Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age‐associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we (...) emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets. Copyright Line: © 2015 The Authors BioEssays Published by Wiley‐VCH Verlag GmbH & Co. KGaA. (shrink)

The “community effect” is necessary for tissue differentiation. In the Xenopus muscle paradigm, e‐FGF has been identified as a candidate community factor. Standley et al.1 now show that the community effect, mediated through FGF signalling, continues to be important at later stages of development in the posterior part of the embryo. In this region, the paraxial mesoderm is still undergoing segmentation into somites, which are the site of early skeletal muscle formation. Indeed, somitogenesis, together with the read‐out of the Hox (...) code, which confers anteroposterior positional identity, is regulated by FGF signalling. This raises the question of the co‐ordination between these events and the community effect which orchestrates myogenesis. BioEssays 25:13–16, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Observations of a sea urchin larvae show that most species adopt one of two life history strategies. One strategy is to make numerous small eggs, which develop into a larva with a required feeding period in the water column before metamorphosis. In contrast, the second strategy is to make fewer large eggs with a larva that does not feed, which reduces the time to metamorphosis and thus the time spent in the water column. The larvae associated with each strategy have (...) distinct morphologies and developmental processes that reflect their feeding requirements, so that those that feed exhibit indirect development with a complex larva, and those that do not feed form a morphologically simplified larva and exhibit direct development. Phylogenetic studies show that, in sea urchins, a feeding larva, the pluteus, is the ancestral form and the morphologically simplified direct‐developing larva is derived. The current hypothesis for evolution of the direct‐developing larval form in sea urchins suggests that major developmental changes occur by neutral loss of larval features after the crucial transition to a nonfeeding life history strategy. We present evidence from Clypeaster rosaceus, a sea urchin with a life history intermediate to the two strategies, which indicates that major developmental changes for accelerated development have been selected for in a larva that can still feed and maintains an outward, pluteus morphology. We suggest that transformation of larval form has resulted from strong selection on early initiation and acceleration of adult development. BioEssays 29:566–571, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

An understanding of underlying mechanisms involved in the activation of HIF‐1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer. Changes in microenvironmental stimuli such as hypoxia and growth factors in combination with genetic lesions, such as loss or inactivation of p53, PTEN or pVHL or oncogenic activation, can all lead to increased HIF‐1 activity. This provides cancer cells with a distinct advantage for survival and proliferation, resulting (...) in their ability to form vascular tumours, which are aggressive and metastatic. Accordingly, upregulation of HIF‐1α, a key component of HIF‐1, correlates with a poor treatment outcome using conventional therapies. A variety of mechanisms exist that regulate expression of HIF‐1α. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF‐1α to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies. BioEssays 26:262–269, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

An understanding of underlying mechanisms involved in the activation of HIF‐1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer. Changes in microenvironmental stimuli such as hypoxia and growth factors in combination with genetic lesions, such as loss or inactivation of p53, PTEN or pVHL or oncogenic activation, can all lead to increased HIF‐1 activity. This provides cancer cells with a distinct advantage for survival and proliferation, resulting (...) in their ability to form vascular tumours, which are aggressive and metastatic. Accordingly, upregulation of HIF‐1α, a key component of HIF‐1, correlates with a poor treatment outcome using conventional therapies. A variety of mechanisms exist that regulate expression of HIF‐1α. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF‐1α to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies. BioEssays 26:262–269, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Margaret Wiley, Women, Wellness, and the Media, Newcastle: Cambridge Scholars Publishing, 2008, reviewed by Chris La Barbera and Melissa Meade.

Margaret Atherton has written an excellent introduction to the work of George Berkeley, in which she systematically walks the reader through the various stages in his argument for immaterialism. By...

Anthony Giddens, Hans Joas, Margaret Archer, Norbert Wiley, and Eugene Halton (to name but a handful of such figures) are social theorists whose philosophical importance is all too often missed (or ignored) by professional philosophers. The main reason for this is obvious: they are by training and appointment social scientists, while professional philosophy tends to be an insular discipline. Disciplinary purity, like most other forms of this misplaced ideal, tends to insure insularity and vit...

If particularism is right, the broad moral claims we make are usually riddled with exceptions. But such generalizations can still be a useful, even necessary part of moral life. They help us show what we should do, and they are essential for understanding why we should do it.

