bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice
Authors: Mooney M H , Fogarty S , Stevenson C , Gallagher A M , Palit P , Hawley S A , Hardie D G , Coxon G D , Waigh R D , Tate R J , Harvey A L , Furman B L
Published: February 2008

Background and purpose: Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight‐reducing effects of galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action.

Experimental approach: Body weight and food intake were examined in mice. Glucose uptake and acetyl‐CoA carboxylase activity were studied in 3T3‐L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3‐L1 adipocytes.

Key results: Galegine administered in the diet reduced body weight in mice. Pair‐feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3‐L1 adipocytes and L6 myotubes, galegine (50 μM‐3 mM) stimulated glucose uptake. Galegine (1–300 μM) also reduced isoprenaline‐mediated lipolysis in 3T3‐L1 adipocytes and inhibited acetyl‐CoA carboxylase activity in 3T3‐L1 adipocytes and L6 myotubes. Galegine (500 μM) down‐regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 μM and above) produced a concentration‐dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3‐L1 adipocytes and L6 myotubes.

Conclusions and implications: Activation of AMPK can explain many of the effects of galegine, including enhanced glucose uptake and inhibition of acetyl‐CoA carboxylase. Inhibition of acetyl‐CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of galegine on body weight.

British Journal of Pharmacology (2008) 153, 1669–1677; doi:10.1038/bjp.2008.37; published online 25 February 2008
9‐Phenanthrol inhibits human TRPM4 but not TRPM5 cationic channels
Authors: Grand T , Demion M , Norez C , Mettey Y , Launay P , Becq F , Bois P , Guinamard R
Published: February 2008

Background and purpose: TRPM4 and TRPM5 are calcium‐activated non‐selective cation channels with almost identical characteristics. TRPM4 is detected in several tissues including heart, kidney, brainstem, cerebral artery and immune system whereas TRPM5 expression is more restricted. Determination of their roles in physiological processes requires specific pharmacological tools. TRPM4 is inhibited by glibenclamide, a modulator of ATP binding cassette proteins (ABC transporters), such as the cystic fibrosis transmembrane conductance regulator (CFTR). We took advantage of this similarity to investigate the effect of hydroxytricyclic compounds shown to modulate ABC transporters, on TRPM4 and TRPM5.

Experimental approach: Experiments were conducted using HEK‐293 cells permanently transfected to express human TRPM4 or TRPM5. Currents were recorded using the whole‐cell and inside‐out variants of the patch‐clamp technique.

Key results: The CFTR channel activator benzo[c]quinolizinium MPB‐104 inhibited TRPM4 current with an IC50 in the range of 2 × 10−5 M, with no effect on single‐channel conductance. In addition, 9‐phenanthrol, lacking the chemical groups necessary for CFTR activation, also reversibly inhibited TRPM4 with a similar IC50. Channel inhibition was voltage independent. The IC50 determined in the whole‐cell and inside‐out experiments were similar, suggesting a direct effect of the molecule. However, 9‐phenanthrol was ineffective on TRPM5, the most closely related channel within the TRP protein family.

Conclusions and implications: We identify 9‐phenanthrol as a TRPM4 inhibitor, without effects on TRPM5. It could be valuable in investigating the physiological functions of TRPM4, as distinct from those of TRPM5.

British Journal of Pharmacology (2008) 153, 1697–1705; doi:10.1038/bjp.2008.38; published online 25 February 2008
Long‐term nitric oxide deficiency causes muscarinic supersensitivity and reduces β3‐adrenoceptor‐mediated relaxation, causing rat detrusor overactivity
Authors: Mónica F Z T , Bricola A A O , Báu F R , Freitas L L Lopes , Teixeira S A , Muscará M N , Abdalla F M F , Porto C S , De Nucci G , Zanesco A , Antunes E
Published: February 2008

Background and purpose:

Overactive bladder is a complex and widely prevalent condition, but little is known about its physiopathology. We have carried out morphological, biochemical and functional assays to investigate the effects of long‐term nitric oxide (NO) deficiency on muscarinic receptor and β‐adrenoceptor modulation leading to overactivity of rat detrusor muscle.

Experimental approach:

Male Wistar rats received Nω‐nitro‐L‐arginine methyl ester (L‐NAME) in drinking water for 7–30 days. Functional responses to muscarinic and β‐adrenoceptor agonists were measured in detrusor smooth muscle (DSM) strips in Krebs–Henseleit solution. Measurements of [3H]inositol phosphate, NO synthase (NOS) activity, [3H]quinuclidinyl benzilate ([3H]QNB) binding and bladder morphology were also performed.

Key results:

Long‐term L‐NAME treatment significantly increased carbachol‐induced DSM contractile responses after 15 and 30 days; relaxing responses to the β3‐adrenoceptor agonist BRL 37‐344 were significantly reduced at 30 days. Constitutive NOS activity in bladder was reduced by 86% after 7 days and maintained up to 30 days of L‐NAME treatment. Carbachol increased sixfold the [3H]inositol phosphate in bladder tissue from rats treated with L‐NAME. [3H]QNB was bound with an apparent KD twofold higher in bladder membranes after L‐NAME treatment compared with that in control. No morphological alterations in DSM were found.

