bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Effectiveness of Common Hospital Hand Disinfectants Against Methicillin-ResistantStaphylococcus aureus,Glycopeptide-Intermediate S.aureus,and Heterogeneous Glycopeptide-IntermediateS. aureus
Authors: Wootton Mandy , Walsh Timothy R. , Davies Eleri M. , Howe Robin A.
Published: January 2009

Background.

The presence of methicillin-resistantStaphylococcus aureus(MRSA) and glycopeptide-intermediateS. aureus(GISA) in hospitals poses a significant challenge to hospital infection control teams. The use of disinfectants for both surface and hand cleaning is an essential part of the infection control measures.

Objective.

To evaluate the effectiveness of common hospital hand disinfectants against MRSA, GISA, and heterogeneous GISA (hGISA).

Methods.

For methicillin-susceptible S.aureus(MSSA), MRSA, GISA, and hGISA, the levels of susceptibility to hand disinfectants and their active ingredients were determined. Suspension tests were performed on commercial handwashing products.

Results.

Minimum inhibitory concentrations (MICs) of 2-propanol, Chlorhexidine, and hexachlorophene were similar for all phenotypes. The MICs of cetrimide and triclosan were higher for the MRSA, GISA, and hGISA strains than for the MSSA strain. The MICs for the chlorhexidine-containing agents Hibisol and Hibiscrub (AstraZeneca) and for the propanol-containing agent Sterillium (Medline) were 1-2-fold lower for the MSSA strains than for the MRSA, GISA, and hGISA strains. Suspension tests showed that the GISA and hGISA strains were less susceptible to the triclosan-containing agent Aquasept (SSL) than were the MRSA and MSSA strains, with resistance increasing with glycopeptide resistance. Products containing Betadine (Purdue) were more effective against the GISA and hGISA strains than against the MRSA and MSSA strains, especially after the strain was exposed to the product for 30 seconds.

Conclusions.

Using the EN 1040 standard criteria for the performance of disinfectants, we determined that all agents, except 50% Aquasept for hGISA and 0.33% hexachlorophene for GISA, performed effectively. However, the GISA and hGISA strains were less susceptible to triclosan-containing products, compared with the MRSA stains, but were more susceptible to products containing Betadine.
MOTIFATOR: detection and characterization of regulatory motifs using prokaryote transcriptome data
Authors: Blom Evert-Jan , Roerdink Jos B. T. M. , Kuipers Oscar P. , van Hijum Sacha A. F. T.
Published: January 2009

Summary: Unraveling regulatory mechanisms (e.g. identification of motifs in cis-regulatory regions) remains a major challenge in the analysis of transcriptome experiments. Existing applications identify putative motifs from gene lists obtained at rather arbitrary cutoff and require additional manual processing steps. Our standalone application MOTIFATOR identifies the most optimal parameters for motif discovery and creates an interactive visualization of the results. Discovered putative motifs are functionally characterized, thereby providing valuable insight in the biological processes that could be controlled by the motif.

Availability: MOTIFATOR is freely available at http://www.motifator.nl

Contact:  o.p.kuipers@rug.nl; sacha.vanhijum@nizo.nl
AssociationViewer: a scalable and integrated software tool for visualization of large-scale variation data in genomic context
Authors: Martin Olivier , Valsesia Armand , Telenti Amalio , Xenarios Ioannis , Stevenson Brian J.
Published: January 2009

Summary: We present a tool designed for visualization of large-scale genetic and genomic data exemplified by results from genome-wide association studies. This software provides an integrated framework to facilitate the interpretation of SNP association studies in genomic context. Gene annotations can be retrieved from Ensembl, linkage disequilibrium data downloaded from HapMap and custom data imported in BED or WIG format. AssociationViewer integrates functionalities that enable the aggregation or intersection of data tracks. It implements an efficient cache system and allows the display of several, very large-scale genomic datasets.

Availability: The Java code for AssociationViewer is distributed under the GNU General Public Licence and has been tested on Microsoft Windows XP, MacOSX and GNU/Linux operating systems. It is available from the SourceForge repository. This also includes Java webstart, documentation and example datafiles.

