bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of NFκB activator Act1 in CD40-mediated signaling in epithelial cells
Authors: Qian Youcun , Zhao Zhendong , Jiang Zhengfan , Li Xiaoxia
Published: July 2002

CD40, a cell surface receptor in the tumor necrosis factor receptor family, first identified and functionally characterized on B lymphocytes, is also expressed on epithelial and other cells and is now thought to play a more general role in immune regulation. Overexpression of the NFκB activator 1 (Act1) leads to the activation of both NFκB and Jun kinase in epithelial cell lines. Endogenous Act1 is recruited to the CD40 receptor in human intestinal (HT29) and cervical (HeLa) epithelial cells upon stimulation with CD40 ligand, indicating that Act1 is involved in this signaling pathway. Act1 also interacts with tumor necrosis factor receptor-associated factor 3, a component involved in CD40-activated pathway. Furthermore, transfection of Act1 into C33A cervical epithelial cells, which do not express it, renders these cells sensitive to CD40 ligand-induced NFκB activation and protects them from CD40 ligand-induced apoptosis. We conclude that Act1 plays an important role in CD40-mediated signaling in epithelial cells.
Ancestral polymorphism and adaptive evolution in the trichothecene mycotoxin gene cluster of phytopathogenic
Fusarium
Authors: Ward Todd J. , Bielawski Joseph P. , Kistler H. Corby , Sullivan Eileen , O'Donnell Kerry
Published: July 2002

Filamentous fungi within the
Fusarium
graminearum
species complex (
Fg
complex) are the primary etiological agents of
Fusarium
head blight (scab) of wheat and barley. Scab is an economically devastating plant disease that greatly limits grain yield and quality. In addition, scabby grain is often contaminated with trichothecene mycotoxins that act as virulence factors on some hosts, and pose a serious threat to animal health and food safety. Strain-specific differences in trichothecene metabolite profiles (chemotypes) are not well correlated with the
Fg
complex phylogeny based on genealogical concordance at six single-copy nuclear genes. To examine the basis for this discord between species and toxin evolution, a 19-kb region of the trichothecene gene cluster was sequenced in 39 strains chosen to represent the global genetic diversity of species in the
Fg
complex and four related species of
Fusarium
. Phylogenetic analyses demonstrated that polymorphism within these virulence-associated genes is transspecific and appears to have been maintained by balancing selection acting on chemotype differences that originated in the ancestor of this important group of plant pathogens. Chemotype-specific differences in selective constraint and evidence of adaptive evolution within trichothecene genes are also reported.
Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair
Authors: Kisiday J. , Jin M. , Kurz B. , Hung H. , Semino C. , Zhang S. , Grodzinsky A. J.
Published: July 2002

Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defect site to initiate
de novo
tissue regeneration. Biocompatible scaffolds assist in providing a template for cell distribution and extracellular matrix (ECM) accumulation in a three-dimensional geometry. A major challenge in choosing an appropriate scaffold for cartilage repair is the identification of a material that can simultaneously stimulate high rates of cell division and high rates of cell synthesis of phenotypically specific ECM macromolecules until repair evolves into steady-state tissue maintenance. We have devised a self-assembling peptide hydrogel scaffold for cartilage repair and developed a method to encapsulate chondrocytes within the peptide hydrogel. During 4 weeks of culture
in vitro
, chondrocytes seeded within the peptide hydrogel retained their morphology and developed a cartilage-like ECM rich in proteoglycans and type II collagen, indicative of a stable chondrocyte phenotype. Time-dependent accumulation of this ECM was paralleled by increases in material stiffness, indicative of deposition of mechanically functional neo-tissue. Taken together, these results demonstrate the potential of a self-assembling peptide hydrogel as a scaffold for the synthesis and accumulation of a true cartilage-like ECM within a three-dimensional cell culture for cartilage tissue repair.
Evidence for a cytopathogenicity determinant in HIV-1 Vpr
Authors: Somasundaran Mohan , Sharkey Mark , Brichacek Beda , Luzuriaga Katherine , Emerman Michael , Sullivan John L. , Stevenson Mario
Published: July 2002

HIV-1 is cytopathic for CD4+T lymphocytesin vitroand this property of HIV-1 is generally considered to account for some of itsin vivocytopathogenicity. Thus, the extent of lymphocyte depletion correlates with the level of viremia whereas low levels of viral replication are typically associated with stable lymphocyte levels and asymptomatic infection such as is observed in non-progressors. Here, we describe a non-progressor who did not fit this general pattern in that CD4+T lymphocyte homeostasis was maintained in the face of high-level viral replication. Biological viral isolates from this patient replicated in primary lymphocytes without inducing cytopathicity. Because this phenotype is reminiscent of Vpr-deleted viruses, we examined the contribution of the Vpr gene to the viral phenotype. Vpr alleles derived from this patient contained both premature stop codons and an unusual Q3R polymorphism. Insertion of patient-derived Vpr alleles or a Q3R substitution into a cytopathic HIV-1 clone resulted in a marked impairment of cytopathicity without affecting viral replication efficiency. The effect of Vpr on cytopathicity was unrelated to reported activities of Vpr including virion association, interaction with uracil DNA glycosylase, G2arrest, or enhancement of macrophage infection but correlated with the ability of Vpr to induce host cell apoptosis. This study suggests the presence of a determinant ofin vivocytopathogenicity within HIV-1 Vpr and further indicates that viral replication can be uncoupled from cytopathicityin vitroandin vivo.
Omnipotent decoding potential resides in eukaryotic translation termination factor eRF1 of variant-code organisms and is modulated by the interactions of amino acid sequences within domain 1
Authors: Ito Koichi , Frolova Ludmila , Seit-Nebi Alim , Karamyshev Andrey , Kisselev Lev , Nakamura Yoshikazu
Published: July 2002

