bluuebunny/crossref_metadata_2025 huggingface dataset:
Consequences to fitness‐related traits of hybridization between farmed and wild Atlantic salmon, Salmo salar
Authors: Lawlor J. L. , Hutchings J. A.
Published: December 2004

Introgression between wild and farmed Atlantic salmon Salmo salar has been hypothesized to influence the persistence of wild populations, particularly those at heightened risk of extinction. Based on pure and hybrid crosses involving one farmed and two wild populations (Tusket River and Stewiacke River, an endangered population) in a common‐garden environment, we examined the consequences of introgression to survival, growth, and disease resistance in the first year of life. Introgression with farmed salmon had either no effect (Stewiacke) or a negative effect (Tusket) on survival. Importantly, the among‐family variance in survival (a negative correlate of population persistence) was higher for the hybrids than it was among the pure crosses. There was also evidence of genetic differences in growth rate and disease susceptibility. Introgression with their farmed counterparts is unlikely to have a positive effect on the fitness of wild Atlantic salmon. The degree to which genetic interactions between farmed and wild salmon threaten the latter's persistence almost certainly depends on the degree to which individuals are adapted to their local environment, on the genetic differentiation between farmed and wild individuals, and on the relative proportions of farmed and wild salmon during spawning.
Domestication, comparative biology and interactions of wild and cultured fish: convenor's synthesis
Authors: Lorenzen K. , Beveridge M. , Mangel M.
Published: December 2004

Aquaculture is expanding rapidly and many fish species are brought into cultivation, entering a process of domestication with consequences for their morphology, physiology, ecology and evolution. In some species the abundance of cultured populations matches or exceeds that of wild stocks, and interactions between cultured and wild fish can pose significant conservation challenges. At the same time, captive breeding and re‐introduction play an important role in the conservation of some of the world's most endangered fishes. Drawing on contributions from the FSBI Symposium and the wider literature, we synthesize current knowledge of the process and extend of fish domestication, interactions between cultured and wild fish, and the use of cultured fish in fisheries enhancement and restoration. We provide a perspective on the role of biological issues within the wider context of aquaculture development and aquatic conservation biology, and conclude with a discussion of promising avenues for further research.
The ontogeny of the alimentary tract of larval pandora, Pagellus erythrinus L.
Authors: Micale V. , Garaffo M. , Genovese L. , Spedicato M. T. , Muglia U.
Published: December 2004

The ontogenesis of the alimentary tract and its associated structures (liver, pancreas, gall bladder) was studied in common pandora Pagellus eythrinus L., a promising species for diversification in Mediterranean aquaculture. Mass production of pandora has been limited so far by high larval and juvenile mortalities, which appear to be related to nutritional deficiencies. The development of the larval digestive system was studied histologically from hatching (0 DAH) until day 50 (50 DAH) in reared specimens, obtained by natural spawning from a broodstock adapted to captivity. At first feeding (3–4 DAH) both the mouth and anus had opened and the digestive tract was differentiated in four portions: buccopharynx, oesophagus, incipient stomach and intestine. The pancreas, liver and gall bladder were also differentiated at this stage. Soon after the commencement of exogenous feeding (5–6 DAH), the anterior intestinal epithelium showed large vacuoles indicating the capacity for absorption of lipids, whereas acidophilic supranuclear inclusions indicating protein absorption were observed in the posterior intestinal epithelium. Both the bile and main pancreatic ducts had opened in the anterior intestine, just after the pyloric sphincter, at this stage. Intestinal coiling was apparent since 4 DAH, while mucosal folding began at 10 DAH. Scattered mucous cells occurred in the oral cavity and the intestine, while they were largely diffused in the oesophagus. Gastric glands and pyloric caeca were firstly observed at 28 DAH and appeared well developed by 41 DAH, indicating the transition from larval to juvenile stage and the acquisition of an adult mode of digestion.
Influence of dietary protein level on growth performance and body composition of juvenile blackspot seabream, Pagellus bogaraveo(Brunnich, 1768)
Authors: Silva P. , Andrade C. A. P. , Timóteo Viriato M. F. A. , Rocha E. , Valente L.M.P.
Published: December 2004

Blackspot seabream Pagellus bogaraveo is a potential candidate species for southern European aquaculture. A 12‐week feeding trial was then conducted to evaluate the effect of dietary protein level on growth performance, body composition and feed use efficiency of blackspot seabream juveniles (22·7 g each). Five isolipidic diets (12·5%) with graded levels of protein (20, 30, 40, 50 and 60%) were hand‐distributed, twice a day, to duplicate groups of fish (120 fish per tank), until satiation. Growth (DGC), survival and feed utilization (FCR) were recorded through monthly sampling. Growth performance was significantly affected by dietary protein level (P < 0·05), and fish fed at the 50% protein level exhibited the highest final body mass. Feed conversion ratio decreased with increasing levels of dietary protein, fish fed 60% protein being the most efficient. No significant differences were found in whole body composition among treatments (P > 0·05). Financed by FCT (Project POCTI/CVT/39239/2001, PhD Grant SFRH‐BD‐14068–2003)
Hatching time as an indicator of environmental incompatibility and outbreeding depression in intraspecific salmon hybrids
Authors: Wang I. A. , Smoker W. W. , Gilk S. E. , Oxman D. S. , Gharrett A. J.
Published: December 2004

