Victor and Cullen (1988) identified several dimensions of ethical climate that exist in organizations and organizational subunits. We tested the relationship between these dimensions of ethical climate and ethical behavior at different levels of analysis. Using Within and Between Analysis (WABA) (cf. Dansereau, Alutto and Yammarino, 1984), partial support was found for a relationship between dimensions of ethical climate and ethical behavior.

The organism is one of the fundamental concepts of biology and has been at the center of many discussions about biological individuality, yet what exactly it is can be confusing. The definition that we find generally useful is that an organism is a unit in which all the subunits have evolved to be highly cooperative, with very little conflict. We focus on how often organisms evolve from two or more formerly independent organisms. Two canonical transitions of this type—replicators clustered in (...) cells and endosymbiotic organelles within host cells—demonstrate the reality of this kind of evolutionary transition and suggest conditions that can favor it. These conditions include co-transmission of the partners across generations and rules that strongly regulate and limit conflict, such as a fair meiosis. Recently, much attention has been given to associations of animals with microbes involved in their nutrition. These range from tight endosymbiotic associations like those between aphids and Buchnera bacteria, to the complex communities in animal intestines. Here, starting with a reflection about identity through time, we consider the distinctions between these kinds of animal–bacteria interactions and describe the criteria by which a few can be considered jointly organismal but most cannot. (shrink)

The purpose of this study was to determine whether the ethical climate dimensions identified by Victor and Cullen (1987, 1988) could be replicated in the subunits of a multi-unit organization and if so, were the dimensions associated with particular types of operating units. We identified three of the dimensions of ethical climate found by Victor and Cullen and also found a new dimension of ethical climate related to service. Partial support was found for Victor and Cullen's hypothesis that certain ethical (...) climate dimensions are associated with particular forms of organizational governance and control. (shrink)

The proteasome family of proteases comprises oligomeric assemblies of very different symmetry. In different sizes, it features ring‐like oligomers with dihedral symmetry that allow the stacking of further rings of regulatory subunits as observed in the modular proteasome system, but also less symmetric helical assemblies. Comprehensive sequence and structural analyses of proteasome homologs reveal a parsimonious scenario of how symmetry may have emerged from a monomeric ancestral precursor and how it may have evolved throughout the proteasome family. The four characterized (...) representatives—ancestral β subunit (Anbu), HslV, betaproteobacterial proteasome homolog (BPH), and the 20S proteasome—are outlasting cornerstones in the family's evolutionary history, each marking a transition in symmetry. This article contextualizes the evolutionary and functional key aspects of these symmetry transitions, explaining how they facilitated the diversification and concurrent evolution of independent proteolytic systems side by side, each with its customized network of auxiliary interactors. -/- . (shrink)

Bacteria use trans‐translation to rescue stalled ribosomes and target incomplete proteins for proteolysis. Despite similarities between tRNAs and transfer‐messenger RNA (tmRNA), the key molecule for trans‐translation, new structural and biochemical data show important differences between translation and trans‐translation at most steps of the pathways. tmRNA and its binding partner, SmpB, bind in the A site of the ribosome but do not trigger the same movements of nucleotides in the rRNA that are required for codon recognition by tRNA. tmRNA‐SmpB moves from (...) the A site to the P site of the ribosome without subunit rotation to generate hybrid states, and moves from the P site to a site outside the ribosome instead of to the E site. During catalysis, transpeptidation to tmRNA appears to require the ribosomal protein bL27, which is dispensable for translation, suggesting that this protein may be conserved in bacteria due to trans‐translation. These differences provide insights into the fundamental nature of trans‐translation, and provide targets for new antibiotics that may have decrease cross‐reactivity with eukaryotic ribosomes. (shrink)