In eukaryotes, a single translational release factor, eRF1, deciphers three stop codons, although its decoding mechanism remains puzzling. In the ciliate
Tetrahymena thermophila
, UAA and UAG codons are reassigned to Gln codons. A yeast eRF1-domain swap containing
Tetrahymena
domain 1 responded only to UGA
in vitro
and failed to complement a defect in yeast eRF1
in vivo
at 37°C. This finding demonstrates that decoding specificity of eRF1 from variant code organisms resides at domain 1. However, the wild-type eRF1 hybrid fully restored the growth of eRF1-deficient yeast at 30°C.
Tetrahymena
eRF1 contains a variant sequence, KATNIKD, at the tip of domain 1. The TASNIKD variant of hybrid eRF1 rendered the eRF1-nullified yeast viable, although in an
in vitro
assay, the same hybrid eRF1 responded only to UGA. Nevertheless, the yeast eRF1 bearing the KATNIKD motif instead of the TASNIKS heptapeptide present in higher eukaryotes remains omnipotent
in vivo
. Collectively, these data suggest that variant genetic code organisms like
Tetrahymena
have an intrinsic potential to decode three stop codons
in vivo
, and that interaction within domain 1 between the KAT tripeptide and other sequences modulates the decoding specificity of
Tetrahymena
eRF1.
Decoupling of unpolluted temperate forests from rock nutrient sources revealed by natural
87
Sr/
86
Sr and
84
Sr tracer addition
Authors: Kennedy Martin J. , Hedin Lars O. , Derry Louis A.
Published: July 2002

An experimental tracer addition of
84
Sr to an unpolluted temperate forest site in southern Chile, as well as the natural variation of
87
Sr/
86
Sr within plants and soils, indicates that mechanisms in shallow soil organic horizons are of key importance for retaining and recycling atmospheric cation inputs at scales of decades or less. The dominant tree species
Nothofagus nitida
feeds nearly exclusively (>90%) on cations of atmospheric origin, despite strong variations in tree size and location in the forest landscape. Our results illustrate that (
i
) unpolluted temperate forests can become nutritionally decoupled from deeper weathering processes, virtually functioning as atmospherically fed ecosystems, and (
ii
) base cation turnover times are considerably more rapid than previously recognized in the plant available pool of soil. These results challenge the prevalent paradigm that plants largely feed on rock-derived cations and have important implications for understanding sensitivity of forests to air pollution.
A R2R3-MYB gene,
AtMYB30
, acts as a positive regulator of the hypersensitive cell death program in plants in response to pathogen attack
Authors: Vailleau Fabienne , Daniel Xavier , Tronchet Maurice , Montillet Jean-Luc , Triantaphylidès Christian , Roby Dominique
Published: July 2002

Hypersensitive response (HR) is a programmed cell death that is commonly associated with disease resistance in plants. Among the different HR-related early induced genes, the
AtMYB30
gene is specifically, rapidly, and transiently expressed during incompatible interactions between
Arabidopsis
and bacterial pathogens. Its expression was also shown to be deregulated in
Arabidopsis
mutants affected in the control of cell death initiation. Here, we demonstrate that overexpression in
Arabidopsis
and tobacco of
AtMYB30
(
i
) accelerates and intensifies the appearance of the HR in response to different avirulent bacterial pathogens, (
ii
) causes HR-like responses to virulent strains, and (
iii
) increases resistance against different bacterial pathogens, and a virulent biotrophic fungal pathogen,
Cercospora nicotianae
. In antisense
AtMYB30 Arabidopsis
lines, HR cell death is strongly decreased or suppressed in response to avirulent bacterial strains, resistance against different bacterial pathogens decreased, and the expression of HR- and defense-related genes was altered. Taken together, these results strongly suggest that
AtMYB30
is a positive regulator of hypersensitive cell death.
Transcription and replication initiate at separate sites on the vesicular stomatitis virus genome
Authors: Whelan Sean P. J. , Wertz Gail W.
Published: July 2002

The RNA-dependent RNA polymerase of the nonsegmented negative-strand RNA viruses carries out two distinct RNA synthetic processes: transcription of monocistronic, capped, and polyadenylated subgenomic messenger RNAs, and replication by means of the synthesis of a full-length positive-sense copy of the genome. The template for both processes is the negative-sense genomic RNA tightly encapsidated by the viral nucleocapsid protein. By applying UV transcriptional mapping to engineered variants of vesicular stomatitis virus, we discovered that, in infected cells, transcription and replication are controlled by initiation at different positions on the viral genome.
Heterogeneous nucleation of supercooled water, and the effect of an added catalyst
Authors: Heneghan A. F. , Wilson P. W. , Haymet A. D. J.
Published: July 2002

