bluuebunny/crossref_metadata_2025 huggingface dataset:
Carboxyl‐Terminal Truncations of Human Anion Exchanger Impair its Trafficking to the Plasma Membrane
Authors: Cordat Emmanuelle , Li Jing , Reithmeier Reinhart A. F.
Published: August 2003

The human anion exchanger AE1 (Band 3) is an abundant glycoprotein localized in plasma membrane of red cells and is responsible for the electro‐neutral exchange of chloride for bicarbonate. In order to determine the role of the carboxyl‐terminal tail of AE1 in its expression, function and trafficking to the plasma membrane, we generated a series of five constructs encoding truncation mutants missing the last 5 (Δ5), 11 (Δ11), 15 (Δ15), 20 (Δ20) or 35 (Δ35) amino‐acids. In transiently transfected HEK 293 cells, immunoblotting of whole cell extracts showed that all the proteins were expressed at the same level as full‐length AE1, except Δ20 and particularly Δ35, which showed a reduced expression. Furthermore, the last 15 amino‐acids were not required for AE1 folding in the membrane, since Δ5, Δ11 and Δ15 were able to bind to an inhibitor affinity matrix, while Δ20 and Δ35 exhibited poor binding. Immunofluorescence and deglycosylation results showed that Δ15 and Δ11 were retained intracellularly, whereas a lower amount of Δ5 compared with WT trafficked to the plasma membrane. These results indicate that an intact C‐terminal tail of human AE1 is important for efficient AE1 trafficking to the plasma membrane.
Kinetics of haematopoietic recovery after dose‐intensive chemo/radiotherapy in mice: optimized erythroid support with darbepoetin alpha
Authors: Hartley Cynthia , Elliott Steve , Begley C. Glenn , McElroy Patricia , Sutherland Weston , Khaja Raheem , Heatherington Anne C. , Graves Tom , Schultz Henry , Del Castillo Juan , Molineux Graham
Published: August 2003

Summary. Despite its frequency and impact on clinical outcomes, anaemia in cancer patients remains poorly understood and suboptimally treated. The definition of optimum treatment schedules with erythropoietic agents requires a suitable model of chemotherapy‐induced progressive anaemia. This study investigated novel strategies such as once‐per‐chemotherapy‐cycle dosing, synchronization between erythroid supportive care and chemotherapy, and definition of the optimum timing of erythroid support. A murine model of carboplatin chemotherapy/radiotherapy (CRT)‐induced anaemia was used, which caused progressive anaemia across multiple cycles. Weekly administration of recombinant human erythropoietin (rHuEPO) was effective, but the longer‐acting darbepoetin alpha resulted in superior responses. In all animals, anaemia became progressive and more refractory across cycles because of accumulated bone marrow damage. Exploiting a specific enzyme‐linked immunosorbent assay, which could distinguish between darbepoetin alpha and endogenous erythropoietin, the effect of CRT upon the pharmacokinetics of darbepoetin alpha showed that clearance of darbepoetin alpha, and presumably erythropoietin, was at least partially dependent on a chemotherapy‐sensitive pathway. Scheduling data suggested that administration of erythropoietic agents prior to chemotherapy was more effective than administration after chemotherapy. There was no evidence that erythropoietic agents exacerbated anaemia, even when administered immediately prior to CRT in an attempt to ‘prime’ erythroid cells for the effects of CRT.
Mycobacterium vaccae administration during allergen sensitization or challenge suppresses asthmatic features
Authors: Smit J. J. , Van Loveren H. , Hoekstra M. O. , Schijf M. A. , Folkerts G. , Nijkamp F. P.
Published: August 2003

Background and objective  The hygiene hypothesis suggests that a lack of bacterial infections would favour the development of allergic disease. For this reason, bacteria or their components can be used as potential treatment for allergic asthma. We investigated whether heat‐killed Mycobacterium vaccae is either able to suppress the induction of allergic asthma or able to suppress already established allergic asthma.

Methods  Mice were sensitized with ovalbumin (OVA)/alum on days 0 and 14. Thereafter, mice were challenged on days 35, 39 and 42 by inhalation of either OVA or saline aerosols. M. vaccae‐treated mice received an injection with 106, 107 or 108 CFU heat‐killed M. vaccae on days 0 and 14 or 107 CFU on days 35 and 39. On day 43, the airway responsiveness of the mice to increasing concentrations of methacholine was assessed, blood was withdrawn to measure serum parameters, and lung lavage was performed to detect cytokines and inflammatory cell number.

Results  Treatment of OVA‐sensitized mice with 107 CFU M. vaccae either during sensitization or challenge suppresses airway hyper‐responsiveness, airway eosinophilia and IL‐5 production after OVA challenge. The increases in OVA‐specific serum IgE and in IL‐4 by respiratory challenges with OVA were only diminished after M. vaccae treatment (107 CFU) during sensitization.

Conclusions  Heat‐killed M. vaccae prevents allergic and asthmatic manifestations in a mouse model and, more importantly, M. vaccae treatment during challenge suppresses features of asthma, which opens up possibilities for new therapeutic interventions.
Promoter polymorphism in the 5‐lipoxygenase (ALOX5) and 5‐lipoxygenase‐activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population
Authors: Sayers I. , Barton S. , Rorke S. , Sawyer J. , Peng Q. , Beghé B. , Ye S. , Keith T. , Clough J. B. , Holloway J. W. , Sampson A.P. , Holgate S.T.
Published: August 2003

Background
5‐Lipoxygenase (5‐LO) and 5‐lipoxygenase‐activating protein (FLAP) are essential for cysteinyl‐leukotriene (cys‐LT) production, critical mediators in asthma.

