprising 40% of the 1,695 folds in the CDD as being non‐autonomous folding units. Although some of this was due to the challenges of grouping similar fold topologies, (...) the dissonance between the cataloguing and structural qualification of protein domains remains surprising. Another potential factor is previously overlooked intrinsic disorder; predictions suggest that 40% of proteins have either local or global disorder. One thing is clear, filtering a structural database and ensuring a consistent definition for protein domains is crucial, and caution is prescribed when generalizations of globular domains are drawn from unfiltered protein domain datasets. (shrink)

Awareness of internal bodily sensations and its connection to complex socioemotional abilities like empathy has been postulated, yet the functional neural circuitry they share remains poorly understood. The present fMRI study employs independent component analysis to investigate which empathy facet shares resting-state functional connectivity and/or BOLD variability with IA. Healthy participants viewed an abstract nonsocial movie demonstrated to evoke strong rsFC in brain networks resembling rest, and resultant rsFC and rsBOLD data were correlated with self-reported empathy and IA questionnaires. We (...) demonstrate a bidirectional behavioral and neurobiological relationship between empathy and IA, depending on the type of empathy interrogated: Affective empathy and IA share both rsFC and rsBOLD, while Cognitive empathy and IA only share rsBOLD. Specifically, increased rsFC in the right inferior frontal operculum of a larger attention network was associated with increased vicarious experience but decreased awareness of inner body sensations. Furthermore, increased rsBOLD between brain regions of an interoceptive network was related to increased sensitivity to internal sensations along with decreased Affective empathy. Finally, increased rsBOLD between brain regions subserving a mentalizing network related to not only an improved ability to take someone’s perspective, but also a better sense of mind-body interconnectedness. Overall, these findings suggest that the awareness of one’s own internal body changes is related to the socioemotional ability of feeling and understanding another’s emotional state and critically, that this relationship is reflected in the brain’s resting state neuroarchitecture. Methodologically, this work highlights the importance of utilizing rsBOLD as a complementary window alongside rsFC to better understand neurological phenomena. Our results may be beneficial in aiding diagnosis in clinical populations such as autism spectrum disorder, where participants may be unable to complete tasks or questionnaires due to the severity of their symptoms. (shrink)

The phenomenology of inner temporalizing developed by Edmund Husserl provides a helpful framework for understanding a type of experiencing that can be part of the Post-Traumatic Stress Disorder (PTSD). My paper extrapolates hints from Husserl's work in order to describe those memories — flashbacks — that come so strongly to consciousness as to overtake the experiencer. Husserl's work offers several clues: his view of inner temporalization by which conscious experiences flow in both a serial and a nonserial manner; a (...) characterization of process memory as distinct from representational memory; and the notion of telos, which takes human subjectivity as intrinsically changeable, for example, by means of a retroactive cancellation that would allow the PTSD experiencer to re-process the original meaning of the traumatic experience into a meaning that fits the current situation and thus allows a recovery. (shrink)

Background: Although previous studies have shown an inverse relation between life meaning and eating disorder symptoms, the correlational nature of this evidence precludes causal inferences. Therefore, this study used an experimental approach to test the causal impact of life meaning on individuals' weight and shape concerns.Methods: Female students at risk for developing an eating disorder were randomly assigned to the control or the meaning condition, which involved thinking about and committing to pursue intrinsically valued life goals. A color-naming (...) interference task was used to assess the motivational salience of body-related stimuli, and self-report measures were used to assess participants' overvaluation of weight and shape.Results: The meaning manipulation was effective in activating intrinsically valued life goals. However, it did not result in lower self-reported overvaluation of weight and shape or lower color-naming interference effects of body-related stimuli, compared to the control condition. Post-hoc analyses suggested that baseline meaning in life was related to the impact of the manipulation.Conclusions: This experimental study did not provide evidence for a causal influence of life meaning on the overvaluation of weight and shape in a high-risk group. The current findings suggest that we first need to examine the relationship between life meaning and eating disorder symptoms in more detail, before implementing brief meaning manipulations in clinical practice. (shrink)

Recent advances in the neuroscience of episodic memory provide a framework to integrate object relations theory, a psychoanalytic model of mind development, with potential neural mechanisms. Object relations are primordial cognitive-affective units of the mind derived from survival- and safety-level experiences with caretakers during phase-sensitive periods of infancy and toddlerhood. Because these are learning experiences, their neural substrate likely involves memory, here affect-enhanced episodic memory. Inaugural object relations are encoded by the hippocampus-amygdala synaptic plasticity, and systems-consolidated by medial prefrontal cortex (...) (mPFC). Self- and object-mental representations, extracted from these early experiences, are at first dichotomized by contradictory affects evoked by frustrating and rewarding interactions (“partial object relations”). Such affective dichotomization appears to be genetically hardwired the amygdala. Intrinsic propensity of mPFC to form schematic frameworks for episodic memories may pilot non-conscious integration of dichotomized mental representations in neonates and infants. With the emergence of working memory in toddlers, an activated self- and object-representation of a particular valence can be juxtaposed with its memorized opposites creating a balanced cognitive-affective frame (conscious “integration of object relations”). Specific events of object relations are forgotten but nevertheless profoundly influence the mental future of the individual, acting (i) as implicit schema-affect templates that regulate attentional priorities, relevance, and preferential assimilation of new information based on past experience, and (ii) as basic units of experience that are, under normal circumstances, integrated as attractors or “focal points” for interactive self-organization of functional brain networks that underlie the mind. A failure to achieve integrated object relations is predictive of poor adult emotional and social outcomes, including personality disorder. Cognitive, cellular-, and systems-neuroscience of episodic memory appear to support key postulates of object relations theory and help elucidate neural mechanisms of psychodynamic psychotherapy. Derived through the dual prism of psychoanalysis and neuroscience, the gained insights may offer new directions to enhance mental health and improve treatment of multiple forms of psychopathology. (shrink)

