bluuebunny/crossref_metadata_2025 huggingface dataset:
Correction for Volz and Meyers, Susceptible-infected-recovered epidemics in dynamic contact networks
Authors: Volz Erik , Meyers Lauren Ancel
Published: October 2009

Correction for ‘Susceptible-infected-recovered epidemics in dynamic contact networks’ by Erik Volz and Lauren Ancel Meyers (Proc. R. Soc. B
274
, 2925–2933.
(doi:
10.1098/rspb.2007.1159
)).

On p. 2928, equations (2.17), (2.18) and table 4 were presented incorrectly.
Correction for Wilkinson
et al.
, Non-display applications and the next generation of liquid crystal over silicon technology
Authors: Wilkinson T. D. , Henderson C. , Gil Leyva D. , Ghannam R. , Crossland W. A.
Published: October 2009

Correction for ‘Non-display applications and the next generation of liquid crystal over silicon technology’ by T. D. Wilkinson, C. Henderson, D. Gil Leyva, R. Ghannam and W. A. Crossland (Phil. Trans. R. Soc. A
364
, 2721–2731.
(doi:
10.1098/rsta.2006.1849
)).

The author name R. Ghannon has been corrected to R. Ghannam as above.
Correction for Koenig
et al.
, Brain connectivity at different time-scales measured with EEG
Authors: Koenig T. , Studer D. , Hubl D. , Melie L. , Strik W. K.
Published: October 2009

Correction for ‘Brain connectivity at different time-scales measured with EEG’ by T. Koenig, D. Studer, D. Hubl, L. Melie and W. K. Strik (Phil. Trans. R. Soc. B
360
, 1015–1023.
(doi:
10.1098/rstb.2005.1649
)).

On page 1017, the lower EEG topography and time-course were missing. The corrected figure and its caption appear below.
Correction for Armstrong and Ball, DNA barcodes for biosecurity: invasive species identification
Authors: Armstrong K. F. , Ball S. L.
Published: October 2009

Correction for ‘DNA barcodes for biosecurity: invasive species identification’ by K. F. Armstrong and S. L. Ball (Phil. Trans. R. Soc. B
360
, 1813–1823.
(doi:
10.1098/rstb.2005.1713
)).

On page 1819, the final sentence of the paragraph ending four lines from the bottom of the right-hand column was
incorrect, and should read as follows: For example, it was possible to place specimens previously identified as ‘
B. dorsalis
complex’ with reasonable bootstrap support and minimal sequence divergence (see figure 2 in the Electronic Appendix) to a likely species,
B. caryeae
.
Correction for Willis
et al.
, How can a knowledge of the past help to conserve the future? Biodiversity conservation and the relevance of long-term ecological studies
Authors: Willis Katherine J. , Araújo Miguel B. , Bennett Keith D. , Figueroa-Rangel Blanca , Froyd Cynthia A. , Myers Norman
Published: October 2009

Correction for ‘How can a knowledge of the past help to conserve the future? Biodiversity conservation and the relevance of long-term ecological studies’ by Katherine J. Willis, Miguel B. Araújo, Keith D. Bennett, Blanca Figueroa-Rangel, Cynthia A. Froyd and Norman Myers (Phil. Trans. R. Soc. B
362
, 175–186.
(doi:
10.1098/rstb.2006.1977
)).

The dates of the textual citations and the entries in the reference list for the following references should have been 2007 but were incorrectly given as 2006. The correct forms of these references are given below.
Adaptation of Porphyromonas gingivalis to microaerophilic conditions involves increased consumption of formate and reduced utilization of lactate
Authors: Lewis Janina P. , Iyer Divya , Anaya-Bergman Cecilia
Published: October 2009

Porphyromonas gingivalis,previously classified as a strict anaerobe, can grow in the presence of low concentrations of oxygen. Microarray analysis revealed alteration in gene expression in the presence of 6 % oxygen. During the exponential growth phase, 96 genes were upregulated and 79 genes were downregulated 1.4-fold. Genes encoding proteins that play a role in oxidative stress protection were upregulated, including alkyl hydroperoxide reductase (ahpCF), superoxide dismutase (sod) and thiol peroxidase (tpx). Significant changes in gene expression of proteins that mediate oxidative metabolism, such as cytochromedubiquinol oxidase-encoding genes,cydAandcydB, were detected. The expression of genes encoding formate uptake transporter (PG0209) and formate tetrahydrofolate ligase (fhs) was drastically elevated, which indicates that formate metabolism plays a major role under aerobic conditions. The concomitant reduction of expression of a gene encoding the lactate transporter PG1340 suggests decreased utilization of this nutrient. The concentrations of both formate and lactate were assessed in culture supernatants and cells, and they were in agreement with the results obtained at the transcriptional level. Also, genes encoding gingipain protease secretion/maturation regulator (porR) and protease transporter (porT) had reduced expression in the presence of oxygen, which also correlated with reduced protease activities under aerobic conditions. In addition, metal transport was affected, and while iron-uptake genes such as the genes encoding the haemin uptake locus (hmu) were downregulated, expression of manganese transporter genes, such asfeoB2, was elevated in the presence of oxygen. Finally, genes encoding putative regulatory proteins such as extracellular function (ECF) sigma factors as well as small proteins had elevated expression levels in the presence of oxygen. AsP. gingivalisis distantly related to the well-studied model organismEscherichia coli, results from our work may provide further understanding of oxygen metabolism and protection in other related bacteria belonging to the phylumBacteroidetes.
Salmonella enterica serotype Typhimurium DT104 ArtA-dependent modification of pertussis toxin-sensitive G proteins in the presence of [32P]NAD
Authors: Uchida Ikuo , Ishihara Ryoko , Tanaka Kiyoshi , Hata Eiji , Makino Sou-ichi , Kanno Toru , Hatama Shinichi , Kishima Masato , Akiba Masato , Watanabe Atsushi , Kubota Takayuki
Published: October 2009