The statistics of liquid-to-crystal nucleation are measured rigorously by using a recently developed automated lag-time apparatus (ALTA). A single sample, in this case a sample of pure water both with and without an (insoluble) AgI crystal, is repeatedly cooled, nucleated, and thawed. Analysis of the data, coupled with a second kind of experiment, shows that the statistics of nucleation are consistent with a first-order kinetic mechanism over a wide range of supercooling temperatures. The limitations of classical nucleation theory are exhibited. Our analysis unifies many related experiments in biology, physics, chemistry, and chemical engineering.
Copulation corrupts immunity: A mechanism for a cost of mating in insects
Authors: Rolff Jens , Siva-Jothy Michael T.
Published: July 2002

There are well documented costs of mating in insects but little evidence for underlying mechanisms. Here, we provide experimental evidence for a hormone-based mechanism that reduces immunity as a result of mating. We examined the mealworm beetleTenebrio molitorand show that (i) mating reduces a major humoral immune effector-system (phenoloxidase) in both sexes, and (ii) that this down-regulation is mediated by juvenile hormone. Because both juvenile hormone and phenoloxidase have highly conserved functions across all insects, the identified mechanism is similarly likely to be highly conserved. The positive physiological function of mating-induced juvenile hormone secretion is gamete and accessory gland production: we propose that its negative effects on immune function are the consequence of physiological antagonism. Therefore, we have identified a physiological tradeoff between mating and immunity. Our results suggest that increasing mating success can result in increasing periods of immune suppression, which in turn implies that reproductively successful individuals may be more vulnerable to infection by, and the negative fitness effects of, pathogens.
SCORE: A computational approach to the identification of cis-regulatory modules and target genes in whole-genome sequence data
Authors: Rebeiz Mark , Reeves Nick L. , Posakony James W.
Published: July 2002

A large fraction of the information content of metazoan genomes resides in the transcriptional and posttranscriptional cis-regulatory elements that collectively provide the blueprint for using the protein-coding capacity of the DNA, thus guiding the development and physiology of the entire organism. As successive whole-genome sequencing projects—–including those of mice and humans—are completed, we have full access to the regulatory genome of yet another species. But our ability to decipher the cis-regulatory code, and hence to link genes into regulatory networks on a global scale, is currently very limited. Here we describe SCORE (Site Clustering Over Random Expectation), a computational method for identifying transcriptional cis-regulatory modules based on the fact that they often contain, in statistically improbable concentrations, multiple binding sites for the same transcription factor. We have carried out a
Drosophila
genomewide inventory of predicted binding sites for the Notch-regulated transcription factor Suppressor of Hairless [Su(H)] and found that the fly genome contains highly nonrandom clusterings of Su(H) sites over a broad range of sequence intervals. We found that the most statistically significant clusters are very heavily enriched in both known and logical targets of Su(H) binding and regulation. The utility of the SCORE approach was validated by
in vivo
experiments showing that proper expression of the novel gene
Him
in adult muscle precursor cells depends both on
Su(H)
gene activity and sequences that include a previously unstudied cluster of four Su(H) sites, indicating that
Him
is a likely direct target of Su(H).
Genetic basis for systems of skeletal quantitative traits: Principal component analysis of the canid skeleton
Authors: Chase Kevin , Carrier David R. , Adler Frederick R. , Jarvik Tyler , Ostrander Elaine A. , Lorentzen Travis D. , Lark Karl G.
Published: July 2002

Evolution of mammalian skeletal structure can be rapid and the changes profound, as illustrated by the morphological diversity of the domestic dog. Here we use principal component analysis of skeletal variation in a population of Portuguese Water Dogs to reveal systems of traits defining skeletal structures. This analysis classifies phenotypic variation into independent components that can be used to dissect genetic networks regulating complex biological systems. We show that unlinked quantitative trait loci associated with these principal components individually promote both correlations within structures (e.g., within the skull or among the limb bones) and inverse correlations between structures (e.g., skull vs. limb bones). These quantitative trait loci are consistent with regulatory genes that inhibit growth of some bones while enhancing growth of others. These systems of traits could explain the skeletal differences between divergent breeds such as Greyhounds and Pit Bulls, and even some of the skeletal transformations that characterize the evolution of hominids.
Amino acid residue 184 of yeast Hsp104 chaperone is critical for prion-curing by guanidine, prion propagation, and thermotolerance
Authors: Jung Giman , Jones Gary , Masison Daniel C.
Published: July 2002

