bluuebunny/crossref_metadata_2025 huggingface dataset:
Genes directly regulated by LEAFY COTYLEDON2 provide insight into the control of embryo maturation and somatic embryogenesis
Authors: Braybrook Siobhan A. , Stone Sandra L. , Park Soomin , Bui Anhthu Q. , Le Brandon H. , Fischer Robert L. , Goldberg Robert B. , Harada John J.
Published: February 2006

The B3 domain protein LEAFY COTYLEDON2 (LEC2) is required for several aspects of embryogenesis, including the maturation phase, and is sufficient to induce somatic embryo development in vegetative cells. Here, we demonstrate that LEC2 directly controls a transcriptional program involved in the maturation phase of seed development. Induction of LEC2 activity in seedlings causes rapid accumulation of RNAs normally present primarily during the maturation phase. Several RNAs encode proteins with known roles in maturation processes, including seed-storage and lipid-body proteins. Clustering analyses identified other LEC2-induced RNAs not previously shown to be involved in the maturation phase. We show further that genes encoding these maturation RNAs all possess in their 5′ flanking regions RY motifs, DNA elements bound by other closely related B3 domain transcription factors. Our finding that recombinant LEC2 specifically binds RY motifs from the 5′ flanking regions of LEC2-induced genes provides strong evidence that these genes represent transcriptional targets of LEC2. Although these LEC2-induced RNAs accumulate primarily during the maturation phase, we show that a subset, includingAGL15andIAA30, accumulate in seeds containing zygotes. We discuss how identification of LEC2 target genes provides a potential link between the roles of LEC2 in the maturation phase and in the induction of somatic embryogenesis.
Evolution of the mammalian placenta revealed by phylogenetic analysis
Authors: Wildman Derek E. , Chen Caoyi , Erez Offer , Grossman Lawrence I. , Goodman Morris , Romero Roberto
Published: February 2006

The placenta is essential for the success of therian mammalian reproduction. Intense selective pressure has shaped changes in placental anatomy and function during mammalian cladogenesis. Here we challenge the view that the hemochorial placenta is a derived feature in haplorhine primates. Using phylogenetic and statistical analyses of molecular and morphological data, we demonstrate that the ancestral eutherian mammalian placenta had the distinctive features of (i) hemochorial placental interface, (ii) a discoid shape, and (iii) a labyrinthine maternofetal interdigitation. These results reveal that the first eutherians had a deeply invasive placenta and imply that the major role of the placenta in sustaining pregnancy and promoting gestational development existed throughout the eutherian lineage that descended to humans from the last common ancestor of placental mammals. The ancestral state reconstructions demonstrate both clade-specific patterns of placentation and specific cases of convergent evolution within individual eutherian clades. Determining the mammalian pattern of change in placental morphology is important for understanding the evolutionary pressures faced by these lineages. The effects of selection pressures on the efficiency of placentation may stem from changes in nutritional demand, gestational length, number of embryos per pregnancy, uterine shape, and maternal body constitution. The influence of these factors on placental development needs further investigation.
Amyloid-β peptide binds with heme to form a peroxidase: Relationship to the cytopathologies of Alzheimer’s disease
Authors: Atamna Hani , Boyle Kathleen
Published: February 2006

Amyloid-β peptide (Aβ) is the toxic agent in Alzheimer’s disease (AD), although the mechanism causing the neurodegeneration is not known. We previously proposed a mechanism in which excessive Aβ binds to regulatory heme, triggering functional heme deficiency (HD), causing the key cytopathologies of AD. We demonstrated that HD triggers the release of oxidants (e.g., H
2
O
2
) from mitochondria due to the loss of complex IV, which contains heme-
a
. Now we add more evidence that Aβ binding to regulatory heme
in vivo
is the mechanism by which Aβ causes HD. Heme binds to Aβ, thus preventing Aβ aggregation by forming an Aβ–heme complex in a cell-free system. We suggest that this complex depletes regulatory heme, which would explain the increase in heme synthesis and iron uptake we observe in human neuroblastoma cells. The Aβ–heme complex is shown to be a peroxidase, which catalyzes the oxidation of serotonin and 3,4-dihydroxyphenylalanine by H
2
O
2
. Curcumin, which lowers oxidative damage in the brain in a mouse model for AD, inhibits this peroxidase. The binding of Aβ to heme supports a unifying mechanism by which excessive Aβ induces HD, causes oxidative damage to macromolecules, and depletes specific neurotransmitters. The relevance of the binding of regulatory heme with excessive Aβ for mitochondrial dysfunction and neurotoxicity and other cytopathologies of AD is discussed.
Weaning marginally affects glucose transporter (GLUT4) expression in calf muscles and adipose tissues
Authors: Hocquette Jean-François , Castiglia-Delavaud Carole , Graulet Benoît , Ferré* Pascal , Picard Brigitte , Vermorel Michel
Published: February 2006