The skin‐cancer‐prone hereditary disease xeroderma pigmentosum is typically characterized by defective nucleotide excision repair (NER) of DNA. However, since all subunits of the core basal transcription factor TFIIH are required for both RNA polymerase II basal transcription and NER, some mutations affecting genes that encode TFIIH subunits can result in clinical phenotypes associated with defective basal transcription. Among these is a syndrome called trichothiodystrophy (TTD) in which the prominent features are brittle hair and nails, and dry scaly skin. A recent (...) study provides dramatic support for the so‐called transcription hypothesis of TTD.(1) Specifically, several patients have been shown to carry a mutation in the XPD gene, which encodes a thermolabile form of XPD protein, resulting in loss of hair during febrile episodes. BioEssays 23:671–673, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The hemidesmosome is a complex junction containing many proteins. The keratin cytoskeleton attaches to its cytoplasmic plaque, while its transmembrane elements interact with components of the extracellular matrix. Hemidesmosome assembly involves recruitment of α6β4 integrin heterodimers, as well as cytoskeletal elements and cytoskeleton-associated proteins to the cell surface. In our cell culture models, these phenomena appear to be triggered by laminin-5 in the extracellular matrix. Cell interaction with laminin-5 apparently induces both phosphorylation and dephosphorylation of subunits of α6β4 integrin. There (...) is emerging evidence that such events are necessary for subsequent cytoskeleton anchorage to the hemidesmosome cytoplasmic plaque. Once assembled, the hemidesmosome plays an essential role in maintaining firm epithelial adhesion to the basement membrane, with hemidesmosome disruption being a hallmark of certain devastating blistering diseases. However, the hemidesmosome is more than just a stable anchor, as it may also be the site of signal transduction, mediated by its α6β4 integrin component. This review discusses our current knowledge of the structure and assembly of the hemidesmosome. BioEssays 20:488–494, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Some metabolic pathways are nearly ubiquitous among organisms: the genes encoding the enzymes for such pathways must therefore be ancient and essential. De novo pyrimidine biosynthesis is an example of one such metabolic pathway. In animals a single protein called CADAbbreviations: CAD, trifunctional protein catalyzing the first three steps of de novo pyrimidine biosynthesis in higher eukaryotes; CPS, carbamyl phosphate synthetase domain; CPSase, carbamyl phosphate synthetase activity; ATC, aspartate transcarbamylase domain; ATCase, aspartate transcarbamylase activity; DHO, dihydroorotase domain; DHOase, dihydroorotase activity; (...) GLN, glutaminase subdomain or subunit of carbamyl phosphate synthetase, GL Nase, glutaminase activity; SYN, synthetase subdomain or subunit of carbamyl phosphate synthetase; SYNase, synthetase activity. carries the first three steps of this pathway. The same three enzymes in prokaryotes are associated with separate proteins. The CAD gene appears to have evolved through a process of gene duplication and DNA rearrangement, leading to an in‐frame gene fusion encoding a chimeric protein. A driving force for the creation of eukaryotic genes encoding multienzymatic proteins such as CAD may be the advantage of coordinate expression of enzymes catalyzing steps in a biosynthetic pathway. The analogous structure in bacteria is the operon. Differences in the translational mechanisms of eukaryotes and prokaryotes may have dictated the different strategies used by organisms to evolve coordinately regulated genes. (shrink)

Light effects on the activity of several genes have recently been exploited in studies of plant gene expression. We discuss here some examples involving nuclear genes of higher plants, with emphasis on responses mediated by the phytochrome system. Recent work has revealed considerable diversity in the responses of different genes, indicating that several different regulatory programs are probably involved. A start has been made in studies of nuclear events associated with the changes in expression. Transcriptional regulation almost certainly occurs, although (...) many details remain to be studied and effects on mRNA processing and turnover have not been ruled out. Recent in vitro mutagenesis and gene transfer experiments with the gene for the small subunit of RuBP carboxylase indicate that sequences involved in regulating the level of expression in the light are located 5′ to the gene within about 1 kb of the start of transcription. (shrink)

Port-wine birthmarks (PWBs) are caused by somatic, mosaic mutations in the G protein guanine nucleotide binding protein alpha subunit q (GNAQ) and are characterized by the formation of dilated, dysfunctional blood vessels in the dermis, eyes, and/or brain. Cutaneous PWBs can be treated by current dermatologic therapy, like laser intervention, to lighten the lesions and diminish nodules that occur in the lesion. Involvement of the eyes and/or brain can result in serious complications and this variation is termed Sturge-Weber syndrome (...) (SWS). Some of the biggest hurdles preventing development of new therapeutics are unanswered questions regarding disease biology and lack of models for drug screening. In this review, we discuss the current understanding of GNAQ signaling, the standard of care for patients, overlap with other GNAQ-associated or phenotypically similar diseases, as well as deficiencies in current in vivo and in vitro vascular malformation models. (shrink)

