Recently opposing effects of cysteine protease inhibitors, the human cystatins, on neurodegeneration have been reported. Human cystatin C is a risk factor for late‐onset Alzheimer's disease (AD), whereas human stefin B (cystatin B) has no direct involvement in AD. Conflicting data show that their target protease, cathepsin B, might be anti‐amyloidogenic, helping in amyloid‐beta (Aβ) clearance or, instead, might be involved in Aβ production. Some reports claim that cystatin C binds soluble Aβ, making transgenic animals healthier, others, in contrast, (...) that deleting cystatins genes may contribute to amyloid pathology in animal models of AD. (shrink)

Transgenic mice constitute an entirely new dimension of mammalian molecular genetics. They allow us to observe genes at work in the intact organism. Virtually every sector of biomedical research is likely to be affected.

The expression "artificial animal" denotes a range of different objects from teddy bears to the results of genetic engineering. As a basis for further investigation, this article first of all presents the main interpretations and traces their systematic interconnections. The subsequent sections concentrate on artificial animals in the context of play. The development of material toys is fueled by robotics. It gives toys artificial sense organs, limbs, and cognitive abilities, thus enabling them to act in the real world. The second (...) line of development, closely related to research into Artificial Life, creates virtual beings "living" on computer screens. Themost essential difference between these variants are the sense modalities involved in interaction. Virtual beings can only be seen and heard, whereas material toys can be touched as well. Therefore, the simulation of haptic qualities plays an important role. In order to complete the proposed typology, two further areas are outlined, namely artificial animals outside play and "artificial animals in the medium of flesh" which are alive but designed and created by man. Research on artificial animals belongs to an extended notion of ecosemiotics, as they are part of ecosystems which may themselves be virtual such as the Internet. (shrink)

Multidrug resistance resulting from expression of an energy‐dependent drug efflux pump encoded by the human MDR1 gene is a major impediment to effective cancer therapy. Pharmacologic intervention aimed at inhibiting this multidrug transporter should improve existing chemotherapy of human cancer, but drug development has been delayed by the difficulty and expense of developing valid animal models. Using recombinant DNA technology, a transgenic mouse has been engineered whose bone marrow is protected from the toxic effects of chemotherapy by expression of (...) the MDR1 gene. This animal system allows the rapid screening of drugs which inhibit the multidrug transporter and heralds a new era of using transgenic animals for pharmacologic screening. (shrink)

Introduction of human plasma protein genes into the mouse genome to produce transgenic mice furnishes an in vivo model for correlating chromosomal DNA sequences with developmental and tissue‐specific expression. The liver produces an array of plasma proteins that circulate throughout the body contributing to homeostasis. Non‐hepatic tissue sites of synthesis have been identified where a local provision of plasma proteins in needed. Analysis of expression of human plasma protein genes in ageing transgenic mice appears especialy promising (...) in identifying DNA sequences that respond to environmental adversities such as inflammatory factors, hormonal changes and metal toxicity. The results indicate that human genes encoding and controlling liver plasma proteins serve as useful models for studying genetic regulation in the background of development and ageing. (shrink)

Mouse models of human genetic disorders provide a valuable resource for investigating the pathogenesis of genetic disease and for testing potential therapies. The high degree of resolution of linkage mapping in the mouse allows mutant phenotypes to be mapped precisely which, combined with the accurate definition of areas of homology between the mouse and human genomes, greatly facilitates the identification of mouse models. We describe here mouse models of human single gene disorders dividing them into three categories depending on the (...) information available; phenotypic similarities, comparative mapping and identification of the underlying genetic lesion. (shrink)

Expression of transgenes in mice, when examined with assays that can distinguish individual cells, is often found to be heterocellular, or variegated. Line‐to‐line variations in expression of a transgene may be due largely to differences in the proportion of cells in which it is expressed. Variegated silencing by centromeric heterochromatin is well described, but other factors may also affect transgene silencing in mice. Tandem arrays of transgenes themselves form heterochromatin, and some cell lineages may tend to silence transgenes (...) because of extensive facultative heterochromatin in their nuclei. The cis‐acting transcriptional control elements within a transgene inhibit silencing, and strainspecific differences in chromatin proteins may strongly influence the extent of variegation. The accessibility of multiple differentiated cell lineages in mice suggests that they may provide a tool for dissecting the role of chromatin‐mediated silencing in cell differentiation and tissue‐specific gene expression. (shrink)

