bluuebunny/crossref_metadata_2025 huggingface dataset:
Propofol and Remifentanil Differentially Modulate Frontal Electroencephalographic Activity
Authors: Liley David T. J. , Sinclair Nicholas C. , Lipping Tarmo , Heyse Bjorn , Vereecke Hugo E. M. , Struys Michel M. R. F.
Published: July 2010

Background

The purpose of this study was to evaluate a new, physiologically inspired method for the analysis of the electroencephalogram during propofol-remifentanil anesthesia. Based on fixed-order autoregressive moving-average modeling, this method was hypothesized to be capable of dissociating the effects that hypnotic and analgesic agents have on brain electrical activity.

Methods

Raw electroencephalographic waves from a previously published study were reanalyzed. In this study, 45 American Society of Anesthesiologists status I patients were randomly allocated to one of three groups according to a specific target effect-site remifentanil concentration (0, 2, and 4 ng/ml). All patients received stepwise-increased targeted effect-site concentrations of propofol (CePROP). At each step change in target CePROP, the Observer's Assessment of Alertness/Sedation score was evaluated. Raw electroencephalograph was continuously acquired from frontal electrodes. Electroencephalography traces were analyzed using a fixed-order autoregressive moving average model to give derived measures of Cortical State and Cortical Input. Response surfaces were visualized and modeled using Hierarchical Linear Modeling.

Results

Cortical State (a measure of cortical responsiveness) and Cortical Input (a measure of the magnitude of cortical input) were shown to respond differently to CePROP and effect-site remifentanil concentration. Cortical Input decreased significantly with increasing effect-site remifentanil concentration, whereas Cortical State remained unchanged with increasing effect-site remifentanil concentration but decreased with increasing CePROP.

Conclusion

Because Cortical State responds principally to variations in CePROP, it is a potential measure of hypnosis, whereas the dependence of Cortical Input on effect-site remifentanil concentration suggests that it may be useful as a measure of analgesic efficacy and the nociceptive-antinociceptive balance.
Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts
Authors: DeMarco Ricardo , Mathieson William , Manuel Sophia J. , Dillon Gary P. , Curwen Rachel S. , Ashton Peter D. , Ivens Alasdair C. , Berriman Matthew , Verjovski-Almeida Sergio , Wilson R. Alan
Published: July 2010

Schistosoma mansoni is a well-adapted blood-dwelling parasitic helminth, persisting for decades in its human host despite being continually exposed to potential immune attack. Here, we describe in detail micro-exon genes (MEG) in S. mansoni, some present in multiple copies, which represent a novel molecular system for creating protein variation through the alternate splicing of short (≤36 bp) symmetric exons organized in tandem. Analysis of three closely related copies of one MEG family allowed us to trace several evolutionary events and propose a mechanism for micro-exon generation and diversification. Microarray experiments show that the majority of MEGs are up-regulated in life cycle stages associated with establishment in the mammalian host after skin penetration. Sequencing of RT-PCR products allowed the description of several alternate splice forms of micro-exon genes, highlighting the potential use of these transcripts to generate a complex pool of protein variants. We obtained direct evidence for the existence of such pools by proteomic analysis of secretions from migrating schistosomula and mature eggs. Whole-mount in situ hybridization and immunolocalization showed that MEG transcripts and proteins were restricted to glands or epithelia exposed to the external environment. The ability of schistosomes to produce a complex pool of variant proteins aligns them with the other major groups of blood parasites, but using a completely different mechanism. We believe that our data open a new chapter in the study of immune evasion by schistosomes, and their ability to generate variant proteins could represent a significant obstacle to vaccine development.
A Genome-Scale Metabolic Model Accurately Predicts Fluxes in Central Carbon Metabolism under Stress Conditions
Authors: Williams Thomas C.R. , Poolman Mark G. , Howden Andrew J.M. , Schwarzlander Markus , Fell David A. , Ratcliffe R. George , Sweetlove Lee J.
Published: July 2010

Flux is a key measure of the metabolic phenotype. Recently, complete (genome-scale) metabolic network models have been established for Arabidopsis (Arabidopsis thaliana), and flux distributions have been predicted using constraints-based modeling and optimization algorithms such as linear programming. While these models are useful for investigating possible flux states under different metabolic scenarios, it is not clear how close the predicted flux distributions are to those occurring in vivo. To address this, fluxes were predicted for heterotrophic Arabidopsis cells and compared with fluxes estimated in parallel by 13C-metabolic flux analysis (MFA). Reactions of the central carbon metabolic network (glycolysis, the oxidative pentose phosphate pathway, and the tricarboxylic acid [TCA] cycle) were independently analyzed by the two approaches. Net fluxes in glycolysis and the TCA cycle were predicted accurately from the genome-scale model, whereas the oxidative pentose phosphate pathway was poorly predicted. MFA showed that increased temperature and hyperosmotic stress, which altered cell growth, also affected the intracellular flux distribution. Under both conditions, the genome-scale model was able to predict both the direction and magnitude of the changes in flux: namely, increased TCA cycle and decreased phosphoenolpyruvate carboxylase flux at high temperature and a general decrease in fluxes under hyperosmotic stress. MFA also revealed a 3-fold reduction in carbon-use efficiency at the higher temperature. It is concluded that constraints-based genome-scale modeling can be used to predict flux changes in central carbon metabolism under stress conditions.
The Levels of Male Gametic Mitochondrial DNA Are Highly Regulated in Angiosperms with Regard to Mitochondrial Inheritance
Authors: Wang Dan-Yang , Zhang Quan , Liu Yang , Lin Zhi-Fu , Zhang Shao-Xiang , Sun Meng-Xiang , Sodmergen
Published: July 2010