Resistance to inhibitors of cholinesterase 8A (Ric‐8A) is a prominent non‐receptor GEF and a chaperone of G protein α‐subunits (Gα). Recent studies shed light on the structure of Ric‐8A, providing insights into the mechanisms underlying its interaction with Gα. Ric‐8A is composed of a core armadillo‐like domain and a flexible C‐terminal tail. Interaction of a conserved concave surface of its core domain with the Gα C‐terminus appears to mediate formation of the initial Ric‐8A/GαGDP intermediate, followed by the formation of a (...) stable nucleotide‐free complex. The latter event involves a large‐scale dislocation of the Gα α5‐helix that produces an extensive primary interface and disrupts the nucleotide‐binding site of Gα. The distal portion of the C‐terminal tail of Ric‐8A forms a smaller secondary interface, which ostensibly binds the switch II region of Gα, facilitating binding of GTP. The two‐site Gα interface of Ric‐8A is distinct from that of GPCRs, and might have evolved to support the chaperone function of Ric‐8A. (shrink)

Heterotrimeric G proteins, consisting of α, β, and γ subunits, couple ligand-bound seven transmembrane domain receptors to the regulation of effector proteins and production of intracellular second messengers. G protein signaling mediates the perception of environmental cues in all higher eukaryotic organisms, including yeast, Dictyostelium, plants, and animals. The nematode Caenorhabditis elegans is the first animal to have complete descriptions of its cellular anatomy, cell lineage, neuronal wiring diagram, and genomic sequence. In a recent paper, Jansen et al.(1) used sequence (...) searches of the C. elegans genome database to identify all heterotrimeric G protein genes (20 Gα, 2 Gβ, 2 Gγ). C. elegans encodes one ortholog of each of the four Gα classes found in metazoans and 16 new Gα genes. The orthologous genes are widely expressed, whereas 14 of the divergent Gα genes are almost exclusively expressed in sensory neurons where they may regulate perception and chemotaxis.BioEssays 21:713–717, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Heterotrimeric G proteins, consisting of α, β, and γ subunits, couple ligand-bound seven transmembrane domain receptors to the regulation of effector proteins and production of intracellular second messengers. G protein signaling mediates the perception of environmental cues in all higher eukaryotic organisms, including yeast, Dictyostelium, plants, and animals. The nematode Caenorhabditis elegans is the first animal to have complete descriptions of its cellular anatomy, cell lineage, neuronal wiring diagram, and genomic sequence. In a recent paper, Jansen et al.(1) used sequence (...) searches of the C. elegans genome database to identify all heterotrimeric G protein genes (20 Gα, 2 Gβ, 2 Gγ). C. elegans encodes one ortholog of each of the four Gα classes found in metazoans and 16 new Gα genes. The orthologous genes are widely expressed, whereas 14 of the divergent Gα genes are almost exclusively expressed in sensory neurons where they may regulate perception and chemotaxis.BioEssays 21:713–717, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Ductin is the highest conserved membrane protein yet found in eukaryotes. It is multifunctional, being the subunit c or proteolipid component of the vacuolar H+‐ATPase and at the same time the protein component of a form of gap junction in metazoan animals. Analysis of its structure shows it to be a tandem repeat of two 8‐kDa domains derived from the subunit c of the F0 proton pore from the F1F0 ATPase. Each domain contains two transmembrane α‐helices, which together (...) may form a four‐helix bundle. In both the V‐ATPase and gap junction channel, ductin is probably arranged as a hexamer of subunits forming a central channel of gap junction‐like proportions. The two functions appear to be seggregated by ductin having two orientations in the bilayer. Ductin is also the major component of the mediatophore, a protein complex which may aid in the release of neurotransmitters across the pre‐synaptic membrane. It is also a target for a class of poorly understood viral polypeptides. These polypeptides are small and highly hydrophobic and some have oncogenic activity. Ductin thus appears to be at the crossroads of a number of biological processes. (shrink)

Vacuolar ATPases (V‐ATPases, V1Vo‐ATPases) are rotary motor proton pumps that acidify intracellular compartments, and, when localized to the plasma membrane, the extracellular space. V‐ATPase is regulated by a unique process referred to as reversible disassembly, wherein V1‐ATPase disengages from Vo proton channel in response to diverse environmental signals. Whereas the disassembly step of this process is ATP dependent, the (re)assembly step is not, but requires the action of a heterotrimeric chaperone referred to as the RAVE complex. Recently, an alternative pathway (...) of holoenzyme disassembly was discovered that involves binding of Oxidation Resistance 1 (Oxr1p), a poorly characterized protein implicated in oxidative stress response. Unlike conventional reversible disassembly, which depends on enzyme activity, Oxr1p induced dissociation can occur in absence of ATP. Yeast Oxr1p belongs to the family of TLDc domain containing proteins that are conserved from yeast to mammals, and have been implicated in V‐ATPase function in a variety of tissues. This brief perspective summarizes what we know about the molecular mechanisms governing both reversible (ATP dependent) and Oxr1p driven (ATP independent) V‐ATPase dissociation into autoinhibited V1 and Vo subcomplexes. (shrink)