The nutritional regulation of glucose transporter GLUT4 was studied in eight muscles and four adipose tissues from two groups of preruminant (PR) or ruminant (R) calves of similar age (170d), empty body weight (194kg) at slaughter, and level of net energy intake from birth onwards. Isocitrate dehydrogenase (EC 1.1.1.41) activity in muscles was not different between PR and R except in masseter muscle from the cheek (+71 % in R; P<0·003), which becomes almost constantly active at weaning for food chewing. Basal and maximally-insulin-stimulated glucose transport rate (GTR) per g tissue wet weight in rectus abdominis muscle were significantly higher in R calves (+31 and 41 % respectively; P<0·05). GLUT4 protein contents did not differ in muscles from PR and R except in masseter (+74 % in R; P<0·05) indicating that the increased GTR in rectus ubdominis cannot be accounted for by an enhanced GLUT4 expression. GLUT4 mRNAlevels did not differ between the two groups of animals in all muscles suggesting a regulation of GLUT4 at the protein level in masseter. GLUT4 number expressed on a per cell basis was lower in adipose tissue from R calves (-39 % P<0·05) and higher in internal than in peripheral adipose tissues. In summary, the regulation of GLUT4 in calves at weaning differs markedly from that previously described in rodents (for review, see Girard et al. 1992). Furthermore, significant inter-individual variations were shown for metabolic activities in muscle and for biochemical variables in adipose tissue.
Protein utilization during energy undernutrition in sheep sustained by intragastric infusion
Authors: Chowdhury S. A. , Ørskovit E. R. , Hovell F. D. DeB. , Scalfe J. R. , Mollison G.
Published: February 2006

The effect of body fat content on the protein metabolism of energy-restricted sheep has been studied in two experiments. In the first experiment, six Suffolk-cross wether sheep, three weighing about 39 kg and three of about 61 kg, were given progressively increasing amounts of casein-N from 0 to 3000 mg N/kg metabolic body weight (W0·75) daily with constant energy, 91 kJ/kg W0·75 daily, from a high-propionic acid mixture of volatile fatty acids (VFA). In the second experiment, two lean and two fat sheep of similar body weights were given progressively increasing amounts of casein with the same VFA mixture. All the animals attained a positive N balance when they were in negative energy balance. N balance was not affected by body fatness of the magnitude studied, although lean animals utilized increasing levels of standard VFA (acetate-propionate-butyrate 65:25:10, molar proportions) infusion for N accretion more efficiently than fat animals. Endogenous energy was utilized for protein accretion with an efficiency of 0·56. Supply of glucogenic VFA equivalent to 28 mmol glucose/kg W0·75 reduced fasting N excretion by 39%. Fasting heat production decreased from 335 to 300 kJ/kg W0·75 with the infusion of casein and glucogenic VFA. It is argued that fasting induces additional heat losses due to raised protein metabolism and is unsuited as a baseline for dietary assessment.
Evaluating Property-led Initiatives in Urban Regeneration: Tracing Vacancy Chains in Cardiff Bay
Authors: Francis Laura , Thomas Huw
Published: February 2006

This paper contributes to the evaluation of property-led regeneration. Intervention in property markets remains an important strand in regeneration initiatives in Britain, and is still under-evaluated. In the mid 1990s, Robson and colleagues piloted a technique for helping to evaluate some of the effects of propertyled regeneration. This consisted of tracing so-called vacancy chains as the supply of new property stimulated turnover among users of buildings. Knowledge of the chains helps policy makers evaluate a particularly contentious aspect of area-based property-led initiatives: the extent to which they are stimulating new investment in a wider region, as opposed to simply moving existing employment around it. Robson's team undertook only a modest exercise in identifying chains (establishing around 40 chains in each UDC), and argued that further work was needed in order to establish the practicality of the approach and also to generate comparative data. This paper reports on a project that did this, tracing over 100 property chains in two parts of the Cardiff Bay Urban Development Area. The paper sets out, and discusses, the data acquisition techniques used, concluding that this is an approach that could have widespread application. It also reports on findings and concludes that the intervention by Cardiff Bay Development Corporation stimulated modest levels of new investment in Cardiff, but very little from beyond the sub-region.
Migration of the breast biopsy localization wire to the pulmonary hilus
Authors: Banitalebi H. , Skaane P.
Published: February 2006

There have been very few reports of severe complications accompanied by wire localization of breast lesions, such as transsection of the wire and wire migration to the extramammary sites. This is a report of wire migration into the pulmonary hilus demanding surgical removal.
Tumour‐Induced Angiogenesis: A Review
Authors: Plank M. J. , Sleeman B. D.
Published: February 2006

Angiogenesis, the formation of new blood vessels, has become a broad subject and is a very active area for current research. This paper describes the main biological events involved in angiogenesis and their importance in cancer progression. In the first section, a fundamental overview of tumour biology is presented. In the second section, the biology of healthy blood vessels is described and, in the third section, the mechanisms of cell migration and proliferation, which are crucial to angiogenesis, are discussed. In the fourth section, a detailed account of tumour‐induced angiogenesis is given, whilst the pro‐ and anti‐angiogenic factors involved are reviewed in the fifth section. Finally, the processes of tumour invasion and metastasis are examined in the sixth section.
Repo-Man recruits PP1γ to chromatin and is essential for cell viability
Authors: Trinkle-Mulcahy Laura , Andersen Jens , Lam Yun Wah , Moorhead Greg , Mann Matthias , Lamond Angus I.
Published: February 2006