We analysed hatching times of hybrids between two spatially separated pink salmon Oncorhynchus gorbuscha populations. We repeated the experiment in independent even‐ and odd‐year broodlines. In 1996 and in 1997, we made F1 hybrids from Auke Creek (Juneau, Alaska) females and Pillar Creek (Kodiak, 1000 km away) males and F1 controls from Auke Creek parents. Families were reared and released at Auke Creek. F2 hybrids, controls, and backcrosses were made from F1 returns in 1998 and 1999. In 2001, we made F1 hybrids at Pillar Creek with native females and Auke Creek males. Pillar Creek ancestry prolonged development: At Auke Creek, hybrid families (half Pillar Creek ancestry) developed more slowly (more Accumulated Temperature Units between fertilization and hatch; P < 0·0001) than did controls (only Auke Creek ancestry). At Pillar Creek, families with only Pillar Creek ancestry developed more slowly than did hybrids with half Auke Creek ancestry. Development times of backcrosses were intermediate between those of hybrids and controls. The variation in development times between Auke Creek and Pillar Creek pink salmon has a genetic component that probably results from local adaptation and illustrates a mechanism that can lead to outbreeding depression in intercrosses between salmon populations (e.g., occurring between wild and translocated stocks).
The Emperor’s New Computers: Y2K (Re)Visited
Authors: Quigley Kevin
Published: December 2004

In order to deal with the threat of Y2K (the Millennium Bug) the UK Government directed an uncreative, resource‐heavy, centralized operation with standardized reporting requirements. The project impacted almost all government systems, from the critical to the mundane. The government’s position was made worse by administrative changes that it had initiated in the 1980s and 1990s that had created a much larger network of delivery partners while at the same time hollowing out IT expertise within the civil service. With little regulation in place, the government was vulnerable to IT opportunists who recognized the financial gains that Y2K offered. An alarmist media also exacerbated the problem. The paper ends by offering some observations regarding the government’s management of IT and how this might be improved to allow the government to pursue its Modernization Agenda.

Things did not go right by accident.

Cabinet Office Press Release on Y2K, inBeckett 2000a
Precautionary Bans or Sacrificial Lambs? Participative Risk Regulation and the Reform of the UK Food Safety Regime
Authors: Rothstein Henry F.
Published: December 2004

This paper considers the impact of contemporary trends towards participative risk regulation on policy processes and outcomes. Using the example of reform of the UK food safety regime, the paper examines whether participative reforms are able to deliver their promised benefits and if not, why not. Empirically, the paper examines how in 2002 the UK's Food Standards Agency used a stakeholder decision‐making process to manage the potential risks from BSE in sheep. The paper finds that the potential benefits of the stakeholder process were mitigated by a number of institutional factors, including: interpretative flexibility in representing consumer interests and the concept of precaution; restricted openness and exclusion of key stakeholders; and the supra‐national regulatory context. The paper concludes that broadening participation per se does not necessarily produce more democratic or robust policy outcomes than closed processes, although it may have some limited value in improving public confidence in the regulatory regime.
Distributed Public Governance in Britain
Authors: Flinders Matthew
Published: December 2004

The structure of the British state is growing increasingly complex. This trend raises a number of questions that focus on the forces stimulating this complexity and its implications both for society‐state relationships and the design and implementation of public policy. This article focuses on one specific element or strand of these debates: the growth in the number and role of quasi‐autonomous public bodies within Britain. It seeks to analyse and reflect upon the distinctive approach taken by the Labour government, since winning office in May 1997, in relation to the sphere of ‘distributed public governance’ in Britain. Moreover, the article seeks to locate this analysis within broader debates surrounding the future of the British state and the Labour government's approach to statecraft through a thematic framework based around: growth, co‐ordination, accountability, depoliticization and power. The central argument of this article is that the Labour government has increased considerably the sphere of distributed public governance in Britain. This process has been largely devoid of an underpinning rationale and this may have significant implications for successful policy delivery, the public's trust in government and the future trajectory of the British state.
The UK BSE Crisis as a Failure of Government
Authors: Gerodimos Roman
Published: December 2004

This paper uses the BSE (‘mad cow disease’) crisis as a case study of the workings of the British core executive during a crisis event. Using the evidence from the Philips Inquiry, which reported on the BSE/vCJD crisis in 2000, the study analyses the patterns of decision making and the structures of institutional and resource dependence. It concludes that the lack of co‐ordination between and within institutions and what was acknowledged to be the mismanagement of expert advice raise serious questions about the executive's ability to manage serious crises. The findings concur with scholarship indicating executive fragmentation and lack of accountability. Consecutive British governments have sought to diminish the centre's responsibility for managing public policy without putting an effective alternative mechanism in place.
A Caregiving Model of Coping with a Partner's Depression*
Authors: Jeglic Elizabeth L. , Pepper Carolyn M. , Ryabchenko Karen A. , Griffith James W. , Miller Allison B. , Johnson Matthew D.
Published: December 2004

Abstract: To test a caregiving model of depression in spouses, 31 married couples completed interview and questionnaire assessments of depressive symptoms and caregiving activities. Spouses living with a partner with depressive symptoms had more symptoms of depression themselves. However, this association was found to be fully mediated by spouses’ perceived level of caregiving stress and burden. Results suggest that feelings of stress associated with caring for a depressed spouse may lead to depressive symptoms in the caregiving spouse and should be addressed in treatment.
Staying Connected While Nurturing an Infant: A Challenge of New Motherhood*
Authors: Paris Ruth , Dubus Nicole
Published: December 2004

