bluuebunny/crossref_metadata_2025 huggingface dataset:
Variable Foreperiods and Temporal Discrimination
Authors: Grondin Simon , Rammsayer Thomas
Published: February 2003

Temporal judgements are often accounted for by a single-clock hypothesis. The output of such a clock is reported to depend on the allocation of attention. In the present series of experiments, the influence of attention on temporal information processing is investigated by systematic variations of the period preceding brief empty intervals to be judged. Two indicators of timing performance, temporal sensitivity, reflecting discrimination performance, and perceived duration served as dependent variables. Foreperiods ranged from 0.3 to 0.6 s in Experiments 1 to 4. When the foreperiod varied randomly from trial to trial, perceived duration was longer with increasing length of foreperiod (Experiments 1 and 3 with brief auditory markers and Experiment 4 with brief visual markers), an effect that disappeared with no trial-to-trial variations (Experiment 2). Longer foreperiods also enhanced performance on temporal discrimination of auditory empty intervals with a base duration of 100 ms (Experiments 1 and 5), whereas discrimination performance was unaffected for auditory intervals with a base duration of 500 ms (Experiment 3). The variable-foreperiod effect on perceived duration also held when foreperiods ranged from 0.6 to 1.5 s (Experiments 5—7). Findings suggest that foreperiods appear to effectively modulate attention mechanisms necessary for temporal information processing. However, alternative explanations such as assimilation or compatibility effects cannot be totally discarded.
Rethinking Temporal Contiguity and the Judgement of Causality: Effects of Prior Knowledge, Experience, and Reinforcement Procedure
Authors: Buehner Marc J. , May Jon
Published: February 2003

Time plays a pivotal role in causal inference. Nonetheless most contemporary theories of causal induction do not address the implications of temporal contiguity and delay, with the exception of associative learning theory. Shanks, Pearson, and Dickinson (1989) and several replications (Reed, 1992, 1999) have demonstrated that people fail to identify causal relations if cause and effect are separated by more than two seconds. In line with an associationist perspective, these findings have been interpreted to indicate that temporal lags universally impair causal induction. This interpretation clashes with the richness of everyday causal cognition where people apparently can reason about causal relations involving considerable delays. We look at the implications of cause-effect delays from a computational perspective and predict that delays should generally hinder reasoning performance, but that this hindrance should be alleviated if reasoners have knowledge of the delay. Two experiments demonstrated that (1) the impact of delay on causal judgement depends on participants’ expectations about the timeframe of the causal relation, and (2) the free-operant procedures used in previous studies are ill-suited to study the direct influences of delay on causal induction, because they confound delay with weaker evidence for the relation in question. Implications for contemporary causal learning theories are discussed.
The Role of Colour in Implicit and Explicit Memory Performance
Authors: Vernon David , Lloyd-Jones Toby J.
Published: February 2003

We present two experiments that examine the effects of colour transformation between study and test (from black and white to colour and vice versa, or from incorrectly coloured to correctly coloured and vice versa) on implicit and explicit measures of memory for diagnostically coloured natural objects (e.g., yellow banana). For naming and coloured-object decision (i.e., deciding whether an object is correctly coloured), there were shorter response times to correctly coloured-objects than to black-and-white and incorrectly coloured-objects. Repetition priming was equivalent for the different stimulus types. Colour transformation did not influence priming of picture naming, but for coloured-object decision priming was evident only for objects remaining the same from study to test. This was the case for both naming and coloured-object decision as study tasks. When participants were asked to consciously recognize objects that they had named or made coloured-object decisions to previously, whilst ignoring their colour, colour transformation reduced recognition efficiency. We discuss these results in terms of the flexibility of object representations that mediate priming and recognition.
Effects of Lexical Competition on Immediate Memory Span for Spoken Words
Authors: Goh Winston D. , Pisoni David B.
Published: February 2003

Current theories and models of the structural organization of verbal short-term memory are primarily based on evidence obtained from manipulations of features inherent in the short-term traces of the presented stimuli, such as phonological similarity. In the present study, we investigated whether properties of the stimuli that are not inherent in the short-term traces of spoken words would affect performance in an immediate memory span task. We studied the lexical neighbourhood properties of the stimulus items, which are based on the structure and organization of words in the mental lexicon. The experiments manipulated lexical competition by varying the phonological neighbourhood structure (i.e., neighbourhood density and neighbourhood frequency) of the words on a test list while controlling for word frequency and intra-set phonological similarity (family size). Immediate memory span for spoken words was measured under repeated and nonrepeated sampling procedures. The results demonstrated that lexical competition only emerged when a nonrepeated sampling procedure was used and the participants had to access new words from their lexicons. These findings were not dependent on individual differences in short-term memory capacity. Additional results showed that the lexical competition effects did not interact with proactive interference. Analyses of error patterns indicated that item-type errors, but not positional errors, were influenced by the lexical attributes of the stimulus items. These results complement and extend previous findings that have argued for separate contributions of long-term knowledge and short-term memory rehearsal processes in immediate verbal serial recall tasks.
Selective Interference with Verbal Short-Term Memory for Serial Order Information: A New Paradigm and Tests of a Timing-Signal Hypothesis
Authors: Henson Richard , Hartley Tom , Burgess Neil , Hitch Graham , Flude Brenda
Published: February 2003

