bluuebunny/crossref_metadata_2025 huggingface dataset:
Slo3 K+ Channels: Voltage and pH Dependence of Macroscopic Currents
Authors: Zhang Xue , Zeng Xuhui , Lingle Christopher J.
Published: August 2006

The mouse Slo3 gene (KCNMA3) encodes a K+ channel that is regulated by changes in cytosolic pH. Like Slo1 subunits responsible for the Ca2+ and voltage-activated BK-type channel, the Slo3 α subunit contains a pore module with homology to voltage-gated K+ channels and also an extensive cytosolic C terminus thought to be responsible for ligand dependence. For the Slo3 K+ channel, increases in cytosolic pH promote channel activation, but very little is known about many fundamental properties of Slo3 currents. Here we define the dependence of macroscopic conductance on voltage and pH and, in particular, examine Slo3 conductance activated at negative potentials. Using this information, the ability of a Horrigan-Aldrich–type of general allosteric model to account for Slo3 gating is examined. Finally, the pH and voltage dependence of Slo3 activation and deactivation kinetics is reported. The results indicate that Slo3 differs from Slo1 in several important ways. The limiting conductance activated at the most positive potentials exhibits a pH-dependent maximum, suggesting differences in the limiting open probability at different pH. Furthermore, over a 600 mV range of voltages (−300 to +300 mV), Slo3 conductance shifts only about two to three orders of magnitude, and the limiting conductance at negative potentials is relatively voltage independent compared to Slo1. Within the context of the Horrigan-Aldrich model, these results indicate that the intrinsic voltage dependence (zL) of the Slo3 closed–open equilibrium and the coupling (D) between voltage sensor movement are less than in Slo1. The kinetic behavior of Slo3 currents also differs markedly from Slo1. Both activation and deactivation are best described by two exponential components, both of which are only weakly voltage dependent. Qualitatively, the properties of the two kinetic components in the activation time course suggest that increases in pH increase the fraction of more rapidly opening channels.
Short-range Molecular Rearrangements in Ion Channels Detected by Tryptophan Quenching of Bimane Fluorescence
Authors: Islas Leon D. , Zagotta William N.
Published: August 2006

Ion channels are allosteric membrane proteins that open and close an ion-permeable pore in response to various stimuli. This gating process provides the regulation that underlies electrical signaling events such as action potentials, postsynaptic potentials, and sensory receptor potentials. Recently, the molecular structures of a number of ion channels and channel domains have been solved by x-ray crystallography. These structures have highlighted a gap in our understanding of the relationship between a channel's function and its structure. Here we introduce a new technique to fill this gap by simultaneously measuring the channel function with the inside-out patch-clamp technique and the channel structure with fluorescence spectroscopy. The structure and dynamics of short-range interactions in the channel can be measured by the presence of quenching of a covalently attached bimane fluorophore by a nearby tryptophan residue in the channel. This approach was applied to study the gating rearrangements in the bovine rod cyclic nucleotide-gated ion channel CNGA1 where it was found that C481 moves towards A461 during the opening allosteric transition induced by cyclic nucleotide. The approach offers new hope for elucidating the gating rearrangements in channels of known structure.
State-independent Block of BK Channels by an Intracellular Quaternary Ammonium
Authors: Wilkens Christina M. , Aldrich Richard W.
Published: August 2006

Intracellular blockade by quaternary ammonium (QA) molecules of many potassium channels is state dependent, where the requirement for channel opening is evidenced by a time-dependent component of block in the macroscopic record. Whether this is the case for Ca2+- and voltage-activated potassium (BK) channels, however, remains unclear. Previous work (Li, W., and R.W. Aldrich. 2004. J. Gen. Physiol. 124:43–57) tentatively proposed a state-dependent, trapping model, but left open the possibility of state-independent block. Here, we found BK channel blockade by a novel QA derivative, bbTBA, was time dependent, raising the possibility of state-dependent, open channel block. Alternatively, the observed voltage dependence of block could be sufficient to explain time-dependent block. We have used steady-state and kinetic measurements of bbTBA blockade in order to discriminate between these two possibilities. bbTBA did not significantly slow deactivation kinetics at potentials between −200 and −100 mV, suggesting that channels can close unhindered by bound bbTBA. We further find no evidence that bbTBA is trapped inside BK channels after closing. Measurements of steady state fractional block at +40 mV revealed a 1.3-fold change in apparent affinity for a 33-fold change in Po, in striking contrast to the 31-fold change predicted by state-dependent block. Finally, the appearance of a third kinetic component of bbTBA blockade at high concentrations is incompatible with state-dependent block. Our results suggest that access of intracellular bbTBA to the BK channel cavity is not strictly gated by channel opening and closing, and imply that the permeation gate for BK channels may not be intracellular.
Regulation of CRAC Channel Activity by Recruitment of Silent Channels to a High Open-probability Gating Mode
Authors: Prakriya Murali , Lewis Richard S.
Published: August 2006