Targeted gene alteration (TGA) is a strategy for correcting single base mutations in the DNA of human cells that cause inherited disorders. TGA aims to reverse a phenotype by repairing the mutant base within the chromosome itself, avoiding the introduction of exogenous genes. The process of how to accurately repair a genetic mutation is elucidated through the use of single‐stranded DNA oligonucleotides (ODNs) that can enter the cell and migrate to the nucleus. These specifically designed ODNs hybridize to the target (...) sequence and act as a beacon for nucleotide exchange. The key to this reaction is the frequency with which the base is corrected; this will determine whether the approach becomes clinically relevant or not. Over the course of the last five years, workers have been uncovering the role played by the cells in regulating the gene repair process. In this essay, we discuss how the impact of the cell on TGA has evolved through the years and illustrate ways that inherent cellular pathways could be used to enhance TGA activity. We also describe the cost to cell metabolism and survival when certain processes are altered to achieve a higher frequency of repair. (shrink)

Protein structure is dynamic: the intrinsic flexibility of polypeptides facilitates a range of conformational fluctuations, and individual protein chains can assemble into complexes. Proteins are also dynamic in evolution: significant variations in secondary, tertiary and quaternary structure can be observed among divergent members of a protein family. Recent work has highlighted intriguing similarities between these structural and evolutionary dynamics occurring at various levels. Here we review evidence showing how evolutionary changes in protein sequence and structure are often closely related (...) to local protein flexibility and disorder, large‐scale motions and quaternary structure assembly. We suggest that these correspondences can be largely explained by neutral evolution, while deviations between structural and evolutionary dynamics can provide valuable functional insights. Finally, we address future prospects for the field and practical applications that arise from a deeper understanding of the intimate relationship between protein structure, dynamics, function and evolution. (shrink)

Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum‐Golgi intermediate compartment (ERGIC). These membranous vesicular‐tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII‐coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI‐dependent transport on to the cis‐Golgi. The mechanisms underlying formation and (...) maintenance of ERGIC membranes are poorly defined. However, recent evidence suggests an important role for Trk‐fused gene (TFG) in regulating the integrity of the ER/ERGIC interface. Moreover, in the absence of cytoskeletal elements to scaffold tracks on which COPII carriers might move, TFG appears to promote anterograde cargo transport by locally tethering COPII carriers adjacent to ERGIC membranes. This action, regulated in part by the intrinsically disordered domain of TFG, provides sufficient time for COPII coat disassembly prior to heterotypic membrane fusion and cargo delivery to the ERGIC. -/- . (shrink)

Fission of cellular membranes is ubiquitous and essential for life. Complex protein machineries, such as the dynamin and ESCRT spirals, have evolved to mediate membrane fission during diverse cellular processes, for example, vesicle budding. A new study suggests that non-specialized membrane-bound proteins can induce membrane fission through mass action due to protein crowding. Because up to 2/3 of the mass of cellular membranes is contributed by proteins, membrane protein crowding is an important physiological parameter. Considering the complexity of membrane shape (...) transitions during a fission reaction, spatial and temporal variability in protein distribution, and the abundance of intrinsically disordered regions in proteins on an invaginating membrane, protein crowding can have diverse consequences for fission in the cell. The question is, how and to what extent this mechanism combines with the action of dedicated fission machineries. Membrane fission, which is required for formation of vesicles or cytokinesis, can be carried out by specialized proteins like dynamin and the ESCRT complex. Recent work suggests that fission of cellular membranes, which are densely packed with proteins, can also be induced by protein crowding due to high entropic tension. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The 2007 Meeting of the Society for Buddhist-Christian StudiesSan Diego, California, November 16–17, 2007Peter A. HuffThe Society for Buddhist-Christian Studies sponsored two sessions in conjunction with the 2007 annual meeting of the American Academy of Religion (AAR). Each session highlighted themes related to the work of a major figure in Buddhist-Christian dialogue. The first session, addressing the topic “Homosexuality, the Church, and the Sangha,” was organized in honor of (...) Roger Corless (1938–2007), longtime member of the society, dual practitioner of Roman Catholicism and Vajrayana Buddhism, and a well-known voice for “queer sangha.” The second session, a panel discussion titled “The Thought and Legacy of Masao Abe,” focused on the career achievements of Abe (1915–2006), widely acknowledged as one of the most innovative and influential scholars in modern Zen studies, interreligious dialogue, and comparative philosophy.The first session, moderated by Harry Wells (Humboldt State University), featured three papers on issues of gender, sexual ethics, and religious identity. Robert Fastiggi, professor of systematic theology at Sacred Heart Major Seminary (Detroit), presented the paper “The Catholic Church and Homosexuality.” Arguing that the Catholic tradition avoids an “either/or” approach to homosexuality, he outlined the church’s official distinction between morally neutral homoerotic identity and what Vatican documents call “intrinsically disordered” homosexual acts. He also noted that Catholic researchers differ significantly on the question of the genetic origins of same-sex attraction. The key to Catholic moral teaching on homosexuality, he explained, is a “theology of the body” that envisions male-female complementarity as the divinely ordained pattern of creation. Fastiggi suggested that further discussion of related ideas such as celibacy, chastity, desire, and concupiscence would enhance future Buddhist-Christian dialogue on homosexuality.Ilene Stanford, a ThD candidate in religion, gender, and culture at Harvard University, presented the next paper, “In or Out? Marriage as a Social Practice.” Describing marriage in the United States as a “site of contestation,” she explored the conflicting [End Page 137] models of sexual union that currently inform public debates in political and ecclesiastical contexts. Using William Johnson’s A Time to Embrace: Same-Gender Relationships in Religion, Law, and Politics (2006) as a point of departure, she argued that many contemporary examinations of sexual relationships, even some of the most inclusive, fail to reckon with the way in which the West’s Augustinian legacy continues to make heterosexual marriage the norm for all moral reflection on sexual identity and expression. The escalating controversy in the international Anglican community, she said, exposes the weaknesses of Johnson’s “deliberative democracy” model and other theoretical models that minimize the role of political and social power in the construction of sexual ideals.José Ignacio Cabezón, who holds the XIV Dalai Lama Chair in Tibetan Buddhism at the University of California, Santa Barbara, presented the final paper: “Is Homosexual Sex ‘Sexual Misconduct’? Critical Reflections on Some Classical Indo-Tibetan Sources.” Analyzing the changing portraits of sexual immorality in the Pali canon, Indian Sanskrit texts, and Tibetan scholastic treatises, Cabezón traced the evolution of monastic commentary on lay sexuality over the course of several centuries. What originated primarily as a simple prohibition against some forms of male adulterous activity, he explained, eventually became an unprecedented attempt to regulate intricate details of sexual behavior. Identifying Ansanga (fourth century ce) as the first Buddhist writer to proscribe same-sex activity between men, Cabezón suggested that changing social mores, intra-Buddhist debates, and the fertile monastic imagination contributed to the gradual elaboration of moral teaching in ancient and classical Buddhist literature.After the paper presentations, Richard Reilly, professor of philosophy at St. Bonaventure University, responded with provocative comments. He raised critical points about the significance of the distinction between sexual acts and erotic relationships, the strategic though limited value of “deliberative democracy” in multicultural faith communities, and the need for more rigorous comparative study of homophobic legislation in Buddhist and Abrahamic religious traditions. Sparking an engaging discussion among presenters and members of the audience, Reilly’s remarks underscored the importance of ongoing interdisciplinary investigations into homosexuality, the church, and the sangha.The society’s second session at the AAR provided a venue for former... (shrink)