Many recent computational models of verbal short-term memory postulate a separation between processes supporting memory for the identity of items and processes supporting memory for their serial order. Furthermore, some of these models assume that memory for serial order is supported by a timing signal. We report an attempt to find evidence for such a timing signal by comparing an “item probe” task, requiring memory for items, with a “list probe” task, requiring memory for serial order. Four experiments investigated effects of irrelevant speech, articulatory suppression, temporal grouping, and paced finger tapping on these two tasks. In Experiments 1 and 2, irrelevant speech and articulatory suppression had a greater detrimental effect on the list probe task than on the item probe task. Reaction time data indicated that the list probe task, but not the item probe task, induced serial rehearsal of items. Phonological similarity effects confirmed that both probe tasks induced phonological recoding of visual inputs. Experiment 3 showed that temporal grouping of items during list presentation improved performance on the list probe task more than on the item probe task. In Experiment 4, paced tapping had a greater detrimental effect on the list probe task than on the item probe task. However, there was no differential effect of whether tapping was to a simple or a complex rhythm. Overall, the data illustrate the utility of the item probe/list probe paradigm and provide support for models that assume memory for serial order and memory for items involve separate processes. Results are generally consistent with the timing-signal hypothesis but suggest further factors that need to be explored to distinguish it from other accounts.
Context-Sensitive Elemental Theory
Authors: Wagner Allan R.
Published: February 2003

My theories of associative learning, like those of N. J. Mackintosh and almost all learning theorists, have employed elemental representations of the stimuli involved. We must take notice when two important contributors to elemental theory, J. M. Pearce and W. K. Estes, find sufficient problems with the theory type to cause them to defect from it. I will describe some of the essential problems, concerning the substantial influence of context on learning and retrieval, characterize the different responses of Pearce and Estes, and, then, propose a variation on a recently developed elemental model that was similarly inspired. The resulting elemental theory has a close quantitative relationship to the “product-rule” of Estes and D. L. Medin, and may help us to rationalize how the same formal experimental design can sometimes produce results that favour the configural interpretation of Pearce and at other times the elemental interpretation of R. A. Rescorla and A. R. Wagner, as these have often been pitted against each other.
Representation and Discrimination on an Artificial Dimension
Authors: Suret Mark , McLaren I. P. L.
Published: February 2003

How we represent stimuli that are drawn from either natural (e.g., hue) or artificial (e.g., morphed face) dimensions is an issue of great significance for human learning. In this paper we outline a model of human dimensional representation in conjunction with some supporting empirical evidence for transfer along a continuum in humans (following Lawrence, 1952) and the first recorded case of transfer after outcome reversal with human subjects (following Mackintosh & Little, 1970). Our results support an elemental representation for dimensional stimuli in conjunction with algorithms that modulate both the salience and the associability of those representations.
Learned Associability and Associative Change in Human Causal Learning
Authors: Le Pelley M. E. , McLaren I. P. L.
Published: February 2003

The Mackintosh (1975) model of associative learning specifies that processing of both the cues presented on a trial and the outcome of that trial will interact to determine the amount of associative change undergone by a given cue. Experiments looking at the distribution of associative change among the elements of a reinforced compound in animal conditioning studies indicate that processing of the outcome of a trial does indeed influence associative change. The work reported here investigates the distribution of associative change among the elements of a reinforced compound in a human causal judgement paradigm, and it indicates that processing of the cues presented on a trial also plays a role in determining associative change (in terms of changes in the associability of cues as a result of experience). Taken in combination, these results provide good support for Mackintosh (1975) and the characterizations of both cue and outcome processing that it offers.
Learned Irrelevance: A Contemporary Overview
Authors: Bonardi Charlotte , Yann Ong Siaw
Published: February 2003

This article reviews the recent literature on the topic of learned irrelevance. It asks whether the retardation of subsequent conditioning produced by uncorrelated preexposure is indeed the result of the animal learning that a conditioned stimulus (CS) and unconditioned stimulus (US) are unrelated, or whether it is better explained either as a result of the context specificity of latent inhibition, or as some other artefact of the uncorrelated schedule employed. The conclusion is that there is as yet no good evidence to support the existence of a “genuine” learned irrelevance effect.
Absence of Overshadowing and Blocking between Landmarks and the Geometric Cues Provided by the Shape of a Test Arena
Authors: Hayward Andrew , McGregor Anthony , Good Mark A. , Pearce John M.
Published: February 2003

In three experiments rats were required to escape from a pool of water by swimming to a submerged platform. The position of the platform was determined by the shape of the pool, which was either rectangular or triangular. A landmark that was located on the surface of the pool near the platform failed to overshadow (Experiment 1) or block (Experiment 2) learning about the position of the platform with reference to the shape of the pool. Experiment 3 revealed a similar outcome with cues outside the pool, which could be used, in addition to the shape of the pool, to identify the location of the platform. These findings imply that theories of learning that assume that stimuli must compete with each other for the control that they acquire may not apply to spatial learning based on the shape of the environment.
H1‐Receptor activation triggers the endogenous nitric oxide signalling system in the rat submandibular gland
Authors: Borda Enri , Stranieri Graciela , Sterin-Borda Leonor
Published: February 2003

Background: Histamine is released from mast cells by immunologic and non‐immunologic stimuli during salivary gland inflammation, regulating salivary secretion. The receptor‐secretory mechanism has not been studied in detail.