Salmonella entericaserotype Typhimurium (S.Typhimurium) definitive phage type (DT) 104 has become a widespread cause of human and other animal infections worldwide. The severity of clinical illness inS.Typhimurium DT104 outbreaks suggests that this strain possesses enhanced virulence. ArtA and ArtB – encoded by a prophage inS.Typhimurium DT104 – are homologues of components of pertussis toxin (PTX), including its ADP-ribosyltransferase subunit. Here, we show that exposing DT104 to mitomycin C, a DNA-damaging agent, induced production of prophage-encoded ArtA/ArtB. Pertussis-sensitive G proteins were labelled in the presence of [32P]NAD and ArtA, and the label was released by HgCl2, which is known to cleave cysteine-ADP-ribose bonds. ADP-dependent modification of G proteins was markedly reduced inin vitro-synthesized ArtA6Arg-Alaand ArtA115Glu-Ala, in which alanine was substituted for the conserved arginine at position 6 (necessary for NAD binding) and the predicted catalytic glutamate at position 115, respectively. A cellular ADP-ribosylation assay and two-dimensional electrophoresis showed that ArtA- and PTX-induced ADP-ribosylation in Chinese hamster ovary (CHO) cells occur with the same type of G proteins. Furthermore, exposing CHO cells to the ArtA/ArtB-containing culture supernatant of DT104 resulted in a clustered growth pattern, as is observed in PTX-exposed CHO cells. Hydrogen peroxide, an oxidative stressor, also induced ArtA/ArtB production, suggesting that these agents inducein vivosynthesis of ArtA/ArtB. These results, taken together, suggest that ArtA/ArtB is an active toxin similar to PTX.
Virulence of Enterococcus faecalis dairy strains in an insect model: the role of fsrB and gelE
Authors: Gaspar Frédéric , Teixeira Neuza , Rigottier-Gois Lionel , Marujo Paulo , Nielsen-LeRoux Christina , Crespo Maria Teresa Barreto , Lopes Maria de Fátima Silva , Serror Pascale
Published: October 2009

Despite the existence of various virulence factors in theEnterococcusgenus, enterococcal virulence is still a debated issue. A main consideration is the detection of the same virulence genes in strains isolated from nosocomial or community-acquired infections, and from food products. The goal of this study was to evaluate the roles of two well-characterized enterococcal virulence factors, Fsr and gelatinase, in the potential virulence ofEnterococcus faecalisfood strains. Virulence of unrelatedEnterococcusisolates, including dairy strains carryingfsrandgelEoperons, was compared in theGalleria mellonellainsect model.E. faecalisdairy strains were able to kill larvae and were as virulent as strain OG1RF, one of the most widely used for virulence studies. In contrast,Enterococcus duransandEnterococcus faeciumstrains were avirulent or poorly virulent forG. mellonella. To evaluate the role offsrBandgelEin virulence ofE. faecalisdairy strains, both genes were deleted independently in two strains. The ΔfsrBand ΔgelEdeletion mutants both produced a gelatinase-negative phenotype. Although both mutations significantly attenuated virulence inG. mellonella, the ΔfsrBstrains were more strongly attenuated. These results agree with previous findings suggesting the involvement offsrBin the control of other cell functions relevant to virulence. Our work demonstrates that the presence of functionalfsrB, and to a lesser extentgelE, in dairy enterococci should be considered with caution.
Characterization of a multimeric, eukaryotic prolyl aminopeptidase: an inducible and highly specific intracellular peptidase from the non-pathogenic fungus Talaromyces emersonii
Authors: Mahon Cathal S. , O'Donoghue Anthony J. , Goetz David H. , Murray Patrick G. , Craik Charles S. , Tuohy Maria G.
Published: October 2009

