Signaling through the Wnt/β‐catenin pathway is relayed through three multiprotein complexes: (1) the membrane‐associated signalosome, which includes the activated Wnt receptors, (2) the cytoplasmic destruction complex that regulates turnover of the transcriptional coactivator β‐catenin, and (3) the nuclear enhanceosome that mediates pathway‐specific transcription. Recent discoveries have revealed that Wnt receptor activities are tightly regulated to maintain proper tissue homeostasis and that aberrant receptor upregulation enhances Wnt signaling to drive tumorigenesis, highlighting the importance of signalosome control. These studies have focused on (...) the detailed process by which Wnt ligands engage their coreceptors, LRP5/6 and Frizzled. However, the components that constitute the signalosome and the regulation of their assembly remain undefined. In this review, we discuss Wnt/β‐catenin signalosome composition and the mechanisms that regulate signalosome assembly, including the role of biomolecular condensates and ubiquitylation. We also summarize the evidence for the presence of Wnt ligand‐independent signalosome formation. (shrink)

This collection brings together a selection of writings on art by the internationally acclaimed novelist, historian and critic Marina Warner. For 30 years Warner has published widely on a range of art-world subjects and objects, from contemporary installation and film works to paintings by Flemish and Italian Renaissance masters, through Victorian photography and twentieth-century political drawings and prints. Warner's extraordinary curiosity in art and culture is conveyed in writing that is at once poetic and playful, elegant and rigorous, training our (...) eyes on the smallest of details while painting a broad-brushstroke landscape of art past and present. Themes familiar to Warner's readers--myth and fantasy, psychic and sexual experience, the vast and marvelous expanse of the human imagination--are treated in the lectures and articles, stories, interviews and essays contained here, some of which are published for the first time or republished from out-of-print sources. For the first of two volumes, editor Vivian Sky Rehberg has assembled themed sections titled "Playing in the Dark," "Telling Tales" and "Phantom Technologies." Texts include interviews with Tacita Dean and Paula Rego; catalogue essays on Leonora Carrington, Henry Fuseli, Zarina Bhimji, Tony Oursler and Fischli/Weiss; articles on Tracy Emin, Marlene Dumas, Louise Bourgeois; stories for artist's books by Kiki Smith and Helen Douglas; and lectures on Francis Bacon, Hieronymous Bosch and William Kentridge. "The Symbol Gives Rise to Thought" invites us to explore new ways of seeing and engaging with the traces of our artistic heritage. Marina Warner is a writer of fiction, criticism and history. Holder of 12 honorary degrees and two honorary fellowships, Warner is a Fellow of the British Academy and of the Royal Society of Literature. She has judged the The Jerwood Drawing Prize and the Turner Prize; she is a regular broadcaster on the BBC, and has taught and given lectures worldwide, including the National Gallery and ICA, London and the Prado in Madrid; she has delivered the Presidential Lecture at Stanford University and the Carpenter Lecture at Harvard. She has been awarded a CBE, Chevalier de l'Ordre des Arts et des Lettres, France and Commendatore dell'Ordine della Stella di Solidareità, Italy. Warner is a winner of the Aby Warburg Prize and a Getty Scholar. Vivian Sky Rehberg is an art historian and critic based in Paris and Rotterdam. A founding editor of "Journal of Visual Culture," she is a contributing editor of "Frieze," and has written for numerous contemporary art publications. Previously Chair of the department of Critical Studies at Parsons Paris School of Art + Design, where she taught modern and contemporary art, Rehberg is currently Course Director for the Masters in Fine Art at Piet Zwart Institute in Rotterdam.. (shrink)