Contact:  brian.stevenson@licr.org

Supplementary information:  Supplementary data are available at http://sourceforge.net/projects/associationview/ online.
Variable locus length in the human genome leads to ascertainment bias in functional inference for non-coding elements
Authors: Taher Leila , Ovcharenko Ivan
Published: January 2009

Motivation: Several functional gene annotation databases have been developed in the recent years, and are widely used to infer the biological function of gene sets, by scrutinizing the attributes that appear over- and underrepresented. However, this strategy is not directly applicable to the study of non-coding DNA, as the non-coding sequence span varies greatly among different gene loci in the human genome and longer loci have a higher likelihood of being selected purely by chance. Therefore, conclusions involving the function of non-coding elements that are drawn based on the annotation of neighboring genes are often biased. We assessed the systematic bias in several particular Gene Ontology (GO) categories using the standard hypergeometric test, by randomly sampling non-coding elements from the human genome and inferring their function based on the functional annotation of the closest genes. While no category is expected to occur significantly over- or underrepresented for a random selection of elements, categories such as ‘cell adhesion’, ‘nervous system development’ and ‘transcription factor activities’ appeared to be systematically overrepresented, while others such as ‘olfactory receptor activity’—underrepresented.

Results: Our results suggest that functional inference for non-coding elements using gene annotation databases requires a special correction. We introduce a set of correction coefficients for the probabilities of the GO categories that accounts for the variability in the length of the non-coding DNA across different loci and effectively eliminates the ascertainment bias from the functional characterization of non-coding elements. Our approach can be easily generalized to any other gene annotation database.

Contact:  ovcharei@ncbi.nlm.nih.gov

Supplementary information:  Supplementary data are available at Bioinformatics Online.
Predictors of fatal and non‐fatal outcomes in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): incremental value of apolipoprotein A‐1, high‐sensitivity C‐reactive peptide and N‐terminal pro B‐type natriuretic peptide
Authors: Wedel Hans , McMurray John J.V. , Lindberg Magnus , Wikstrand John , Cleland John G.F. , Cornel Jan H. , Dunselman Peter , Hjalmarson Åke , Kjekshus John , Komajda Michel , Kuusi Timo , Vanhaecke Johan , Waagstein Finn ,   on behalf of the CORONA Study Group
Published: January 2009

Aims

Few prognostic models in heart failure have been developed in typically elderly patients treated with modern pharmacological therapy and even fewer included simple biochemical tests (such as creatinine), new biomarkers (such as natriuretic peptides), or, especially, both. In addition, most models have been developed for the single outcome of all‐cause mortality.

Methods and results

We built a series of models for nine different fatal and non‐fatal outcomes. For each outcome, a model was first built using demographic and clinical variables (Step 1), then with the addition of biochemical measures (serum creatinine, alanine aminotransferase, creatine kinase, thyrotrophin, apolipoproteins A‐1 and B, and triglycerides) (Step 2) and finally with the incorporation of high‐sensitivity C‐reactive protein (hsCRP) and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP). Ranked according to the Wald χ2 value, age (56), ejection fraction (44), and body mass index (42) were most predictive of all‐cause mortality in Step 1 (total model χ2 343). Creatinine was the most powerful predictor at Step 2 (48) and ApoA‐1 ranked fifth (25), with the overall χ2 increasing to 440. Log NT‐proBNP (167) was the most powerful of the 14 independently predictive variables identified at Step 3 and the overall χ2 increased to 600. NT‐proBNP was the most powerful predictor of each other outcome. hsCRP was not a predictor of all‐cause mortality but did predict the composite atherothrombotic outcome.

Conclusion

Of the two new biomarkers studied in prognostic models in heart failure, NT‐proBNP, but not hsCRP, added substantial and independent predictive information, for a range of clinical outcomes, to that provided by simple demographic, clinical, and biochemical measures. ApoA‐1 was more predictive than LDL or HDL.
A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress
Authors: Kang Jinsuk , Gemberling Matthew , Nakamura Mitsuhiro , Whitby Frank G. , Handa Hiroshi , Fairbrother William G. , Tantin Dean
Published: January 2009