Inactivation of Hsp104 by guanidine is contended to be the mechanism by which guanidine cures yeast prions. We now find an Hsp104 mutation (D184N) that confers resistance to guanidine-curing of the yeast [
PSI
+
] prion. In an independent screen we isolated an
HSP104
allele altered in the same residue (D184Y) that dramatically impairs [
PSI
+
] propagation in a temperature-dependent manner. Directed mutagenesis of
HSP104
produced additional alleles that conferred varying degrees of resistance to guanidine-curing or impaired [
PSI
+
] propagation. The mutations similarly affected propagation of the [
URE3
] prion. Basal and induced abundance of all mutant proteins was normal. Thermotolerance of cells expressing mutant proteins was variably resistant to guanidine, and the degree of thermotolerance did not correlate with [
PSI
+
] stability. We thus show that guanidine cures yeast prions by inactivating Hsp104 and identify a highly conserved Hsp104 residue that is critical for yeast prion propagation. Our data suggest that Hsp104 activity can be reduced substantially without affecting [
PSI
+
] stability, and that Hsp104 interacts differently with prion aggregates than with aggregates of thermally denatured protein.
Delayed mating reduces reproductive output of female European grapevine moth, Lobesia botrana (Lepidoptera: Tortricidae)
Authors: Torres-Vila L.M. , Rodríguez-Molina M.C. , Stockel J.
Published: July 2002

Virgin females of Lobesia botrana Denis & Schiffermüller were mated at ages of 1, 3, 5, 8, 12 and 16 days and the effect of mating delay on reproductive output assessed. Delayed mating did not affect female mating success but fertilization was reduced in 16-day-old females. Increased mating delays substantially affected daily oviposition pattern and resulted in a significant reduction of both fecundity and fertility, so that mean number of viable eggs laid decreased from 150 to 22 in 1- and 16-day-old mated females, respectively. Heavier females were more constrained than lighter ones by mating delays and female reproductive efficiency (no. viable eggs/female body weight) was also significantly reduced. Female longevity significantly increased and oviposition period gradually declined with mating delay. The number of viable eggs was positively correlated with both female weight and oviposition period; female longevity and female weight were also significantly correlated. However, the significance of these correlations declined with increased mating delay. Results overall indicated that mating delay drastically reduces female L. botrana reproductive output. The implications of delayed mating of females are discussed from an ecological perspective in relation to L. botrana control using mating disruption.
Modelled impact of insecticide-contaminated dung on the abundance and distribution of dung fauna
Authors: Vale G.A. , Grant I.F.
Published: July 2002

Deterministic models assessed the effects that contaminated dung from insecticide-treated cattle had on populations of three hypothetical species of dung fauna that dispersed randomly and could double their numbers every 1–28 weeks at low density. Insecticide was allowed to kill 2–98 % of adults and prevent 16–100% of breeding in pats produced immediately after cattle treatment, with toxicity declining to < 1% in pats produced 2–23 days later. Treatment intervals were 10–40 days. The modelled impact of insecticide was affected little by approximately four-fold variations in: length and density dependence of the attractive life span of pats, frequency of pat occupation by immature adults, distribution of pat toxicity during treatment interval, and changes in dispersal rates due to age and population density. Of greater importance were variations in: pat toxicity, treatment interval, frequency of pat occupation by breeding adults, density dependence of recruitment and death, natural adversity and mortality in dormancy, general rate of dispersal, and the size and shape of the area with treated cattle. Overall, it seemed that wide variations in the impact of contamination will occur in the field, but in many situations the risk to dung fauna can be substantial, especially for slow breeding beetles, and muscoids contacting insecticide on cattle. Risk extends outside the treated areas, for a distance equal to several daily displacements of the insects. Untreated refuges for species survival should be compact blocks at least 25 daily displacements wide.
The use of alarm pheromones to enhance bait harvest by grass-cutting ants
Authors: Hughes W.O.H. , Goulson D.
Published: July 2002

The enhancement of bait for the control of grass-cutting ants was investigated using two species of grass-cutting ant, Atta bisphaerica (Forel) and Atta capiguara (Gonçalves) (Hymenoptera: Formicidae). Bait was applied in loose piles to obtain a direct relationship between ant attraction and bait harvest. Enhancement with alarm pheromone compounds significantly increased the attractiveness and harvest of bait under certain conditions. A large proportion of the ants attracted to the enhanced bait were minor workers. These ants rarely transport bait because of their small size, and so it may be possible to increase the effect of bait enhancement by using smaller bait granules. Foragers of A. capiguara were less inclined to transport citrus-pulp bait than were those of Atta laevigata (Fr. Smith), a species that also harvests dicotyledonous plants. This emphasizes the importance of developing a bait matrix that is more acceptable to grass-cutting species. Nevertheless, the results suggest that alarm pheromone compounds have significant potential to improve the efficacy of baits for the control of grass-cutting ants.
Operating the production calculus: ordering a production system in the print industry
Authors: Button Graham , Sharrock Wes
Published: July 2002

The topic of shop‐floor work has been extensively examined within sociology. However, the organizational structures within which this work takes place have, in the most part, been taken as unexamined givens. Yet, their operation is also the shop‐floor work of some people. This paper examines the way in which the stable organizational structures within which shop‐floor work takes place are achieved. It is based upon a fieldwork investigation of a large commercial printer and focuses upon the collaborative work of those who are involved in scheduling the production of a job and their use of ‘the production calculus’ in planning the work of the site. The print industry is undergoing considerable technological change and scheduling technologies have been developed to automate this work. However, there has been little take up of these technologies and the paper also considers how the characteristics of operating the production calculus in practice may account for this.
Demography or respect?: work group demography versus organizational dynamics as determinants of meaning and satisfaction at work*
Authors: Hodson Randy
Published: July 2002