Objective
We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5‐LO (ALOX5) Sp1 promoter polymorphism in asthma susceptibility.

Methods
To assess genetic association with asthma phenotypes, we genotyped 341 Caucasian families (containing two asthmatic siblings) and non‐asthmatic control subjects (n=184). Genetic association was determined by case–control and transmission disequilibrium test (TDT) analyses. To determine the functional role of polymorphisms on basal transcription, we generated ALOX5AP‐promoter‐luciferase constructs and transiently transfected human HeLa cells.

Results
A novel G/A substitution at –336 bp and a poly(A) repeat (n=19 or 23) at position −169 to −146 bp were identified in the ALOX5AP promoter. Genotyping found the −336 A and poly(A19) alleles at frequencies of q=0.06 and 0.12, respectively. No ALOX5AP allele was associated with asthma or asthma‐related phenotypes in case–control or TDT analyses. ALOX5AP‐promoter‐luciferase analyses did not support a functional role of the −336 or poly(A) polymorphism in determining basal transcription. The ALOX5 Sp1 polymorphism was predominantly homozygous wild‐type 5/5 (frequency q=0.70) and heterozygous 4/5 (q=0.23) genotypes and no allele was associated with asthma or asthma‐related phenotypes.

Conclusion
Taken together, these data do not support a significant role for these polymorphisms in genetic susceptibility to asthma in the Caucasian population.
Concurrent cereal allergy in children with cow's milk allergy manifested with atopic dermatitis
Authors: Järvinen K.‐M. , Turpeinen M. , Suomalainen H.
Published: August 2003

Background
There is increasing consensus about the significance of food allergens in the pathogenesis of atopic dermatitis (AD) in infancy and childhood, with cow's milk and egg accounting for most of the reactions. Previous studies have indicated that multiple food sensitization, such as cereals, is very common in patients with cow's milk allergy (CMA). Evidence is lacking, however, as to its clinical relevance.

Objective
The purpose of this study was to determine the concurrent occurrence of cereal allergy among children with challenge‐proven CMA who have residual symptoms, such as AD and/or gastrointestinal symptoms, during cow's milk elimination diet. Further, we sought to evaluate the utility of patch testing in prescreening foods other than cow's milk behind allergic symptoms in children.

Methods
The study population comprised 90 children, aged from 2.5 to 36 months (mean 1.1 years), with challenge‐proven CMA. As a result of residual symptoms during meticulous cow's milk elimination diet (AD: n=80, and gastrointestinal: n=10), the children were put on a cereal elimination diet (oats, wheat, rye, and barley) and skin prick tests (SPT) and patch testing with cereals were performed. Open cereal challenge was performed to confirm cereal allergy.

Results
Cereal challenge was positive in 66 (73%) of the children with CMA. Of them, 17% reacted with immediate reactions and delayed‐onset reactions were seen in 83% of the children. SPT was positive in 23%, patch test in 67%, and either SPT or patch test was positive in 73% of the children with cereal allergy. SPT gave the best positive predictive value, whereas SPT together with patch test gave the best negative predictive value.

Conclusions
Residual symptoms, such as eczema or gastrointestinal symptoms in CMA children may be a sign of undetected allergy to other food antigens. SPT with cereals aids in diagnosing cereal allergy in small children, especially when used together with patch testing.
Methotrexate therapy in asthma increases T cell susceptibility to corticosteroid inhibition
Authors: Corrigan C. J. , Shiner R. , Shakur B. H. , Ind P. W.
Published: August 2003

Background  Concomitant methotrexate (MTX) therapy of severe, oral corticosteroid‐dependent asthmatics has been shown to be corticosteroid sparing, but the mechanism is unknown. We hypothesized that MTX therapy of these patients increases the susceptibility of their T cells to corticosteroid inhibition.

Objective  To measure prednisolone inhibition of lectin‐induced proliferation of peripheral blood T cells from a group of these patients before, during and following MTX therapy.

Methods  Eighteen severe asthmatics (median (range) age 56 (33–68) years, FEV1 61 (38–69)% predicted, dependent on oral prednisolone 15 (7.5–25) mg/day in addition to high‐dose, inhaled corticosteroids) were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. After 12 weeks of MTX, oral prednisolone dosages were reduced systematically over 16 weeks, provided that asthma control did not deteriorate. Patients were followed for a further 12 weeks after MTX withdrawal. Concentration‐dependent, prednisolone inhibition of lectin‐induced proliferation of peripheral blood T cells was measured just prior to MTX therapy (week 1) and at weeks 12, 28 and 40, and IC50 concentrations were interpolated.

Results  By week 28 of MTX therapy, patients were able to reduce oral prednisolone dosages from (median, SIQR) 15 (10–20.5) to 5.9 (1.4–9.4) mg/day (P<0.01) without alteration of lung function and symptoms, while median IC50 values for prednisolone inhibition of peripheral blood T cell proliferation were reduced from 49 (21–144) to 4 (1–9) nm (P<0.0001). These increased again to 15 (9.4–25.7) mg/day and 36 (18–67) nm, respectively, following MTX withdrawal. A correlation (P<0.01) was observed between percentage reductions in prednisolone dosages in vivo and fold changes in prednisolone IC50in vitro between weeks 12 and 28.