Abstract: Fifteen at‐risk new mothers participating in a volunteer home‐visiting program were interviewed about their experiences with these home‐visitors and their relationships with close family and friends after their babies were born. Results of the qualitative analysis, viewed through the lens of Relational Cultural Theory (RCT), detail the social isolation and personal disconnection that they experienced. Their narratives also provide insights about the volunteers’ use of techniques—such as validation, affirmation, consistency, and emotional and instrumental aid—to enhance the mothers’ self‐confidence in caring for their babies, to reduce painful feelings, and to increase interpersonal connections. Recommendations are included for working with couples anticipating a new baby.
Gender and Sexual Orientation in Family Therapy: Toward a Postgender approach
Authors: Knudson‐Martin Carmen , Laughlin Martha J.
Published: December 2004

Abstract: We examine how the issues of gender and sexual orientation have been addressed in family therapy and identify critical issues as the field defines itself in a postmodern, inclusive era. We show how unintentional bias and creation of the category of “other” persist throughout the history of clinical practice despite a rise of interest in diversity. We suggest that family therapy approaches have been based on a view of sex‐gender that creates dichotomous categories, confounds gender and sexual orientation, and limits flexibility. A postgender approach organized around a relationship model based on equality rather than gender is advocated. Obstacles to postgender practice are identified, and guidelines for practice and challenges for the future are discussed.
Comparative evaluation of sturgeon larvae and juveniles reared under control of seasonal propogation of the wild and domestic breeders
Authors: Galich E. V. , Chebanov M. S.
Published: December 2004

Sturgeon populations (Acipenser gueldenstaedtii and A. stellatus) in the Sea of Azov basin are maintained largely through stock enhancement. A monitoring is in operation for biological characteristics of juveniles, including body length and mass, physiological‐biochemical indices, teratology, thermal stability, salt resistance, oxygen deficiency resistance and melanophore adaptive response as indicators of physiological fitness, and neuro‐pharmacological testing with a sedative (MS‐222). Behavioural experiments include the assessment of background movement and reactivity to the effect of low/high frequency sounds and light of long/short duration. Juveniles obtained from breeders in which the reproductive cycle had been delayed for up to 90 days did not show significantly different levels of morphological anomalies compared to juveniles obtained with conventional reproductive techniques. The most frequent defects are observed in pectoral fins (up to 20 per cent) and olfactory organs (up to 10 per cent). Fingerlings showed and adequate and timely adaptive reaction of melanophores towards dark and light background. The experiment demonstrated that sturgeon fingerlings produced under controlled conditions are euryhaline and robust to thermal and oxygen stress. Some differences in biological attributes were noted between juveniles obtained from wild and domesticated breeders of A. gueldenstaedtii and A. stellatus.
Gene expression patterns in Atlantic salmon Salmo salar: gene expression during osmoregulation in intestine tissue
Authors: Hubert S. , O'Keeffe A. M. , Cotter D. , Wilkins N. P. , Cairns M. T.
Published: December 2004

Ireland has the world's largest stocks of wild Atlantic salmon. A better understanding of gene expression will benefit conservation of wild stock as well as salmon aquaculture. We describe the PRTLI project designed to advance the fundamental understanding of the genome of Atlantic Salmon Salmo salar. The major objective is to create the first comprehensive database of gene expression and functional information using cDNA libraries and Microarray technology. One key area of interest to salmon biology is osmoregulation, which is critical to the ability of salmon to adapt in seawater. Tissues implicated in this process are the gills, intestine and skin. To initiate studies, SSH (suppression subtractive hybridization) libraries were constructed from intestine RNA extracted from smolts sampled in January and May. A number of potentially interesting clones have been identified, among those a heat shock protein, hsp90 in the reverse library. Others SSH libraries from various tissues (pituitary, hypothalamus, brain, gill, intestine, head kidney and spleen) have also been constructed and will be used to construct a 5000 clone microarray slide. This slide will then be used to elucidate gene expression profiles in various tissues. Further sample collection has been carried out to answer questions regarding biologicaldifferences between one‐ year and two‐year old parr and wild and hatchery smolt.
The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)‐ibuprofen enantiomer in healthy subjects
Authors: Martínez Carmen , García‐Martín Elena , Blanco Gerardo , Gamito Francisco J. G. , Ladero José M. , Agúndez José A. G.
Published: December 2004

Aims

To study the effect of CYP2C8*3, the most common CYP2C8 variant allele on the dis‐position of (R)‐ibuprofen and the association of CYP2C8*3 with variant CYP2C9 alleles.

Methods

Three hundred and fifty‐five randomly selected Spanish Caucasians were screened for the common CYP2C8 and CYP2C9 mutations. The pharmacokinetics of (R)‐ibuprofen were studied in 25 individuals grouped into different CYP2C8 genotypes.