Oct1 and Oct4 are homologous transcription factors with similar DNA-binding specificities. Here we show that Oct1 is dynamically phosphorylated in vivo following exposure of cells to oxidative and genotoxic stress. We further show that stress regulates the selectivity of both proteins for specific DNA sequences. Mutation of conserved phosphorylation target DNA-binding domain residues in Oct1, and Oct4 confirms their role in regulating binding selectivity. Using chromatin immunoprecipitation, we show that association of Oct4 and Oct1 with a distinct group of in vivo targets is inducible by stress, and that Oct1 is essential for a normal post-stress transcriptional response. Finally, using an unbiased Oct1 target screen we identify a large number of genes targeted by Oct1 specifically under conditions of stress, and show that several of these inducible Oct1 targets are also inducibly bound by Oct4 in embryonic stem cells following stress exposure.
N-myc alters the fate of preneoplastic cells in a mouse model of medulloblastoma
Authors: Kessler Jessica D. , Hasegawa Hiroshi , Brun Sonja N. , Emmenegger Brian A. , Yang Zeng-Jie , Dutton John W. , Wang Fan , Wechsler-Reya Robert J.
Published: January 2009

Studying the early stages of cancer can provide important insight into the molecular basis of the disease. We identified a preneoplastic stage in the patched (ptc) mutant mouse, a model for the brain tumor medulloblastoma. Preneoplastic cells (PNCs) are found in most ptc mutants during early adulthood, but only 15% of these animals develop tumors. Although PNCs are found in mice that develop tumors, the ability of PNCs to give rise to tumors has never been demonstrated directly, and the fate of cells that do not form tumors remains unknown. Using genetic fate mapping and orthotopic transplantation, we provide definitive evidence that PNCs give rise to tumors, and show that the predominant fate of PNCs that do not form tumors is differentiation. Moreover, we show that N-myc, a gene commonly amplified in medulloblastoma, can dramatically alter the fate of PNCs, preventing differentiation and driving progression to tumors. Importantly, N-myc allows PNCs to grow independently of hedgehog signaling, making the resulting tumors resistant to hedgehog antagonists. These studies provide the first direct evidence that PNCs can give rise to tumors, and demonstrate that identification of genetic changes that promote tumor progression is critical for designing effective therapies for cancer.
Promoter-specific control of E. coli RNA polymerase by ppGpp and a general transcription factor
Authors: Roberts Jeffrey W.
Published: January 2009

The stringent response of Escherichia coli reflects a global influence of the nucleotide ppGpp on gene expression in response to nutrient starvation. For critical elements of the response, the target of ppGpp is RNA polymerase, which can be either repressed or activated in a promoter-dependent way. A small protein, DksA, which binds in the secondary channel of RNA polymerase, possibly along with other general regulatory factors, contributes to ppGpp-dependent transcription regulation. Rutherford and colleagues (pp. 236–248) identify mutations in genes for the core subunits of RNA polymerase that circumvent the need for DksA in the regulation; the sites of these mutations suggest that DksA acts allosterically through the RNA polymerase active site to destabilize transcription initiation complexes.
A phosphorylation-acetylation switch regulates STAT1 signaling
Authors: Krämer Oliver H. , Knauer Shirley K. , Greiner Georg , Jandt Enrico , Reichardt Sigrid , Gührs Karl-Heinz , Stauber Roland H. , Böhmer Frank D. , Heinzel Thorsten
Published: January 2009

Cytokines such as interferons (IFNs) activate signal transducers and activators of transcription (STATs) via phosphorylation. Histone deacetylases (HDACs) and the histone acetyltransferase (HAT) CBP dynamically regulate STAT1 acetylation. Here we show that acetylation of STAT1 counteracts IFN-induced STAT1 phosphorylation, nuclear translocation, DNA binding, and target gene expression. Biochemical and genetic experiments altering the HAT/HDAC activity ratio and STAT1 mutants reveal that a phospho-acetyl switch regulates STAT1 signaling via CBP, HDAC3, and the T-cell protein tyrosine phosphatase (TCP45). Strikingly, inhibition of STAT1 signaling via CBP-mediated acetylation is distinct from the functions of this HAT in transcriptional activation. STAT1 acetylation induces binding of TCP45, which catalyzes dephosphorylation and latency of STAT1. Our results provide a deeper understanding of the modulation of STAT1 activity. These findings reveal a new layer of physiologically relevant STAT1 regulation and suggest that a previously unidentified balance between phosphorylation and acetylation affects cytokine signaling.
Empowered by Wolf
Authors: Rebel Hermann
Published: January 2009

