bluuebunny/crossref_metadata_2025 huggingface dataset:
Aprotinin Abolishes Sevoflurane Postconditioning by Inhibiting Nitric Oxide Production and Phosphorylation of Protein Kinase C-δ and Glycogen Synthase Kinase 3β
Authors: Inamura Yoshitaka , Miyamae Masami , Sugioka Shingo , Kaneda Kazuhiro , Okusa Chika , Onishi Anna , Domae Naochika , Kotani Junichiro , Figueredo Vincent M.
Published: October 2009

Background

It remains controversial whether aprotinin use during cardiac surgery is cardioprotective or detrimental. In contrast, volatile anesthetics may offer cardioprotection perioperatively. Increased nitric oxide, protein kinase C activation, and glycogen synthase kinase 3beta inhibition play a role in sevoflurane-induced cardioprotection. The authors investigated whether aprotinin affects sevoflurane postconditioning.

Methods

Isolated guinea pig hearts underwent 30 min of global ischemia and 120 min of reperfusion (control [CTL]). Postconditioning was elicited with sevoflurane (2%) for 2 min at reperfusion onset (POST). Aprotinin (250 kallikrein inhibitor units/ml) was administered for 5 min at reperfusion onset (POST + APRO and CTL + APRO). In additional experiments, both sevoflurane and aprotinin were given before ischemia and throughout the reperfusion period (SEVO + APRO (throughout)) to mimic clinical conditions. Left ventricular developed and end-diastolic pressures and infarct size were measured. Western blot analysis determined phosphorylated protein kinase C-delta, protein kinase C-delta, Akt, and glycogen synthase kinase 3beta expression. Nitric oxide production during reperfusion was measured by nitric oxide sensor.

Results

After ischemia-reperfusion, POST had significantly higher left ventricular developed (56 +/- 11 vs. 26 +/- 8 mmHg [mean +/- SD]) and lower end-diastolic pressures (20 +/- 9 vs. 47 +/- 15 mmHg) and reduced infarct size (15 +/- 3% vs. 41 +/- 10%) versus CTL. Aprotinin abolished these improvements. Expressions of phospho-Akt (activated), phospho-protein kinase C-delta (activated), and phospho-glycogen synthase kinase 3beta (inhibited) were significantly increased in POST. Aprotinin attenuated these increased expressions. Nitric oxide production after reperfusion was higher in POST than in CTL, but not in POST + APRO.

Conclusions

Aprotinin abolishes sevoflurane postconditioning, associated with inhibited phosphorylation of Akt, protein kinase C-delta, and glycogen synthase kinase 3beta and reduced nitric oxide production.
Etomidate Targets α5γ-Aminobutyric Acid Subtype A Receptors to Regulate Synaptic Plasticity and Memory Blockade
Authors: Martin Loren J. , Oh Gabriel H. T. , Orser Beverley A.
Published: October 2009

Background

The memory-blocking properties of general anesthetics have recently received considerable attention because of concerns related to intraoperative awareness and postoperative cognitive dysfunction. The goal of this study was to identify the mechanisms by which gamma-aminobutyric acid subtype A receptors that contain the alpha5 subunit (alpha5GABAARs) induce memory-blockade by etomidate and a pharmacologic strategy to reverse this impairment.

Methods

The effects of etomidate and the alpha5GABAAR-preferring inverse agonist L-655,708 on the plasticity of glutamatergic excitatory transmission in hippocampal slices and behavioral memory for spatial navigational and fear-associated memory tasks were studied in wild-type and null mutant mice for the gene that encodes the alpha5 subunit (Gabra5-/- mice). Long-term potentiation of field excitatory postsynaptic potentials was induced in CA1 pyramidal neurons following high-frequency stimulation of Schaffer collaterals. Memory performance was studied in contextual, cued, and trace fear conditioning assays and the Morris water maze.

Results

Robust synaptic plasticity induced by high-frequency stimulation and memory performance for contextual fear and spatial navigational memory were not influenced by a decrease in the function of alpha5GABAARs. Nevertheless, etomidate, via an increase in alpha5GABAAR activity, completely blocked long-term potentiation and impaired memory performance, and these effects were reversed by pretreatment with L-655,708.

Conclusions

The results provide the first proof of concept that memory blockade by a general anesthetic can be reversed by inhibiting the function of alpha5GABAARs. The findings suggest a mechanism and model for awareness during anesthesia.
Ultrasound Evaluation of the Sacral Area and Comparison of Sacral Interspinous and Hiatal Approach for Caudal Block in Children
Authors: Shin Seo K. , Hong Jeong Yeon , Kim Won Oak , Koo Bon Nyeo , Kim Jee Eun , Kil Hae Keum
Published: October 2009

Background

Although caudal block via the sacral hiatus is a common regional technique in children, it is sometimes difficult to identify the hiatus. A needle approach via the S2-3 interspace can be used as an alternative to the conventional approach. The authors compared the feasibility and clinical characteristics between the S2-3 approach and hiatal approach, in addition to ultrasound study.

Methods

Sacral space depth, dural sac end level, and caudal space depth were evaluated using ultrasound with high-frequency linear probe in the lateral decubitus position in 317 anesthetized children (study 1). In another 162 children who underwent ambulatory urological surgeries, success rate, drug spread, and clinical characteristics were compared between the hiatal and S2-3 approaches (study 2).