Current theories of breast cancer progression have been greatly influenced by the development and refinement of mouse transgenic and gene targeting technologies. Early transgenic mouse models confirmed the involvement of oncogenes, previously implicated in human breast cancer, by establishing a causal relationship between overexpression or activation of these genes and mammary tumorigenesis. More recently, the importance of genes located at sites of loss of heterozygosity in human breast cancer have been examined in mice by their targeted disruption (...) via homologous recombination. The union of these two approaches allows the generation of complex animal models that more accurately reflect the multistep nature of human breast cancer. This review will examine how the study of transgenic mice has increased our understanding of the molecular events responsible for oncogenic transformation of the mammary gland. BioEssays 22:554–563, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Modest_Witness@Second_Millennium. FemaleMan_Meets_OncoMouse explores the roles of stories, figures, dreams, theories, facts, delusions, advertising, institutions, economic arrangements, publishing practices, scientific advances, and politics in twentieth- century technoscience. The book's title is an e-mail address. With it, Haraway locates herself and her readers in a sprawling net of associations more far-flung than the Internet. The address is not a cozy home. There is no innocent place to stand in the world where the book's author figure, FemaleMan, encounters DuPont's controversial laboratory rodent, OncoMouse. (...) Haraway sees the world of contemporary technoscience as a drama. Information sciences and life sciences are at the center of the dramatic action. Scenes are set in landscapes where maps of human genetic differences are stored in databases, racialized bodies are reconfigured by morphing for photographs in popular magazines, and transgenic mice important to breast cancer research are patented intellectual property. The actors are many, and not all are human. Beginning with the Modest Witness, the key figure in the Science Revolution, Haraway shows us the trouble lurking in race and gender- marked practices for attesting to matters of fact. In later scenes, Haraway explores the kinship relations among the many cyborg creatures produced in the late twentieth-century--in nuclear research, genetic engineering, reproductive technologies, computer-mediated representational practices, and mutations in biological approaches to "race.". (shrink)

Donna Haraway's work has transformed the fields of cyberculture, feminist studies, and the history of science and technology. Her subjects range from animal dioramas in the American Museum of Natural History to research in transgenic mice, from gender in the laboratory to the nature of the cyborg. Trained as an historian of science, she has produced a series of books and essays that have become essential reading in cultural studies, gender studies, and the history of science. The Haraway (...) Reader brings together a generous selection of Donna Haraway's work. Included is her "Manifesto for Cyborgs," in which she famously wrote that she "would rather be a cyborg than a goddess." Other selections are taken from her three major works, Primate Visions, Modest Witness , and Simians, Cyborgs and Women , as well as some of her more recent writing on animals. For readers in cultural studies, feminist theory, science studies, and cyberculture, Donna Haraway is one of our keenest observers of nature, science, and the social world. This volume is the best introduction to her thought. (shrink)

The use of a reporter gene in transgenic mice indicates that there are many local mutations and large genomic rearrangements per somatic cell that accumulate with age at different rates per organ and without visible effects. Dissociation of the cells for monolayer culture brings out great heterogeneity of size and loss of function among cells that presumably reflect genetic and epigenetic differences among the cells, but are masked in organized tissue. The regulatory power of a mass of contiguous (...) normal cells is expressed in its capacity to normalize the appearance and growth behavior of solitary homophilic neoplastic cells, and to redirect differentiation of solitary heterophilic stem‐like cells. Intimate contact between the interacting cells is required to induce these changes. The normalization of the neoplastic phenotype does not require gap junctional communication between cells, though transdifferentiation might. These varied relationships are manifestations of the unifying biological principle of “order in the large over heterogeneity in the small”. BioEssays 28: 515–524, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The development of the vertebrate skeleton is under complex genetic control, and good progress is being made towards identifying the genes responsible. A recent paper(1) contributes to this progress by describing transgenic mice in which the homeobox‐containing MHox gene has been disrupted. MHox(−/−) mice have a range of skeletal defects, involving loss or shortening of structures in the skull, face and limb. Puzzling features of the MHox(−/−) mutation, which has similar effects on bones with very different embryological (...) origins and yet spares other bones completely, may hold clues to the mechanisms that shape the skeleton. MHox(−/−) mice, used in conjunction with other skeletal mutants, will be important tools for exploring these mechanisms further. (shrink)