Results

The allele frequency of CYP2C8*3 (0.17) was found to be higher than that reported for other Caucasian populations (P = 0.0001). The frequencies of CYP2C9*2 and CYP2C9*3 were 0.19 (0.16–0.21) and 0.10 (0.08–0.12), respectively. An association between CYP2C8*3 and CYP2C9*2 alleles was observed, occurring together at a frequency 2.4‐fold higher than expected for a random association of alleles (P = 0.0001). The presence of the CYP2C8*3 allele was found to influence the pharmacokinetics of (R)‐ibuprofen in a gene–dose effect manner. Thus, after administration of 400 mg ibuprofen, the plasma half‐life (95% confidence intervals) for individuals with genotypes CYP2C8*1/*1, CYP2C8*1/*3 and CYP2C8*3/*3, was 2.0 h (1.8–2.2), 4.2 h (1.9–6.5; P < 0.05) and 9.0 h (7.8–10.2; P < 0.002), respectively. A statistically significant trend with respect to the number of variant CYP2C8*3 alleles was also observed for the area under the concentration‐time curve (P < 0.025), and drug clearance (P < 0.03).

Conclusion

Polymorphism of the CYP2C8 gene was found to be common, with nearly 30% of the population studied carrying the variant CYP2C8*3 allele. The presence of the latter caused a significant effect on the disposition of (R)‐ibuprofen. This suggests that a substantial proportion of Caucasian subjects may show alterations in the disposition of drugs that are CYP2C8 substrates.
Dose‐response to salbutamol via a novel palm sized nebuliser (Aerodose® Inhaler), conventional nebuliser (Pari LC Plus) and metered dose inhaler (Ventolin™ Evohaler™) in moderate to severe asthmatics
Authors: Lipworth Brian J. , Sims Erika J. , Taylor Karla , Cockburn Wendy , Fishman Robert
Published: December 2004

Aims

The Aerodose® inhaler is a novel, palm‐sized, breath actuated device which requires little patient coordination. This study compared the dose–response of salbutamol delivered by the Aerodose® Inhaler (Aerogen Inc., Mountain View, USA) vs Pari LC Plus jet nebulizer (Pari LC Plus; Pari GmbH, Starnberg, Germany) and Ventolin™ Evohaler™ HFA pMDI (Evohaler; Allen & Hanburys [GlaxoSmithkline], Uxbridge, UK).

Methods

Twenty‐two moderate to severe asthmatic patients, mean (s.d.) age: 44.7 (9.4), FEV1: 58.1 (12.0), received 4 cumulative doubling doses of salbutamol in a randomised, investigator blind, balanced crossover design. Spirometry and systemic safety variables (heart rate, blood pressure, T wave amplitude, QTc interval and potassium) were measured at baseline and after each dose.

Results

Parallel regression analysis revealed that microgram relative potency ratios for the Aerodose® Inhaler to be five times more efficient for FEV1 than either the Pari LC Plus (0.202, 90% CI: 0.189–0.216) or the Evohaler (0.202, 90% CI: 0.189–0.216), while there was no difference between Pari LC Plus vs Evohaler. Similarly, Aerodose® Inhaler vs. Pari LC Plus showed approximately five‐fold greater potency for all systemic parameters, except blood pressure. As compared to the Evohaler, Aerodose® Inhaler had equivalent potency for plasma potassium and T wave amplitude, but demonstrated greater potency for heart rate and QTc interval.

Conclusions

This study has indicated therefore, that Aerodose® Inhaler is approximately five times as efficient as the Pari LC Plus and Evohaler in relative lung delivery of salbutamol in moderate to severe asthmatics.
Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype
Authors: Zhang Yifan , Zhong Dafang , Si Dayong , Guo Yingjie , Chen Xiaoyan , Zhou Hui
Published: December 2004

Aims

To investigate the pharmacokinetics of lornoxicam and the relationship with CYP2C9 polymorphism in healthy Chinese subjects.

Methods

A single oral dose of 8 mg lornoxicam was administered to 18 healthy Chinese male subjects. Plasma was sampled for 24 h post dose, and plasma concentrations of lornoxicam were measured using a validated LC/MS/MS method. CYP2C9 genotype was determined by polymerase chain reaction‐based restriction fragment length polymorphism or by direct sequencing of the coding region of the CYP2C9 gene.

Results

Of the18 subjects, one subject was found to be a very poor metabolizer of lornoxicam with a long t1/2 of 106 h, a low CL/F of 0.71 ml min−1, and a high AUC0–∞ of 187.6 µg ml−1 h. Genotyping studies revealed that this subject was heterozygous for CYP2C9*3 and a new variant CYP2C9 allele. Of the other 17 subjects, 13 were *1/*1 carriers, three were *1/*3 carriers, and one was a *1/*2 carrier. Mean AUC0–∞ values (95% confidence intervals) of lornoxicam were 9.25 (6.55, 11.95) vs. 4.75 (3.55, 5.95) µg ml−1 h in *1 heterozygotes vs.*1 homozygotes, and mean CL/F values were 14.8 (10.2, 19.4) vs. 32.9 (24.5, 41.3) ml min−1, respectively (P < 0.05 for both AUC and CL/F).

Conclusions

The results show that the pharmacokinetics of lornoxicam are dependent on CYP2C9 polymorphism. In particular, the presence of the CYP2C9*3 allele impairs the oral clearance of lornoxicam.
A population‐based assessment of the potential interaction between serotonin‐specific reuptake inhibitors and digoxin
Authors: Juurlink David N. , Mamdani Muhammad M. , Kopp Alexander , Herrmann Nathan , Laupacis Andreas
Published: December 2004

Aim

In vitro evidence suggests that some serotonin‐specific reuptake inhibitors (SSRIs) inhibit P‐glycoprotein, a multidrug efflux pump responsible for the elimination of several drugs including digoxin. We sought to determine if some SSRIs cause digoxin toxicity in the clinical setting.