During the AAA annual meeting in Philadelphia, the PhD Program in anthropology of the City U of New Your, together with the U of California Press, hosted a reception to celebrate publication of Eric R Wolf's new book. Hermann Rebel, Professor of History at the U of Arizona, and author of several works at the intersection of anthropology and history, presented his review of the book (Focal Journal for Anthropology, March 1999), excerpts of which are reprinted here.
Inclusion of prey data improves prediction of bluefin tuna (Thunnus thynnus) distribution
Authors: SCHICK R. S. , LUTCAVAGE M. E.
Published: January 2009

We examined the distribution of Atlantic bluefin tuna (Thunnus thynnus) in the Gulf of Maine, Northwest Atlantic Ocean, from 17 to 23 August 1995, in relation to physical and biological parameters. Specifically, we fit a binomial GLM to the bluefin tuna presence–absence data and predictor variables that include: sea surface temperature (SST), ocean depth, distance to an SST front, time‐lagged density of SST fronts, and an interpolated surface of Atlantic herring (Clupea harengus) density. In addition, we use simple and partial Mantel tests to examine whether bluefin tuna presence–absence data are significantly associated with these predictors, once spatial autocorrelation is accounted for. Results suggest that the distribution of bluefin tuna significantly correlated with herring density (z = 3.525, P = 0.000424), and that inclusion of biological variables results in a more parsimonious model. Mantel tests results indicate that bluefin tuna abundance is significantly correlated with herring density after the effect of spatial structure is removed (Mantel r = 0.043, P < 0.019).
Importance of tumour cell invasion in blood and lymphatic vasculature among patients with endometrial carcinoma
Authors: Mannelqvist Monica , Stefansson Ingunn , Salvesen Helga B , Akslen Lars A
Published: January 2009

Aims:  Vascular invasion is a prognostic marker for many cancers, including endometrial carcinoma. Immunohistochemistry using D2‐40 and CD31 antibodies makes it possible to differentiate between lymphatic vascular invasion (LVI) and blood vessel invasion (BVI). The aim was to examine lymphatic and blood vessel invasion separately and their associations with clinicopathological characteristics and prognosis.

Methods and results:  Immunohistochemistry was performed on a retrospective population‐based series of endometrial carcinoma. Altogether, 31% of the 276 tumours showed lymphatic involvement, whereas 18% showed blood vessel invasion. LVI and BVI were associated with histopathological variables such as histological grade and tumour growth pattern. Patients without vascular invasion had the best prognosis and those with BVI (with or without LVI) had the worst outcome, whereas patients with LVI had an intermediate survival on univariate analysis. Multivariate models indicated that both LVI and especially BVI had independent prognostic importance. Among endometrioid carcinomas, BVI was still significant.

Conclusions:  Our findings support the biological importance of vascular spread through the haematogenic and lymphatic routes in endometrial cancer. The significant correlation found with clinical phenotype indicates that these markers may be relevant for patient management.
A genetic network of flowering‐time genes in wheat leaves, in which an APETALA1/FRUITFULL‐like gene, VRN1, is upstream of FLOWERING LOCUS T
Authors: Shimada Sanae , Ogawa Taiichi , Kitagawa Satoshi , Suzuki Takayuki , Ikari Chihiro , Shitsukawa Naoki , Abe Tomoko , Kawahigashi Hiroyuki , Kikuchi Rie , Handa Hirokazu , Murai Koji
Published: January 2009