Membranous organelles allow sub‐compartmentalization of biological processes. However, additional subcellular structures create dynamic reaction spaces without the need for membranes. Such membrane‐less organelles (MLOs) are physiologically relevant and impact development, gene expression regulation, and cellular stress responses. The phenomenon resulting in the formation of MLOs is called liquid–liquid phase separation (LLPS), and is primarily governed by the interactions of multi‐domain proteins or proteins harboring intrinsically disordered regions as well as RNA‐binding domains. Although the presence of RNAs affects the formation and (...) dissolution of MLOs, it remains unclear how the properties of RNAs exactly contribute to these effects. Here, the authors review this emerging field, and explore how particular RNA properties can affect LLPS and the behavior of MLOs. It is suggested that post‐transcriptional RNA modification systems could be contributors for dynamically modulating the assembly and dissolution of MLOs. (shrink)

Changes in the abundance of protein and RNA molecules can impair the formation of complexes in the cell leading to toxicity and death. Here we exploit the information contained in protein, RNA and DNA interaction networks to provide a comprehensive view of the regulation layers controlling the concentration‐dependent formation of assemblies in the cell. We present the emerging concept that RNAs can act as scaffolds to promote the formation ribonucleoprotein complexes and coordinate the post‐transcriptional layer of gene regulation. We describe (...) the structural and interaction network properties that characterize the ability of protein and RNA molecules to interact and phase separate in liquid‐like compartments. Finally, we show that presence of structurally disordered regions in proteins correlate with the propensity to undergo liquid‐to‐solid phase transitions and cause human diseases. Also see the video abstract here https://youtu.be/kfpqibsNfS0. (shrink)

Following new scientific evidence, removal of the fallopian tubes or the ovaries, or both, are options for reducing the risk of ovarian cancer. This paper examines the new scientific evidence on the origin of ovarian cancer and argues that the removal of fallopian tubes or ovaries in high-risk patients for the purpose of reducing risk of cancer is not intrinsically disordered. Although a present and serious pathology may not exist, this removal constitutes an indirect sterilization, because the immediate and primary (...) effect is the reduction in risk of a pathological condition. This effect occurs immediately, directly, and effectively, and sterilization is a secondary effect. The paper then reflects on the subsequent inadequacy of the language of “present and serious pathology” given the new evidence on ovarian cancer. National Catholic Bioethics Quarterly 14.1 : 67–79. (shrink)

In Genesis 27 Jacob is depicted as lying to Isaac. Jacob, however, was held in Christian tradition to be both a moral exemplar and to be speaking prophetically in this episode with his father. This raises the question of how Doctors of the Church such as St. Augustine and St. Thomas Aquinas were able reconcile these interpretive commitments with their stance on the intrinsically disordered nature of lying. In examining their resolution of this tension, we discover an important exegetical distinction (...) for interpreting troubling words as nevertheless being divinely inspired. Yet, it is only in light of another interpretive distinction, recently highlighted by Nicholas Lombardo OP, that we can both hold to the inspired nature of Jacob's words and also a natural reading of the account in Genesis 27. The detailed examination of Genesis 27 by both Augustine and Aquinas is an important case study for understanding how we can interpret troubling language as still being the word of God. This undertaking, spanning centuries between Augustine and Aquinas, is now taken one step further thanks to the exegetical proposal of Fr. Lombardo. (shrink)

Cis‐regulatory elements govern gene expression programs to determine cell identity during development. Recently, the possibility that multiple enhancers are orchestrated in clusters of enhancers has been suggested. How these elements are arranged in the 3D space to control the activation of a specific promoter remains unclear. Our recent work revealed that the TGFβ pathway drives the assembly of enhancer clusters and precise gene activation during neurogenesis. We discovered that the TGFβ pathway coactivator JMJD3 was essential in maintaining these structures in (...) the 3D space. To do that, JMJD3 required an intrinsically disordered region involved in forming phase‐separated biomolecular condensates found in the enhancer clusters. Our data support the existence of a relationship between 3D‐conformation of the chromatin, biomolecular condensates, and TGFβ‐driven response during mammalian neurogenesis. In this review, we discuss how signaling (TGFβ), epigenetics (JMJD3), and biochemical properties (biomolecular condensates nucleation) are coordinated to modulate the genome structure to guarantee proper neural development. Moreover, we comment on the potential underlying mechanisms and implications of the enhancer‐mediated regulation. Finally, we point out the knowledge gaps that still need to be addressed. (shrink)