The nematode C. elegans exhibits a variety of reponses to touch. When specific sets of mechanosensory neurons are killed with a laser, specific touch responses are abolished. Many mutations that result in defective mechanosensation have been identified. Some of the mutations define genes that specify the fate of a set of mechanoreceptors called the touch cells, which mediate response to light touch to the body of the worm. Genes specifying touch cell fate appear to regulate genes that encode touch‐cell differentiation (...) proteins, including apparent subunits of a touch‐cell‐specific ion channel, rare mutant forms of which lead to swelling and lysis of the touch cells. Molecular attachments of the ion channel, both to extracellular matrix components and, intracellularly, to a special large‐diameter microtubule, may be required for mechanical gating of the channel. A mechanoreceptor‐interneuron‐motorneuron reflex circuit for response to light touch has been proposed. (shrink)

Despite 250 years of work in systematics, the majority of species remains to be identified. Rising extinction rates and the need for increased biological monitoring lend urgency to this task. DNA sequencing, with key sequences serving as a “barcode”, has therefore been proposed as a technology that might expedite species identification. In particular, the mitochondrial cytochrome c oxidase subunit 1 gene has been employed as a possible DNA marker for species and a number of studies in a variety of (...) taxa have accordingly been carried out to examine its efficacy. In general, these studies demonstrate that DNA barcoding resolves most species, although some taxa have proved intractable. In some studies, barcoding provided a means of highlighting potential cryptic, synonymous or extinct species as well as matching adults with immature specimens. Higher taxa, however, have not been resolved as accurately as species. Nonetheless, DNA barcoding appears to offer a means of identifying species and may become a standard tool. BioEssays 29: 188–197, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

During the eukaryotic cell cycle, chromosomes undergo large structural transitions and spatial rearrangements that are associated with the major cell functions of genome replication, transcription and chromosome condensation to metaphase chromosomes. Eukaryotic cells have evolved cell cycle dependent processes that modulate histone:DNA interactions in chromosomes. These are; (i) acetylations of lysines; (ii) phosphorylations of serines and threonines and (iii) ubiquitinations of lysines. All of these reversible modifications are contained in the well‐defined very basic N‐ and C‐ terminal domains of histones. (...) Acetylations and phosphorylations markedly affect the charge densities of these domains whereas ubiquitination adds a bulky globular protein, ubiquitin, to lysines in the C‐terminal tails of H2A and H2B. Histone acetylations are strictly associated with genome replication and transcription; histone H1 and H3 phosphorylations correlate with the process of chromosome condensation. The subunits of histone H1 kinase have now been shown to be cyclins and the p34CDC2 kinase product of the cell cycle control gene CDC2. It is probable that all of the processes that control chromosome structure:function relationships are also involved in the control of the cell cycle. (shrink)

MutL family proteins contain an N‐terminal ATPase domain (NTD), an unstructured interdomain linker, and a C‐terminal domain (CTD), which mediates constitutive dimerization between subunits and often contains an endonuclease active site. Most MutL homologs direct strand‐specific DNA mismatch repair by cleaving the error‐containing daughter DNA strand. The strand cleavage reaction is poorly understood; however, the structure of the endonuclease active site is consistent with a two‐ or three‐metal ion cleavage mechanism. A motif required for this endonuclease activity is present in (...) the unstructured linker of Mlh1 and is conserved in all eukaryotic Mlh1 proteins, except those from metamonads, which also lack the almost absolutely conserved Mlh1 C‐terminal phenylalanine‐glutamate‐arginine‐cysteine (FERC) sequence. We hypothesize that the cysteine in the FERC sequence is autoinhibitory, as it sequesters the active site. We further hypothesize that the evolutionary co‐occurrence of the conserved linker motif with the FERC sequence indicates a functional interaction, possibly by linker motif‐mediated displacement of the inhibitory cysteine. This role is consistent with available data for interactions between the linker motif with DNA and the CTDs in the vicinity of the active site. (shrink)

The T lymphocyte receptor for antigen, which operates in conjunction with gene products of the major histocompatibility complex (MHC), is a molecular complex comprised of five polypeptide chains. Both the 49 kDa alpha and 43 kDa beta chains are immunoglobulin‐like and thus contain variable domains responsible for ligand binding. In contrast, the 20–25 kDa T3 gamma, delta and epsilon chains are monomorphic structures presumably involved in transmembrane signalling. The alpha and beta subunits are disulfide bonded to each other and held (...) in noncovalent association with the T3 chains. T3‐Ti receptor crosslinking leads to conformational modification of a second T lineage specific molecule, termed the 50 kDa T11 structure which in turn leads to protein kinase C activation, elevation in intracytoplasmic free calcium and Na+/H+ antiport stimulation. (shrink)