CRAC (calcium release-activated Ca2+) channels attain an extremely high selectivity for Ca2+ from the blockade of monovalent cation permeation by Ca2+ within the pore. In this study we have exploited the blockade by Ca2+ to examine the size of the CRAC channel pore, its unitary conductance for monovalent cations, and channel gating properties. The permeation of a series of methylammonium compounds under divalent cation-free conditions indicates a minimum pore diameter of 3.9 Å. Extracellular Ca2+ blocks monovalent flux in a manner consistent with a single intrapore site having an effective Ki of 20 μM at −110 mV. Block increases with hyperpolarization, but declines below −100 mV, most likely due to permeation of Ca2+. Analysis of monovalent current noise induced by increasing levels of block by extracellular Ca2+ indicates an open probability (Po) of ∼0.8. By extrapolating the variance/mean current ratio to the condition of full blockade (Po = 0), we estimate a unitary conductance of ∼0.7 pS for Na+, or three to fourfold higher than previous estimates. Removal of extracellular Ca2+ causes the monovalent current to decline over tens of seconds, a process termed depotentiation. The declining current appears to result from a reduction in the number of active channels without a change in their high open probability. Similarly, low concentrations of 2-APB that enhance ICRAC increase the number of active channels while open probability remains constant. We conclude that the slow regulation of whole-cell CRAC current by store depletion, extracellular Ca2+, and 2-APB involves the stepwise recruitment of silent channels to a high open-probability gating mode.
Markov Chain Monte Carlo Algorithm based metabolic flux distribution analysis on Corynebacterium glutamicum
Authors: Kadirkamanathan Visakan , Yang Jing , Billings Stephen A. , Wright Phillip C.
Published: August 2006

Motivation: Metabolic flux analysis via a 13C tracer experiment has been achieved using a Monte Carlo method with the assumption of system noise as Gaussian noise. However, an unbiased flux analysis requires the estimation of fluxes and metabolites jointly without the restriction on the assumption of Gaussian noise. The flux distributions under such a framework can be freely obtained with various system noise and uncertainty models.

Results: In this paper, a stochastic generative model of the metabolic system is developed. Following this, the Markov Chain Monte Carlo (MCMC) approach is applied to flux distribution analysis. The disturbances and uncertainties in the system are simplified as truncated Gaussian multiplicative models. The performance in a real metabolic system is illustrated by the application to the central metabolism of Corynebacterium glutamicum. The flux distributions are illustrated and analyzed in order to understand the underlying flux activities in the system.

Availability: Algorithms are available upon request.

Contact:  visakan@sheffield.ac.uk
A new representation for protein secondary structure prediction based on frequent patterns
Authors: Birzele Fabian , Kramer Stefan
Published: August 2006

Motivation: A new representation for protein secondary structure prediction based on frequent amino acid patterns is described and evaluated. We discuss in detail how to identify frequent patterns in a protein sequence database using a level-wise search technique, how to define a set of features from those patterns and how to use those features in the prediction of the secondary structure of a protein sequence using support vector machines (SVMs).

Results: Three different sets of features based on frequent patterns are evaluated in a blind testing setup using 150 targets from the EVA contest and compared to predictions of PSI-PRED, PHD and PROFsec. Despite being trained on only 940 proteins, a simple SVM classifier based on this new representation yields results comparable to PSI-PRED and PROFsec. Finally, we show that the method contributes significant information to consensus predictions.

Availability: The method is available from the authors upon request.

Contact:  kramer@in.tum.de
Tropical—parameter estimation and simulation of reaction–diffusion models based on spatio-temporal microscopy images
Authors: Ulrich Markus , Kappel Constantin , Beaudouin Joel , Hezel Stefan , Ulrich Jochen , Eils Roland
Published: August 2006

Summary: Tropical is a software for simulation and parameter estimation of reaction–diffusion models. Based on spatio-temporal microscopy images, Tropical estimates reaction and diffusion coefficients for user-defined models. Tropical allows the investigation of systems with an inhomogeneous distribution of molecules, making it well suited for quantitative analyses of microscopy experiments such as fluorescence recovery after photobleaching (FRAP).

Availability: Tropical is available free of charge for academic use at after signing a material transfer agreement.

Contact:  r.eils@dkfz.de

Supplementary information:
iFold: a platform for interactive folding simulations of proteins
Authors: Sharma Shantanu , Ding Feng , Nie Huifen , Watson Daniel , Unnithan Aditya , Lopp Jameson , Pozefsky Diane , Dokholyan Nikolay V.
Published: August 2006

Summary: We built a novel web-based platform for performing discrete molecular dynamics simulations of proteins. In silico protein folding involves searching for minimal frustration in the vast conformational landscape. Conventional approaches for simulating protein folding insufficiently address the problem of simulations in relevant time and length scales necessary for a mechanistic understanding of underlying biomolecular phenomena. Discrete molecular dynamics (DMD) offers an opportunity to bridge the size and timescale gaps and uncover the structural and biological properties of experimentally undetectable protein dynamics. The iFold server supports large-scale simulations of protein folding, thermal denaturation, thermodynamic scan, simulated annealing and pfold analysis using DMD and coarse-grained protein model with structure-based Gō-interactions between amino acids.