As a direct consequence of the sophisticated arrangement of its intrinsic neurons, the gastrointestinal tract is unique among peripheral organs, in its ability to mediate its own reflexes. Neurons of the enteric nervous system are intimately associated with enteric glial cells. These supporting cells do not resemble Schwann cells, the glial cell found in all other parts of the peripheral nervous system, but share many similarities with astrocytes of the central nervous system. Ablation of enteric glial cells in adult (...) class='Hi'>transgenic mice has demonstrated that these cells are essential to maintain the integrity of the small intestine. Acute loss of enteric glial cells induces massive pathological changes with similarities to necrotizing enterocolitis (NEC) and early Crohn's disease. These human conditions share some mechanistic similarities. Identification of enteric glial cell dysfunction/loss as sufficient to induce necrotic/inflammatory bowel disease may be important to understand the pathogenesis of both NEC and Crohn's disease. BioEssays 24:130–140, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Development of biopharmaceuticals is a challenging issue in bioethics. Unlike conventional, small molecular weight drugs, biopharmaceuticals are proteins derived from DNA technology and hybrid techniques with complex three dimensional structures. Immunogenicity of biopharmaceuticals should always be tested in clinical settings due to low predictive value of preclinical animal models. However, non-human primates and transgenic mice could be used to address certain aspects of immunogenicity. Substantial efforts have been made to reduce NHP use in biopharmaceutical drug development, e.g. study (...) design improvements and changes in regulatory policy. In addition, several expert groups are active in this field. Despite that, there is an increasing trend of use of NHP in preclinical safety testing of biopharmaceuticals, especially regarding monoclonal antibodies. Other potential bioethical issues related biopharmaceutical drug development are their cost/effectiveness ratio, clinical safety assessment, production of biosimilars, and comparison of their efficacy with placebo in countries without intention to market. Identification of the human genome has opened many new bioethical issues. Development of biopharmaceuticals is an important bioethical issue for several reasons. It connects all aspects of contemporary bioethics: bio?medicine, animal welfare and the most recent ad?vances in biotechnology. In particular, biopharmaceutical drug development is a challenging issue regarding treatment of rare diseases. Razvoj biofarmaceutika predstavlja izazov u bioetici. Za razliku od uobicajenih lekova male molekulske mase, biofarmaceutici su proteini kompleksne trodimenzionalne strukture koji se dobijaju tehnologijom rekombinantne DNK i tehnikom hibridoma. Imunogenost biofarmaceutika treba uvek proveriti u klinickim studijama zbog male prediktivne prednosti pretklinickih animalnih modela. Medjutim, primati i transgeni sojevi miseva mogu se upotrebiti da bi se naznacili neki aspekti imunogenosti. Znacajni napori su ucinjeni u cilju smanjenja upotrebe primata u razvoju biofarmaceutika, npr. poboljsanja dizajna istrazivanja i promene u zakonskoj regulativi. Osim toga, u ovoj oblasti su aktivne i pojedine ekspertske grupe. Uprkos tome, postoji rastuci trend upotrebe primata izuzev coveka u pretklinickom ispitivanju bezbednosti biofarmaceutika, posebno kada su u pitanju monoklonska antitela. Druga bioeticka pitanja koja se mogu dovesti u vezu sa razvojem biofarmaceutika su odnos njihove cene i efikasnosti, procena bezbednosti u klinickim uslovima, proizvodnja bioloski slicnih lekova i uporedjivanje njihove efikasnosti sa placebom u zemljama u kojima ne postoji namera o plasmanu. Upoznavanje humanog genoma otvorilo je mnoga bioeticka pitanja. Razvoj biofarmaceutika je vazno bioeticko pitanje iz vise razloga. Ono povezuje sve aspekte savremene bioetike: biomedicinu, dobrobit zivotinja i najnovija dostignuca u biotehnologiji. Posebno, razvoj biofarmaceutika je izazov kada je u pitanju lecenje retkih bolesti. (shrink)