Conclusion  This effect of MTX may at least partly account for its oral corticosteroid‐sparing effect in severe asthma.
Parents' perceptions of staff competency in a neonatal intensive care unit
Authors: Cescutti‐Butler Luisa , Galvin Kathleen
Published: August 2003

• The aim of this study was to explore and describe parents' perceptions of staff competency in a neonatal intensive care unit (NICU). The study set out to use a grounded theory approach that was modified because of a number of constraints. Eight parents whose babies met a number of inclusion criteria were interviewed using focused conversational interviews. They were then transcribed and thematically analysed. The research approach was modified as the study developed because of practical and ethical access reasons: the sampling strategy and lack of opportunity to exploit fully the constant comparative method.

• Four key themes which conceptualize competency as caring emerged from the data: parents are facilitated to integrate into the unit and do not feel a burden; parents feel in control whilst in the unit; parents have a choice to opt out from observing tasks and procedures on their baby; parents and the interprofessional team communicate well and provide appropriate information. These are discussed in the context of available literature.

• In conclusion, the results of the study serve to highlight how parents' perceptions of competence in a professional are not based solely on skills and tasks but on many caring behaviours. The grounded theory approach has generated a number of areas for exploration, in particular, ideas about the conceptual basis of caring in an NICU context and its links to competence. The caring behaviours involve learning to share responsibility with families. The findings suggest that when there is ‘a handing over’ of control to parents and a greater emphasis on parent support, they feel less like ‘guests’. These ideas are supported by the available literature. A number of methodological issues are raised.
Multidisciplinary nursing: re‐thinking role boundaries
Authors: Pearson Alan
Published: August 2003

• The ambiguous role of nurses within the health care team has been a subject of much debate, evident in current practice and the study of the early development of nursing in Australia.

• Early nursing work was broad and uncontested. Debates about nursing and ‘non‐nursing’ tasks are thought to have emerged after the establishment of ‘Nightingale reforms’ in the 1870s.

• Nursing role conflicts may be due in part to the rise in technology and medical intervention, the demise of ‘generalist’ doctors, nurses and patient‐centred care, the creation of nursing specialists who moved to other community care positions and nursing's drive for professionalization.

• Nurses’ role in mealtimes provides one example of the ambiguous and contentious issue of nursing and non‐nursing work.

• Health services need a generic worker who is client‐focused, possesses multidisciplinary skills, manages the care environment, humanizes the system at the point of contact and acts therapeutically. This broad and flexible role ascribed to nurses is threatened by cost containment and the scramble for new occupations within the broad field of health services, which is plagued with increasingly rigid role boundaries.

• The examination of nursing workforce planning arrangements is needed to ensure greater coherence and clearer lines of nurses’ roles and responsibilities.
Children's nursing: can it justify a separate existence in the UK?
Authors: Lee Polly
Published: August 2003

• There is currently debate about how the professional register for nurses is organized in the UK. Children's nurses, like the other minority registrants of mental health and learning disabilities nurses felt threatened with the potential loss of a separate register.

• Children's nurses should be able to articulate their own unique body of knowledge.

• Using Fawcett's framework for the hierarchy of contemporary nursing knowledge, the development of children's nursing knowledge is examined to determine if, indeed, children's nursing is a separate discipline, by having its own metaparadigm of children's nursing, philosophy, conceptual model of nursing, nursing theories and, finally, empirical indicators.

• Although some levels of knowledge appear to have been developed, it is considered that children's nursing is still lacking in some levels of knowledge, thus suggesting that the continuing development of children's nursing knowledge is necessary.
Pharmacological assessment of the role of nitric oxide in mice infected with lethal and nonlethal species of malaria
Authors: Dascombe Michael J. , Nahrevanian Hossein
Published: August 2003

This pharmacological investigation sought to determine whether nitric oxide (NO) had an antiparasitic effect and/or mediated pathology in mice infected with nonlethal P. chabaudi or lethal P. berghei. Nitric oxide synthase (NOS) inhibitors were evaluated for their ability to inhibit the rise in reactive nitrogen intermediates (RNI) induced by bacterial lipopolysaccharide (LPS) in mice. The more effective compound, aminoguanidine (AG) inhibited the rise in RNI induced by P. chabaudi and increased mortality, but had no effect on parasitaemia. Inducers and donors of NO were screened for their ability to increase RNI and the most effective agents evaluated for their ability to modify P. berghei infection. S‐Nitrosoglutathione had little effect, but LPS decreased parasitaemia and mortality. An inconsistent relationship is evident between the abilities of these agents to modify NO activity and their effects on malaria in mice. Increased mortality in mice with P. chabaudi treated with AG indicates a reduction in resistance. The absence of an effect on parasitaemia by a NOS inhibitor or NO donor indicates either RNI have insignificant antimalarial action in vivo or the efficacy of the compounds is inadequade. Resistance to P. berghei in LPS‐treated mice demonstrates an antiparasitic effect, but this may be attributable to factors other than NO.
Kinetics of eosinophil and IgE‐mast cell changes following infection with Angiostrongylus costaricensis in Wistar rats
Authors: Serra M. F. , Barreto E. O. , Silva J. P. , Azevedo V. , Mota E. M. , Pelajo‐Machado M. , Lucena S. , Pires A. L. A. , Carvalho V. , Cordeiro R. S. B. , Lenzi H. L. , Silva P. M. R. , Martins M. A.
Published: August 2003

