bluuebunny/crossref_metadata_2025 huggingface dataset:
Mellowing with age: older parents are less responsive to a stressor in a long‐lived seabird
Authors: Heidinger Britt J. , Chastel Olivier , Nisbet Ian C. T. , Ketterson Ellen D.
Published: June 2010

1. Reproductive success often increases with age; however the mechanisms underlying this commonly observed pattern are poorly understood. One mechanism that may be important is a set of physiological responses (the stress response) that allows organisms to evade and cope with stressors, but often inhibits reproduction.

2. If older parents respond less strongly to stressors than younger parents, this age‐related difference in the stress response may contribute to the higher reproductive success that often characterizes older parents.

3. Typically the stress response is measured as an increase in plasma glucocorticoid (CORT) concentration, and we have previously reported that stress‐induced CORT levels decline with age in the common tern (Sterna hirundo). Another hormone, prolactin (PRL), has been reported to decrease in response to stressors in breeding birds and is often positively associated with parental behaviour. We predicted that like the CORT stress response, the PRL stress response would also be suppressed with age.

4. To test this prediction, we captured known‐age, incubating common terns ranging in age from 3 to 29 years and measured stress‐induced changes in PRL and CORT levels within the same individuals.

5. We found that PRL levels decreased less rapidly in response to capture and restraint stress in older than in younger parents. In these same birds, we also found that stress‐induced maximum CORT levels decreased with age, which is consistent with what we have previously reported for this species. Measures of PRL and CORT were not, however, correlated within individuals.

6. Taken together, these results support the hypothesis that modulations of both the PRL and CORT stress response are flexible hormonal mechanisms that help to account for the increase in reproductive success that occurs with age.
Effects of agricultural intensification on plant diversity in Mediterranean dryland cereal fields
Authors: José‐María Laura , Armengot Laura , Blanco‐Moreno José M. , Bassa Montserrat , Sans F. Xavier
Published: June 2010

1. Agricultural intensification, at field and landscape scales, has caused a decrease in weed richness and changes in species composition. In order to prevent this loss of diversity and develop efficient management regimes, it is important to understand how both aspects of intensification affect plant diversity and the way in which they interact.

2. This study assessed plant diversity at the centre, edges and boundaries of 29 organic and 29 conventional cereal fields distributed in 15 agrarian localities of the NE Iberian Peninsula. We focused on the composition of plant assemblages and on the specific richness at the field level, which was calculated for the whole set of species and for that of characteristic arable weeds. The percentage of arable land together with human settlements was used as a surrogate for landscape complexity and the amount of nitrogen inputs for land‐use intensity.

3. Our results show that both scales of agricultural intensification have a similar negative effect on the total plant species and characteristic arable weed richness, and they also affect plant assemblages. Furthermore, we found no strong interaction between landscape and land‐use intensity for explaining total plant richness.

4. The relative importance of farming intensity and landscape varies depending on the location within the field, which can be attributed to differences in the agricultural impact and limited seed dispersal from adjacent habitats. Management is the main factor in explaining differences among field centres, whereas changes at boundaries are mainly due to landscape characteristics, and at edges both factors are relevant.

5. Synthesis and applications. To preserve agricultural plant diversity it is equally important to prevent agricultural intensification at field and landscape scales. Policies enhancing low‐intensity management techniques, such as organic farming, are the main way to promote diversity inside the fields and will be equally beneficial in simple and complex landscapes for total plant species richness. To maintain diversity within agricultural areas, it is also important to reduce farming intensity at the edges, which would favour characteristic arable weeds and margins’ overall plant diversity.
Still walking on the wild side? Management actions as steps towards ‘semi‐domestication’ of hunted ungulates
Authors: Mysterud Atle
Published: June 2010

1. Domestication is a process involving adaptations to man and the man‐made environment. Semi‐domestic animals are those for which humans have only partial control over breeding, mortality, space use and food supply, and that have not been greatly modified by artificial selection. They therefore appear more similar to their wild counterparts.

2. The degree of domestication depends on the level of (i) human control over breeding, mortality, food supply, space use and thereby selection pressures; (ii) how much these differ from original states; and (iii) how strongly the phenotypic traits have been affected.

3. Synthesis and applications. Both natural and sexual selection in man‐made environments may differ, and some management actions move traits of hunted ungulates closer to those associated with a semi‐domestic stage; depending on the harvest pressure and selectivity, fencing, artificial feeding and predator control. There is a trade‐off between high productivity of hunted ungulate populations and retaining wild traits.
Do changes in the frequency, magnitude and timing of extreme climatic events threaten the population viability of coastal birds?
Authors: Van De Pol Martijn , Ens Bruno J. , Heg Dik , Brouwer Lyanne , Krol Johan , Maier Martin , Exo Klaus‐Michael , Oosterbeek Kees , Lok Tamar , Eising Corine M. , Koffijberg Kees
Published: June 2010

1. Climate change encompasses changes in both the means and the extremes of climatic variables, but the population consequences of the latter are intrinsically difficult to study.

2. We investigated whether the frequency, magnitude and timing of rare but catastrophic flooding events have changed over time in Europe’s largest estuary. Subsequently, we quantified how this has affected the flooding risk of six saltmarsh nesting bird species.