The mechanisms that regulate mitochondrial inheritance are not yet clear, even though it is 100 years since the first description of non-Mendelian genetics. Here, we quantified the copy numbers of mitochondrial DNA (mtDNA) in the gametic cells of angiosperm species. We demonstrate that each egg cell from Arabidopsis thaliana, Antirrhinum majus, and Nicotiana tabacum possesses 59.0, 42.7, and 73.0 copies of mtDNA on average, respectively. These values are equivalent to those in Arabidopsis mesophyll cells, at 61.7 copies per cell. On the other hand, sperm or generative cells from Arabidopsis, A. majus, and N. tabacum possess minor amounts of mtDNA, at 0.083, 0.47, and 1 copy on average, respectively. We further reveal a 50-fold degradation of mtDNA during pollen development in A. majus. In contrast, markedly high levels of mtDNA are found in the male gametic cells of Cucumis melo and Pelargonium zonale (1296.3 and 256.7 copies, respectively). Our results provide direct evidence for mitochondrial genomic insufficiency in the eggs and somatic cells and indicate that a male gamete of an angiosperm may possess mtDNA at concentrations as high as 21-fold (C. melo) or as low as 0.1% (Arabidopsis) of the levels in somatic cells. These observations reveal the existence of a strong regulatory system for the male gametic mtDNA levels in angiosperms with regard to mitochondrial inheritance.
ArabidopsisPHYTOCHROME INTERACTING FACTOR Proteins Promote Phytochrome B Polyubiquitination by COP1 E3 Ligase in the Nucleus
Authors: Jang In-Cheol , Henriques Rossana , Seo Hak Soo , Nagatani Akira , Chua Nam-Hai
Published: July 2010

Many plant photoresponses from germination to shade avoidance are mediated by phytochrome B (phyB). In darkness, phyB exists as the inactive Pr in the cytosol but upon red (R) light treatment, the active Pfr translocates into nuclei to initiate signaling. Degradation of phyB Pfr likely regulates signal termination, but the mechanism is not understood. Here, we show that phyB is stable in darkness, but in R, a fraction of phyB translocates into nuclei and becomes degraded by 26S proteasomes. Nuclear phyB degradation is mediated by COP1 E3 ligase, which preferentially interacts with the PhyB N-terminal region (PhyB-N). PhyB-N polyubiquitination by CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) in vitro can be enhanced by different PHYTOCHROME INTERACTING FACTOR (PIF) proteins that promote COP1/PhyB interaction. Consistent with these results, nuclear phyB accumulates to higher levels in pif single and double mutants and in cop1-4. Our results identify COP1 as an E3 ligase for phyB and other stable phytochromes and uncover the mechanism by which PIFs negatively regulate phyB levels.
Effect of salinity on the refractive index of water: considerations for archer fish aerial vision
Authors: Temple S. E.
Published: July 2010

The change in the refractive index between fresh and salt water was shown to cause a small shift in the apparent image location of an aerial object viewed from below the water’s surface. The impact of this shift may be nominal with respect to archer fish Toxotes spp. spitting accuracy as its magnitude in the direction perpendicular to the spit is close to the width of the spit itself.
Changes in RNA, DNA, protein contents and growth of turbot Scophthalmus maximus larvae and juveniles
Authors: Tong X. H. , Liu Q. H. , Xu S. H. , Li J. , Xiao Z. Z. , Ma D. Y.
Published: July 2010

The growth potential of turbot Scophthalmus maximus larvae and juveniles was studied using nucleic acid‐based indices and protein variables. The experiment was carried out from 4 to 60 days post hatching (dph). A significant increase in instantaneous growth rate during metamorphosis and retarded growth rate during post‐metamorphic phase were observed. Ontogenetic patterns of DNA, RNA and protein all showed developmental stage‐specific traits. The RNA:DNA ratio decreased up to 12 dph, then increased rapidly till 19 dph and fluctuated until 35 dph followed by a decline to the end. The RNA:DNA ratio was positively correlated with growth rate of juveniles during the post‐metamorphic phase, whereas this ratio was not a sensitive indicator of growth during the pre‐metamorphic phase and metamorphosis. The protein:DNA ratio showed a similar tendency to the RNA:DNA ratio. Changes of DNA content and protein:DNA ratio revealed that growth of S. maximus performed mainly by hyperplasia from 4 to 12 dph and hypertrophy until 21 dph during the pre‐metamorphic larval phase. Growth was dominantly hypertrophical from the early‐ to mid‐metamorphosing phase and hyperplastic thereafter. The results show that the DNA content and protein:DNA ratio can evaluate growth rates of larval and juvenile S. maximus on a cellular level.
Hsa‐mir‐27a genetic variant contributes to gastric cancer susceptibility through affecting miR‐27a and target gene expression
Authors: Sun Qingmin , Gu Haijuan , Zeng Ying , Xia Yi , Wang You , Jing Yali , Yang Li , Wang Bin
Published: July 2010

