bluuebunny/crossref_metadata_2025 huggingface dataset:
Arginine 60 in the ArsC arsenate reductase of E. coli plasmid R773 determines the chemical nature of the bound As(III) product
Authors: DeMel Srini , Shi Jin , Martin Philip , Rosen Barry P. , Edwards Brian F.P.
Published: August 2004

Arsenic is a ubiquitous environmental toxic metal. Consequently, organisms detoxify arsenate by reduction to arsenite, which is then excreted or sequestered. The ArsC arsenate reductase from Escherichia coli plasmid R773, the best characterized arsenic‐modifying enzyme, has a catalytic cysteine, Cys 12, in the active site, surrounded by an arginine triad composed of Arg 60, Arg 94, and Arg 107. During the reaction cycle, the native enzyme forms a unique monohydroxyl Cys 12‐thiol‐arsenite adduct that contains a positive charge on the arsenic. We hypothesized previously that this unstable intermediate allows for rapid dissociation of the product arsenite. In this study, the role of Arg 60 in product formation was evaluated by mutagenesis. A total of eight new structures of ArsC were determined at resolutions between 1.3 Å and 1.8 Å, with Rfree values between 0.18 and 0.25. The crystal structures of R60K and R60A ArsC equilibrated with the product arsenite revealed a covalently bound Cys 12‐thiol‐dihydroxyarsenite without a charge on the arsenic atom. We propose that this intermediate is more stable than the monohydroxyarsenite intermediate of the native enzyme, resulting in slow release of product and, consequently, loss of activity.
Lipid binding in rice nonspecific lipid transfer protein‐1 complexes from Oryza sativa
Authors: Cheng Hui‐Chun , Cheng Pei‐Tsung , Peng Peiyu , Lyu Ping‐Chiang , Sun Yuh‐Ju
Published: August 2004

Nonspecific lipid transfer proteins (nsLTPs) facilitate the transfer of phospholipids, glycolipids, fatty acids and steroids between membranes, with wide‐ranging binding affinities. Three crystal structures of rice nsLTP1 from Oryza sativa, complexed with myristic (MYR), palmitic (PAL) or stearic acid (STE) were determined. The overall structures of the rice nsLTP1 complexes belong to the four‐helix bundle folding with a long C‐terminal loop. The nsLTP1–MYR and the nsLTP1–STE complexes bind a single fatty acid while the nsLTP1–PAL complex binds two molecules of fatty acids. The C‐terminal loop region is elastic in order to accommodate a diverse range of lipid molecules. The lipid molecules interact with the nsLTP1‐binding cavity mainly with hydrophobic interactions. Significant conformational changes were observed in the binding cavity and the C‐terminal loop of the rice nsLTP1 upon lipid binding.
Delineation and analysis of the conceptual data model implied by the “IUPAC Recommendations for Biochemical Nomenclature”
Authors: Fox‐Erlich Susan , Martyn Timothy O. , Ellis Heidi J.C. , Gryk Michael R.
Published: August 2004

Computational analysis of the bonding, geometric, and topological relationships within proteins typically takes on the order of hours, mainly devoted to the writing of scripts and code to correctly parse the data. The Structured Query Language (SQL) built into modern database management systems eliminates the need for data parsing, effectively reducing the analysis time to seconds. To this end, we have formulated a conceptual data model (CDM) for proteins based on the IUPAC recommendations for biochemical nomenclature. This conceptual data model makes explicit the inherent bonding relationships between the atoms of a protein, as well as the geometric (bond angle and torsion angle) and topological (chirality) relationships between the bonds. The validity of the CDM has been tested with a reduced implementation using commercial database software. The ease in both populating the database with data from the Protein Data Bank and formulating/executing queries supports the correctness of the model. The ability to conduct truly interactive analyses of protein structure is essential to fully capitalize on the explosion in postgenomic protein structure data.
Stabilizing roles of residual structure in the empty heme binding pockets and unfolded states of microsomal and mitochondrial apocytochrome b5
Authors: Cowley Aaron B. , Rivera Mario , Benson David R.
Published: August 2004

The microsomal (Mc) and mitochondrial (OM) isoforms of mammalian cytochrome b5are the products of different genes, which likely arose via duplication of a primordial gene and subsequent functional divergence. Despite sharing essentially identical folds, heme‐polypeptide interactions are stronger in OM b5s than in Mc b5s due to the presence of two conserved patches of hydrophobic amino acid side chains in the OM heme binding pockets. This is of fundamental interest in terms of understanding heme protein structure–function relationships, because stronger heme–polypeptide interactions in OM b5s in comparison to Mc b5s may represent a key source of their more negative reduction potentials. Herein we provide evidence that interactions amongst the amino acid side chains contributing to the hydrophobic patches in rat OM (rOM) b5persist when heme is removed, rendering the empty heme binding pocket of rOM apo‐b5more compact and less conformationally dynamic than that in bovine Mc (bMc) apo‐b5. This may contribute to the stronger heme binding by OM apo‐b5by reducing the entropic penalty associated with polypeptide folding. We also show that when bMc apo‐b5unfolds it adopts a structure that is more compact and contains greater nonrandom secondary structure content than unfolded rOM apo‐b5. We propose that a more robust β‐sheet in Mc apo‐b5s compensates for the absence of the hydrophobic packing interactions that stabilize the heme binding pocket in OM apo‐b5s.
Crystal structure of a dimeric form of streptococcal pyrogenic exotoxin A (SpeA1)
Authors: Baker Matthew D. , Gendlina Inessa , Collins Carleen M. , Acharya K. Ravi
Published: August 2004