New molecular markers for epidermal stem cells have enabled their isolation both in vitro and from the epidermis lying between hair follicles. Micro‐dissection experiments have localised a second population of stem cells within hair follicles. Epidermal stem cells have a patterned distribution in vivo. The patterning can be reconstituted in vitro, showing that it is generated by interactions between keratinocytes and that the differentiation of epidermal stem cells is regulated by signals from other keratinocytes. Recent evidence from transgenic (...) class='Hi'>mice suggests that stem cell behaviour in the gut may be regulated by similar cell‐cell interactions in vivo. Candidate genes for mediating these interactions are the homologues of Drosophila cell fate patterning genes such as Notch and Wingless and the Cadherin family of cell‐cell adhesion molecules. The roles of stem cells and of mutations of the Patched gene in epithelial carcinogenesis are discussed. (shrink)

The sudden infant death syndrome (SIDS) is the sudden, unexpected death of an infant that is not explained by autopsy, death scene examination, and history. The etiology is unknown. Recent postmortem studies have discovered abnormalities in brainstem serotonergic neurons, but how these translate into dysfunction and cause SIDS is uncertain. Recently, lethal effects in transgenic mice with overexpression of the serotonin 1A autoreceptor have been described. Many die spontaneously between postnatal day 40 (P40) and P80, and some spontaneously (...) exhibit bradycardias and drops in body temperature. The severity of the autonomic dysfunction and its age dependence suggest relevance to SIDS. However, SIDS cases have decreased serotonin 1A autoreceptor binding, which is opposite to its overexpression in the mice, and the peak incidence of SIDS is between 2 and 6 months of age, which is arguably younger (in relative terms) than the ages at which the mice die. Nevertheless, the description of an animal model with serotonin defects that has autonomic dysfunction and spontaneous mortality at a young age is an exciting finding of possible importance for understanding SIDS. (shrink)

Alzheimer's disease, a form of senile dementia, is characterised by two kinds of pathological deposits in the brain, called plaques and tangles. The molecular nature of the deposits has been identified but there is as yet little understanding of the underlying biochemistry and cell biology that lead to their formation. Progress in this area would be greatly aided by a realistic animal model. Two recent papers describe the production of transgenic mice that develop significant aspects of Alzheimer‐like pathology. (...) The mice produced by Games et al.(1) develop plaques while those produced by Götz et al.(2) display the early stages of tangle pathology. (shrink)