Results

The dural sac end level was S2U (S3M-L5M). The median depth of the sacral space at the S2-3 level was 7.3 mm, whereas the caudal space depth at the hiatus was 2.9 mm. The overall success rate was 96.3% in both groups. The success rates at the first puncture attempt were 96.2% in the S2-3 group and 77.5% in the hiatus group. Drug spread level and clinical characteristics were similar between the two groups.

Conclusions

The S2-3 approach can be applied as a useful fallback method to the conventional landmark approach in children, especially in those older than 36 months who present with difficult identification of the sacral hiatus.
Redistribution of Pulmonary Blood Flow Impacts Thermodilution-based Extravascular Lung Water Measurements in a Model of Acute Lung Injury
Authors: Easley R Blaine , Mulreany Daniel G. , Lancaster Christopher T. , Custer Jason W. , Fernandez-Bustamante Ana , Colantuoni Elizabeth , Simon Brett A.
Published: October 2009

Background

Studies using transthoracic thermodilution have demonstrated increased extravascular lung water (EVLW) measurements attributed to progression of edema and flooding during sepsis and acute lung injury. The authors hypothesized that redistribution of pulmonary blood flow can cause increased apparent EVLW secondary to increased perfusion of thermally silent tissue, not increased lung edema.

Methods

Anesthetized, mechanically ventilated canines were instrumented with PiCCO (Pulsion Medical, Munich, Germany) catheters and underwent lung injury by repetitive saline lavage. Hemodynamic and respiratory physiologic data were recorded. After stabilized lung injury, endotoxin was administered to inactivate hypoxic pulmonary vasoconstriction. Computed tomographic imaging was performed to quantify in vivo lung volume, total tissue (fluid) and air content, and regional distribution of blood flow.

Results

Lavage injury caused an increase in airway pressures and decreased arterial oxygen content with minimal hemodynamic effects. EVLW and shunt fraction increased after injury and then markedly after endotoxin administration. Computed tomographic measurements quantified an endotoxin-induced increase in pulmonary blood flow to poorly aerated regions with no change in total lung tissue volume.

Conclusions

The abrupt increase in EVLW and shunt fraction after endotoxin administration is consistent with inactivation of hypoxic pulmonary vasoconstriction and increased perfusion to already flooded lung regions that were previously thermally silent. Computed tomographic studies further demonstrate in vivo alterations in regional blood flow (but not lung water) and account for these alterations in shunt fraction and EVLW.
Pseudomonas syringae pv. syringae B728a hydrolyses indole‐3‐acetonitrile to the plant hormone indole‐3‐acetic acid
Authors: HOWDEN ANDREW J. M. , RICO ARANTZA , MENTLAK THOMAS , MIGUET LAURENT , PRESTON GAIL M.
Published: October 2009

Nitrilase enzymes catalyse the hydrolysis of nitrile compounds to the corresponding carboxylic acid and ammonia, and have been identified in plants, bacteria and fungi. There is mounting evidence to support a role for nitrilases in plant–microbe interactions, but the activity of these enzymes in plant pathogenic bacteria remains unexplored. The genomes of the plant pathogenic bacteria Pseudomonas syringae pv. syringae B728a and Pseudomonas syringae pv. tomato DC3000 contain nitrilase genes with high similarity to characterized bacterial arylacetonitrilases. In this study, we show that the nitrilase of P. syringae pv. syringae B728a is an arylacetonitrilase, which is capable of hydrolysing indole‐3‐acetonitrile to the plant hormone indole‐3‐acetic acid, and allows P. syringae pv. syringae B728a to use indole‐3‐acetonitrile as a nitrogen source. This enzyme may represent an additional mechanism for indole‐3‐acetic acid biosynthesis by P. syringae pv. syringae B728a, or may be used to degrade and assimilate aldoximes and nitriles produced during plant secondary metabolism. Nitrilase activity was not detected in P. syringae pv. tomato DC3000, despite the presence of a homologous nitrilase gene. This raises the interesting question of why nitrilase activity has been retained in P. syringae pv. syringae B728a and not in P. syringae pv. tomato DC3000.
Forage production and plant diversity in two managed rangelands in the Main Ethiopian Rift
Authors: Mohammed Ali Seid , Bekele Tamrat
Published: October 2009

The purpose of this study was to investigate the floristic diversity and productivity of managed rangelands in the Main Ethiopian Rift (MER). The relationships between forage production and plant diversity among four native range sites (i.e. Alagae hay‐field, Alagae woodland, Neteli hay‐field and Neteli woodland) that were different in range condition were examined. The major variables studied include floristic diversity, herbaceous biomass production and range condition assessment. A total of 213 species, representing 143 genera and 40 families, were identified from the study sites. The range conditions ranked from poor to good. Herbaceous biomass production followed a quadratic relationship with range condition. The humpback model was tested and found to be applicable to the MER rangelands. The study results reflect on the need for optimizing productivity and biodiversity conservation and put emphasis on the need for integrating agricultural production and biodiversity conservation interests for the sustainable utilization of rangelands.
Variation in chicken populations may affect the enzymatic activity of lysozyme
Authors: Downing T. , O’Farrelly C. , Bhuiyan A. K. , Silva P. , Naqvi A. N. , Sanfo R. , Sow R.‐S. , Podisi B. , Hanotte O. , Bradley D. G.
Published: October 2009