The shortage of organs for transplantation by its nature prompts ethical dilemmas. For example, although there is an imperative to save human life and reduce suffering by maximising the supply of vital organs, there is an equally important obligation to ensure that the process by which we increase the supply respects the rights of all stakeholders. In a relatively unexamined practice in the USA, organs are procured from unrepresented decedents without their express consent. Unrepresented decedents have no known healthcare wishes (...) or advance care planning document; they also lack a surrogate. The Revised Uniform Anatomical Gift Act (RUAGA) of 2006 sends a mixed message about the procurement of organs from this patient population and there are hospitals that authorise donation. In addition, in adopting the RUAGA, some states included provisions that clearly allow organ procurement from unrepresented decedents. An important unanswered question is whether this practice meets the canons of ethical permissibility. The current Brief Report presents two principled approaches to the topic as a way of highlighting some of the complexities involved. Concluding remarks offer suggestions for future research and discussion. (shrink)

Ample research links mothers’ postpartum depression (PPD) to adverse interactions with their infants. However, most studies relied on general population samples, whereas a substantial number of women are at elevated depression risk. The purpose of this study was to describe mothers’ interactions with their 6- and 12-month-old infants among women at elevated risk, although with a range of symptom severity. We also identified higher-order factors that best characterized the interactions and tested longitudinal consistency of these factors from 6 to 12 (...) months of infant age. We leveraged data from eight projects across the United States (n = 647), using standardized depression measures and an adaptation of the NICHD Mother-Infant Interaction Scales. Overall, these depression-vulnerable mothers showed high levels of sensitivity and positive regard and low levels of intrusiveness, detachment, and negative regard with their infants. Factor analyses of maternal behaviors identified two overarching factors—“positive engagement” and “negative intrusiveness” that were comparable at 6 and 12 months of infant age. Mothers’ ability to regulate depressed mood was a key behavior that defined “positive engagement” in factor loadings. An exceptionally strong loading of intrusiveness on the second factor suggested its central importance for women at elevated depression risk. Mothers with severe depressive symptoms had significantly more “negative intrusiveness” and less “positive engagement” with their 6-month-old infants than women with moderate or fewer depressive symptoms, suggesting a potential tipping point at which symptoms may interfere with the quality of care. Results provide the foundation for further research into predictors and moderators of women’s interactions with their infant among women at elevated risk for PPD. They also indicate a need for evidence-based interventions that can support more severely depressed women in providing optimal care. (shrink)

V. 1. Structures and processes -- v. 2. Domains and categories.

Legal decision-support systems have the potential to improve access to justice, administrative efficiency, and judicial consistency, but broad adoption of such systems is contingent on development of technologies with low knowledge-engineering, validation, and maintenance costs. This paper describes two approaches to an important form of legal decision support—explainable outcome prediction—that obviate both annotation of an entire decision corpus and manual processing of new cases. The first approach, which uses an attention network for prediction and attention weights to highlight salient case (...) text, was shown to be capable of predicting decisions, but attention-weight-based text highlighting did not demonstrably improve human decision speed or accuracy in an evaluation with 61 human subjects. The second approach, termed semi-supervised case annotation for legal explanations, exploits structural and semantic regularities in case corpora to identify textual patterns that have both predictable relationships to case decisions and explanatory value. (shrink)

This essay considers biotrophic cyst and root‐knot nematodes in relation to their biology, host–parasite interactions and molecular genetics. These nematodes have to face the biological consequences of the physical constraints imposed by the soil environment in which they live while their hosts inhabit both above and below ground environments. The two groups of nematodes appear to have adopted radically different solutions to these problems with the result that one group is a host specialist and reproduces sexually while the other has (...) an enormous host range and reproduces by mitotic parthenogenesis. We consider what is known about the modes of parasitism used by these nematodes and how it relates to their host range, including the surprising finding that parasitism genes in both nematode groups have been recruited from bacteria. The nuclear and mitochondrial genomes of these two nematode groups are very different and we consider how these findings relate to the biology of the organisms. BioEssays 30:249–259, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In his response to my article, “Historicism and Science: Thoughts on Quine” , Paul Bernays distinguishes between two aspects of the article: my criticism of Quine's theory of knowledge and my contention that the epistemological foundations of modern science lead to historicism. Bernays substantially accepts my criticism of Quine, particularly insofar as I reject Quine's behaviorism and “physicalism”. He opposes, however, my claim that historicism is implicit in the presuppositions of modern science. I argued that the historicism inherent in modern (...) science is due to the essentially changeable character of modern science. Quine's theory of knowledge tacitly takes account of this changeable character a) through his view of sense experience as being constituted by posits, b) through his recognition that individual scientific statements are dependent upon a broad linguistic‐conceptual framework that is itself subject to change, and c) through his pragmatic conception of reason and the concomitant emphasis upon the criterion of simplicity. (shrink)