The retrotransposon Long Interspersed Element 1 (LINE‐1 or L1) has played a major role in shaping the sequence composition of the mammalian genome. In our recent publication, “Heritable L1 retrotransposition in the mouse primordial germline and early embryo,” we systematically assessed the rate and developmental timing of de novo, heritable endogenous L1 insertions in mice. Such heritable retrotransposition events allow L1 to exert an ongoing influence upon genome evolution. Here, we place our findings in the context of earlier studies, (...) and highlight how our results corroborate, and depart from, previous research based on human patient samples and transgenic mouse models harboring engineered L1 reporter genes. In parallel, we outline outstanding questions regarding the stage‐specificity, regulation, and functional impact of embryonic and germline L1 retrotransposition, and propose avenues for future research in this field. -/- . (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 12.3 (2002) 305-323 [Access article in PDF] Scope Note 41 Bioethics and Cloning, Part I Susan Cartier Poland and Laura Jane Bishop This is Part One of a two part Scope Note on Bioethics and Cloning. Part Two will be published in the December 2002 issue of the Kennedy Institute of Ethics Journal and as a separate reprint. Contents For Parts 1 And 2 (...) Part 1Part 2I.History of the ScienceI.Ethical PerspectivesII.Historical CommentaryII.Religious PerspectivesIII.Animal WelfareIII.Fiction and FilmIV.Laws and Legal Literature"Clone" is a collective noun (I, Stewart 1997, p. 771). A collective noun names a group and is composed of individual members, such as "herd" or "flock." Derived from the Greek kl¯on for twig or slip, "clone" was first used in biology to describe the aggregate of asexually produced progeny of an individual, either naturally occurring or man-made; the definition later expanded to mean a group of genetically identical members who originate from a single ancestor. Thus, a clone is a group that results from the process of asexual reproduction.In nature, cloning occurs either by parthenogenesis (reproduction without fertilization) or by fission (embryo splitting). In a pioneering experiment in 1952, Robert Briggs and Thomas J. King (I, 1952), cancer researchers at the Institute for Cancer Research (today part of the Fox Chase Cancer Center) in Philadelphia, demonstrated on frogs another method of cloning by transplanting nuclei into enucleated cells, a technique called "nuclear transplantation," which John B. Gurdon and colleagues (I, 1958, 1975) used to create clones of frogs.Then, in the late 1970s and early 1980s, two back-to-back frauds in cloning occurred. First, the cloning of a human described by American science journalist David Rorvik in the 1978 book In His Image was called a hoax by a court in [End Page 305] 1982. Second, the cloning of three mice, announced by German wunderkind Karl Illmensee to scientific circles in 1979 (and to the public in 1981), could not be proven to be true, according to convincing evidence by McGrath and Solter (I) published in 1984.With their pronouncement that mammalian cloning was impossible, McGrath and Solter essentially stopped cloning research and funding for such biological research. So by the mid-1980s, instead of further investigating cloning, developmental biologists studied embryology related to in vitro fertilization, while molecular biologists studied recombinant DNA under the newly relaxed NIH guidelines. These two strands of scientific investigation came together in the work of Ian Wilmut, who created in vitro embryos using nuclear transplantation to reproduce genetically engineered cattle. Wilmut was seeking a way to increase the successful birth rate when, in the 1990s, he produced identical twin sheep, Megan and Morag, cloned from an embryonic cell, followed by another sheep, Dolly, cloned from an adult cell. The birth of a mammal from an embryo whose genetic material came from an adult cell firmly re-established the possibility of cloning from adults. Prior to Dolly's birth, scientists believed that adult cells lost the ability to dedifferentiate—i.e., to become unspecialized—and so could not direct the development of an embryo through to birth.The 1997 announcement of Dolly's birth initiated the present widespread discussion of cloning. Because of its potentially vast applications across human health, medicine, agriculture, and business/economics, cloning raises a host of issues including those concerning: genetics and genetic engineering, patenting, animal rights and/or animal welfare (especially for transgenic, research, or cloned animals), organ transplantation, reproduction, eugenics, pharmacology (drug production using transgenic animals), research practices, informed consent, stem cell research, women's rights, children's rights, parental rights and responsibilities, and theology and philosophy. It fosters questions about the meaning and purpose of life, the limits of human powers to intervene in research and therapy, and what it means to be human or animal. In addition, environmentalists and organic farmers raise concerns about the effect of novel animals and plants on the environment, while nutritionists and the lay public wonder... (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, (...) class='Hi'>mice with a targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

When successful and ethical managers are alerted to possible organizational wrongdoing, they take corrective action before the problems become crises. However, recent research [e.g., Rynes et al. (2007, Academy of Management Journal50(5), 987–1008)] indicates that many organizations fail to implement evidence-based practices (i.e., practices that are consistent with research findings), in many aspects of human resource management. In this paper, we draw from years of research on whistle-blowing by social scientists and legal scholars and offer concrete suggestions to managers who (...) are interested in encouraging internal reporting of problems requiring attention, and to observers of questionable activity who are considering reporting it. We also identify ways that research suggests policy-makers can have a more positive influence. We hope that these suggestions will help foster evidence-based practice regarding whistle-blowing. (shrink)