The chicken lysozyme gene encodes a hydrolase that has a key role in defence, especially in ovo. This gene was resequenced in global chicken populations [red, grey, Ceylon and green jungle fowl (JF)] and related bird species. Networks, summary statistics and tests of neutrality indicate that although there is extensive variation at the gene, little is present at coding sites, with the exception of one non‐synonymous site. This segregating site and a further fixed non‐synonymous change between red JF and domestic chicken populations are spatially close to the catalytic sites of the enzyme and so might affect its activity.
Remote European mountain lake ecosystems: regionalisation and ecological status
Authors: CATALAN J. , CURTIS C. J. , KERNAN M.
Published: October 2009

1. A survey of c. 350 remote high altitude and high latitude lakes from 12 different mountain regions across Europe was undertaken to explore ecosystem variability, climate forcing, environmental conditions and pollution threats at a scale not previously attempted.

2. Lakes were sampled for a range of contemporary and sub‐fossil organisms including planktonic crustaceans, rotifers, littoral invertebrates, chironomids, diatoms and cladocerans. Survey and cartographic data were used to determine environmental characteristics at each site. Organic pollutants and trace metal concentrations were measured in the lake sediment.

3. A number of separate studies were undertaken which examined the environmental characteristics of the surveyed lakes (climate forcing and chemical composition), distribution of biota relative to local, regional and biogeographical factors and pollution threats (acidification, heavy metals and persistent organic pollutants) to these sensitive ecosystems.

4. There is a strong regional element to the way that environmental factors combine (including climate and pollution threats) and the biota responds in mountain lakes across Europe. From a management perspective it is clear that lake classification and the development of useful typologies and assessments of reference conditions should be undertaken at regional rather than pan‐European scales.

5. There are some common features across lake districts related to the timing of industrialisation, but the studies carried out on metals, organic pollutants and nitrate deposition indicate that each lake district has distinct pollution threats. Climate warming already affects most of the lake districts and there are considerable uncertainties as to how this will modify conditions in remote European mountain systems.

6. The lake district concept goes beyond a geographical construct and merits further theoretical and experimental development as an ecological concept.
A unique domain in RANK is required for Gab2 and PLCγ2 binding to establish osteoclastogenic signals
Authors: Taguchi Yuu , Gohda Jin , Koga Takako , Takayanagi Hiroshi , Inoue Jun‐ichiro
Published: October 2009

TRAF6 is essential for osteoclastogenesis and for both RANK‐ and CD40‐mediated activation of IKK and MAPKs. RANK, but not CD40, can promote osteoclastogenesis because only RANK induces NFATc1 activation through PLCγ2‐induced Ca2+ oscillations together with the co‐stimulatory signals emanating from immune receptors linked to ITAM‐containing adaptors. These previous data suggest that RANK harbors a unique domain that functions in concert with the TRAF6‐binding site in osteoclastogenesis. Here we identify such a domain, highly conserved domain in RANK (HCR), which is dispensable for the early phase of RANK and ITAM signaling but is essential for their late‐phase signaling, including sustained activation of NF‐κB and PLCγ2 leading to NFATc1 activation. HCR recruits an adaptor protein, Gab2, which further associates with PLCγ2 in the late phase. Formation of the HCR‐mediated signaling complex could account for the sustained activation of NF‐κB and PLCγ2. The present study identifies HCR as a unique domain that plays a critical role in the long‐term linkage between RANK and ITAM signals, providing a molecular basis for therapeutic strategies.
Interactions of slope and canopy of herbage of three herbage species on transport of faecal indicator bacteria by rain splash
Authors: Boyer D. G. , Belesky D. P.
Published: October 2009

The movement of faecal pathogens from land to surface and ground‐water are of great interest because of the public and livestock health implications. Knowledge of canopy structure and how it might be managed to help mitigate nutrient and pathogen movement in pasture is needed to create management practices that balance livestock production with environmental benefits. An experiment was conducted using a rainfall‐simulating device to test whether canopy structure of species common to pastures in Appalachia, USA could be managed to influence dispersion of faecal pathogens. Seven pots (30‐cm diameter) of white clover, orchardgrass and perennial ryegrass were lined up on horizontal and sloping surfaces under a rainfall simulator. The centre pot was inoculated at the soil surface with 4 × 1010 faecal coliform bacteria (FC) just before rainfall simulation started. The species were maintained under short, moderate and tall canopy management treatments. White clover exhibited the greatest rates of lateral and vertical dispersion of FC into the canopy, especially in the short canopy management treatment following 30 min of rainfall (about 40 mm). Low concentrations of faecal coliform bacteria also dispersed into the canopies of the grass species but the differences in concentration of FC between the grass species were not different. When the proportion of white clover in a pasture is high, the canopy should be relatively taller to reduce the likelihood of infection associated with faecal coliform‐contaminated herbage.
Effects of pasture management and fertilizer regimes on botanical changes in species‐rich mountain calcareous grassland in Central Europe
Authors: Lanta V. , Doležal J. , Lantová P. , Kelíšek J. , Mudrák O.
Published: October 2009