Human abdominal angiostrongyliasis is a severe eosinophilic disease caused by Angiostrongylus costaricensis. Previous studies have demonstrated that wild rodents are critically involved as definitive hosts to this nematode in nature. In this study, we have evaluated the susceptibility of Wistar rats (Rattus norvegicus) to A. costaricensis infection. Kinetics of parasitological and pathological changes, including the number of adult worms recovered from mesenteric arteries, and of IgE, mast cell and eosinophil levels in several compartments have been assessed. The oral inoculation of third‐stage larvae (L3) into adult Wistar rats led to a marked accumulation of worms in the branches of the mesenteric arteries 25 and 50 days post‐inoculation. Intense bone marrow eosinophilia ranging from 7 to 50 days was accompanied by marked accumulation of eosinophils in the blood, peritoneal and bronchoalveolar spaces. Eosinophilic periarteritis, oedema and granuloma in the intestinal and lung tissues were also histologically evident. Total serum IgE and specific anti‐parasite IgE peaked at 25 days post‐infection, as measured by ELISA and by the passive cutaneous anaphylaxis test, respectively. At that time point, there was a drastic reduction in the number of intact mast cells in the peritoneal effluent. These findings indicate that Wistar rats are permissive to A. costaricensis infection. IgE‐mast cell activation and massive tissue eosinophil infiltration are marked features in the process and are likely to play a crucial role in the immune‐response evoked by this parasite.
Constitutive expression of nitrate reductase changes the regulation of nitrate and nitrite transporters in Chlamydomonas reinhardtii
Authors: Navarro María Teresa , Prieto Rafael , Fernández Emilio , Galván Aurora
Published: August 2003

The effect of constitutive expression of nitrate reductase (NR) on the regulation pattern of nitrite and nitrate transporters (NT) has been analysed in Chlamydomonas reinhardtii. Strain Tx11‐8, bearing the chimeric Nia1 gene for NR under the control of the cabll‐1 gene promoter, showed a constitutive NR which was inactive in ammonium‐grown cells. In contrast to the wild‐type, incubation of Tx11‐8 in ammonium media containing nitrate at micromolar concentrations resulted in reactivation of inactive NR and excretion of nitrite. In addition, negligible amounts of NT gene transcripts were induced by nitrate in this strain. However, NT transcripts from Tx11‐8 cells were induced in amounts similar to those in the wild‐type, by preventing constitutive NR expression from the cabll‐1 gene promoter in the dark. Strains lacking high‐affinity NT and nitrite reductase activity and having the chimeric Nia1 gene have been constructed by genetic crosses. All these strains were sensitive to chlorate in ammonium‐containing media and excreted nitrite when nitrate was present at millimolar concentrations. Spontaneous chlorate‐resistant mutants isolated from these strains lacked constitutive NR activity though they constitutively expressed NR mRNA. The data strongly suggest that nitrate plays an important post‐transcriptional regulatory role and that NR is involved in the regulation of the nitrate/ nitrite transport activities in C. reinhardtii.
The Arabidopsis XET‐related gene family: environmental and hormonal regulation of expression
Authors: Xu Wei , Campbell Paul , Vargheese Ajay K. , Braam Janet
Published: August 2003

Enzymes that modify cell wall components most likely play critical roles in altering size, shape, and physical properties of plant cells. Regulation of such modifying activity is expected to be important during morphogenesis and in eliciting developmental and physiological alterations that arise in response to environmental conditions. Previous work has shown that the Arabidopsis TCH4 gene encodes a xyloglucan endotransglycosylase (XET) which acts on the major hemicellulose of the plant cell wall. The expression of TCH4 is dramatically upregulated in response to several environmental stimuli (including touch, wind, darkness, heat shock, and cold shock) as well as the growth‐enhancing hormones, auxin and brassinosteroids. This paper reports the presence of an extensive XET,related (XTR) gene family in Arabidopsis. In addition to TCH4, this family includes two previously identified genes, EXT and Meri‐5, and at least five additional genes. The cDNAs of the XTR family share between 46 and 79% sequence identity and the predicted XTR proteins share from 37 to 84% identity. All eight proteins include potential N‐terminal signal sequences and most have a conserved motif (DEIDFEFLG) that is also found in Bacillusβ‐glucanase and may be important for enzyme activity. The members of the XTR gene family are differentially sensitive to environmental and hormonal stimuli. Magnitude and kinetics of regulation are distinct for the different genes. Differential regulation of expression of this complex gene family suggests a recruitment of related, yet distinct, cell wall‐modifying enzymes that may control the properties of cell walls and tissues during development and in response to environmental cues.
Use of Ac as an insertional mutagen in Arabidopsis
Authors: Bhatt Anuj M. , Page Tania , Lawson Emily J.R. , Lister Clare , Dean Caroline
Published: August 2003

A pilot‐scale transposon mutagenesis experiment using a modified autonomous Activator (Ac) element, AcΔNael, was carried out in Arabidopsis thaliana. Four different transformants carrying Ac elements in different and defined genomic locations were used to generate 1000 plants carrying approximately 500 independent germinal transposition events. These plants were then selfed and the 1000 families screened in tissue culture and soil for phenotypic mutants. Fifty different families segregated mutations in their progeny. Preliminary Southern blot analysis of 29 families which segregated mutant progeny, showed that 28 had a transposed Ac. Six of the families were further tested for linkage between the transposed Ac and the mutant phenotype, and instability of the putatively tagged locus. Two of the mutants were shown to be tagged as they were tightly linked to a transposed Ac, and somatic and germinal reversion was associated with loss of Ac. One other mutant locus was shown to be closely linked to a transposed Ac, and therefore was likely to be tagged. The remaining three mutations were not tagged as they were not linked to a transposed Ac. In two of the tagged mutants Ac had transposed to closely linked sites, while in a third mutant the co‐segregating Ac had transposed to a site which was not tightly linked to the donor T‐DNA. Multiple insertions into the DIF1 locus were found, due to the preferential transposition of Ac to a linked site.
Identification of the epidermal growth factor‐like domains of thrombomodulin essential for the acceleration of thrombin‐mediated inactivation of single‐chain urokinase‐type plasminogen activator
Authors: Schenk‐Braat Ellen A. M. , Morser John , Rijken Dingeman C.
Published: August 2003