3. We show that maximum high tide has increased twice as fast as mean high tide over the past four decades (0·8 vs. 0·4 cm year−1), resulting in more frequent and more catastrophic flooding of nests, especially around the time when most eggs have just hatched.

4. Using data on species’ nest elevations, on their timing of egg‐laying and on the duration that their eggs and chicks are at risk from flooding, we show that flooding risks increased for all six studied species (even after accounting for compensatory land accretion) and this is expected to worsen in the near future if they do not adapt. Moreover, our study provides the first evidence that increasing flooding risks have reduced the reproductive output below stable population levels in at least one species, the Eurasian oystercatcher Haematopus ostralegus.

5. Sensitivity analyses show that currently birds would benefit most from adapting their nest‐site selection to higher areas. However, historically the lower marsh has been favoured for its proximity to the feeding grounds and for its low vegetation aiding predator detection.

6. Synthesis and applications. We argue that it is more difficult for birds to infer that habitat quality has decreased from changes in the frequency of rare and unpredictable extreme events than from trends in climatic means. Consequently, at present the lower parts of the saltmarsh may function as an ecological trap. The creation of new (i.e. low) saltmarshes – currently a restoration priority – may thus counteract the goal of increasing the avian biodiversity of an area. Management tools to mitigate the effects of climate change, either by making the higher saltmarsh more attractive (mowing, predator control) or by reducing the flooding risk of the lower marsh (building elevated plots), await to be tested.
Herbarium records identify the role of long‐distance spread in the spatial distribution of alien plants in New Zealand
Authors: Aikio Sami , Duncan Richard P. , Hulme Philip E.
Published: June 2010

Aim To use herbarium records to characterize important correlates of spatial spread, areal occupancy and clustering of 100 alien plant species of conservation concern in the North and South Islands of New Zealand.

Location New Zealand.

Methods Using herbarium data of 6294 records representing 100 alien plant species, we assessed spatial heterogeneity in the distribution of alien species by examining the role of major urban areas as sources of sampling bias. A novel method to account for spatial biases in sampling effort was developed and applied to two simple distance metrics: nearest‐ and furthest‐neighbour spread rate. The relative importance of these two distance metrics in determining the range, areal extent and dispersion of alien species across both the North and South Islands of New Zealand was also assessed.

Results The spatial distribution of herbarium records was highly clustered with a significant bias towards the more populated regions. Once sampling bias was taken into account, there was no indication that species were found closer to these urban centres than might be expected based on sampling effort. The nearest‐neighbour spread rates were usually 1–5 km yr−1and correlated positively with the furthest‐neighbour spread rates that were an order of magnitude higher. Range and area increased and clustering decreased with higher spread rates and longer recording time span. The spread rates divided species into five groups that were clearly distinguishable in terms of the extent of their distribution and the degree of clustering. Species occurring on both islands did not exhibit similar spread rates or spatial patterns.

Main conclusions The nearest‐ and furthest‐neighbour spread rates from herbarium records can explain the area and pattern of alien plant distributions and improve the understanding of the dynamics of their spread. Five groups emerge from the spread rates in relation to a null model. Fast‐spreading plants had the widest, least clustered distribution, which suggests widespread chronic problems; slow‐spreading plants had localized, but dense, clustered distributions, indicating acutely problematic weeds. These patterns appear robust and may be useful in predicting the future patterns of spread and in planning long‐term management strategies in New Zealand.
Planning and decision making about the future care of older group home residents and transition to residential aged care
Authors: Bigby C. , Bowers B. , Webber R.
Published: June 2010

Background  Planning for future care after the death of parental caregivers and adapting disability support systems to achieve the best possible quality of life for people with intellectual disability as they age have been important issues for more than two decades. This study examined perceptions held by family members, group home staff and organisational managers about the future of older residents and the decisions made that a move to residential aged care was necessary.

Methods  Grounded Dimensional Analysis was used to guide data collection and analysis by an interdisciplinary research team. Three sets of interviews over a period of 18 months were conducted with a family member, house supervisor and the programme manager for each of seventeen older group home residents in Victoria. For the eight people for whom it was decided a move was necessary and the six who eventually moved focussed questions were asked about the decision‐making process.

Results  While plans for lifelong accommodation in a group home proved unfounded, key person succession plans were effective. However, decisions to move to a residential aged care facility where necessary were made in haste and seen as a fait accompli by involved family members.

Conclusions  Although family members take seriously their mandate to oversee well‐being of their older relative, they have little knowledge about their rights or avenues to safeguard untimely or inappropriate decisions being made by professionals.
Core neuropsychological characteristics of children and adolescents with 22q11.2 deletion
Authors: Jacobson C. , Shearer J. , Habel A. , Kane F. , Tsakanikos E. , Kravariti E.
Published: June 2010

Background  The 22q11.2 deletion syndrome (22qDS) confers high risk for intellectual disability and neuropsychological/academic impairment, although a minority of patients show average intelligence. Intellectual heterogeneity and the high prevalence of psychiatric diagnoses in earlier studies may have obscured the prototypical neuropsychological profile in 22qDS.

Methods  We examined intelligence, memory, reading and mathematical processes in 31 children/adolescents with 22qDS, selected for educational underachievement and an absence of psychiatric diagnoses, using standardised, psychometrically matched instruments that specify how typical a score is for a given intelligence quotient (IQ).