Moral virtue is, for Aristotle, a state to which an agent’s motivation is central. For anyone interested in Aristotle’s account of moral development this invites reflection on two questions: how is it that virtuous motivational dispositions are established? And what contribution do the moral learner’s existing motivational states make to the success of her habituation? I argue that views which demand that the learner act with virtuous motives if she is to acquire virtuous dispositions misconstrue the nature and structure of (...) the habituation process, but also obscure Aristotle’s crucial insight that the very practice of virtuous actions affords a certain discovery and can be transformative of an agent’s motivational states. Drawing attention, in Aristotle’s account, to an asymmetry between the agential perspective and the observation of others, I consider what the agential perspective affords the learner, and offer a novel interpretation of the role a learner’s existing motives play in her habituation. (shrink)

Businesses that produce bioscience products—gene tests and therapies, pharmaceuticals, vaccines, and medical devices—are regularly confronted with ethical issues concerning these technologies. Conflicts exist between those who support advancements in bioscience and those who fear the consequences of unfettered scientific license. As the debate surrounding bioscience grows, it will be increasingly important for business managers to consider the larger consequences of their work. This groundbreaking book follows industry research, development, and marketing of medical and bioscience products across a variety of fields, (...) including biotechnology, pharmaceuticals, and bio-agriculture. Compelling and current case studies highlight the ethical decisions business managers frequently face. With the increasing visibility and public expectation placed on businesses in this sector, managers need to understand the ethical and social issues. This book addresses that need and provides a framework for incorporating ethical analysis in business decision making. (shrink)

"Most modern legal theorists seek to limit their enquiries to a particular sort of law, on the assumption that law is necessarily restricted in its interactions with other social practices. margaret Davies deliberately - and provocatively - questions the usefulness of such 'positivist' dogmas, asserting that the law can and should be seen as multi-dimensional. Davies argues that the law is everywhere - in metaphysics, the social environment, language and the psyche. In a persuasive meeting of postmodern discourse, deconstruction, (...) feminism and legal theory, Davies creates new ways of thinking about the law by creating links with other practices and disciplines where none previously existed. This is a powerful critique of the ideology and theory of law in the West, providing a much-needed link between conventional legal philosophy and modern movements in legal theory." --From back cover. (shrink)

In this paper I argue for a distinction between subjective and value laden aspects of judgements showing why equating the former with the latter has the potential to confuse matters when the goal is uncovering the influence of political influences on scientific practice. I will focus on three separate but interrelated issues. The first concerns the issue of ‘verification’ in computational modelling. This is a practice that involves a number of formal techniques but as I show, even these allegedly objective (...) methods ultimately rely on subjective estimation and evaluation of different types of parameters. This has implications for my second point which relates to uncertainty quantification—an assessment of the degree of uncertainty present in a particular modelling scenario. I argue that while this practice also involves subjective elements, in no way does that detract from its status as an epistemic exercise. Finally I discuss the relation between accuracy and uncertainty and how each relates to judgements that embody social/ethical/political concerns, in particular those associated with high consequence systems. (shrink)

In a well-known series of articles, Norman Daniels has drawn a contrast between wide reflective equilibrium and a more traditional method of theory acceptance in ethics that would be employed by a sophisticated moral intuitionist. The more traditional method is geared towards achieving a narrow equilibrium, or ‘an ordered pair of a set of considered moral judgments acceptable to a given person P at a given time, and a set of moral principles that economically systematizes.’ Although we might achieve narrow (...) reflective equilibrium by deducing particular moral judgments from self-evident moral principles, the more plausible approach is to start from our particular moral judgments. Here we begin by screening our intial moral judgments to eliminate those in which we have little confidence and those made under circumstances conducive to error. We then search for general moral principles that best account for the remaining ‘considered’ moral judgments. (shrink)

This essay argues that the concept of ‘reasonableness’plays an important role in Scanlon's, Rawls's, and Barry's theories of justice (or morality). The relationship between moral motivation and reasonableness is critically analysed. Specifically, the paper questions whether it is plausible to impute to the agents of construction the desire ‘to justify our actions to others on impartial terms’. It also argues that most of the work is done by the assumption that people are reasonable rather than by the contractarian formulation. Indeed, (...) the paper argues, the argument could proceed entirely by making explicit and arguing for the moral assumptions embedded in the concept of reasonableness [1]. (shrink)

Many have asked how and why feminist theory makes a distinctive contribution to bioethics. In this essay, I outline two ways in which feminist reflection can enrich bioethical studies. First, feminist theory may expose certain themes of androcentric reasoning that can affect, in sometimes crude but often subtle ways, the substantive analysis of topics in bioethics; second, it can unearth the gendered nature of certain basic philosophical concepts that form the working tools of ethical theory.