Fungi are capable of degrading proteins in their environment by secreting peptidases. However, the link between extracellular digestion and intracellular proteolysis has scarcely been investigated. Mycelial lysates of the filamentous fungus Talaromyces emersonii were screened for intracellular peptidase production. Five distinct proteolytic activities with specificity for the p-nitroanilide (pNA) peptides Suc-AAPF-pNA, Suc-AAA-pNA, K-pNA, F-pNA and P-pNA were identified. The native enzyme responsible for the removal of N-terminal proline residues was purified to homogeneity by ammonium sulfate fractionation followed by five successive chromatographic steps. The enzyme, termed Talaromyces emersonii prolyl aminopeptidase (TePAP), displayed a 50-fold specificity for cleaving N-terminal Pro–X (k
cat/K
m=2.1×106 M−1 s−1) compared with Ala–X or Val–X bonds. This intracellular aminopeptidase was optimally active at pH 7.4 and 50 °C. Peptide sequencing facilitated the design of degenerate oligonucleotides from homologous sequences encoding putative fungal proline aminopeptidases, enabling subsequent cloning of the gene. TePAP was shown to be relatively uninhibited by classical serine peptidase inhibitors and to be sensitive to selected cysteine- and histidine-modifying reagents, yet gene sequence analysis identified the protein as a serine peptidase with an α/β hydrolase fold. Northern analysis indicated that Tepap mRNA levels were regulated by the composition of the growth medium. Highest Tepap transcript levels were observed when the fungus was grown in medium containing glucose and the protein hydrolysate casitone. Interestingly, both the induction profile and substrate preference of this enzyme suggest potential co-operativity between extracellular and intracellular proteolysis in this organism. Gel filtration chromatography suggested that the enzyme exists as a 270 kDa homo-hexamer, whereas most bacterial prolyl aminopeptidases (PAPs) are monomers. Phylogenetic analysis of known PAPs revealed two diverse subfamilies that are distinguishable on the basis of primary and secondary structure and appear to correlate with the subunit composition of the native enzymes. Sequence comparisons revealed that PAPs with key conserved topological features are widespread in bacterial and fungal kingdoms, and this study identified many putative PAP candidates within sequenced genomes. This work represents, to our knowledge, the first detailed biochemical and molecular analysis of an inducible PAP from a eukaryote and the first intracellular peptidase isolated from the thermophilic fungus T. emersonii.
Isolation and characterization of a suppressor mutation that restores Myxococcus xanthus exopolysaccharide production
Authors: Black Wesley P. , Xu Qian , Cadieux Christena Linn , Suh Sang-Jin , Shi Wenyuan , Yang Zhaomin
Published: October 2009

Myxococcus xanthus, a Gram-negative soil bacterium, undergoes multicellular development when nutrients become limiting. Aggregation, which is part of the developmental process, requires the surface motility of this organism. One component of M. xanthus motility, the social (S) gliding motility, enables the movement of cells in close physical proximity. Previous studies demonstrated that the cell surface-associated exopolysaccharide (EPS) is essential for S motility and that the Dif proteins form a chemotaxis-like pathway that regulates EPS production in M. xanthus. DifA, a homologue of methyl-accepting chemotaxis proteins (MCPs) in the Dif system, is required for EPS production, S motility and development. In this study, a spontaneous extragenic suppressor of a difA deletion was isolated in order to identify additional regulators of EPS production. The suppressor mutation was found to be a single base pair insertion in cheW7 at the che7 chemotaxis gene cluster. Further examination indicated that mutations in cheW7 may lead to the interaction of Mcp7 with DifC (CheW-like) and DifE (CheA-like) to reconstruct a functional pathway to regulate EPS production in the absence of DifA. In addition, the cheW7 mutation was found to partially suppress a pilA mutation in EPS production in a difA+
background. Further deletion of difA from the pilA cheW7 double mutant resulted in a triple mutant that produced wild-type levels of EPS, implying that DifA (MCP-like) and Mcp7 compete for interactions with DifC and DifE in the modulation of EPS production.
Regulation of tartrate metabolism by TtdR and relation to the DcuS–DcuR-regulated C4-dicarboxylate metabolism of Escherichia coli
Authors: Kim Ok Bin , Reimann Julia , Lukas Hanna , Schumacher Uwe , Grimpo Jan , Dünnwald Pia , Unden Gottfried
Published: October 2009

Escherichia coli catabolizes l-tartrate under anaerobic conditions to oxaloacetate by the use of l-tartrate/succinate antiporter TtdT and l-tartrate dehydratase TtdAB. Subsequently, l-malate is channelled into fumarate respiration and degraded to succinate by the use of fumarase FumB and fumarate reductase FrdABCD. The genes encoding the latter pathway (dcuB, fumB and frdABCD) are transcriptionally activated by the DcuS–DcuR two-component system. Expression of the l-tartrate-specific ttdABT operon encoding TtdAB and TtdT was stimulated by the LysR-type gene regulator TtdR in the presence of l- and meso-tartrate, and repressed by O2 and nitrate. Anaerobic expression required a functional fnr gene, and nitrate repression depended on NarL and NarP. Expression of ttdR, encoding TtdR, was repressed by O2, nitrate and glucose, and positively regulated by TtdR and DcuS. Purified TtdR specifically bound to the ttdR–ttdA promoter region. TtdR was also required for full expression of the DcuS–DcuR-dependent dcuB gene in the presence of tartrate. Overall, expression of the ttdABT genes is subject to l-/meso-tartrate-dependent induction, and to aerobic and nitrate repression. The control is exerted directly at ttdA and in addition indirectly by regulating TtdR levels. TtdR recognizes a subgroup (l- and meso-tartrate) of the stimuli perceived by the sensor DcuS, which responds to all C4-dicarboxylates; both systems apparently communicate by mutual regulation of the regulatory genes.
N-Acylhomoserine lactones involved in quorum sensing control the type VI secretion system, biofilm formation, protease production, and in vivo virulence in a clinical isolate of Aeromonas hydrophila
Authors: Khajanchi Bijay K. , Sha Jian , Kozlova Elena V. , Erova Tatiana E. , Suarez Giovanni , Sierra Johanna C. , Popov Vsevolod L. , Horneman Amy J. , Chopra Ashok K.
Published: October 2009