Results  Corroborating earlier findings, verbal IQ was significantly superior to performance IQ; verbal memory and basic reading were relative strengths; and visual/spatial memory was a relative weakness. All four findings transcended performance characteristics that are typical of low‐IQ individuals. Rote learning yielded the highest score; reading comprehension, numerical operations and mathematical reasoning were among the lowest‐performed academic domains. Albeit in the expected direction, performance in the respective components could not be clearly differentiated from what is IQ‐appropriate.

Conclusions  A superiority of verbal intelligence over non‐verbal intelligence, relative strengths in verbal memory and basic reading, and a relative weakness in visual/spatial memory are likely to be core characteristics of children/adolescents with 22qDS, transcending performance features that are typical of individuals with low IQ.
Polysomnographic and quantitative electroencephalographic correlates of subjective sleep complaints in chronic tinnitus
Authors: HÉBERT SYLVIE , FULLUM STEPHAN , CARRIER JULIE
Published: June 2010

Chronic tinnitus, or the perception of hearing sounds without the presence of external stimulation, is estimated at about 10–15% of the population, with highest prevalence after 50 years of age. Sleep complaints are among the most prominent complaints accompanying tinnitus, but objective data are rare. In this study, we examined prospectively the subjective and objective sleep parameters of this patient population in order to determine differences in sleep disturbances associated with chronic tinnitus compared to matched controls. Forty‐four subjects (22 with tinnitus and 22 controls without tinnitus), unselected with respect to sleep complaints, participated in this study. The analysis involved 1‐week sleep diaries, subjective sleep questionnaires and 1 night of polysomnographic (PSG) assessment. Compared to matched controls, the tinnitus group showed lower subjective sleep quality as measured with the Pittsburgh Sleep Quality Index (PSQI) and sleep diaries, but no significant difference in objective polysomnograph sleep parameters (i.e. sleep latency, efficiency). However, quantitative non‐rapid eye movement sleep analysis revealed lower spectral power in the delta frequency band in the tinnitus group compared to controls, and this decrease was correlated with subjective sleep complaints (the lower the delta spectral power, the greater the complaints). This is the first report of an electrophysiological correlate of sleep difficulties supportive of subjective sleep complaints in the tinnitus population.
Microsatellites reveal origin and genetic diversity of Eurasian invasions by one of the world’s most notorious marine invader, Mnemiopsis leidyi (Ctenophora)
Authors: REUSCH THORSTEN B. H. , BOLTE SÖREN , SPARWEL MAXIMILIANE , MOSS ANTHONY G. , JAVIDPOUR JAMILEH
Published: June 2010

Marine invasions are taking place at an increasing rate. When occurring in blooms, zooplanktivorous comb jellies of the genus Mnemiopsis are able to cause pelagic regime shifts in coastal areas and may cause the collapse of commercially important fish populations. Using microsatellites, developed for the first time in the phylum Ctenophora, we show that Mnemiopsis leidyi has colonized Eurasia from two source regions. Our preliminary data set included four sites within the putative source region (US East Coast and Gulf of Mexico) and 10 invaded locations in Eurasian waters. Bayesian clustering and phylogeographic approaches revealed the origin of earlier invasions of the Black and Caspian Sea in the 1980s/1990s within or close to the Gulf of Mexico, while the 2006 invasion of the North and Baltic Seas can be directly traced to New England (pairwise FST = 0). We found no evidence for mixing among both gene pools in the invaded areas. While the genetic diversity (allelic richness) remained similar in the Baltic Sea compared to the source region New England, it was reduced in the North Sea, supporting the view of an initial invasion of Northern Europe to a Baltic Sea port. In Black and Caspian Sea samples, we found a gradual decline in allelic richness compared to the Gulf of Mexico region, supporting a stepping‐stone model of colonization with two sequential genetic founder events. Our data also suggest that current practices of ballast water treatment are insufficient to prevent repeated invasions of gelatinous zooplankton.
The change in genetic diversity down the core‐edge gradient in the eastern spadefoot toad (Pelobates syriacus)
Authors: MUNWES INBAR , GEFFEN ELI , ROLL URI , FRIEDMANN ADAM , DAYA ALON , TIKOCHINSKI YARON , GAFNY SARIG
Published: June 2010

Several hypotheses are available to predict change in genetic diversity when approaching peripheral populations. We used the eastern spadefoot toad in Israel as a model system to examine these hypotheses using population genetics analyses and network theory. Our results contradicted most of the predictions from the ‘abundant centre’ model, that edge populations should have lower density and lower genetic diversity than core populations. Furthermore, dispersal rate between core and peripheral populations is expected to be asymmetric, mostly directed outwards from the core population, but we did not detect such a trend. Our data did not support the hypothesis of no change or a non‐linear change in genetic diversity towards the range edge. However, our results did fit the Fisher (The Genetical Theory of Natural Selection, Clarendon Press, Oxford, 1930) hypothesis, which predicts increase in genetic variability from core to edge of distribution. We attributed this finding to the much harsher climatic and abiotic conditions at the edge, which must be tolerated over generations by both tadpoles and post‐metamorphic individuals in this region. Finally, our results have significant conservation implications for the survival of this species in Israel, where it is critically endangered. We identified two distinct communities, which are genetically linked through two specific rain pools in the Upper Galilee. Details on the spatial subdivision of this species are cardinal for future management and restoration of temporary wetlands in Israel.
Using creation science to demonstrate evolution: application of a creationist method for visualizing gaps in the fossil record to a phylogenetic study of coelurosaurian dinosaurs
Authors: SENTER P.
Published: June 2010