Single‐chain urokinase‐type plasminogen activator (scu‐PA) can be cleaved by thrombin into a virtually inactive form called thrombin‐cleaved two‐chain urokinase‐type plasminogen activator (tcu‐PA/T), a process accelerated by thrombomodulin, which contains six epidermal growth factor (EGF)‐like domains. In this study, we identified the EGF‐like domains of thrombomodulin required for the acceleration of the inactivation of scu‐PA by thrombin using various forms of thrombomodulin (TM). scu‐PA was treated with thrombin in the absence and presence of full‐length rabbit TM (containing EGF1‐6), recombinant TM comprising all of the extracellular domains including EGF1‐6 (TMLEO) and recombinant TM comprising EGF4‐6 plus the interconnecting region between EGF3 and EGF4 (TMEi4‐6), and the tcu‐PA/T generated was quantitated in each case. Rabbit TM accelerated the inactivation of scu‐PA ≈ 35‐fold, while both recombinant forms accelerated it only threefold due to the absence of a critical chondroitin sulfate moiety. Subsequently, TME5‐6 was prepared by cyanogen bromide digestion of TMEi4‐6. TME5‐6 bound to thrombin but did not accelerate the activation of protein C. In contrast, the inactivation of scu‐PA by thrombin was accelerated to the same extent as that induced by TMLEO and TMEi4‐6. This study demonstrates that, in addition to the chondroitin sulfate moiety, only EGF‐like domains 5 and 6 are essential for the acceleration of the inactivation of scu‐PA by thrombin. This differs from the domains that are critical for activation of protein C (EGF‐like domains i4–6) and thrombin activatable fibrinolysis inhibitor (EGF‐like domains 3–6).
Unfolding of apomyoglobin helices by synchrotron radiolysis and mass spectrometry
Authors: Maleknia Simin D. , Downard Kevin M.
Published: August 2003

The synchrotron X‐ray protein radiolysis technique is based on a quantitative determination of the extent and the site of millisecond radiolytic oxidation of amino‐acid side chains by mass spectrometry. The amino acids most susceptible to radiolytic oxidation are cysteine, methionine, phenylalanine, tyrosine, tryptophan, proline, histidine, and leucine. These residues serve as reactive markers within a protein structure that can be used to monitor changes in solvent accessibility during folding or as part of macromolecular interactions. To monitor the unfolding, the extent of radiolytic products of side chains of reactive amino acids is quantitatively measured by mass spectrometry as a function of the denaturant concentration following proteolysis. This approach provides site‐specific unfolding isotherms for various segments of a protein without the use of mutation or labeling techniques. Application of this technique to the equilibrium urea unfolding of apomyoglobin at pH 7.8 has demonstrated the cooperative unfolding of helices A to C consistent with midpoints, ΔG, and m values derived from fluorescence data. The G helix, in contrast, showed a local unfolding behavior. The similarity of the thermodynamic data derived by this synchrotron‐based method for helix A (containing two oxidizable tryptophan residues) to that of the fluorescence data indicates that the limited oxidation of proteins by exposure to X‐rays on millisecond timescales does not alter the structure of apomyglobin. This supports the viability of the method for the study of protein folding and the mapping of protein interaction sites.
Social learning in fishes: a review
Authors: Brown Culum , Laland Kevin N
Published: August 2003

Animals acquire skills and knowledge from other animals, and fish are no exception. There is now strong experimental evidence that many species of fish exhibit social learning and traditional behaviours. Here, we review the literature pertaining to social learning in fish, focusing on (i) antipredator behaviour, (ii) migration and orientation, (iii) foraging, (iv) mate choice and (v) eavesdropping.
Learned recognition of conspecifics by fishes
Authors: Griffiths Siân W
Published: August 2003

The study of partner‐choice decisions of individual fish is a good way in which insights into patterns of school structure or territorial assemblages can be gained. Most initial work has focused on the recognition abilities and association patterns of fish in situations where the potential for adaptive costs and benefits is great, such as in the contexts of foraging or antipredator behaviour. However, the benefits of condition‐independent recognition and kin recognition may also have profound effects on patterns of movement and dispersal. Information regarding group membership may be especially important in understanding the spatial position of fish in threatened stocks, and may therefore have implications for fisheries management policies. Future work may therefore benefit from an exploration of the ecological contexts in which learned recognition is important in natural streams and rivers.
Social organisation, shoal structure and information transfer
Authors: Hoare D J , Krause J
Published: August 2003

Recent work suggests that the social structure of fish shoals is nonrandom with strong tendencies for self‐sorting by phenotype in individuals of several species. The frequency of shoal encounters is high in most freshwater species but lower in pelagic fishes where intershoal distances tend to be greater. Detailed knowledge of the encounter rates between shoals and the exchange rates of individuals between shoals during encounters makes it possible to predict the transmission of learned behaviours through a population.
Evaluation of Restoration Techniques for the Succulent Karoo, South Africa
Authors: Beukes P. C. , Cowling R. M.
Published: August 2003