Methods

Population‐based nested case–control study set in Ontario, Canada from 1994 to 2001. We studied all patients 66 years or older treated with digoxin. Prescription and hospital admission records were analysed to determine the relationship between the initiation of SSRI therapy and hospital admission for digoxin toxicity in the subsequent 30 days.

Results

Among 245 305 older patients treated with digoxin, we identified 3144 cases of digoxin toxicity. After adjusting for potential confounders, we observed an increased risk of digoxin toxicity following initiation of paroxetine [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.6, 4.7], fluoxetine (OR 2.9; 95% CI 1.5, 5.4), sertraline (OR 3.0; 95% CI 1.9, 4.7), and fluvoxamine (OR 3.0; 95% CI 1.5, 5.7). However, an elevated risk was also seen with tricyclic antidepressants (OR 1.5; 95% CI 1.0, 2.4) and benzodiazepines (OR 2.1; 95% CI 1.7, 2.5), drugs classes having no known pharmacokinetic interaction with digoxin. There was no statistical difference in the risk of digoxin toxicity among any of the agents tested.

Conclusions

We found no major discrepancy in the risk of digoxin toxicity after initiation of various SSRI antidepressants, suggesting that the inhibition of P‐glycoprotein by sertraline and paroxetine observed in vitro is unlikely to be of major clinical significance.
National differences in publishing papers on adverse drug reactions
Authors: Ferner R. E. , Aronson J. K.
Published: December 2004

Aims

To examine how countries differ in attitudes to adverse drug reactions by examining published scientific papers.

Methods

We searched Ovid EMBASE for publications indexed by the category ′therapeutic agents′, and the subcategory ′adverse effects′, by country for 43 countries.

Results

We counted 1 810 202 papers world‐wide regarding therapeutic agents during 14 years, of which 195 154 (10.8%) were included in the adverse effects subcategory. There were substantial differences between countries, not explained by population, economic variation, overall publication rate on therapeutic agents, or the presence of large indigenous pharmaceutical companies.

Conclusions

Many local cultural factors influence the ratio of papers on adverse reactions to all drug effects, so it may be difficult to improve their recognition and reporting by international efforts.
How do follicular dendritic cells interact intimately with B cells in the germinal centre?
Authors: Park Chan‐Sik , Choi Yong Sung
Published: December 2004

The germinal centre is a dynamic microenvironment where antigen‐activated B cells rapidly expand and differentiate, generating plasma cells and memory B cells. These cellular events are accompanied by dramatic changes in the antibody molecules that undergo somatic hypermutation and isotype switching. Follicular dendritic cells (FDCs) are the stromal cells located in the germinal centre. Although the capacity of FDCs to present antigen to B cells through antigen–antibody complexes has been recognized for many years, additional critical functions of FDCs have only recently been recognized. FDCs prevent apoptosis of germinal centre B cells and stimulate cellular interaction and proliferation. Here, we review the FDC signalling molecules that have recently been identified, some of which offer potential therapeutic targets for autoimmune diseases and B‐cell lymphomas.
Identification of novel heat shock factor‐dependent genes and biochemical pathways in Arabidopsis thaliana
Authors: Busch Wolfgang , Wunderlich Markus , Schöffl Fritz
Published: December 2004

In order to assess specific functional roles of plant heat shock transcription factors (HSF) we conducted a transcriptome analysis of Arabidopsis thaliana hsfA1a/hsfA1b double knock out mutants and wild‐type plants. We used Affymetrix ATH1 microarrays (representing more than 24 000 genes) and conducted hybridizations for heat‐treated or non‐heat‐treated leaf material of the respective lines. Heat stress had a severe impact on the transcriptome of mutant and wild‐type plants. Approximately 11% of all monitored genes of the wild type showed a significant effect upon heat stress treatment. The difference in heat stress‐induced gene expression between mutant and wild type revealed a number of HsfA1a/1b‐regulated genes. Besides several heat shock protein and other stress‐related genes, we found HSFA‐1a/1b‐regulated genes for other functions including protein biosynthesis and processing, signalling, metabolism and transport. By screening the profiling data for genes in biochemical pathways in which known HSF targets were involved, we discovered that at each step in the pathway leading to osmolytes, the expression of genes is regulated by heat stress and in several cases by HSF. Our results document that in the immediate early phase of the heat shock response HSF‐dependent gene expression is not limited to known stress genes, which are involved in protection from proteotoxic effects. HsfA1a and HsfA1b‐regulated gene expression also affects other pathways and mechanisms dealing with a broader range of physiological adaptations to stress.
High‐throughput protein localization in Arabidopsis using Agrobacterium‐mediated transient expression of GFP‐ORF fusions
Authors: Koroleva Olga A. , Tomlinson Matthew L. , Leader David , Shaw Peter , Doonan John H.
Published: December 2004