The gelsolin gene family encodes a number of higher eukaryotic actin-binding proteins that are thought to function in the cytoplasm by severing, capping, nucleating or bundling actin filaments. Recent evidence, however, suggests that several members of the gelsolin family may have adopted unexpected nuclear functions including a role in regulating transcription. In particular, flightless I, supervillin and gelsolin itself have roles as coactivators for nuclear receptors, despite the fact that their divergence appears to predate the evolutionary appearance of nuclear receptors. (...) Flightless I has been shown to bind both actin and the actin-related BAF53a protein, which are subunits of SWI/SNF-like chromatin remodelling complexes. The primary sequences of some actin-related proteins such as BAF53a exhibit conservation of residues that, in actin itself, are known to interact with gelsolin-related proteins. In summary, there is a growing body of evidence supporting a biological role in the nucleus for actin, Arps and actin-binding proteins and, in particular, the gelsolin family of actin-binding proteins. (c) 2005 Wiley Periodicals, Inc. (shrink)

SUR2, similar to SUR1, is a regulatory subunit of the ATP‐sensitive potassium channel (KATP), which plays a key role in numerous important physiological processes and is implicated in various diseases. Recent structural studies have revealed that, like SUR1, SUR2 can undergo ligand‐dependent dynamic conformational changes, transitioning between an inhibitory inward‐facing conformation and an activating occluded conformation. In addition, SUR2 possesses a unique inhibitory Regulatory helix (R helix) that is absent in SUR1. The binding of the activating Mg‐ADP to NBD2 (...) of SUR2 competes with the inhibitory Mg‐ATP, thereby promoting the release of the R helix and initiating the activation process. Moreover, the signal generated by Mg‐ADP binding to NBD2 might be directly transmitted to the TMD of SUR2, prior to NBD dimerization. Furthermore, the C‐terminal 42 residues (C42) of SUR2 might allosterically regulate the kinetics of Mg‐nucleotide binding on NBD2. These distinctive properties render SUR2 intricate sensors for intracellular Mg‐nucleotides. (shrink)

The reovirus cell attachment protein σ1 is a lollipopshaped structure with the fibrous tail anchored to the virion. Since it interacts with the cell receptor, σ1 is a major determinant of reovirus infectivity and tissue tropism. Studies on its structure‐function relationships have been facilitated by the fact that protein σ1 produced in any expression system is capable of binding to cell receptors. The use of site‐specific and deletion mutants has led to the identification and characterization of its virion anchorage and (...) receptor binding domains. Studies on the oligomeric status of σ1 have revealed that σ1 is a homotrimer and that two independent trimerization events at different loci (the N‐ and C‐terminal halves, respectively) of the protein, are involved in its generation. This also accounts for a clearly demonstrable dominant negative effect by a mutant subunit in a wild‐type/mutant σ1 heterotrimer. Current efforts are focused on the involvement of chaperones in the generation of σ1 and on events that take place upon σ1 binding to the cell receptor. Protein σ1 has therefore become an excellent model system for the study of both virus attachment and protein oligomerization and folding mechanisms. (shrink)

Clamp loaders are pentameric AAA+ assemblies that use ATP to open and close circular DNA sliding clamps around DNA. Clamp loaders show homology in all organisms, from bacteria to human. The eukaryotic PCNA clamp is loaded onto 3′ primed DNA by the replication factor C (RFC) hetero‐pentameric clamp loader. Eukaryotes also have three alternative RFC‐like clamp loaders (RLCs) in which the Rfc1 subunit is substituted by another protein. One of these is the yeast Rad24‐RFC (Rad17‐RFC in human) that loads (...) a 9‐1‐1 heterotrimer clamp onto a recessed 5′ end of DNA. Recent structural studies of Rad24‐RFC have discovered an unexpected 5′ DNA binding site on the outside of the clamp loader and reveal how a 5′ end can be utilized for loading the 9‐1‐1 clamp onto DNA. In light of these results, new studies reveal that RFC also contains a 5′ DNA binding site, which functions in gap repair. These studies also reveal many new features of clamp loaders. As reviewed herein, these recent studies together have transformed our view of the clamp loader mechanism. (shrink)

