The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto‐oncogene int‐1. Homology between these two genes connected oncogenesis to cell‐cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell‐to‐cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell‐nonautonomy of wingless in patterning multiple embryonic and (...) adult structures solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int‐1 was then isolated, and predicted to encode a secreted proto‐oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell‐cell signal had been identified and connected cancer to development. (shrink)

Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a “transcriptional switch,” repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to (...) contribute to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway. Wnt targets are regulated by a “switch” where TLE co-repressors are displaced from TCFs by β-catenin, leading to activation of transcription. Recent reports challenge this view and suggest that additional processes, including exchange of specific TCF proteins and Wnt-dependent ubiquitination of TLEs, play important roles in the Wnt transcriptional switch. (shrink)

The Wnt signalling cascade is a highly conserved signalling pathway throughout the animal kingdom. In Xenopus, Wnt signalling functions in mesodermal dorsoventral patterning. Earlier work on deciphering the components of the wnt signalling cascade left a gap between cytosolic β‐catenin, the final member of the cascade, and the nuclear target genes. Several recent papers now reveal how the Wnt signal is transmitted into the nucleus. Surprisingly, β‐catenin directly interacts with the transcription factor LEF‐1/XTCF‐3, and thereby is not only translocated into (...) the nucleus but also modulates the properties of LEF‐1/XTCF‐3 as a transcription factor(1–5). (shrink)

Recent studies indicate that plakoglobin may have a similar function to that of β-catenin within the Wnt signaling pathway. β-catenin is known to be an oncogene in many forms of human cancer, following acquisition of stabilizing mutations in amino terminal sequences. Kolligs1 and coworkers show, however, that unlike β-catenin, plakoglobin induces neoplastic transformation of rat epithelial cells in the absence of such stabilizing mutations. Cellular transformation by plakoglobin also appears to be distinct from that of β-catenin in that it requires (...) activation of the proto-oncogene c-myc. Surprisingly, c-myc is activated more efficiently by plakoglobin than β-catenin, despite its previous identification as a target of Tcf/β-catenin.2 In contrast, a synthetic Tcf reporter gene is activated to a much greater extent by β-catenin than plakoglobin. Plakoglobin and β-catenin may therefore have different roles in Wnt signaling and cancer, which reflect their differential effects on target gene activity. BioEssays 22:961–965, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Wnt signaling plays pivotal roles during our entire lives, from conception to death, through the regulation of morphogenesis in developing embryos and the maintenance of tissue homeostasis in adults. The regulation of Wnt signaling occurs on several levels: at the receptor level on the plasma membrane, at the β‐catenin protein level in the cytoplasm, and through transcriptional regulation in the nucleus. Several recent studies have focused on the mechanisms of Wnt receptor regulation, following the discovery that the Wnt receptor frizzled (...) (Fzd) is a target of the ubiquitin ligases, RNF43 and ZNRF3. RNF43 and ZNRF3 are homologous genes that are mutated in several cancers. The details underlying their mechanism of action continue to unfold, while at the same time raising many new questions. In this review, we discuss advances and controversies in our understanding of Wnt receptor regulation. (shrink)

Wnt glycoproteins are signaling molecules that control a wide range of developmental processes in organisms ranging from the simple metazoan Hydra to vertebrates. Wnt signaling also plays a key role in the development of the nematode C. elegans, and is involved in cell fate specification and determination of cell polarity and cell migration. Surprisingly, the first genetic studies of Wnt signaling in C. elegans revealed major differences with the established (canonical) Wnt signaling pathways of Drosophila and vertebrates. Thus, the Wnt-dependent (...) induction of endoderm in the early embryo and the specification of several asymmetric cell divisions during larval development are mediated by as yet novel Wnt signaling pathways that repress, rather than activate the TCF/LEF-1 transcription factor POP-1. Recently, however, it has been shown that, in addition to these divergent Wnt pathways, C. elegans also has a canonical Wnt pathway that converts POP-1 into an activator and controls the expression of several homeobox genes. Interestingly, these different Wnt pathways use distinct beta-catenins to control POP-1 function: the endoderm induction pathway requires the beta-catenin WRM-1 and parallel input from a mitogen-activated kinase (MAPK) pathway to downregulate POP-1, whereas the canonical Wnt pathway employs the beta-catenin BAR-1 to activate Wnt target gene expression. (shrink)