In his paper “Whatever next? Predictive brains, situated agents, and the future of cognitive science,” Andy Clark seminally proposed that the brain's job is to predict whatever information is coming “next” on the basis of prior inputs and experiences. Perception fundamentally subserves survival and self-preservation in biological agents, such as humans. Survival however crucially depends on rapid and accurate information processing of what is happening in the here and now. Hence, the term “next” in Clark's seminal formulation must include not (...) only the temporal dimension (i.e., what is perceivednow) but also the spatial dimension (i.e., what is perceivedhereor next-to-my-body). In this paper, we propose to focus on perceptual experiences that happen “next,” i.e., close-to-my-body. This is because perceptual processing of proximal sensory inputs has a key impact on the organism's survival. Specifically, we focus on tactile experiences mediated by the skin and what we will call the “extended skin” or “second skin,” that is, immediate objects/materials that envelop closely to our skin, namely, clothes. We propose that the skin and tactile experiences are not a mere border separating the self and world. Rather, they simultaneously and inherently distinguishandconnect the bodily self to its environment. Hence, these proximal and pervasive tactile experiences can be viewed as a “transparent bridge” intrinsically relating and facilitating exchanges between the self and the physical and social world. We conclude with potential implications of this observation for the case of Depersonalization Disorder, a condition that makes people feel estranged and detached from their self, body, and the world. (shrink)

Psychopaths are often regarded as a scourge of contemporary society and, as such, are the focus of much public vilification and outrage. But, arguably, psychopaths are both sinned against as well as sinners. If that is true, then their status as the victims of abusive subcultures partially mitigates their moral responsibility for the harms they cause. We argue, from the neuroethics of psychopathy and antisocial personality disorder (ASPD), that communities have a moral obligation to psychopaths as well as a (...) case against them. A reflection on the genesis and developmental epidemiology of psychopathy reveals an individualist, attribution-type error evident in much Western psychological and legal thinking—an error that obscures important moral truths about psychopaths. The resulting analysis makes us reconsider the distinction between disorders and moral failings and the ethical significance of the biological or neurocognitive mechanisms underpinning psychopathy. We claim that casting aside the deficit model (based on the presupposition that psychopaths are intrinsically unlike the rest of us) in favor of a relational and holistic view of personality potentiates a more informed and inclusive set of ethical, forensic, and therapeutic attitudes. (shrink)

The neurodiversity paradigm is presented by its proponents as providing a philosophical foundation for the activism of the neurodiversity movement. Its central claims are that autism and other neurodivergent conditions are not disorders because they are not intrinsically harmful, and that they are valuable, natural and/or normal parts of human neurocognitive variation. This paper: (a) identifies the non‐disorder claim as the most central of these, based on its prominence in the literature and connections with the practical policy claims that (...) the paradigm is supposed to support; (b) describes the heterogeneity of autism at the behavioural and causal levels, and argues that at the behavioural level this encompasses ways of being autistic that are harmful in ways that cannot be not wholly attributed to discrimination or unjust social arrangements, challenging the claim that autism is not a disorder; (c) considers and rejects responses to this challenge based on separation of high‐ and low‐functioning autism, separation of autism from co‐occurring conditions, and viewing autism as part of an individual’s identity. Two of these responses fail for reasons that are themselves connected with the behavioural and/or causal heterogeneity of autism. (shrink)

Cognitive functions are directly related to interactions between the brain's functional networks. This functional organization changes in the autism spectrum disorder (ASD). However, the heterogeneous nature of autism brings inconsistency in the findings, and specific pattern of changes based on the cognitive theories of ASD still requires to be well-understood. In this study, we hypothesized that the theory of mind (ToM), and the weak central coherence theory must follow an alteration pattern in the network level of functional interactions. The (...) main aim is to understand this pattern by evaluating interactions between all the brain functional networks. Moreover, the association between the significantly altered interactions and cognitive dysfunctions in autism is also investigated. We used resting-state fMRI data of 106 subjects (5–14 years, 46 ASD: five female, 60 HC: 18 female) to define the brain functional networks. Functional networks were calculated by applying four parcellation masks and their interactions were estimated using Pearson's correlation between pairs of them. Subsequently, for each mask, a graph was formed based on the connectome of interactions. Then, the local and global parameters of the graph were calculated. Finally, statistical analysis was performed using a two-sample t-test to highlight the significant differences between autistic and healthy control groups. Our corrected results show significant changes in the interaction of default mode, sensorimotor, visuospatial, visual, and language networks with other functional networks that can support the main cognitive theories of autism. We hope this finding sheds light on a better understanding of the neural underpinning of autism. (shrink)

This book defends the much-disputed view that emotions are what Hume referred to as ‘original existences’: feeling states that have no intentional or representational properties of their own. In doing so, the book serves as a valuable counterbalance to the now mainstream view that emotions are representational mental states. Beginning with a defence of a feeling theory of emotion, Whiting opens up a whole new way of thinking about the role and centrality of emotion in our lives, showing how emotion (...) is key to a proper understanding of human motivation and the self. Whiting establishes that emotions as types of bodily feelings serve as the categorical bases for our behavioural dispositions, including those associated with moral thought, virtue, and vice. The book concludes by advancing the idea that emotions make up our intrinsic nature - the characterisation of what we are like in and of ourselves, when considered apart from how we are disposed to behave. The conclusion additionally draws out the implications of the claims made throughout the book in relation to our understanding of mental illness and the treatment of emotional disorders. (shrink)

During recent decades various researchers from health and social sciences have been debating what it means for a person to be disabled. A rather overlooked approach has developed alongside this debate, primarily inspired by the philosophical tradition called phenomenology. This paper develops a phenomenological model of disability by arguing for a different methodological and conceptual framework from that used by the existing phenomenological approach. The existing approach is developed from the phenomenology of illness, but the paper illustrates how the case (...) of congenital disabilities, looking at the congenital disorder called cerebral palsy (CP), presents a fundamental problem for the approach. In order to understand such congenital cases as CP, the experience of disability is described as being gradually different from, rather than a disruption of, the experience of being abled, and it is argued that the experience of disability is complex and dynamically influenced by both intrinsic and extrinsic factors. Different experiential aspects of disability— pre-reflective, attuned and reflective aspects—are described, demonstrating that the experience of disability comes in different degrees. Overall, this paper contributes to the debates about disability by further describing the personal aspects and experience of persons living with disabilities. (shrink)