European Journal of Political Theory, Volume 21, Issue 1, Page 25-46, January 2022. This article explains how 19th-century radical republicans answered the following question: how is it possible to be free in a social order that fosters economic dependence on others? I focus on the writings of a group of French thinkers called the solidarists who advocated “liberty organized for everyone.” Mutualism and social right were two components of the solidarist strategy for limiting domination in commercial/industrial society. While the doctrine (...) of mutualism was rooted in pre-industrial artisan culture, social right was a novel idea that built on Durkheim’s analysis of the division of labour. In this article, I describe the main features of the solidarist account: solidarity, social property, quasi-contractual debt, and restorative justice. Classical republicanism was deeply concerned with citizen participation and the balance between popular and elite power, but 19th-century radical republicans thought that these goals must be approached differently in market societies in which enormous power is exercised outside the state. The solidarists cautiously embraced the state as a mechanism for regulating the market in order to ensure equal liberty. Social right and mutualism were also conceived as ways of limiting the centralization of state power. (shrink)

What is a social rule? This paper first notes three important problems for H.L.A. Hart’s famous answer in the Concept of Law. An alternative account that avoids the problems is then sketched. It is less individualistic than Hart’s and related accounts. This alternative account can explain a phenomenon observed but downplayed by Hart: the parties to a social rule feel that they are in some sense ‘bound’ to conform to it.

How is one to act so as to do as well as possible according to one’s ranking of the possible outcomes? How—as it may be put—is one to act rationally? Sometimes the possible outcomes are not under one’s own control: an outcome is a combination of one’s own and another agent’s action. Often, then, one must try to work out what the other agent will do, in order to do as well as possible in one’s own lights. It is situations (...) of this sort—situations of “strategic interaction”—that most concern the game theorist. (shrink)

A high level of citizen involvement in civic life is presumed crucial to the well-being of democracy, but the actual discourse of citizen involvement has rarely been analyzed. This article analyzes citizen participation in the school board meetings of one US community that was in the midst of conflict. After providing background on education governance practices and the community that was studied, citizen participation is examined. Citizen commentaries at school board meetings are shown to be a distinct speech genre and (...) the genre is described. Then, we characterize the discourse practices used to express negative sentiment. Feeling-limned description, avowal of feelings, rhetorical questions, reported speech, use of god and devil terms, and using meeting rules as weapons were the main negative sentiment strategies. In the conclusion we suggest when low levels of citizen involvement should be acceptable, and why `reasonable hostility' is a desirable form of citizen expression. (shrink)

Russell Hardin writes from a particular perspective, that of rational choice theory. His broad—and ambitious—overall project is to “understand the sway of groups in our time” or, in an alternative formulation, “to understand the motivations of those who act on behalf of groups and to understand how they come to identify with the groups for which they act”.

This article examines two modalities of law, depicted spatially as the vertical and the horizontal. The intellectual background for seeing law in vertical and horizontal dimensions is to be found in much socio-legal scholarship. These approaches have challenged the modernist, legal positivist and essentially vertical view of law as a system of imperatives emanating from a hierarchically superior source such as a sovereign. In keeping with the socio-legal critical tradition, but approaching it from the perspective of legal philosophy, my aim (...) is to address three matters. First, why is vertical law problematic for feminists? Second, what are the theoretical characteristics of law in its horizontal register? Third, how is an appreciation of this ‘flat’ law useful for feminist legal theory and practice? In particular, I consider the ways in which feminist legal theory operating in the horizontal dimension can transgress, without transcending, the vertically determined perimeters of the nation state. (shrink)

This chapter contains sections titled: Introduction Observations on Collective Action Approaches to Collective Action The Personal Intentions Approach The ‘We ‐ Intentions’ Approach The Joint Commitment Approach Concluding Remarks Further reading.

Drawing on earlier work of the author that is both clarified and amplified here, this article explores the question: what is it for two or more people to intend to do something in the future? In short, what is it for people to share an intention? It argues for three criteria of adequacy for an account of shared intention (the disjunction, concurrence, and obligation criteria) and offers an account that satisfies them. According to this account, in technical terms explained in (...) the paper, people share an intention when and only when they are jointly committed to intend as a body to do such-and-such in the future. This account is compared and contrasted with the common approach that treats shared intention as a matter of the correlative personal intentions, with particular reference to the work of Michael Bratman. (shrink)