Aberrant microRNA (miRNA) expression is presently proposed to correlate with various human cancers and common single‐nucleotide polymorphisms (SNP) at miRNA genes can influence the maturation of miRNAs or miRNA‐mediated transcriptional regulation. However, whether miRNAs SNP alter gastric cancer susceptibility is still unclear. Here we investigated the possible role of a common A/G polymorphism (rs895819) within hsa‐mir‐27a in the development or progression of gastric cancer, and assessed the effect of rs895819 on the expression of miR‐27a and its target gene Zinc finger and BTB domain containing 10 (ZBTB10). In the present case‐control study, we found that subjects with the variant genotypes (AG + GG) showed a significantly increased risk of gastric cancer relative to AA carriers (adjusted odds ratio = 1.48, 95% confidence interval 1.06–2.05; P = 0.019). The elevated risk was especially evident in older subjects (age >58 years), men, nonsmokers and rural subjects. A significant association of hsa‐mir‐27a variant genotypes with lymph node metastasis was also observed. Further functional analyses indicated that variant genotypes might be responsible for elevated miR‐27a levels and reduced ZBTB10 mRNA. Moreover, an inverse correlation was found between ZBTB10 and miR‐27a levels. In conclusion, we were the first to show that a common polymorphism (rs895819) in hsa‐mir‐27a, by modulating miR‐27a and ZBTB10 levels, acted as an important factor of the gastric cancer susceptibility. (Cancer Sci 2010)
In silico analysis reveals multiple putative type VI secretion systems and effector proteins in Pseudomonas syringae pathovars
Authors: SARRIS PANAGIOTIS F. , SKANDALIS NICHOLAS , KOKKINIDIS MICHAEL , PANOPOULOS NICKOLAS J.
Published: July 2010

Type VI secretion systems (T6SS) of Gram‐negative bacteria form injectisomes that have the potential to translocate effector proteins into eukaryotic host cells. In silico analysis of the genomes in six Pseudomonas syringae pathovars revealed that P. syringae pv. tomato DC3000, pv. tabaci ATCC 11528, pv. tomato T1 and pv. oryzae 1‐6 each carry two putative T6SS gene clusters (HSI‐I and HSI‐II; HSI: Hcp secretion island), whereas pv. phaseolicola 1448A and pv. syringae B728 each carry one. The pv. tomato DC3000 HSI‐I and pv. tomato T1 HSI‐II possess a highly similar organization and nucleotide sequence, whereas the pv. tomato DC3000, pv. oryzae 1‐6 and pv. tabaci 11528 HSI‐II are more divergent. Putative effector orthologues vary in number among the strains examined. The Clp‐ATPases and IcmF orthologues form distinct phylogenetic groups: the proteins from pv. tomato DC3000, pv. tomato T1, pv. oryzae and pv. tabaci 11528 from HSI‐II group together with most orthologues from other fluorescent pseudomonads, whereas those from pv. phaseolicola, pv. syringae, pv. tabaci, pv. tomato T1 and pv. oryzae from HSI‐I group closer to the Ralstonia solanacearum and Xanthomonas orthologues. Our analysis suggests multiple independent acquisitions and possible gene attrition/loss of putative T6SS genes by members of P. syringae.
Affinity of Avr2 for tomato cysteine protease Rcr3 correlates with the Avr2‐triggered Cf‐2‐mediated hypersensitive response
Authors: VAN'T KLOOSTER JOHN W. , VAN DER KAMP MARC W. , VERVOORT JACQUES , BEEKWILDER JULES , BOEREN SJEF , JOOSTEN MATTHIEU H. A. J. , THOMMA BART P. H. J. , DE WIT PIERRE J. G. M.
Published: July 2010

The Cladosporium fulvum Avr2 effector is a novel type of cysteine protease inhibitor with eight cysteine residues that are all involved in disulphide bonds. We have produced wild‐type Avr2 protein in Pichia pastoris and determined its disulphide bond pattern. By site‐directed mutagenesis of all eight cysteine residues, we show that three of the four disulphide bonds are required for Avr2 stability. The six C‐terminal amino acid residues of Avr2 contain one disulphide bond that is not embedded in its overall structure. Avr2 is not processed by the tomato cysteine protease Rcr3 and is an uncompetitive inhibitor of Rcr3. We also produced mutant Avr2 proteins in which selected amino acid residues were individually replaced by alanine, and, in one mutant, all six C‐terminal amino acid residues were deleted. We determined the inhibitory constant (Ki) of these mutants for Rcr3 and their ability to trigger a Cf‐2‐mediated hypersensitive response (HR) in tomato. We found that the two C‐terminal cysteine residues and the six amino acid C‐terminal tail of Avr2 are required for both Rcr3 inhibitory activity and the ability to trigger a Cf‐2‐mediated HR. Individual replacement of the lysine‐17, lysine‐20 or tyrosine‐21 residue by alanine did not affect significantly the biological activity of Avr2. Overall, our data suggest that the affinity of the Avr2 mutants for Rcr3 correlates with their ability to trigger a Cf‐2‐mediated HR.
Review article: the optimal medical management of acute severe ulcerative colitis
Authors: Hart A. L. , Ng S. C.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 615–627

Background  Management of acute severe ulcerative colitis (UC) is a clinical challenge, with a mortality rate of approximately 1–2%. The traditional management with intravenous corticosteroids has been modified by introduction of ciclosporin and more recently, infliximab.

Aim  To provide a detailed and comprehensive review of the medical management of acute severe UC.

Methods  PubMed and recent conference abstracts were searched for articles relating to treatment of acute severe UC.