A 3‐year experiment was conducted in Central Europe to examine the effects of three managements, viz. continuous cattle grazing from April to September, mowing once in July and abandonment of grazing, and two levels of fertilizer application, no fertilizer and 400 kg ha−1of a NPK fertilizer, on changes in plant species composition and summer biomass of dry matter (DM) in a calcareous mountain grassland containing many plant functional types. Different managements led to changes in species composition due to species‐specific responses. Low creeping and rosette species were associated with grazing, while grasses and tall forbs correlated with mowing and abandonment of grazing, probably because of their ability to outcompete rosette species. There was a negative relationship between the number of species and above‐ground biomass and a positive relationship between number of species and below‐ground biomass, suggesting that these species‐rich communities allocate more to below‐ground organs when not grazed. The application of fertilizer had no effect on species composition but it indirectly increased competitive asymmetry for light and increased the number of plant extinctions. It is concluded that continuation of cattle grazing is an acceptable form of grassland management at the study site and that species and functional group compositions can rapidly change with changing environmental conditions such as abandonment of grazing or application of fertilizer.
Relationship of bite mass of cattle to sward structure of four temperate grasses in short‐term grazing sessions
Authors: Soder K. J. , Sanderson M. A. , Gregorini P. , Orr R. J. , Rubano M. D. , Rook A. J.
Published: October 2009

The effect of sward structure of four temperate grass species on the bite mass of cattle was evaluated. Micro‐swards (79 cm × 47 cm; approximately the area of a feeding station) of orchardgrass (Dactylis glomerata L.), quackgrass [Elymus repens (L.) Gould], meadow fescue [Schedonorus pratensis (Huds.) P. Beauv] and reed canarygrass (Phalaris arundinacea L.) were offered to Holstein dairy cows in short‐term grazing sessions in 2006 and 2007 using a 4 × 4 Latin square design. Cows were allowed to take fifty bites in each session. Bite mass was calculated by dividing the adjusted change in weight of the micro‐sward by the number of bites. Sward surface height, bulk density and distribution of herbage dry matter (DM) in the canopy were measured pre‐ and post‐grazing. Sward structure differed among the grass species within years but bite mass (on a fresh or DM basis) was not affected. Higher surface heights and bulk densities in 2006 compared with 2007 (averaged across grass species) resulted in greater bite masses of DM in 2006. Values were 25·7 cm vs. 17·0 cm for surface height; 1219 g m−3 vs. 926 g m−3 for bulk density; and 1·05 g DM bite−1 vs. 0·50 g DM bite−1 for 2006 and 2007 respectively. Within the context of this study, differences between years in bite mass, associated with greater changes in sward structure, were more important than differences among grass species.
Histological grading of invasive breast carcinoma – a simplification of existing methods in a large conservation series with long‐term follow‐up
Authors: Thomas Jeremy St J , Kerr Gillian R , Jack Wilma J L , Campbell Fiona , McKay Laura , Pedersen Hans‐Christian , Kunkler Ian H , Cameron David A , Chetty Udi , Bartlett John M S
Published: October 2009

Aims:  To assess the validity of grading in the Edinburgh Breast Conservation Series; a consecutive cohort of 1812 early breast cancer patients treated by breast conservation and radiotherapy between 1981 and 1998 in a single specialist centre with ≥9 years’ follow‐up and full staging data.

Methods and results:  A single pathologist (J.St.J.T) graded 1650 cases using the Elston and Ellis method (EE) with particular reference to the component data: acinar differentiation, nuclear pleomorphism and mitotic counts. The original method was then compared with binary scoring of the same components and the relationship to prognosis reassessed. EE grades and individual grade components were prognostic (P < 0.0001) with 10‐year cause‐specific survival of 95.6%, 86.4% and 74.7% for EE grades 1, 2 and 3, respectively. A binary scoring of grade components produces four groups, splitting EE grade 2 tumours into two groups with different outcomes – 10‐year survival rates for the four revised grades were 96.0%, 89.0%, 79.7% and 75.4%, respectively.

Conclusions:  Existing grading methodology is fully applicable in the narrower context of a conservation series but can be simplified. Subdivision of EE grade 2 into a true intermediate prognosis group and a second group with a worse prognosis also adds benefit.
Caffeine induces ram sperm hyperactivation independent of cAMP‐dependent protein kinase
Authors: Colás C. , Cebrián‐Pérez J. A. , Muiño‐Blanco T.
Published: October 2009