Progress in solving the structure of insulin bound to its receptor has been slow and stepwise, but a milestone has now been reached with a refined structure of a complex of insulin with a “microreceptor” that contains the primary binding site. The insulin receptor is a dimeric allosteric enzyme that belongs to the family of receptor tyrosine kinases. The insulin binding process is complex and exhibits negative cooperativity. Biochemical evidence suggested that insulin, through two distinct binding sites, crosslinks two receptor (...) sites located on each α subunit. The structure of the unliganded receptor ectodomain showed a symmetrical folded‐over conformation with an antiparallel disposition. Further work resolved the detailed structure of receptor site 1, both without and with insulin. Recently, a missing piece in the puzzle was added: the C‐terminal portion of insulin's B‐chain known to be critical for binding and negative cooperativity. Here I discuss these findings and their implications. (shrink)

PDZ (also called DHR or GLGF) domains are found in diverse membraneassociated proteins including members of the MAGUK family of guanylate kinase homologues, several protein phosphatases and kinases, neuronal nitric oxide synthase, and several dystrophin‐associated proteins, collectively known as syntrophins. Many PDZ domain‐containing proteins appear to be localised to highly specialised submembranous sites, suggesting their participation in cellular junction formation, receptor or channel clustering, and intracellular signalling events. PDZ domains of several MAGUKs interact with the C‐terminal polypeptides of a subset (...) of NMDA receptor subunits and/or with Shaker‐type K+ channels. Other PDZ domains have been shown to bind similar ligands of other transmembrane receptors. Recently, the crystal structures of PDZ domains, with and without ligand, have been determined. These demonstrate the mode of ligand‐binding and the structural bases for sequence conservation among diverse PDZ domains. (shrink)

Nicotinic acetylcholine receptors (nAChRs) are ligand‐gated ion channels that bring about a diversity of fast synaptic actions. Analysis of the Caenorhabditis elegans genome has revealed one of the most‐extensive and diverse nAChR gene families known, consisting of at least 27 subunits. Striking variation with possible functional implications has been observed in normally conserved motifs at the acetylcholine‐binding site and in the channel‐lining region. Some nAChR subunits are particular to neurons whilst others are present in both neurons and muscles. The localization (...) of subunits in non‐synaptic regions suggests novel roles for nAChRs. Genetic and heterologous expression studies have identified a subset of nAChR subunits that are important drug targets while the study of mutants has identified genes functionally‐linked to nAChRs. Future studies using C. elegans offer the prospect of increasing our understanding of the functional diversity of a complex nAChR gene family as well as addressing the role of nAChRs and associated proteins in human disorders. BioEssays 26:39–49, 2004.© 2003 Wiley Periodicals, Inc. (shrink)

Mutations in the daf-2 and age-1 genes cause constitutive dauer larva formation and double adult life span in C. elegans. Their effect on life span has excited considerable interest and their effect on dauer formation has facilitated rapid progress in their genetic and molecular analysis. Two recent papers12,13 report that daf-2 encodes a member of the insulin-receptor family and that age-1 encodes a PI3 kinase subunit, a second-messenger producing enzyme known to act downstream of the mammalian insulin receptor. These (...) findings provide the first mechanistic insight into the well-established link between metabolism and aging. BioEssays 20:113–115, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

This book describes a program of research in computable structure theory. The goal is to find definability conditions corresponding to bounds on complexity which persist under isomorphism. The results apply to familiar kinds of structures (groups, fields, vector spaces, linear orderings Boolean algebras, Abelian p-groups, models of arithmetic). There are many interesting results already, but there are also many natural questions still to be answered. The book is self-contained in that it includes necessary background material from recursion theory (ordinal notations, (...) the hyperarithmetical hierarchy) and model theory (infinitary formulas, consistency properties). (shrink)

Aristotle's treatise De Interpretatione is one of his central works; it continues to be the focus of much attention and debate. C. W. A. Whitaker presents the first systematic study of this work, and offers a radical new view of its aims, its structure, and its place in Aristotle's system, basing this view upon a detailed chapter-by-chapter analysis.By treating the work systematically, rather than concentrating on certain selected passages, Whitaker is able to show that, contrary to traditional opinion, it forms (...) an organized and coherent whole. He argues that the De Interpretatione is intended to provide the underpinning for dialectic, the system of argument by question and answer set out in Aristotle's Topics; and he rejects the traditional view that the De Interpretatione concerns the assertion and is oriented towards the formal logic of the Prior Analytics. In doing so, he sheds valuable new light on some of Aristotle's most famous texts. (shrink)