Aims: The studies reported were directed toward elucidating signal transduction/second messenger pathways within the rat submandibular gland associated with 2‐thiazolylethylamine (ThEA)‐induced H1‐receptor responses.

Materials and methods: To assess the H1 receptor subtype expression in the rat submandibular gland, a radioligand binding assay was performed. The study also included inositolphosphates and cyclic GMP accumulation, protein kinase C and nitric oxide synthase activities, and amylase release.

Results: The histamine H1 receptor subtype is expressed on the rat submandibular gland with high‐affinity binding sites. The ThEA effect was associated with activation of phosphoinositide‐specific phospholipase C, translocation of protein kinase C, stimulation of nitric oxide synthase activity and increased production of cyclic GMP. ThEA stimulation of nitric oxide synthase and cyclic GMP was blunted by agents able to interfere with calcium movilization, while a protein kinase C inhibitor was able to stimulate ThEA action. On the other hand, ThEA stimulation evoked amylase release via the H1 receptor but was not followed by the L‐arginine/nitric oxide pathway activation.

Conclusions: These results suggest that, apart from the effect of ThEA on amylase release, it also appears to be a vasoactive chemical mediator that triggers vasodilatation, modulating the course of inflammation.
Gene expression of cell surface antigens in the early phase of murine influenza pneumonia determined by a cDNA expression array technique
Authors: Sakai Shinya , Mantani Naoki , Kogure Toshiaki , Ochiai Hiroshi , Shimada Yutaka , Terasawa Katsutoshi
Published: February 2003

Background: Influenza virus is a worldwide health problem with significant economic consequences. To study the gene expression pattern induced by influenza virus infection, it is useful to reveal the pathogenesis of influenza virus infection; but this has not been well examined, especially in vivo study.

Aims: To assess the influence of influenza virus infection on gene expression in mice, mRNA levels in the lung and tracheal tissue 48 h after infection were investigated by cDNA array analysis.

Methods: Four‐week‐old outbred, specific pathogen free strain, ICR female mice were infected by intra‐nasal inoculation of a virus solution under ether anesthesia. The mice were sacrificed 48 h after infection and the tracheas and lungs were removed. To determine gene expression, the membrane‐based microtechnique with an Atlas cDNA expression array (mouse 1.2 array II) was performed in accordance with the manual provided.

Results and conclusions: We focused on the expression of 46 mRNAs for cell surface antigens. Of these 46 mRNAs that we examined, four (CD1d2 antigen, CD39 antigen‐like 1, CD39 antigen‐like 3, CD68 antigen) were up‐regulated and one (CD36 antigen) was down‐regulated. Although further studies are required, these data suggest that these molecules play an important role in influenza virus infection, especially the phase before specific immunity.
Equilibrium and Disequilibrium in Walrasian and Neo-Walrasian Economics
Authors: De Vroey Michel
Published: February 2003

In his 1989 Cambridge doctoral dissertation,The Concept of Equilibrium in Neoclassical Theory, Franco Donzelli observed that, “The history of the neoclassical approach over the last one hundred and twenty years can be interpreted as a history of the relationship between instantaneous and stationary equilibrium models, on the one hand, and of the developments internal to either class of models, on the other” (Donzelli 1989, p. 31).
Anarchism, Socialism, and Social Reform
Authors: Clark John Bates
Published: February 2003

[First page missing from the archive] … embitterment against society; but anarchism assimilates to itself that hostility to law which naturally results from evil doing. The antipathy of the rogue for the halter reinforces this movement. It gathers to itself disreputable elements, and by its outbreaks moves society to resistance. It is a self-terminating movement.

Socialism appeals to better classes and has far more strength. Attack the state and you excite feelings of loyalty even among the disaffected classes; but attack the industrial system and appeal to the state, and you may have loyalty in your favor.
Which was the “Real” Kondratiev: 1925 or 1928?
Authors: Barnett Vincent
Published: February 2003

It is to be regretted that Nikolai Kondratiev's 1928 paper on long cycles—“The price dynamics of industrial and agricultural commodities: the theory of relative dynamics and conjuncture”—was omitted from the Pickering and Chatto English language edition of his works published in 1998. This is one of the two most important papers excluded from this edition, the other being the full text of his plan for agriculture and forestry, 1924–28. In response, this note discusses some modifications that occurred in Kondratiev's explanation of long cycles between 1925 and 1928, and puts to rest the suggestion that these changes might have taken place as the result of political factors rather than a genuine change of mind. I also counter some ofmy critics who have taken issue with my presentation of Kondratiev's conception of long cycles (most notably Jan Reijnders (2001) in this journal), and link this with a more general discussion of some of the methodological issues involved.
Adam Smith and All That
Authors: Creedy John
Published: February 2003