Streptococcal pyrogenic exotoxin A (SpeA1) is a bacterial superantigen associated with scarlet fever and streptococcal toxic shock syndrome (STSS). SpeA1 is found in both monomeric and dimeric forms, and previous work suggested that the dimer results from an intermolecular disulfide bond between the cysteines at positions 90 of each monomer. Here, we present the crystal structure of the dimeric form of SpeA1. The toxin crystallizes in the orthorhombic space group P212121, with two dimers in the crystallographic asymmetric unit. The final structure has a crystallographic R‐factor of 21.52% for 7248 protein atoms, 136 water molecules, and 4 zinc atoms (one zinc atom per molecule). The implications of SpeA1 dimer on MHC class II and T‐cell receptor recognition are discussed.
Assimilation, Faith and Identity: Educational Implications of Change and Continuity
Authors: Johnson Helen
Published: August 2004

In England, the presence of an established church places its adherents within the social mainstream. Other religious groups have been tolerated though suffering social and educational disadvantages. With the passage of time through the nineteenth and twentieth centuries, minority religious groups such as Irish Catholics have been assimilated into the host culture, and allowed to have their own schools.

However, it would appear that contemporary movements of people to the United Kingdom have retained loyalties not only to their own religion, but, in some instances to their own language, which they perceive as a vital element of their own culture and identity. Demands for schools, within the state‐funded system, for minority religious groups have not lessened. As faith schools in England increase in number, their role in a multicultural society becomes increasingly problematic. Lessons about changing models of assimilation and identity can be learnt from a brief review of the historic Irish Catholic experience that, in turn, can illuminate the current experience of a Greek Orthodox school in south London.
Whose Faith? What Feeling? Whose Identity?
Authors: Glackin Maureen
Published: August 2004

Faith, feeling and identity look to be essential ingredients in personal growth, but what do they mean ‘on the ground’? Drawing on the results of a survey of teachers and school chaplains, and on her own experiences as a student, teacher and chaplain in Catholic education, Maureen Glackin explores some of the questions which face schools seeking to promote spiritual development and personal identity. Contrasting a model which emphasizes received doctrine and traditional authority with one which sees the spiritual journey as an open‐ended, shared encounter, she argues that teachers must be spiritually aware and open to possibilities for their own spiritual growth if they are to be able to help their students develop in these ways.
High‐Technology Service Innovation Success: A Decision‐Making Perspective
Authors: Van Riel Allard C. R. , Lemmink Jos , Ouwersloot Hans
Published: August 2004

Successful innovation is crucial for firm survival in high‐technology service industries. This article reports on an empirical study, exploring internal innovation success factors—success factors associated with the innovating firm's competencies—by taking a decision‐making perspective. The likelihood of innovation success is associated with the systematic reduction of decision‐making uncertainty, as a result of organizational information gathering, diffusion, and processing activities. Effects of interfirm differences are investigated in the new service development phase of the innovation process. Cross‐sectional data were collected about 251 innovation projects from companies in Europe, the United States, and Japan. Innovation success is found to be related positively and directly to how well informed and knowledgeable decision‐makers are. Furthermore, the study provides evidence that a market orientation contributes as an internal success factor: An organizational climate favorable to information sharing powerfully mediates the positive effects of intelligence gathering with respect to customers and technology. The effects of competitor orientation carry a negative sign, and managerial seniority appears not to play a major role in this turbulent business. Managerial and research implications are provided.
Successful treatment of oesophageal candidiasis by micafungin: a novel systemic antifungal agent
Authors: Pettengell K. , Mynhardt J. , Kluyts T. , Lau W. , Facklam D. , Buell D. ,   the FK463 South African Study Group
Published: August 2004

Aim : To determine the minimum effective dose and safety of micafungin in the treatment of HIV‐related oesophageal candidiasis.

Method : A total of 120 patients were enrolled in this open label study of the effects of daily 1 h infusions of micafungin on endoscopically proven fungal oesophagitis. Patients were randomly assigned to receive 12.5, 25, 50, 75 and 100 mg of micafungin daily. Response was evaluated clinically and endoscopically.

Results : The protocol defined minimum effective dose of micafungin was 12.5 mg. The percentage of patients experiencing clearing of physical signs and symptoms showed a dose–response relationship and reached 94.7% in the 100 mg dose group. All patients in the 50, 75 and 100 mg dose groups achieved an endoscopically verified improvement in oesophagitis. Adverse effects of micafungin were generally mild and not dose‐related. No serious renal, hepatic or drug‐related infusion reactions were encountered.

Conclusion : Micafungin was found to be effective, well‐tolerated and safe. The minimum effective dose was found to be 12.5 mg and a significant linear trend in the successful treatment of oesophageal candidiasis was observed across the doses used with 75 and 100 mg dose levels achieving high rates of clinical and endoscopic cure.
Erythropoietin increases platelet reactivity and platelet counts in patients with alcoholic liver cirrhosis: a randomized, double‐blind, placebo‐controlled study
Authors: Homoncik M. , Jilma‐Stohlawetz P. , Schmid M. , Ferlitsch A. , Peck‐Radosavljevic M.
Published: August 2004

Background: Patients with liver cirrhosis have a complex haemostasis disturbance including thrombocytopenia and abnormal bleeding time. Erythropoietin is the primary stimulator for erythrocyte production and also induces megakaryocyte formation. In healthy men erythropoietin increased platelet count and platelet reactivity.