The link between oncogenesis and normal development is well illustrated by the study of the Wnt family of proteins. The first Wnt gene (int‐1) was identified over a decade ago as a proto‐oncogene, activated in response to proviral insertion of a mouse mammary tumor virus. Subsequently, the discovery that Drosophila wingless, a developmentally important gene, is homologous to int‐1 supported the notion that int‐1 may have a role in normal development. In the last few years it has been (...) recognized that int‐1 and Wingless belong to a large family of related glyco‐proteins found in vertebrates and invertebrates. In recognition of this, members of this family have been renamed Wnts, an amalgam of int and Wingless. Investigation of Wnt genes in Xenopus and mouse indicates that Wnts have a role in cell proliferation, differentiation and body axis formation. Further analysis in Drosophila has revealed that Wingless function is required in several developmental processes in the embryo and imaginal discs. In addition, a genetic approach has identified some of the molecules required for the transmission and reception of the Wingless signal. We will review recent data which have contributed to our growing understanding of the function and mechanism of Drosophila Wingless signaling in cell fate determination, growth and specification of pattern. (shrink)

Wnts are a recently described family of secreted glycoproteins related to the Drosophila segment polarity gene, wingless, and to the proto‐oncogene, int‐1. Wnts are thought to function as developmental modulators, with signalling distances of only a few cell diameters. In Xenopus, at least six Wnts, including Xwnts‐1, ‐3A, and ‐4, are expressed initially in the developing central nervous system, with some regions expressing multiple Xwnts. Xwnt‐8 is expressed by mid‐blastula stage, in ventral and lateral mesoderm. Xwnt‐5A mRNAs are stored (...) in the egg, and later are expressed throughout the embryo in both ectoderm and mesoderm, but with a pronounced enrichment in the head and tail. Recent studies in Xenopus have pursued the diverse roles of Xwnts in early development, the mechanisms by which Xwnts signal information between cells, and the cell physiological responses to Xwnt signals. (shrink)

Until recently, sex determination in mammals has often been described as a male determination process, with male differentiation being the active and dominant pathway, and only in its absence is the passive female pathway followed. This picture has been challenged recently with the discovery that the gene encoding R-spondin1 is mutated in human patients with female-to-male sex reversal.((1)) These findings might place R-spondin1 in the exceptional position of being the female-determining gene in mammals. In this review, possible roles (...) of R-spondin1 during sex determination as well as questions arising from this study will be discussed. (shrink)

The problem Plato sounds from the first lines of LAWS, his final dialogue, might be put in Jean-François Lyotard's term: it is the problem of the differend. Lyotard's position is briefly explained, shown to be applicable to the discussion in several ways (not the least of which is the three different gods appealed to as sources of the laws). We then see how Plato makes a chorus of the differend, resolving Lyotard's modern problem.

Discussion of partial grounds that aren't parts of full grounds; definition of full grounding in terms of partial grounding.

This study is the most comprehensive account to date of modern treatments of the love commandment. Gene Outka examines the literature on agape from Nygren's Agape and Eros in 1930. Both Roman Catholic and Protestant writings are considered, including those of D'Arcy, Niebuhr, Ramsey, Tillich, and above all, Karl Barth. The first seven chapters focus on the principal treatments in the theological literature as they relate to major topics in ethical theory. The last chapter explores further the basic normative (...) content of agape and discusses some of the most characteristic problems. "The book is in my judgment the best recent work in religious ethics. Outka brings together analytic moral philosophy and theological ethics, providing a masterly survey of views and issues arising in the past forty years.... I can think of few books of interest to scholars in both philosophy and theology, but Outka's is one. Unlike some scholars who are at home in continental theology, Outka is also at home in secular analytic philosophy; he brings them together in a mutually illuminating way."--Donald Evans "Outka has mastered this vast literature on love, and has brought a critical and clarifying analysis to bear upon it. This is a most important book on a most important subject, and brings the whole discussion into a new phase."--John Macquarrie "The first thing to be said about Outka's book quite simply is that it is excellent; in fact, it is probably the very best available book about contemporary Christian ethical theory."--The Humanities Association Review. (shrink)