Students of economics no longer study the history of economic thought for the simple reason that it is much too difficult. It requires a lot of reading of books that do not have convenient introductions and summaries, and so it takes up far too much time. As a consequence, most economists are not familiar with the great names of the past and are unable to place modern analyses in historical, or any other, perspective.
Is all of the endoplasmic reticulum created equal? The effects of the heterogeneous distribution of endoplasmic reticulum Ca2+-handling proteins
Authors: Papp S. , Dziak E. , Michalak M. , Opas M.
Published: February 2003

The endoplasmic reticulum is a heterogeneous compartment with respect to the distribution of its Ca2+-handling proteins, namely the Ca2+-binding proteins, the Ca2+ pumps and the Ca2+ release channels. The nonuniform distribution of these proteins may explain the functional heterogeneity of the endoplasmic reticulum, such as the generation of spatially complex Ca2+ signals, Ca2+ homeostasis, and protein folding and quality control.
A tumor-associated β1 integrin mutation that abrogates epithelial differentiation control
Authors: Evans Richard D. , Perkins Vivienne C. , Henry Alistair , Stephens Paul E. , Robinson Martyn K. , Watt Fiona M.
Published: February 2003

SCC4 human keratinocytes are derived from a squamous cell carcinoma of the tongue and undergo very little spontaneous differentiation. Introduction of a wild-type β1 integrin subunit into SCC4 cells stimulates differentiation, suggesting either that the cells have a defect in the integrin signaling pathways that control differentiation or that the β1 subunit itself is defective. Here we describe a heterozygous mutation in the SCC4 β1 subunit. The mutation, T188I, maps to the I-like domain. It results in constitutive activation of ligand binding, irrespective of the partner α subunit, in solid phase assays with recombinant protein and in living cells. The mutation promotes cell spreading, but not proliferation, motility, or invasiveness. It results in sustained activation of Erk MAPK independent of cell spreading. When introduced into SCC4 keratinocytes, the wild-type β1 integrin stimulates differentiation, whereas the mutant is inactive. Activation of β1 integrins in normal keratinocytes also suppresses differentiation. These results establish, for the first time, mutation as a mechanism by which integrins can contribute to neoplasia, because the degree of differentiation in epithelial cancers is inversely correlated with prognosis. They also provide new insights into how integrins regulate keratinocyte differentiation.
The molecular function of Ase1p
Authors: Schuyler Scott C. , Liu Jenny Y. , Pellman David
Published: February 2003

The midzone is the domain of the mitotic spindle that maintains spindle bipolarity during anaphase and generates forces required for spindle elongation (anaphase B). Although there is a clear role for microtubule (MT) motor proteins at the spindle midzone, less is known about how microtubule-associated proteins (MAPs) contribute to midzone organization and function. Here, we report that budding yeast Ase1p is a member of a conserved family of midzone-specific MAPs. By size exclusion chromatography and velocity sedimentation, both Ase1p in extracts and purified Ase1p behaved as a homodimer. Ase1p bound and bundled MTs in vitro. By live cell microscopy, loss of Ase1p resulted in a specific defect: premature spindle disassembly in mid-anaphase. Furthermore, when overexpressed, Ase1p was sufficient to trigger spindle elongation in S phase–arrested cells. FRAP revealed that Ase1p has both a very slow rate of turnover within the midzone and limited lateral diffusion along spindle MTs. We propose that Ase1p functions as an MT cross-bridge that imparts matrix-like characteristics to the midzone. MT-dependent networks of spindle midzone MAPs may be one molecular basis for the postulated spindle matrix.
Changes in Chromatin Accessibility Across the GM-CSF Promoter upon T Cell Activation Are Dependent on Nuclear Factor κB Proteins
Authors: Holloway Adele F. , Rao Sudha , Chen Xinxin , Shannon M. Frances
Published: February 2003

Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a key cytokine in myelopoiesis and aberrant expression is associated with chronic inflammatory disease and myeloid leukemias. This aberrant expression is often associated with constitutive nuclear factor (NF)-κB activation. To investigate the relationship between NF-κB and GM-CSF transcription in a chromatin context, we analyzed the chromatin structure of the GM-CSF gene in T cells and the role of NF-κB proteins in chromatin remodeling. We show here that chromatin remodeling occurs across a region of the GM-CSF gene between −174 and +24 upon T cell activation, suggesting that remodeling is limited to a single nucleosome encompassing the proximal promoter. Nuclear NF-κB levels appear to play a critical role in this process. In addition, using an immobilized template assay we found that the ATPase component of the SWI/SNF chromatin remodeling complex, brg1, is recruited to the GM-CSF proximal promoter in an NF-κB–dependent manner in vitro. These results suggest that chromatin remodeling across the GM-CSF promoter in T cells is a result of recruitment of SWI/SNF type remodeling complexes by NF-κB proteins binding to the CD28 response region of the promoter.
Eukaryotic genome evolution: rearrangement and coevolution of compartmentalized genetic information
Authors: Herrmann Reinhold G. , Maier Rainer M. , Schmitz-Linneweber Christian
Published: February 2003