It is important to demonstrate evolutionary principles in such a way that they cannot be countered by creation science. One such way is to use creation science itself to demonstrate evolutionary principles. Some creation scientists use classic multidimensional scaling (CMDS) to quantify and visualize morphological gaps or continuity between taxa, accepting gaps as evidence of independent creation and accepting continuity as evidence of genetic relatedness. Here, I apply CMDS to a phylogenetic analysis of coelurosaurian dinosaurs and show that it reveals morphological continuity betweenArchaeopteryx, other early birds, and a wide range of nonavian coelurosaurs. Creation scientists who use CMDS must therefore accept that these animals are genetically related. Other uses of CMDS for evolutionary biologists include the identification of taxa with much missing evolutionary history and the tracing of the progressive filling of morphological gaps in the fossil record through successive years of discovery.
A new concept for non‐invasive renal tumour ablation using real‐time MRI‐guided radiation therapy
Authors: Kerkhof Ellen M. , Raaymakers Bas W. , van Vulpen Marco , Zonnenberg Bernard A. , Bosch J.L.H. Ruud , van Moorselaar R. Jeroen A. , Lagendijk Jan J.W.
Published: June 2010

Study Type – Therapy (case series) Level of Evidence 4

What’s known on the subject? and What does the study add?

The increasing use of imaging techniques resulted in an enormous increase of incidentally diagnosed renal cell carcinomas (RCC). At the moment surgery is the only established curative approach for the treatment of RCC. The smaller size of these incidental RCC tumours demands far less invasive treatment techniques, preferably without piercing the tumour.

This study presents the latest developments in the field of radiation therapy, which provides treatment alternatives for tumour sites currently not treated with radiation therapy. Real‐time magnetic resonance imaging guided radiation therapy might become a valuable non‐invasive alternative to treat renal cell carcinoma.

OBJECTIVE To present a new concept for non‐invasive renal tumour ablation using real‐time magnetic resonance imaging (MRI)‐guided radiation therapy. All currently available treatment techniques for localized renal cell carcinoma (RCC) have to be performed in a laparoscopic or percutaneous way.

MATERIALS AND METHODS A technical prototype MRI‐accelerator which performs real‐time 1.5 T MRI imaging during the irradiation has been constructed. We performed a technical feasibility study on real‐time MRI‐guided arc therapy using repeated breath‐holds for renal tumour ablation by (i) investigating renal mobility during breath‐holding, (ii) performing dose calculation and (iii) measuring the radiation delivery time on a phantom. The renal mobility during free breathing and end‐expiration breath‐holding during 15 s was investigated for three patients with renal tumour appearance. Conventional MRI screening data of four patients was used for arc therapy dose calculation. Tumour and normal tissues were delineated and a tumour margin of 3 mm was applied. The radiation delivery time of a 25‐Gy arc therapy plan was measured on a phantom.

RESULTS Renal mobility during free breathing varied from 10 to 25 mm, whereas breath‐holding resulted in nearly non‐moving kidneys (0 to 2 mm) for all patients. Arc therapy dose calculation resulted in an adequate tumour coverage. The radiation delivery time of the arc therapy plan was about 10 min. This means that 20 to 40 repeated breath‐holds of 15 to 30 s will be needed for a single session treatment. A higher maximum dose rate would reduce the number of breath‐holds needed and improve patient comfort. A phase I study will be started to proof the clinical feasibility.

CONCLUSION Real‐time MRI‐guided radiation therapy using an MRI‐accelerator might become a valuable non‐invasive alternative to the current RCC treatment options.
The Public Participation Act: A Comprehensive Model Approach to End Strategic Lawsuits Against Public Participation in the USA
Authors: Brown Samantha , Goldowitz Mark
Published: June 2010

Commentators have documented the disturbing use of the courtroom to silence those who speak out on important issues. Too often, parties resort to meritless lawsuits in response to another's free expression or communication with the government. These lawsuits are called SLAPPs, or Strategic Lawsuits Against Public Participation. In the USA, they have emerged as a significant threat to the rights of expression and petition guaranteed in the First Amendment to the US Constitution. A majority of the US States have passed ‘anti‐SLAPP laws’, but there is no uniform protection. The model legislation outlined in this paper is intended to guide those who seek uniform, comprehensive protection against SLAPPs.
SLAPPs: Intent or Content? Anti‐SLAPP Legislation Goes International
Authors: Shapiro Pamela
Published: June 2010

Due to the increasing interest in adopting anti‐SLAPP legislation outside of the USA (where it was first implemented), the definition of what constitutes a SLAPP is being questioned. Some commentators have advanced the suggestion that, in order to account for jurisdictional differences, outside of the USA it is the motivation to intimidate or chill public speech that is the aspect of a SLAPP on which anti‐SLAPP legislation must focus. However, defining SLAPPs by the initiator's alleged intent to intimidate can render anti‐SLAPP legislation, in any jurisdiction, ineffective. SLAPPs should be defined by the involvement of public participation, rather than by the intent of the SLAPP plaintiff. Effective anti‐SLAPP legislation employs procedural protections that are engaged once a threshold demonstration has been made that the case involves protected public interest communications. Generally, this approach is appropriate to adopt in any jurisdiction where the legislature desires to protect public interest communications.
Anti‐SLAPP Law Reform in Australia
Authors: Ogle Greg
Published: June 2010