Aim: As patients with liver cirrhosis often undergo invasive procedures, we were interested to study whether erythropoietin could improve platelet function in addition to thrombocytopenia.

Methods: In total, 22 thrombocytopenic (platelet counts < 120 g/L) patients with alcoholic liver cirrhosis received either 100 IE/kg erythropoietin or placebo on days 1, 3 and 5 in a 2:1 randomized, placebo‐controlled double‐blind fashion. Platelet counts and platelet reactivity (activator‐stimulated expression of P‐selectin on platelets measured by flow cytometry) were determined on study days 1, 3, 5 and 9.

Results: Median platelet count was 80 g/L which is borderline for major elective surgical interventions. Baseline values were not different between groups (P > 0.05). Treatment with erythropoietin increased platelet count by 25% (P = 0.01) and platelet reactivity twofold (P < 0.01) vs. baseline. The increase in platelet count vs. baseline was more pronounced in patients with platelet counts <80 g/L. No significant effect was observed in the placebo group.

Conclusions: Treatment with erythropoietin significantly increased platelet counts and platelet reactivity in patients with alcoholic liver cirrhosis. Preoperative treatment with erythropoietin is therefore expected to yield higher platelet levels and better platelet function.
The hepatotoxicity of non‐steroidal anti‐inflammatory drugs
Authors: Rubenstein J. H. , Laine L.
Published: August 2004

Background : Non‐steroidal anti‐inflammatory drugs have been implicated in reports of liver injury. However, the precise risk of non‐steroidal anti‐inflammatory drugs for this rare complication is unknown.

Aim : To review systematically the published literature of population‐based epidemiological studies reporting the incidence or comparative risk of non‐steroidal anti‐inflammatory drugs for liver injury resulting in clinically significant events, defined as hospitalization or death.

Data extraction : Duplicate extraction of the methodological quality, design, source, population, years studied, particular non‐steroidal anti‐inflammatory drugs studied, definitions, patient counts and follow‐up, and the adjustment for confounders.

Results : Seven articles met inclusion criteria. The comparative risk of liver injury resulting in hospitalization for current non‐steroidal anti‐inflammatory drug users compared with past non‐steroidal anti‐inflammatory drug users ranged from 1.2 to 1.7, but none was statistically significant. The incidence of liver injury resulting in hospitalization ranged from 3.1 to 23.4/100 000 patient‐years of current use of non‐steroidal anti‐inflammatory drugs, with an excess risk compared with past non‐steroidal anti‐inflammatory drugs users of 4.8–8.6/100 000 patient‐years of exposure. There were zero deaths from liver injury associated with non‐steroidal anti‐inflammatory drugs use in over 396 392 patient‐years of cumulative exposure.

Conclusion : These findings allow for the possibility of a small increase in the risk of clinically relevant hepatotoxicity with non‐steroidal anti‐inflammatory drugs use, but do not document that such a risk occurs.
Treatment of gastro‐oesophageal reflux disease with rabeprazole in primary and secondary care: does Helicobacter pylori infection affect proton pump inhibitor effectiveness?
Authors: de Wit N. J. , de Boer W. A. , Geldof H. , Hazelhoff B. , Bergmans P. , Tytgat G. N. J. , Smout A. J. P. M.
Published: August 2004

Background : The presence of the gastric pathogen, Helicobacter pylori influences acid suppression by proton pump inhibitors and treatment outcome in patients with gastro‐oesophageal reflux disease.

Aim : To determine the influence of H. pylori infection on effectiveness of rabeprazole in primary and secondary care patients with gastro‐oesophageal reflux disease.

Methods : Patients from primary and secondary care centres with uninvestigated gastro‐oesophageal reflux disease (based on symptoms only) and investigated gastro‐oesophageal reflux disease (endoscopically confirmed oesophagitis or endoscopy‐negative reflux disease) were tested for H. pylori and treated with rabeprazole 20 mg once daily for 4–8 weeks in a non‐randomized, multicentre, open‐label study. Primary end‐point for treatment effectiveness was complete resolution of both heartburn and acid regurgitation at 4–8 weeks; secondary end‐point was quality of life as registered with the Psychological General Well‐being Index.

Results : Data of 1787 patients could be analysed; mean duration of treatment was 36.3 days. At the evaluation visit 76.9% were heartburn‐free, 77.7% regurgitation‐free and 71% had complete symptom resolution. Overall Psychological General Well‐being Index scores improved accordingly. Treatment was equally effective in patients with or without H. pylori infection, but more effective in patients with oesophagitis when compared with symptomatic gastro‐oesophageal reflux disease.