Conclusions and implications:

Long‐term NO deficiency increased rat DSM contractile responses to a muscarinic agonist, accompanied by significantly enhanced KD values for muscarinic receptors and [3H]inositol phosphate accumulation in bladder. This supersensitivity for muscarinic agonists along with reductions of β3‐adrenoceptor‐mediated relaxations indicated that overactive DSM resulted from chronic NO deficiency.

British Journal of Pharmacology (2008) 153, 1659–1668; doi:10.1038/bjp.2008.39; published online 25 February 2008
Pharmacological profile of the clonidine‐induced inhibition of vasodepressor sensory outflow in pithed rats: correlation with α2A/2C‐adrenoceptors
Authors: Villalón C M , Albarrán‐Juárez J A , Lozano‐Cuenca J , Pertz H H , Görnemann T , Centurión D
Published: February 2008

Background and purpose: Resistance blood vessels are innervated by sympathetic and primary sensory nerves, which modulate vascular tone through the release of noradrenaline and calcitonin gene‐related peptide (CGRP), respectively. Moreover, electrical stimulation of the perivascular sensory outflow in pithed rats results in vasodepressor responses which are mainly mediated by CGRP release. The present study has investigated the role of α2‐adrenoceptors in the inhibition of these vasodepressor responses.

Experimental approach: 144 pithed male Wistar rats were pretreated with hexamethonium (2 mg kg−1 min−1) followed by i.v. continuous infusions of either methoxamine (15 and 30 μg kg−1 min−1) or clonidine (3, 10 and 30 μg kg−1 min−1). Under these conditions, electrical stimulation (0.56–5.6 Hz; 50 V and 2 ms) of the spinal cord (T9–T12) resulted in frequency‐dependent decreases in diastolic blood pressure.

Key results: The infusion of clonidine (10 μg kg−1 min−1), as compared to those of methoxamine (15 or 30 μg kg−1 min−1), inhibited the vasodepressor responses to electrical stimulation without affecting those to i.v. bolus injections of α‐CGRP (0.1–1 μg kg−1). This inhibition by clonidine was: (i) antagonized by 300 μg kg−1 rauwolscine (α2A/2B/2C), 300 and 1000 μg kg−1 BRL44408 (α2A), or 10 and 30 μg kg−1 MK912 (α2C); and (ii) unaffected by 1 ml kg−1 saline, 100 μg kg−1 BRL44408, 3000 and 10000 μg kg−1 imiloxan (α2B) or 3 μg kg−1 MK912.

Conclusions and implications: The inhibition produced by 10 μg kg−1 min−1 clonidine on the vasodepressor (perivascular) sensory outflow in rats may be mainly mediated by prejunctional α2A/α2C‐adrenoceptors.
A role for the RISK pathway and KATPchannels in pre‐ and post‐conditioning induced by levosimendan in the isolated guinea pig heart
Authors: Du Toit E F , Genis A , Opie L H , Pollesello P , Lochner A
Published: February 2008

Background and purpose:Myocardial reperfusion injury prevents optimal salvage of the ischaemic myocardium, and adjunct therapy that would significantly reduce reperfusion injury is still lacking. We investigated whether (1) the heart could be pre‐ and/or post‐conditioned using levosimendan (levosimendan pre‐conditioning (LPC) and levosimendan post‐conditioning (LPostC)) and (2) the prosurvival kinases and/or the sarcolemmal or mitochondrial KATPchannels are involved.

Experimental approach:Isolated guinea pig hearts were treated with two 5 min cycles of levosimendan (0.1 μM) interspersed with vehicle perfusion, or two 5 min cycles of ischaemia/reperfusion, before coronary artery ligation (CAL) for 40 min at 36.5 °C. Hearts were treated with mitochondrial or sarcolemmal KATPchannel blockers before LPC or LPostC. For post‐conditioning, hearts received three 30 s cycles of ischaemia/reperfusion or levosimendan/vehicle. Hearts were pretreated with levosimendan immediately before CAL (without washout). Cardiac function, infarct size and reperfusion injury salvage kinase activity was assessed.

Key results:LPC and LPostC halved the infarct size compared with controls (P<0.05). Treatment with KATPchannel blockers before LPC or LPostC reversed this decrease. Pretreating hearts with levosimendan increased activity of extracellular signal‐regulated kinase (ERK) 42/44 on reperfusion and had the most marked infarct‐lowering effect (P<0.05).

Conclusions and implications:(1) Hearts could be pharmacologically pre‐ and post‐conditioned with levosimendan; (2) levosimendan pretreatment is the most effective way to reduce infarct size, possibly by increasing ERK 42/44 activity; (3) benefits of LPC and LPostC were abolished by both KATPchannel blockers and (4) LPC may be useful before elective cardiac surgery, whereas LPostC may be used after acute coronary artery events.
A potent and selective p38 inhibitor protects against bone damage in murine collagen‐induced arthritis: a comparison with neutralization of mouse TNFα
Authors: Mihara K , Almansa C , Smeets R L , Loomans E E M G , Dulos J , Vink P M F , Rooseboom M , Kreutzer H , Cavalcanti F , Boots A M , Nelissen R L
Published: February 2008

Background and purpose: The p38 kinase regulates the release of proinflammatory cytokines including tumour‐necrosis factor‐α (TNFα) and is regarded as a potential therapeutic target in rheumatoid arthritis (RA). Using the novel p38 inhibitor Org 48762‐0, we investigated the therapeutic potential of p38 inhibition and compared this to anti‐mouse (m)TNFα antibody treatment in murine collagen‐induced arthritis (CIA).