This experimental study evaluated the influence of stated organizational concern for ethical conduct upon managerial behavior. Using an in-basket to house the manipulation, a sample of 113 MBA students with some managerial experience reacted to scenarios suggesting illegal conduct and others suggesting only unethical behavior. Stated organizational concern for ethical conduct was varied from none (control group) to several other situations which included a high treatment consisting of a Code of Ethics, an endorsement letter by the CEO and specific sanctions (...) for managerial misconduct. Only in the case of suggested illegal behavior tempered by high organizational concern were managers influenced by organizational policy to modify the morality of their actions. However, the responses to the illegal scenarios were significantly more ethical than the reactions given to the unethical (but not illegal) situations. The implications of these findings are then discussed. (shrink)

A substantial guide providing an overview of both physicalism and metaphysical naturalism, reviewing both questions of formulation and justification for both doctrines. Includes a diagnostic strategy for understanding talk of naturalism as a metaphysical thesis.

Abstract:This study examined the relationship between the individual difference variables of personal moral philosophy, locus of control, Machiavellianism, and just world beliefs and ethical judgments and behavioral intentions. A sample of 602 marketing practitioners participated in the study. Structural equation modeling was used to test hypothesized relationships. The results either fully or partially supported hypothesized direct effects for idealism, relativism, and Machiavellianism. Findings also suggested that Machiavellianism mediated the relationship between individual difference variables and ethical judgments/behavioral intentions.

The Ethical Journalist gives aspiring journalists the tools they need to make responsible professional decisions. Provides a foundation in applied ethics in journalism Examines the subject areas where ethical questions most frequently arise in modern practice Incorporates the views of distinguished print, broadcast and online journalists, exploring such critical issues as race, sex, and the digitalization of news sources Illustrated with 24 real-life case studies that demonstrate how to think in 'shades of gray' rather than 'black and white' Includes questions (...) for class discussion and guides for putting important ethical concepts to use in the real world Accompanying website includes model course schedules, discussion guides, PowerPoint slides, sample quiz and exam questions and links to additional readings online: www.wiley.com/go/foreman. (shrink)

ONE OF THE MOST prominent theorists of anarcho-capitalism is Hans- Hermann Hoppe. In what is perhaps his most famous result, the argumentation ethic for libertarianism, he purports to establish an a priori defense of the justice of a social order based exclusively on pri- vate property. Hoppe claims that all participants in a debate must presuppose the libertarian principle that every person owns himself, since the principle underlies the very concept of argumentation. Some libertarians (e.g., Rothbard 1988) have celebrated Hoppe’s (...) argument as the final nail in the coffin for collectivism of any type; following Hoppe, they believe that to deny the libertarian ethic is not only wrong, but also internally contradictory. On the other hand, a number of other prominent libertarians characterized Hoppe’s initial statement of his case as “one muddle after another” (Steele 1988, p. 47) or “a tissue of bald assertions” (Yeager 1988, p. 45). (shrink)

A societal goal to which more and more people in the United States appear to be committed--at least officially--is the assurance of comprehensive health services for every person irrespective of income or geographic location. This paper offers one possible moral justification of the goal. It does so by attempting to apply various standard conceptions of social justice to considerations about health care and to reflect about the reasons why some of the conceptions seem more relevant than others. Several institutional implications (...) are also identified. (shrink)

This paper begins by examining several potentially unethical recent marketing practices. Since most marketing managers face ethical dilemmas during their careers, it is essential to study the moral consequences of these decisions. A typology of ways that managers might confront ethical issues is proposed. The significant organizational, personal and societal costs emanting from unethical behavior are also discussed. Both relatively simple frameworks and more comprehensive models for evaluating ethical decisions in marketing are summarized. Finally, the fact that organizational commitment to (...) fostering ethical marketing decisions can be accomplished by top management leadership, codes of ethics, ethics seminars/programs and ethical audits is examined. (shrink)

Peter Winch famously critiqued Michael Oakeshott's view of human conduct. He argued that Oakeshott had missed the fact that truly human conduct is conduct that 'follows a rule.' This paper argues that, as is sometimes the case with Oakeshott, what seems, on the surface, to be a disagreement with another, somewhat compatible thinker about a matter of detail in some social theory in fact turns out to point to a deeper philosophical divide. In particular, I contend, Winch, as typical of (...) those who only picked up on Oakeshott's work in the 1940s and 1950s, when Oakeshott became known for his critique of rationalism, failed to understand the idealist metaphysics underlying that critique. (shrink)