Availability:  

Contact:  dokh@med.unc.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Configurational‐bias sampling technique for predicting side‐chain conformations in proteins
Authors: Jain Tushar , Cerutti David S. , McCammon J. Andrew
Published: August 2006

Prediction of side‐chain conformations is an important component of several biological modeling applications. In this work, we have developed and tested an advanced Monte Carlo sampling strategy for predicting side‐chain conformations. Our method is based on a cooperative rearrangement of atoms that belong to a group of neighboring side‐chains. This rearrangement is accomplished by deleting groups of atoms from the side‐chains in a particular region, and regrowing them with the generation of trial positions that depends on both a rotamer library and a molecular mechanics potential function. This method allows us to incorporate flexibility about the rotamers in the library and explore phase space in a continuous fashion about the primary rotamers. We have tested our algorithm on a set of 76 proteins using the all‐atom AMBER99 force field and electrostatics that are governed by a distance‐dependent dielectric function. When the tolerance for correct prediction of the dihedral angles is a <20° deviation from the native state, our prediction accuracies for χ1 are 83.3% and for χ1 and χ2 are 65.4%. The accuracies of our predictions are comparable to the best results in the literature that often used Hamiltonians that have been specifically optimized for side‐chain packing. We believe that the continuous exploration of phase space enables our method to overcome limitations inherent with using discrete rotamers as trials.
Revisiting the Voronoi description of protein–protein interfaces
Authors: Cazals Frédéric , Proust Flavien , Bahadur Ranjit P. , Janin Joël
Published: August 2006

We developed a model of macromolecular interfaces based on the Voronoi diagram and the related alpha‐complex, and we tested its properties on a set of 96 protein–protein complexes taken from the Protein Data Bank. The Voronoi model provides a natural definition of the interfaces, and it yields values of the number of interface atoms and of the interface area that have excellent correlation coefficients with those of the classical model based on solvent accessibility. Nevertheless, some atoms that do not lose solvent accessibility are part of the interface defined by the Voronoi model. The Voronoi model provides robust definitions of the curvature and of the connectivity of the interfaces, and leads to estimates of these features that generally agree with other approaches. Our implementation of the model allows an analysis of protein–water contacts that highlights the role of structural water molecules at protein–protein interfaces.
Model of the toxic complex of anthrax: Responsive conformational changes in both the lethal factor and the protective antigen heptamer
Authors: Tama Florence , Ren Gang , Brooks Charles L. , Mitra Alok K.
Published: August 2006

The toxic complex of anthrax is formed when the monomeric protective antigen (PA) (83 kDa), while bound to its cell‐surface receptor, is first converted to PA63 heptamers (PA63h) following N‐terminal proteolytic cleavage, and then lethal (LF) (90 kDa) or edema factor (EF) binds to the heptamer. We report a “pseudoatomic” model for the complex of PA63h and full‐length LF determined by applying the normal‐mode flexible fitting procedure to a ∼18 Å cryo‐electron microscopy (EM) density map of the complex. The model describes the interacting surface that buries a total area of ∼10,140 Å2 comprising ∼40% charged, and ∼30% each of polar and hydrophobic residues. For the heptamer, the buried surface, composed of ∼110 residues, involves primarily three monomers and includes for two, similar stretches of the polypeptide chain from domain 1. For LF, the interface again involves ∼110 residues, mostly from the N‐terminal domain I (LFN), and the structurally homologous C‐terminal domain IV. Most interestingly, bound LF displays a marked conformational change resulting from a “collapse” of domains I, III, and IV on domain II, with the largest movement of ∼9 Å noted for domain I. On the other hand, primarily, rigid‐body movements, larger than ∼10 Å for three PA63 monomers, cause the hourglass‐shaped heptamer lumen to enlarge by as much as ∼50% near the middle of the molecule. Such concerted structural rearrangements in LF and the heptamer can facilitate ingress of the ligand into the heptamer lumen prior to unfolding and release through the PA63h channel formed in the acidic late endosomal membrane.
Comparative analysis and “expression space” coverage of the production of prokaryotic membrane proteins for structural genomics
Authors: Surade Sachin , Klein Markus , Stolt‐Bergner Peggy C. , Muenke Cornelia , Roy Ankita , Michel Hartmut
Published: August 2006

Membrane proteins comprise up to one‐third of prokaryotic and eukaryotic genomes, but only a very small number of membrane protein structures are known. Membrane proteins are challenging targets for structural biology, primarily due to the difficulty in producing and purifying milligram quantities of these proteins. We are evaluating different methods to produce and purify large numbers of prokaryotic membrane proteins for subsequent structural and functional analysis. Here, we present the comparative expression data for 37 target proteins, all of them secondary transporters, from the mesophilic organism Salmonella typhimurium and the two hyperthermophilic organisms Aquifex aeolicus and Pyrococcus furiosus in three different Escherichia coli expression vectors. In addition, we study the use of Lactococcus lactis as a host for integral membrane protein expression. Overall, 78% of the targets were successfully produced under at least one set of conditions. Analysis of these results allows us to assess the role of different variables in increasing “expression space” coverage for our set of targets. This analysis implies that to maximize the number of nonhomologous targets that are expressed, orthologous targets should be chosen and tested in two vectors with different types of promoters, using C‐terminal tags. In addition, E. coli is shown to be a robust host for the expression of prokaryotic transporters, and is superior to L. lactis. These results therefore suggest appropriate strategies for high‐throughput heterologous overproduction of membrane proteins.
Engineered lanthanide‐binding metallohomeodomains: Designing folded chimeras by modular turn substitution
Authors: Lim Sunghyuk , Franklin Sonya J.
Published: August 2006