The paper considers whether psychiatric kinds can be natural kinds and concludes that they can. This depends, however, on a particular conception of ‘natural kind’. We briefly describe and reject two standard accounts – what we call the ‘stipulative account’ (according to which apparently a priori criteria, such as the possession of intrinsic essences, are laid down for natural kindhood) and the ‘Kripkean account’ (according to which the natural kinds are just those kinds that obey Kripkean semantics). We then (...) rehearse a more permissive account: Richard Boyd’s ‘homeostatic property cluster’ (HPC) account. We argue that psychiatric kinds can in principle count as natural kinds on the HPC account. Moreover, specific psychiatric kinds (Tourette’s, schizophrenia, etc.) can be natural kinds even if the category psychiatric disorder is not itself a natural kind. (shrink)

In this article, I consider the structure of interpersonal emotional relations. I argue that current cognitive-developmental theory has overestimated the role of conceptual thinking, and underestimated the role of intrinsic social-emotional organization, in the early development of such feelings as jealousy, shame, and concern. I suggest that human forms of social experience are shaped by a process through which one individual identifies with the bodily expressed attitudes of other people, and stress the diversity of self–other relational states. I draw (...) on studies in developmental psychopathology, and specifically research in autism and borderline personality disorder, to illustrate some implications of this viewpoint. (shrink)

In this paper we suggest the existence of a generalized task-related cortical network that is up-regulated whenever the task to be performed requires the allocation of generalized non-specific cognitive resources, independent of the specifics of the task to be performed. We have labeled this general purpose network, the extrinsic mode network (EMN) as complementary to the default mode network (DMN), such that the EMN is down-regulated during periods of task-absence, when the DMN is up-regulated, and vice versa. We conceptualize the (...) EMN as a cortical network for extrinsic neuronal activity, similar to the DMN as being a cortical network for intrinsic neuronal activity. The EMN has essentially a fronto-temporo-parietal spatial distribution, including the inferior and middle frontal gyri, inferior parietal lobule, supplementary motor area, inferior temporal gyrus. We hypothesize that this network is always active regardless of the cognitive task being performed. We further suggest that failure of network up- and down-regulation dynamics may provide neuronal underpinnings for cognitive impairments seen in many mental disorders, such as, e.g., schizophrenia. We start by describing a common observation in functional imaging, the close overlap in fronto-parietal activations in healthy individuals to tasks that denote very different cognitive processes. We now suggest that this is because the brain utilizes the EMN network as a generalized response to tasks that exceeds a cognitive demand threshold and/or requires the processing of novel information. We further discuss how the EMN is related to the DMN, and how a network for extrinsic activity is related to a network for intrinsic activity. Finally, we discuss whether the EMN and DMN networks interact in a common single brain system, rather than being two separate and independent brain systems. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Ought We to Require Emotional Capacity as Part of Decisional Competence?Paul S. Appelbaum* (bio)AbstractThe preceding commentary by Louis Charland suggests that traditional cognitive views of decision-making competence err in not taking into account patients’ emotional capacities. Examined closely, however, Charland’s argument fails to escape the cognitive bias that he condemns. However, there may be stronger arguments for broadening the focus of competence assessment to include emotional capacities, centering on (...) the ways in which emotions aid humans in processing information. Before emotional capacities are added to the list of functions essential for decisional competence, though, the feasibility and utility of such a reorientation must be demonstrated.To what extent ought persons’ capacities to experience emotion be taken into account when determining whether they should be deemed competent to make their own decisions? In the previous article, Louis Charland (1998) argues that traditional models of decision-making competence—of which the MacArthur Competence Treatment Study is a typical example—are mistaken in focusing narrowly on persons’ cognitive abilities to the neglect of emotional factors. In contrast, he suggests, constructs of competence ought explicitly to require a capacity to experience emotions, which he believes is central to meaningful decision making, before deeming persons competent.Charland, as he acknowledges, is not the first to suggest that the presence of some degree of emotional capacity is a necessary element of competence, but his argument is among the most elaborate to date and is certainly worth closer examination. Looked at carefully, however, Charland’s argument does not make quite the case for the determination of emotional capacity in competence assessment that he claims for it. Indeed, as I demonstrate below, Charland may share the same “pernicious [End Page 377] cognitive bias” that he ascribes to more traditional approaches. However, despite what I identify as the problems in Charland’s argument, others have raised more disturbing questions about the lack of attention to emotional issues in competence assessment. Thus, I am not ready to reject entirely the possibility that determinations of decisional competence ought to consider emotional factors. I conclude by outlining the questions that remain to be answered to identify more clearly the potential benefits of such an approach.The Construct of Decision-Making CompetenceSome preliminary comments about the nature of the dominant construct of decision-making competence may provide a useful frame for my response to Charland’s paper. Contemporary ideas of competence are tied inextricably to the ideal of self-determination in modern Western societies. Such societies are committed to respect for individual choice, both as a good in its own right and on the grounds that each person knows best what choices will maximize his or her own welfare. In general, therefore, states will not intervene to prevent persons from acting on their decisions, even when the choices they make—like the decision to smoke or to refuse potentially life-saving medical care—may objectively be thought to be detrimental to them.In some cases, however, the presumption that people will act in their own interests, as well as the notion that there is something intrinsically valuable in respecting their choices, fails (Buchanan and Brock 1989). When people’s minds are so disordered that they cannot be said to be making meaningful choices, other values come into play. Such people are called “incompetent.” When persons reach that point, the state’s interest in protecting its citizens becomes primary and someone else must make decisions on their behalf. Note that the size of this group must be sharply limited, lest a liberal society’s commitment to self-determination be undermined: There is no more profound infringement of the rights of citizens than the determination that they are incompetent. Thus, the criteria for incompetence must be selected in a deliberately narrow fashion—alternately, one might say that the standards for competence are made intentionally broad—so that all but a tiny percentage of citizens will be permitted to make decisions on their own.In the Anglo-American world, the process of formulating criteria of competence by and large has been left to the common law courts. Over the course of centuries they have identified the capacities that are, in... (shrink)