The plant cell operates with an integrated, compartmentalized genome consisting of nucleus/cytosol, plastids and mitochondria that, in its entirety, is regulated in time, quantitatively, in multicellular organisms and also in space. This genome, as do genomes of eukaryotes in general, originated in endosymbiotic events, with at least three cells, and was shaped phylogenetically by a massive and highly complex restructuring and intermixing of the genetic potentials of the symbiotic partners and by lateral gene transfer. This was accompanied by fundamental changes in expression signals in the entire system at almost all regulatory levels. The gross genome rearrangements contrast with a highly specific compartmental interplay, which becomes apparent in interspecific nuclear-plastid cybrids or hybrids. Organelle exchanges, even between closely related species, can greatly disturb the intracellular genetic balance (‘hybrid bleaching’), which is indicative of compartmental coevolution and is of relevance for speciation processes. The photosynthetic machinery of plastids, which is embedded in that genetic machinery, is an appealing model to probe into genomic and organismic evolution and to develop functional molecular genomics. We have studied the reciprocalAtropa belladonna-Nicotiana tabacumcybrids, which differ markedly in their phenotypes, and found that transcriptional and post-transcriptional processes can contribute to genome/plastome incompatibility. Allopolyploidy can influence this phenomenon by providing an increased, cryptic RNA editing potential and the capacity to maintain the integrity of organelles of different taxonomic origins.
Coordination of plastid and nuclear gene expression
Authors: Gray John C. , Sullivan James A. , Wang Jun-Hui , Jerome Cheryl A. , MacLean Daniel
Published: February 2003

The coordinated expression of genes distributed between the nuclear and plastid genomes is essential for the assembly of functional chloroplasts. Although the nucleus has a pre–eminent role in controlling chloroplast biogenesis, there is considerable evidence that the expression of nuclear genes encoding photosynthesis–related proteins is regulated by signals from plastids. Perturbation of several plastid–located processes, by inhibitors or in mutants, leads to decreased transcription of a set of nuclear photosynthesis–related genes. Characterization of arabidopsis
gun
(
genomes uncoupled
) mutants, which express nuclear genes in the presence of norflurazon or lincomycin, has provided evidence for two separate signalling pathways, one involving tetrapyrrole biosynthesis intermediates and the other requiring plastid protein synthesis. In addition, perturbation of photosynthetic electron transfer produces at least two different redox signals, as part of the acclimation to altered light conditions. The recognition of multiple plastid signals requires a reconsideration of the mechanisms of regulation of transcription of nuclear genes encoding photosynthesis–related proteins.
Evolution of photosynthetic prokaryotes: a maximum-likelihood mapping approach
Authors: Raymond Jason , Zhaxybayeva Olga , Gogarten J. Peter , Blankenship Robert E.
Published: February 2003

Reconstructing the early evolution of photosynthesis has been guided in part by the geological record, but the complexity and great antiquity of these early events require molecular genetic techniques as the primary tools of inference. Recent genome sequencing efforts have made whole genome data available from representatives of each of the five phyla of bacteria with photosynthetic members, allowing extensive phylogenetic comparisons of these organisms. Here, we have undertaken whole genome comparisons using maximum likelihood to compare 527 unique sets of orthologous genes from all five photosynthetic phyla. Substantiating recent whole genome analyses of other prokaryotes, our results indicate that horizontal gene transfer (HGT) has played a significant part in the evolution of these organisms, resulting in genomes with mosaic evolutionary histories. A small plurality phylogenetic signal was observed, which may be a core of remnant genes not subject to HGT, or may result from a propensity for gene exchange between two or more of the photosynthetic organisms compared.
The redox protein construction kit: pre-last universal common ancestor evolution of energy-conserving enzymes
Authors: Baymann Frauke , Lebrun Evelyne , Brugna Myriam , Schoepp–Cothenet Barbara , Giudici–Orticoni Marie–Thérèse , Nitschke Wolfgang
Published: February 2003

Genome analyses and the resolution of three–dimensional structures have provided evidence in recent years for hitherto unexpected family relationships between redox proteins of very diverse enzymes involved in bioenergetic electron transport. Many of these enzymes appear in fact to be constructed from only a limited set of building blocks. Phylogenetic analysis of selected units from this ‘redox enzyme construction kit’ indicates an origin for several prominent bioenergetic enzymes that is very early, lying before the divergence of Bacteria and Archaea. Possible scenarios for the early evolution of selected complexes are proposed based on the obtained tree topologies.
Redox and light regulation of gene expression in photosynthetic prokaryotes
Authors: Bauer Carl , Elsen Sylvie , Swem Lee R. , Swem Danielle L. , Masuda Shinji
Published: February 2003