Protein phosphatase 1 (PP1) is a ubiquitous serine/threonine phosphatase regulating many cellular processes. PP1α and -γ are closely related isoforms with distinct localization patterns, shown here by time-lapse microscopy of stably expressed fluorescent protein fusions. A pool of PP1γ is selectively loaded onto chromatin at anaphase. Using stable isotope labeling and proteomics, we identified a novel PP1 binding protein, Repo-Man, which selectively recruits PP1γ onto mitotic chromatin at anaphase and into the following interphase. This approach revealed both novel and known PP1 binding proteins, quantitating their relative distribution between PP1α and -γ in vivo. When overexpressed, Repo-Man can also recruit PP1α to chromatin. Mutating Repo-Man's PP1 binding domain does not disrupt chromatin binding but abolishes recruitment of PP1 onto chromatin. RNA interference–induced knockdown of Repo-Man caused large-scale cell death by apoptosis, as did overexpression of this dominant-negative mutant. The data indicate that Repo-Man forms an essential complex with PP1γ and is required for the recruitment of PP1 to chromatin.
Targeting and activation of Rac1 are mediated by the exchange factor β-Pix
Authors: ten Klooster Jean Paul , Jaffer Zahara M. , Chernoff Jonathan , Hordijk Peter L.
Published: February 2006

Rho guanosine triphosphatases (GTPases) are critical regulators of cytoskeletal dynamics and control complex functions such as cell adhesion, spreading, migration, and cell division. It is generally accepted that localized GTPase activation is required for the proper initiation of downstream signaling events, although the molecular mechanisms that control targeting of Rho GTPases are unknown. In this study, we show that the Rho GTPase Rac1, via a proline stretch in its COOH terminus, binds directly to the SH3 domain of the Cdc42/Rac activator β-Pix (p21-activated kinase [Pak]–interacting exchange factor). The interaction with β-Pix is nucleotide independent and is necessary and sufficient for Rac1 recruitment to membrane ruffles and to focal adhesions. In addition, the Rac1–β-Pix interaction is required for Rac1 activation by β-Pix as well as for Rac1-mediated spreading. Finally, using cells deficient for the β-Pix–binding kinase Pak1, we show that Pak1 regulates the Rac1–β-Pix interaction and controls cell spreading and adhesion-induced Rac1 activation. These data provide a model for the intracellular targeting and localized activation of Rac1 through its exchange factor β-Pix.
Functional modulation of IFT kinesins extends the sensory repertoire of ciliated neurons in Caenorhabditis elegans
Authors: Evans James E. , Snow Joshua J. , Gunnarson Amy L. , Ou Guangshuo , Stahlberg Henning , McDonald Kent L. , Scholey Jonathan M.
Published: February 2006

The diversity of sensory cilia on Caenorhabditis elegans neurons allows the animal to detect a variety of sensory stimuli. Sensory cilia are assembled by intraflagellar transport (IFT) kinesins, which transport ciliary precursors, bound to IFT particles, along the ciliary axoneme for incorporation into ciliary structures. Using fluorescence microscopy of living animals and serial section electron microscopy of high pressure–frozen, freeze-substituted IFT motor mutants, we found that two IFT kinesins, homodimeric OSM-3 kinesin and heterotrimeric kinesin II, function in a partially redundant manner to build full-length amphid channel cilia but are completely redundant for building full-length amphid wing (AWC) cilia. This difference reflects cilia-specific differences in OSM-3 activity, which serves to extend distal singlets in channel cilia but not in AWC cilia, which lack such singlets. Moreover, AWC-specific chemotaxis assays reveal novel sensory functions for kinesin II in these wing cilia. We propose that kinesin II is a “canonical” IFT motor, whereas OSM-3 is an “accessory” IFT motor, and that subtle changes in the deployment or actions of these IFT kinesins can contribute to differences in cilia morphology, cilia function, and sensory perception.
TLR9/MyD88 signaling is required for class switching to pathogenic IgG2a and 2b autoantibodies in SLE
Authors: Ehlers Marc , Fukuyama Hidehiro , McGaha Tracy L. , Aderem Alan , Ravetch Jeffrey V.
Published: February 2006

Loss of tolerance in systemic lupus erythematosus (SLE) leads to the generation of autoantibodies, which accumulate in end-organs where they induce disease. Here we show that immunoglobulin (Ig)G2a and 2b autoantibodies are the pathogenic isotypes by recruiting FcγRIV expressing macrophages. Class switching, but not development, of IgM anti-self B cells to these pathogenic subclasses requires the innate immune receptor Toll-like receptor (TLR)9 and MyD88 signaling. In their absence, switching of autoreactive B cells to the IgG2a and 2b subclasses is blocked, resulting in reduced pathology and mortality. In contrast, switching of anti-self B cells to IgG1 is not perturbed and generation of nonautoreactive IgG2a and 2b antibodies is not impaired in TLR9-deficient mice. Thus, the TLR9 pathway is a potential target for therapeutic intervention in SLE.
Underlying Disease Severity as a Major Risk Factor for Nosocomial Clostridium difficile Diarrhea
Authors: Kyne Lorraine , Sougioultzis Stavros , McFarland Lynne V. , Kelly Ciarán P.
Published: February 2006

Objective:

To determine the diagnostic accuracy of an index of underlying disease severity (Horn's index) in identifying patients with a high probability of having nosocomial Clostridium difficile diarrhea as a complication of antimicrobial therapy.