Experimental approach: Pharmacological profiles of Org 48762‐0 were characterized in kinase assays, cellular assays and in lipopolysaccharide (LPS)‐induced inflammation in mice. The effects of Org 48762‐0 and of mTNFα‐neutralization on established arthritis were examined in murine CIA.

Key results: Org 48762‐0 potently inhibited p38α kinase with a high degree of kinase selectivity. In cellular assays, Org 48762‐0 reduced LPS‐induced TNFα release. Oral administration of Org 48762‐0 in mice showed drug‐like pharmacokinetic properties and inhibited LPS‐induced cytokine production. These pharmacological characteristics of Org 48762‐0 prompted a comparison of therapeutic efficacy with mTNFα‐neutralization in CIA. Org 48762‐0 and anti‐mTNFα antibody treatment equally inhibited development of arthritis when evaluated macroscopically. Radiological analyses revealed protection against bone damage for both treatments, although statistical difference was reached with Org 48762‐0 treatment only. Further, micro‐computed tomographical and histopathological analyses confirmed the protective effects of Org 48762‐0 on joint damage.

Conclusions and implications: Pharmacological targeting of p38 kinase provided good protection against joint tissue damage in CIA. In our experiments, neutralization of mTNFα produced less prominent suppression of bone damage. Our data suggest a therapeutic potential for selective and potent p38 inhibitors in RA.
Thermal effect on slider flight height in heat assisted magnetic recording
Authors: Xu B. X. , Yuan H. X. , Zhang J. , Yang J. P. , Ji R. , Chong T. C.
Published: February 2008

In this paper, the real time thermal effect of the heat assisted magnetic recording (HAMR) on the slider flying height is investigated with HAMR spin stand. In the experiment, a modulated laser beam is used to heat the media and the slider vibration is measured with laser Doppler vibrometer. The slider vibrations at different laser modulation frequencies and different laser powers are investigated and near 0.2nm flying height change is observed. Analysis shows that the main reason to cause the flying height change results from the disk surface thermal distortion caused by thermal expansion.
Three-dimensional endoluminal ultrasound-guided interstitial brachytherapy in patients with anal cancer
Authors: Christensen A. F. , Nielsen Bachmann M. , Engelholm S. A.
Published: February 2008

Background: New techniques using image guidance other than computed tomography (CT) and traditional two-dimensional (2D) endosonography might improve interstitial brachytherapy in patients with anal cancer.

Purpose: To investigate a new technique guided by three-dimensional (3D) endosonography used in our institution.

Material and Methods: Seventeen patients with anal carcinoma were referred to interstitial brachytherapy under 3D endosonographic guidance after external radiotherapy. The procedure was initiated by anal endosonography performed with a 10-MHz rotating endoprobe. Cross-sectional images of the anal sphincters were stored on a 3D system during retraction of the endoprobe through the anal canal. Afterward, any projection could be reconstructed. From this scanning, the optimal positioning of the needles was determined. The needles were inserted through holes in an externally fixated anal template. A repeated endosonography assured that optimal tumor coverage could be obtained by adjusting the number, dwell positions, and/or position of the needles.

Results: In all patients, endosonography was able to visualize the extension of the tumors and the position of each needle in 3D.

Conclusion: 3D endosonography guidance of interstitial brachytherapy in anal carcinoma seems to optimize the implant procedure and offer better information for dose planning.
Troponin and Titin Coordinately Regulate Length-dependent Activation in Skinned Porcine Ventricular Muscle
Authors: Terui Takako , Sodnomtseren Munguntsetseg , Matsuba Douchi , Udaka Jun , Ishiwata Shin'ichi , Ohtsuki Iwao , Kurihara Satoshi , Fukuda Norio
Published: February 2008

We investigated the molecular mechanism by which troponin (Tn) regulates the Frank-Starling mechanism of the heart. Quasi-complete reconstitution of thin filaments with rabbit fast skeletal Tn (sTn) attenuated length-dependent activation in skinned porcine left ventricular muscle, to a magnitude similar to that observed in rabbit fast skeletal muscle. The rate of force redevelopment increased upon sTn reconstitution at submaximal levels, coupled with an increase in Ca2+ sensitivity of force, suggesting the acceleration of cross-bridge formation and, accordingly, a reduction in the fraction of resting cross-bridges that can potentially produce additional active force. An increase in titin-based passive force, induced by manipulating the prehistory of stretch, enhanced length-dependent activation, in both control and sTn-reconstituted muscles. Furthermore, reconstitution of rabbit fast skeletal muscle with porcine left ventricular Tn enhanced length-dependent activation, accompanied by a decrease in Ca2+ sensitivity of force. These findings demonstrate that Tn plays an important role in the Frank-Starling mechanism of the heart via on–off switching of the thin filament state, in concert with titin-based regulation.
Tait’s conjectures and odd crossing number amphicheiral knots
Authors: Stoimenow A.
Published: February 2008

We give a brief historical overview of the Tait conjectures, made 120 years ago in the course of his pioneering work in tabulating the simplest knots, and solved a century later using the Jones polynomial. We announce the solution, again based on a substantial study of the Jones polynomial, of one (possibly his last remaining) problem of Tait, with the construction of amphicheiral knots of almost all odd crossing numbers. An application to the non-triviality problem for the Jones polynomial is also outlined.
Regularity properties in the classification program for separable amenable C*-algebras
Authors: Elliott George , Toms Andrew
Published: February 2008