This article tests two competing models of meaning and satisfaction at work. First, meaning and satisfaction at work can be influenced by the demographic composition of work groups, especially their racial and gender compositions. Second, meaning and satisfaction can be influenced by management behaviour, especially by leadership in maintaining a productive environment and by respect for workers’ rights. We evaluate these determinants, along with more traditional determinants that focus on socio‐technical characteristics, using a unique data set derived from content analysing the reports provided by book‐length organizational ethnographies (N = 108). Work group composition is found to have only a minor and selective influence on meaning at work. In contrast, management leadership and respect for workers’ rights are found to have much stronger and more widespread effects. The well established role of socio‐technical factors such as job autonomy as foundations for meaning and satisfaction in work is also replicated in the analysis. When contrasted with both work group demography and traditional job and organizational characteristics, a well run organization is found to be the single most important underpinning for a meaningful and satisfying work life. In the concluding section we develop the implication of these findings for organizational analysis.
History, Memory and Nation Building in the Post-Soviet Colonial Space
Authors: Kuzio Taras
Published: July 2002

The disintegration of the Soviet Union in December 1991 led to the de-colonization of the world's last remaining empire. Taking this into account, this article seeks to argue two points. Firstly, many of the imperial policies imposed by the imperial core in the Soviet empire were similar in nature to those imposed by imperial powers in Ireland, Africa, and Asia. Secondly, the nation and state building policies of the post-Soviet colonial states are therefore similar to those adopted in many other post-colonial states because they also seek to remove some—or all—of the inherited colonial legacies. A central aspect of overcoming this legacy is re-claiming the past from the framework imposed by the former imperial core and thereby creating, or reviving, a national historiography that helps to consolidate the new national state. All states, including those traditionally defined as lying in the “civic West,” have in the past—and continue to—use national historiography, myths, and legends as a component of their national identities.
Causal judgement from contingency information: Judging interactions between two causal candidates
Authors: White Peter A.
Published: July 2002

In two experiments participants judged the extent to which occurrences and non-occurrences of an effect could be attributed to an interaction between two causal candidates A and B. In Experiment 1 judgements were influenced by the proportion of instances normatively evaluated as confirmatory for the interaction interpretation, when the objective contingency was held constant. Information about instances in which both candidates were present and the effect occurred was more influential than information about instances in which both candidates were absent and the effect did not occur. In Experiment 2 the occurrence rate of the effect when both candidates were present, when A alone was present, when B alone was present, and when both were absent was manipulated. Interaction judgements were mainly determined by occurrence rate when both were present. There was also a significant effect of occurrence rate when both were absent, but the other two occurrence rates had no significant effect. These results are interpreted as supporting a general model in which causal judgements are made according to the proportion of instances evaluated as supporting the interpretation being judged.
The correspondence between sentence production and corpus frequencies in modifier attachment
Authors: Desmet Timothy , Brysbaert Marc , De Baecke Constantijn
Published: July 2002

We examined the production of relative clauses in sentences with a complex noun phrase containing two possible attachment sites for the relative clause (e.g., “Someone shot the servant of the actress who was on the balcony.”). On the basis of two corpus analyses and two sentence continuation tasks, we conclude that much research about this specific syntactic ambiguity has used complex noun phrases that are quite uncommon. These noun phrases involve the relationship between two humans and, at least in Dutch, induce a different attachment preference from noun phrases referring to non-human entities. We provide evidence that the use of this type of complex noun phrase may have distorted the conclusions about the processes underlying relative clause attachment. In addition, it is shown that, notwithstanding some notable differences between sentence production in the continuation task and in coherent text writing, there seems to be a remarkable correspondence between the attachment patterns obtained with both modes of production.
Speeding up an Internal Clock in Children? Effects of Visual Flicker on Subjective Duration
Authors: Droit-Volet Sylvie , Wearden John
Published: July 2002

Children of 3, 5, and 8 years of age were trained on a temporal bisection task where visual stimuli in the form of blue circles of 200 and 800 ms or 400 and 1600 ms duration, preceded by a 5-s white circle, served as the short and long standards. Following discrimination training between the standards, stimuli in the ranges 200-800 ms or 400-1600 ms were presented with the white circle either constant or flickering. Relative to the constant white circle, the flicker (1) increased the proportion of “long” responses (responses appropriate to the long standard), (2) shifted the psychophysical functions to the left, (3) decreased bisection point values, at all ages, and (4) did not systematically affect measures of temporal sensitivity, such as difference limen and Weber ratio. The results were consistent with the idea that the repetitive flicker had increased the speed of the pacemaker of an internal clock in children as young as 3 years. The “pacemaker speed” interpretation of the results was further strengthened by a greater effect of flicker in the 400/1600-ms condition than in the 200/800-ms condition.
Judgement Frequency, Belief Revision, and Serial processing of Causal Information
Authors: Catena Andrés , Maldonado Antonio , Megías Jesús L. , Frese Bettina
Published: July 2002