I hypothesize that people engage in religious practices, in part, because such practices activate the frontal lobes. Activation of the frontal lobes is both intrinsically rewarding and necessary for acquisition of many of the behaviors that religions seek to foster, including self‐responsibility, impulse and emotion modulation, empathy, moral insight, hope, and optimism. Although direct tests of the hypothesis are as yet nonexistent, there is reasonably strong circumstantial evidence (reviewed herein) for it. Recent brain‐imaging studies indicate greater anterior activation values and (...) increased blood flow to frontal sites during prayer and meditation. Regular prayer is positively correlated with better overall mental health. Religiosity is correlated with higher levels of self‐monitoring, empathy, and moral insight and other positive behaviors and negatively correlated with depression and impulsive and risky behaviors. Independent data show that self‐monitoring, empathy, hope, and moral insight are all selectively associated with intact frontal function, whereas depression, impulsiveness, and drug and alcohol abuse are associated selectively with frontal dysfunction. If religious practices do indeed preferentially activate and stimulate development of the frontal lobes, (a) religious practices should be considered as possible adjuncts for some patients in treatment for mental health disorders, and (b) the frontal lobes (rather than the temporal lobes) should be considered the major brain site that supports the core components of religious experience. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Commentary on “Epistemic Value Commitments”W. John Livesley (bio)A disquieting feature of contemporary psychiatric nosology is the tendency to adopt positions that imply that current classifications are simply statements of fact. Clinicians and researchers alike seem to assume that the DSM diagnostic concepts are factual descriptions based only on scientific analysis that reflect the essential nature of psychiatric disorders. The architects of the DSM acknowledge in various ways that this (...) is not the case. Frances et al. (1991), for example, noted the provisional and pragmatic nature of DSM-IV. Nevertheless, these cautions are largely ignored. The DSM is partly responsible. The assertion that the DSM is atheoretical with regard to etiology, although clearly incorrect, tends to generalize to other aspects of the system. Similarly, the emphasis on description that has proved so valuable in improving diagnosis is presented as if clinical description is unencumbered by values and assumptions. Moreover, the failure to state explicitly the assumptions underlying the classification encourages the conclusion that the system is free from theoretical and other influences.In fact the DSM is theory laden. Implicit theoretical models and etiological concepts lie behind many diagnoses, including adjustment, dissociative, and posttraumatic stress disorders. Assumptions about the nature of mental disorders and the way psychopathology is organized underlie the entire system (Livesley and Jackson 1992). Pragmatic and political considerations influenced the final structure. Moreover, as Dr. Sadler and others working on the same issues (Fulford 1989, 1994; Agich 1994) point out, the DSM is also value laden. It is value laden not only in the obvious sense that some diagnostic concepts are highly evaluative or biased against certain groups (Kaplan 1983), but also in the fundamental sense that values are built into the very structure of the system (Agich 1994; Russell 1994; Wakefield 1992).Value influences begin with the definition of mental disorder. As Wakefield (1992) and others have argued, the concept of disorder cannot be value free. Values are also involved in the descriptive terms adopted as diagnostic criteria (Agich 1994) and, as Dr. Sadler convincingly demonstrates, they are intrinsic to the way that the classification is constructed and evaluated—the very aspects of the classification that are generally assumed to be value free. By emphasizing this aspect, Dr. Sadler draws attention to the fact that despite being implicit and informal, these values exert a major influence. They influence kinds of information considered relevant to the classification, the way this information is weighted and evaluated, and the way it is organized into diagnostic concepts. Thus, values shape the classification and the research agenda. This point has not [End Page 223] been fully recognized, or at least not fully acknowledged, by those responsible for developing contemporary classifications. There is a tendency to assume that any values involved in the DSM are largely evaluative and incidental, as if they crept into the system inadvertently due to our limited knowledge. The implication is that their presence is merely a temporary embarrassment to be eliminated automatically as clinical description and phenomenology are refined. But this is not the case; any classification of mental disorders inevitably consists of fact plus value (Fulford 1994). Acknowledgment of the evaluative element does not detract from the achievements of the DSM. It is not a limitation but an essential component.The general failure to attend to the non-factual or non-descriptive aspects of classification means that important aspects of classifications are neglected. The impact of pragmatic considerations, political and economic factors, and ethical and epistemic values on the organization and evaluation of scientific information has not received appropriate attention given the social, clinical, and scientific consequences of contemporary psychiatric classifications. In essence, only a limited aspect of classification has been studied, and even this has been studied in isolation from its context. Under these circumstances there is much to be gained from explicit acknowledgment and analysis of the value component. We are more likely to make progress in resolving nosological issues if we take a broad perspective.For the nosologist, Dr. Sadler makes two useful contributions to understanding the broader view. First, the analysis of value is extended beyond discussion of evaluative or ethical values into a detailed analysis of the epistemic values that... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Aristotle Rules, OK?José M. Villagrán (bio) and Rogelio Luque (bio)KeywordsAristotle, causes, philosophy, psychiatry, psychopathologyPérez-Alvarez, Sass, and García-Montes (2008) propose a theoretical approach to the nature of mental disorders (MD) that attempts to explain the type of reality they constitute. In line with this approach, they argue that (1) MDs should be considered not from within psychology and psychiatry, but rather from the realm of philosophy, so as to avoid (...) what they call the Charcot effect; (2) the resulting theoretical model is in contrast to naturalist models such as that of internal dysfunction, and involves “strong” constructivist assumptions from which they develop an anthropological perspective based on the clinician–patient situation; 3) this model is applicable, in principle, to all MDs (“at least to some extent”); and (4) it is based on the Aristotelian theory of the four causes.We would argue, however, that (1) it is precisely from within psychology and psychiatry that conceptual models accounting for MDs should be proposed; (2) the naturalist–constructivist dichotomy in these models should be deconstructed, and primacy given not to the ontological approach but to the epistemological one; (3) a theoretical model of this scope should account not only for MDs but also for physical disorders; and (4) only in this way would the Aristotelian theory of causes, understood as types of explanation (and therefore as epistemological approaches) be useful.Approaches from within and from WithoutFor Berrios (2006), the theoretical discourse in relation to the conceptualization of MDs in a particular sociocultural context can be formulated in two ways: on the one hand, in a centripetal fashion, using established philosophical systems (be it phenomenology [Jaspers 1977], logical empiricism [Hempel 1994], or analytic philosophy [Fulford, Thornton, and Graham 2006]). This centripetal approach can be used both by professional philosophers and by psychiatrists/psychologists. When developed by professional philosophers, such proposals, despite their possible brilliance, run the risk of being tangential to the psychiatric issues owing to a lack of first-hand experience of them (Murphy 2006). When developed by psychiatrists and psychologists, the majority of the proposals simply mix fragments of different philosophical systems, in either a kind of syncretism or collage that fails to take into account the contradictions between fragments, or a kind of pluralism that reflects, without entering into analysis, a sort of consensus among the different paradigms (Ghaemi 2003; Kendler 2005).A second way of formulating this theoretical discourse (according to Berrios) would employ a centrifugal approach from the very core of the disciplines, through the reflection of professionals (primarily, although not only, psychiatrists/psychologists with philosophical training) who would conceptualize the problems from within and develop a specific metalanguage for analyzing [End Page 265] them (Lanteri-Laura 1991; Reznek 1991; Sass 1992). Not all problems are of the same type. For those that are extrinsic to psychiatry/psychology (definition of the mental, the mind–body relationship, the distinction between causes and reasons, or interdisciplinary reduction), the methods common to the philosophy of science and of the mind can be used. However, issues intrinsic to the disciplines themselves (the nature of mental symptoms and how they are generated, how to explain their heterogeneity, what a MD is, how to diagnose and classify it, or how to implement a psychopathological project) cannot be dealt with using preestablished formulas, and require new and original proposals that take into account the nature of the disciplines and their object of study (Villagrán 2007).The authors of the target article base their preference for the centripetal approach for responding to one of the intrinsic questions of psychiatry (what MDs are) on the consequences of what they call the Charcot effect, a kind of variant of observer bias applied to psychiatric diagnosis. They offer as an example the classic diagnosis ad iuvantibus in its postmodern version, namely, the efficacy of the pharmaceutical industry in contributing to creating nosological entities for which their drugs are indicated. Consequently, clinicians are not only unable to surmount the substantial epistemological obstacles that hamper attempts to theorize, but also find themselves doomed to assuming an ingenuous essentialism that considers MDs as natural kinds (such as apples, trees, or dogs) determined... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Commentary on “Epistemic Value Commitments”Michael Luntley (bio)Keywordsvalue, classificationThe case for treating the underdetermination of psychiatric classification with just the same tools as are employed in solving the more general underdetermination of theory by data is well made by Sadler. Quite what that treatment amounts to, however, raises a number of issues that are not only central to any philosophical conception of the rationality of theory choice, but cut deep (...) into issues about the appropriate model for rational clinical practice.On the face of it, Sadler’s recommendation is plain and looks to clarify the central problems confronting the authors of DSM nosology. The central problem for the construction of DSM guidelines is that there is no algorithm for turning input data concerning observables (behavior patterns) into theoretical classification. A simple-minded positivism would have had us expect that the production of an adequate nosology by symptoms as a mechanical algorithm—plug in the data at one end and the nosology pops out the other end. The interesting philosophical issue concerns how we respond to this underdetermination. I want to note two stages to the response we make.The first stage turns on deciding between thinking (a), that with sufficient further non-observational input some sort of modified algorithm can be produced for psychiatric classification, and thinking (b), that no such modified algorithm is available and that psychiatric classification irredeemably involves an element of judgment. The second stage that I want to explore concerns whether taking option (b) at the first stage seriously undermines the rationality of psychiatric classification and theory choice in general.Sadler seems to favor option (a). He notes that some have responded to the Kuhnian diagnosis of the lack of effective decision procedure for the production of theory by impugning the possibility of any rationality to theory choice and by seeing the activity of theory choice as thoroughly soaked in value commitments that bear the hallmark of ideology rather than rationality. Sadler’s response, however, is to draw attention to a set of values that he calls “epistemic values” that are “intrinsic to the theorizing about and construction of the classification itself.” I see this as a version of what I have called option (a) because Sadler seems to treat these values as extra “bolt-ons” to the algorithm that turns observation into classification. His aim is to clarify the character of these non-observational constraints and then plot the way that their application renders tractable a current dispute in psychiatric nosology between categorical vs. dimensional classifications of personality disorders.Suppose this is the option (a) strategy. The option (a) strategy involves a universalist model [End Page 227] of rationality. What I mean by “universalist” is this: A universalist model of rationality holds that if a transition from input to theory (input to classification) is rational, it is subsumable under a typology of such transitions that issues universal guides such as: Given inputs i 1, i 2... under constraints c 1, c 2..., conclude output/theory T n. A universalist model is distinct from a generalist model, for it accommodates the thought that the permissible routes from input to theory may include routes that are heavily conditioned by all sorts of particularities in the constraints cited in the transition rule. What the universalist does require, however, is that all rational transitions are instances of such a rule, even though the rule is not generalizable to cover all eventualities but is specific to certain particular circumstances. Sadler’s account of epistemic values is then an account that locates the place of these values as constraints that, in tandem with the inputs, determine output in a rule-governed manner.There are a number of problems with this approach that I want to touch on before turning to the main philosophical moral that I would like to draw from Sadler’s paper. The universalist model is a model in which judgment plays no role in the transition from input to output. It is, however, unclear that such a model will really work on the evidence of Sadler’s investigations for a number of reasons. First, his initial definition of a “value” is that of a descriptor... (shrink)

