The origin of eukaryotes is one of the major challenges of evolutionary cell biology. Other than the endosymbiotic origin of mitochondria and chloroplasts, the steps leading to eukaryotic endomembranes and endoskeleton are poorly understood. Ras‐family small GTPases are key regulators of cytoskeleton dynamics, vesicular trafficking and nuclear function. They are specific for eukaryotes and their expansion probably traces the evolution of core eukaryote features. The phylogeny of small GTPases suggests that the first endomembranes to evolve during (...) eukaryote evolution had secretory, and not phagocytic, function. Based on the reconstruction of putative roles for ancestral small GTPases, a hypothetical scenario on the origins of the first endomembranes, the nucleus, and phagocytosis is presented. BioEssays 25:1129–1138, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Small GTPases in the Rho family act as major nodes with functions beyond cytoskeletal rearrangements shaping the Caenorhabditis elegans embryo during development. These small GTPases are key signal transducers that integrate diverse developmental signals to produce a coordinated response in the cell. In C. elegans, the best studied members of these highly conserved Rho family small GTPases, RHO‐1/RhoA, CED‐10/Rac, and CDC‐42, are crucial in several cellular processes dealing with cytoskeletal reorganization. In this review, we (...) update the functions described for the Rho family small GTPases in spindle orientation and cell division, engulfment, and cellular movements during C. elegans embryogenesis, focusing on the Rho subfamily Rac.Please also see the video abstract here. (shrink)

Tumor progression involves the transition from normal to malignant cells, through a series of cumulative alterations. During this process, invasive and migratory properties are acquired, enabling cells to metastasize (reach and grow in tissues far from their origin). Numerous cellular changes take place during epithelial malignancy, and disruption of E‐cadherin based cell‐cell adhesion is a major event. The small Rho GTPases (Rho, Rac and Cdc42) have been implicated in multiple steps during cellular transformation, including alterations on the adhesion (...) status of the tumor cells. This review focuses on recent in vivo evidence that implicates RhoGTPases in epithelial tumor progression. In addition, we discuss different hypotheses to explain disruption of cadherin‐mediated cell–cell adhesion, directly or indirectly, through activation of Rho GTPases. Understanding the molecular mechanism of how cadherin adhesion and RhoGTPases interplay in normal cells and how this balance is altered during cellular transformation will provide clues as to how to interfere with tumor progression. © 2003 Wiley Periodicals, Inc. BioEssays 25:452–463, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Ran is one of the most abundant and best conserved of the small GTP binding and hydrolyzing proteins of eukaryotes. It is located predominantly in cell nuclei. Ran is a member of the Ras family of GTPases, which includes the Ras and Ras‐like proteins that regulate cell growth and division, the Rho and Rac proteins that regulate cytoskeletal organization and the Rab proteins that regulate vesicular sorting. Ran differs most obviously from other members of the Ras family in (...) both its nuclear localization, and its lack of sites required for post‐translational lipid modification. Ran is, however, similar to other Ras family members in requiring a specific guanine nucleotide exchange factor (GEF) and a specific GTPase activating protein (GAP) as stimulators of overall GTPase activity. In this review, the multiple cellular functions of Ran are evaluated with respect to its known biochemistry and molecular interactions. (shrink)

Rho proteins belong to the small GTPases superfamily. They function as molecular switches that, in response to diverse stimuli, control key signaling and structural aspects of the cell. Although early studies proposed a role for Rho GTPases in cellular transformation, this effect was underestimated due to the fact that no genetic mutations affecting Rho‐encoding genes were found in tumors. Recently, it has become evident that Rho GTPases participate in the carcinogenic process by either overexpression of some (...) of the members of the family with oncogenic activity, downmodulation of other members with suggested tumor suppressor activity, or by alteration of upstream modulators or downstream effectors. Thus, alteration of the levels of expression of different members of the family of Rho GTPases has been detected in many types of human tumors leading to a great interest in the cellular effects elicited by these oncoproteins. This essay reviews the current evidence of dysregulation of Rho signaling by overexpression in human tumors. BioEssays 27:602–613, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Rho, a member of the Ras superfamily of small GTPases, has multiple biological roles: it regulates signal trasduction pathways linking extracellular growth factors to the assembly of actin stress fibres and focal adhesion complexes; it is required for G1 progression and activates the SRF transcription factor when quiescent fibroblasts are stimulated to grow; and it plays a role later in the cell cycle during cytokinesis. Two groups have recently succeeded in identifying downstream effectors of Rho that may mediate (...) some of these biological effects. One protein identified by both groups is protein kinase N (PKN), a serine/threonine kinase whose catalytic domain is closely related to that of protein kinase C(1,2). (shrink)