Results  Two‐thirds of patients respond to intravenous steroids in the short term. In those who fail steroids, low‐dose intravenous ciclosporin at 2 mg/kg/day is effective. Approximately 75% and 50% of patients treated with ciclosporin avoid colectomy in the short and long‐terms, respectively. Long‐term outcome of ciclosporin therapy is improved by introduction of azathioprine on discharge from hospital, together with oral ciclosporin as a bridging therapy. Controlled data show that infliximab is effective as rescue therapy for acute severe UC and the effect appears to be durable, although longer‐term follow‐up data are needed.

Conclusions  Both ciclosporin and infliximab have demonstrated efficacy as rescue medical therapies in patients with acute severe UC, but surgery needs to be considered if there is failure to improve or clinical deterioration.
High levels of serum angiogenic growth factors in patients with AL amyloidosis: comparisons with normal individuals and multiple myeloma patients
Authors: Kastritis Efstathios , Roussou Maria , Michael Michalis , Gavriatopoulou Maria , Michalis Evridiki , Migkou Magdalini , Delimpasi Sossana , Kyrtsonis Marie Christine , Gogos Dimitrios , Liapis Konstantinos , Charitaki Evangelia , Repousis Panagiotis , Terpos Evangelos , Dimopoulos Meletios A. ,   On behalf of the Greek Myeloma Study Group
Published: July 2010

Serum levels of five angiogenic cytokines were evaluated in 82 patients with primary systemic amyloidosis (AL). Angiopoietin‐1, vascular endothelial growth factor, basic fibroblast growth factor and angiogenin were higher in AL patients than in controls (n = 35) and newly‐diagnosed, symptomatic, myeloma patients (n = 35). Angiopoetin‐1/Angiopoetin‐2 ratio was lower in AL compared to controls but higher than in myeloma patients. Angiopoetin‐2 correlated with cardiac dysfunction indices; however, none of the angiogenic growth factors was prognostically significant. The increased angiogenic cytokine levels observed in AL seem to represent either a toxic effect of amyloid fibrils or light chains, or a compensatory response to organ dysfunction.
Tamoxifen counteracts the allergic immune response and improves allergen‐induced dermatitis in mice
Authors: Babina M. , Kirn F. , Hoser D. , Ernst D. , Rohde W. , Zuberbier T. , Worm M.
Published: July 2010

Background
Tamoxifen (TX) represents the prototype selective oestrogen receptor modulator. In addition to its use in breast cancer, TX possesses immunomodulatory functions and displays beneficial effects in models of systemic lupus erythematosus. We hypothesized that TX might inhibit type I allergic reactions, which are also characterized by deviations in humoral immunity.

Objective
To evaluate the effects of TX on the allergic immune response in appropriate mouse models.

Methods
Balb/c mice were sensitized with ovalbumin (OVA)‐alum by the intraperitoneal route, and humoral parameters, T cell cytokine patterns and OVA‐induced ear swelling responses were determined in a preventive (start of TX treatment before sensitization) and a therapeutic setting (start after sensitization), respectively. In addition, the impact of TX on clinical signs, epidermal thickness and leucocyte infiltration of the skin was investigated in a model of allergen‐induced dermatitis.

Results
Preventive TX treatment interfered with all aspects of the allergic immune response, leading to a reduction of allergen‐specific Ig levels (IgE, IgG1 and IgG2a), a skewing effect in the T cell compartment with the inhibition of IL‐4 and an abrogation of ear swelling responses. Interestingly, a therapeutic TX administration was also effective in reducing Ig levels and ear swelling responses. The vigorous systemic effects were additionally mirrored by local changes in allergen‐dependent dermatitis with reduced clinical symptoms, diminished epidermal thickness and decreased CD4+ and CD8+ cell infiltrates.

Conclusion
TX inhibits allergic responses when given preventively and also therapeutically, and improves allergen‐induced dermatitis. Because of its effectiveness, TX could bear significant therapeutic potential for the treatment of allergies.

Cite this as: M. Babina, F. Kirn, D. Hoser, D. Ernst, W. Rohde, T. Zuberbier and M. Worm, Clinical & Experimental Allergy, 2010 (40) 1256–1265.
British Society for Allergy and Clinical Immunology guidelines for the management of egg allergy
Authors: Clark A. T. , Skypala I. , Leech S. C. , Ewan P. W. , Dugué P. , Brathwaite N. , Huber P. A. J. , Nasser S. M.
Published: July 2010

This guideline advises on the management of patients with egg allergy. Most commonly, egg allergy presents in infancy, with a prevalence of approximately 2% in children and 0.1% in adults. A clear clinical history and the detection of egg white‐specific IgE (by skin prick test or serum assay) will confirm the diagnosis in most cases. Egg avoidance advice is the cornerstone of management. Egg allergy often resolves and re‐introduction can be achieved at home if reactions have been mild and there is no asthma. Patients with a history of severe reactions or asthma should have reintroduction guided by a specialist. All children with egg allergy should receive measles, mumps and rubella (MMR) vaccination. Influenza and yellow fever vaccines should only be considered in egg‐allergic patients under the guidance of an allergy specialist. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for allergists and others with a special interest in allergy. The recommendations are evidence‐based but where evidence was lacking consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, diagnosis, treatment, prognosis and co‐morbid associations.

Cite this as: A. T. Clark, I. Skypala, S. C. Leech, P. W. Ewan, P. Dugué, N. Brathwaite, P. A. J. Huber and S. M. Nasser, Clinical & Experimental Allergy, 2010 (40) 1116–1129.
Iloprost has potent anti‐inflammatory properties on human monocyte‐derived dendritic cells
Authors: Müller T. , Dürk T. , Blumenthal B. , Herouy Y. , Sorichter S. , Grimm M. , Panther E. , Cicko S. , Norgauer J. , Idzko M.
Published: July 2010

Background
The stable prostaglandin I2 analogue (iloprost) iloprost has been shown to inhibit allergic airway inflammation in mice by modulating the function of myeloid dendritic cells (DCs).