Design:

A prospective cohort study of 252 adult patients admitted to the hospital and receiving antibiotics. Risk factors for C. difficile diarrhea were first determined retrospectively in a different cohort of 300 hospitalized patients (primary cobort) and then prospectively in this cohort of 252 hospitalized patients receiving antibiotics (secondary cohort). At the time of hospital admission, disease was rated by clinicians as mild (1), moderate (2), severe (3), or extremely severe (4) using a modified Horn's index. Multivariable logistic regression analysis was used to determine the odds ratio (OR) for C. difficile diarrhea associated with increasing levels of disease severity.

Setting:

An urban teaching hospital affiliated with a medical school in Boston, Massachusetts.

Results:

The incidence of nosocomial C. difficile diarrhea was 8.7% in the primary cohort and 11% in the secondary cohort. In the prospective cohort study (secondary cohort), the OR for C. difficile diarrhea associated with extremely severe disease was 17.6 (95% confidence interval, 5.8 to 53.5). The sensitivity, specificity, and positive and negative predictive values of a Horn's index score of 3 or more (severe to extremely severe disease) as a predictor of nosocomial C. difficile diarrhea were 79%, 73%, 27%, and 96%, respectively.

Conclusions:

These findings provide a means of early stratification of hospitalized patients receiving antibiotics according to their risk for nosocomial C. difficile diarrhea. Patients with severe to extremely severe disease at the time of admission may benefit from careful monitoring of antibiotic prescribing and early attention to infection control issues. In the future, these “high-risk” patients may benefit from prophylaxis studies of novel agents being developed to prevent C. difficile diarrhea.
An Outbreak ofSerratia marcescensBacteremia After General Anesthesia
Authors: Sebert Michael E. , Manning Mary Lou , McGowan Karin L. , Alpern Elizabeth R. , Bell Louis M.
Published: February 2006

Objective:

To investigate an outbreak ofSerratia marcescensbacteremia among patients after general anesthesia.

Design:

A case-control study.

Setting:

A 304-bed, pediatric teaching hospital.

Patients:

Twenty-three pediatric patients who developedS. marcescensbacteremia within 2 weeks after general anesthesia between June 15 and September 22, 1999, were compared with 46 age-matched control-patients who had undergone procedures on the same clinical services of the hospital during the same period.

Results:

Cases were distributed over a wide range of surgical services and were not correlated with exposure to any of the surgical, anesthesia, or nursing staff. Case-patients were significantly more likely than control-patients to have received cefazolin (odds ratio [OR], 11.1; 90% confidence interval [CI90], 1.9 to 24.3) or to have had perioperative placement of a central vascular catheter (OR, 4.2; CI90, 1.2 to 18.8). The timing of the procedures of patients who subsequently developedS. marcescensbacteremia was significantly associated with the shifts of one or more of five operating room technicians (OR, 2.9 to 6.8) who were responsible for preparing intravenous fluids used both to reconstitute perioperatively administered antibiotics and to prime central vascular catheter assemblies.

Conclusions:

Our findings are consistent with a pattern of intermittent contamination due to periodic breaches in sterile technique, rather than a point-source of contamination. The unique challenges that such a procedural breakdown presents to an epidemiologic investigation are discussed. This outbreak stresses the importance of providing comprehensive training in antisepsis when multifunctional personnel are incorporated into an operating room work environment.
Staphylococcus AureusRectal Carriage and its Association with Infections in Patients in a Surgical Intensive Care Unit and a Liver Transplant Unit
Authors: Squier Cheryl , Rihs John D. , Risa Kathleen J. , Sagnimeni Asia , Wagener Marilyn M. , Stout Janet , Muder Robert R. , Singh Nina
Published: February 2006

Background:

The role of rectal carriage ofStaphylococcus aureusas a risk factor for nosocomialS. aureusinfections in critically ill patients has not been fully discerned.

Methods:

Nasal and rectal swabs forS. aureuswere obtained on admission and weekly thereafter until discharge or death from 204 consecutive patients admitted to the surgical intensive care unit and liver transplant unit.

Results:

Overall, 49.5% (101 of 204) of the patients never harboredS. aureus, 21.6% (44 of 204) were nasal carriers only, 3.4% (7 of 204) were rectal carriers only, and 25.5% (52 of 204) were both nasal and rectal carriers. Infections due toS. aureusdeveloped in 15.7% (32 of 204) of the patients; these included 3% (3 of 101) of the non-carriers, 18.2% (8 of 44) of the nasal carriers only, 0% (0 of 7) of the rectal carriers only, and 40.4% (21 of 52) of the patients who were both nasal and rectal carriers (P= .001). Patients with both rectal and nasal carriage were significantly more likely to developS. aureusinfection than were those with nasal carriage only (odds ratio, 3.9; 95% confidence interval, 1.18 to 7.85;P= .025). By pulsed-field gel electrophoresis, the infecting rectal and nasal isolates were clonally identical in 82% (14 of 17) of the patients withS. aureusinfections.