The author considers maimonides' ethics in the context of the following problem: how can concepts be transmitted from one language to a radically different language? he examines how maimonides conveyed as well as transformed key greek moral concepts within rabbinic hebrew, Which has no words to translate literally such terms as 'virtue,' 'passion,' 'happiness,' or even 'ethics.' the one word found to be indispensable is that for 'ethics' in the original greek sense, I.E., 'character traits.' the author discusses in some (...) detail the significance of the term 'de'ah' (character trait) developed by maimonides to refer to "ethics." the point is made that just as a word for "nature" is necessary before there can be natural science, A word for "character traits" is necessary before there can be ethics. (edited). (shrink)

In this book Raymond L. Weiss examines how a seminal Jewish thinker negotiates the philosophical conflict between Athens and Jerusalem in the crucial area of ethics. Maimonides, a master of both the classical and the biblical-rabbinic traditions, reconciled their differing views of morality primarily in the context of Jewish jurisprudence. Taking into consideration the entire corpus of Maimonides' writings, Weiss focuses on the ethical sections of the Commentary on the Mishnah and the Mishneh Torah , but also discusses (...) the Guide of the Perplexed , the letters of Maimonides, and his medical works. The gulf between classical philosophy and the Torah made the task of Maimonides extraordinarily difficult. Weiss shows that Maimonides subtly preserves the tension between those traditions while producing a practical accommodation between them. To explain how Maimonides was able to accomplish this twofold goal, Weiss takes seriously the multilevel character of Maimonides' works. Weiss interrupts Maimonides as a heterodox thinker who, with utter integrity, faces the Law's encounter with philosophy and gives both the Torah and philosophy their due. (shrink)

This study used the latent profile transition analysis to analyze whether emotional labor profiles change across time and how these profiles relate to occupational well-being (i.e., job satisfaction, quality of work life, psychological distress, and work–family conflict). A total of 155 full-time Chinese employees completed the questionnaire survey at two time points. Three latent profiles were identified at Time 1 and the same profiles were replicated at Time 2. We determined that the majority of the participants retained the original profiles. (...) Lastly, occupational well-being differed significantly across the identified profiles. The limitations and implications of this study were also provided. (shrink)

Schizophrenia affects more than 1% of the world's population, causing great personal suffering and socioeconomic burden. These costs associated with schizophrenia necessitate inquiry into the causes and treatment of the illness but generate ethical challenges related to the specific nature and deficits of the illness itself. In this article, we present a systematic analysis of narrative data from 63 people living with the illness of schizophrenia collected through semistructured interviews about their attitudes, beliefs, and experiences related to psychiatric research. In (...) the comments of these individuals, half of whom had had prior personal experience in research protocols, we identified factors influencing openness toward research involvement as well as deterrents that appear to lessen interest in participation. Clear response pattern differences emerged between those with prior research experience and those without such experience. In the discussion, we explore these key findings and outline the implications for safeguards in mental illness research. (shrink)

The effects of research ethics training on medical students' attitudes about clinical research are examined. A preliminary randomized controlled trial evaluated 2 didactic approaches to ethics training compared to a no-intervention control. The participant-oriented intervention emphasized subjective experiences of research participants (empathy focused). The criteria-oriented intervention emphasized specific ethical criteria for analyzing protocols (analytic focused). Compared to controls, those in the participant-oriented intervention group exhibited greater attunement to research participants' attitudes related to altruism, trust, quality of relationships with researchers, desire (...) for information, hopes about participation and possible therapeutic misconception, importance of consent forms, and deciding quickly about participation. The participant-oriented group also agreed more strongly that seriously ill people are capable of making their own research participation decisions. The criteria-oriented intervention did not affect learners' attitudes about clinical research, ethical duties of investigators, or research participants' decision making. An empathy-focused approach affected medical students' attunement to research volunteer perspectives, preferences, and attributes, but an analytically oriented approach had no influence. These findings underscore the need to further examine the differential effects of empathy-versus analytic-focused approaches to the teaching of ethics. (shrink)