The last 20 years has seen a growth in litigation against public participation in Australia and a broadening of the mechanisms used. Following changes to the defamation laws in 2005, commercial torts are increasingly being used against critics and protest groups. Australia's highest profile example, the so‐called ‘Gunns 20’ case, brought the problems of such litigation into the public realm and provided a major impetus for law reform. One Australian jurisdiction has now adopted limited anti‐Strategic Litigation Against Public Participation (SLAPP) legislation and SLAPPs are being raised in the context of national debates over a Human Rights Act. However, comprehensive anti‐SLAPP law reform is still some way off.
Strategic Lawsuits Against Public Participation: The British Columbia Experience
Authors: Scott Michaelin , Tollefson Chris
Published: June 2010

In 2001, the province of British Columbia (BC) became the first Canadian jurisdiction to enact anti‐SLAPP legislation. While this legislation proved to be short lived, the BC experience around the issue of SLAPPs is instructive for law reformers both in Canada and beyond. In this article, the authors describe the legal and political processes that set the stage for the passage of the 2001 law, and its subsequent repeal. They also provide a detailed analysis and critique of key aspects of the debate surrounding the design of the law, and consider its efficacy in identifying, dismissing and deterring SLAPP lawsuits. They conclude with some observations with respect to the current status of the SLAPP issue in BC.
Faster rate of cognitive decline in essential tremor cases than controls: a prospective study
Authors: Louis E. D. , Benito‐León J. , Vega‐Quiroga S. , Bermejo‐Pareja F. ,   the Neurological Disorders in Central Spain (NEDICES) Study Group
Published: June 2010

Background:  Mild cognitive deficits have been reported in essential tremor (ET). However, these cognitive deficits have been assessed in cross‐sectional rather than longitudinal analyses.

Objective:  To determine whether decline in cognitive test scores occurs at a faster rate in ET cases than controls.

Methods:  In a population‐based study of older people (≥ 65 years) in central Spain (Neurological Disorders in Central Spain, NEDICES), non‐demented ET cases and controls were followed prospectively. Participants with baseline or incident Parkinson’s disease or dementia were excluded as were participants who developed incident ET. At baseline (1994–1995) and at follow‐up (1997–1998), a 37‐item version of the mini‐mental state examination (37‐MMSE) was administered.

Results:  A total of 2319 participants (72.4 ± 5.8 years) included 135 prevalent ET cases and 2184 controls. At baseline, the mean 37‐MMSE in cases was 28.8 ± 5.8 vs. 30.2 ± 4.8 in controls (P = 0.02). During the 3‐year follow‐up period, the 37‐MMSE declined by 0.70 ± 3.2 points in cases vs. 0.11 ± 3.8 points in controls (P = 0.03). In analyses that adjusted for age, education, and other potential confounders, the case–control difference remained robust.

Discussion:  In this population‐based, prospective study of non‐demented elders, baseline cognitive test scores were lower in ET cases than controls; moreover, during the 3‐year follow‐up period, these scores declined at a rate that was seven‐times faster in ET cases. This study provides evidence that cognitive deficits in ET are not static, and they appear to be progressing at a faster rate than in elders without this disease.
The Impact of Incomplete Linkage Disequilibrium and Genetic Model Choice on the Analysis and Interpretation of Genome‐wide Association Studies
Authors: Iles Mark M.
Published: June 2010

When conducting a genetic association study, it has previously been observed that a multiplicative risk model tends to fit better at a disease‐associated marker locus than at the ungenotyped causative locus. This suggests that, while overall risk decreases as linkage disequilibrium breaks down, non‐multiplicative components are more affected. This effect is investigated here, in particular the practical consequences it has on testing for trait/marker associations and the estimation of mode of inheritance and risk once an associated locus has been found. The extreme significance levels required for genome‐wide association studies define a restricted range of detectable allele frequencies and effect sizes. For such parameters there is little to be gained by using a test that models the correct mode of inheritance rather than the multiplicative; thus the Cochran‐Armitage trend test, which assumes a multiplicative model, is preferable to a more general model as it uses fewer degrees of freedom. Equally when estimating risk, it is likely that a multiplicative risk model will provide a good fit to the data, regardless of the underlying mode of inheritance at the true susceptibility locus. This may lead to problems in interpreting risk estimates.
Association of SLC6A12 variants with aspirin‐intolerant asthma in a Korean population
Authors: Pasaje Charisse Flerida A. , Kim Jeong‐Hyun , Park Byung‐Lae , Cheong Hyun Sub , Chun Ji‐Yong , Park Tae‐Joon , Lee Jin‐Sol , Kim Yongha , Bae Joon Seol , Park Jong Sook , Yoon Sang‐Hyuk , Uh Soo‐Taek , Choi Jae‐Sung , Kim Yong‐Hoon , Kim Mi‐Kyeong , Choi Inseon S. , Cho Sang Heon , Choi Byoung Whui , Park Choon‐Sik , Shin Hyoung Doo
Published: June 2010