In their simplest form, hybrid languages are propositional modal languages which can refer to states. They were introduced by Arthur Prior, the inventor of tense logic, and played an important role in his work: because they make reference to specific times possible, they remove the most serious obstacle to developing modal approaches to temporal representation and reasoning. However very little is known about the computational complexity of hybrid temporal logics.In this paper we analyze the complexity of the satisfiability problem of (...) a number of hybrid temporal logics: the basic hybrid language over transitive trees; nominal Until logic; and referential interval logic. We discuss the effects of including nominals, the @ operator, the somewhere modality E, and the difference operator D. Adding nominals to tense logic leads for several frame-classes to an increase in complexity of the satisfiability problem from PSPACE to EXPTIME. On transitive trees, however, the satisfiability problem for this language can be decided in PSPACE. Along the way we make a detour through hybrid propositional dynamic logic: we establish upper bounds for a number of temporal logics by generalizing results due to Passy and Tinchev [29] and De Giacomo [16]. We conclude with some remarks on the relevance of our results to description logic, and draw attention to the utility of the spypoint technique for proving upper and lower bounds. (shrink)

BackgroundResuscitation and treatment of critically ill newborn infants is associated with relatively high mortality, morbidity and cost. Guidelines relating to resuscitation have traditionally focused on the best interests of infants. There are, however, limited resources available in the neonatal intensive care unit, meaning that difficult decisions sometimes need to be made. This study explores the intuitions of lay people regarding resource allocation decisions in the NICU.MethodsThe study design was a cross-sectional quantitative survey, consisting of 20 hypothetical rationing scenarios. There were (...) 119 respondents who entered the questionnaire, and 109 who completed it. The respondents were adult US and Indian participants of the online crowdsourcing platform Mechanical Turk. Respondents were asked to decide which of two infants to treat in a situation of scarce resources. Demographic characteristics, personality traits and political views were recorded. Respondents were also asked to respond to a widely cited thought experiment involving rationing.ResultsThe majority of respondents, in all except one scenario, chose the utilitarian option of directing treatment to the infant with the higher chance of survival, higher life expectancy, less severe disability, and less expensive treatment. As discrepancy between outcomes decreased, however, there was a statistically significant increase in egalitarian responses and decrease in utilitarian responses in scenarios involving chance of survival, life expectancy, and cost of treatment. In the classic ‘lifeboat’ scenario, all but two respondents were utilitarian.ConclusionsThis survey suggests that in situations of scarcity and equal clinical need, non-health professionals support rationing of life-saving treatment based on probability of survival, duration of survival, cost of treatment or quality of life. However, where the difference in prognosis or cost is very small, non-health professionals preferred to give infants an equal chance of receiving treatment. (shrink)

C W Evers, J C Walker; Knowledge, Partitioned Sets and Extensionality: a refutation of the forms of knowledge thesis, Journal of Philosophy of Education, Volume.

Research in the fields of complex problem solving (CPS) and dynamic decision making using microworlds has been mainly conducted in Western industrialized countries. This study analyzes the CPS process by investigating thinking‐aloud protocols in five countries. Participants were 511 students from Brazil, Germany, India, the Philippines, and the United States who worked on two microworlds. On the basis of cultural‐psychological theories, specific cross‐national differences in CPS strategies were hypothesized. Following theories of situatedness of cognition, hypotheses about the specific frequency of (...) problem‐solving strategies in the two microworlds were developed. Results of the verbal protocols showed (a) modification of the theoretical CPS model, (b) task dependence of CPS strategies, and (c) cross‐national differences in CPS strategies. Participants’ CPS processes were particularly influenced by country‐specific problem‐solving strategies. (shrink)

Theories of truth and vagueness are closely connected; in this article, I draw another connection between these areas of research. Gupta and Belnap’s Revision Theory of Truth is converted into an approach to vagueness. I show how revision sequences from a general theory of definitions can be used to understand the nature of vague predicates. The revision sequences show how the meaning of vague predicates are interconnected with each other. The approach is contrasted with the similar supervaluationist approach.