To elucidate the genetic mechanism of flowering in wheat, we performed expression, mutant and transgenic studies of flowering‐time genes. A diurnal expression analysis revealed that a flowering activator VRN1, an APETALA1/FRUITFULL homolog in wheat, was expressed in a rhythmic manner in leaves under both long‐day (LD) and short‐day (SD) conditions. Under LD conditions, the upregulation of VRN1 during the light period was followed by the accumulation of FLOWERING LOCUS T (FT) transcripts. Furthermore, FT was not expressed in a maintained vegetative phase (mvp) mutant of einkorn wheat (Triticum monococcum), which has null alleles of VRN1, and never transits from the vegetative to the reproductive phase. These results suggest that VRN1 is upstream of FT and upregulates the FT expression under LD conditions. The overexpression of FT in a transgenic bread wheat (Triticum aestivum) caused extremely early heading with the upregulation of VRN1 and the downregulation of VRN2, a putative repressor gene of VRN1. These results suggest that in the transgenic plant, FT suppresses VRN2 expression, leading to an increase in VRN1 expression. Based on these results, we present a model for a genetic network of flowering‐time genes in wheat leaves, in which VRN1 is upstream of FT with a positive feedback loop through VRN2. The mvp mutant has a null allele of VRN2, as well as of VRN1, because it was obtained from a spring einkorn wheat strain lacking VRN2. The fact that FT is not expressed in the mvp mutant supports the present model.
Shoot apical meristem function in Arabidopsis requires the combined activities of three BEL1‐like homeodomain proteins
Authors: Rutjens Bas , Bao Dongping , Van Eck‐Stouten Evelien , Brand Marco , Smeekens Sjef , Proveniers Marcel
Published: January 2009

In plants, most of the above‐ground body is formed post‐embryonically by the continuous organogenic potential of the shoot apical meristem (SAM). Proper function of the SAM requires maintenance of a delicate balance between the depletion of stem cell daughters into developing primordia and proliferation of the central stem cell population. Here we show that initiation and maintenance of the Arabidopsis SAM, including that of floral meristems, requires the combinatorial action of three members of the BELL‐family of TALE homeodomain proteins, ARABIDOPSIS THALIANA HOMEOBOX 1 (ATH1), PENNYWISE (PNY) and POUND‐FOOLISH (PNF). All three proteins interact with the KNOX TALE homeodomain protein STM, and combined lesions in ATH1, PNY and PNF result in a phenocopy of stm mutations. Therefore, we propose that ath1 pny pnf meristem defects result from loss of combinatorial BELL‐STM control. Further, we demonstrate that heterodimerization‐controlled cellular localization of BELL and KNOX proteins involves a CRM1/exportin‐1‐mediated nuclear exclusion mechanism that is probably generic to control the activity of BELL and KNOX combinations. We conclude that in animals and plants corresponding mechanisms regulate the activity of TALE homeodomain proteins through controlled nuclear‐cytosolic distribution of these proteins.
Calcium depletion and calmodulin inhibition affect the import of nuclear‐encoded proteins into plant mitochondria
Authors: Kuhn Sabine , Bussemer Johanna , Chigri Fatima , Vothknecht Ute C.
Published: January 2009

Many metabolic processes essential for plant viability take place in mitochondria. Therefore, mitochondrial function has to be carefully balanced in accordance with the developmental stage and metabolic requirements of the cell. One way to adapt organellar function is the alteration of protein composition. Since most mitochondrial proteins are nuclear encoded, fine‐tuning of mitochondrial protein content could be achieved by the regulation of protein translocation. Here we present evidence that the import of nuclear‐encoded mitochondrial proteins into plant mitochondria is influenced by calcium and calmodulin. In pea mitochondria, the calmodulin inhibitor ophiobolin A as well as the calcium ionophores A23187 and ionomycin inhibit translocation of nuclear‐encoded proteins in a concentration‐dependent manner, an effect that can be countered by the addition of external calmodulin or calcium, respectively. Inhibition was observed exclusively for proteins translocating into or across the inner membrane but not for proteins residing in the outer membrane or the intermembrane space. Ophiobolin A and the calcium ionophores further inhibit translocation into mitochondria with disrupted outer membranes, but their effect is not mediated via a change in the membrane potential across the inner mitochondrial membrane. Together, our results suggest that calcium/calmodulin influences the import of a subset of mitochondrial proteins at the inner membrane. Interestingly, we could not observe any influence of ophiobolin A or the calcium ionophores on protein translocation into mitochondria of yeast, indicating that the effect of calcium/calmodulin on mitochondrial protein import might be a plant‐specific trait.
Impact of allergic rhinitis on asthma: effects on bronchial hyperreactivity
Authors: Cirillo I. , Pistorio A. , Tosca M. , Ciprandi G.
Published: January 2009

Background:  Remarkable relationship exists between upper and lower airways. Bronchial hyperreactivity (BHR) is a paramount feature of asthma and may be considered a strong risk factor for the onset of asthma in patients with allergic rhinitis.