Aspirin‐intolerant asthma (AIA) occurs from asthma exacerbation after exposure to aspirin. However, the underlying mechanisms of AIA occurrence are still unclear. The critical role of the solute carrier family 6 (neurotransmitter transporter, betaine/GABA) member 12 (SLC6A12) gene in GABAergic transmission, which is associated with mucus production in asthma, makes it a candidate gene for AIA association study. Eight single nucleotide polymorphisms (SNPs) in SLC6A12 were genotyped in 163 aspirin‐intolerant asthma (AIA) and 429 aspirin‐tolerant asthma (ATA) patients of Korean ethnicity. Associations between polymorphisms of SLC6A12 and AIA were analysed using multivariate logistic analysis. Results showed that two polymorphisms and a haplotype in SLC6A12, rs499368 (P= 0.005; Pcorr= 0.03), rs557881 (non‐synonymous C10R, P= 0.007; Pcorr= 0.04), and SLC6A12_BL1_ht1 (P= 0.009; Pcorr= 0.05) respectively, were significantly associated with AIA after multiple testing corrections. In addition, SNPs of SLC6A12 were significantly associated with the fall rate of FEV1 by aspirin provocation suggesting that SLC6A12 could affect reversibility of lung function abnormalities in AIA patients. Although these results are preliminary and future replications are needed to confirm these findings, this study showed evidence of association between variants in SLC6A12 and AIA occurrence among asthmatics in a Korean population.
Elucidation of CYP2D6 Genetic Diversity in a Unique African Population: Implications for the Future Application of Pharmacogenetics in the Xhosa Population
Authors: Wright Galen E. B. , Niehaus Dana J. H. , Drögemöller Britt I. , Koen Liezl , Gaedigk Andrea , Warnich Louise
Published: June 2010

Genetic variation of the CYP2D6 gene has been associated with altered drug metabolism; however, limited studies have investigated CYP2D6 sequence diversity in African populations. We devised a CYP2D6 genotyping strategy to analyse the South African Xhosa population and genotype a Xhosa schizophrenia cohort, as CYP2D6 metabolises many antipsychotics and antidepressants.

The entire CYP2D6 gene locus was sequenced in 15 Xhosa control individuals and the data generated were used to design a comprehensive genotyping strategy. Over 25 CYP2D6 alleles were genotyped in Xhosa controls and Xhosa schizophrenia patients using long‐range PCR, DNA sequencing and single nucleotide primer extension analysis. Bioinformatic algorithms were used to predict the functional consequences of relevant mutations and samples were assigned CYP2D6 activity scores.

A unique allele distribution was revealed and two rare novel alleles, CYP2D6*73 and CYP2D6*74, were identified. No significant differences in allele frequencies were detected between Xhosa controls and schizophrenia patients. This study provides i) comprehensive data on a poorly characterised population, ii) a valuable CYP2D6 genotyping strategy and iii) due to their unique genetic profile, provides the basis for pharmacogenetic intervention for Xhosa individuals.
Neurones express glutamine synthetase when deprived of glutamine or interaction with astrocytes
Authors: Fernandes Samantha P. , Dringen Ralf , Lawen Alfons , Robinson Stephen R.
Published: June 2010

J. Neurochem. (2010) 114, 1527–1536.

Glutamine synthetase (GS) forms glutamine by catalyzing the ATP‐dependent amidation of glutamate. In healthy brains, GS is restricted to astrocytes but in Alzheimer’s disease and cell culture, GS has been detected in neurones. The present study demonstrates the expression of functional GS in cultured cerebellar granule cells and investigates conditions required to reduce this expression. Cerebellar granule cells from neonatal rats were grown in the absence of glutamine. Immunostaining revealed that the majority of neurones contained GS in their somata and dendrites. Treatment of neuronal cultures with glutamine greatly reduced the enzymatic activity of GS and also reduced the intensity of GS immunolabelling in dendrites. GS activity was reduced by 32% in neurones that had been transiently co‐cultured with astrocytes, wherreas GS immunoreactivity was largely abolished from neurones that had been directly seeded onto astrocytic monolayers. These results imply that GS expression in neurones occurs in response to a reduced availability of glutamine from astrocytes, and that neuronal GS expression represents a default phenotype which is normally suppressed via direct contacts with astrocytes. The aberrant expression of GS in sporadic neurones in Alzheimer’s disease may indicate an impairment of such interactions.
Comparative pharmacology of chemically distinct NADPH oxidase inhibitors
Authors: Wind S , Beuerlein K , Eucker T , Müller H , Scheurer P , Armitage ME , Ho H , Schmidt HHHW , Wingler K
Published: June 2010

BACKGROUND AND PURPOSE Oxidative stress [i.e. increased levels of reactive oxygen species (ROS)] has been suggested as a pathomechanism of different diseases, although the disease‐relevant sources of ROS remain to be identified. One of these sources may be NADPH oxidases. However, due to increasing concerns about the specificity of the compounds commonly used as NADPH oxidase inhibitors, data obtained with these compounds may have to be re‐interpreted.