A series of chimeric metallohomeodomains are described, engineered by rational design of a flexible Ca/Ln binding site into a DNA‐binding scaffold. A modular turn‐substitution approach was used to create proteins that both bind DNA and lanthanide ions, while retaining the secondary structure of the full homeodomain (determined by circular dichroism [CD]). Four similar metallohomeodomains were designed (C1–C4), their structural stability predicted by molecular dynamics (MD) simulation of loop‐mutations into the known homeodomain structure, and each designed protein cloned, expressed, and purified using standard molecular biology techniques. Two of the four loop insertions resulted in folded, metal‐ and DNA‐binding proteins (EuC2 Kd = 2.1 ± 0.4 μM; EuC4 Kd = 3.2 ± 1.0 μM). These results show the successful incorporation of a metal site into a full protein domain, without compromising long‐range structure. This is an important achievement in biomolecular design, as it provides a critical starting point for exploring metallonuclease function and substrate accessibility in a well‐organized chimeric protein domain (rather than only in small HTH peptide systems).
Comparison of genetic models for analysing the effects of a PvuII polymorphism in the oestrogen receptor 1 (ESR1) gene on prolificacy in an Iberian × Meishan pig population
Authors: Braglia S. , Ramírez O. , Noguera J. L. , Tomás A. , Ovilo C. , Varona L.
Published: August 2006

The effect of a previously reported PvuII polymorphism in oestrogen receptor 1 (ESR1) was analysed in an F2 population of Iberian × Meishan pigs. We tested three hypotheses: (1) that a causal mutation was fixed in the parental populations, (2) that a causal mutation existed that was in complete linkage disequilibrium with the alleles of the PvuII polymorphism and (3) that a causal mutation existed in linkage disequilibrium within each parental population. The third model was the most plausible based on the available data. ESR1 alleles displayed different patterns of linkage disequilibrium with the causal mutation in each of the parental populations and the PvuII polymorphism was clearly not the causal mutation. As a consequence, the use of the ESR1 mutation for selection must be evaluated for a particular pig population before it is applied.
Risk of falls after withdrawal of fall‐risk‐increasing drugs: a prospective cohort study
Authors: Van Der Velde Nathalie , Stricker Bruno H. Ch. , Pols Huib A. P. , Van Der Cammen Tischa J. M.
Published: August 2006

What is already known about this subject

• In observational studies, several drugs have been associated with an increased fall risk. A meta‐analysis in 1999 found a significant association for neuroleptics, antidepressants, sedatives, diuretics, type IA antiarrhythmics, and digoxin.

• Nevertheless, knowledge on the effect of withdrawal of these drugs on fall risk is scarce. Only one randomized controlled trial has been carried out in 1999, showing a significantly lowered fall risk after withdrawal of sedatives and antidepressants in community‐dwelling older persons.

What this study adds

• This study indicates that withdrawal of all fall‐risk‐increasing drugs, including both cardiovascular and psychotropic drugs, is an effective intervention for lowering of falls incidence. This effect appears to be highest for withdrawal of cardiovascular drugs.

Aims

Falling in older persons is a frequent and serious clinical problem. Several drugs have been associated with increased fall risk. The objective of this study was to identify differences in the incidence of falls after withdrawal (discontinuation or dose reduction) of fall‐risk‐increasing drugs as a single intervention in older fallers.

Methods

In a prospective cohort study of geriatric outpatients, we included 139 patients presenting with one or more falls during the previous year. Fall‐risk‐increasing drugs were withdrawn, if possible. The incidence of falls was assessed within 2 months of follow‐up after a set 1 month period of drug withdrawal. Multivariate adjustment for potential confounders was performed with a Cox proportional hazards model.

Results

In 67 patients, we were able to discontinue a fall‐risk‐increasing drug, and in eight patients to reduce its dose. The total number of fall incidents during follow‐up was significantly lower in these 75 patients, than in those who continued treatment (mean number of falls: 0.3 vs. 3.6; P value 0.025). The hazard ratio of a fall during follow‐up was 0.48 (95% confidence interval (CI) 0.23, 0.99) for overall drug withdrawal, 0.35 (95% CI 0.15, 0.82) for cardiovascular drug withdrawal and 0.56 (95% CI 0.23, 1.38) for psychotropic drug withdrawal, after adjustment for age, gender, use of fall‐risk‐increasing drugs, baseline falls frequency, comorbidity, Mini‐Mental State Examination score, and reason for referral.

Conclusions

Withdrawal of fall‐risk‐increasing drugs appears to be effective as a single intervention for falls prevention in a geriatric outpatient setting. The effect was greatest for withdrawal of cardiovascular drugs.
Polypharmacy as commonly defined is an indicator of limited value in the assessment of drug‐related problems
Authors: Viktil Kirsten K. , Blix Hege S. , Moger Tron A. , Reikvam Aasmund
Published: August 2006

What is already known about this subject

• Polypharmacy has been linked to heightened risk of occurrence of drug‐related problems (DRPs) and a detrimental health outcome.