With this issue we initiate the policy of expanding the scope of Tulane Studies in Philosophy to include, in addition to the work of members of the department, contributions from philosophers who have earned advanced degrees from Tulane and who are now teaching in other colleges and universities. The Editor THE LOGIC OF OUR LANGUAGE ROBERT L. ARRINGTON Wittgenstein wrote in the Tractatus that "logic is not a body of doctrine, but a mirror-image of the world. " 1 In line (...) with his suggestion that a proposition is a 'picture', Wittgenstein argued that propositions 'show' the logical structure of the real. He was insistent, however, that "the apparent logical form of a proposition need not be its real one. " 2 As a result of this we can misunderstand the structure of fact. Philosophical problems arise just when "the logic of our language is mis understood. " 3 It is common knowledge that much of this view of logic was rejected by Wittgenstein himself in the Philosophical Investi gations. There we are told that language has no ideal or sublime 4 logic which mirrors the structure of the extra-linguistic world. Consequently, inferences from the structure of language to the structure of that extra-linguistic world are invalid. Reality can be 'cut up' in any of a number of ways by language. Wittgenstein adopted a view of philosophy which would render that discipline a non-explanatory, non-critical study of the multiple ways in which language can be used. (shrink)

Cet ouvrage, destiné aux étudiants, enseignants et chercheurs, s’adresse aussi bien aux philosophes qu’aux historiens de l’art et, plus généralement, à tous ceux qui s’intéressent aux phénomènes artistiques. Il propose une approche novatrice et résolument interdisciplinaire des dispositifs artistiques dans leur dimension historique et discursive comme des œuvres d’art dans leur dimension symbolique. À la faveur d’études iconographiques précises, notamment d’œuvres relevant de l’art roman, les propositions théoriques faites initialement trouvent leur application concrète et montrent leur fécondité. De nombreuses illustrations (...) en noir et blanc dans le corps du texte et un cahier central en couleurs permettent de visualiser les oeuvres étudiées. Un glossaire à la fin du texte fourni une définition précise des concepts utilisés. (shrink)

Little is known about how researchers view ethically salient aspects of human studies. As part of a National Institutes of Mental Health-funded study, the authors performed a confidential written survey to assess the attitudes, views, and experiences of researchers with institutional review board approved protocols at the University of New Mexico. A total of 363 researchers (57% response rate) participated. Investigators overall held favorable views of general ethical aspects of research and ethics-based safeguards, and they identified a positive role of (...) ethics training. Investigators with more experience encountering ethical problems (p < .001), more ethics training (p = .001), and a PhD or MD/PhD (p = .003) held more favorable general ethical perspectives. Women investigators (p < .03), nonphysician investigators (p < .001), those whose training had been helpful in resolving ethical dilemmas (p = .006), and those for whom spirituality is important (p = .008) more strongly endorsed ethical safeguards. Investigators perceive the scientific and ethical aspects of their work as valuable and linked, and they affirm the role of safeguards in human studies. Formal ethics preparation and training initiatives were also viewed positively by investigators. (shrink)

The private physicians of the Roman emperors with the exception of Galen are shadowy figures whose origins, friends, and political influence can only rarely be glimpsed. G. Stertinius Xenophon obtained immunity from taxation for his native island of Cos, and ‘L’. Statilius Griton may have secured certain privileges from Trajan for the Museum of Ephesus, but these are isolated instances. Their social position is similarly hard to define: no doctor entered the senate and equestrian rank was the most that could (...) be obtained. But, if social prejudices prevented them from becoming senators, their descendants were free from such restraints, and in the turbulent Roman society of the late second century upward mobility was not difficult. (shrink)