We report on recent progress in the program to classify separable amenable C∗^*-algebras. Our emphasis is on the newly apparent role of regularity properties such as finite decomposition rank, strict comparison of positive elements, andZ\mathcal {Z}-stability, and on the importance of the Cuntz semigroup. We include a brief history of the program’s successes since 1989, a more detailed look at the Villadsen-type algebras which have so dramatically changed the landscape, and a collection of announcements on the structure and properties of the Cuntz semigroup.
The NADPH oxidase Cpnox1 is required for full pathogenicity of the ergot fungus Claviceps purpurea
Authors: GIESBERT SABINE , SCHÜRG TIMO , SCHEELE SANDRA , TUDZYNSKI PAUL
Published: February 2008

The role of reactive oxygen species (ROS) in interactions between phytopathogenic fungi and their hosts is well established. An oxidative burst mainly caused by superoxide formation by membrane‐associated NADPH oxidases is an essential element of plant defence reactions. Apart from primary effects, ROS play a major role as a second messenger in host response. Recently, NADPH oxidase (nox)‐encoding genes have been identified in filamentous fungi. Functional analyses have shown that these fungal enzymes are involved in sexual differentiation, and there is growing evidence that they also affect developmental programmes involved in fungus–plant interactions. Here we show that in the biotrophic plant pathogen Claviceps purpurea deletion of the cpnox1 gene, probably encoding an NADPH oxidase, has impact on germination of conidia and pathogenicity: Δcpnox1 mutants can penetrate the host epidermis, but they are impaired in colonization of the plant ovarian tissue. In the few cases where macroscopic signs of infection (honeydew) appear, they are extremely delayed and fully developed sclerotia have never been observed. C. purpurea Nox1 is important for the interaction with its host, probably by directly affecting pathogenic differentiation of the fungus.
Quantitative trait loci for chemical body composition traits in pigs and their positional associations with body tissues, growth and feed intake
Authors: Duthie C. , Simm G. , Doeschl‐Wilson A. , Kalm E. , Knap P. W. , Roehe R.
Published: February 2008

In this study, quantitative trait loci (QTL) for chemical and physical body composition, growth and feed intake in pigs were identified in a three‐generation full‐sib population, developed by crossing Pietrain sires with a commercial dam line. Phenotypic data from 315 F2 animals were available for protein and lipid deposition measured in live animals by the deuterium dilution technique at 30‐, 60‐, 90‐, 120‐ and 140‐kg body weight. At 140‐kg body weight, carcass characteristics were measured by the AutoFOM grading system and after dissection. Three hundred and eighty‐six animals from 49 families were genotyped for 51 molecular markers covering chromosomes SSC2, SSC4, SSC8, SSC9, SSC10 and SSC14. Novel QTL for protein (lipid) content at 60‐kg body weight and protein (lipid) accretion from 120 to 140 kg were detected on SSC9 near several previously detected QTL for lean and fat tissue in neck, shoulder and ham cuts. Another QTL for lipid accretion was found on SSC8, closely associated with a QTL for intramuscular fat content. QTL for daily feed intake were detected on SSC2 and SSC10. The favourable allele of a QTL for food conversion ratio (FCR) on SSC2 was associated with alleles for increased lean tissue and decreased fat tissue. Because no QTL for growth rate were found in the region, the QTL for FCR is most likely due to a change in body composition. These QTL provide insights into the genomic regulation of chemical or physical body composition and its association with feed intake, feed efficiency and growth.
Characterization of peptidic and carbohydrate cross‐reactive determinants in pollen polysensitization
Authors: Chardin H. , Sénéchal H. , Wal J. M. , Desvaux F. X. , Godfrin D. , Peltre G.
Published: February 2008

Background
Cross‐reactivity may be due to protein sequence or domain homologies and/or the existence of cross‐reactive carbohydrate determinants (CCDs). The clinical relevance of peptidic cross‐reactivities is well known, whereas that of CCDs is still a question of debate. The aim of this study is to characterize the IgE specificity of various patients suffering from pollen polysensitization to identify both peptidic and carbohydrate cross‐reactive determinants.

Material and methods
Rapeseed, grass and Arabidopsis proteins were separated by isoelectric focusing, followed by SDS‐PAGE, and transferred to a nitrocellulose sheet. The sheets were incubated either with an individual serum from a birch+grass‐sensitive patient, followed by anti‐human IgE, or with labelled Concanavalin A (ConA). Binding inhibition was tested by incubation of the sera with a mixture of sugar residues.

Results
The results showed two different patterns of cross‐reacting sera: a pattern that implies few proteins, not always glycosylated and known as allergens, and a pattern that implies numerous proteins with molecular masses over 30 kDa. This second pattern was very close to the ConA ‐binding pattern. The IgE binding was abolished by pre‐incubation with sugar residues only in the case of the second pattern.

Discussion
This study shows that multiple pollen sensitizations could result from multiple sensitizations to specific proteins or from a cross‐sensitization to a wide range of glycoproteins. Two‐D blots allow to characterize a cross‐sensitization due to carbohydrate determinants, and thus to improve the diagnosis of allergy and its medical treatment.
Clinical and immunologic findings of methylene diphenyl diisocyanate‐induced occupational asthma in a car upholstery factory
Authors: Hur G‐Y. , Koh D‐H. , Choi G‐S. , Park H‐J. , Choi S‐J. , Ye Y‐M. , Kim K‐S. , Park H‐S.
Published: February 2008

Background
Although methylene diphenyl diisocyanate (MDI) is widely used in many industries, there have been few immunological studies of MDI‐induced occupational asthma.