The political systems of the Roman Republic were based almost entirely on tradition, “the way of the ancestors”, rather than on a written constitution. While the founders of the American Republic looked to ancient Rome as a primary model for their enterprise, nevertheless, in line with the rationalist spirit of their age, the American founders attempted to create a rational set of rules that would guide the conduct of American politics, namely, the US Constitution.These two examples offer a striking case (...) of the ideal types, famously delineated by Michael Oakeshott in “Rationalism in Politics” and elsewhere, between politics as a practice grounded in tradition and politics as a system based on principles flowing from abstract reasoning.This book explores how the histories of the two republics can help us to understand Oakeshott’s claims about rational versus traditional politics. Through examining such issues we may come to understand better not only Oakeshott’s critique of rationalism, but also modern constitutional theory, issues in the design of the European Union, and aspects of the revival of republicanism. (shrink)

This volume centers on debates about how far moral judgments bind across traditions and epochs. Nowadays such debates appear especially volatile, both in popular culture and intellectual discourse: although there is increasing agreement that the moral and political criteria invoked in human rights documents possess cross-cultural force, many modern and postmodern developments erode confidence in moral appeals that go beyond a local consensus or apply outside a particular community. Often the point of departure for discussion is the Enlightenment paradigm of (...) a common morality, in which it is assumed that certain unchanging beliefs inhere in the structure of human reason. Whereas some thinkers continue to defend this paradigm, others modify it in diverse ways without abandoning entirely the attempt to address a universal audience, and still others jettison virtually all of its distinguishing features. Exhibiting a range of positions Western participants take in these debates, this volume seeks to advance the substance of the debates themselves without prejudging the outcome. Rival assessments of the Enlightenment paradigm are offered from various philosophical and theological points of view. In addition to the editors, the contributors include Robert Merrihew Adams, Annette C. Baier, Alan Donagan, Margaret A. Farley, Alan Gewirth, David Little, Richard Rorty, Jeffrey Stout, and Lee H. Yearley. (shrink)

The role of imagery in encoding event-based prospective memories has yet to be fully clarified. Herein, it is argued that imagery augments a cue-to-context association that supports event-based prospective memory performance. By this account, imagery encoding not only improves prospective memory performance but also reduces interference to intention-related information that occurs outside of context. In the current study, when lure words occurred outside of the appropriate responding context, the use of imagery encoding strategies resulted in less interference when compared with (...) a standard event-based intention condition. This difference was eliminated when participants were not given a specific context to associate their intention . These results support a cue-to-context association account of how imagery operates in certain event-based prospective memory tasks. (shrink)

While self-report data is a staple of modern psychological studies, they rely on participants accurately self-reporting. Two constructs that impede accurate results are insufficient effort responding and response styles. These constructs share conceptual underpinnings and both utilized to reduce cognitive effort when responding to self-report scales. Little research has extensively explored the relationship of the two constructs. The current study explored the relationship of the two constructs across even-point and odd-point scales, as well as before and after data cleaning procedures. (...) We utilized IRTrees, a statistical method for modeling response styles, to examine the relationship between IER and response styles. To capture the wide range of IER metrics available, we employed several forms of IER assessment in our analyses and generated IER factors based on the type of IER being detected. Our results indicated an overall modest relationship between IER and response styles, which varied depending on the type of IER metric being considered or type of scale being evaluated. As expected, data cleaning also changed the relationships of some of the variables. We posit the difference between the constructs may be the degree of cognitive effort participants are willing to expend. Future research and applications are discussed. (shrink)

A number of social theorists have contended that the essence of historical analysis is the employment of ideal types to comprehend past goings-on. But, while acknowledging that the study of history through ideal types can yield genuine insight, we may still ask if it represents the full emancipation of historical understanding from other modes of conceiving the past. This paper follows Michael Oakeshott's work on the philosophy of history in arguing that explaining the historical past by means of ideal types, (...) even though offering a coherent and fruitful enterprise, nevertheless falls short of fully embodying the characteristics that differentiate historical understanding. -/- This dispute involves fundamental issues regarding the nature of the social sciences. Furthermore, I suggest that it is of more than purely theoretical interest, in that social theorists who have accepted the Weberian view of historical inquiry will tend to be unaware of the defects inherent in all attempts to capture the nature of past events in a net of generalizations, and thus may be lead to ignore the inherent partiality of the understanding of historical happenings provided by ideal typification. (shrink)