Objective:  This study is aimed at evaluating the presence of BHR in a large group of patients with moderate‐severe persistent allergic rhinitis alone, and at investigating possible risk factors related to severe BHR.

Methods:  Three hundred and forty‐two patients with moderate‐severe persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test, spirometry and bronchial methacholine (MCH) test were performed in all patients.

Results:  Twenty‐two (6.4%) patients had severe BHR, 74 (21.6%) patients had mild BHR and 192 (56.2%) had borderline BHR; 54 (15.8%) patients had a negative MCH test. The logistic regression analysis evidenced that trees and house dust mites sensitization (ORAdj: 8.1), rhinitis duration > 5 years (ORAdj: 5.4) and FEV1 ≤ 86% of predicted (ORAdj: 4.0) were significantly associated with severe BHR. The discriminative ability of this model is appreciably satisfactory, being the AUC = 0.90.

Conclusion:  This study highlights the close link between upper and lower airways and the role of some risk factors, such as tree and mite sensitization, > 5‐year duration, and ≤ 86% FEV1 values, as risk factors for severe BHR in patients with moderate‐severe persistent allergic rhinitis alone. Therefore, BHR is frequently present in patients with chronic rhinitis and should be suspected in the presence of defined risk factors.
Comparative enzymology of native and recombinant house dust mite allergen Der p 1
Authors: Zhang J. , Saint‐Remy J.‐M. , Garrod D. R. , Robinson C.
Published: January 2009

Background:  The cysteine peptidase activity of group 1 house dust mite allergens is important for their allergenicity and may offer new therapeutic targets for allergy treatment. Hitherto, the design of specific inhibitors has been impeded because the availability of pure, fully active allergens has limited the implementation of drug screening campaigns. Similarly, investigation of the mechanisms by which peptidase allergens promote sensitization has also been restricted. Our aim was to compare the enzymology of recombinant and native forms of Der p 1 to establish if an easily expressed recombinant form of Der p 1 could be used as a drug discovery tool.

Methods:  Enzymatic activity of natural and recombinant Der p 1 was compared fluorimetrically using a novel specific substrate (ADZ 50,059) and a novel specific active site titrant (ADZ 50,000). The effect of recombinant Der p 1 prodomain on the catalytic activity of both Der p 1 preparations was also examined.

Results:  Although differing substantially in molecular weight, the enzymological properties of recombinant and native Der p 1 were indistinguishable. Our data show clearly by experiment that, in contrast to some suggestions, Der p 1 is not an enzyme of bifunctional mechanism.

Conclusion:  The catalytic activity of Der p 1 is tolerant of glycosylation differences that occur at N150 when the protein is expressed in Pichia pastoris. This suggests that this recombinant protein may be suitable for drug design studies and in the elucidation of how peptidase activity promotes sensitization to peptidase and nonpeptidase bystander allergens.
Asthma and atopy are associated with chromosome 17q21 markers in Chinese children
Authors: Leung T. F. , Sy H. Y. , Ng M. C. Y. , Chan I. H. S. , Wong G. W. K. , Tang N. L. S. , Waye M. M. Y. , Lam C. W. K.
Published: January 2009

Background:  Single‐nucleotide polymorphism (SNP)‐based genome‐wide association study revealed that markers on chromosome 17q21 were linked to childhood asthma but not atopy in Caucasians, with the strongest signal being detected for the SNP rs7216389 in the ORMDL3 gene. Such association was unknown in Chinese. This study delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21, and investigated the relationship between these SNPs and asthma and plasma IgE in southern Chinese children.

Methods:  Asthmatic children and non‐allergic controls were recruited from pediatric clinics. Their plasma total and aeroallergen‐specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21 region were genotyped by multiplex SNaPshot™, and their genotype associations with asthma traits analyzed using multivariate regression.

Results:  315 patients and 192 controls were enrolled. The allele frequency for C allele of rs7216389 varied significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs including rs7216389 (P = 0.019–0.034), whereas atopy was associated only with rs11650680 (P = 0.0004). Linear regression revealed the covariates for plasma total IgE to be significant for rs11650680 (P = 0.008–0.0002). Haplotypic associations were found with atopy and increased plasma total IgE, with the respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be 0.21 and 0.09–0.52 (P = 0.0002) and 0.41 and 0.18–0.90 (P = 0.025).