Abstract Possible constraints on the passive recovery of bare areas in the Karoo, a semiarid region in South Africa, include inadequate supply of seed, availability of suitable microsites for plant establishment, altered soil properties, and the truncation of key soil biotic processes. Here we investigate the possibility of initiating the restoration of bare areas by soil surface treatments with gypsum (CaSO4) and/or organic mulch. We also apply an exogenous seed source to test the hypothesis that seed availability limits autogenic recovery. Both gypsum and mulch improved rain water infiltration, gypsum more so than mulch, and both treatments resulted in significantly higher numbers of reseeded seedlings compared with controls. Gypsum also improved the survival of the cohorts of seedlings of the larger seeded Tripteris sinuata. Tripteris showed the highest number of seedlings (maximum count of 150 seedlings/1,000 viable seeds sown) and surviving plants of the three reseeded species, which included two small‐seeded species, Ruschia spinosa and Chaetobromus dregeanus. Throughout the study period significantly higher plant volumes of naturally seeded annuals and perennials were recorded in the gypsum and/or mulch treatments compared with the controls. Germination and emergence of reseeded and naturally seeded plants appears to be determined by the availability of cool season (autumn to spring ) soil moisture, whereas follow‐up rainfall during this time is important for plant survival. Mulching of bare areas in the Succulent Karoo has the potential to re‐create vegetated areas that will further capture and conserve water, soil, and nutrients. Gypsum also showed positive results but might not be a cost‐effective option because of transport costs to these remote arid areas.
Regeneration and functional recovery in the upper extremity of rats after various types of nerve injuries
Authors: Bontioti Eleana N. , Kanje Martin , Dahlin Lars B.
Published: August 2003

Abstract  The aim was to establish an accurate, reproducible, and simple method to evaluate functional recovery after different types of nerve injuries to the brachial plexus of rats. To that end, pawprints, measured as distance between the first and fourth and second and third digits, were used for evaluation of injuries including crush injury, transection/repair, or graft repair of the median, ulnar, and radial nerves. Immunocytochemistry of the C‐terminal flanking peptide of neuropeptide Y (CPON) and neurofilaments was used to investigate the cell body response and axonal outgrowth, respectively. Functional recovery was dependent on the severity as well as on the level of the lesion. Neither a single injury to the median nerve nor an injury to the ulnar nerve affected the pawprint, while an injury to both these nerves or a single injury to the radial nerve caused impairment of pawprints. There was a rapid recovery after crush injury to these nerves compared to previous reports of a similar injury to the sciatic nerve. The pattern of axonal outgrowth was related to the severity of the lesion. A conditioning lesion, i.e., an initial lesion of the same nerve preceding a test injury by a few days, of both motor/sensory fibers led to a quicker functional recovery. Surprisingly, conditioning of only sensory fibers had nearly the same effect. The cell body response was dependent on the level of the nerve lesion. The upper extremity of rats might be useful to evaluate the effects of new repair methods after nerve injuries using functional evaluation with pawprints as a simple and accurate method.
Remodeling of Sinus Node Function After Catheter Ablation of Right Atrial Flutter
Authors: Daoud Emile G. , Weiss Raul , Augostini Ralph S. , Kalbfleisch Steven J. , Schroeder Jason , Polsinelli Georgia , Hummel John D.
Published: August 2003

Sinus Node Remodeling.
Introduction: The purpose of this study was to investigate the effect of ablation of right atrial flutter upon sinus node function in humans.

Methods and Results:This study enrolled 35 patients. Twenty‐four patients (16 men and 8 women; age 68 ± 11 years) were referred for ablation of persistent atrial flutter (duration 8 ± 11 months). After ablation, there was abnormal sinus node function defined as a corrected sinus node recovery time (CSNRT) > 550 msec. The control group consisted of 11 patients who were undergoing pacemaker implantation for sinus node disease but did not have a history of atrial dysrhythmias or ablation. Within 24 hours of ablation or pacemaker implantation, baseline maximal CSNRT was measured through a permanent pacemaker by AAI pacing at six cycle lengths: 600, 550, 500, 450, 400, and 350 msec. CSNRT then was measured in the same manner at 48 hours, 14 days, and 3 months after ablation/pacemaker implantation. P wave amplitude and duration, and percent atrial sensing also were assessed at the same intervals. For patients undergoing atrial flutter ablation, there was progressive temporal recovery of CSNRT (1,204 ± 671 msec at baseline vs 834 ± 380 msec at 3 months; P < 0.001) and a significant increase in the percent atrial sensing and P wave amplitude at 3 months compared with baseline (P < 0.001). In control subjects, there was no change in the CSNRT, percent atrial pacing, or P wave amplitude.

Conclusion: After ablation of persistent atrial flutter, there is temporal recovery of CSNRT and increase in spontaneous atrial activity. These findings suggest that atrial flutter induces reversible changes in sinus node function.
Response of Pulmonary Vein Potentials to Premature Stimulation
Authors: TADA HIROSHI , ORAL HAKAN , OZAYDIN MEHMET , GREENSTEIN RADMIRA , PELOSI FRANK , KNIGHT BRADLEY P. , STRICKBERGER S. ADAM , MORADY FRED
Published: August 2003

Pulmonary Vein Potentials.
Introduction: Pulmonary vein potentials reflect depolarization of muscle fascicles within the myocardial sleeves that surround the pulmonary veins. The response of pulmonary vein potentials to premature stimulation has not been described.