The main aim of this research was to study the cognitive architecture underlying causal/covariation learning by investigating the frequency of judgement effect. Previous research has shown that decreasing the number of trials between opportunities to make a judgement in a covariation learning task led to a higher score after an a or d type of trial (positive cases) than after b and c trials (negative cases). Experiment 1 replicated this effect using a trial-by-trial procedure and examined the conditions under which it occurs. Experiment 2 demonstrated a similar frequency of judgement effect when the information was presented in the form of contingency tables. Associative or statistical single-mechanism accounts of causal and covariation learning do not provide a satisfactory explanation for these findings. An alternative belief revision model is presented.
The History of the Concept of Transaction Costs: Neglected Aspects
Authors: Klaes Matthias
Published: July 2002

According to the folk history of transaction costs, the concept is due to a seminal article by Ronald H. Coase, written in the 1930s. Failing to provide an operational framework, Coase's article was neglected for a long time, or so the story continues. In the 1970s, after the limits of the Arrow-Debreu paradigm had become obvious, several authors, including Oliver E. Williamson, Kenneth J. Arrow, Armen A. Alchian, and Harold Demsetz, took up the notion of transaction costs and turned it into a useful analytical tool. Partly responsible for this sudden upsurge of interest was an article by Coase in which he allegedly proposed the now famous “Coase Theorem.”
The Influence of Scottish Enlightenment on Darwin's Theory of Cultural Evolution
Authors: Marciano Alain , Pelissier Maud
Published: July 2002

Since the 1980s, institutional change has become a matter of great interest as economists faced the necessity and the challenge to provide a theory of economic or cultural evolution. Their first reaction was to refer to biology, a field in which theories of evolution have reached a high degree of sophistication. This was all the more legitimate and relevant given that biology has been largely influenced by economics (Schweber 1977, 1980; Gordon 1991; Kresge and Wenar 1994; Depew and Weber 1995). Indeed, the influence of classical political economy on the views of one of the fathers of the modern theory of evolution, Charles Darwin, is widely admitted. Darwin borrowed from economists fundamental ideas such as spontaneous order and methodological individualism (from Adam Smith), the positive role of diversity and variety (from Charles Babbage) and the concept of the struggle for life (from Thomas Malthus). Therefore, the ideas promoted by the founding fathers of political economy, sometimes called “Darwinians before Darwin” (Hayek 1973, p. 23), have shaped Darwin's theory of biological evolution.
Interference with the cytoplasmic tail of gp210 disrupts “close apposition” of nuclear membranes and blocks nuclear pore dilation
Authors: Drummond Sheona P. , Wilson Katherine L.
Published: July 2002

We tested the hypothesis that gp210, an integral membrane protein of nuclear pore complexes (NPCs), mediates nuclear pore formation. Gp210 has a large lumenal domain and small COOH-terminal tail exposed to the cytoplasm. We studied the exposed tail. We added recombinant tail polypeptides to Xenopus nuclear assembly extracts, or inhibited endogenous gp210 tails using anti-tail antibodies. Both strategies had no effect on the formation of fused flattened nuclear membranes, but blocked NPC assembly and nuclear growth. Inhibited nuclei accumulated gp210 and some nucleoporin p62, but failed to incorporate nup214/CAN, nup153, or nup98 and were defective for nuclear import of lamin B3. Scanning and transmission EM revealed a lack of “closely apposed” inner and outer membranes, and the accumulation of novel arrested structures including “mini-pores.” We conclude that gp210 has early roles in nuclear pore formation, and that pore dilation is mediated by gp210 and its tail-binding partner(s). We propose that membrane fusion and pore dilation are coupled, acting as a mechanism to control nuclear pore size.
PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone
Authors: Mollinari Cristiana , Kleman Jean-Philippe , Jiang Wei , Schoehn Guy , Hunter Tony , Margolis Robert L.
Published: July 2002

Midzone microtubules of mammalian cells play an essential role in the induction of cell cleavage, serving as a platform for a number of proteins that play a part in cytokinesis. We demonstrate that PRC1, a mitotic spindle-associated Cdk substrate that is essential to cell cleavage, is a microtubule binding and bundling protein both in vivo and in vitro. Overexpression of PRC1 extensively bundles interphase microtubules, but does not affect early mitotic spindle organization. PRC1 contains two Cdk phosphorylation motifs, and phosphorylation is possibly important to mitotic suppression of bundling, as a Cdk phosphorylation-null mutant causes extensive bundling of the prometaphase spindle. Complete suppression of PRC1 by siRNA causes failure of microtubule interdigitation between half spindles and the absence of a spindle midzone. Truncation mutants demonstrate that the NH2-terminal region of PRC1, rich in α-helical sequence, is important for localization to the cleavage furrow and to the center of the midbody, whereas the central region, with the highest sequence homology between species, is required for microtubule binding and bundling activity. We conclude that PRC1 is a microtubule-associated protein required to maintain the spindle midzone, and that distinct functions are associated with modular elements of the primary sequence.
Cell cycle–dependent localization of macroH2A in chromatin of the inactive X chromosome
Authors: Chadwick Brian P. , Willard Huntington F.
Published: July 2002