Objective
The aim of the current study was to investigate the biological activity of iloprost on human monocyte‐derived DCs.

Methods
I prostanoid (IP) receptor expression was analysed by RT‐PCR. Cytokine secretion by DCs and CD4+ T cells was measured by ELISA. The expression of the transcription factor FoxP3 after co‐culture of DCs with CD4+ CD45RA+ T cells was analysed by flow cytometry.

Results
Human monocyte‐derived DCs were found to express mRNA specific for the PGI2 receptor IP, and stimulation with iloprost resulted in increased cyclic AMP levels in both immature DCs (iDCs) and mature DCs (mDCs). Moreover, iloprost dose dependently inhibited the secretion of TNF‐α, IL‐6, IL‐8 and IL‐12p70 in mDCs, while it enhanced IL‐10 production. Changes in cytokine secretion were paralleled by an altered T‐cell priming capacity of DCs: in co‐culture experiments of iloprost‐treated mDC and naïve CD45RA+ T cells, an induction of regulatory T cells could be observed, as demonstrated by increased intracellular FoxP3 expression and IL‐10 production. Additionally, iloprost inhibited the MIP‐3β‐induced migration of mDCs.

Conclusion
In summary, our results provide evidence that iloprost profoundly affects the function of human myeloid DCs. Therefore, iloprost might also be a new therapeutical option for the treatment of asthma in humans.

Cite this as: T. Müller, T. Dürk, B. Blumenthal, Y. Herouy, S. Sorichter, M. Grimm, E. Panther, S. Cicko, J. Norgauer and M. Idzko, Clinical & Experimental Allergy, 2010 (40) 1214–1221.
Infections and asthma: new insights into old ideas
Authors: Sevin C. M. , Peebles R. S.
Published: July 2010

Cite this as: C. M. Sevin and R. S. Peebles Jr, Clinical & Experimental Allergy, 2010 (40) 1142–1154.

A relationship between infections and allergic airway disease has long been recognized, and many reviews have been written on this topic. However, both clinical and basic science studies published in the last 3 years provide new insights into the relationship between infection and allergic conditions. In this review, we focus on these very recent studies, which address the role of infection in the development, maintenance, and exacerbation of asthma. Bacterial, viral, fungal, and parasitic infections have each been examined and provide a framework for these novel concepts.
Effect of acute hyperglycaemia on sensory processing in diabetic autonomic neuropathy
Authors: Frøkjær Jens B. , Søfteland Eirik , Graversen Carina , Dimcevski Georg , Drewes Asbjørn M.
Published: July 2010

Eur J Clin Invest 2010; 40 (10): 883–886

Background  Acute hyperglycaemia is known to increase gastrointestinal (GI) sensitivity in healthy subjects and may contribute to the increased prevalence of GI symptoms in diabetes patients. The aim of this study was to evaluate the effect of acute hyperglycaemia on perception and brain responses to painful visceral and somatic stimuli in diabetic patients.

Materials and methods  The sensitivity and evoked brain potentials (EPs) to electrical oesophageal and median nerve stimulations were assessed in 14 type‐1 diabetes patients with autonomic neuropathy and GI symptoms using a hyperinsulinaemic clamp at 6 and 15 mM.

Results  No differences between the normo‐ and hyperglycaemic conditions were found in sensitivity to both oesophageal (P = 0·72) and median nerve (P = 0·66) stimulations. The latencies and amplitudes of EPs did not differ between the normo‐ and hyperglycaemic conditions following oesophageal (P = 0·53 and 0·57) and median nerve (P = 0·78 and 0·52) stimulations.

Conclusions  Acute hyperglycaemia itself does not contribute to the sensations in patients with longstanding diabetes and autonomic neuropathy. Any potential sensory effects of acute hyperglycaemia can likely be blurred by the neuropathic‐like changes in the sensory nervous system.
The recent breakthroughs in the understanding of host genomics in hepatitis C
Authors: Rauch Andri , Rohrbach Janine , Bochud Pierre‐Yves
Published: July 2010

Eur J Clin Invest 2010; 40 (10): 950–959

Background  Hepatitis C Virus (HCV) infection is spontaneously resolved in about 30% of acutely infected individuals. In those who progress to chronic hepatitis C, HCV therapy permanently eradicates infection in about 40% of cases. It has long been suspected that host genetic factors are key determinants for the control of HCV infection.

Design  We will review in this study four genome‐wide association studies (GWAS) and two large candidate gene studies that assessed the role of host genetic variation for the natural and treatment‐induced control of HCV infection.

Results  The studies consistently identified genetic variation in interleukin 28B (IL28B) as the strongest predictor for the control of HCV infection. Importantly, single nucleotide polymorphisms (SNPs) in IL28B strongly predicted both spontaneous and treatment‐induced HCV recovery. IL28B is located on chromosome 19 and encodes interferon‐λ, a type III interferon with antiviral activity, which is mediated through the JAK‐STAT pathway by inducing interferon‐stimulated genes. The SNPs identified in the GWAS are in high linkage disequilibrium with coding or functional non‐coding SNPs that might modulate function and/or expression of IL28B. The role of the different IL28B alleles on gene expression and cytokine function has not yet been established.