We describe a streamlined and systematic method for cloning green fluorescent protein (GFP)‐open reading frame (ORF) fusions and assessing their subcellular localization in Arabidopsis thaliana cells. The sequencing of the Arabidopsis genome has made it feasible to undertake genome‐based approaches to determine the function of each protein and define its subcellular localization. This is an essential step towards full functional analysis. The approach described here allows the economical handling of hundreds of expressed plant proteins in a timely fashion. We have integrated recombinational cloning of full‐length trimmed ORF clones (available from the SSP consortium) with high‐efficiency transient transformation of Arabidopsis cell cultures by a hypervirulent strain of Agrobacterium. To demonstrate its utility, we have used a selection of trimmed ORFs, representing a variety of key cellular processes and have defined the localization patterns of 155 fusion proteins. These patterns have been classified into five main categories, including cytoplasmic, nuclear, nucleolar, organellar and endomembrane compartments. Several genes annotated in GenBank as unknown have been ascribed a protein localization pattern. We also demonstrate the application of flow cytometry to estimate the transformation efficiency and cell cycle phase of the GFP‐positive cells. This approach can be extended to functional studies, including the precise cellular localization and the prediction of the role of unknown proteins, the confirmation of bioinformatic predictions and proteomic experiments, such as the determination of protein interactions in vivo, and therefore has numerous applications in the post‐genomic analysis of protein function.
CpG methylation of the CENP‐B box reduces human CENP‐B binding
Authors: Tanaka Yoshinori , Kurumizaka Hitoshi , Yokoyama Shigeyuki
Published: December 2004

In eukaryotes, CpG methylation is an epigenetic DNA modification that is important for heterochromatin formation. Centromere protein B (CENP‐B) specifically binds to the centromeric 17 base‐pair CENP‐B box DNA, which contains two CpG dinucleotides. In this study, we tested complex formation by the DNA‐binding domain of CENP‐B with methylated and unmethylated CENP‐B box DNAs, and found that CENP‐B preferentially binds to the unmethylated CENP‐B box DNA. Competition analyses revealed that the affinity of CENP‐B for the CENP‐B box DNA is reduced nearly to the level of nonspecific DNA binding by CpG methylation.
The importance of being dimeric
Authors: Mei Giampiero , Di Venere Almerinda , Rosato Nicola , Finazzi‐Agrò Alessandro
Published: December 2004

Why are there so many dimeric proteins and enzymes? While for heterodimers a functional explanation seems quite reasonable, the case of homodimers is more puzzling. The number of homodimers found in all living organisms is rapidly increasing. A thorough inspection of the structural data from the available literature and stability (measured from denaturation–renaturation experiments) allows one to suggest that homodimers can be divided into three main types according to their mass and the presence of a (relatively) stable monomeric intermediate in the folding–unfolding pathway. Among other explanations, we propose that an essential advantage for a protein being dimeric may be the proper and rapid assembly in the cellular milieu.
Transient receptor potential and other ion channels as pharmaceutical targets in airway smooth muscle cells
Authors: ONG Hwei L. , BARRITT Greg J.
Published: December 2004

Abstract:  Regardless of the triggering stimulus in asthma, contraction of the airway smooth muscle (ASM) is considered to be an important pathway leading to the manifestation of asthmatic symptoms. Therefore, the various ion channels that modulate ASM contraction and relaxation are particularly attractive targets for therapy. Although voltage‐operated Ca2+ channels (VOCC) are the most extensively characterised Ca2+‐permeable channels in ASM cells and are obvious pharmacological targets, blockers of VOCC have not been successful in alleviating ASM contraction in asthma. Similarly, although the Cl– and K+ channels also modulate ASM contraction and relaxation by regulating plasma membrane potential, pharmacological interventions directed against these channels have failed to abrogate ASM contraction in asthma. A large body of evidence suggests that store‐operated Ca2+ channels (SOCC) and Ca2+‐permeable second messenger‐activated non‐selective cation channels (NSCC) predominantly mediate ASM contraction. However, development of pharmacological interventions involving these channels has been hampered by the paucity of information regarding their molecular identity. Members of the mammalian transient receptor potential (TRP) protein family, which form voltage‐independent channels with variable Ca2+ selectivity that are activated by store depletion and/or by intracellular messengers, are potential molecular candidates for SOCC and NSCC in ASM cells. While the function of TRP channels in ASM cells remains to be elucidated and there are, at present, essentially no good TRP channel antagonists, this group of proteins is a potentially valuable pharmaceutical target for the treatment of asthma.
Immunoglobulin A‐deficient mice exhibit altered T helper 1‐type immune responses but retain mucosal immunity to influenza virus
Authors: Zhang Yongxin , Pacheco Susan , Acuna Catherine L. , Switzer Kirsten C. , Wang Ying , Gilmore Xyanthine , Harriman Gregory R. , Mbawuike Innocent N.
Published: December 2004