In this study, we delineated the role of N-acylhomoserine lactone(s) (AHLs)-mediated quorum sensing (QS) in the virulence of diarrhoeal isolate SSU of Aeromonas hydrophila by generating a double knockout ΔahyRI mutant. Protease production was substantially reduced in the ΔahyRI mutant when compared with that in the wild-type (WT) strain. Importantly, based on Western blot analysis, the ΔahyRI mutant was unable to secrete type VI secretion system (T6SS)-associated effectors, namely haemolysin coregulated protein and the valine-glycine repeat family of proteins, while significant levels of these effectors were detected in the culture supernatant of the WT A. hydrophila. In contrast, the production and translocation of the type III secretion system (T3SS) effector AexU in human colonic epithelial cells were not affected when the ahyRI genes were deleted. Solid surface-associated biofilm formation was significantly reduced in the ΔahyRI mutant when compared with that in the WT strain, as determined by a crystal violet staining assay. Scanning electron microscopic observations revealed that the ΔahyRI mutant was also defective in the formation of structured biofilm, as it was less filamentous and produced a distinct exopolysaccharide on its surface when compared with the structured biofilm produced by the WT strain. These effects of AhyRI could be complemented either by expressing the ahyRI genes in trans or by the exogeneous addition of AHLs to the ΔahyRI/ahyR+
complemented strain. In a mouse lethality experiment, 50 % attenuation was observed when we deleted the ahyRI genes from the parental strain of A. hydrophila. Together, our data suggest that AHL-mediated QS modulates the virulence of A. hydrophila SSU by regulating the T6SS, metalloprotease production and biofilm formation.
Transcription of the phage-encoded Panton–Valentine leukocidin of Staphylococcus aureus is dependent on the phage life-cycle and on the host background
Authors: Wirtz Christiane , Witte Wolfgang , Wolz Christiane , Goerke Christiane
Published: October 2009

Panton-Valentine leukocidin (PVL) is a pore-forming, bi-component toxin secreted by Staphylococcus aureus strains epidemiologically associated with diseases such as necrotizing pneumonia and skin and soft-tissue infections. Here we demonstrate that transcription of the phage-encoded PVL (encoded in the luk-PV operon) is dependent on two major determinants: the phage life-cycle and the host chromosomal background. Mitomycin C induction of PVL-encoding prophages from different community-acquired MRSA strains led to an increase in the amount of luk-PV mRNA as a result of read-through transcription from latent phage promoters and an increase in phage copy numbers. Failing prophage excision was reflected in a constant expression of luk-PV as in the case of strain USA300, suggesting that φSa2USA300 is a replication-defective prophage. Additionally, we could show that luk-PV transcription is influenced by the S. aureus global virulence regulators agr and sae. We found a strong impact of the host background on prophage induction and replication when analysing PVL phages in different S. aureus strains. For example phage φSa2mw was greatly induced by mitomycin C in its native host MW2 and in strain Newman but to a considerably lesser extent in strains 8325-4, RN6390 and ISP479c. This discrepancy was not linked to the SOS response of the bacteria since recA transcription did not vary between the strains. These results suggest a fine tuning between certain phages and their host, with major impact on the expression of phage-encoded virulence genes.
Biodiversity of cyanobacteria and green algae on monuments in the Mediterranean Basin: an overview
Authors: Macedo Maria Filomena , Miller Ana Zélia , Dionísio Amélia , Saiz-Jimenez Cesareo
Published: October 2009

The presence and deteriorating action of micro-organisms on monuments and stone works of art have received considerable attention in the last few years. Knowledge of the microbial populations living on stone materials is the starting point for successful conservation treatment and control. This paper reviews the literature on cyanobacteria and chlorophyta that cause deterioration of stone cultural heritage (outdoor monuments and stone works of art) in European countries of the Mediterranean Basin. Some 45 case studies from 32 scientific papers published between 1976 and 2009 were analysed. Six lithotypes were considered: marble, limestone, travertine, dolomite, sandstone and granite. A wide range of stone monuments in the Mediterranean Basin support considerable colonization of cyanobacteria and chlorophyta, showing notable biodiversity. About 172 taxa have been described by different authors, including 37 genera of cyanobacteria and 48 genera of chlorophyta. The most widespread and commonly reported taxa on the stone cultural heritage in the Mediterranean Basin are, among cyanobacteria, Gloeocapsa, Phormidium and Chroococcus and, among chlorophyta, Chlorella, Stichococcus and Chlorococcum. The results suggest that cyanobacteria and chlorophyta colonize a wide variety of substrata and that this is related primarily to the physical characteristics of the stone surface, microclimate and environmental conditions and secondarily to the lithotype.
Ensifer, Phyllobacterium and Rhizobium species occupy nodules of Medicago sativa (alfalfa) and Melilotus alba (sweet clover) grown at a Canadian site without a history of cultivation
Authors: Bromfield E. S. P. , Tambong J. T. , Cloutier S. , Prévost D. , Laguerre G. , van Berkum P. , Thi T. V. Tran , Assabgui R. , Barran L. R.
Published: October 2009