Spontaneous polarization without spatial cues, or symmetry breaking, is a fundamental problem of spatial organization in biological systems. This question has been extensively studied using yeast models, which revealed the central role of the small GTPase switch Cdc42. Active Cdc42‐GTP forms a coherent patch at the cell cortex, thought to result from amplification of a small initial stochastic inhomogeneity through positive feedback mechanisms, which induces cell polarization. Here, I review and discuss the mechanisms of Cdc42 activity self‐amplification and (...) dynamic turnover. A robust Cdc42 patch is formed through the combined effects of Cdc42 activity promoting its own activation and active Cdc42‐GTP displaying reduced membrane detachment and lateral diffusion compared to inactive Cdc42‐GDP. I argue the role of the actin cytoskeleton in symmetry breaking is not primarily to transport Cdc42 to the active site. Finally, negative feedback and competition mechanisms serve to control the number of polarization sites. (shrink)

Lysophosphatidic acid (LPA) is a lipid mediator with a wide variety of biological actions, particularly as an inducer of cell proliferation, migration and survival. LPA binds to specific G‐protein‐coupled receptors and thereby activates multiple signal transduction pathways, including those initiated by the small GTPases Ras, Rho, and Rac. LPA signaling has been implicated in such diverse processes as wound healing, brain development, vascular remodeling and tumor progression. Knowledge of precisely how and where LPA is produced has long proved (...) elusive. Excitingly, it has recently been discovered that LPA is generated from precursors by ‘autotaxin’, a once enigmatic exo‐phosphodiesterase implicated in tumor cell motility. Exogenous phospholipases D can also produce LPA, which may contribute to their toxicity. Here we review recent progress in our understanding of LPA bioactivity, signaling and synthesis. BioEssays 26:870–881, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Proteins and RNAs move between the nucleus and cytoplasm by translocation through nuclear pore complexes in the nuclear envelope. To do this, they require specific targeting signals, energy, and a cellular apparatus that catalyzes their transport. Several of the factors involved in nucleocytoplasmic trafficking of proteins have been identified and characterized in some detail. The emerging picture for nuclear transport proposes a central role for the small GTPase Ran and proteins with which it interacts. In particular, asymmetric distribution of (...) these proteins between nucleus and cytoplasm appears to be responsible for the vectorial nature of nucleocytoplasmic transport. Here, we summarize the role of Ran and Ran-binding proteins in nuclear trafficking of proteins with classical nuclear localisation signals. We also discuss examples of the growing number of alternative pathways that are involved in transport of proteins across the nuclear envelope. BioEssays 21:579–589, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Signal transduction pathways constructed around a core module of three consecutive protein kinases, the most distal being a member of the extracellular signal‐regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent work has defined two cascades activated preferentially by the inflammatory cytokines TNF‐α and IL‐1‐β, as well as by a wide variety of cellular stresses such as UV and ionizing radiation, hyperosmolarity, heat stress, oxidative stress, etc. One pathway converges on the ERK subfamily known as the ‘stress activated’ protein kinases (...) (SAPKs, also termed Jun N‐terminal kinases, JNKs), whereas the second pathway recruits the p38 kinases. Upstream inputs are diverse, and include small GTPases (primarily Rac and Cdc42; secondarily Ras) acting through mammalian homologs of the yeast Ste20 kinase, other kinase subfamilies (e.g. GC kinase) and ceramide, a putative second messenger for certain TNF‐α actions. These two cascades signal cell cycle delay, cellular repair or apoptosis in most cells, as well as activation of immune and reticuloendothelial cells. (shrink)

The generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth,1,2 but a recent paper has also raised questions about how control of Cdc42 activity is integrated (...) into a proposed hierarchical regulatory pathway that specifies a unique site of bud formation.3 BioEssays 25:833–836, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Transient receptor potential vanilloid 4 (TRPV4), a member of the TRP superfamily, is a broadly expressed, cell surface‐localized cation channel that is activated by a variety of environmental stimuli. Importantly, TRPV4 has been increasingly implicated in the regulation of cellular morphology. Here we propose that TRPV4 and the cytoskeletal remodeling small GTPase RhoA together constitute an environmentally sensitive signaling complex that contributes to pathological cell cytoskeletal alterations during neurological injury and disease. Supporting this hypothesis is our recent work demonstrating (...) direct physical and bidirectional functional interactions of TRPV4 with RhoA, which can lead to activation of RhoA and reorganization of the actin cytoskeleton. Furthermore, a confluence of evidence implicates TRPV4 and/or RhoA in pathological responses triggered by a range of acute neurological insults ranging from stroke to traumatic injury. While initiated by a variety of insults, TRPV4–RhoA signaling may represent a common pathway that disrupts axonal regeneration and blood–brain barrier integrity. These insights also suggest that TRPV4 inhibition may represent a safe, feasible, and precise therapeutic strategy for limiting pathological TRPV4–RhoA activation in a range of neurological diseases. (shrink)

The Segregation Distorter (SD) system of Drosophila melanogaster is one the best‐characterized meiotic drive complexes known. SD gains an unfair transmission advantage through heterozygous SD/SD+ males by incapacitating SD+‐bearing spermatids so that virtually all progeny inherit SD. Segregation distorter (Sd), the primary distorting locus in the SD complex, is a truncated duplication of the RanGAP gene, a major regulator of the small GTPase Ran, which has several functions including the maintenance of the nucleocytoplasmic RanGTP concentration gradient that mediates nuclear (...) transport. The truncated Sd‐RanGAP protein is enzymatically active but mislocalizes to the nucleus where it somehow causes distortion. Here I present data consistent with the idea that wild‐type RanGAP, and possibly other loci able to influence the RanGTP gradient, has been caught up in an ancient genetic conflict that predates the SD complex. The legacy of this conflict could include the unexpectedly rapid evolution of nuclear transport‐related proteins, the accumulation of chromosomal inversions, the recruitment of gene duplications, and the turnover of repetitive sequences in the centric heterochromatin. BioEssays 29:386–391, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Adherens junctions play pivotal roles in cell and tissue organization and patterning by mediating cell adhesion and cell signaling. These junctions consist of large multiprotein complexes that join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The best-known adherens junction is the zonula adherens (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent studies in Drosophila have further illuminated the structure of adherens junctions. Scaffolding proteins (...) encoded by the stardust gene are novel components of the Crumbs complex, which plays a critical role in ZA assembly.1-3 The small GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4 Finally, the asymmetric distribution of adherens junction material regulates spindle orientation during asymmetric cell division in the sensory organ lineage.5 BioEssays 24:690–695, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

There are many morphologically distinct membrane structures with different functions at the surface of epithelial cells. Among these, adherens junctions (AJ) and tight junctions (TJ) are responsible for the mechanical linkage of epithelial cells and epithelial barrier function, respectively. In the process of new cell–cell adhesion formation between two epithelial cells, such as after wounding, AJ form first and then TJ form on the apical side of AJ. This process is very complicated because AJ formation triggers drastic changes in the (...) organization of actin cytoskeleton, the activity of Rho family of small GTPases, and the lipid composition of the plasma membrane, all of which are required for subsequent TJ formation. In this review, the authors focus on the relationship between AJ and TJ as a representative example of specialization of plasma membrane regions and introduce recent findings on how AJ formation promotes the subsequent formation of TJ. (shrink)