• Polypharmacy has been variously defined; in research studies a commonly applied definition has been the concomitant use of five or more drugs.

• The value of using a definite number of drugs as a cut‐off to describe polypharmacy as a risk factor for the occurrence of DRPs has not been validated.

What this study adds

• Nearly half of the patients admitted to general hospitals used five or more drugs; during the hospital stay these patients were prescribed as many new drugs as those admitted with fewer drugs.

• The presence of DRPs increased approximately linearly with the number of drugs used, for the range of one to >11 drugs.

• To set a strict cut‐off to identify polypharmacy and declare that using more than this number of drugs represents a potential risk for occurrence of DRPs, is of limited value in clinical practice.

Aim

To investigate whether polypharmacy defined as a definite number of drugs is a suitable indicator for describing the risk of occurrence of drug‐related problems (DRPs) in a hospital setting.

Methods

Patients admitted to six internal medicine and two rheumatology departments in five hospitals were consecutively included and followed during the hospital stay, with particular attention to medication and DRPs. Comparisons were made between patients admitted with five or more drugs and with less than five drugs. Clinical pharmacists assessed DRPs by reviewing medical records and by participating in multidisciplinary team discussions.

Results

Of a total of 827 patients, 391 (47%) used five or more drugs on admission. Patients admitted with five or more and less than five drugs were prescribed the same number of drugs after admission: 4.1 vs. 3.9 drugs [P = 0.4, 95% confidence interval (CI) − 0.57, 0.23], respectively. The proportion of drugs used on admission which was associated with DRPs was similar in the patient group admitted with five or more drugs and in those admitted with less than five drugs. The number of DRPs per patient increased approximately linearly with the increase in number of drugs used; one unit increase in number of drugs yielded a 8.6% increase in the number of DRPs (95% CI 1.07, 1.10).

Conclusion

The number of DRPs per patient was linearly related to the number of drugs used on admission. To set a strict cut‐off to identify polypharmacy and declare that using more than this number of drugs represents a potential risk for occurrence of DRPs, is of limited value when assessing DRPs in a clinical setting.
Dose selection and population pharmacokinetics of PEG‐Intron in patients with chronic myelogenous leukaemia
Authors: Gupta Samir , Jen Juif , Kolz Karen , Cutler David
Published: August 2006

Aims

To assess the dose selection using population pharmacokinetics of Pegylated Intron‐α2b (PEG‐Intron) in patients with chronic myelogenous leukaemia (CML).

Methods

PEG‐Intron 3–6 µg kg−1 was administered subcutaneously once a week and blood samples were collected up to 48 weeks of treatment. A total of 624 samples collected from 137 patients were included in the analysis. Nonlinear mixed‐effects modelling was used to analyse the sparsely sampled concentration data from a clinical efficacy trial. Covariates in the analysis included weight, sex, age, race, serum creatinine and estimated creatinine clearance (CLcr).

Results

The apparent clearance of PEG‐Intron decreased after repeated dosing. The clearance at treatment week 4 was 42.3 l day−1 (patients with CLcr 120 ml min−1) with interpatient variability 30%. At treatment week 48, the clearance value was reduced to 69% of its week 4 value. CLcr, a composite variable calculated from body weight, sex, age and serum creatinine, had a small but statistically significant influence on the clearance of PEG‐Intron. The clearance of PEG‐Intron in patients with CML was 40% higher than that of hepatitis C virus‐infected patients.

Conclusion

The dose of PEG‐Intron 6.0 µg kg−1 week−1 appeared appropriate in the treatment of patients with CML.
Comparative bioequivalence study between a novel matrix transdermal delivery system of fentanyl and a commercially available reservoir formulation
Authors: Marier Jean‐Francois , Lor Mary , Morin Josée , Roux Lionel , Di Marco Marika , Morelli Gaetano , Sædder Eva Aggerholm
Published: August 2006

Aim

To determine the pharmacokinetics, safety and performance of a novel matrix formulation of fentanyl.

Methods

Transdermal fentanyl was administered as the novel matrix and the Durogesic® reservoir formulations (24 subjects, 100 µg h−1) in a randomized, fully replicate, four‐way crossover study. Serum concentrations of fentanyl were assayed by LC/MS/MS. Pharmacokinetic parameters of fentanyl and performance (adherence and skin irritability) were evaluated.

Results

Test/reference ratio (90% confidence intervals) for AUC0–t, AUCinf and Cmax were 105.5% (99.4, 112.0), 105.3% (99.3, 111.6) and 111.4% (100.4, 123.6), respectively. Adherence and skin irritability results of the two formulations were similar.

Conclusion

The two formulations are expected to result in similar efficacy for the management of severe pain.
Integration of visual and olfactory cues of hosts and non‐hosts by three bark beetles (Coleoptera: Scolytidae)
Authors: CAMPBELL STUART A. , BORDEN JOHN H.
Published: August 2006

Abstract 1. There has been a long‐standing pre‐occupation with how phytophagous insects use olfactory cues to discriminate hosts from non‐hosts. Foragers, however, should use whatever cues are accurate and easily assessed, including visual cues.