We have previously demonstrated that immunoglobulin A (IgA)−/− knockout (KO) mice exhibit levels of susceptibility to influenza virus infection that are similar to those of their normal IgA+/+ littermates. To understand the mechanism of this apparent mucosal immunity without IgA, immunoglobulin isotype and T helper 1 (Th1)‐type [interferon‐γ (IFN‐γ)] and Th2‐type [interleukin (IL)‐4, IL‐5)] cytokine responses to influenza vaccine were evaluated. Intranasal immunization with influenza virus subunit vaccine plus cholera toxin/cholera toxin B subunit (CT/CTB) induced significant influenza virus‐specific immunoglobulin G (IgG) antibody in the serum and nasal passages of both IgA−/− and IgA+/+ mice, while IgA antibodies were induced only in IgA+/+ mice. IgA KO mice exhibited an IgG1 subclass haemagglutinin (HA)‐specific response but no detectable IgG2a and IgG2b responses. In contrast, IgA+/+ mice exhibited significant IgG1 as well as IgG2a responses. This indicates a predominant Th2‐type response in IgA KO mice compared to normal mice. Following stimulation with influenza virus in vitro, splenic lymphocytes from immunized IgA−/− mice produced significantly lower levels of IFN‐γ than IgA+/+ mice (P < 0·001), but elaborated similar levels of IL‐4 and IL‐5. This was true at both protein and mRNA levels. Immunized mice were challenged intranasally with a small inoculum of influenza virus to allow deposition of virus in the nasal mucosal passages. Compared to non‐immunized mice, immunized IgA−/− and IgA+/+ mice exhibited significant, but similar levels of reduction in virus titres in the nose and lung. These results demonstrate that in addition to IgA deficiency, IgA gene deletion also resulted in down‐regulated Th1‐type immune responses and confirm our previous data that IgA antibody is not indispensable for the prevention of influenza virus infection.
Beta diversity of angiosperms in temperate floras of eastern Asia and eastern North America
Authors: Qian Hong , Ricklefs Robert E. , White Peter S.
Published: December 2004

The diversity of a region reflects both local diversity and the turnover of species (beta diversity) between areas. The angiosperm flora of eastern Asia (EAS) is roughly twice as rich as that of eastern North America (ENA), in spite of similar area and climate. Using province/state‐level angiosperm species floras, we calculated beta diversity as the slope of the relationship between the log of species similarity (S ) and either geographic distance or difference in climate. Distance‐based beta diversity was 2.6 times greater in the north–south direction in EAS than in ENA and 3.3 times greater in the east–west direction. When ln S was related to distance and climate difference in multiple regressions, both distance and climate PC1 were significant effects in the north–south direction, but only geographic distance had a significant, unique influence in the east–west direction. The general predominance of distance over environment in beta diversity suggests that history and geography have had a strong influence on the regional diversity of these temperate floras.
Interactions between spatially separated herbivores indirectly alter plant diversity
Authors: van Ruijven Jasper , De Deyn Gerlinde B. , Raaijmakers Ciska E. , Berendse Frank , van Der Putten Wim H.
Published: December 2004

Above‐ and belowground herbivores promote plant diversity when selectively feeding on dominant plant species, but little is known about their combined effects. Using a model system, we show that neutral effects of an aboveground herbivore and positive effects of a belowground herbivore on plant diversity became profoundly negative when adding these herbivores in combination. The non‐additive effects were explained by differences in plant preference between the aboveground‐ and the belowground herbivores and their consequences for indirect interactions among plant species. Simultaneous exposure to aboveground‐ and belowground herbivores led to plant communities being dominated by a few highly abundant species. As above‐ and belowground invertebrate herbivores generally differ in their mobility and local distribution patterns, our results strongly suggest that aboveground–belowground interactions contribute to local spatial heterogeneity of diversity patterns within plant communities.
Resource competition and adaptive radiation in a microbial microcosm
Authors: Craig MacLean R. , Dickson Alison , Bell Graham
Published: December 2004

Theory predicts that competition for shared resources in a monomorphic population generates divergent selection for adaptation to alternative resources. Experimental tests of this hypothesis are scarce. We selected populations of the bacteriumPseudomonas fluorescensin spatially homogeneous microcosms containing a complex mixture of resources. Initially, all populations consisted of two isogenic clones. The outcome of selection was the evolution of a diverse community of genotypes within each population. Sympatric genotypes exhibited differentiation in metabolic traits related to resource acquisition and frequency‐dependent trade‐offs in competitive ability, as we would expect if different genotypes consumed different resources. These results are consistent with the hypothesis of adaptive radiation driven by resource competition. Reconciling the results of this study with those of earlier experiments provides a new interpretation of the ecological causes of adaptive radiation in microbial microcosms.
Effects of mycorrhizal symbiosis on tallgrass prairie plant–herbivore interactions
Authors: Kula Abigail A. R. , Hartnett David C. , Wilson Gail W. T.
Published: December 2004

Complex relationships occur among plants, mycorrhizal fungi, and herbivores. By altering plant nutrient status, mycorrhizas may alter herbivory or plant tolerance to herbivory via compensatory regrowth. We examined these interactions by assessing grasshopper preference and plant growth and fungal colonization responses to herbivory under mycorrhizal and non‐mycorrhizal conditions within tallgrass prairie microcosms. Mycorrhizal symbiosis increased plant regrowth following defoliation, and some strongly mycotrophic plant species showed overcompensation in response to herbivory when they were mycorrhizal. Although grasshoppers spent more time on mycorrhizal plants, herbivory intensity did not differ between mycorrhizal and non‐mycorrhizal plants. Aboveground herbivory by grasshoppers significantly increased mycorrhizal fungal colonization of plant roots. Thus mycorrhizas may greatly benefit plants subjected to herbivory by stimulating compensatory growth, and herbivores, in turn, may increase the development of the symbiosis. Our results also indicate strong interspecific differences among tallgrass prairie plant species in their responses to the interaction of aboveground herbivores and mycorrhizal symbionts.
Mechanisms of disease‐induced extinction
Authors: De Castro Francisco , Bolker Benjamin
Published: December 2004