Methods and Results: In 31 patients with paroxysmal atrial fibrillation referred for segmental isolation of the pulmonary veins, programmed stimulation with a single atrial extrastimulus was performed from the coronary sinus. Bipolar and unipolar electrograms were recorded with a decapolar Lasso catheter positioned sequentially within the left superior, left inferior, and right superior pulmonary veins, near the ostium. Premature stimulation often resulted in greater separation of the atrial and pulmonary vein potentials recorded within the pulmonary veins, fractionation of the pulmonary vein potentials, a change in the circumferential activation sequence of the pulmonary vein potentials, and dropout of pulmonary vein potentials.

Conclusion: In response to premature stimulation, the muscle fascicles within the myocardial sleeves that surround the pulmonary veins display a greater degree of decremental conduction than do the myocardial fibers in the adjacent left atrium, and they display heterogeneity in conduction properties and refractoriness. Discrimination of pulmonary vein potentials from atrial electrograms is facilitated by premature stimulation.
Acute and Chronic Electrophysiologic Changes Surrounding Radiofrequency Lesions
Authors: WOOD MARK A. , FULLER ITHIEL A.
Published: August 2003

Electrophysiologic Changes Surrounding RF Lesions.
Introduction: Arrhythmia recurrences may occur after acutely successful radiofrequency (RF) ablation, suggesting reversible electrophysiologic effects on myocardial tissue. The aim of this study was to examine the electrophysiologic changes occurring in myocardium surrounding acute and chronic RF lesions.

Methods and Results: RF lesions (60°C for 30 sec) were produced on the epicardial left ventricular surface of 35 isolated perfused rabbit hearts. Microelectrode transmembrane action potential recordings were made at 0.25‐mm intervals along the epicardial (n = 20) or intramural (n = 6) aspects of the lesions for up to 3.5 mm from the lesion edge at baseline and after acute RF lesion formation. In nine hearts, chronic lesions were studied with epicardial recordings made 22 ± 13 days after RF lesion formation. In the acute hearts at 600‐msec paced cycle length, action potential duration at 50% repolarization (APD50) and 90% repolarization (APD90) were reduced by up to 41% and 19%, respectively, within 2.5 mm from the lesion edge (all P < 0.05). Maximal action potential amplitude (APDmax) was reduced by 16% at 0.25 mm from the lesion edge (P = 0.009) but dV/dt was not changed. Conduction time (CT) from the outermost recording site to the lesion edge (3.5‐mm distance) was reduced from 16 ± 3 msec at baseline to 13 ± 4 msec post ablation (P = 0.006). Qualitatively similar findings occurred at 200‐msec cycle lengths. There were no changes in APD, CT, APDmax, or dV/dt surrounding the chronic lesions at 22 ± 13 days after lesion formation.

Conclusion: Acutely following RF energy delivery, APD, APDmax, and CT are reduced in the tissue surrounding the lesion. These electrophysiologic changes resolve within 22 ± 13 days of lesion formation.
Interaction Between the Autonomic Nervous System and Atrial Tachyarrhythmias
Authors: TAI CHING‐TAI , CHIOU CHUEN‐WANG , CHEN SHIH‐ANN
Published: August 2003

Autonomic Nervous System and Atrial Arrhythmias. Atrial tachyarrhythmias are the most common arrhythmias in the general population. The abundant experimental evidence suggests that the autonomic nervous system plays an important role in the occurrence of atrial arrhythmias. However, complex interactions of the autonomic nervous system with the arrhythmogenic substrate make it difficult to correlate human arrhythmias with the laboratory data. Development of new methods to explore the subtle modulation of the autonomic nervous system may have implications for understanding the arrhythmogenic mechanism and providing an effective therapy.
Paroxysmal Cycle Length Shortening in the Pulmonary Veins During Atrial Fibrillation Correlates with Arrhythmogenic Triggering Foci in Sinus Rhythm
Authors: O'DONNELL DAVID , FURNISS STEVE S. , BOURKE JOHN P.
Published: August 2003

Identifying Arrhythmogenic PVs in AF.
Introduction: The focal origin of atrial fibrillation (AF) is identified by recording atrial ectopic beats or the ectopic activity that precedes AF. We hypothesized that arrhythmogenic pulmonary veins (PVs) also could be identified during persistent AF.

Methods and Results: Patients with persistent AF referred for focal ablation were enrolled prospectively. During AF, bipolar electrograms were recorded from each PV for a minimum of 120 seconds, as well as from the right atrium and coronary sinus. The cycle length of activity in each PV was measured during AF and plotted on a frequency histogram. Following cardioversion to sinus rhythm, arrhythmogenic PVs were identified from reinitiation of AF or from ectopic beats. Ten patients were enrolled and 37 PVs analyzed. During AF, 17 PVs demonstrated bimodal cycle length frequency histograms, with periods of paroxysmal short cycle length recording. Following cardioversion, 14 PVs were identified as arrhythmogenic as defined earlier. Each of these arrhythmogenic PVs showed paroxysmal short cycle length recording during AF. Sensitivity was 87%, specificity 91%, positive predictive value 87%, and negative predictive value 100%.