Conclusions : The effectiveness of rabeprazole in gastro‐oesophageal reflux disease is not affected by the presence of H. pylori infection.
IS911 partial transposition products and their processing by the Escherichia coli RecG helicase
Authors: Turlan Catherine , Loot Celine , Chandler Michael
Published: August 2004

Insertion of bacterial insertion sequence IS911 can often be directed to sequences resembling its ends. We have investigated this type of transposition and shown that it can occur via cleavage of a single end and its targeted transfer next to another end. The single end transfer (SET) events generate branched DNA molecules that contain a nicked Holliday junction and can be considered as partial transposition products. Our results indicate that these can be processed by the Escherichia coli host independently of IS911‐encoded proteins. Such resolution depends on the presence of homologous DNA regions neighbouring the cross‐over point in the SET molecule. Processing is often accompanied by sequence conversion between donor and target sequences, suggesting that branch migration is involved. We show that resolution is greatly reduced in a recG host. Thus, the branched DNA‐specific helicase, RecG, involved in processing of potentially lethal DNA structures such as stalled replication forks, also intervenes in the resolution of partial IS911 transposition products.
Targeting of the chemotaxis methylesterase/deamidase CheB to the polar receptor–kinase cluster in an Escherichia coli cell
Authors: Banno Satomi , Shiomi Daisuke , Homma Michio , Kawagishi Ikuro
Published: August 2004

Chemotactic adaptation to persisting stimulation involves reversible methylation of the chemoreceptors that form complexes with the histidine kinase CheA at a cell pole. The methyltransferase CheR targets to the C‐terminal NWETF sequence of the chemoreceptor. In contrast, localization of the methylesterase CheB is largely unknown, although regulation of its activity via phosphorylation is central to adaptation. In this study, green fluorescent protein was fused to full‐length CheB or its various parts: the N‐terminal regulatory domain (N), the C‐terminal catalytic domain (C) and the linker (L). The full‐length and NL fusions and, to a lesser extent, the LC fusion localized to a pole. Deletion of the P2 domain from CheA abolished polar localization of the full‐length and NL fusions, but did not affect that of the LC fusion. Pull‐down assays demonstrated that the NL fragment, but not the LC fragment, binds to the P2 fragment of CheA. These results indicate that binding of the NL domain to the P2 domain targets CheB to the polar signalling complex. The LC fusion, like the chemoreceptor, partially localized in the absence of CheA, suggesting that the LC domain may interact with its substrate sites, either as part of the protein or as a proteolytic fragment.
Coupling of the pathway of sulphur oxidation to dioxygen reduction: characterization of a novel membrane‐bound thiosulphate:quinone oxidoreductase
Authors: Müller Fabian H. , Bandeiras Tiago M. , Urich Tim , Teixeira Miguel , Gomes Cláudio M. , Kletzin Arnulf
Published: August 2004

Thiosulphate is one of the products of the initial step of the elemental sulphur oxidation pathway in the thermoacidophilic archaeon Acidianus ambivalens. A novel thiosulphate:quinone oxidoreductase (TQO) activity was found in the membrane extracts of aerobically grown cells of this organism. The enzyme was purified 21‐fold from the solubilized membrane fraction. The TQO oxidized thiosulphate with tetrathionate as product and ferricyanide or decyl ubiquinone (DQ) as electron acceptors. The maximum specific activity with ferricyanide was 73.4 U (mg protein)−1 at 92°C and pH 6, with DQ it was 397 mU (mg protein)−1 at 80°C. The Km values were 2.6 mM for thiosulphate (kcat = 167 s−1),  3.4 mM  for  ferricyanide  and  5.87 µM for DQ. The enzymic activity was inhibited by sulphite (Ki = 5 µM), metabisulphite, dithionite and TritonX‐100, but not by sulphate or tetrathionate. A mixture of caldariella quinone, sulfolobus quinone and menaquinone was non‐covalently bound to the protein. No other cofactors were detected. Oxygen consumption was measured in membrane fractions upon thiosulphate addition, thus linking thiosulphate oxidation to dioxygen reduction, in what constitutes a novel activity among Archaea. The holoenzyme was composed of two subunits of apparent molecular masses of 28 and 16 kDa. The larger subunit appeared to be glycosylated and was identical to DoxA, and the smaller was identical to DoxD. Both subunits had been described previously as a part of the terminal quinol:oxygen oxidoreductase complex (cytochrome aa3).
The gate controlling cell wall synthesis in Staphylococcus aureus
Authors: Komatsuzawa Hitoshi , Fujiwara Tamaki , Nishi Hiromi , Yamada Sakuo , Ohara Masaru , McCallum Nadine , Berger‐Bächi Brigitte , Sugai Motoyuki
Published: August 2004

Glucosamine‐6‐P occupies a central position between cell wall synthesis and glycolysis. In the initial steps leading to peptidoglycan precursor formation glucosamine‐6‐P is processed sequentially to UDP‐N‐acetylglucosamine, while to enter the glycolysis pathway, glucosamine‐6‐P is isomerized by NagB to fructose‐6‐P. Although we could not demonstrate NagB activity, nagB inactivation significantly reduced growth. Mutational analysis showed that NagA was involved in glucosamine‐6‐P formation from N‐acetylglucosamine‐6‐P, and GlmS in that from fructose‐6‐P. Inactivation of glmS prevented growth on glucose as sole carbon source, which resumed after complementation with N‐acetylglucosamine. Transcription of glmS as well as the amount of GlmS was reduced in the presence of N‐acetylglucosamine. This and the preferential incorporation of N‐acetylglucosamine over glucose into cell wall material showed that N‐acetylglucosamine was used exclusively for cell wall synthesis, while glucose served both cell wall synthesis and glycolysis. These observations suggest furthermore GlmS to be the key and only enzyme leading from glucose to cell wall synthesis in Staphylococcus aureus, and show that there exists a tight regulation and hierarchy in sugar utilization. Inactivation of nagA, nagB or glmS affected the susceptibility of S. aureus to cell wall synthesis inhibitors, suggesting an interdependence between efficiency of cell wall precursor formation and resistance levels.
Bacteriophage T7 DNA ejection into cells is initiated by an enzyme‐like mechanism
Authors: Kemp Priscilla , Gupta Manisha , Molineux Ian J.
Published: August 2004