Phage-resistant and -susceptible bacteria from nodules of alfalfa and sweet clover, grown at a site without a known history of cultivation, were identified as diverse genotypes ofEnsifer,RhizobiumandPhyllobacteriumspecies based on sequence analysis of ribosomal (16S and 23S rRNA) and protein-encoding (atpDandrecA) genes, Southern hybridization/RFLP and a range of phenotypic characteristics. Among phage-resistant bacteria, one genotype ofRhizobiumsp. predominated on alfalfa (frequency ∼68 %) but was recovered infrequently (∼1 %) from sweet clover. A second genotype was isolated infrequently only from alfalfa. These genotypes fixed nitrogen poorly in association with sweet clover andPhaseolus vulgaris, but were moderately effective with alfalfa. They produced a near-neutral reaction on mineral salts agar containing mannitol, which is atypical of the genusRhizobium. A single isolate ofEnsifersp. and two ofPhyllobacteriumsp. were recovered only from sweet clover. All were highly resistant to multiple antibiotics. Phylogenetic analysis indicated thatEnsifersp. strain T173 is closely related to, but separate from, the non-symbiotic species ‘Sinorhizobium morelense’. Strain T173 is unique in that it possesses a 175 kb symbiotic plasmid and elicits ineffective nodules on alfalfa, sweet clover,Medicago lupulinaandMacroptilium atropurpureum.The twoPhyllobacteriumspp. were non-symbiotic and probably represent bacterial opportunists. Three genotypes ofE. melilotithat were symbiotically effective with alfalfa and sweet clover were encountered infrequently. Among phage-susceptible isolates, two genotypes ofE. medicaewere encountered infrequently and were highly effective with alfalfa, sweet clover andMedicago polymorpha. The ecological and practical implications of the findings are discussed.
Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis
Authors: Valastyan Scott , Benaich Nathan , Chang Amelia , Reinhardt Ferenc , Weinberg Robert A.
Published: October 2009

It remains unclear whether a microRNA (miRNA) affects a given phenotype via concomitant down-regulation of its entire repertoire of targets or instead by suppression of only a modest subset of effectors. We demonstrate that inhibition of breast cancer metastasis by miR-31—a miRNA predicted to modulate >200 mRNAs—can be entirely explained by miR-31's pleiotropic regulation of three targets. Thus, concurrent re-expression of integrin-α5, radixin, and RhoA abrogates miR-31-imposed metastasis suppression. These effectors influence distinct steps of the metastatic process. Our findings have implications concerning the importance of pleiotropy for the biological actions of miRNAs and provide mechanistic insights into metastasis.
Memory reconsolidation and extinction in the crab: Mutual exclusion or coexistence?
Authors: Pérez-Cuesta Luis María , Maldonado Héctor
Published: October 2009

A conditioned stimulus (CS) exposure has the ability to induce two qualitatively different mnesic processes: memory reconsolidation and memory extinction. Previous work from our laboratory has shown that upon a single CS presentation the triggering of one or the other process depends on CS duration (short CS exposure triggers reconsolidation, whereas a long CS exposure triggers extinction), both being mutually exclusive processes. Here we show that either process is triggered only after CS offset, ruling out an interaction as the mechanism of this mutual exclusion. Also, we show here for the first time that reconsolidation and extinction can occur simultaneously without interfering with each other if they are serially triggered by respective short and long CS exposures. Thus, we conclude that (1) one single CS presentation triggers one single process, after CS offset, and (2) whether memory reconsolidation and extinction mutually exclude each other or whether they coexist depends only on whether they are triggered by single or multiple CS presentations.
Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia
Authors: Matsuda Kazuyuki , Sakashita Kazuo , Taira Chiaki , Tanaka‐Yanagisawa Miyuki , Yanagisawa Ryu , Shiohara Masaaki , Kanegane Hirokazu , Hasegawa Daiichiro , Kawasaki Keiichiro , Endo Mikiya , Yajima Shuhei , Sasaki Shinya , Kato Keisuke , Koike Kazutoshi , Kikuchi Akira , Ogawa Atsushi , Watanabe Akihiro , Sotomatsu Manabu , Nonoyama Shigeaki , Koike Kenichi
Published: October 2009

To evaluate minimal residual disease (MRD) after chemotherapy and haematopoietic stem cell transplantation in juvenile myelomonocytic leukaemia (JMML), a locked nucleic acid‐allele specific quantitative polymerase chain reaction (LNA‐AS‐qPCR) was developed for 13 patients (four types of PTPN11 mutation and four types of RAS mutation). The post‐transplant MRD detected by LNA‐AS‐qPCR analysis was well correlated with chimerism assessed by short tandem repeat PCR analysis. Non‐intensive chemotherapy exerted no substantial reduction of the tumour burden in three patients. There was no significant difference in the quantity of RAS mutant DNA after spontaneous haematological improvement in 4 patients with NRAS or KRAS 34G > A during a 2‐ to 5‐year follow‐up. PTPN11, NRAS, or KRAS mutant DNA was detected from Guthrie card dried blood in five of seven patients (who were aged <2 years at diagnosis) at a level of 1·0–6·5 × 10−1 of the values at diagnosis. Accordingly, these five patients might have already reached a subclinical status at birth. Considering the negative correlation between mutant DNA level in neonatal blood spots and age at diagnosis, JMML patients with a larger tumour burden at birth appeared to show earlier onset.
Mannitol challenge for assessment of airway responsiveness, airway inflammation and inflammatory phenotype in asthma
Authors: Wood L. G. , Powell H. , Gibson P. G.
Published: October 2009

Background
Assessment of airway inflammation in asthma is becoming increasingly important, as the inflammatory phenotype underpins the treatment response.

Objective
This study aimed to evaluate mannitol as a tool for assessing airway responsiveness and airway inflammation in asthma, compared with hypertonic saline.

Methods
Fifty‐five subjects with stable asthma completed a hypertonic (4.5%) saline challenge and a mannitol challenge at two separate visits, performed 48–72 h apart, in random order.