The paper aims to explore what it means for something to be a social cycle, for a theory to be a social cycle theory, and to offer a suggestion for a simple, yet, we believe, fundamentally grounded schema for categorizing them. We show that a broad range of cycle theories can be described within the concept of disruption and adjustments. Further, many important cycle theories are true endogenous social cycle theories in which the theory provides a reason why the cycle (...) should recur. We find that many social cycle theories fit with a two-population disruption and adjustment model similar to the well-known predator-prey model. This implies that a general modeling framework could be established for creating agent-based models of many social cycle theories. (shrink)

: The medical and clinical promise of stem cell research is widely heralded, but moral judgments about it collide. This article takes general stock of such judgments and offers one specific resolution. It canvasses a spectrum of value judgments on sources, complicity, adult stem cells, and public and private contexts. It then examines how debates about abortion and stem cell research converge and diverge. Finally, it proposes to extend the principle of "nothing is lost" to current debates. This extension links (...) historic discussions of the ethics of direct killing with unprecedented possibilities that in vitro fertilization procedures yield. A definite normative region to inhabit is located, within a larger range of rival value judgments. The creation of embryos for research purposes only should be resisted, yet research on "excess" embryos is permissible by virtue of an appeal to the "nothing is lost" principle. (shrink)

This volume centers on debates about how far moral judgments bind across traditions and epochs. Nowadays such debates appear especially volatile, both in popular culture and intellectual discourse: although there is increasing agreement that the moral and political criteria invoked in human rights documents possess cross-cultural force, many modern and postmodern developments erode confidence in moral appeals that go beyond a local consensus or apply outside a particular community. Often the point of departure for discussion is the Enlightenment paradigm of (...) a common morality, in which it is assumed that certain unchanging beliefs inhere in the structure of human reason. Whereas some thinkers continue to defend this paradigm, others modify it in diverse ways without abandoning entirely the attempt to address a universal audience, and still others jettison virtually all of its distinguishing features. Exhibiting a range of positions Western participants take in these debates, this volume seeks to advance the substance of the debates themselves without prejudging the outcome. Rival assessments of the Enlightenment paradigm are offered from various philosophical and theological points of view. In addition to the editors, the contributors include Robert Merrihew Adams, Annette C. Baier, Alan Donagan, Margaret A. Farley, Alan Gewirth, David Little, Richard Rorty, Jeffrey Stout, and Lee H. Yearley. (shrink)

Often different schools or styles of doing economics are seen as inevitably at odds with each other, so that one must be crowned 'correct' and the others vanquished as defective. However, if they actually represent alternative but potentially enlightening views of economic phenomena, then it will be foolish exclusively to pursue one approach at the expense of all others. This paper argues that the latter is a more accurate view of economics than is the former.

A themed issue on the work of Michael Oakeshott.

Recent work by Jaegwon Kim and others suggest that functionalism leaves mental properties causally inefficacious in some sense. I examine three lines of argument for this conclusion. The first appeals to Occam's Razor; the second appeals to a ban on overdetermination; and the third charges that the kind of response I favor to these arguments forces me to give up "the homogeneity of mental and physical causation". I show how each argument fails. While I concede that a positive theory of (...) mental causation is desirable, there is no reason to think that functionalism renders such a theory unattainable. (shrink)

The advance of technology has influenced marketing in a number of ways that have ethical implications. Growth in use of the Internetand e-commerce has placed electronic “cookies,” spyware, spam, RFIDs, and data mining at the forefront of the ethical debate. Some marketers have minimized the significance of these trends. This overview paper examines these issues and introduces the two articles that follow. It is hoped that these entries will further the important “marketing and technology” ethical debate.

The advance of technology has influenced marketing in a number of ways that have ethical implications. Growth in use of the Internetand e-commerce has placed electronic “cookies,” spyware, spam, RFIDs, and data mining at the forefront of the ethical debate. Some marketers have minimized the significance of these trends. This overview paper examines these issues and introduces the two articles that follow. It is hoped that these entries will further the important “marketing and technology” ethical debate.