In a normal infection about 850 bp of the bacteriophage T7 genome is ejected into the cell, the remainder of the genome is internalized through transcription by Escherichia coli and then T7 RNA polymerase. Rates of T7 DNA internalization by the E. coli enzyme in vivo are constant across the whole genome. As expected for an enzyme‐catalysed reaction, rates vary with temperature and can be fitted to Arrhenius kinetics. Phage virions containing a mutant gp16, a protein known to be ejected from the phage capsid into the cell at the initiation of infection, allow complete entry of the T7 genome in the absence of transcription. The kinetics of DNA ejection from such a mutant virion into the bacterial cytoplasm have also been measured at different temperatures in vivo. Between 15 and 43°C the entire 40 kb T7 genome is translocated into the cell at a constant rate that is characteristic for each temperature, and the temperature‐dependence of DNA translocation rates can be fitted to Arrhenius kinetics. The data are consistent with the idea that transcription‐independent DNA translocation from the T7 virion is also enzyme‐catalysed. The proton motive force is necessary for this mode of DNA translocation, because collapsing the membrane potential while the T7 genome is entering the cell abruptly halts further DNA transfer.
Haemophore‐mediated signalling in Serratia marcescens: a new mode of regulation for an extra cytoplasmic function (ECF) sigma factor involved in haem acquisition
Authors: Biville Francis , Cwerman Hélène , Létoffé Sylvie , Rossi Maria‐Silvia , Drouet Valérie , Ghigo J. M. , Wandersman Cécile
Published: August 2004

Bacterial extra cytoplasmic function (ECF) sigma factors control a wide range of cell envelope activities including iron and haem uptake systems. Sigma activity is usually inhibited by membrane‐bound antisigma. An extra cytoplasmic signal modulates sigma–antisigma interactions and thereby leads to the transcription of the target operon. Sigma and antisigma genes generally belong to one autoregulated operon. However, ECF sigma and antisigma genes involved in iron acquisition, also called iron starvation ECF, are non‐autoregulated exceptions to this rule.

We fully reconstituted the has signalling cascade of Serratia marcescens in Escherichia coli. Binding of the haem‐loaded haemophore to the outer membrane receptor, HasR, inactivates the antisigma HasS, turning on HasI and thereby allowing has operon transcription. Deletion of the HasR N‐terminal extension, present in all characterized outer membrane receptors endowed with signal transduction capacity, abolished the inducing activity but not the transport activity. Induction required the TonB‐ExbB‐ExbD complex. HasI, like the other iron starvation sigma, is iron repressed but not autoregulated. We found an entirely new regulation for the antisigma hasS gene, the transcription of which is HasI dependent. We suggest that the has system is both activated and repressed by the availability of external haem. When there is enough haem, the HasS antisigma activity is turned off and HasI induces the transcription of hasS. This leads to the storage of inactive HasS molecules which become active when HasR is not occupied by holo‐haemophore ligand molecules: as soon as there is a haem shortage transcription is turned off. Positive autoregulation of ECF sigma and antisigma genes is usually considered as a mechanism for amplifying a perceived signal. However, our findings suggest, on the contrary, that antisigma regulation allows fine‐tuning to the external signal. The biological significance of ECF sigma and antisigma autoregulation may need to be reconsidered.
Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine
Authors: Pellissier S. , Sasaki K. , Le‐Nguyen D. , Bataille D. , Jarrousse C.
Published: August 2004

Abstract  Glicentin (GLIC) and oxyntomodulin (OXM or GLIC 33‐69) are gut hormones which regulate digestion. They are known to reduce digestive secretions and to delay gastric emptying. Their biological activities on intestinal motility are still unknown. The effect of a systemic GLIC or OXM increase was investigated in rats on the food intake, the postprandial myoelectrical activity of small intestine and the orocaecal transit. An OXM or GLIC i.v. infusion was applied during the 5 min preceding food onset and during the first 15 min of food intake. This determined a three‐ to fourfold increase of the preprandial OXM–GLIC level. The OXM or GLIC plasma increase did not modify food intake. OXM infusion slowed down gastric emptying when the stomach contained 3/4 of the ingested food (before T 3 h). The quantity of food delivered in jejunum was subsequently smaller (P < 0.05). In the small intestine, the duration of postprandial myoelectrical activity (50–60 min g−1 of ingested food) was reduced by 70% (P < 0.001) on duodenum or jejunum and by 54% (P < 0.01) on ileum in OXM‐treated rats. An interdigestive motility profile was settled and an acceleration of both gastric emptying and transit rate was thereafter evidenced (after T 3 h). GLIC also reduced the duration of the postprandial myoelectrical activity on duodenum and jejunum (65 and 63% respectively, P < 0.05), but was not as efficient as OXM on ileum. In pathological states such as acute adult gastroenteritis, OXM and GLIC exhibit a two‐ to fivefold increase in their plasma concentrations. The present findings suggest that OXM and GLIC could, in that disease, contribute to exclude pathogens, due to their joined action on gut motility.
A non‐invasive method for measurement of gastric emptying in mice: effects of altering fat content and CCK A receptor blockade
Authors: Whited K. L. , Hornof W. J. , Garcia T. , Bohan D. C. , Larson R. F. , Raybould H. E.
Published: August 2004