Although the concept of intelligence is difficult to define, research has provided evidence for a significant genetic component. Attempts are now being made to use molecular genetic approaches to identify genes contributing to intelligence, and to determine the ways in which they interact with environmental variables. This research is then likely to determine the developmental pathways of intelligence, in an effort to understand mental handicap and learning disorders and develop new treatment strategies. This paper reviews research on the genetic basis (...) of intelligence, and discusses the ethical concerns, including the role of genetic information, the value we place on intelligence and the allocation of resources. It will be argued that the objections raised are problematic, and that because of the value of this knowledge and the prospect of improving lives, this research is morally required. We will then provide a brief analysis of the issues raised by enhancement of intelligence using genetic technology, and will argue that there is no intrinsic difference between this and other means of optimising intelligence. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Autism and Intersubjectivity:Beyond Cognitivism and the Theory of MindRichard Gipps (bio)The papers that make up this special issue of Philosophy, Psychiatry, & Psychology are obviously united by both topic and approach. They all look at autism through a philosophical lens—both at infantile autism (Gallagher 2004a, 2004b; McGeer 2004; Shanker 2004) and at schizophrenic autism (Stanghellini and Ballerini 2004). Moreover, they are all concerned with the foundations of our understanding (...) of people and their minds, both the minds of others (Gallagher 2004a, 2004b; Shanker 2004; Stanghellini and Ballerini 2004) and that of oneself (McGeer 2004). The developmental disorder of infantile autism provides a conspicuous example of a disruption in the ability to develop such an understanding and enter into the social world, whilst schizophrenic autism provides a conspicuous example of what happens when one falls out of it (Stanghellini and Ballerini 2004).Yet what further affords the opportunity of this introduction is the possibility of discerning a strong common theme that runs through the philosophical treatment the papers provide. For they are united in their rejection of the primarily cognitive approach toward our capacity to relate to one another (or to ourselves) as to minded people taken by many in the mainstream of developmental psycho(patho)logy today.1 Such mainstream approaches ascribe to the developing child a 'theory of mind,' tacit knowledge of which supposedly enables them to negotiate the social world. In place of such an intellectualist, disengaged, cognition-focused psychology, we are offered perspectives that stress the primitive foundational character of our pre-reflective (noncognitive) engagement with one another, our emotion, our expression, and our embodiment.The grounds for this stressing of the affective and praxical dimensions of personal life over the cognitive and representational are twofold. First there is the developmental trajectory itself, and the claim is that the autistic child's interpersonal lacunae manifest themselves considerably before they develop the cognitive capacities for social knowledge (Gallagher 2004a; Shanker 2004). The principle ground, however, is philosophical, and the claim here is that what needs to be rejected in the developmental psycho(patho)logy is an alienated ontology and estranged epistemology that has implicitly become inscribed within it, constraining its explanatory project and limiting its vision of possibilities.2 That at least is how I [End Page 195] would put it and, by way of providing an overarching philosophical presentation of the papers of this issue, what follows shall be its elaboration.The ontology in question has it that the mind is an inner domain, that bodily behavior is an outer domain, that belief and thought epitomize the former, that intentionality is a function of the former and only derivatively manifest in the latter, that the form of our embodiment is contingent, that understanding is manifest primarily in thought and not intrinsically in praxis, that the mind is populated by free-standing inner representations, and that perception and the emotions are extrinsic to the understanding (Gallagher 2004a, 2004b; McGeer 2004; Shanker 2004). And such an ontology carries a host of epistemological implications. The self retreats from the interpersonal interactive domain, taking up residence even behind the subject's own mind, which itself becomes an objectified domain. In our own case, we are left in the predicament of needing to inspect (or intro-spect) our own inner states to find out how things are for us; our self-reports (avowals of what we think and feel) thereby become avowals of judgments of what we take ourselves to think and feel (McGeer 2004). And when we confront others the task becomes one of cognitively figuring out, from merely 'outer' clues, how things stand with them on the inside. The encounter with others is then epistemologically fraught, relying on inference and theory to take us from an outer domain of mere movement to a hidden inner world of intentionality (Gallagher 2004a, 2004b; Shanker 2004).Thus, an alienated ontology of the person and their mind bequeaths its own epistemological problematic, and the estranged epistemology gives to developmental psychology the task of filling in the details of the actual cognitive states and mechanisms which instantiate the theories and inferences which it has discerned a priori to be required. And psychopathology... (shrink)