Both RalA and RalB interact with the ubiquitous calcium sensor, calmodulin (CaM). New structural and biophysical characterisation of these interactions strongly suggests that, in the native membrane‐associated state, only RalA can be extracted from the membrane by CaM and this non‐canonical interaction could underpin the divergent signalling roles of these closely related GTPases. The isoform specificity for RalA exhibited by CaM is hypothesised to contribute to the disparate signalling roles of RalA and RalB in mitochondrial dynamics. This would lead (...) to CaM shuttling RalA to the mitochondrial membrane but leaving RalB localisation unperturbed, and in doing so triggering mitochondrial fission pathways rather than mitophagy. (shrink)

The establishment of a functional vascular system requires multiple complex steps throughout embryogenesis, from endothelial cell (EC) specification to vascular patterning into venous and arterial hierarchies. Following the initial assembly of ECs into a network of cord‐like structures, vascular expansion and remodeling occur rapidly through morphogenetic events including vessel sprouting, fusion, and pruning. In addition, vascular morphogenesis encompasses the process of lumen formation, critical for the transformation of cords into perfusable vascular tubes. Studies in mouse, zebrafish, frog, and human endothelial (...) cells have begun to outline the cellular and molecular requirements underlying lumen formation. Although the lumen can be generated through diverse mechanisms, the coordinated participation of multiple conserved molecules including transcription factors, small GTPases, and adhesion and polarity proteins remains a fundamental principle, leading us closer to a more thorough understanding of this complex event. (shrink)

Intercellular communication is an essential process in all multicellular organisms. During this process, molecules secreted by one cell will bind to a receptor on the cognate cell leading to the subsequent uptake of the receptor‐ligand complex. Once inside, the cell then determines the fate of the receptor‐ligand complex and any other proteins that were endocytosed together. Approximately 80% of endocytosed material is recycled back to the plasma membrane either directly or indirectly via the Golgi apparatus and the remaining 20% is (...) delivered to the lysosome for degradation. Although most pathways have been identified, we still lack understanding on how specificity in sorting of recycling cargos into different pathways is achieved, and how the cell reaches high accuracy of these processes in the absence of clear sorting signals in the bulk of the client proteins. In this review, we will summarize our current understanding of the mechanism behind recycling cargo sorting and propose a model of differential affinities between cargo and cargo receptors/adaptors with regards to iterative sorting in endosomes. (shrink)

Cilia are slender, micrometer‐long organelles present on the surface of eukaryotic cells. They function in signaling and locomotion and are constructed by intraflagellar transport (IFT). The assembly of IFT complexes into so‐called IFT trains to initiate ciliary entry at the base of the cilium remains a matter of debate. Here, we use structural modeling to provide an architectural framework for how RabL2 is anchored at the ciliary base via CEP19 before being handed over to IFT trains for ciliary entry. Our (...) models suggest that the N‐terminal domain of CEP43 forms a homo‐dimer to anchor at the subdistal appendages of cilia through a direct interaction with CEP350. A long linker region separates the N‐terminal domain of CEP43 from the C‐terminal domain, which captures CEP19 above the subdistal appendages and close to the distal appendages. Furthermore, we present a structural model for how RabL2‐CEP19 associates with the IFT‐B complex, providing insight into how RabL2 is handed over from CEP19 to the IFT complex. Interestingly, RabL2 association with the IFT‐B complex appears to induce a significant conformational change in the IFT complex via a kink in the coiled‐coils of the IFT81/74 proteins, which may prime the IFT machinery for entry into cilia. (shrink)