We have previously shown that a cocktail‐containing phosphodiesterase inhibitors (theophylline and caffeine), a phosphatase inhibitor (okadaic acid) and dibutyryl‐cAMP promoted specific protein tyrosine phosphorylation in ram spermatozoa during incubation in capacitating conditions. Here, we show, for the first time, that this cocktail induced a progressive time‐dependent increase in the capacitated‐sperm subpopulation.The addition of either the analogue of adenosine, 2‐chloro‐2′‐deoxyadenosine (Cl‐Ado) or caffeine provided a significant increase in the proportion of capacitated spermatozoa and total tyrosine phosphorylation. Computer‐assisted semen analysis was used to identify hyperactivated spermatozoa by setting maximum threshold for linearity (≤45%) and minimum for amplitude of lateral head displacement (≥3.5 μm). Our results showed that ram spermatozoa can be capacitated in vitro without displaying hyperactivated movement. Among the above‐mentioned compounds, only caffeine was able to induce hyperactivation that achieved the maximal response at 8 min of incubation, with a significant increase in hyperactivated spermatozoa of 44.4 ± 5.6% related to control samples. Flow cytometry analyses showed that caffeine induced a significant increase in the content of calcium in viable spermatozoa during the time‐course of incubation in capacitating conditions. BAPTA‐AM, a cell‐permeable calcium chelator, did not suppress the caffeine‐dependent hyperactivation. Quantitative analysis revealed that the addition of caffeine or Cl‐Ado accounted for an increase in intracellular cAMP level. However, this increase in cAMP does not seem to be responsible for the caffeine‐induced hyperactivation because the cAMP‐elevating agents (cocktail) did not promote hyperactivation either, although they greatly induced capacitation and protein tyrosine phosphorylation. The inhibition of PKA with H89 reduced both capacitation and protein tyrosine phosphorylation although hyperactivation increased. These results suggest that calcium from internal stores would be enough to initiate the hyperactivated movement, and that protein tyrosine phosphorylation implicated in ram sperm hyperactivation would be regulated by calcium rather than by PKA‐dependent cAMP.
The predictive value of testicular ultrasound abnormalities for carcinoma in situ of the testis in men at risk for testicular cancer
Authors: Elzinga‐Tinke J. E. , Sirre M. E. , Looijenga L. H. J. , Van Casteren N. , Wildhagen M. F. , Dohle G. R.
Published: October 2009

Testicular microlithiasis (TM) is sometimes observed during scrotal ultrasound examinations in men. It has been suggested that TM is more prevalent in testes of men at risk for testicular carcinoma in situ (CIS), the precursor cells of all testicular germ cell tumours (TGCT). We have performed a retrospective analysis of ultrasound images and additional clinical data of a selected cohort of men and have determined the risk factor of TM and other ultrasound abnormalities for testicular CIS. Between 2002 and 2007, 176 testicular biopsies were performed in men with abnormalities found on the scrotal ultrasound. TM was found in 76/176 men (43.2%) and CIS was diagnosed in 20 of these men (26.3%). Here, we focused on the group of 76 men with TM to determine additional risk factors, besides TM, for CIS. In both groups, those with and without CIS, reproductive hormones, scrotal ultrasound images and patient history were compared. Predictive ultrasound findings for CIS were TM (sensitivity 100%, 95% CI: 0.8–1.0; specificity 64.1%, 95% CI: 0.6–0.7; PPV 26.3%, 95% CI: 0.2–0.4) and within this group an inhomogeneous testicular parenchyma (OR 16.1, 95% CI 2.4–106.8; sensitivity 75.0%, 95% CI: 0.5–0.9; specificity 79.0%, 95% CI: 0.7–0.9; PPV 50.0%, 95% CI: 0.3–0.7). Other significantly ultrasound characteristics for CIS in this population with TM were clusters of TM (p = 0.02) and intra‐testicular lesions (p = 0.01). Men with CIS were found to have significantly lower values of inhibin‐B (p = 0.02). Clusters of TM, intra‐testicular lesions and lower values of inhibin‐B were not significantly different in logistic regression analysis. TM on scrotal ultrasound of men with risk factors for TGCT and men with clinical signs of testicular maldevelopment has a high predictive value for CIS. However, the predictive value of an inhomogeneous testicular parenchyma, besides TM, for CIS is much higher.
Genetic relatedness in groups of the humbug damselfish Dascyllus aruanus: small, similar‐sized individuals may be close kin
Authors: BUSTON PETER M. , FAUVELOT CÉCILE , WONG MARIAN Y. L. , PLANES SERGE
Published: October 2009

Kin selection plays an important role in the evolution of social behaviour in terrestrial systems. The extent to which kin selection influences the evolution of social behaviour in marine systems is largely unexplored. Generally, it is considered that kin selection is irrelevant in marine systems, because it is assumed that the dispersing larval phase of marine organisms will break up kin associations. Here, we challenge this assumption and investigate the opportunity for kin selection in a coral reef fish: the humbug damselfish Dascyllus aruanus. This fish lives in groups composed of a large male and a number of smaller females and nonbreeders. We use 10 polymorphic microsatellite loci to assess the relatedness of 265 individuals from 35 groups. The mean coefficient of relatedness among group members is 0.01 ± 0.04, suggesting that individuals are not associated with close relatives. However, the distribution of pairwise relatedness of individuals within groups has an overabundance of positive values, and indicates that there might be 35 pairs of close relatives within groups. Further analyses reveal that close relatives likely are similar in size and small in size, suggesting that they might have recruited together. We conclude that it is possible for kin selection to operate in D. aruanus, but kin recognition will be a prerequisite for such selection. This study reveals that individuals can be associated with close relatives, and there is a hidden potential for kin selection, during certain parts of the life cycle of coral reef fishes.
Contrasting mtDNA diversity and population structure in a direct‐developing marine gastropod and its trematode parasites
Authors: KEENEY DEVON B. , KING TANIA M. , ROWE DIANE L. , POULIN ROBERT
Published: October 2009