All photosynthetic organisms control expression of photosynthesis genes in response to alterations in light intensity as well as to changes in cellular redox potential. Light regulation in plants involves a well–defined set of red– and blue–light absorbing photoreceptors called phytochrome and cryptochrome. Less understood are the factors that control synthesis of the plant photosystem in response to changes in cellular redox. Among a diverse set of photosynthetic bacteria the best understood regulatory systems are those synthesized by the photosynthetic bacterium
Rhodobacter capsulatus
. This species uses the global two–component signal transduction cascade, RegB and RegA, to anaerobically de–repress anaerobic gene expression. Under reducing conditions, the phosphate on RegB is transferred to RegA, which then activates genes involved in photosynthesis, nitrogen fixation, carbon fixation, respiration and electron transport. In the presence of oxygen, there is a second regulator known as CrtJ, which is responsible for repressing photosynthesis gene expression. CrtJ responds to redox by forming an intramolecular disulphide bond under oxidizing, but not reducing, growth conditions. The presence of the disulphide bond stimulates DNA binding activity of the repressor. There is also a flavoprotein that functions as a blue–light absorbing anti–repressor of CrtJ in the related bacterial species
Rhodobacter sphaeroides
called AppA. AppA exhibits a novel long–lived photocycle that is initiated by blue–light absorption by the flavin. Once excited, AppA binds to CrtJ thereby inhibiting the repressor activity of CrtJ. Various mechanistic aspects of this photocycle will be discussed.
The function of genomes in bioenergetic organelles
Authors: Allen John F.
Published: February 2003

Mitochondria and chloroplasts are energy-transducing organelles of the cytoplasm of eukaryotic cells. They originated as bacterial symbionts whose host cells acquired respiration from the precursor of the mitochondrion, and oxygenic photosynthesis from the precursor of the chloroplast. The host cells also acquired genetic information from their symbionts, eventually incorporating much of it into their own genomes. Genes of the eukaryotic cell nucleus now encode most mitochondrial and chloroplast proteins. Genes are copied and moved between cellular compartments with relative ease, and there is no obvious obstacle to successful import of any protein precursor from the cytosol. So why are any genes at all retained in cytoplasmic organelles? One proposal is that these small but functional genomes provide a location for genes that is close to, and in the same compartment as, their gene products. This co-location facilitates rapid and direct regulatory coupling. Redox control of synthesisde novois put forward as the common property of those proteins that must be encoded and synthesized within mitochondria and chloroplasts. This testable hypothesis is termed CORR, forco-location forredoxregulation. Principles, predictions and consequences of CORR are examined in the context of competing hypotheses and current evidence.
C-type cytochromes: diverse structures and biogenesis systems pose evolutionary problems
Authors: Allen James W. A. , Daltrop Oliver , Stevens Julie M. , Ferguson Stuart J.
Published: February 2003

C
-type cytochromes are a structurally diverse group of haemoproteins, which are related by the occurrence of haem covalently attached to a polypeptide via two thioether bonds formed by the vinyl groups of haem and cysteine side chains in a CXXCH peptide motif. Remarkably, three different post-translational systems for forming these cytochromes have been identified. The evolution of both the proteins themselves and the biogenesis systems poses many questions to which answers are currently being sought. In this article we review the progress that has been made in understanding the need for covalent attachment of haem to proteins in cytochromes
c
and the complex systems involved in their formation.
StarLogo under the hood and in the classroom
Authors: Klopfer Eric , Begel Andrew
Published: February 2003

StarLogo is a computer modeling tool that empowers students to understand the world through the design and creation of complex systems models. StarLogo enables students to program software creatures to interact with one another and their environment, and study the emergent patterns from these interactions. Building an easy‐to‐understand, yet powerful tool for students required a great deal of thought about the design of the programming language, environment, and its implementation. The salient features are StarLogo's great degree of transparency (the capability to see how a simulation is built), its support to let students create their own models (not just use models built by others), its efficient implementation (supporting simulations with thousands of independently executing creatures on desktop computers), and its flexible and simple user interface (which enables students to interact dynamically with their simulation during model testing and validation). The resulting platform provides a uniquely accessible tool that enables students to become full‐fledged practitioners of modeling. In addition, we describe the powerful insights and deep scientific understanding that students have developed through the use of StarLogo.
Exploring cellular automata with MCell
Authors: Wo´jtowicz Mirek
Published: February 2003

Discusses MCell (version 4.2), a popular cellular automata explorer for Windows™. Gives a brief overview of the program, demonstrates its capabilities and shows possible applications, presents the library of collected rules and patterns, and explains how user‐defined extensions can be programmed.
On wonder and betrayal: creating artificial life software to meet aesthetic goalsaland@csse.monash.edu.au
Authors: Dorin Alan
Published: February 2003

Examines the way in which works of generative computer‐based art, specifically those which reference Artificial Life, may gain aesthetic appeal through instilling a sense of “wonder” in a viewer. This idea is examined from its roots in our fascination with natural phenomena and the sublime, through its representation in terms of the basic elements of drawing off and on‐screen, and into the computational realm in which Artificial Life software finds its form. Further explores the artistic potential of the approach which takes computationally‐realized works with a single level of emergent organizational structure, to those capable of giving rise to interactions built yet again on top of these in an ever‐increasing hierarchy of added complexity. The difficulties of coding such software systems successfully will be briefly discussed.
Aesthetic selection of morphogenetic art forms
Authors: Thomas Dale
Published: February 2003