Parasites are important determinants of ecological dynamics. Despite the widespread perception that parasites (in the broad sense, including microbial pathogens) threaten species with extinction, the simplest deterministic models of parasite dynamics (i.e. of specialist parasites with density‐dependent transmission) predict that parasites will always go extinct before their hosts. We review the primary theoretical mechanisms that allow disease‐induced extinction and compare them with the empirical literature on parasitic threats to populations to assess the importance of different mechanisms in threatening natural populations. Small pre‐epidemic population size and the presence of reservoirs are the most commonly cited factors for disease‐induced extinction in empirical studies.
The Quality of Social Security Benefit Data in the British Family Resources Survey: Implications for Investigating Income Support Take-Up by Pensioners
Authors: Hancock Ruth , Barker Geraldine
Published: December 2004

Family Resources Survey (FRS) data for April 1997 to March 2000 are used to estimate the take-up of income support (IS) by a subset of pensioners. We scrutinize the quality of FRS data for this purpose and describe a process of identifying and correcting inconsistencies in the data. Comparisons are made, before and after corrections to the data, of take-up estimates, logistic regression take-up models and predictions of take-up responses to changes in IS rates. Overall, the corrections do not have large effects on estimated take-up rates but suggest that non-take-up is marginally less serious than the uncorrected data imply. Logistic regressions using corrected and uncorrected data were in broad agreement on the factors influencing take-up. There were some differences in the scale of these influences, with implications for predictions of take-up responses to changes in the generosity of IS. Desirable improvements in the FRS are identified.
Exploring Road Mortality Ratios in Europe: NationalVersusRegional Realities
Authors: Lassarre Sylvain , Thomas Isabelle
Published: December 2004

The paper analyses the geographical pattern(s) of road mortality in western Europe for three standard levels of data aggregation. A new adjusted road mortality ratio is proposed. Unlike most mortality ratios, the standardization uses population density rather than age and sex. The hypothesis to be tested is that changes in the level of spatial aggregation of the data produce significant differences in the values of some basic descriptive statistics, and hence in operational conclusions. The paper shows that population density works as a proxy for structural factors that may be difficult to change by policies and that working with 264 regions confirms the north–south divergences in terms of road safety in Europe but also stresses the local or regional differences due to political, geographical, economic, environmental and statistical disparities. Safe countries include unsafe regions, and there are safe regions in unsafe countries. Decision makers should be aware of this when comparing countries.
Why McNemar's Procedure Needs to be Included in the Business Statistics Curriculum
Authors: Berenson Mark L. , Koppel Nicole B.
Published: December 2004

In business research situations it is often of interest to examine the differences in the responses in repeated measurements of the same subjects or from among matched or paired subjects. A simple and useful procedure for comparing differences between proportions in two related samples was devised by McNemar (1947) nearly 60 years ago. Although the technique has enjoyed widespread usage in both behavioral and medical research, it has unfortunately not received proper attention in marketing, advertising, consumer research, public relations, operations management, or organizational behavior endeavors—disciplines wherein it is particularly desirable to evaluate the significance of changes in attitudes, opinions, or beliefs regarding some campaign or strategy. Perhaps the major reason for this obscurity is simply a general lack of awareness as to its value and practical power. The McNemar test is generally not currently being taught to business statistics students. It is the purpose of this article to demonstrate the usefulness and applicability of the McNemar procedure to these aforementioned disciplines so that it may be more appropriately employed as an important confirmatory data analysis tool within the basic business statistics curriculum.
The levels of plasma and salivary antioxidants in the patient with recurrent aphthous stomatitis
Authors: Karincaoglu Yelda , Batcioglu Kadir , Erdem Tamer , Esrefoglu Muammer , Genc Metin
Published: December 2004

Background:  Despite plenty of research, the cause of recurrent aphthous stomatitis (RAS) remains obscure. It has been proposed that, the aetiological factors such as local trauma, smoking, vitamin deficiencies and viral infections lead to aphthae formation via final common pathway based on increased oxidative stress. The aim of this investigation was to evaluate the antioxidant enzyme superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) alterations in plasma and saliva, and in addition uric acid (UA) in saliva, in patients with RAS and healthy controls.

Methods:  Thirty‐two patients with RAS and 30 healthy controls were included into the study. The SOD, CAT, GSHPx and UA levels were measured in plasma and saliva in study and control groups.

Results:  In the RAS group, although the mean SOD (P < 0.001) and CAT (P < 0.05) levels of plasma were lower, GSHPx (P < 0.001) levels were higher than control group. The salivary concentrations of the SOD (P < 0.001), CAT (P < 0.05) and GSHPx (P < 0.001) in RAS group were entirely opposite to plasma concentrations. UA were not significant between RAS group and controls.

Conclusion:  Since we found salivary SOD and CAT levels were high whereas plasma levels were low, it has been thought that, salivary defence mechanisms via antioxidant agents may be stimulated against to the ulcerous lesion. We consider that the organism might mobilize the antioxidant potential to the sites where they were needed. At this point, decrease of SOD and CAT levels in the plasma may be related to this shift. It is also thought that GSHPx secretion in the saliva may also be increased but the increase in its turnover may be responsible for the diminished activity.