Psychedelic-assisted Psychotherapy combines the use of psychedelic compounds, such as psilocybin, with psychotherapy. PAP has shown some promise as a novel treatment for Major Depressive Disorder, and empirical research suggests that its efficacy turns on the altered states induced by psychedelic compounds. In this paper we draw on the literature of phenomenology to explain the therapeutic potential of psychedelic experiences. Svenaeus characterises mental illness as a form of suffering that entails three distinct but related experiences of alienation or “unhomelike being-in-the-world”: (...) illness suffering, which relates to embodiment; existential suffering, which relates to self-narratives, and political suffering, which relates to social relationships. Ratcliffe further characterises the experience of MDD in phenomenological terms as a loss of pre-intentional possibility that manifests as excessive noematic feeling in the experience of embodiment, restrictive narratives in the construction of self, and disconnectedness in experience of the social world. We contend that PAP ameliorates the suffering associated with MDD by inducing and consolidating a state of broadened pre-intentional possibility—one that entails sudden, profound and enduring changes in embodiment, self-narratives, and social experience. We argue further that this phenomenological account is consistent with a bio-psycho-social model of mental health and illness, and we frame it as an argument supporting the plausibility of recent claims about treatment success. This helps to justify ongoing future empirical research in this setting. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Commentary on “Towards a Design-Based Analysis of Emotional Episodes”Cristiano Castelfranchi (bio) and Maria Miceli (bio)Keywordsgrief, suffering, attachment, agent architectureThis paper is significant in many respects: its approach (the design-based analysis); its proposed architecture; its description of grief; and its self-control/perturbance theory. We would offer some remarks on each of these aspects.AI: Back to the FutureAfter some years of crisis, AI seems now to have recovered its original challenging attitude (...) and its identity. In particular all the original ambitions of AI have been renewed under the label of “autonomous agents” (see, for example, Russell and Norvig 1995; Wooldridge and Jennings 1995). This paper and its authors are good representatives of this challenging attitude. Of course, the AI appearing at century’s end is different from, say, the AI of the 1980s. AI systems and models are now conceived for reasoning and acting in open unpredictable worlds, with limited and uncertain knowledge, in real time, with bounded (both cognitive and material) resources, with hybrid architectures, interfering—either co-operatively or competitively—with other systems. The new password for the AI of the 1990s is interaction (Bobrow 1991): interaction with an evolving environment; among several, distributed and heterogeneous artificial systems in a network; with human users; and among humans through computers.This renewed AI, however different though it is in some ways, can be understood as returning to its original aim of modeling “intelligence”: not only static and isolated sub-functions of intelligence but the integrated and pragmatic functioning of autonomous agent architectures as against algorithms. Our renewed AI, based on architectures, can again have important exchanges with other (psychological and social) sciences. This paper is a good example of the fruitful cross-fertilization of ideas which may result from such exchanges. It was indeed just this which originally gave rise to cognitive science.The ArchitectureThe proposed architecture, although quite speculative, and—as the authors themselves emphasize—very much a first sketch, is directly relevant to this new AI. In fact, recent research efforts in the agent-architecture domain are focused exactly on the problem of “goal dynamics” [End Page 129] or “motive processing,” which is the core of this architecture, and on the problem of integrating reactivity and deliberation. Compared with current AI architectures (for example, BDI systems) it is important to note that this “motive-processing” architecture is not yet formalized or implemented to the same extent. On the other hand, it is more interesting from a psychological point of view, and is already able to give us some important insights into human emotions, in particular those emotions (like grief) that involve all or total loss of control of management processes.The Report-Based Analysis of GriefThe report-based description of grief provides a persuasive and rich basis for both modeling and discussing the model. The relevant features of this emotion are well characterized with reference to the self-control problem and motive-processing (though, as we shall see, to use grief as an example of those emotions that involve all or total loss of control of thought processes may provide a partially distorted view of grief itself). In particular, we would stress the relevance of the “intrusive” character of grief-related contents; the rejection of certain beliefs due to the psychic pain they cause; the coping strategies people describe; and the second order motivations related to the control of the emotional state. We believe that psychological models especially of these aspects are usually less specific and explanatory.Let us now try to synthesize some criticisms one could advance of this analysis. We will first address two core notions of the model—perturbance and self-control—and then consider more specifically the treatment of grief.PerturbanceThis notion is potentially very interesting, unless it is reduced to an information processing perspective (e.g., perturbance of attentive processes). An information processing perspective is much more limited than a motive-processing one—at least in the limitative sense of the term, as it is generally used in the psychology of cognitive processes—and is in our view insufficient for understanding human emotions and their role. This limiting interpretation of perturbance fails... (shrink)

Contempt and disgust share a number of features which distinguish them from other hostile emotions: they both present two distinct facets—a nonmoral facet and a moral one; they both imply a negative evaluation of the dispositional kind as well as disrespect towards the target of the feeling; and they trigger avoidance and exclusion action tendencies. However, while sharing a common core, contempt and disgust are in our view distinct emotions, qualified by different cognitive-motivational features. Contempt is felt exclusively towards human (...) targets, and implies sense of superiority over them, pessimistic feelings about their possibility of betterment, detachment from them, and avoidance driven by detachment; whereas disgust can be directed at a wide range of possible targets, and implies contamination sensitivity, fear of contamination, and fear-driven avoidance. The differences between contempt and disgust are related to the different kinds of standard against which the target is evaluated, and the different kinds of disrespect engendered by the negative evaluation. (shrink)

The mind is a powerful anticipatory device. It frequently makes predictions about the future, telling us not only how the world might or will be, but also how it should be - or better - how we would like it to be. This book explores anticipation-based emotions - the emotions associated with the interaction between 'what is' and 'what is not '.