Kengo Miyazono, in his work Delusions and Beliefs, defends a teleo-functional account of delusions. In my contribution to this symposium, I question one of Miyazono’s motivations for appealing to teleo-functionalism over its main rival, dry-functionalism. Miyazono suggests that teleo-functionalism, unlike dry-functionalism, can account for the compatibility of the theses (i) that delusions are genuine doxastic states (doxasticism about delusions) and (ii) that delusions do not perform the typical causal roles of beliefs (the causal difference thesis). I argue, however, that there (...) are also ways for dry-functionalism to account for this compatibility. If what I have to say is correct, then Miyazono is perhaps too hasty—at least in one important respect—to opt for teleo-functionalism over dry-functionalism. Dry-functionalism has an equally good chance of satisfying some of Miyazono’s explanatory goals. (shrink)

Visit the author's Web site at www.11PicsOfTime.com Time is a mystery that has perplexed humankind since time immemorial. Resolving this mystery is of significance not only to philosophers and physicists but is also a very practical concern. Our perception of time shapes our values and way of life; it also mediates the interaction between science and religion both of which rest fundamentally on assumptions about the nature of time. C K Raju begins with a critical exposition of various time-beliefs, ranging (...) from the earliest times through Augustine, Newton and Einstein to Stephen Hawking and current notions of chaos and time travel. He traces the role of organised religion in subverting time beliefs for its political ends. The book points out how this resulted in a facile dichotomy between 'linear' and 'cyclic' time, thereby inaugurating a confusion which, according to the author, has handicapped Western thought ever since, eventually influencing the content of science itself. Thus, this book daringly asserts that physical theory, traditionally regarded as amoral and objective, has depended on cultural beliefs about time. The author points out that time beliefs are again being manipulated today as the credibility of science is being exploited to promote a picture of time and, hence, a pattern of human behaviour which is convenient to the agenda of globalisation of culture. The linkages between modern theology and this 'brave new physics' are traced against the wider context of the so-called 'clash of civilisations', and the attempts to remake the world order. The conclusions point to the need to de-theologise time. The author challenges Einstein's understanding of relativity theory and suggests that a 'tilt in the arrow of time', or a small tendency towards cyclicity, will help repair the prevalent confusion about time. A 'tilt' also enables a physics that permits both memory and creativity, so that purpose and spontaneous growth of order are returned to human life. The book ends with a vision of Man as Creator, surprising God. Extensive research in physics, the history of science, comparative religions, and sociology lend weight to the important and challenging conclusions reached by the author. Written as a rejoinder to Stephen Hawking's A Brief History of Time, this book goes much further and, unlike any previous book, it gives a critical exposition of various world religions-Buddhism, Christianity, Hinduism, Islam, and Jainism-while exploring their intricate links, through time beliefs, to current physics on the one hand, and to global political and economic trends, on the other. This book will appeal to scholars and laypersons equally. It will fascinate anyone who reads it and will teach its readers to question the unquestionable. (shrink)

Peter C. Hodgson engages the speculative reconstruction of Christian theology that is accomplished by Hegel's Lectures on the Philosophy of Religion, and provides a close reading of the critical edition of the lectures. He analyses Hegel's concept of the object and purpose of the philosophy of religion, his critique of the theology of his time, his approach to Christianity within the framework of the concept of religion, his concept of God, his reconstruction of central Christian themes, and his placing of (...) Christianity among the religions of the world. Hodgson makes a case for the contemporary theological significance of Hegel by identifying currently contested sites of interpretation and their Hegelian resolution. (shrink)

This volume of essays examines the problem of mind, looking at how the problem has appeared to neuroscientists from classical antiquity through to contemporary times. Beginning with a look at ventricular neuropsychology in antiquity, this book goes on to look at Spinozan ideas on the links between mind and body, Thomas Willis and the foundation of Neurology, Hooke’s mechanical model of the mind and Joseph Priestley’s approach to the mind-body problem. The volume offers a chapter on the 19th century Ottoman (...) perspective on western thinking. Further chapters trace the work of nineteenth century scholars including George Henry Lewes, Herbert Spencer and Emil du Bois-Reymond. The book covers significant work from the twentieth century, including an examination of Alfred North Whitehead and the history of consciousness, and particular attention is given to the development of quantum consciousness. Chapters on slavery and the self and the development of an understanding of Dualism bring this examination up to date on the latest 21st century work in the field. At the heart of this book is the matter of how we define the problem of consciousness itself: has there been any progress in our understanding of the working of mind and brain? This work at the interface between science and the humanities will appeal to experts from across many fields who wish to develop their understanding of the problem of consciousness, including scholars of Neuroscience, Behavioural Science and the History of Science. (shrink)

In this paper I present a range of substructural logics for a conditional connective ↦. This connective was original introduced semantically via restriction on the ternary accessibility relation R for a relevant conditional. I give sound and complete proof systems for a number of variations of this semantic definition. The completeness result in this paper proceeds by step-by-step improvements of models, rather than by the one-step canonical model method. This gradual technique allows for the additional control, lacking in the canonical (...) model method, that is required. (shrink)