Conclusion: The arrhythmogenic PVs responsible for the focal activity that triggers AF also demonstrate paroxysmal short cycle length recording during sustained AF. These results demonstrate that arrhythmogenic PVs still can be identified reliably, even during sustained AF.
Analysis of Troponin I Levels After Spontaneous Implantable Cardioverter Defibrillator Shocks
Authors: HASDEMIR CAN , SHAH NAYYAR , RAO ARUN P. , ACOSTA HELBERT , MATSUDAIRA KAGARI , NEAS BARBARA R. , REYNOLDS DWIGHT W. , PO SUNNY , LAZZARA RALPH , BECKMAN KAREN J.
Published: August 2003

Troponin I Levels After Spontaneous ICD Shocks.
Introduction: Serum cardiac troponin I (cTnI) is a sensitive and specific marker for myocardial injury. Myocardial ischemia and/or injury can be a trigger for ventricular arrhythmias. The aim of this study was to assess the frequency and significance of elevated serum cTnI levels after spontaneous implantable cardioverter defibrillator (ICD) shocks.

Methods and Results: Serial cTnI measurements and ECGs were performed in 35 patients with transvenous ICDs who were admitted after spontaneous ICD shocks. Elevated cTnI levels were found in 18 patients (51%). Acute coronary syndrome was diagnosed in 5 (22%) of 23 patients with known coronary artery disease. After excluding the patients with acute coronary syndrome, elevated cTnI levels were present in 13 (43%) of 30 patients: 18% of patients with < 3 shocks and 58% of patients with > 3 shocks. Patients with elevated cTnI levels received a higher number of shocks (16 ± 18 vs 5 ± 7; P < 0.05) and had higher total delivered energies (475 ± 538 J vs 128 ± 184 J; P < 0.05) compared with patients with normal cTnI. Patients with acute coronary syndrome had higher peak cTnI levels (18 ± 16 ng/mL) compared with patients with elevated cTnI without acute coronary syndrome (3.8 ± 4.3 ng/mL; P < 0.01).

Conclusion: Serum cTnI rises occur in the majority of patients after multiple (> 3) spontaneous ICD discharges but are due to acute coronary syndrome only 14% of the time (22% of the time in patients with known coronary artery disease).
Calmodulin and the Philosopher's Stone: Changing Ca2+ into Arrhythmias
Authors: ANDERSON MARK E.
Published: August 2003

Calmodulin and the Philosopher's Stone. It has been recognized for some time that intracellular Ca2+ ([Ca2+]i) can contribute to the genesis of cardiac arrhythmias, but understanding of the molecular signaling machinery that links disordered [Ca2+]i to arrhythmias has been lacking. Exciting recent work has focused on the ubiquitous intracellular Ca2+–binding protein calmodulin. Calmodulin is a molecular sensor that can translate increases in [Ca2+]I into modulatory signals for ion channels and activate other Ca2+–dependent signaling molecules. This article will examine the implications of these recent findings for arrhythmogenesis and the development of new antiarrhythmic therapies.
Excitability of Isolated Hearts from Rats During Postnatal Development
Authors: GOMES PAULO ALBERTO PAES , GALVÃO KLEBER DE MAGALHÃES , MATEUS EVANDRO FALLACI
Published: August 2003

Excitability of Developing Rat Hearts.
Introduction: After birth, cardiac myocytes undergo substantial growth and differentiation that affect their stimulation threshold. Cells from younger animals have a higher stimulation threshold than cells from adults. The aim of this work was to compare the excitability of isolated hearts of rats during postnatal development by measuring the stimulation threshold at several pulse durations.

Methods and Results: Stimulation threshold of isolated hearts were measured at eight different pulse durations between 0.1 to 20 msec. For each heart, a strength‐duration curve was constructed and data were fitted using both Weiss‐Lapicque and Blair models. Analysis of variance showed significant age‐dependent differences in both rheobase field (Ereob) and chronaxie (c). Ereob decreased while c increased during development (Ereob was 0.21, 0.16, 0.13, 0.10, and 0.09 V/cm and c was 2.0, 2.2, 2.3, 2.7, and 3.2 msec for rats aged 1, 2, 4, 8, and 20 weeks, respectively). There was a decrease in the threshold field with heart weight between 0.1 and 0.7 g, whereas the threshold was almost constant in the range from 0.7 to 2.0 g. Estimation of the energy density needed to defibrillate the heart was performed and appeared to be higher for younger than for adult animals.

Conclusion: Hearts from younger animals have higher stimulation threshold than those from adults. This probably is due to changes in the cellular threshold as a result of maturation. The smaller excitability of younger hearts can have consequences with regard to the energy levels required for younger patients.
High‐Resolution Mapping of Tachycardia Originating from the Superior Vena Cava: Evidence of Electrical Heterogeneity, Slow Conduction, and Possible Circus Movement Reentry
Authors: SHAH DIPEN C. , HÄISSAGUERRE MICHEL , JÄIS PIERRE , CLÉMENTY JACQUES
Published: August 2003

Superior Vena Cava Reentry. High‐resolution mapping of a tachycardia originating from the superior vena cava (SVC) in a patient with atrial fibrillation is described. Unidirectional circuitous repetitive activation encompassing the full tachycardia cycle length was documented around a line of block within the myocardial sleeve of the SVC. Intermittent conduction to the right atrium resulted in an irregular atrial tachycardia. Evidence of electrical heterogeneity and slow conduction persisted in sinus rhythm and was exaggerated by premature stimulation but did not reproduce the activation pattern during tachycardia. All the available evidence is best compatible with circus movement reentry within the SVC, with marked slow and anisotropic conduction responsible for the restricted dimensions of the reentrant circuit. These findings may suggest a similar substrate and arrhythmia mechanism in the myocardium of the pulmonary veins.