Conclusions  These findings provide strong genetic evidence for the influence of interferon‐λ for both the natural and treatment‐induced control of HCV infection, and support the further investigation of interferon‐λ for the treatment of chronic hepatitis C. Furthermore, genetic testing before HCV therapy could provide important information towards an individualized HCV treatment.
Warming increases the proportion of primary production emitted as methane from freshwater mesocosms
Authors: YVON‐DUROCHER GABRIEL , MONTOYA JOSÉ M. , WOODWARD GUY , JONES J. IWAN , TRIMMER MARK
Published: July 2010

Methane (CH4) and carbon dioxide (CO2) are the dominant gaseous end products of the remineralization of organic carbon and also the two largest contributors to the anthropogenic greenhouse effect. We investigated whether warming altered the balance of CH4 efflux relative to gross primary production (GPP) and ecosystem respiration (ER) in a freshwater mesocosm experiment. Whole ecosystem CH4 efflux was strongly related to temperature with an apparent activation energy of 0.85 eV. Furthermore, CH4 efflux increased faster than ER or GPP with temperature, with all three processes having sequentially lower activation energies. Warming of 4 °C increased the fraction of GPP effluxing as CH4 by 20% and the fraction of ER as CH4 by 9%, in line with the offset in their respective activation energies. Because CH4 is 21 times more potent as a greenhouse gas, relative to CO2, these results suggest freshwater ecosystems could drive a previously unknown positive feedback between warming and the carbon cycle.
Forage density effect on sound insulation properties
Authors: Green O. , Gasso‐Tortajada V. , Gislum R. , Jørgensen R. N. , Sørensen C. G.
Published: July 2010

One of the main parameters affecting forage management and quality is density. Existing methods used for measuring physical properties of forage involve costly destructive analysis. A frequent and appropriate control of the forage density is required for optimizing the management of silage, hay and straw production; therefore, there is a need to develop a new measurement method. The sound insulation properties of a material are governed by its physical structure. Based on this, an inexpensive, non‐destructive acoustic measurement method using sound insulation properties was developed to determine forage density. The method has been used to analyse the correlation of the density with the sound insulation spectra produced by small‐scale models of hay, silage and straw. Results show that the sound insulation spectra of forage have a high correlation with the density and a significant congruence with the physical structure of the targeted forage types. The findings are highly relevant for innovative applications in agriculture, animal nutrition and bio‐energy production in terms of material properties monitoring, materials classification and quality determination.
An evaluation of the hygienic quality in single‐species hays and commercial forages used in equine nutrition
Authors: Seguin V. , Lemauviel‐Lavenant S. , Garon D. , Bouchart V. , Gallard Y. , Blanchet B. , Diquelou S. , Personeni E. , Gauduchon P. , Ourry A.
Published: July 2010

Pulmonary diseases such as recurrent airway obstruction have become a major concern in the horse industry. Airborne dust, including aeroallergens from forages, is suspected to be the main factor in its aetiology. Hypothesizing that grassland flora could affect hay hygienic quality, and therefore have implications for the respiratory health of horses, we compared five single‐species hays (Trifolium repens, Lolium perenne, Alopecurus geniculatus, Poa trivialis and Holcus lanatus). Multi‐species hay from Normandy, and different commercial forages (single‐species haylage, multi‐species haylage, Crau hay and hay from Swiss mixing), chosen to represent current horse forages, were also investigated. Dust, moulds, pollens and endotoxins were different among forage types, while mycotoxins were not detected in any of the forage types. Holcus lanatus hay was the dustiest among the single‐species hays but also the least contaminated by moulds. A particular mould profile was associated with each plant species. The four commercial forages appeared to have a better hygienic quality than the multi‐species hay. Among commercial forages, the single‐species haylage was the least dusty but also the most contaminated by moulds. Overall the results suggest that the hygienic quality of equine forages could be improved by an appropriate choice of grassland species.
Current regeneration patterns at the tree line in the Pyrenees indicate similar recruitment processes irrespective of the past disturbance regime
Authors: Batllori Enric , Camarero J. Julio , Gutiérrez Emilia
Published: July 2010

Aim  Impacts of global change, such as land‐use and climate changes, could produce significant alterations in the elevational patterns of alpine tree line ecotones and their adjacent vegetation zones. Because the responses of the tree line to environmental variations are directly related to successful tree regeneration, understanding recruitment dynamics is an indispensable step in tree line research. We aimed to compare potential ecological limitations on recent tree line regeneration in undisturbed and disturbed sites by analysing the demographic structure and spatiotemporal patterns of recruits and large trees.

Location  Alpine tree line ecotones comprising Pinus uncinata in the Catalan Pyrenees (north‐east Spain) and Andorra.

Methods  We assessed the demographic structure and spatial pattern of recent recruitment using techniques of point‐pattern and autocorrelation analyses. A total of 3639 P. uncinata individuals were mapped, measured and aged at 12 sites. To evaluate the effects of past disturbances on recent tree line response we compared tree lines that had either been recently affected by human‐induced disturbances or had remained undisturbed for many years.

Results  The age structure of the tree lines, together with the lack of an age gap between seedlings and saplings, did not indicate recent episodes of high seedling mortality and suggest that recruitment has been frequent under current climate conditions. Seedlings appeared highly aggregated at short distances (up to 3 m), irrespective of disturbance history, and were spatially segregated with respect to large trees. However, we found no evidence of patches of even‐aged seedlings, and our results suggest that dispersal events at intermediate distances (10–17 m) may be frequent. Autocorrelation analyses revealed different patterns of density and age of recruits between disturbed and undisturbed tree lines, but the strength and small‐scale clustering of seedlings and saplings were very similar between sites.