Objectives
We investigated the effects of MDI exposure on the clinical and immunologic condition of workers in a single car upholstery factory.

Methods
Fifty‐eight MDI‐exposed workers were studied. Work‐related lower‐respiratory symptoms (WRRS) were identified using a questionnaire. Serum‐specific IgE and IgG antibodies to MDI‐human serum albumin conjugate were detected by ELISA. Atopy was evaluated using a skin prick test. MDI‐induced occupational asthma was confirmed in the symptomatic workers with a positive result on an MDI‐specific inhalation test.

Results
Thirteen (22.4%) of the subjects complained of WRRS. MDI‐induced occupational asthma was confirmed in five (8.6%) of the workers, and occupational eosinophilic bronchitis was confirmed in two (3.5%). The prevalence of specific IgG antibodies (20.7%) was higher than that of specific IgE antibodies (8.6%). The prevalence of MDI‐induced occupational asthma/eosinophilic bronchitis was strongly associated with the presence of both WRRS and serum‐specific IgG antibodies to an MDI‐human serum albumin conjugate (P<0.01, <0.05, respectively).

Conclusion
These findings suggest that MDI could be a causative agent of occupational asthma among MDI‐exposed workers. The prevalence of MDI‐induced occupational asthma was 8.6%, and MDI‐induced eosinophilic bronchitis was confirmed in two workers. The presence of work‐related lower‐respiratory symptoms and serum‐specific IgG antibodies to an MDI‐human serum albumin conjugate may be used to predict MDI‐induced occupational asthma/eosinophilic bronchitis in MDI‐exposed workers.
Early skin sensitization to aeroallergens
Authors: De Bilderling G. , Mathot M. , Agustsson S. , Tuerlinckx D. , Jamart J. , Bodart E.
Published: February 2008

Background
Early detection of aeroallergen sensitization is important as a prognosis factor but may be more difficult in young children.

Objective
We sought to demonstrate that skin sensitization to aeroallergens was present in a selected group of 0–2‐year‐old children and that it was associated with environmental exposure and a family history of allergic disease.

Methods
Data on exposure and history were extracted from the files of 824 children seen in the asthma clinic and who were skin tested to a panel of aero‐ and food allergens.

Results
Forty percent of our children demonstrated atopy, 28% were sensitized to aeroallergens, the majority of which to house dust mite. Higher sensitization rates were found in children with large weals to histamine (P<0.001) and in those who slept with soft toys [odds ratio (OR) 1.45, 95% confidence interval (CI) 1.02–2.08]. With a definition of sensitization including the size of the weal to histamine, there was a negative association with a personal history of eczema only (OR 0.66, 95% CI 0.45–0.99). There was no gender‐dependent effect and no association with day‐care attendance.

Conclusion
This is one of the largest studies to evaluate skin testing in a selected population of young children. We found a high prevalence of sensitization to aeroallergens, which was associated with exposure to soft toys. Further follow‐up of this population will allow assessment of the predictive value of this sensitization.
Exhaled breath condensate in patients with asthma: implications for application in clinical practice
Authors: Kostikas K. , Koutsokera A. , Papiris S. , Gourgoulianis K. I. , Loukides S.
Published: February 2008

Exhaled breath condensate (EBC) analysis, a rather appealing and promising method, can be used to evaluate conveniently and non‐invasively a wide range of molecules from the respiratory tract, and to understand better the pathways propagating airway inflammation. A large number of mediators of inflammation, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results to date, the introduction of EBC in everyday clinical practice requires the resolution of some methodological pitfalls, the standardization of EBC collection and finally the identification of a reliable biomarker that is reproducible has normal values and provides information regarding the underlying inflammatory process and the response to treatment. So far, none of the parameters studied in EBC fulfils the aforementioned requirements with one possible exception: pH. EBC pH is reproducible, has normal values, reflects a significant part of asthma pathophysiology and is measurable on‐site with standardized methodology although some methodological aspects of measurement of pH in EBC (e.g. the effect of ambient CO2, sample de‐aeration, time for pH measurement) require further research. However, EBC pH has not been evaluated prospectively as a guide for treatment, in a manner similar to exhaled NO and sputum eosinophils. EBC represents a simple and totally non‐invasive procedure that may contribute towards our understanding of asthma pathophysiology. Besides the evaluation of new biomarkers, the standardization of the already existing procedures is warranted for the introduction of EBC in clinical practice.
Incorporating life histories and diet quality in stable isotope interpretations of crustacean zooplankton
Authors: VENTURA MARC , CATALAN JORDI
Published: February 2008

1. Stable isotope studies have been extremely useful for improving general food web descriptions due to their ability to simultaneously summarize complex trophic networks and track the energy flow through them. However, when considering trophic relationships involving only two or few species, application of general isotopic interpretations based on average fractionation values may easily lead to misleading conclusions. In these cases a more accurate consideration of the current processes involved in the isotopic fractionation should be considered.