Results
Induced sputum was obtained from 49 (89%) subjects during the saline challenge and 42 (76%) subjects during the mannitol challenge (P>0.05). There was a significant correlation between the greatest percentage fall in forced expiratory volume in 1 s (FEV1) (r=0.6, P<0.0001), the dose–response slope (r=0.73), cumulative dose (r=0.55) and PD15 (r=0.46) for mannitol and hypertonic saline. The greatest percentage fall in FEV1 to mannitol was less in non‐eosinophilic asthma. There was a lower total cell count in mannitol vs. hypertonic‐saline‐induced sputum. However, sputum eosinophils and neutrophils were not significantly different. Using mannitol, a higher proportion of subjects were classified as having eosinophilic asthma. There were no differences in IL‐8, neutrophil elastase or matrix‐metalloproteinase 9 concentrations in sputum samples induced with mannitol or hypertonic saline.

Conclusion
We conclude that mannitol can be used to induce good‐quality sputum, useful for analysis of inflammatory mediators and for predicting the inflammatory phenotype in asthma.

Cite this as: L. G. Wood, H. Powell and P. G. Gibson, Clinical & Experimental Allergy, 2010 (40) 232–241.
6th International Immunoglobulin Symposium: Poster presentations
Authors: Fernandez-Cruz E , Kaveri S V , Peter H-H , Durandy A , Cantoni N , Quinti I , Sorensen R , Bussel J B , Danieli M G , Winkelmann A , Bayry J , Käsermann F , Späth P , Helbert M , Salama A , Van Schaik I N , Yuki N
Published: October 2009

The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on immunodeficiencies, autoimmunity and basic research. The immunodeficiency presentations dealt with novel, rare class-switch recombination (CSR) deficiencies, attenuation of adverse events following IVIg treatment, association of immunoglobulin (Ig)G trough levels and protection against acute infection in patients with X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVID), and the reduction of class-switched memory B cells in patients with specific antibody deficiency (SAD). The impact of intravenous immunoglobulin on fetal alloimmune thrombocytopenia, pregnancy and postpartum-related relapses in multiple sclerosis and refractory myositis, as well as experiences with subcutaneous immunoglobulin in patients with multi-focal motor neuropathy, were the topics presented in the autoimmunity session. The interaction of dendritic cell (DC)-SIGN and α2,6-sialylated IgG Fc and its impact on human DCs, the enrichment of sialylated IgG in plasma-derived IgG, as wells as prion surveillance and monitoring of anti-measles titres in immunoglobulin products, were covered in the basic science session. In summary, the presentations illustrated the breadth of immunoglobulin therapy usage and highlighted the progress that is being made in diverse areas of basic and clinical research, extending our understanding of the mechanisms of immunoglobulin action and contributing to improved patient care.
Milder clinical hyperimmunoglobulin E syndrome phenotype is associated with partial interleukin-17 deficiency
Authors: Van De Veerdonk F L , Marijnissen R , Joosten L A B , Kullberg B J , Drenth J P H , Netea M G , van Der Meer J W M
Published: October 2009

Mutations in the signal transducer and activator of transcription 3 (STAT3) were reported to cause hyperimmunoglobulin E syndrome (HIES). The present study investigates T helper type 17 (Th17) responses triggered by the relevant stimuli Staphylococcus aureus and Candidia albicans in five ‘classical’ HIES patients, and a family with three patients who all had a milder HIES phenotype. We demonstrate that patients with various forms of HIES have different defects in their Th17 response to S. aureus and C. albicans, and this is in line with the clinical features of the disease. Interestingly, a partial deficiency of interleukin (IL)-17 production, even when associated with STAT3 mutations, leads to a milder clinical phenotype. We also observed defective Th17 responses in patients with the ‘classical’ presentation of the disease but without STAT3 mutations. These data demonstrate that defective IL-17 production in response to specific pathogens can differ between patients with HIES and that the extent of the defective Th17 response determines their clinical phenotype.
Vibroseis productivity: shake and go
Authors: Krohn Christine , Johnson Marvin , Ho Rachel , Norris Michael
Published: October 2009

We use both model and field data to compare three methods for increasing vibroseis productivity and decreasing acquisition costs. The first method, HFVS (high‐fidelity vibratory seismic), allows us to separate the responses from individual vibrators when multiple vibrators are operating simultaneously. The data quality of the separated records is superior to that of conventional correlated data because they are processed with measured ground‐force signals, but the number of sweeps must be greater than or equal to the number of vibrators. The second method, cascaded sweep, eliminates the listening time between multiple sweeps and partially mitigates harmonic noise observed at later times on near‐offset traces. Finally, a combined method, continuous‐HFVS (C‐HFVS), allows source separation with a single, long, segmented sweep. Separation is as good as with HFVS and interference noise is limited to times near the end of a sweep‐segment length. All three methods produce acceptable seismic images for post‐stack and prestack amplitude interpretation.