2. It was hypothesised that three bark beetles, the mountain pine beetle (MPB), Dendroctonus ponderosae Hopkins, the Douglas‐fir beetle (DFB), D. pseudotsugae Hopkins, and the western balsam bark beetle (WBBB), Dryocoetes confusus Swaine, integrate visual and olfactory information to avoid non‐host angiosperms (e.g. paper birch, trembling aspen), that differ in visual and semiochemical profile from their respective host conifers (lodgepole pine, Douglas‐fir, interior fir), and tested this hypothesis in a series of field trapping experiments.

3. All three species avoided attractant‐baited, white (non‐host simulating) multiple‐funnel traps, and preferred attractant‐baited black (host‐simulating) traps. In experiments combining white, non‐host traps with non‐host angiosperm volatiles, bark beetles were repelled by these stimuli in an additive or redundant manner, confirming that these species could integrate visual and olfactory information to avoid non‐host angiosperms while flying.

4. When antiaggregation pheromones were released from white traps, the DFB and MPB were repelled in an additive‐redundant manner, suggesting that beetles can integrate diverse and potentially anomalous stimuli.

5. The MPB demonstrated the most consistent visual preferences, suggesting that it may be more of a ‘visual specialist’ than the DFB or WBBB, for which visual responses may be more contingent on olfactory inputs.
Statistical power analysis of a 2‐year field study and design of experiments to evaluate non‐target effects of genetically modified Bacillius thuringiensis corn
Authors: DUAN JIAN J. , JIANG CHANGJIAN , HEAD GRAHAM P. , BHATTI MUHAMMAD A. , WARD DENNIS P. , LEVINE STEVE L. , NICKSON THOMAS E. , NEMETH MARGARET A.
Published: August 2006

Abstract 1. A 2‐year field study was conducted in 2000 and 2001 at a farm in Monmouth, Illinois to evaluate the effect of MON 863, a transgenic corn event that expresses the Cry3Bb1 protein for control of corn rootworms, on diverse groups of arthropod populations in a corn ecosystem.

2. The field study employed a split‐plot design with MON 863 and conventional corn as the main plots and several insecticide treatments as subplots; each main plot was replicated four times (i.e. n = 4 block replications for each corn variety). A large number of arthropod taxa were trapped, taxonomically characterised, and counted in all plots. A mixed linear repeated‐measures model was used for analysis of each taxon collected to determine if there was an effect of MON 863 or insecticide regime on that taxonomic group.

3. This report describes the results of a power analysis to determine the ability of the study design to detect an effect of MON 863 corn on the abundance of different groups of arthropods. A 50% difference in average taxon abundance between MON 863 and conventional corn plots was the criterion used in assessing the power.

4. A statistical power analysis of the taxonomic group comparisons made in the 2‐year field study (with independent assignment of treatments each year) showed that only about 28% (22 of 56) of the statistical comparisons made with single years of data achieved ≥80% power to detect a 50% difference in population density. When data from both years of the study were analysed jointly, this level of power was obtained for 86% (24 of 28) the comparisons made.

5. Graphical examination of the mean abundance and coefficient of variation (CV) for different taxa indicated that high abundance (> 5 trap captures per plot per sampling period) and low CV (< 100%) contributed to high statistical power (> 80%). Taxa with extremely low abundance (mean trap captures < 1 individual per plot per sampling period) generally had high CV (> 100%), and statistical comparisons for those taxa had lower power (< 80%).

6. The relevance of these findings for designing field studies on the effects of genetically modified crops on non‐target arthropods with desired levels of power is discussed.
Nocturnal migration of dragonflies over the Bohai Sea in northern China
Authors: FENG HONG‐QIANG , WU KONG‐MING , NI YUN‐XIA , CHENG DENG‐FA , GUO YU‐YUAN
Published: August 2006

Abstract 1. A sudden increase and subsequent sharp decrease of catches of dragonflies in a searchlight trap, with Pantala flavescens Fabricius (Odonata: Libellulidae) predominating, observed at Beihuang Island in the centre of the Bohai Gulf, in 2003 and 2004, indicated a seasonal migration of these insects over the sea during the night in China. The movements were associated with the onset of fog.

2. Simultaneous radar observations indicated that the nocturnally migrating dragonflies generally flew at altitudes of up to 1000 m above sea level, with high density concentrations at about 200–300 or 500 m; these concentrations were coincident with the temperature inversion.

3. During early summer, the dragonflies oriented in a downwind direction, so that the displacement direction varied between different altitudes. In contrast, during late summer, the dragonflies were able to compensate for wind drift, even headwind drift, so as to orient south‐westward no matter how the wind changed, and thus the displacement direction was towards the south‐west.

4. The duration of flight, estimated from the variation of area density derived from radar data and hourly catches in the searchlight trap through the night, was about 9–10 h. The displacement speed detected using radar was ≈5–11 m s−1. Therefore, the dragonflies might migrate 150–400 km in a single flight.