Conclusions:

Rectal carriage represents an underappreciated reservoir forS. aureusin patients in the intensive care unit and liver transplant recipients. Rectal plus nasal carriage may portend a greater risk forS. aureusinfections in these patients than currently realized.
POLKADOTS Are Foci of Functional Interactions in T-Cell Receptor–mediated Signaling to NF-κB
Authors: Rossman Jeremy S. , Stoicheva Natalia G. , Langel Felicia D. , Patterson George H. , Lippincott-Schwartz Jennifer , Schaefer Brian C.
Published: February 2006

Stimulation of the T-cell receptor (TCR) results in the activation of several transcription factors, including NF-κB, that are crucial for T-cell proliferation and gain of effector functions. On TCR engagement, several proteins within the TCR-directed NF-κB signaling pathway undergo dynamic spatial redistribution, but the significance of these redistribution events is largely unknown. We have previously described TCR-induced cytoplasmic structures called POLKADOTS (punctate and oligomeric killing or activating domains transducing signals) that are enriched in the NF-κB signaling intermediate, Bcl10. We now show that these structures are formed only under conditions that promote efficient NF-κB activation. Furthermore, POLKADOTS formation is dependent on functional domains of specific NF-κB signal transducers. Through use of a photoactivatable GFP, we demonstrate that POLKADOTS contain both a highly stable and a rapidly equilibrating protein component. FRET analyses show that POLKADOTS are sites of enriched interactions between Bcl10 and partner signaling proteins. These observations strongly suggest that POLKADOTS are focal sites of dynamic information exchange between cytosolic intermediates in the process of TCR activation of NF-κB.
Caspase-2–induced Apoptosis Requires Bid Cleavage: A Physiological Role for Bid in Heat Shock–induced Death
Authors: Bonzon Christine , Bouchier-Hayes Lisa , Pagliari Lisa J. , Green Douglas R. , Newmeyer Donald D.
Published: February 2006

The mechanisms through which Caspase-2 leads to cell death are controversial. Here we show, using a combination of cell-free and cell culture-based approaches, that cleavage of the Bcl-2-family protein Bid is required for the induction of apoptosis by Caspase-2. Caspase-2 promoted cytochrome c release from mitochondria in the presence of cytosol from wild-type, but not Bid-deficient, mouse embryonic fibroblasts (MEFs). Recombinant wild-type Bid, but not a noncleavable mutant (D59E), restored cytochrome c release. Similarly, Bid-null MEFs were relatively resistant to apoptosis triggered by active Caspase-2, and apoptosis was restored in Bid-null cells by the expression of wild-type, but not D59E, Bid. Finally, Bid-null MEFs were substantially more resistant to apoptosis induced by heat shock, which has been shown to be dependent on apical activation of Caspase-2. The data are consistent with a model in which Caspase-2 induces apoptosis via cleavage of Bid at D59 and the subsequent engagement of the mitochondrial (intrinsic) pathway.
Profound Offense
Authors: Feinberg Joel
Published: February 2006

Profound offenses are misleadingly characterized as simply “offensive nuisances” because of their perceived qualitative difference from mere nuisances, and because of their independence of actual perception. The nub of the offensiveness in the “profound” cases is not personal resentment over a disagreeable experience, but outrage at the offending conduct on grounds quite independent of its effect on oneself. Examples of profound offenses include voyeurism, Nazis and Klansmen, execrated but “harmless” deviant religious moral practices, desecration of venerated symbols, and abortion and mistreatment of corpses. The offense principle does not warrant legal interference in a person’s private conduct on the grounds that those who know that the conduct is (or may be) taking place need protection from the profound offensiveness of their own bare knowledge.
Obscenity as Pornography
Authors: Feinberg Joel
Published: February 2006

The term “pornographic” is a purely descriptive word referring to sexually explicit writing and pictures designed to induce sexual excitement in the reader or observer. To use the terms “obscene” and “pornographic” interchangeably, as if they referred to the same thing, is to beg the question of whether any or all pornographic materials are obscene. Whether any given acknowledged form of pornography is really obscene is an open question to be settled by argument and not by definitional fiat. The following subjects are discussed: the contrast between pornographic writing and literature and drama; artful pornography; pornographic pictorial art, poetry, and program music; how sex can be obscene; the feminist case against pornography; and violent pornography.
Wittgenstein on Mind and Language
Authors: Stern David G.
Published: February 2006

Drawing on 10 years of research on the unpublished Wittgenstein papers, this book investigates Wittgenstein’s early conception of the nature of representation, and how his later revision and criticism of that work led to a radically different way of looking at mind and language. The book casts new light on the Tractatus and Philosophical Investigations, and traces the development of a number of central themes in Wittgenstein’s philosophy. These include his conception of philosophical method, logical atomism and the picture theory of meaning, the nature of representation and the limits of language, the application of language to experience, his treatment of practice and private language, and what he called the “flow of life”. It also explains how the unpublished manuscripts and typescripts were put together, and why they often provide better evidence of the development of his ideas than can be found in his published writing. The book argues that Wittgenstein’s views are often much more simple (and more radical) than we have been led to believe. It provides an overview of the development of Wittgenstein’s thought and brings to light aspects of his philosophy that have been almost universally neglected.
Subject and Object
Authors: Stern David G.
Published: February 2006