The comparative genetic structure of hosts and their parasites has important implications for their coevolution, but has been investigated in relatively few systems. In this study, we analysed the genetic structure and diversity of the New Zealand intertidal snail Zeacumantus subcarinatus (n = 330) and two of its trematode parasites, Maritrema novaezealandensis (n = 269) and Philophthalmus sp. (n = 246), using cytochrome c oxidase subunit I gene (COI) sequences. Snails and trematodes were examined from 11 collection sites representing three regions on the South Island of New Zealand. Zeacumantus subcarinatus displayed low genetic diversity per geographic locality, strong genetic structure following an isolation by distance pattern, and low migration rates at the scale of the study. In contrast, M. novaezealandensis possessed high genetic diversity, genetic homogeneity among collection sites and high migration rates. Genetic diversity and migration rates were typically lower for Philophthalmus sp. compared to M. novaezealandensis and it displayed weak to moderate genetic structure. The observed patterns likely result from the limited dispersal ability of the direct developing snail and the utilization of bird definitive hosts by the trematodes. In addition, snails may occasionally experience long‐distance dispersal. Discrepancies between trematode species may result from differences in their effective population sizes and/or life history traits.
Major histocompatibility complex variation at class II DQA locus in the brown hare (Lepus europaeus)
Authors: KOUTSOGIANNOULI E. A. , MOUTOU K. A. , SARAFIDOU T. , STAMATIS C. , SPYROU V. , MAMURIS Z.
Published: October 2009

The major histocompatability complex (MHC) is a multigene family of receptors that bind and present antigenic peptides to T‐cells. Genes of the MHC are characterized by an outstanding genetic polymorphism, which is considered to be maintained by positive selection. Sites involved in peptide binding form binding pockets (P) that are collectively termed the peptide‐binding region (PBR). In this study, we examined the level of MHC genetic diversity within and among natural populations of brown hare (Lepus europaeus) from Europe and Anatolia choosing for analysis of the second exon of the DQA locus, one of the most polymorphic class II loci. We aimed at an integrated population genetic analysis of L. europeaus by (i) correlating MHC polymorphism to genetic variability and phylogenetic status estimated previously from maternally (mtDNA) and biparentally (allozymes, microsatellites) inherited loci; and (ii) comparing full‐length exon amino acid polymorphism with functional polymorphism in the PBR and the binding pockets P1, P6 and P9. A substantial level of DQA exon 2 polymorphism was detected with two completely different set of alleles between the Anatolian and European populations. However, the phylogeny of full‐length exon 2 Leeu‐DQA alleles did not show a strong phylogeographic signal. The presence of balancing selection was supported by a statistically significant excess of nonsynonymous substitutions over synonymous in the PBR and a trans‐species pattern of evolution detected after phylogenetic reconstruction. The differentiating patterns detected between genetic and functional polymorphism, i.e. the number and the distribution of pocket variants within and among populations, indicated a hierarchical action of selection pressures.
Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1
Authors: Nyström AM , Ekvall S , Allanson J , Edeby C , Elinder M , Holmström G , Bondeson ML , Annerén G
Published: October 2009

Noonan syndrome (NS) and neurofibromatosis type I (NF1) belong to a group of clinically related disorders that share a common pathogenesis, dysregulation of the RAS‐MAPK pathway. NS is characterized by short stature, heart defect, pectus deformity and facial dysmorphism, whereas skin manifestations, skeletal defects, Lisch nodules and neurofibromas are characteristic of NF1. Both disorders display considerable clinical variability. Features of NS have been observed in individuals with NF1 –a condition known as neurofibromatosis–Noonan syndrome (NFNS). The major gene causing NFNS is NF1. Rarely, a mutation in PTPN11 in addition to an NF1 mutation is present.

We present the clinical and molecular characterization of a family displaying features of both NS and NF1, with complete absence of neurofibromas. To investigate the etiology of the phenotype, mutational analysis of NF1 was conducted, revealing a novel missense mutation in exon 24, p.L1390F, affecting the GAP‐domain. Additional RAS‐MAPK pathway genes were examined, but no additional mutations were identified. We confirm that NF1 mutations are involved in the etiology of NFNS. Furthermore, based on our results and previous studies we suggest that evaluation of the GAP‐domain of NF1 should be prioritized in NFNS.
A high‐throughput Taqman® approach for the discrimination of HLA‐E alleles
Authors: Paquay M. M. , Schellekens J. , Tilanus M. G. J.
Published: October 2009

An association between human leukocyte antigen (HLA) molecules and the incidence of various diseases has been recognized for years. Molecules of the HLA system also exert an important role on the clinical outcome after transplantation such as stem cell transplantation. The conventional HLA typing method is sequence based typing (SBT) which is reliable but laborious. The goal of this study was to develop a high‐throughput Taqman® assay to screen large panels for HLA‐E alleles. Two functional HLA‐E alleles, *0101 and *0103, have been identified. We set up the Taqman® assay with genomic DNA as template to discriminate the three HLA‐E genotypes: homozygous HLA‐E*0101, heterozygous *0101, *0103 and homozygous *0103. This Taqman® approach was validated by the comparison of results obtained with the typing results acquired by sequenced base typing (SBT). Additional screening of a large panel showed the pronounced discriminative capacity of the Taqman® assay for HLA‐E allele typing. The Taqman® assay is a fast, reliable and consistent HLA‐E allele typing method, especially useful to screen large panels.
IL‐21: roles in immunopathology and cancer therapy
Authors: Søndergaard H. , Skak K.
Published: October 2009