One of several features acquired by chromatin of the inactive X chromosome (Xi) is enrichment for the core histone H2A variant macroH2A within a distinct nuclear structure referred to as a macrochromatin body (MCB). In addition to localizing to the MCB, macroH2A accumulates at a perinuclear structure centered at the centrosome. To better understand the association of macroH2A1 with the centrosome and the formation of an MCB, we investigated the distribution of macroH2A1 throughout the somatic cell cycle. Unlike Xi-specific RNA, which associates with the Xi throughout interphase, the appearance of an MCB is predominantly a feature of S phase. Although the MCB dissipates during late S phase and G2 before reforming in late G1, macroH2A1 remains associated during mitosis with specific regions of the Xi, including at the X inactivation center. This association yields a distinct macroH2A banding pattern that overlaps with the site of histone H3 lysine-4 methylation centered at the DXZ4 locus in Xq24. The centrosomal pool of macroH2A1 accumulates in the presence of an inhibitor of the 20S proteasome. Therefore, targeting of macroH2A1 to the centrosome is likely part of a degradation pathway, a mechanism common to a variety of other chromatin proteins.
Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones
Authors: Schaefer Andrew W. , Kabir Nurul , Forscher Paul
Published: July 2002

We have used multimode fluorescent speckle microscopy (FSM) and correlative differential interference contrast imaging to investigate the actin–microtubule (MT) interactions and polymer dynamics known to play a fundamental role in growth cone guidance. We report that MTs explore the peripheral domain (P-domain), exhibiting classical properties of dynamic instability. MT extension occurs preferentially along filopodia, which function as MT polymerization guides. Filopodial bundles undergo retrograde flow and also transport MTs. Thus, distal MT position is determined by the rate of plus-end MT assembly minus the rate of retrograde F-actin flow. Short MT displacements independent of flow are sometimes observed. MTs loop, buckle, and break as they are transported into the T-zone by retrograde flow. MT breakage results in exposure of new plus ends which can regrow, and minus ends which rapidly undergo catastrophes, resulting in efficient MT turnover. We also report a previously undetected presence of F-actin arc structures, which exhibit persistent retrograde movement across the T-zone into the central domain (C-domain) at ∼1/4 the rate of P-domain flow. Actin arcs interact with MTs and transport them into the C-domain. Interestingly, although the MTs associated with arcs are less dynamic than P-domain MTs, they elongate efficiently as a result of markedly lower catastrophe frequencies.
Calcium-independent stimulation of membrane fusion and SNAREpin formation by synaptotagmin I
Authors: Mahal Lara K. , Sequeira Sonia M. , Gureasko Jodi M. , Söllner Thomas H.
Published: July 2002

Ñeurotransmitter release requires the direct coupling of the calcium sensor with the machinery for membrane fusion. SNARE proteins comprise the minimal fusion machinery, and synaptotagmin I, a synaptic vesicle protein, is the primary candidate for the main neuronal calcium sensor. To test the effect of synaptotagmin I on membrane fusion, we incorporated it into a SNARE-mediated liposome fusion assay. Synaptotagmin I dramatically stimulated membrane fusion by facilitating SNAREpin zippering. This stimulatory effect was topologically restricted to v-SNARE vesicles (containing VAMP 2) and only occurred in trans to t-SNARE vesicles (containing syntaxin 1A and SNAP-25). Interestingly, calcium did not affect the overall fusion reaction. These results indicate that synaptotagmin I can directly accelerate SNARE-mediated membrane fusion and raise the possibility that additional components might be required to ensure tight calcium coupling.
Cytokine Signaling and Hematopoietic Homeostasis Are Disrupted in Lnk-deficient Mice
Authors: Velazquez Laura , Cheng Alec M. , Fleming Heather E. , Furlonger Caren , Vesely Shirly , Bernstein Alan , Paige Christopher J. , Pawson Tony
Published: July 2002

The adaptor protein Lnk, and the closely related proteins APS and SH2B, form a subfamily of SH2 domain-containing proteins implicated in growth factor, cytokine, and immunoreceptor signaling. To elucidate the physiological function of Lnk, we derived Lnk-deficient mice. Lnk−/− mice are viable, but display marked changes in the hematopoietic compartment, including splenomegaly and abnormal lymphoid and myeloid homeostasis. The in vitro proliferative capacity and absolute numbers of hematopoietic progenitors from Lnk−/− mice are greatly increased, in part due to hypersensitivity to several cytokines. Moreover, an increased synergy between stem cell factor and either interleukin (IL)-3 or IL-7 was observed in Lnk−/− cells. Furthermore, Lnk inactivation causes abnormal modulation of IL-3 and stem cell factor–mediated signaling pathways. Consistent with these results, we also show that Lnk is highly expressed in multipotent cells and committed precursors in the erythroid, megakaryocyte, and myeloid lineages. These data implicate Lnk as playing an important role in hematopoiesis and in the regulation of growth factor and cytokine receptor–mediated signaling.
Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing
Authors: Yamano Taketoshi , Murata Shigeo , Shimbara Naoki , Tanaka Noriaki , Chiba Tomoki , Tanaka Keiji , Yui Katsuyuki , Udono Heiichiro
Published: July 2002