This chapter argues that the ontology of the Tractatus is best understood as the consequence of Wittgenstein’s conception of logic and representation in general, and the postulate of the determinacy of sense in particular. Once it is recognized that Wittgenstein arrived at the idea of simple objects based on an abstract argument about the nature of complexes and analysis without providing any specific examples of such analyses, it is easy to see the need for caution in attributing any characteristics to the objects over and above those demanded by Wittgenstein’s logicolinguistic commitments. Commentators have taken the Tractatus to be setting out a bewildering variety of highly specific views about the nature of objects. But the truth is that the book is so programmatic that its ontology can be elaborated in any number of ways. The final section of this chapter analyzes Wittgenstein’s treatment of the self in the Tractatus and his writing from the 1930s as a central example of the extreme tensions between the positivisistic doctrines stated in the Tractatus and the antipositivistic subtext it aims to convey or “show”: if the exoteric doctrine of the Tractatus is that there is no such thing as the subject of experience, the esoteric doctrine is that there is. This leads to a close reading of his proposal in the early 1930s that is considered a “subjectless” language as a way of clarifying the nature of experience, and his subsequent critique of the notions of the “metaphysical self” and the “visual world”. He had transmuted the difference between the first person and third person modes of speech into differences between two worlds and then had tried to put them back together again.
Introduction: Realism and Naturalism in the Philosophy of Science
Authors: Trout J. D.
Published: February 2006

This introductory chapter leads the reader through the major positions, issues, and disputes in 20th century philosophy of science, and describes the evidential conditions that authorize an argument for realism about the social and behavioral sciences. Realist interpretations of the entities, laws, and theories of the natural sciences have become familiar fare for contemporary philosophers of science. Along with their empiricist and various antirealist opponents, realists draw their evidence exclusively from the mature sciences of physics, chemistry, and biology. However, the cumulative effect has been the nearly universal neglect of the social sciences and psychology in this dispute. It is argued that despite the empiricism taught from textbooks in psychology and the social sciences, only a realist understanding of scientific theories can account for the success of quantitative methods in the social sciences and psychology.
Measurement as Population‐Guided Estimation
Authors: Trout J. D.
Published: February 2006

Measurement is a central epistemic category in science, one crucial way to test and improve theories. This chapter offers a general account of measurement, covering cases in the social, psychological, and physical sciences. According to the account of population-guided estimation (PGE), measurement values depend on real values of the population dimensions, and measurement procedures are refined with respect to these unobservable phenomena. Parameter values are real, stable features of the world that sustain conditional dependencies and whose magnitudes can be measured.
Realism: Minimal and Robust
Authors: Trout J. D.
Published: February 2006

The sort of realism supported by statistical principles and experimental design is a thin one. Populations or their members have a real value independent of attempts to measure them, and independent of observations concerning them. As a result, the realist can invoke these unobserved, real values in their explanations of observed behavior or correlations. That there could be a general argument for realism required to account for the reliability of specific statistical principles is a novel contention. Although it is a familiar idea that the theoretical considerations raised in good experimental design require a realist interpretation, no such presumption in favor of realism has accompanied the treatment of general statistical principles. Robust realism, by contrast, holds that the approximate truth of mature scientific theories is the best explanation for their success. This strong version of realism has only mature sciences as its subject matter, and the evidence for it in the social and behavioral sciences is uneven.
Conclusion
Authors: Trout J. D.
Published: February 2006

This chapter summarizes the virtues of measured realism about the social and behavioral sciences, and reviews its comparative advantages over antirealism as well as minimal (local) and robust (global) variants of scientific realism. It also makes a projection about the fate of the naturalistic research begun here. This projection is based on track record of inference to the best explanation, and the current state of understanding of natural laws and causation.
What the Social Text Affair Does and Does Not Prove Alan D. Sokal
Authors: Sokal Alan D.
Published: February 2006

This essay analyzes what Social Text’s publication of a parody of the author’s article does and does not prove about the prevailing intellectual standards in the cultural studies of science. It discusses and criticizes two types of writing: one characterized by meaningless or absurd statements, name-dropping, and the display of false erudition; the other by sloppy thinking and poor philosophy, which come together notably in the form of glib relativism. It concludes with some critical comments on the misnamed “Science Wars”.
What the Sokal Hoax Ought to Teach Us Paul A. Boghossian
Authors: Boghossian Paul A.
Published: February 2006

The essay explores the meaning and implications of Alan Sokal’s hoax on the editors of Social Text. It examines the role that relativist/postmodernist views about knowledge may have played in that episode, and briefly explores the cogency of such conceptions.
A Plea for Science Studies Philip Kitcher
Authors: Kitcher Philip
Published: February 2006

This essay contrasts two views of science that are popular in Science Studies: the realist-rationalist approach, and the socio-historical perspective, and calls for an integration of the best features of each. It discusses appeals to the theory-ladenness of observation and the undertermination of theories by evidence. It analyzes the historiographic program of relying on actor’s categories.
In Defense of Bacon
Authors: Soble Alan
Published: February 2006