Abstract The ability to make repetitive non‐invasive measurements of gastric emptying of nutritive solids in awake, unstressed mice is highly desirable. The aim of the present study was to develop such a technique using nuclear scintigraphy and diets differing in triglyceride content. Awake mice were accustomed to light restraint and to feeding cooked, egg white (0.00 g fat g−1), whole egg (0.10 g fat g−1), or egg yolk (0.31 g fat g−1). Gastric emptying of each diet was measured by labelling the test meals with Technetium99mMebrofenin and using a conventional gamma camera equipped with a high resolution, parallel hole collimator. Gastric emptying of cooked whole egg was also determined following administration of either vehicle or CCK A receptor antagonist, devazepide. The half‐emptying time (t1/2) significantly increased with increasing triglyceride content from 14 ± 5 min to 51 ± 6 min and 82 ± 4 min for egg white, whole egg and egg yolk, respectively. Administration of devazepide significantly decreasedt1/2of whole egg to 28 ± 2 min. These results demonstrate the sensitivity and predictability of this technique in mice and importantly, provide an opportunity to alter the macronutrient or caloric content of the meal to determine effects on gastric emptying.
Results of 24‐h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation
Authors: Hervé S. , Savoye G. , Behbahani A. , Leroi A. M. , Denis P. , Ducrotté P.
Published: August 2004

Abstract  The aims of this study were to assess the prevalence of manometric colonic abnormalities and to evaluate the motor effect of intraluminal bisacodyl in a cohort of refractory constipated patients. Twenty‐four hour colonic motility recordings were performed in 40 patients referred for a severe intractable chronic constipation. At the end of each recording session the motor effects of the endoluminal instillation of 10 mg bisacodyl were assessed. These patients were compared with 20 healthy subjects. The number of high‐amplitude propagating contractions (HAPC) was significantly decreased in patients with slow transit constipation (12 ± 11.6 vs 1 ± 8.6, P < 0.001). Based on manometric patterns four groups of patients were isolated. Ten patients had no spontaneous HAPC, no food‐induced colonic motor response and significantly lower colonic activity in transverse colon (374 ± 1220 vs 3249 ± 3458, P < 0.05). Five patients had significantly increased sigmoid segmental motility (20298 ± 6364 vs 88780 ± 3643, P < 0.001) and eight patients had significantly lower number of HAPC without other manometric abnormalities while 17 patients had normal colonic motility recordings. Endoluminal bisacodyl was able to induce HAPCs in all groups of patients. Patients with severe slow transit refractory constipation represented a heterogeneous group and endoluminal bisacodyl was able to promote a propagated motor activity in a majority of patients even in those suspected of having an inert colon.
The East Asian Dollar Standard, Fear of Floating, and Original Sin
Authors: McKinnon Ronald , Schnabl Gunther
Published: August 2004

Before the crisis of 1997/98, the East Asian economies—except for Japan but including China—pegged their currencies to the US dollar. To avoid further turmoil, the IMF argues that these currencies should float more freely. However, the authors’ econometric estimations show that the dollar's predominant weight in East Asian currency baskets has returned to its pre‐crisis levels. By 2002, the day‐to‐day volatility of each country's exchange rate against the dollar had again become negligible. Most governments were rapidly accumulating a “war chest” of official dollar reserves, which portends that this exchange rate stabilization will come to extend over months or quarters. From the doctrine of “original sin” applied to emerging‐market economies, the authors argue that this fear of floating is entirely rational from the perspective of each individual country. And their joint pegging to the dollar benefits the East Asian dollar bloc as a whole, although Japan remains an important outlier.
R&D‐induced Growth in the OECD?
Authors: Zachariadis Marios
Published: August 2004

The study uses aggregate and manufacturing sector data for a group of ten OECD countries for the period 1971 to 1995 to estimate a system of two equations implied by a model of R&D‐induced growth in steady state. These equations relate R&D intensity to productivity growth and the latter to output growth. The author finds evidence of a positive impact of aggregate R&D intensity on the growth rates of productivity and output. The null hypothesis that growth is not induced by R&D is rejected in favor of the Schumpeterian endogenous growth framework without scale effects. The R&D impact for the aggregate economy is distinctly larger than for the manufacturing sector. Finally, an extension of the empirical model shows that openness has a positive impact on productivity growth.
Reexamination of Economic Growth, Tax Policy, and Distributive Politics
Authors: Bao Yong , Guo Jang‐Ting
Published: August 2004