2. We investigated the trophic relationships of the crustacean zooplankton assemblage in an alpine lake (Lake Redon, Pyrenees) by means of stable isotopes of carbon and nitrogen and applied information on their life history and biochemical composition in the interpretation.

3. The three species occurring in the lake had distinct isotopic signatures: the two copepod species (the cyclopoid Cyclops abyssorum and the calanoid Diaptomus cyaneus) had higher nitrogen isotopic composition than the cladoceran (Daphnia pulicaria), indicative of a higher trophic position of the two copepods. Most intra‐specific isotopic variability was associated with growth, while the effect of metabolic turnover was negligible. The effects of changes in the proportion of lipids was restricted to the adults of the two copepods.

4. Daphnia Juveniles showed ontogenetic shifts in their carbon, and nitrogen isotopic composition. Cyclops copepodites only showed changes in carbon isotopic composition. These isotopic shifts with changes in size were the result of: (i) the prevalence of growth over metabolic turnover as the main factor for isotopic variability and (ii) feeding, during the growth period, on isotopically depleted food in the case of Daphnia, and on isotopically enriched food in the case of Cyclops.

5. The carbon isotopic variation in Cyclops juveniles could be explained by fitting an isotopic growth model that considered that they fed entirely on Daphnia. However this was not the case for nitrogen isotopic variability. Cyclops nitrogen isotopic composition variation and the Cyclops to Daphnia nitrogen isotopic enrichment were closely correlated to the quantity of Daphnia protein and to the dissimilarity in the essential amino acid composition between the two species, which can be interpreted as an indication of consumer nitrogen limitation.
Expression of TNF‐receptor associated factor 2 correlates with poor progression‐free survival time in ABC‐like primary nodal diffuse large B‐cell lymphomas
Authors: Van Galen J C , Muris J J F , Giroth C P E , Vos W , Ossenkoppele G J , Meijer C J L M , Oudejans J J
Published: February 2008

Aims:  Tumour necrosis factor (TNF)‐receptor associated factor 2 (TRAF2) is an adaptor molecule involved in nuclear factor (NF)‐κB activation, which is characteristic of in vitro activated B‐cell (ABC)‐like diffuse large B‐cell lymphomas (DLBCL) and may result in expression of anti‐apoptotic genes and poor response to chemotherapy. TRAF2 also has direct anti‐apoptotic properties via interference with the apoptosis signalling cascade. The aim was to determine whether TRAF2 is preferentially expressed in ABC‐like DLBCL, and whether expression correlates with clinical outcome.

Methods and results:  TRAF2 was expressed in nine of 20 tested ABC‐like DLBCLs and in only one of 13 tested germinal centre B‐lymphocyte (GCB)‐like DLBCLs. High TRAF2 expression was correlated with high International Prognostic Index at time of presentation, high chance of relapse and short progression‐free survival time in 44 tested DLBCLs. Furthermore, when analysis was restricted to ABC‐like DLBCL only, TRAF2 expression was significantly associated with poor progression‐free survival time.

Conclusions:  TRAF2 might be involved in activation of NF‐κB in a subset of ABC‐like DLBCL, and its expression is associated with a particularly poor outcome in primary nodal DLBCL patients. Because of its possible effect on to chemotherapy resistance, resistance, TRAF2 might be an attractive candidate as a molecular target for TRAF2+ DLBCL.
Near‐field optical images of subwavelength annular aperture arrays exhibiting an extraordinary transmission
Authors: POUJET Y. , SALVI J. , BAIDA F. I. , VAN LABEKE D. , PERENTES A. , SANTSCHI C. , HOFFMANN P.
Published: February 2008

In this paper, we present near‐field optical images of nanostructures exhibiting an extraordinary transmission. These structures consist of annular aperture arrays engraved in a metallic film: they are quite promising structures for nanophotonics because of their high transmission directly linked to a guided mode mediated by each annular aperture. We first briefly explain our fabrication process (focused ion beam milling), then we expose the experimental setup of the near‐field optical microscope working both in reflection and transmission modes. For the reflection mode, the ‘coffee‐bean’ structure of the electromagnetic field predicted by the theory has been quite well reproduced. For the transmission mode, we present preliminary experimental results concerning the influence of the wavelength and the polarization of the incident beam on the obtained near‐field images.
On the optimum form of an aperture for a confinement of the optically excited electric near field
Authors: BORTCHAGOVSKY E. , COLAS DES FRANCS G. , NABER A. , FISCHER U.C.
Published: February 2008

A triangular nanoaperture in an aluminium film was used previously as a probe in a scanning near‐field optical microscope to image single fluorescent molecules with an optical resolution down to 30 nm. The high‐resolution capability of the triangular aperture probe is because of a highly confined spot of the electric near field which emerges at an edge of the aperture, when the incident light is polarized perpendicular to this edge. Previous numerical calculations of the near‐field distribution of a triangular aperture in a planar metal film using the field susceptibility technique yielded a nearly quantitative agreement with the experimental results. Using the same numerical technique we now explored the possibility for a further confinement of the electric near field and an increase in its intensity by modifications of the form of a triangular aperture. By introducing a kink on an edge pointing into the aperture, an arrow‐shaped aperture is formed with one convex and three concave metal corners. It turns out that this form leads to a substantial further confinement of the near‐field intensity at the convex corner. By extending the wings of this arrow‐shaped aperture a further 5‐fold increase of the intensity can be obtained without a deterioration of the confined spot.
Real‐time monitoring of the surface relief formation on azo‐polymer films upon near‐field excitation
Authors: AMBROSIO A. , CAMPOSEO A. , MADDALENA P. , PATANÈ S. , ALLEGRINI M.
Published: February 2008