Main conclusions  We found no recruitment limitation on recent tree line dynamics in the Pyrenees. Furthermore, processes affecting tree recruitment seem to be similar among populations regardless of their past disturbance regime. Our results suggest that constraints on tree line dynamics causing differential responses between sites may operate on older life stages and not upon recruits, and that such constraints may be more contingent on local site conditions than on disturbance history.
Fine‐scale heterogeneity in beetle assemblages under co‐occurring Eucalyptus in the same subgenus
Authors: Barton Philip S. , Manning Adrian D. , Gibb Heloise , Lindenmayer David B. , Cunningham Saul A.
Published: July 2010

Aim  Insect biodiversity is often positively associated with habitat heterogeneity. However, this relationship depends on spatial scale, with most studies focused on differences between habitats at large scales with a variety of forest tree species. We examined fine‐scale heterogeneity in ground‐dwelling beetle assemblages under co‐occurring trees in the same subgenus: Eucalyptus melliodora A. Cunn. ex Schauer and E. blakelyi Maiden (Myrtaceae).

Location  Critically endangered grassy woodland near Canberra, south‐eastern Australia.

Methods  We used pitfall traps and Tullgren funnels to sample ground‐dwelling beetles from the litter environment under 47 trees, and examined differences in diversity and composition at spatial scales ranging from 100 to 1000 m.

Results  Beetle assemblages under the two tree species had distinctive differences in diversity and composition. We found that E. melliodora supported a higher richness and abundance of beetles, but had higher compositional similarity among samples. In contrast, E. blakelyi had a lower abundance and species richness of beetles, but more variability in species composition among samples.

Main conclusions  Our study shows that heterogeneity in litter habitat under co‐occurring and closely related eucalypt species can influence beetle assemblages at spatial scales of just hundreds of metres. The differential contribution to fine‐scale alpha and beta diversity by each eucalypt can be exploited for conservation purposes by ensuring an appropriate mix of the two species in the temperate woodlands where they co‐occur. This would help not only to maximize biodiversity at landscape scales, but also to maintain heterogeneity in species richness, trophic function and biomass at fine spatial scales.
Epitheliocystis in Atlantic salmon, Salmo salar L., farmed in fresh water in Ireland is associated with ‘Candidatus Clavochlamydia salmonicola’ infection
Authors: Mitchell S O , Steinum T , Rodger H , Holland C , Falk K , Colquhoun D J
Published: July 2010

Intracellular inclusions containing chlamydia‐like organisms are frequently observed in the gill epithelial cells of Atlantic salmon, Salmo salar L., cultured in fresh water in Ireland. In this study, the causative agent was identified in four separate freshwater sites, using 16s rRNA sequencing, as ‘Candidatus Clavochlamydia salmonicola’. Histopathology and real‐time (RT) PCR were used to further assess infections. The prevalence of infection ranged from 75–100% between sites and infection intensity was highly variable. No significant lesions were associated with these infections. As a diagnostic tool, RT‐PCR proved marginally more sensitive than histopathology. The fate of ‘Candidatus Clavochlamydia salmonicola’ in Atlantic salmon post‐seawater transfer was investigated in a 12‐week marine longitudinal study. Both RT‐PCR and histopathological examination indicate that the organism disappears from the gills 4–6 weeks post‐transfer.
The effects of a fruit and vegetable promotion intervention on unhealthy snacks during mid‐morning school breaks: results of the Dutch Schoolgruiten Project
Authors: Tak N. I. , Te Velde S. J. , Singh A. S. , Brug J.
Published: July 2010

Background:  Ample fruit and vegetable (F&V) intake has been associated with a decreased risk of chronic disease. The health‐enhancing effects of increased F&V consumption, however, would be even more apparent if the increased F&V consumption additionally led to a lower intake of unhealthy, high calorie snacks. Therefore, the present study aimed to investigate whether a primary school‐based intervention (the Dutch Schoolgruiten Project) that promoted F&V intake could additionally reduce the intake of unhealthy, high calorie snacks during school breaks.

Methods:  The study applied a longitudinal design with baseline and two follow‐up measurements. Children were aged 9–10 years old at baseline; 705 children were included. The main strategy was a F&V scheme that improved the availability, accessibility and exposure to F&V at school by providing one serving of fruit or vegetables twice a week at no cost. The amounts of F&V and unhealthy snacks for consumption at school were measured using a single‐item question included in a questionnaire. Multilevel autoregressive logistic regression models with a three‐level structure (school, child and time) were used to assess the effect of the intervention on both F&V and unhealthy snack consumption.

Results:  The children of the intervention group brought F&V from home to school at follow‐up significantly more often than the children of the control schools [odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.04; 1.90] and brought fewer unhealthy snacks (OR = 0.56, 95% CI = 0.34; 0.92).