The choice of which option to use depends upon the area being investigated. HFVS has numerous benefits, especially when fine sampling is required to mitigate static problems and elevation changes. Due to the ability to separate individual responses, fine sampling can be achieved without sacrificing productivity. For deeper targets, cascaded sweep can be more efficient but data quality suffers from harmonic noise. C‐HFVS, which combines features of HFVS and cascaded sweep, has the potential to result in the highest productivity, without sacrificing either fine sampling or data quality.
How do hydraulic vibrators work? A look inside the black box
Authors: Sallas John J.
Published: October 2009

In order to have realistic expectations of what output is achievable from a seismic vibrator, an understanding of the machine's limitations is essential. This tutorial is intended to provide some basics on how hydraulic vibrators function and the constraints that arise from their design. With these constraints in mind, informed choices can be made to match machine specifications to a particular application or sweeps can be designed to compensate for performance limits.
Nonlinear structure‐enhancing filtering using plane‐wave prediction*
Authors: Liu Yang , Fomel Sergey , Liu Guochang
Published: October 2009

Attenuation of random noise and enhancement of structural continuity can significantly improve the quality of seismic interpretation. We present a new technique, which aims at reducing random noise while protecting structural information. The technique is based on combining structure prediction with either similarity‐mean filtering or lower‐upper‐middle filtering. We use structure prediction to form a structural prediction of seismic traces from neighbouring traces. We apply a non‐linear similarity‐mean filter or an lower‐upper‐middle filter to select best samples from different predictions. In comparison with other common filters, such as mean or median, the additional parameters of the non‐linear filters allow us to better control the balance between eliminating random noise and protecting structural information. Numerical tests using synthetic and field data show the effectiveness of the proposed structure‐enhancing filters.
Physical activity levels and participation in sport in Irish people with haemophilia
Authors: SHERLOCK E. , O’DONNELL J. S. , WHITE B. , BLAKE C.
Published: October 2009

Summary.  Physical activity and sport are associated with a range of health and social benefits. The aim of this study was to assess the level of sports participation and physical activity of Irish people with haemophilia (PWH). A questionnaire was administered to Irish PWH attending the National Centre for Hereditary Coagulation Disorders over a 3‐month period. This included the International Physical Activity Questionnaire (IPAQ) and the Haemophilia Activities List (HAL). Comparisons with EU average data from European Physical Activity Surveillance System for physical activity scores (IPAQ) were made using independent t‐tests and percentage variance. Relationships between age, functional limitation (based on HAL) and IPAQ scores were tested with Pearson’s correlation. Sixty‐one questionnaires were completed, representing 12% of the Irish haemophilia population. Age ranged from 16 to 63; all levels of severity were included. Forty‐six percent of Irish PWH achieved a high level of physical activity, but overall physical activity [total metabolic equivalents of task (MET) min] in the group was only 66% of the EU average. Elderly patients and those with more functional limitations (with lower HAL scores) were significantly less active. Sports participation levels were in line with other PWH at 66%. Although 55% reported bleeds resulting from sport and 31% reported having had a significant injury attributable to sport, overall sport was viewed in a positive light. Irish PWH are physically active and play a wide range of sports. Further efforts are needed to achieve optimal safety and to ensure that maximum benefit is gained.
Comparative proteomic analysis of Orobanche and Phelipanche species inferred from seed proteins
Authors: CASTILLEJO M A , FERNÁNDEZ‐APARICIO M , SATOVIC Z , RUBIALES D
Published: October 2009

Orobanche and Phelipanche species are root parasitic plants some of which infect important crops, causing extensive damage. In an attempt to unravel molecular systematic in these genera using protein markers, we established the protein profile of twelve species by two‐dimensional gel electrophoresis (2‐DE). Proteins were detected by Sypro Ruby staining and the gel images were digitalised and analysed. The 2‐DE maps contained from 30 to 140 protein spots for the analysed species. A virtual master gel was built with spots present in all species and revealing the presence of 260 protein spots. Only one protein was monomorphic, while 143 were unique to a single species. Proteins were scored for the presence or absence of homologous spots to create a binary matrix. Phylogenetic analysis was carried out using maximum parsimony and distance method. The trees obtained were rooted using Cistanche phelypaea as an out‐group. Both analyses showed Orobanche as a monophyletic group. AMOVA analysis revealed phenotypic diversity between species within genera, as well as a considerable level of variation between genera. This is a first step to help in the phylogenetic classification of parasitic plants by means of proteomics.
Examining the social landscapes of alternative reproductive strategies
Authors: FORMICA V. A. , TUTTLE E. M.
Published: October 2009

Social environments are inherently dynamic, often changing depending on the frequency and outcomes of conspecific interactions – they can be simultaneously the targets and agents of selection. Understanding how organisms settle in heterogeneous social environments and the effects this has on reproductive success is vital to our understanding of the selective forces at work in wild populations. From an intensive behavioural and ecological study of territoriality in the polymorphic white‐throated sparrow (Zonotrichia albicollis), we demonstrate that males of the two morphs inhabit social niches that correspond to their respective alternative reproductive strategies. By integrating molecular ecology and Geographic Information Systems, we generated continuous, socio‐spatial models of local conspecific density and cuckoldry risk. Our results suggest that the morphs segregate their territories based on socio‐spatial variables, creating a heterogeneous social landscape that matches each behavioural phenotype with a favourable social environment. Specifically, the monogamous tan males tended to settle in low‐density areas that were also low for cuckoldry risk, while the opposite was true for the promiscuous white males. This pattern of socio‐spatial heterogeneity, combined with the social niche partitioning we observed, might act as asocialniche polymorphism, and play an important role in maintenance of the alternative reproductive strategies of the white‐throated sparrow. Socio‐spatial factors, similar to those observed in the white‐throated sparrow, may play important roles in the evolution of mating systems in other species, even those with more continuous or cryptic variation.
Single and multigenerational responses of body mass to atmospheric oxygen concentrations in Drosophila melanogaster : evidence for roles of plasticity and evolution
Authors: KLOK C. J. , HUBB A. J. , HARRISON J. F.
Published: October 2009