EXPERIMENTAL APPROACH We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4‐(2‐amino‐ethyl)‐benzolsulphonyl‐fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947. We used several assays for detecting cellular and tissue ROS, as none of them is specific and artefact free.

KEY RESULTS DPI abolished NADPH oxidase‐mediated ROS formation, but also inhibited other flavo‐enzymes such as NO synthase (NOS) and xanthine oxidase (XOD). Apocynin interfered with ROS detection and varied considerably in efficacy and potency, as did AEBSF. Conversely, the novel NADPH oxidase inhibitor, VAS3947, consistently inhibited NADPH oxidase activity in low micromolar concentrations, and interfered neither with ROS detection nor with XOD or eNOS activities. VAS3947 attenuated ROS formation in aortas of spontaneously hypertensive rats (SHRs), where NOS or XOD inhibitors were without effect.

CONCLUSIONS AND IMPLICATIONS Our data suggest that triazolo pyrimidines such as VAS3947 are specific NADPH oxidase inhibitors, while DPI and apocynin can no longer be recommended. Based on the effects of VAS3947, NADPH oxidases appear to be a major source of ROS in aortas of SHRs.
The roles and mechanisms of PAR4 and P2Y12/phosphatidylinositol 3‐kinase pathway in maintaining thrombin‐induced platelet aggregation
Authors: Wu Chin‐Chung , Wu Shih‐Yun , Liao Chieh‐Yu , Teng Che‐Ming , Wu Yang‐Chang , Kuo Sheng‐Chu
Published: June 2010

BACKGROUND AND PURPOSE Activation of human platelets by thrombin is mediated predominately through two proteinase‐activated receptors (PARs), PAR1 and PAR4. Phosphatidylinositol 3‐kinase (PI3K) inhibition leads to reversible PAR1‐mediated platelet aggregation, but has no effect on the stability of platelet aggregation induced by thrombin. In the present study, the molecular mechanisms underlying this difference were investigated.

EXPERIMENTAL APPROACH The functions of PI3K and PAR4 were assessed using specific inhibitors and aggregometry. The duration of platelet glycoprotein (GP) IIb/IIIa exposure was determined by flow cytometry with the antibody PAC‐1. Western blotting and fluo‐3 was used to evaluate the activation of Akt and protein kinase C (PKC) and intracellular Ca2+ mobilization respectively.

KEY RESULTS When PAR4 function was inhibited either by the PAR4 antagonist YD‐3 [1‐benzyl‐3‐(ethoxycarbonylphenyl)‐indazole] or by receptor desensitization, the PI3K inhibitor wortmannin turned thrombin‐elicited platelet aggregation from an irreversible event to a reversible event. Moreover, wortmannin plus YD‐3 markedly accelerated the inactivation of GPIIb/IIIa in thrombin‐stimulated platelets. The aggregation‐reversing activity mainly resulted from inhibition of both PI3K‐dependent PKC activation and PAR4‐mediated sustained intracellular Ca2+ rises. Blockade of ADP P2Y12 receptor with 2‐methylthioadenosine 5′‐monophosphate triethylammonium salt mimicked the inhibitory effect of wortmannin on PI3K‐dependent PKC activation and its ability to reverse PAR1‐activating peptide‐induced platelet aggregation. Co‐administration of 2‐methylthioadenosine 5′‐monophosphate triethylammonium salt with YD‐3 also decreased the stability of thrombin‐induced platelet aggregation.

CONCLUSIONS AND IMPLICATIONS These results suggest that PAR4 acts in parallel with the P2Y12/PI3K pathway to stabilize platelet aggregates, and provide new insights into the mechanisms of thrombus stabilization and potential applications for antithrombotic therapy.
Glioblastoma chemotherapy adjunct via potent serotonin receptor‐7 inhibition using currently marketed high‐affinity antipsychotic medicines
Authors: Kast RE
Published: June 2010

Glioblastoma treatment as now constituted offers increased survival measured in months over untreated patients. Because glioblastomas are active in synthesizing a bewildering variety of growth factors, a systematic approach to inhibiting these is being undertaken as treatment adjunct. The serotonin 7 receptor is commonly overexpressed in glioblastoma. Research documentation showing agonists at serotonin receptor 7 cause increased extracellular regulated kinase 1/2 activation, increased interleukin‐6 synthesis, increased signal transducer and activator of transcription‐3 activation, increased resistance to apoptosis and other growth enhancing changes in glioblastoma is reviewed in this paper. Because three drugs in wide use to treat thought disorders – paliperidone, pimozide and risperidone – are also potent and well‐tolerated inhibitors at serotonin receptor 7, these drugs should be studied for growth factor deprivation in an adjunctive role in glioblastoma treatment.
Informed Public Preferences for Electricity Portfolios with CCS and Other Low‐Carbon Technologies
Authors: Fleishman Lauren A. , De Bruin Wändi Bruine , Morgan M. Granger
Published: June 2010