Feminist critics, particularly, Sandra Harding, Carolyn Merchant, and Evelyn Fox Keller, claim that misogynous sexual metaphors played an important role in the rise of modern science. The writings of Francis Bacon have been singled out as an especially egregious instance of the use of misogynous (“rape”) metaphors in scientific philosophy to promote the scientific method and to justify technological innovation. This chapter presents a defense of Bacon, arguing that the feminist reading of Bacon is based on misquotations, passages taken out of context, projection, and scholarly uncharitability.
What Is Wrong with the Strong Programme's Case Study of the “Hobbes–Boyle Dispute”?Cassandra L. Pinnick
Authors: Pinnick Cassandra L.
Published: February 2006

This essay argues that Shapin and Schaffer’s reasoning in their book, Leviathan and the Air-Pump: Hobbes, Boyle, and the Experimental Life, begins from the faulty premise that Hobbes and Boyle represent as clearly defined, and unquestionably different, methodological stances. If Shapin and Schaffer’s history of science is incorrect, then their desired conclusions about the epistemology of science are not motivated.
The Epistemic Charity of the Social Constructivist Critics of Science and Why the Third World Should Refuse the Offer Meera Nanda
Authors: Nanda Meera
Published: February 2006

Recent claims that all science is parochial and that ethnosciences are more appropriate for developing countries have been eagerly taken up intellectuals in these countries to repudiate the heritage of colonialism. This essay uses case studies from India, Pakistan, and China to argue that an appreciation of the scientific attitude is the only way to ensure political progress.
The Chosen People
Authors: Graziano Frank
Published: February 2006

This chapter analyzes how symbolic inversion operates in millennial communities to alter the meanings and interrelations of above and below, center and periphery, good and evil, pure and impure, and other opposites. Also treated are the reduction of complexities into simplified dualities that are polarized in diametrical opposition; the emergence of a New Humanity in religious and political thought; the belief that God is fighting for one’s cause; and the ways millennial movements provide new moral and religious options.
Return of the Cultural Hero
Authors: Graziano Frank
Published: February 2006

This chapter studies how the death of heroes is undone in myths through resurrection, reconstitution, reawakening, mistaken or assumed identity, exile or hiding, ascension into heaven, mysterious disappearance-reappearance, and other representations that acknowledge absence but deny death. Following a general discussion, the case studies include the Aztec deity Quetzalcóatl in his relation to Saint Thomas, the Andean myth of Inkarrí, and colonial and modern versions of the hero as Son of the Sun.
Causation in Spinoza
Authors: Koistinen Olli
Published: February 2006

This essay argues that Spinoza’s theory of causation provides another way to reconcile God’s causation with causation between finite individuals. It analyzes and identifies problems in Descartes’s theory of causation and Malebranche’s occasionalism. It is argued that Spinoza was aware of the problems that causation posed for ontologies which allowed substance-pluralism. In Spinoza’s monism, the view that God is the cause of everything is reconcilable with the determinism of the new physics. It is shown that Leibniz’s account of intrasubstantial causation closely resembles Spinoza’s view.
What Counts as an Individual for Spinoza?
Authors: Barbone Steven
Published: February 2006

This essay explores Spinoza’s concept of an individual. It focuses on the ontological status of the political state, and rejects Matheron’s view that political states are individuals. For Spinoza, the individual is first and foremost, and it follows that political institutions take second place in importance to the individuals who live in them. The state exists for the benefit of each individual, and it cannot be the case that an individual exists for the benefit of the state.
Spinoza's Conatus Argument
Authors: Garrett Don
Published: February 2006

This essay contends that Spinoza’s argument for the conatus doctrine does not commit any of the five fallacies of equivocation. The key to a better understanding of his argument lies in a Spinoza’s “theory of inherence” — that is, his theory of what it is to be “in” something. Spinoza’s conatus argument is a valid demonstration from Spinozistic premises about inherence, conception, causation, and related matters. These premises reflect his deep commitment to a rigorous Principle of Sufficient Reason, to a conception of things as causing their own properties through their essences, and to a closely-related conception of causation as identical with or parallel to logical consequence.
Spinoza on the Relativity of Good and Evil
Authors: Jarrett Charles
Published: February 2006

This essay argues that Spinoza sees good and evil as relative in at least three ways. It distinguishes between speaker-relativity, correlativity, and model-relativity. It considers the conceptual and interpretative problems arising in two arguments of the Ethics: one argument attempts to show that rationality is a maximizing principle, that is, that a rational individual will choose the best option available, even among distasteful or bad ones; the other attempts to show that anyone who always had adequate ideas would be incapable of conceiving of goodness. It is shown that both arguments appear to have a confusion of one type of relativity with another.
Spinoza, Thoughtful Teleology, and the Causal Significance of Content
Authors: Manning Richard N.
Published: February 2006