Cytokines are secreted signalling molecules with decisive effects on haematopoiesis, innate and adaptive immunity, and immunopathology. Interleukin (IL)‐21 is a novel cytokine produced by activated CD4+ T cells and natural killer T (NKT) cells. IL‐21 is part of a family of cytokines which include IL‐2, ‐4, ‐7, ‐9 and ‐15 that all share the common IL‐2 receptor γ chain (γc) in their individual receptor complexes. IL‐21 receptor (IL‐21R) is widely expressed on both myeloid and lymphoid cell lineages and IL‐21 actions include co‐stimulation of B cell differentiation and immunoglobulin (Ig) production, co‐mitogen of T cells, and stimulation of NK and CD8+ T cell cytotoxic function. Initially, IL‐21 was recognized for its anti‐tumour effects in several preclinical tumour models, warranting its currently ongoing clinical development as a cancer immunotherapeutic. More recently, IL‐21 has been associated with the development of a panel of autoimmune and inflammatory diseases, where neutralization of IL‐21 has been suggested as a potential new therapy. In this review, we will cover the latest discoveries of IL‐21 as a cancer therapy and its implications in immunopathologies.
Pathogenicity of Ceratocystis resinifera to Norway spruce
Authors: Krokene Paal , Roux Jolanda , Solheim Halvor , Wingfield Michael J.
Published: October 2009

The blue‐stain fungus Ceratocystis resinifera colonizes wounds on living Picea spp. and other conifers in Europe and North America. Little is known regarding the pathogenicity of this fungus and consequently, four Norwegian C. resinifera isolates were inoculated on to Norway spruce (Picea abies) using two different techniques. These included single‐point inoculations on young trees (two inoculations per tree on 14‐year‐old trees) and mass‐inoculations on older trees (∼200 inoculations per tree on 34‐year‐old trees). In both experiments, C. resinifera induced minor symptoms that in most cases did not differ significantly from inoculation with sterile agar. The virulent blue‐stain fungus C. polonica, which was inoculated for comparative purposes, induced extensive symptoms, causing 83% dead cambium circumference and 82% blue‐stained sapwood, and long necrotic lesions in the phloem. The results suggest that C. resinifera is non‐pathogenic or only mildly pathogenic to Norway spruce and does not present a threat to these trees.
Suppressing Secrecy Through Metacognitive Ease
Authors: Alter Adam L. , Oppenheimer Daniel M.
Published: October 2009

Understanding when people reveal unfavorable information about themselves is both practically and theoretically important. Existing research suggests that people tend not to adopt stable disclosure strategies, and consequently disclose too much information in some situations (e.g., embarrassing personal information on Face-book) and too little in other situations (e.g., risky sexual behavior to a physician during diagnosis of a possible sexually transmitted disease). We sought to identify a domain-general cue that predicts self-disclosure patterns. We found that metacognitive ease, or fluency, promoted greater disclosure, both in tightly controlled lab studies (Studies 1a, 1b, and 3) and in an ecologically valid on-line field study (Study 4). Disfluency tended to prime thoughts and emotions associated with risk, which might be one reason why people who experience disfluency are less comfortable with self-disclosure (Studies 2 and 3). We conclude by discussing the implications of these results for theory and clinical practice.
Evidence That Self-Relevant Motives and Metaphoric Framing Interact to Influence Political and Social Attitudes
Authors: Landau Mark J. , Sullivan Daniel , Greenberg Jeff
Published: October 2009

We propose that metaphor is a mechanism by which motivational states in one conceptual domain can influence attitudes in a superficially unrelated domain. Two studies tested whether activating motives related to the self-concept influences attitudes toward social topics when the topics' metaphoric association to the motives is made salient through linguistic framing. In Study 1, heightened motivation to protect one's own body from contamination led to harsher attitudes toward immigrants entering the United States when the country was framed in body-metaphoric, rather than literal, terms. In Study 2, a self-esteem threat led to more positive attitudes toward binge drinking of alcohol when drinking was metaphorically framed as physical self-destruction, compared with when it was framed literally or metaphorically as competitive other-destruction.
Brain natriuretic peptide as a predictor of delayed atrial fibrillation after ischaemic stroke and transient ischaemic attack
Authors: Okada Y. , Shibazaki K. , Kimura K. , Iguchi Y. , Miki T.
Published: October 2009

Background and purpose:  We investigated whether the brain natriuretic peptide (BNP) level can serve as a predictive biological marker of delayed atrial fibrillation (AF).

Methods:  Two hundred and thirty seven consecutive patients admitted to our institution with acute ischaemic stroke or transient ischaemic attack (TIA) within 24 h of onset were enrolled. The patients were classified according to the presence or absence of AF upon admission [AF and sinus rhythm (SR) groups]. The SR group was subdivided based on the development of AF after admission (new‐ and non‐AF groups). We compared the characteristics between the AF and SR groups, and between the new‐ and non‐AF groups. The factors associated with new‐AF were investigated by multivariate logistic regression analysis.

Results:  Amongst the enrolled patients, 72 (30.4%) had AF upon admission (AF group), and 13 (5.5%) developed AF thereafter (new‐AF group). The plasma BNP level was significantly higher in the AF, than in the SR group (401.7 vs. 92.1 pg/ml, P < 0.001). Moreover, the plasma BNP level was significantly higher in the new‐, than in the non‐AF group (184.7 vs. 84.1 pg/ml, P < 0.001). The optimal cutoff BNP level required to distinguish new‐, from non‐AF groups was 85.0 pg/ml, and the sensitivity and specificity was 83.3% and 76.2%, respectively. On multivariate logistic regression analysis, plasma BNP level >85.0 pg/ml (odds ratio, 7.20; 95% confidence interval, 1.71 to 30.43, P = 0.007) was an independent factor associated with new‐AF.