The paper examines the relationship between economic growth, tax policy, and distribution of capital and labor ownership in a one‐sector political‐economy model of endogenous growth with productive government spending financed by a proportional tax on capital income. The analysis shows that inequality in wealth and income can be positively or negatively related to the optimal tax rate. In either environment, higher inequality leads to a lower after‐tax return to capital, thereby reducing the economy's growth rate.
ARDL Approach to Test the Productivity Bias Hypothesis
Authors: Bahmani‐Oskooee Mohsen , Nasir A. B. M.
Published: August 2004

The productivity bias hypothesis states that a relatively more productive country should experience a real appreciation of its currency. Most studies in the literature that have tested the hypothesis have employed cross‐sectional data. Only a few studies have used time‐series data and they have tested the hypothesis for only a small number of countries. In this paper the authors test the hypothesis by using time‐series data over the 1960–90 period for a sample of 44 countries and with a relatively new method of cointegration known as the ARDL approach. For most countries there is strong evidence supporting the hypothesis.
Filial Obligations and Child Labor
Authors: López‐Calva Luis Felipe , Miyamoto Koji
Published: August 2004

The model presented here reproduces the empirical fact that poorer countries show a higher incidence of child labor and time‐intensive care of retired parents, whereas richer countries have negligible child labor and people indulge in money‐intensive care of the old. For that purpose, the effect of social norms of filial obligations on child labor and schooling decisions is analyzed. It is shown that norms of filial obligations are sustainable as an equilibrium in the intergenerational game. Widely discussed contracting problems à la Becker, which allegedly explain underinvestment in schooling by poor households, are thus solved. However, this alone does not induce the elimination of child labor. Technological parameters and relative returns to schooling also play a fundamental role.
LOCKE ON IDEAS OF SUBSTANCE AND THE VEIL OF PERCEPTION
Authors: YAFFE GIDEON
Published: August 2004

Abstract:  John Yolton has argued that Locke held a direct realist position according to which sensory ideas are not perceived intermediaries, as on the representational realist position, but acts that take material substances as objects. This paper argues that were Locke to accept the position Yolton attributes to him he could not at once account for appearance‐reality discrepancies and maintain one of his most important anti‐nativist arguments. The paper goes on to offer an interpretation of Locke's distinction between ideas of substances and modes, a distinction that helps Locke to explain appearance‐reality discrepancies, although not in a large enough range of cases to strengthen Yolton's interpretation.
THE LOGIC OF IDEAS AND THE LOGIC OF THINGS: A REPLY TO CHAPPELL
Authors: LENNON THOMAS M.
Published: August 2004

Abstract:  A continuation of the debate over the intelligibility, and plausibility, of Yolton's reading of Locke's account of perception. Here, the issue turns on the de‐reification of ideas and its implications for the putative axioms of symmetry and transitivity governing the identity of ideas. The issue is illustrated by what Locke says about confused ideas.
Class and Other Identifications in Managerial Careers: The Case of the Lemon Dress
Authors: Hughes Christina
Published: August 2004

This article responds to concerns that research in the field of careers needs to bring together an action perspective with a recognition of the continuing impact of structural and cultural imperatives. To do so this article presents a symptomatic study. Through the concept of pedagogies of the everyday, this combines an action orientation with a recognition of how such pedagogies operate within networks of power. Specifically, the article argues that the development of new gendered understandings of management careers requires greater recognition of the continuing, though now relatively neglected, saliency of class. The article offers a summary of contemporary theorizations of class and concludes with a discussion of possible future directions for this field of research.
En‐Trusting Appraisal to the Trust
Authors: Coates Grant
Published: August 2004

Contemporary performance appraisal (henceforth appraisal) has become an important tool in overseeing employees’ work. Little of the vast literature however, has focused on its effects on the individual, beyond simple descriptions informing its implementation by management. This article firstly examines the changing nature of employee management under appraisal, then investigates its contemporary usage and the effects on women. This is illustrated with research gathered from a case study in the Midlands. The article also examines the changing focus of appraisal as a means through which the marginal and not so marginal performer can be controlled. Analysis focuses on the use of subjective perception of ‘women’ through appraisal to create ‘excellent’ employees in a ‘quality’ environment and examines management's attempts to apply the powerful subjective manipulation of knowledge over women. The use of a hospital case study highlights some of these issues in relation to the changes taking place in the public service sector. This sector faces fundamental transformations in its concept of ‘service’.
Retraining the injured spinal cord
Authors: Edgerton V. Reggie , de Leon Ray D. , Harkema Susan J. , Hodgson John A. , London Nikolas , Reinkensmeyer David J. , Roy Roland R. , Talmadge Robert J. , Tillakaratne Niranjala J. , Timoszyk W. , Tobin Allan
Published: August 2004

The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up‐regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down‐regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.
Mechanism of Ba2+ block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues
Authors: Alagem Noga , Dvir Miri , Reuveny Eitan
Published: August 2004

The block of the IRK1/Kir2.1 inwardly rectifying K+ channel by a Ba2+ ion is highly voltage dependent, where the ion binds approximately half‐way within the membrane electrical field. The mechanism by which two distinct mutations, E125N and T141A, affect Ba2+ block of Kir2.1 was investigated using heterologous expression in Xenopus oocytes.

Analysis of the blocking kinetics showed that E125 and T141 affect the entry and binding of Ba2+ to the channel, respectively. Replacing the glutamate at position 125 with an asparagine greatly decreased the rate at which the Ba2+ ions enter and leave the pore. In contrast, replacing the polar threonine at position 141 with an alanine affected the entry rate of the Ba2+ ions while leaving the exit rate unchanged.