The widespread assumption that anger is a response to wrongdoing and motivates people to sanction it, as well as the lack of distinction between resentment and indignation, obscure notable differences among these three emotions in terms of their specific beliefs, goals, and action tendencies, their nonmoral or moral character, and the kinds of moral claim implied. We provide a cognitive-motivational analysis of anger, resentment, and indignation, showing that, while sharing a common core, they are distinguishable from one another because they (...) comprise nonoverlapping belief–goal compounds. We also emphasize the usefulness of applying a belief–goal analysis to kin emotions because, by comparison, one can sharpen the analysis and identify the distinctive features of each of them. (shrink)

This work provides an analysis of the basic cognitive components of envy. In particular, the roles played by the envious party's social comparison with, and ill will against, the better off are emphasised. The ill will component is characterised by the envier's ultimate goal or wish that the envied suffer some harm, and is distinguished from resentment and sense of injustice, which have often been considered part of envy. The reprehensible nature of envy is discussed, and traced back to the (...) analysis of its components. Finally, we explore both points of overlap and distinguishing features between envy and other emotions such as jealousy or emulation, and make a few general remarks, pointing to the necessity of overcoming conceptual looseness in the notion of envy. (shrink)

The aim of the article is to analyze the double movement around the legal construct “Señor Natural” that takes place in Las Siete Partidas by Alfonso X, a key concept in the wise King’s political program. On the one hand, the concept of “Señor natural” is reworked and becomes legal, placing the king above any other order; on the other, the obligation regarding the “Señor natural” is established as the best of all “natural obligations”. All this conflates into a new (...) concept of “Señor natural” based on men and the land, which becomes a natural obligation in Partidas, a monarch’s reinforcement to exercise dominium in the totality of the kingdom. (shrink)

This work proposes an analysis of the cognitive and motivational components of hope, its basic properties, and the affective dispositions and behaviors it is likely to induce. In our view current treatments of hope do not fully account for its specificity, by making hope overlap with positive expectation or some specification of positive expectation. In contrast, we attempt to highlight the distinctive features of hope, pointing to its differences from positive expectation, as well as from a sense of successful agency, (...) optimism, trust, and faith. Fear and anxiety are also addressed, and the latter is analyzed as a state of mind implying both fear and hope. Finally, the relationship between hope and motivation is explored, and “active” hope is compared with “passive” hope. Some concluding remarks summarize the results of our analysis, and stress the role of hope in fostering the individual’s well-being. (shrink)

This work presents an analysis of the feeling of guilt and in particular of the cognitive defenses against it. It shows how the need to avoid or mitigate the feeling, with the suffering implied, affects the perception and judgment of oneself and others. It is in fact claimed that to copy with their guilt people try to alter the appraisal processes implied by the emotion. Once described the main cognitive components of the feeling of guilt, an analysis is offered of (...) the interventions of the cognitive defenses on such components, to alter the original appraisal processes underlying the feeling. (shrink)

This work aims to identify the constituents of forgiveness in terms of the forgiver's beliefs and motivating goals. After addressing the antecedents of forgiveness—a perceived wrong—and distinguishing the notion of mere harm from that of offense, we describe the victim's typical retributive reactions—revenge and resentment—and discuss their advantages and disadvantages. Then we focus on the forgiver's mind-set, pointing to the relationship between forgiveness and acceptance of the wrong, addressing the forgiver's motivating goals, and discussing both their self-interested and altruistic implications. (...) In so doing we also discuss the role of the forgiver's positive feelings towards the offender, arguing that, however important, they are unnecessary to forgiveness. We finally identify two kinds of forgiveness—conditional and unconditional—suggesting that they are grounded on different notions of “worth.”. (shrink)