Conclusion:  Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but such association may involve genes other than ORMDL3 in this region.
Intracellular localisation of PPI1 (proton pump interactor, isoform 1), a regulatory protein of the plasma membrane H+‐ATPase of Arabidopsis thaliana
Authors: Bonza M. C. , Fusca T. , Homann U. , Thiel G. , De Michelis M. I.
Published: January 2009

PPI1 (proton pump interactor isoform 1) is a novel protein able to interact with the C‐terminal autoinhibitory domain of the Arabidopsis thaliana plasma membrane (PM) H+‐ATPase. In vitro, PPI1 binds the PM H+‐ATPase in a site different from the known 14‐3‐3 binding site and stimulates its activity. In this study, we analysed the intracellular localisation of PPI1. The intracellular distribution was monitored in A. thaliana cultured cells by immunolocalisation using an antiserum against the PPI1 N‐terminus and in Vicia faba guard cells and epidermal cells by transient expression of a GFP::PPI1 fusion. The results indicate that the bulk of PPI1 is localised at the endoplasmic reticulum, from which it might be recruited to the PM for interaction with the H+‐ATPase in response to as yet unidentified signals.
Bathymetric patterns of deep‐sea gastropod species diversity in 10 basins of the Atlantic Ocean and Norwegian Sea
Authors: Stuart Carol T. , Rex Michael A.
Published: January 2009

Bathymetric patterns of macrofaunal species diversity are best documented in the western North Atlantic where diversity is a unimodal function of depth, peaking in the mid‐bathyal zone and being depressed in the upper slope and abyss. There are few inter‐basin studies of diversity‐depth trends that are controlled for taxonomy, sampling gear, and diversity measures. In this paper, we compare gastropod diversity gradients in the North American Basin of the Atlantic to estimates of diversity in 9 other regions: the Norwegian Sea, West European Basin, Guiana Basin, Gambia Basin, Equatorial Mid‐Atlantic, Brazil Basin, Angola Basin, Cape Basin and Argentine Basin. All samples were collected with epibenthic sleds, and diversity calculated by the Sanders‐Hurlbert normalized expected number of species. While sampling in other regions is generally less complete than in the western North Atlantic, results indicate that a unimodal pattern is not universal. Diversity can increase, decrease or show no relationship with depth. The level of diversity also varies among basins relative to the western North Atlantic, being depressed in the Norwegian Sea, at bathyal depths in the eastern North Atlantic, and below an oxygen minimum zone in the Cape Basin, and generally elevated at tropical latitudes and in abyssal regions where food supply is high. Associations between gastropod diversity and the ecology and geology of basins suggest that productivity, oxygen concentration, hydrographic disturbance and evolutionary‐historical processes may be implicated in shaping bathymetric diversity gradients, but specific causes are difficult to discern. Much more intensive sampling, analyses of other major taxa, and more detailed ecological data are necessary to understand deep‐sea biogeography at within‐ and between‐basin spatial scales.
Comparison of vasa vasorum after intravascular stent placement with sirolimis drug‐eluting and bare metal stents
Authors: Sahler LG , Davis D , Saad WEA , Patel NC , Lee DE , Waldman DL
Published: January 2009

The cytostatic drug, sirolimis has shown prevention in neointimal hyperplasia after stent placement. Recent studies have shown persistent inflammation seen with drug‐eluting stents (DES) may result in late stent thrombosis. The aim of this study is to compare effects of bare metal stents (BMS) and sirolimis DES on the neointima and vasa vasorum in stented rabbit aortas. Stents were implanted in eight New Zealand rabbits for 9 weeks. Group I rabbits received BMS. Group II rabbits received sirolimis DES. A balloon‐mounted BMS or DES was placed in the infrarenal aorta. Following euthanasia, aortas were perfused with barium sulfate and sectioned for histology. After 9 weeks the qualitative intrastent luminal diameter was fairly uniform in both the DES and the BMS. The thickness of neointima was similar in both groups. The number of vasa vasorum in the sirolimis DES increased compared with the BMS (P < 0.05). An increased number of vasa vasorum produced by the DES when compared with the BMS shows a difference in response to local vessel injury in rabbits. This result suggests that vasa vasorum may play a role in the persistent inflammation generated by sirolimis‐coated stents.
Stereotactic radiotherapy for the treatment of neurosarcoidosis involving the pituitary gland and hypothalamus
Authors: Sundaresan P , Jayamohan J
Published: January 2009