Major histocompatibility complex (MHC) class I ligands are mainly produced by the proteasome. Herein, we show that the processing of antigens is regulated by two distinct pathways, one requiring PA28 and the other hsp90. Both hsp90 and PA28 enhanced the antigen processing of ovalbumin (OVA). Geldanamycin, an inhibitor of hsp90, almost completely suppressed OVA antigen presentation in PA28α−/−/β−/− lipopolysaccharide blasts, but not in wild-type cells, indicating that hsp90 compensates for the loss of PA28 and is essential in the PA28-independent pathway. In contrast, treatment of cells with interferon (IFN)-γ, which induces PA28 expression, abrogated the requirement of hsp90, suggesting that IFN-γ enhances the PA28-dependent pathway, whereas it diminishes hsp90-dependent pathway. Importantly, IFN-γ did not induce MHC class I expressions in PA28-deficient cells, indicating a prominent role for PA28 in IFN-γ–stimulated peptide supply. Thus, these two pathways operate either redundantly or specifically, depending on antigen species and cell type.
Delayed Apoptotic Cell Clearance and Lupus-like Autoimmunity in Mice Lacking the c-mer Membrane Tyrosine Kinase
Authors: Cohen Philip L. , Caricchio Roberto , Abraham Valsamma , Camenisch Todd D. , Jennette J. Charles , Roubey Robert A.S. , Earp H. Shelton , Matsushima Glenn , Reap Elizabeth A.
Published: July 2002

Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macro-phage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer–deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity.
Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T Cells
Authors: Goldrath Ananda W. , Sivakumar Pallavur V. , Glaccum Moira , Kennedy Mary K. , Bevan Michael J. , Benoist Christophe , Mathis Diane , Butz Eric A.
Published: July 2002

Both naive and memory T cells undergo antigen-independent proliferation after transfer into a T cell–depleted environment (acute homeostatic proliferation), whereas only memory T cells slowly divide in a full T cell compartment (basal proliferation). We show, first, that naive and memory CD8+ T cells have different cytokine requirements for acute homeostatic proliferation. Interleukin (IL)-7 receptor(R)α–mediated signals were obligatory for proliferation of naive T cells in lymphopenic hosts, whereas IL-15 did not influence their division. Memory T cells, on the other hand, could use either IL-7Rα– or IL-15–mediated signals for acute homeostatic proliferation: their proliferation was delayed when either IL-7Rα was blocked or IL-15 removed, but only when both signals were absent was proliferation ablated. Second, the cytokine requirements for basal and acute homeostatic proliferation of CD8+ memory T cells differ, as basal division of memory T cells was blocked completely in IL-15–deficient hosts. These data suggest a possible mechanism for the dearth of memory CD8+ T cells in IL-15– and IL-15Rα–deficient mice is their impaired basal proliferation. Our results show that naive and memory T lymphocytes differ in their cytokine dependence for acute homeostatic proliferation and that memory T lymphocytes have distinct requirements for proliferation in full versus empty compartments.
Cbl-b Positively Regulates Btk-mediated Activation of Phospholipase C-γ2 in B Cells
Authors: Yasuda Tomoharu , Tezuka Tohru , Maeda Akito , Inazu Tetsuya , Yamanashi Yuji , Gu Hua , Kurosaki Tomohiro , Yamamoto Tadashi
Published: July 2002

Genetic studies have revealed that Cbl-b plays a negative role in the antigen receptor–mediated proliferation of lymphocytes. However, we show that Cbl-b–deficient DT40 B cells display reduced phospholipase C (PLC)-γ2 activation and Ca2+ mobilization upon B cell receptor (BCR) stimulation. In addition, the overexpression of Cbl-b in WEHI-231 mouse B cells resulted in the augmentation of BCR-induced Ca2+ mobilization. Cbl-b interacted with PLC-γ2 and helped the association of PLC-γ2 with Bruton's tyrosine kinase (Btk), as well as B cell linker protein (BLNK). Cbl-b was indispensable for Btk-dependent sustained increase in intracellular Ca2+. Both NH2-terminal tyrosine kinase-binding domain and COOH-terminal half region of Cbl-b were essential for its association with PLC-γ2 and the regulation of Ca2+ mobilization. These results demonstrate that Cbl-b positively regulates BCR-mediated Ca2+ signaling, most likely by influencing the Btk/BLNK/PLC-γ2 complex formation.
Constitutive Expression of the B7h Ligand for Inducible Costimulator on Naive B Cells Is Extinguished after Activation by Distinct B Cell Receptor and Interleukin 4 Receptor–mediated Pathways and Can Be Rescued by CD40 Signaling
Authors: Liang Linda , Porter Evelyn M. , Sha William C.
Published: July 2002

The recently described ligand–receptor pair, B7h–inducible costimulator (ICOS), is critical for germinal center formation and antibody responses. In contrast to the induced expression of the related costimulatory ligands B7.1 and B7.2, B7h is constitutively expressed on naive B cells and is surprisingly extinguished after antigen engagement and interleukin (IL)-4 cytokine signaling. Although signaling through both B cell receptor (BCR) and IL-4 receptor (R) converge on the extinction of B7h mRNA levels, BCR down-regulation occurs through Ca2+ mobilization, whereas IL-4R down-regulation occurs through a distinct Stat6-dependent pathway. During antigen-specific B cell activation, costimulation through CD40 signaling can reverse both BCR- and IL-4R–mediated B7h down-regulation. These data suggest that the CD40–CD40 ligand signaling pathway regulates B7h expression on activated B cells and may control whether antigen-activated B cells can express B7h and costimulate cognate antigen–activated T cells through ICOS.