The mitogenic action of cytokines such as epidermal growth factor (EGF)d̊ or platelet dericed growth factor (PDGF) involves the stimulation of a signal cascade controlled by a small G protein called Ras. Mutations of Ras can cause its constitutive activation and, as a consequence, bypass the regulation of cell growth by cytokines. Both growth factor‐induced and oncogenic activation of Ras involve the conversion of Ras from the GDP‐bound (D‐Ras) to the GTP‐bound (T‐Ras) forms. T‐Ras activates a network of protein (...) kinases including c‐Mos, c‐Raf‐1 and MAP kinase. Eventually the activation of MAP kinase leads to the activation of the elongation factor 4E and several transcription factors such as c‐Jun, c‐Myc and c‐Fos. There are several modulators of Ras activity, such as the GTPase activating proteins (GAP1 and NF1), which stimulate the coversion of T‐Ras to D‐Ras. A series of small NF1 fragments, which bind T‐Ras, as well as truncated forms or derivatives of c‐Raf‐1, c‐Jun and c‐Myc, are capable of blocking the T‐Ras‐activated mitogenesis in a competitive manner. These agents offer a unique opportunity to control the proliferation of T‐Ras‐associated tumors, which represent more than 30% of total human carcinomas. (shrink)

The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy‐related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple (...) regulatory pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification. (shrink)

The translocation of tRNAs through the ribosome proceeds through numerous small steps in which tRNAs gradually shift their positions on the small and large ribosomal subunits. The most urgent questions are: (i) whether these intermediates are important; (ii) how the ribosomal translocase, the GTPase elongation factor G (EF‐G), promotes directed movement; and (iii) how the energy of GTP hydrolysis is coupled to movement. In the light of recent advances in biophysical and structural studies, we argue that intermediate states (...) of translocation are snapshots of dynamic fluctuations that guide the movement. In contrast to current models of stepwise translocation, kinetic evidence shows that the tRNAs move synchronously on the two ribosomal subunits in a rapid reaction orchestrated by EF‐G and GTP hydrolysis. EF‐G combines the energy regimes of a GTPase and a motor protein and facilitates tRNA movement by a combination of directed Brownian ratchet and power stroke mechanisms. (shrink)

Nietzsche's thinking on justice and punishment explores the motives and forces which lie behind moral concepts and social institutions. His dialogue with several writers of his time is discussed here. Eugen Dühring had argued that a natural feeling of ressentiment against those who have harmed us is the source of the concept of injustice, so that punishment, even in its most impersonal form, is always a form of revenge. In attacking this theory, Nietzsche developed his own powerful critique of moral (...) concepts such as responsibility and guilt. He borrowed his ‘historical’ approach to moral concepts from Paul Ree, who suggested that the utilitarian function of punishment had been obscured by its practice, which appears to be directly linked with moral guilt. Nietzsche responds that punishment has quite different purposes and meanings at different times, so that any single explanation or justification is inadequate. In this way, he rejects the pre-suppositions common to the retributivists and utilitarians of his time. (shrink)

Though everyday life accords a great deal of significance to practical abilities—such as the ability to walk, to speak French, to play the piano—philosophers of action pay surprisingly little attention to them. By contrast, abilities are discussed in various other philosophical projects. From these discussions, a partial theory of abilities emerges. If the partial theory—which is at best adequate only to a few examples of practical abilities—were correct, then philosophers of action would be right to ignore practical abilities, because they (...) could play no fundamental role in an account of human agency. For the idea that practical abilities *do* play a fundamental role in human agency to be worth considering, an alternative conception of them is needed. As a first step, I attempt some of the necessary ground-clearing work. (shrink)

In The Value of the Humanities prize-winning critic Helen Small assesses the value of the Humanities, eloquently examining five historical arguments in defence of the Humanities.

We respond in this paper to various counter arguments advanced against our stance on conscientious objection accommodation. Contra Maclure and Dumont, we show that it is impossible to develop reliable tests for conscientious objectors' claims with regard to the reasonableness of the ideological basis of their convictions, and, indeed, with regard to whether they actually hold they views they claim to hold. We demonstrate furthermore that, within the Canadian legal context, the refusal to accommodate conscientious objectors would not constitute undue (...) hardship for such objectors. We reject concerns that refusing to accommodate conscientious objectors would limit the equality of opportunity for budding professionals holding particular ideological positions. We also clarify various misrepresentations of our views by respondents Symons, Glick and Jotkowitz, and Lyus. (shrink)