It seems obvious that phenomenally conscious experience is something of great value, and that this value maps onto a range of important ethical issues. For example, claims about the value of life for those in a permanent vegetative state, debates about treatment and study of disorders of consciousness, controversies about end-of-life care for those with advanced dementia, and arguments about the moral status of embryos, fetuses, and non-human animals arguably turn on the moral significance of various facts about consciousness. However, (...) though work has been done on the moral significance of elements of consciousness, such as pain and pleasure, little explicit attention has been devoted to the ethical significance of consciousness. In this book Joshua Shepherd presents a systematic account of the value present within conscious experience. This account emphasizes not only the nature of consciousness, but the importance of items within experience such as affect, valence, and the complex overall shape of particular valuable experiences. Shepherd also relates this account to difficult cases involving non-humans and those with disorders of consciousness, arguing that the value of consciousness influences and partially explains the degree of moral status a being possesses, without fully determining it. The upshot is a deeper understanding of both the moral importance of phenomenal consciousness and its relations to moral status. This book will be of great interest to philosophers and students of ethics, bioethics, philosophy of psychology, philosophy of mind and cognitive science. (shrink)

The aim of this collection is to show how work in the analytic philosophical tradition can shed light on the nature, value, and experience of anxiety. Contrary to widespread assumptions, anxiety is not best understood as a mental disorder, or an intrinsically debilitating state, but rather as an often valuable affective state which heightens our sensitivity to potential threats and challenges. As the contributions in this volume demonstrate, learning about anxiety can be relevant for debates, not only in the (...) philosophy of emotion, but also in epistemology, value theory, and the philosophy of psychopathology. In this introductory article, we also show that there is still much to discover about the relevance that anxiety may have for moral action, self-understanding, and mental health. (shrink)