5. The dragonflies were thought to originate in Jiangsu province and they migrated into north‐east China to exploit the temporary environment of paddy fields in early summer. Their offspring probably migrated back south during late summer and autumn.
Costs and benefits of gregarious feeding in the meadow spittlebug, Philaenus spumarius
Authors: WISE MICHAEL J. , KIEFFER DWIGHT L. , ABRAHAMSON WARREN G.
Published: August 2006

Abstract 1. To study the function of group living in a non‐social animal, costs and benefits of feeding in different group sizes (one to eight) were measured for nymphs of the meadow spittlebug (Philaenus spumarius) on tall goldenrod (Solidago altissima).

2. In a controlled greenhouse experiment, the number of nymphs per plant had a significant influence on their mass as adults. Adult mass increased as group size went from one to five nymphs per plant, but fell as the group size increased beyond five. In contrast, the density of nymphs on a plant had no effect on the duration of nymphal development.

3. Nymphal mortality increased linearly as the number of nymphs increased from one to eight per plant.

4. These performance results suggest that the optimal group size of spittlebug nymphs reflects a compromise between bottom‐up influences (e.g. overcoming physical barriers to feeding on xylem) and within‐trophic‐level influences (e.g. avoiding competition for limited plant resources).

5. In a survey of local populations of goldenrod, spittlebug nymphs were found to be slightly but significantly aggregated among host‐plant individuals. In addition, when more than one nymph occurred on a plant, the nymphs tended to feed in shared spittle masses.

6. It is concluded that the aggregated dispersion pattern of spittlebug nymphs reflects an adaptive balance of coping with potentially conflicting demands from different trophic levels.
The relationships between net primary productivity, human population density and species conservation
Authors: Luck Gary W.
Published: August 2006

Aim  In this study, I determine the relationships between net primary productivity (NPP), human population density, species richness and land use. I also examine the implications of human settlement patterns for species conservation.

Location  Australia.

Methods  I document the associations between NPP, human population density and the species richness of birds, butterflies and mammals using correlations and spatial regressions. I also assess changes in land‐use with NPP and population density, focussing particularly on protected areas. An initial exploration into the implications of the NPP‐population density relationship for regional conservation strategies is provided.

Results  Human population density increases with NPP suggesting that available energy may be a key driving force of human settlement patterns. The species richness of each taxonomic group and geographically restricted species also increases with NPP leading to substantial overlap between species diversity and populated regions. The percentage of land designated as minimal use decreases considerably with increasing human population density and NPP, while intensive agriculture is confined entirely to areas of high NPP. There are strong negative relationships between the size of Australia's National Parks and human population density and NPP. Small parks are often surrounded by relatively dense settlements, but have high average NPP, while large parks are mostly isolated and characterized by low productivity. There are no areas in the highest quartile of NPP that also occur in the most sparsely populated regions, presenting challenges for conservation strategies wanting to protect productive areas under the least threat of human development.

Main conclusions  Human population density and species richness respond similarly to variation in NPP, leading to spatial congruence between human settlements and productive, species rich regions. Planning strategies are required that minimize the potential threat posed by human development to diverse ecosystems and maximize the underlying productivity of protected areas. Reducing the level of threat may require stabilizing the size of the human population, while capturing larger areas of relatively high productivity in the conservation reserve system would lead to greater protection of local diversity.
Handling of peripheral intravenous cannulae: effects of evidence‐based clinical guidelines
Authors: Ahlqvist Margary , Bogren Agneta , Hagman Sari , Nazar Isabel , Nilsson Katarina , Nordin Karin , Valfridsson Berit Sunde , Söderlund Mona , Nordström Gun
Published: August 2006

Aim.  This study aimed at evaluating the outcome of implemented evidence‐based clinical guidelines by means of surveying the frequency of thrombophlebitis, nurses’ care, handling and documentation of peripheral intravenous cannulae.

Background.  Peripheral intravenous cannulae are frequently used for vascular access and, thereby, the patients will be exposed to local and systemic infectious complications. Evidence‐based knowledge of how to prevent these complications and how to care for patients with peripheral intravenous cannula is therefore of great importance. Deficient care, handling and documentation of peripheral intravenous cannulae have previously been reported.

Design.  A cross‐sectional survey was conducted by a group of nurses at three wards at a university hospital before and after the implementation of the evidence‐based guidelines.

Method.  A structured observation protocol was used to review the frequency of thrombophlebitis, the nurses’ care, handling and the documentation of peripheral intravenous cannulae in the patient's record.

Results.  A total of 107 and 99 cannulae respectively were observed before and after the implementation of the guidelines. The frequency of peripheral intravenous cannulae without signs of thrombophlebitis increased by 21% (P < 0·01) and the use of cannula size 0·8 mm increased by 22% (P < 0·001). Nurses’ documentation of peripheral intravenous cannula improved significantly (P < 0·001).

Conclusion.  We conclude that implementation of the guidelines resulted in significant improvements by means of decreased frequency of signs of thrombophlebitis, increased application of smaller cannula size (0·8 mm), as well as of the nurses’ documentation in the patient's record.

Relevance to clinical practice.  Further efforts to ameliorate care and handling of peripheral intravenous cannulae are needed. This can be done by means of increasing nurses’ knowledge and recurrent quality reviews. Well‐informed patients can also be more involved in the care than is common today.
A new research agenda: improving health care in general hospitals
Authors: Brown Michael , MacArthur Juliet
Published: August 2006

Aim and objectives. To set out the research required to improve the health of people with learning disabilities in general hospital settings. The objectives are: (i) to share service developments in a mapping exercise to provide a picture of current work in this area, and (ii) to identify practice issues and experiences that can contribute to a broader research agenda.