The ideas (i) that skill is a form of knowledge and (ii) that it can be taught are commonplace in both ancient philosophy and everyday life. I argue that contemporary epistemology lacks the resources to adequately accommodate them. Intellectualist and anti-intellectualist accounts of knowledge how struggle to represent the transmission of skill via teaching and learning (§II), in part because each adopts a fundamentally individualistic approach to the acquisition of skill that focuses on individual practice and experience; consequently, learning from (...) an expert’s teaching is rendered at best peripheral (§III). An account of the transmission of skill that focuses on guided practice is shown to be immanent in an anti-individualist account of skill (§IV) that takes seriously the Aristotelian ideas that skills are rational capacities and second natures by developing the thought that doing, teaching, and practising are three moments of an a priori unity: the life-cycle of a skill (§V). (shrink)

The first major consideration of old age in Western philosophy and literature since Simone de Beauvoir's The Coming of Age, Helen Small ranges widely from Plato through to recent work by Derek Parfit, Bernard Williams and others, and from King Lear through Balzac, Dickens, Beckett, Stevie Smith, Bellow, Roth, and Coetzee.

The idea underlying this article was that the humanities in general and business ethics in particular should be more firmly embedded in business management programs. A number of areas have been identified for students to use as topics for research projects in management ethics. These ranged from Biblical and classical times to the present day. Some were drawn from sources that were less well known e.g. the De consolatione philosphiae ‘The Consolation of Philosophy’ by Boethius 524 AD. This was chosen (...) partly for its ethical content, but also because Boethius was magister officiorum i.e. head of the civil service. Aelfred the Great (849–899) King of Wessex (he who burnt those cakes) was chosen because he promoted the intellectual, moral and spiritual qualities that were to serve as guidelines for his executives. Nineteenth century literature (Dickens, Thackeray, Trollope and Galsworthy) was also chosen as a source of topics for research projects in business ethics. The writer acknowledges the work of earlier writers in the fields of management, organisation theory, and business ethics. (shrink)

Recent work on testimony has raised questions about the extent to which testimony is a distinctively second-personal phenomenon and the possible epistemic significance of its second-personal aspects. However, testimony, in the sense primarily investigated in recent epistemology, is far from the only way in which we acquire knowledge from others. My goal is to distinguish knowledge acquired from testimony (learning from being told) from knowledge acquired from teaching (learning from being taught), and to investigate the similarities and differences between the (...) two with respect to the interpersonal dimensions of their structures. (shrink)

Preface -- Introduction -- Absolute becoming -- From becoming to time -- The time-atom theory -- Motion, ways, and time -- Gateway and lanes -- Linear and circular time -- The eternal perspective -- The way of greatness.

I trace the development of one aspect of Fred Stoutland’s thought about action by considering the central role given by contemporary philosophy of action to bodily movement. Those who tell the so-called standard story of action think that actions are bodily movements (arm raisings, leg bendings, etc.) caused by beliefs and desires, that cause further effects in the world (switch flippings, door movements, etc.) in virtue of which they can be described (as flippings of switches, shuttings of doors, etc.). Those (...) who hold a disjunctive conception of bodily movement think that actions are bodily movements that involve intentions essentially, but they too think that when an agent raises a glass, there is an action (an arm raising, perhaps) that causes a distinct event (a glass rising), in virtue of which the action (= the bodily movement) may be redescribed as a raising of a glass. Against both views, it might be held that actions may constitutively involve the changes wrought on their patients—that action is, in the first instance, transaction. But if action consists fundamentally not in an agent’s moving herself, but in her moving (or otherwise changing) something else, then how should we think about the nature and philosophical significance of bodily movement? (shrink)