Describes a system designed for public use as an “edutainment” system. It allows a user to direct the evolution of three‐dimensional shapes as a form of interactive art. The objects under evolution are defined by artificial DNA, which ultimately defines their final form and characteristics through an intermediate growth phase using interacting chemical reactions. The forms are part of a small population and the fitness is entirely defined by the user. The evolution continues and allows the user to design objects interactively or simply to explore the range of possible forms of the system.
Nerve garden: germinating biological metaphors in net‐based virtual worlds
Authors: Damer Bruce , Marcelo Karen , Revi Frank
Published: February 2003

Nerve Garden is a biologically‐inspired multi‐user collaborative 3D virtual world available to a wide Internet audience. The project combines a number of methods and technologies, including L‐systems, Java, cellular automata, and virtual reality modeling language. Nerve Garden is a work in progress designed to provide a compelling experience of a virtual terrarium which exhibits properties of growth, decay and energy transfer reminiscent of a simple ecosystem. The goals of the Nerve Garden project are to create an on‐line “collaborative artificial life laboratory” which can be extended by a large number of users for purposes of education and research.
Validating components of a falls risk assessment instrument
Authors: Donoghue Judith , Graham Jenny , Gibbs Julie , Mitten‐Lewis Suzanne , Blay Nicole
Published: February 2003

Falls are a significant burden on the Australian health care budget and can result in loss of personal independence, injury or death. A sustained high rate of inpatient falls in a 550‐bed acute care hospital has made it imperative for nurses to identify patients at highest risk, in order to implement preventive interventions. This study examined the prevalence of “intrinsic high risk” characteristics identified by the literature in people who fell during hospitalisation, to confirm the validity of these predictors in detecting risk. Over ten weeks 91 inpatients fell (total 118 falls) and were assessed for intrinsic risk factors. Most prevalent was impaired ambulatory status resulting in balance instability. Other high prevalence factors included cognitive impairment and age > 75. Commonly cited factors, such as urinary or faecal incontinence, medications and history of prior falls, were found less frequently. No significant differences in risk factors by gender were identified.
The staff’s views on what’s the job – the starting point for quality improvement in health care
Authors: Lindberg Eva , Rosenqvist Urban
Published: February 2003

Describes 12 members of staff’s views of their job and tasks in an intensive care unit of a middle‐sized Swedish hospital. Open‐ended questions were asked and the interviews were analysed using thematic technique. The character of the work and the work tasks was the key variable in the analysis. The participants thought of intensive care as turbulent and ambiguous, powerful but also menacing and a concept comprised of a dichotomy of fundamental values. The work task of the participants was conceptualised in terms of managing the health status of the patient, seeking to appreciate the patient’s needs and ensuring that the staff worked harmoniously and effectively as a team. Speculates that the existence of a real dichotomy in fundamental values might be caused by the difficult medical reality on the ward. The study confirms a necessity for a two‐dimensional quality system where the deeper dimension deals with the disparate set of meaning status in the future perspective.
The conserved Glu‐60 residue in Thermoanaerobacter brockii alcohol dehydrogenase is not essential for catalysis
Authors: Kleifeld Oded , Shi Shu Ping , Zarivach Raz , Eisenstein Miriam , Sagi Irit
Published: February 2003

Glu‐60 of the zinc‐dependent Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) is a strictly conserved residue in all members of the alcohol dehydrogenase (ADH) family. Unlike most other ADHs, the crystal structures of TbADH and its analogs, ADH from Clostridium beijerinckii (CbADH), exhibit a unique zinc coordination environment in which this conserved residue is directly coordinated to the catalytic zinc ion in the native form of the enzymes. To explore the role of Glu‐60 in TbADH catalysis, we have replaced it by alanine (E60A‐TbADH) and aspartate (E60D‐TbADH). Steady‐state kinetic measurements show that the catalytic efficiency of these mutants is only four‐ and eightfold, respectively, lower than that of wild‐type TbADH. We applied X‐ray absorption fine‐structure (EXAFS) and near‐UV circular dichroism to characterize the local environment around the catalytic zinc ion in the variant enzymes in their native, cofactor‐bound, and inhibited forms. We show that the catalytic zinc site in the studied complexes of the variant enzymes exhibits minor changes relative to the analogous complexes of wild‐type TbADH. These moderate changes in the kinetic parameters and in the zinc ion environment imply that the Glu‐60 in TbADH does not remain bound to the catalytic zinc ion during catalysis. Furthermore, our results suggest that a water molecule replaces this residue during substrate turnover.
Structural basis for sequential displacement of Ca2+ by Yb3+ in a protozoan EF‐hand calcium binding protein
Authors: Atreya Hanudatta S. , Mukherjee Sulakshana , Chary Kandala V.R. , Lee Yong‐Min , Luchinat Claudio
Published: February 2003