Greater oxygen availability has been hypothesized to be important in allowing the evolution of larger invertebrates during the Earth’s history, and across aquatic environments. We tested for evolutionary and developmental responses of adult body size of Drosophila melanogaster to hypoxia and hyperoxia. Individually reared flies were smaller in hypoxia, but hyperoxia had no effect. In each of three oxygen treatments (hypoxia, normoxia or hyperoxia) we reared three replicate lines of flies for seven generations, followed by four generations in normoxia. In hypoxia, responses were due primarily to developmental plasticity, as average body size fell in one generation and returned to control values after one to two generations of normoxia. In hyperoxia, flies evolved larger body sizes. Maximal fly mass was reached during the first generation of return from hyperoxia to normoxia. Our results suggest that higher oxygen levels could cause invertebrate species to evolve larger average sizes, rather than simply permitting evolution of giant species.
Safety of blood donation from individuals with treated hypertension or non‐insulin dependent type 2 diabetes – a systematic review
Authors: Stainsby D. , Brunskill S. , Chapman C. E. , Dorée C. , Stanworth S.
Published: October 2009

Background and Objectives  This systematic review was aimed at finding evidence for the safety of blood donation by individuals with treated hypertension or type 2 diabetes. It was undertaken as part of a wider project to re‐evaluate exclusion criteria for UK blood donors with a view to increasing eligibility.

Materials and Methods  Searches were undertaken in the Cochrane Library to 2008, MEDLINE (1950 onwards), EMBASE (1974 onwards), CINAHL (1982 onwards), BNID (1994 onwards), the NHSBT SRI Handsearching Database and the Web of Science (all years) to February 2008. Planned analysis was largely descriptive.

Results  We identified only 16 relevant papers. None of the identified studies directly addressed the review questions and methodological appraisal highlighted a number of deficiencies. However all included papers provided contributory data and the findings were consistent. No study found any evidence of increased risk to homologous (allogeneic) or autologous blood donors with treated hypertension or with raised baseline systolic blood pressure up to 200 mmHg. We found very few data relating to blood donation by diabetic subjects.

Conclusions  No identified study indicated that raised baseline blood pressure level, treated hypertension or diabetes was predictive of increased adverse reactions in blood donors but the level of overall evidence was limited. This is the first attempt to systematically review a donor area as part of an approach to change longstanding practice recommendations, and may have implications for other recommendations for changes in donor acceptance criteria.
Impact of preoperative serum sodium concentration in living donor liver transplantation
Authors: Fukuhara Takasuke , Ikegami Toru , Morita Kazutoyo , Umeda Kenji , Ueda Shigeru , Nagata Shigeyuki , Sugimachi Keishi , Gion Tomonobu , Yoshizumi Tomoharu , Soejima Yuji , Taketomi Akinobu , Maehara Yoshihiko
Published: October 2009

Background and Aims:  The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre‐transplant sodium concentration on postoperative clinical outcomes.

Methods:  One hundred and thirty‐four patients who underwent LDLT for end‐stage liver diseases were examined to evaluate the significance of pre‐transplant hyponatremia (Na ≤ 130 mEq/L) on the short‐term clinical outcomes and the efficacy of the Model for End‐Stage Liver Disease and serum sodium (MELD‐Na) score using the sodium concentration and original MELD score.

Results:  The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109–142) and 16.2 (range: 6–38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short‐term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD‐Na score was 19.6 (range: 6–51) and the area under the receiver–operator curve of that (c‐statistics: 0.867) was higher than MELD score and sodium concentration (c‐statistics: 0.820 and 0.842, respectively).

Conclusion:  Preoperative hyponatremia was a significant risk for postoperative complications and short‐term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post‐transplant short‐term mortality in LDLT.
Toward elimination and eradication of hepatitis B
Authors: Chen Ding‐Shinn
Published: October 2009

Hepatitis B virus (HBV) causes important human health problems. It has infected one‐third of the world's population and approximately 360 million people are chronic carriers. Worldwide, 0.5–1.2 million deaths are attributed to HBV infection annually. Therefore, global control of HBV infection is important. HBV infection can be intervened by interrupting routes of transmission, treating the chronically infected, and preventing the susceptibles with immunoprophylaxis. All these measures are effective. Nevertheless, although pegylated interferons or nucleos(t)ide analogs are effective for the treatment of chronic hepatitis B, chronic carriage of HBV is not easy to eliminate, as revealed by the frequent persistence of hepatitis B surface antigen, despite satisfactory responses to these treatments. On the other hand, hepatitis B vaccination has been shown to preclude HBV infection effectively. This is particularly true for pre‐exposure prophylaxis. Worthy of note is the universal vaccination of newborn infants. This is the most effective means of preventing HBV infection, especially for those born to HBV carrier mothers. To eliminate and eradicate hepatitis B, first, HBV in the chronically infected should be eradicated or strongly and efficiently suppressed, so that the infection does not spread rampantly. Second, all the transmission routes should be interrupted. Lastly, but most effectively, is to immunize all susceptibles. The difficulties and possible solutions of each approach are discussed. In conclusion, the existing means to prevent and treat HBV infection render our goal toward eliminating and eradicating hepatitis B possible, although it will take much time and effort to achieve this objective.