Conclusion:  High plasma BNP level should be a strong predictor of delayed AF after ischaemic stroke or TIA.
Management development in China: a policy analysis
Authors: Wang Greg G. , Rothwell William J. , Sun Judy Y.
Published: October 2009

This study analyzes the current structure of Chinese management development (MD) policy. It identifies three critical challenges facing Chinese managers and reviews related MD policies. It considers the evolution of major MD‐related policies in the context of broader social, economic and institutional changes in China. Five principal findings inform the conclusion that with the experience accumulated in three decades of reform practices, MD policy in China should no longer be based on the principle of ‘groping for stones to cross the river’. Rather, there should be established an accountability and evaluation mechanism for a well‐defined MD policy implementation process. This should accelerate the management learning process in China and overcome the country's shortage of management skills.
A model for evaluating the effectiveness of middle managers' training courses: evidence from a major banking organization in Greece
Authors: Galanou Ekaterini , Priporas Constantinos‐Vasilios
Published: October 2009

Contemporary management thinking embraces the organizational training theory that sustainable success rests, to a great extent, upon a systematic evaluation of training interventions. However, the evidence indicates that few organizations take adequate steps to assess and analyse the quality and outcomes of their training. The authors seek to develop the existing literature on training evaluation by proposing a new model, specific to management training, which might encourage more and better evaluation by practitioners. Their thesis is that training evaluation is best if it can be based on criteria derived from the objectives of the training and they draw on the management effectiveness literature to inform their proposed model. The study seeks to examine the effect of six evaluation levels – reactions, learning, job behaviour, job performance, organizational team performance and some wider, societal effects – in measuring training interventions with regard to the alterations to learning, transfer and organizational impact. The model was tested with data obtained from 190 middle managers employed by a large banking organization in Greece and the results suggest that there is considerable consistency in the evaluation framework specified. The paper discusses these results and draws conclusions about their practical implications. The study's limitations are considered and some future research needs identified.
The moderating effect of individual differences on the relationship between the framing of training and interest in training
Authors: Cox Cody B. , Beier Margaret E.
Published: October 2009

The moderating effect of individual differences on the relationship between framing training as ‘basic’ or ‘advanced’ and interest in training was examined for technical and nontechnical content areas. Participants were 109 working‐age adults (mean age = 38.14 years, SD = 12.20 years). Self‐efficacy and goal orientation were examined as moderators. Results showed a three‐way interaction between performance orientation (a dimension of goal orientation reflecting the desire to demonstrate competence in an achievement setting), age, and frame for technical training and a three‐way interaction between performance orientation, self‐efficacy, and frame for nontechnical training. Implications for future research as well as framing training to enhance interest are discussed.
The TRPC6 channel activator hyperforin induces the release of zinc and calcium from mitochondria
Authors: Tu Peng , Gibon Julien , Bouron Alexandre
Published: October 2009

J. Neurochem. (2010) 112, 204–213.

Hyperforin, an extract of the medicinal plant hypericum perforatum (also named St John’s wort), possesses antidepressant properties. Recent data showed that it elevates the intracellular concentration of Ca2+ by activating diacylglycerol‐sensitive C‐class of transient receptor potential (TRPC6) channels without activating the other isoforms (TRPC1, TRPC3, TRPC4, TRPC5, and TRPC7). This study was undertaken to further characterize the cellular neuronal responses induced by hyperforin. Experiments conducted on cortical neurons in primary culture and loaded with fluorescent probes for Ca2+ (Fluo‐4) and Zn2+ (FluoZin‐3) showed that it not only controls the activity of plasma membrane channels but it also mobilizes these two cations from internal pools. Experiments conducted on isolated brain mitochondria indicated that hyperforin, like the inhibitor of oxidative phosphorylation, carbonyl cyanide 4‐(trifluoromethoxy)phenylhydrazone (FCCP), collapses the mitochondrial membrane potential. Furthermore, it promotes the release of Ca2+ and Zn2+ from these organelles via a ruthenium red‐sensitive transporter. In fact, hyperforin exerts complex actions on CNS neurons. This antidepressant not only triggers the entry of cations via plasma membrane TRPC6 channels but it displays protonophore‐like properties. As hyperforin is now use to probe the functions of native TRPC6 channels, our data indicate that caution is required when interpreting results obtained with this antidepressant.
The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes
Authors: Zwisler Stine T. , Enggaard Thomas P. , Noehr‐Jensen Lene , Mikkelsen Soeren , Verstuyft Céline , Becquemont Laurent , Sindrup Soeren H. , Brosen Kim
Published: October 2009

The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty‐three healthy subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25% for the wild‐type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild‐type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild‐type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild‐type genotype 3435CC‐2677GG was associated with less antinociceptive effect of oxycodone in the discomfort rating of the cold pressor test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions than the carriers of the variant alleles. We found a moderate association between less antinociceptive effect of oxycodone and the variant allele of A118G. There was strong association between less adverse drug reactions of oxycodone and the variant alleles of C3435T and G2677T/A.