Conclusion:  The present study provides some evidence that the Schoolgruiten intervention effect on F&V intake also reduced unhealthy snacking during school breaks.
Spurious correlations and inference in landscape genetics
Authors: CUSHMAN SAMUEL A. , LANDGUTH ERIN L.
Published: July 2010

Reliable interpretation of landscape genetic analyses depends on statistical methods that have high power to identify the correct process driving gene flow while rejecting incorrect alternative hypotheses. Little is known about statistical power and inference in individual‐based landscape genetics. Our objective was to evaluate the power of causal‐modelling with partial Mantel tests in individual‐based landscape genetic analysis. We used a spatially explicit simulation model to generate genetic data across a spatially distributed population as functions of several alternative gene flow processes. This allowed us to stipulate the actual process that is in action, enabling formal evaluation of the strength of spurious correlations with incorrect models. We evaluated the degree to which naïve correlational approaches can lead to incorrect attribution of the driver of observed genetic structure. Second, we evaluated the power of causal modelling with partial Mantel tests on resistance gradients to correctly identify the explanatory model and reject incorrect alternative models. Third, we evaluated how rapidly after the landscape genetic process is initiated that we are able to reliably detect the effect of the correct model and reject the incorrect models. Our analyses suggest that simple correlational analyses between genetic data and proposed explanatory models produce strong spurious correlations, which lead to incorrect inferences. We found that causal modelling was extremely effective at rejecting incorrect explanations and correctly identifying the true causal process. We propose a generalized framework for landscape genetics based on analysis of the spatial genetic relationships among individual organisms relative to alternative hypotheses that define functional relationships between landscape features and spatial population processes.
Treatment of gastro‐esophageal reflux disease: the new kids to block
Authors: Blondeau K.
Published: July 2010

Refractory gastro‐esophageal reflux disease (GERD), defined as persistent symptoms despite proton pump inhibitor (PPI) therapy, is an increasingly prevalent condition and is becoming a major challenge for the clinician. Since non‐acidic reflux may be associated with symptoms persisting during PPI treatment, the lower esophageal sphincter (LES), the most important barrier protecting against reflux, has become an important target for the treatment of (refractory) GERD. Preclinical research has identified several receptors that are involved in the control of transient lower esophageal sphincter relaxations (TLESRs), the predominant mechanism of both acid and non‐acidic reflux events, and several drugs have now been tested in humans. The GABAB agonist baclofen has demonstrated to effectively reduce the rate of TLESRs and the amount of reflux in both GERD patients and healthy volunteers. Nevertheless, the occurrence of central side effects limits its clinical use for the treatment of GERD. Several analogues are being developed to overcome this limitation and have shown promising results. Additionally, metabotropic glutamate receptor 5 (mGluR5) receptor antagonists have shown to reduce both acid and non‐acidic reflux in GERD patients and several molecules are currently being evaluated. Although CB1 antagonists have been shown to reduce TLESRs, they are also associated with central side effects, limiting their clinical applicability. Despite the identification of several potentially interesting drugs, the main challenge for the future remains the reduction of central side effects. Moreover, future studies will need to demonstrate the efficacy of these treatments in patients with refractory GERD.
The role of hen’s egg‐specific IgE, IgG and IgG4 in the diagnostic procedure of hen’s egg allergy
Authors: Ahrens B. , Lopes de Oliveira L. C. , Schulz G. , Borres M. P. , Niggemann B. , Wahn U. , Beyer K.
Published: July 2010

To cite this article: Ahrens B, Lopes de Oliveira LC, Schulz G, Borres MP, Niggemann B, Wahn U, Beyer K. The role of hen’s egg‐specific IgE, IgG and IgG4 in the diagnostic procedure of hen’s egg allergy. Allergy 2010; 65: 1554–1557.

Background:  Hen’s egg (HE) allergy is a common disease in childhood. HE‐specific serum IgE has been correlated with the outcome of oral food challenge tests, and diagnostic decision points have been described as helpful but still not sufficient to reduce the requirement for oral food challenges. The aim of the study was to correlate HE‐specific IgE, IgG and IgG4 levels with the outcome of double‐blind, placebo‐controlled food challenges (DBPCFC) in patients with suspected HE allergy to improve diagnostic procedures.

Methods:  HE‐specific IgE, IgG, and IgG4 levels were compared between 150 children with suspected HE allergy based on sensitization and/or patient’s history who underwent DBPCFC. Sixty‐six patients were HE‐allergic (HE‐sensitized with a positive DBPCFC), 48 HE‐sensitized but tolerant (negative DBPCFC), and 36 patients were nonsensitized and tolerant (negative DBPCFC). Prior to food challenge HE‐specific serum IgE, IgG, and IgG4 were measured with the Phadia CAP‐system.

Results:  HE‐specific IgE was significantly higher in HE‐allergic patients than in clinically tolerant ones. However, there was no difference in HE‐specific IgG and IgG4 concentrations between the patient groups.

Conclusion:  A proposed cut‐off level of 12 kU/l IgE would identify children above this level correctly as HE‐allergic. The level of HE‐specific IgG or IgG4 in serum of children with suspected HE allergy does not add any additional information in the diagnostic procedure of HE allergy. For diagnostic purposes, specific IgG or IgG4 should not routinely be tested.
Gastrointestinal tuberculosis in renal transplant recipients: case report and review of the literature
Authors: Jarrett O. , Grim S.A. , Benedetti E. , Clark N.M.
Published: July 2010

O. Jarrett, S.A. Grim, E. Benedetti, N.M. Clark. Gastrointestinal tuberculosis in renal transplant recipients: case report and review of the literature Transpl Infect Dis 2011:13:52–57. All rights reserved

Abstract:Mycobacterium tuberculosisis an important opportunistic pathogen following renal transplantation and is often associated with adverse outcomes. Gastrointestinal tuberculosis (GITB) is an infrequent manifestation of TB but a potentially lethal one. We present a case of a renal allograft recipient with GITB 18 months after transplant and review other published cases to identify the typical presenting symptoms, risk factors, and natural history. Treatment of GITB is also discussed.