Background. It is recognized that people with learning disabilities are high users of all healthcare systems and have different pattern of health needs that often go unidentified, with some requiring general hospital care. The research evidence base in this area of practice needs to be developed to promote and improve health care.

Method. A facilitated focus group design was employed at a conference event to identify areas for research in the future and determined that action is required on four broad research fronts.

Results. Research is required to establish core principles of care, service developments, practical care measures and influencing change in practice.

Conclusion. Research collaborations need to be established to support activity in this area and requires action in the future.

Relevance to clinical practice. The evidence base and understanding of the high and differing pattern of health needs of people with learning disabilities continues to evolve and develop, with considerable scope to identify new areas for research. A conference approach was used to identify research questions to improve the care of this group in general hospital settings and offers a model that may be helpful in defining new areas of enquiry in the future.
The meaning of living with dementia and disturbing behaviour as narrated by three persons admitted to a residential home
Authors: Graneheim Ulla H , Jansson Lilian
Published: August 2006

Aim.  The aim of our study was to illuminate the meaning of living with dementia and disturbing behaviour, as narrated by three persons admitted to a residential home.

Background.  Living with dementia and so‐called disturbing behaviour in an institution involves interaction with care providers and fellow residents and poses a challenge to all who are involved.

Methods.  We asked the head nurses at a residential home to select persons with dementia and disturbing behaviour who were willing to be interviewed and able to communicate verbally. We performed 10 informal conversational interviews with three persons. The interviews were transcribed into text and interpreted using a phenomenological hermeneutic method inspired by Ricoeur's philosophy.

Results.  The findings indicate that the meaning of living with dementia and disturbing behaviour, as narrated by three persons admitted to a residential home, is about being surrounded by disorder, being trapped by restriction and being set aside, as well as about being included. The findings are interpreted as a collapse of relations to self and others intertwined with occasional episodes of togetherness. This is reflected on in relation to the literature on homelessness and at‐homeness and loss and maintenance of personal and social selves.

Relevance to clinical practice.  The view others have of the person with dementia and of disturbing behaviour determines the nursing care given. Taking the residents’ personal history and actual context into account, disturbing behaviour may be seen as a way persons with dementia express their story and maintain their self.
Nurses’ perceptions of their documentation experiences in a computerized nursing care planning system
Authors: Lee Ting‐Ting
Published: August 2006

Aim.  To explore how the content design of a computerized nursing care plan affects nurses’ perceptions of their documentation experience, specifically in making care plans.

Background.  Nurses’ attitudes towards and experiences of computer use in daily practice have been studied. However, no studies have examined how using a computerized nursing care planning system affects nurses’ perceptions of the documentation process.

Methods.  A descriptive, exploratory qualitative approach was used to conduct one‐on‐one, in‐depth interviews with 20 nurses. The major interview question was, ‘What do you think the content of the computerized care plan provided in making care plans?’ Data analysis was based on Miles and Huberman's data reduction, data display, and a conclusion verification process.

Findings.  Nurses generally viewed the content of the computerized nursing care planning system as a reference to aid memory, a learning tool for patient care, and a vehicle for applying judgement to modify care plan content.

Conclusions.  Although computer technology is designed to streamline nurses’ work, using a computerized care plan system can also enhance their knowledge, experience and judgement of descriptions of patient problems and care strategies. Thus, the effects of using technology on documentation behaviours or patterns may deserve further exploration.

Relevance to clinical practice.  While computerized documentation systems have been used widely in patient care, little attention has been given to how the design of care plan content affects the documentation process. Electronic documentation systems can introduce nurses to new skills and knowledge that may improve care quality.
RT01 Veterinary education: teaching the unteachable
Authors: FINK‐GREMMELS J.
Published: August 2006

Objective

After the Bologna declaration, signed by 29 European countries in 1999, a strong debate on veterinary education arose. Although at present none of the European veterinary schools have officially introduced the Bologna process to veterinary curricula, the discussion about the definition of competence and professional skill of graduates in veterinary medicine is controversial. In this context, veterinary pharmacology and toxicology are disciplines undergoing continuous development and becoming increasingly important in the different areas of veterinary profession. In this round‐table, different points of view on the challenge to teach Veterinary Pharmacology and Toxicology at a high quality level in the third millennium will be considered.
RT02 The Research teaching nexus in veterinary pharmacology
Authors: McKELLAR Q.
Published: August 2006

Objective

After the Bologna declaration, signed by 29 European countries in 1999, a strong debate on veterinary education arose. Although at present none of the European veterinary schools have officially introduced the Bologna process to veterinary curricula, the discussion about the definition of competence and professional skill of graduates in veterinary medicine is controversial. In this context, veterinary pharmacology and toxicology are disciplines undergoing continuous development and becoming increasingly important in the different areas of veterinary profession. In this round‐table, different points of view on the challenge to teach Veterinary Pharmacology and Toxicology at a high quality level in the third millennium will be considered.