Recent events in Western Australia culminating in the Royal Commission into Commercial Activities of Government and Other Matters 1992, and the subsequent publication of the Report, highlighted the fact that the commercial activities of the State Government in Western Australia had been in disarray for some time. However, in spite of some early interest in the outcomes of the Report, the general reaction by the public was largely one of disinterest. This paper traces some of the events which took place (...) after the main hearings. A number of leading citizens felt that some action was warranted. In brief, a series of lectures on different apects of business ethics were planned and given to business students at Curtin Business School. This paper highlights some of the observations made during this series of lectures. (shrink)

Constructivism comes in a number of forms. Some are models of learning which involve few, if any, startling epistemological claims. On the other hand, what has been promoted as ‘radical constructivism’ holds that our concepts cannot be related directly to an external reality, and that claims for the objectivity of knowledge are therefore unjustified. This standpoint is an anti-realist version of evolutionary epistemology. I argue that it relies on a mistaken interpretation of the Darwinian theory of evolution by natural selection, (...) and that its application of this model to the relation between knowledge and the world is also mistaken. (shrink)

Tammy A. Kinsey 'Let us Never Speak of It?: Edward S. Small's _Direct Theory_' _Film-Philosophy_, vol. 7 no. 51, December 2003.

I explore philosophically the phenomenon of home wireless networks as used to share broadband Internet connections. Because such networks are frequently unsecured, third parties can use them to access the Internet. Here I consider carefully whether this kind of behaviour should be properly called theft. I begin with a brief non-technical introduction to 802.11 wireless networks. Subsequently, I present a four part argument – appealing to the unsecured nature of the networks discussed, entrenched software and hardware behaviours, trespass law, and (...) the openness of ‹public park’ spectrum – suggesting that this kind of behaviour is permissible and should not be construed as theft. Substantively, I conclude that, despite the quite compelling considerations that these arguments bring to bear, this behaviour is theft. Additionally, I draw attention to significant flaws in the design and implementation of wireless technology (specifically in the out-of-the-box configuration for wireless access points and in the wireless connectivity of early versions of Windows XP) that facilitate the intentional and unintentional theft of Internet bandwidth. I suggest some simple mechanisms that could be incorporated into the technology which would serve to remove the ethical ambiguity in its usage by third parties, including adding the ability for a network owner to explicitly mark her network as not for public use,␣and changes to default hardware and software behaviours. I conclude by encouraging increased use of value-sensitive design practices in the development of future wireless technologies. (shrink)

Smooth muscle cells have developed a contractile machinery that allows them to exert tension on the surrounding extracellular matrix over their entire length. This has been achieved by coupling obliquely organized contractile filaments to a more‐or‐less longitudinal framework of cytoskeletal elements. Earlier structural data suggested that the cytoskeleton was composed primarily of intermediate filaments and played only a passive role. More recent findings highlight the segregation of actin isotypes and of actin‐associated proteins between the contractile and cytoskeletal domains and raise (...) the possibility that the cytoskeleton performs a more active function. Current efforts focus on defining the relative contributions of myosin cross‐bridge cycling and actin‐associated protein interactions to the maintenance of tension in smooth muscle tissue. (shrink)

It is a commonplace in philosophy of action that there is and must be teleologically basic action: something done on an occasion without doing it by means of doing anything else. It is widely believed that basic actions are exercises of skill. As the source of the need for basic action is the structure of practical reasoning, this yields a conception of skill and practical reasoning as complementary but mutually exclusive. On this view, practical reasoning and complex intentional action depend (...) on skill and basic action, but the latter pair are not themselves rationally structured: the movements a basic action comprises are not intentional actions, and they are not structured as means to an end. However, Michael Thompson and Douglas Lavin have argued that action that bears no inner rational structure is not intentional action at all, and that therefore there can be no such thing as basic action. In this paper, I argue that their critique shows that standard conceptions of basic action are indeed untenable, but not that we can do without an alternative. I develop an alternative conception of skill and basic action on which their basicness is not to be equated with simplicity: like deliberation and non-basic action, they are teleologically complex, but their complexity takes a different form. On this view, skill contrasts with deliberation—not because it is not a manifestation of practical reason, but because the two are specifically different manifestations of practical reason. (shrink)

Journal of Chinese Philosophy, EarlyView.