We use near‐field optical microscopy to investigate the early state formation of photo‐induced topographical structures on the free surface of azobenzene‐containing polymers. The near‐field technique is employed to monitor in real time the mass migration during the embossing of the surface of 50/50 copolymer films of polymethacrylate and polymethacrylate containing 3‐methyl‐4′‐pentyloxy‐azobenzene units. The dynamic of surface relief formation induced by light have been investigated as a function of the sample temperature. Furthermore, a formula derived from Navier–Stokes equations for classical laminar flow has been used to fit the mass displacement data during the embossing process. Excellent agreements between the experimental data and the fitting formula have been found for all the temperature considered.
Evanescent field enhancement due to plasmonic resonances of a metamaterial slab
Authors: CHIU K. P. , KAO T. S. , TSAI D. P.
Published: February 2008

The characteristics of plasmonic resonance in a dielectric‐sandwiched metamaterial film at visible wavelengths of 650 and 568 nm have been investigated (for both p‐ and s‐polarized light). Our calculated results demonstrate that each mode of plasmonic resonance has maximum resonance strength at a particular film thickness of the metamaterial. We also demonstrated that the effect of evanescent field enhancement is due to plasmonic resonances of the sandwiched metamaterial system. And the stronger the plasmonic resonance strength the larger the evanescent field is enhanced at the interfaces of the metamaterial film. Also we see that the plasmonic resonances in a sandwiched metamaterial are influenced not only by the materials that constitute the interfaces but also by the thickness of surrounding dielectrics or distance between evanescent light source and metamaterial film. Finally, our results show that there might be an effective light propagation length that will let the coupling efficiency between evanescent light source and SPs resonance become a maximum. These properties of plasmonic resonances to structure parameters of metamaterial film and its surrounding dielectrics provide a useful way to control the optical responses of an optoelectronic device when the wavelength of light source is fixed. That is, by suitably choosing light polarizations, thickness of the metamaterial thin film or the surrounding dielectrics and the position of evanescent light source, it is possible to modulate the plasmonic resonance wavenumber or resonance strength of the system. Therefore, the optical responses of the system can be modulated. Our results will be helpful for the structure design to control the behaviours of coupled plasmonic resonances and consequently the optical properties of the dielectric‐sandwiched metamaterial film.
Polarization‐maintaining near‐field optical probes
Authors: PATANÈ S. , CEFALÌ E. , SPADARO S. , GARDELLI R. , ALBANI M. , ALLEGRINI M.
Published: February 2008

We demonstrate that tapered optical fibre probes can be easily modified in the taper cone to realize an electric dipole producing a well‐defined near‐field polarized light. This novel structure is made of a Short‐cut Double C–shaped probe design combined to the usual full metal coating near the tapered end of the fibre. Hence, the cone at the apex of the probe is excited by an equivalent dipole whose spatial orientation is dictated by the probe geometry, regardless the polarization state of the incoming light. Properties and performances of such a configuration are first predicted by a finite‐difference time domain simulation, showing that the near field coming out from the probe is linearly polarized. Following this novel design, a probe prototype is manufactured and tested. Its measured polar diagram confirms the polarization maintenance property in the near field.
Cord serum immunoglobulin E as a risk factor for allergic symptoms and sensitization in children and young adults
Authors: Pesonen Maria , Kallio Markku J. T. , Siimes Martti A. , Elg Peter , Björksten Fred , Ranki Annamari
Published: February 2008

Early markers of atopic predisposition are needed for targeting allergy preventive measures to high‐risk infants. An elevated cord serum immunoglobulin E (CS‐IgE) level is considered a risk factor for subsequent allergy in childhood. However, the previous studies have not assessed the predictive value of CS‐IgE in a follow‐up extended to adulthood. We aimed at clarifying whether CS‐IgE is useful in predicting subsequent atopic manifestations up to age 20 yr. A cohort of 200 unselected, full‐term newborns were prospectively followed up from birth to age 20 yr. The CS‐IgE level was successfully measured in 190 subjects at birth. The subjects were re‐examined at ages of 5, 11 and 20 yr with assessment of the occurrence of allergic symptoms during the preceding year, skin prick testing and measurement of serum total IgE. An elevated CS‐IgE level was associated with allergic symptoms and skin prick test positivity at age 5 yr (p = 0.03 and 0.01), with allergic rhinoconjunctivitis at age 20 yr (p = 0.04) and with an elevated serum total IgE at ages of 11 and 20 yr (p = 0.02 and 0.01). The sensitivity of CS‐IgE, i.e. the probability of an elevated CS‐IgE in an infant who subsequently develops atopy, in predicting skin prick test‐verified atopy at ages of 5 and 20 yr was 50% and 26%, respectively. The combination of elevated CS‐IgE and positive family history of allergy was strongly associated with subsequent atopic manifestations. Nevertheless, it showed a reduced sensitivity as compared to CS‐IgE or family history of allergy. We conclude that an elevated CS‐IgE level predicts subsequent atopy up to age 20 yr.
Ambient UV‐B radiation decreases photosynthesis in high arctic Vaccinium uliginosum
Authors: Albert Kristian R. , Mikkelsen Teis N. , Ro‐Poulsen Helge
Published: February 2008