Acidification of the extracellular solution slowed the exit rate of the Ba2+ from the wild‐type channel, but had no such effect on the Kir2.1(E125N) mutant.

These results thus reveal two unique roles for the amino acids at positions 125 and 141 in aiding the interaction of Ba2+ with the channel. Their possible roles in K+ permeation are discussed.
Serotonin facilitates AMPA‐type responses in isolated siphon motor neurons of Aplysia in culture
Authors: Chitwood Raymond A. , Li Quan , Glanzman David L.
Published: August 2004

Serotonin (5‐HT) facilitates the connections between sensory and motor neurons in Aplysia during behavioural sensitization. The effect of 5‐HT on sensorimotor synapses is believed to be primarily presynaptic. Here we tested whether 5‐HT can have an exclusively postsynaptic facilitatory effect.

Siphon motor neurons were individually dissociated from the abdominal ganglion of Aplysia and placed into cell culture. Brief pulses of glutamate, the putative sensory neuron transmitter, were focally applied (0.1 Hz) to solitary motor neurons in culture, and the glutamate‐evoked postsynaptic potentials (Glu‐PSPs) were recorded.

When 5‐HT was perfused over the motor neuron for 10 min, the amplitude of the Glu‐PSPs was significantly increased. The 5‐HT‐induced enhancement of the Glu‐PSPs persisted for at least 40 min after washout.

Prior injection into the motor neuron of the calcium chelator BAPTA, GDP‐β‐S or GTP‐γ‐S blocked the 5‐HT‐induced facilitation of the Glu‐PSPs. However, the facilitation was not blocked when APV, an NMDA receptor antagonist, was applied together with the 5‐HT.

The enhancement of the Glu‐PSPs by 5‐HT was reversed by the AMPA receptor antagonist DNQX, indicating that 5‐HT increased the functional expression of AMPA‐type receptors in the motor neuron.

The presence of botulinum toxin in the motor neuron blocked the 5‐HT‐induced enhancement of the Glu‐PSPs. As botulinum toxin prevents exocytosis we hypothesize that during sensitization 5‐HT causes the insertion of additional AMPA‐type receptors into the postsynaptic membrane of sensorimotor synapses via exocytosis. This postsynaptic mechanism may contribute to facilitation of the synapses.
Organisation of inputs to spinal interneurone populations
Authors: Edgley S. A.
Published: August 2004

In order to use electrical stimulation or biological repair to attempt to alleviate spinal cord dysfunction, a key problem will be how to target the intervention. Since the majority of inputs to spinal motoneurones originate from intrinsic spinal premotor interneurones, these are key targets for interventions that may help restore function. Information on the organisation of these neurones could thus be crucially important to determine how to proceed. Understanding the organisation of spinal interneurones is no easy task. In this article I review evidence of the connectivity of some of the groups of spinal premotor interneurones that have been studied, focusing particularly on whether they form subgroups and how these can be identified.
Adrenomedullin increases fluid extravasation from the splenic circulation of the rat
Authors: Kaufman S. , Andrew P. , Sultanian R. , Deng Y.
Published: August 2004

We studied the effect of adrenomedullin (ADM) on fluid efflux from the splenic vasculature into extravascular spaces.

Splenic arterial infusion of ADM (1, 3 and 9 ng min−1; n = 9, 11 and 10, respectively) caused a dose‐dependent increase in intrasplenic fluid efflux (+0.6 ± 0.3 (saline) vs.+2.0 ± 0.3 ml min−1 (9 ng min−1 ADM), P < 0.05), and in splenic (venous minus arterial) haematocrit (+0.8 ± 0.1 (saline, n = 6) vs.+3.1 ± 0.3 % (9 ng min−1 ADM, n = 7), P < 0.05). There was no change in splenic weight (0.99 ± 0.02 (saline, n = 6) vs. 0.99 ± 0.02 g (9 ng min−1 ADM, n = 7), P > 0.05).

There was no change in MAP before (97.5 ± 2.2 mmHg), during (98.4 ± 3.4 mmHg), or after (100.2 ± 2.2 mmHg) intrasplenic infusion of ADM (9 ng min−1) (n = 11, P < 0.05).

ADM (9 ng min−1) caused an increase in intrasplenic microvascular pressure (11.3 ± 0.3 (saline, n = 5) vs. 13.0 ± 0.3 mmHg (9 ng min−1 ADM, n = 6), P < 0.05).

ADM (1 × 10−11 to 1 × 10−6m) induced greater vasorelaxation of isolated preconstricted splenic resistance arteries than veins (maximal relaxation: 60 ± 0.9 (artery, n = 9) vs. 43 ± 1.7 % (vein, n = 8), P < 0.05). l‐NMMA (10−4m) partially inhibited the ADM‐induced relaxation in splenic arteries (maximal relaxation: 38 ± 3 (ADM +l‐NMMA, n = 5) vs. 60 ± 3 % (ADM +d‐NMMA, n = 5), P < 0.05).

It is concluded that ADM increases fluid efflux from the splenic vasculature by differentially reducing pre‐ vs. post‐capillary resistance, thus increasing intrasplenic microvascular pressure.