Just a decade ago, requests by students to establish groups to support gay and lesbian students were rare and generally met with shock and confusion by school administrators and local communities. Today there are more than 1600 gay straight alliances across the country._ Standing Out, Standing Together _documents the emergence of gay straight alliances in public schools across America - from factors that have contributed to the relatively rapid spread of GSA to those that stirred controversy and posed roadblocks. Using (...) over 10 years of interviews with students, teachers, administrators and political activists; case studies; and local and national media reports, Miceli explores the personal and political stakes involved in the battles over GSAs. Although the book acknowledges and documents the harassment, abuse and problems suffered by many gay, lesbian, transgendered, and bisexual students, its primary focus is on these students as political activists, rather than as passive victims, making it a unique contribution to sociologists, educators, political activists and LGBTreaders alike. (shrink)

Codified ethics for journalists in Australia has a long history, almost as long as that in the United States. Unlike the United States, however, Australia has a unified code of ethics, that of the Australian Journalists' Association, which is generally accepted by the whole industry, both print and broadcast. But over the last 20 years, media consumers have shown they have a poor and declining view of the ethics of Australian journalists, despite the checks and balances that exist. Recent signs, (...) both from within and outside Australia, indicate growing dissatisfaction with the media, suggesting Australian journalists can expect increasing criticism of their behavior and mounting pressure on them to be more accountable. (shrink)

Surveys the contributions that economic theory has made to the often contentious debate over the government's use of its power of eminent domain, as prescribed by the Fifth Amendment. It addresses such questions as: when should the government be allowed to take private property without the owner's consent? Does it depend on how the land will be used? Also, what amount of compensation is the landowner entitled to receive? The recent case of Kelo v. New London revitalized the debate, but (...) it was only the latest skirmish in the ongoing struggle between advocates of strong governmental powers to acquire private property in the public interest and private property rights advocates. Written for a general audience, the book advances a coherent theory that views eminent domain within the context of the government's proper role in an economic system whose primary objective is to achieve efficient land use. (shrink)

The recent renaissance in research on psychedelic-assisted psychotherapy is showing great promise for the treatment of many psychiatric conditions. Interestingly, therapeutic outcomes for patients undergoing these treatments are predicted by the occurrence of a mystical experience—an experience characterised in part by a sense of profound meaning. This has led to hypotheses that psychedelic-assisted psychotherapy is therapeutic because it enhances perception of meaning, and consequently leads to a meaning response. The putative mechanism of action of psychedelics as meaning enhancers raises normative (...) ethical questions as to whether it can be justified to pharmacologically increase the perception of meaning in order to heal patients. Using the perspectives of hedonistic moral theories, this paper argues that if psychedelics operate as meaning enhancers, psychedelic-assisted psychotherapy can be ethically justified. An anti-hedonistic objection is presented by applying Robert Nozick’s Experience Machine thought experiment to the case of psychedelic-assisted psychotherapy. However, it is argued that this objection falls short for two reasons. First, even if pleasure and pain are not the only consequences which have moral value they are not morally irrelevant, therefore, therapeutic meaning enhancement can still be justified in cases of extreme suffering. Second, it is possible that psychedelic states of consciousness do not represent a false reality, hence their therapeutic meaning enhancement is not problematic according to Nozick’s standards. (shrink)

We argue in favor of the adaptive value of acceptance and that it deserves a definite status within the 'positive paradigm'. Acceptance currently suffers from ambiguous connotations because of its lack of optimistic biases and its similarity to resignation. We endeavor to show that acceptance and resignation are distinct attitudes by exploring their relationships with various phenomena-frustration, disappointment, expectation, positive thinking, replanning, and accuracy. The resulting distinguishing features of acceptance-thriving versus returning to baseline; realistic optimism versus hopelessness; persistence and flexible (...) replanning versus disengagement-are crucial for adaptive coping, and appear to be in keeping with the positive paradigm. (shrink)

Comparable worth is a controversial compensation strategy. In this paper, research issues that arise when employers perform point-based job evaluations, but deviate from them because of market factors, are discussed. Greater research attention to the actual operation of markets and to the consequences of conflicts in equity perceptions is encouraged.

The author presents a theory of institutional inequality in which, in analysing taxation she shows that tax incidence depends upon the causes of inequality.