This essay contends that Jonathan Bennett gave a passive reading of conatus, and that he misunderstood Spinoza’s conception of mental representation, mistakenly attributing to Spinoza the common, contemporary view that representational content does not supervene on the intrinsic features of representations. A reading of the conatus as an active, motive principle of opposition is presented. It is argued that Spinoza’s notion of representation is best understood as grounded in a conception of causation on which effects bear intrinsic, distinctive structural marks of their causes.
Aesthetics I. The Nature of Art
Authors: Berger Karol
Published: February 2006

The cultural media allow us to objectify and store away our immediate experiences, with the fundamental structure of each medium consisting of the work, the real object produced in the process of encoding an experience in a medium, and the imaginary world so encoded. Media can be either visual (as in sculpture or painting), allowing us to grasp, represent, and explore an outer, spatial, world of experience; or aural (as in music), making it possible to grasp, represent, and explore an inner, temporal world of experiencing. It can be both, as in language, a medium that possesses not only representational but also logical powers, allowing us not only to represent the objects of our desire as well as the desire itself, but also to represent thinking about our aims and means, deliberating on the questions whether our desire is justified, and if so, how can it be realized. A work can be an enduring object or an ephemeral event; a world can be a representation or an argument. Representations subdivide into those of actual and those of fictional objects, while arguments subdivide into those about the world as it is and those about the world as it should be. A place for art results from the superimposition of these classifications: art involves representations of fictional objects. While works in all media, language included, can evoke worlds that are representations, only a linguistic work can also evoke a world that is an argument that consists of general intellectual concepts and logical relations among them.
Aesthetics III. The Genealogy of Modern European Art Music
Authors: Berger Karol
Published: February 2006

Modern European art music is a social practice with internal aims on which its claim to relative autonomy rests (relative, because the contrast between autonomous and functional music, as well as the parallel contrast between art and popular music, is the contrast between ideal types). A profound transformation of these aims marks a revolution or a paradigm shift in the history of this practice. With each successive paradigm shift, the specific relation and proportion between its artistic-autonomous and popular-functional components, specifically between the idea of music as the abstract embodiment of harmony and the idea of music as the representation or mimesis of passions, changed. The formalism and abstraction that characterize the musical and artistic modernity celebrates the modern absolute freedom of a subjectivity that intends everything, but is committed to nothing. At its most radical, it faces the same loss of significance and sterility that is faced by the subjectivity it celebrates.
Poetics I: Diegesis and Mimesis. The Poetic Modes and the Matter of Artistic Presentation
Authors: Berger Karol
Published: February 2006

This chapter explores the nature of the diegetic and mimetic modes in literature, the question of their applicability to painting and music, and the relationship between the author and the voices he employs in his work. The categories of elements that constitute the world presented in the literary work are the setting, the personage, and the narrator. While we may easily find analogues for the setting and the personage in painting and music, a true narrative voice is more difficult to locate and may be something of a rarity in these two arts, although it may appear under specific circumstances. The real author is the creator of the immediately speaking voices he employs to present the world of his work, but himself does not belong to this world. As for the implied author, the arguments for postulating the existence of this entity are examined, and the conclusion reached is that the concept is a theoretical fiction with no useful task to perform.
Introduction
Authors: Sorensen Roy A.
Published: February 2006

This introductory chapter begins with a brief description of the purpose of this book, which is to present a general theory of thought experiments. The discussion includes thought experiments from many disparate fields, ranging from aesthetics to zoology. The primary goal is to establish true and interesting generalizations about them. Success here will radiate to the secondary goal of understanding philosophical thought experiments. An overview of the subsequent chapters is presented.
Our Most Curious Device
Authors: Sorensen Roy A.
Published: February 2006

This chapter illustrates the power of thought experiments by assembling influential thought experiments from the history of science. It lays out the book's plan to understand philosophical thought experiments by concentrating on their resemblance to scientific relatives. Points of difference between philosophical and scientific thought experiments give a preview of obstacles that must be overcome in the course of the campaign. Naive and sophisticated reservations about the philosophical cases are registered for the same purpose.
Scepticism About Thought Experiments
Authors: Sorensen Roy A.
Published: February 2006

This chapter presents and motivates the issues surrounding thought experiments by assembling the case against their use. It begins by exploring the more specific charge that thought experiment is just introspection, then concentrates on the charge that it is merely an atavistic appeal to ordinary language. Even if thought experiment is distinct from either of these methods, it strongly resembles them. Hence, details of both introspection and the appeal to ordinary language will be discussed in the hope of illuminating thought experiment at least by analogy. Finally, a more general problem about the informativeness of thought experiment is developed.
The Wonder of Armchair Inquiry
Authors: Sorensen Roy A.
Published: February 2006

This chapter focuses on armchair inquiry. Thought experiment has the feel of clairvoyance, thus eliciting awe in some and suspicion in others. But the wonder of thought experiment is just a special case of our vague puzzlement about how a question could be answered by merely thinking. There is no mystery when investigators look, measure, and manipulate. Their answers come from the news borne by observation and experiment. But if you just ponder, then the information you have leaving the armchair is the same as the information you had when you sat down. It is argued that part of our wonder is based on a modal fallacy. The theories of armchair inquiry that promise answers to the legitimate portion of our wonder are surveyed. Finally, a cleansing model of rationality that sets the stage for a detailed analysis of how thought experiments work is developed.