An UV‐B‐exclusion experiment was established in high arctic Zackenberg, Northeast Greenland, to investigate the possible effects of ambient UV‐B on plant performance. During almost a whole growing season, canopy gas exchange and Chl fluorescence were measured on Vaccinium uliginosum (bog blueberry). Leaf area, biomass, carbon, nitrogen and UV‐B‐absorbing compounds were determined from a late season harvest. Compared with the reduced UV‐B treatment, the plants in ambient UV‐B were found to have a higher content of UV‐B‐absorbing compounds, and canopy net photosynthesis was as an average 23% lower during the season. By means of the JIP‐test, it was found that the potential of processing light energy through the photosynthetic machinery was slightly reduced in ambient UV‐B. This indicates that not only the UV‐B effects on PSII may be responsible for some of the observed reduction of photosynthesis but also the effects on other parts of the photosynthetic machinery, e.g. the Calvin cycle, might be important. The 60% reduction of the UV‐B irradiance used in this study implies a higher relative change in the UV‐B load than many of the supplemental experiments do, but the substantial effect on photosynthesis clearly indicates that V. uliginosum is negatively affected by the current level of UV‐B.
Functional genomics in a non‐model crop: transcriptomics or proteomics?
Authors: Carpentier Sebastien Christian , Coemans Bert , Podevin Nancy , Laukens Kris , Witters Erwin , Matsumura Hideo , Terauchi Ryohei , Swennen Rony , Panis Bart
Published: February 2008

There is no question that protein‐ and RNA‐based measurements are complementary, but which approach has the highest return in the case of a non‐model crop and what is the correlation between mRNA and proteins? We describe and evaluate in detail the advantages and pitfalls of both a proteomics and a transcriptomics approach. The information on the abundance of transcripts was obtained by serial analysis of gene expression (SAGE), while information on the abundance of proteins was obtained via two‐dimensional gel electrophoresis.
Mutualism, market effects and partner control
Authors: JOHNSTONE R. A. , BSHARY R.
Published: February 2008

Intraspecific cooperation and interspecific mutualism often feature a marked asymmetry in the scope for exploitation. Cooperation may nevertheless persist despite one‐sided opportunities for cheating, provided that the partner vulnerable to exploitation has sufficient control over the duration of interaction. The effectiveness of the threat of terminating an encounter, however, depends upon the ease with which both the potential victim and the potential exploiter can find replacement partners. Here, we extend a simple, game‐theoretical model of this form of partner control to incorporate variation in the relative abundance of potential victims and exploiters, which leads to variation in the time required for individuals of each type to find a new partner. We show that such market effects have a dramatic influence on the stable level of exploitation (and consequent duration of interaction). As the relative abundance of victims decreases, they become less tolerant to exploitation, terminating encounters earlier (for a given level of exploitation), whereas exploiters behave in a more cooperative manner. As a result, the stable duration of interaction actually increases, despite the decreasing tolerance of the victims. Below a critical level of relative victim abundance, the model suggests that the cost of finding a replacement partner becomes so great that it does not pay to exploit at all.
Radiation and divergence in the Rhagoletis Pomonella species complex: inferences from DNA sequence data
Authors: XIE X. , MICHEL A. P. , SCHWARZ D. , RULL J. , VELEZ S. , FORBES A. A. , ALUJA M. , FEDER J. L.
Published: February 2008

Here, we investigate the evolutionary history and pattern of genetic divergence in the Rhagoletis pomonella (Diptera: Tephritidae) sibling species complex, a model for sympatric speciation via host plant shifting, using 11 anonymous nuclear genes and mtDNA. We report that DNA sequence results largely coincide with those of previous allozyme studies. Rhagoletis cornivora was basal in the complex, distinguished by fixed substitutions at all loci. Gene trees did not provide reciprocally monophyletic relationships among US populations of R. pomonella, R. mendax, R. zephyria and the undescribed flowering dogwood fly. However, private alleles were found for these taxa for certain loci. We discuss the implications of the results with respect to identifiable genetic signposts (stages) of speciation, the mosaic nature of genomic differentiation distinguishing formative species and a concept of speciation mode plurality involving a biogeographic contribution to sympatric speciation in the R. pomonella complex.
Genetic variation in pathogen‐induced early hatching of toad embryos
Authors: GOMEZ‐MESTRE I. , TOUCHON J. C. , SACCOCCIO V. L. , WARKENTIN K. M.
Published: February 2008

Accelerated hatching is one of few defences available to embryos, and is effective against many egg‐stage risks. We present the first analysis of genetic variation in hatching plasticity, examining premature hatching of American toad embryos in response to pathogenic water moulds. We reared eggs from half‐ and full‐sib families in the presence and absence of water mould. Hatching age and hatchling size showed low cross‐environment genetic correlations, suggesting that early‐induced hatching can evolve largely independently of spontaneous hatching. We found less phenotypic and additive genetic variation for early‐induced hatching than spontaneous hatching, and a stronger correlation between egg and induced hatchling sizes. Directional selection by the pathogen may have eroded variation in early‐induced hatching, pushing it against the constraint of hatching gland development. Later hatching has a second, muscular component. This pattern of variation may characterize defences based on developmental transitions, although other inducible defences show more variation in induced phenotypes.