Public perceptions of carbon capture and sequestration (CCS) and other low‐carbon electricity‐generating technologies may affect the feasibility of their widespread deployment. We asked a diverse sample of 60 participants recruited from community groups in Pittsburgh, Pennsylvania to rank 10 technologies (e.g., coal with CCS, natural gas, nuclear, various renewables, and energy efficiency), and seven realistic low‐carbon portfolios composed of these technologies, after receiving comprehensive and carefully balanced materials that explained the costs and benefits of each technology. Rankings were obtained in small group settings as well as individually before and after the group discussions. The ranking exercise asked participants to assume that the U.S. Congress had mandated a reduction in carbon dioxide emissions from power plants to be built in the future. Overall, rankings suggest that participants favored energy efficiency, followed by nuclear power, integrated gasification combined‐cycle coal with CCS and wind. The most preferred portfolio also included these technologies. We find that these informed members of the general public preferred diverse portfolios that contained CCS and nuclear over alternatives once they fully understood the benefits, cost, and limitations of each. The materials and approach developed for this study may also have value in educating members of the general public about the challenges of achieving a low‐carbon energy future.
ISO 31000:2009—Setting a New Standard for Risk Management
Authors: Purdy Grant
Published: June 2010

Last year saw the publication of IS0 31000:2009, a new globally accepted standard for risk management together with a new, associated vocabulary in ISO Guide 73:2009. These were developed through a consensus‐driven process over four years, through seven drafts, and involving the input of hundreds of risk management professionals around the world. The new standard supports a new, simple way of thinking about risk and risk management and is intended to begin the process of resolving the many inconsistencies and ambiguities that exist between many different approaches and definitions. While most decisionmakers seem to welcome the new standard and it has so far received very good reviews, it does create challenges for those who use language and approaches that are unique to their area of work but different from the new standard and guide. The need for compromise and change is the inevitable consequence of standardization
Differential Effect of Biventricular and Right Ventricular DDD Pacing on Coronary Flow Reserve in Patients With Ischemic Cardiomyopathy
Authors: DEFTEREOS SPYRIDON , GIANNOPOULOS GEORGIOS , KOSSYVAKIS CHARALAMPOS , RAISAKIS KONSTANTINOS , KAOUKIS ANDREAS , DRIVA METAXIA , PANAGOPOULOU VASILIKI , NTZOUVARA OLGA , THEODORAKIS ANDREAS , TOUTOUZAS KONSTANTINOS , PYRGAKIS VLASIOS , STEFANADIS CHRISTODOULOS
Published: June 2010

CRT and Coronary Flow Reserve. Background: Cardiac resynchronization therapy (CRT) has become a mainstay in heart failure management. There are also indications that upgrading of existing pacemakers to CRT systems may be of benefit. The aim of this study was to assess the effect of biventricular (BiV), compared with right ventricular (RV), pacing, on coronary flow reserve (CFR), in patients with ischemic cardiomyopathy.

Methods and Results: From our database of heart failure patients implanted with BiV pacemakers, 20 patients (10 responders and 10 non‐responders to CRT) were randomly selected. Left anterior descending artery coronary flow reserve was measured invasively, under BiV and RV pacing, using intracoronary adenosine to induce hyperemia. In all the 20 patients, there was a significant difference in the pairwise comparison between CFR recorded during BiV and RV pacing (mean difference 0.15, 95% confidence interval 0.07–0.23, P = 0.001). When comparing responders to non‐responders, there was a significant difference as to the effect of BiV, compared with RV, pacing on CFR: mean difference (BiV minus RV CFR) was 0.26 ± 0.06 (95% confidence interval 0.13–0.39; P = 0.002), while in non‐responders the difference was 0.04 ± 0.03 (95% confidence interval −0.02 to 0.10; P = 0.168).

Conclusion: BiV pacing is overall associated to higher CFR, compared with RV DDD pacing. This difference is almost exclusively attributable to the beneficial effect of CRT on coronary flow reserve in CRT‐responders. This effect may contribute to the beneficial action of resynchronization in the failing heart and can be viewed in the context of reports of the usefulness of upgrading RV pacemakers to CRT systems. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1233‐1239, November 2010)
Ultrastructure of the Harmful Unarmored Dinoflagellate Cochlodinium polykrikoides (Dinophyceae) with Reference to the Apical Groove and Flagellar Apparatus
Authors: IWATAKI MITSUNORI , HANSEN GERT , MOESTRUP ØJVIND , MATSUOKA KAZUMI
Published: June 2010

ABSTRACT. The external and internal ultrastructure of the harmful unarmored dinoflagellate Cochlodinium polykrikoides Margalef has been examined with special reference to the apical groove and three‐dimensional structure of the flagellar apparatus. The apical groove is U‐shaped and connected to the anterior sulcal extension on the dorsal side of the epicone. The eyespot is located dorsally and composed of two layers of globules situated within the chloroplast. A narrow invagination of the plasma membrane is associated with the eyespot. The nuclear envelope has normal nuclear pores similar to other eukaryotes but different from the Gymnodinium group with diagnostic nuclear chambers. The longitudinal and transverse basal bodies are separated by approximately 0.5–1.0 μm and interconnected directly by a striated basal body connective and indirectly by microtubular and fibrous structures. Characteristic features of the flagellar apparatus are as follows: (1) a nuclear extension projects to the R1 (longitudinal microtubular root) and is connected to the root by thin fibrous material; (2) fibrillar structures are associated with the longitudinal and transverse flagellar canal; and (3) a striated ventral connective extends toward the posterior end of the cell along the longitudinal flagellar canal. We conclude, based on both morphological and molecular evidence, that Cochlodinium is only distantly related to Gymnodinium.