We have studied the displacement of Ca2+by the trivalent lanthanide ions (Yb3+) in a protozoan (Entamoeba histolytica) Ca2+‐binding protein (EhCaBP), by NMR and thermodynamics. We have demonstrated, for the first time, how one can use in a combined fashion the utility of NMR and thermodynamics to have an insight to the relative binding specificities/affinity between Ca2+ and Yb3+. As revealed by the titration experiments, Yb3+ displaces Ca2+ from the four metal binding sites present in EhCaBP in a sequential manner. The study provides a structural origin for such a sequential Ca2+ displacement by Yb3+ in EhCaBP.
Interplay between hydrophobic cluster and loop propensity in β‐hairpin formation: A mechanistic study
Authors: Colombo Giorgio , De Mori Giacomo M.S. , Roccatano Danilo
Published: February 2003

We investigated the structural determinants of the stability of a designed β‐hairpin containing a natural hydrophobic cluster from the protein GB1 and a D‐Pro‐Gly turn forming sequence. The results of our simulations shed light on the factors leading to an ordered secondary structure in a model peptide: in particular, the importance of the so‐called diagonal interactions in forming a stable hydrophobic nucleus in the β‐hairpin, together with the more obvious lateral interactions, is examined. With the use of long timescale MD simulations in explicit water, we show the role of diagonal interactions in driving the peptide to the correct folded structure (formation of the hydrophobic core with Trp 2, Tyr 4, and Phe 9 in the first stages of refolding) and in keeping it in the ensemble of folded conformations. The combination of the stabilizing effects of the D‐Pro‐Gly turn sequence and of the hydrophobic nucleus formation thus favors the attainment of an ordered secondary structure compatible with the one determined experimentally. Moreover, our data underline the importance of the juxtapositions of the side chains of amino acids not directly facing each other in the three‐dimensional structure. The combination of these interactions forces the peptide to sample a nonrandom portion of the conformational space, as can be seen in the rapid collapse to an ordered structure in the refolding simulation, and shows that the unfolded state can be closely correlated to the folded ensemble of structures, at least in the case of small model peptides.
Probing the structure of falcipain‐3, a cysteine protease from Plasmodium falciparum: Comparative protein modeling and docking studies
Authors: Sabnis Yogesh A. , Desai Prashant V. , Rosenthal Philip J. , Avery Mitchell A.
Published: February 2003

Increasing resistance of malaria parasites to conventional antimalarial drugs is an important factor contributing to the persistence of the disease as a major health threat. The ongoing search for novel targets has resulted in identification and expression of several enzymes including cysteine proteases that are implicated in hemoglobin degradation. Falcipain‐2 and falcipain‐3 are considered to be the two principal cysteine proteases in this degradation, and hence, are potential drug targets. A homology model of falcipain‐3 was built and validated by various structure/geometry verification tools as well as docking studies of known substrates. The correlation coefficient of 0.975 between interaction energies and Km values of these substrates provided additional support for the model. On comparison with the previously reported falcipain‐2 homology model, the currently constructed falcipain‐3 structure showed important differences between the S2 pockets that might explain the variations in the Km values of various substrates for these enzymes. Further, docking studies also provided insight into possible binding modes and interactions of ligands with falcipain‐3. Results of the current study could be employed in de novo drug design leading to development of new antimalarial agents.
Asparagine 285 plays a key role in transition state stabilization in rabbit muscle creatine kinase
Authors: Borders Charles L. , MacGregor Katherine M. , Edmiston Paul L. , Gbeddy Elikem R.K. , Thomenius Michael J. , Mulligan Guy B. , Snider Mark J.
Published: February 2003

To explore the possibility that asparagine 285 plays a key role in transition state stabilization in phosphagen kinase catalysis, the N285Q, N285D, and N285A site‐directed mutants of recombinant rabbit muscle creatine kinase (rmCK) were prepared and characterized. Kinetic analysis of phosphocreatine formation showed that the catalytic efficiency of each N285 mutant was reduced by approximately four orders of magnitude, with the major cause of activity loss being a reduction in kcat in comparison to the recombinant native CK. The data for N285Q still fit a random‐order, rapid‐equilibrium mechanism, with either MgATP or creatine binding first with affinities very nearly equal to those for native CK. However, the affinity for the binding of the second substrate is reduced approximately 10‐fold, suggesting that addition of a single methylene group at position 285 disrupts the symphony of substrate binding. The data for the N285A mutant only fit an ordered binding mechanism, with MgATP binding first. Isosteric replacement to form the N285D mutant has almost no effect on the KM values for either creatine or MgATP, thus the decrease in activity is due almost entirely to a 5000‐fold reduction in kcat. Using the quenching of the intrinsic CK tryptophan fluorescence by added MgADP (Borders et al. 2002), it was found that, unlike native CK, none of the mutants have the ability to form a quaternary TSAC. We use these data to propose that asparagine 285 indeed plays a key role in transition state stabilization in the reaction catalyzed by creatine kinase and other phosphagen kinases.