We report the case of a 38‐year‐old, female patient with neurosarcoidosis involving the pituitary gland and hypothalamus, who was treated with stereotactic radiotherapy (24 Gy in 12 fractions) with an excellent result. The purpose of this case report was to illustrate and discuss the diagnostic and therapeutic challenges faced in the management of neurosarcoidosis, as well as document our experience with the use of stereotactic radiotherapy in the treatment of neurosarcoidosis.
Salvage definitive chemo‐radiotherapy for locally recurrent oesophageal carcinoma after primary surgery: Retrospective review
Authors: Baxi SH , Burmeister B , Harvey JA , Smithers M , Thomas J
Published: January 2009

To determine the overall survival and gastrointestinal toxicity for patients treated with salvage definitive chemo‐radiotherapy after primary surgery for locoregional relapse of oesophageal carcinoma. A retrospective review of 525 patients who had a resection for oesophageal or oesophagogastric carcinoma at Princess Alexandra Hospital identified 14 patients treated with salvage definitive radiotherapy or chemo‐radiotherapy, following localized recurrence of their disease. We analysed the patient and treatment characteristics to determine the median overall survival as the primary end point. Gastrointestinal toxicity was examined to determine if increased toxicity occurred when the stomach was irradiated within the intrathoracic radiotherapy field. The median overall survival for patients treated with curative intent using salvage definitive chemo‐radiotherapy was 16 months and the 2‐year overall survival is 21%. One patient is in clinical remission more than 5 years after therapy. Age <60 years old and nodal recurrence were favourable prognostic factors. Treatment compliance was 93% with only one patient unable to complete the intended schedule. Fourteen per cent of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage definitive chemo‐radiotherapy should be considered for good performance status patients with oesophageal carcinoma who have a locoregional relapse after primary surgery. The schedule is tolerable with low toxicity and an acceptable median survival.
A simple and inexpensive method to routinely produce customized neck supports for patient immobilization during radiotherapy
Authors: McKernan B , Bydder S , Ebert M , Waterhouse D , Joseph D
Published: January 2009

Accurate and reproducible patient positioning is fundamental to the success of fractionated radiotherapy. Poor patient positioning could result in geographic misses. We have recently reported on an improved method of customized face mask production using laser surface scanning. In this report, we sought to identify and develop a method to routinely make customized neck supports for patients prescribed radiotherapy to the brain or head and neck regions. We identified a potentially suitable product—sealed packs containing two liquids that produce expanding polyurethane foam when mixed—and developed a method for their use. The neck supports are inexpensive and simple to produce (taking less than 5 min of radiation therapist labour). We assessed the customized neck supports in several ways. The effect on setup accuracy was assessed by comparing two consecutive cohorts of patients. Statistically significant differences favouring the customized neck supports included a reduced total displacement error (mean 3.4 vs. 2.1 mm) and a reduced left–right setup error (mean 1.8 vs. 1.1 mm). This is consistent with the greater support provided by the customized neck supports. This method could easily be undertaken by other departments.
Tissue inhibitor of metalloproteinases‐1 (TIMP‐1) modulates neuronal death, axonal plasticity, and learning and memory
Authors: Jourquin Jérôme , Tremblay Evelyne , Bernard Anne , Charton Gérard , Chaillan Franck A. , Marchetti Evelyne , Roman François S. , Soloway Paul D. , Dive Vincent , Yiotakis Athanasios , Khrestchatisky Michel , Rivera Santiago
Published: January 2009

The tissue inhibitor of metalloproteinases‐1 (TIMP‐1) belongs to a family of multifunctional proteins that inhibit matrix metalloproteinases (MMPs), but also regulate cell growth, proliferation, migration and apoptosis in non‐nervous tissues. We had previously reported that kainate (KA)‐mediated excitotoxic seizures induce the expression of TIMP‐1 in resistant neurons and reactive astrocytes of the rat CNS, but the functional implications of these changes had not been elucidated. In the present work we used a targeted gene null mutation in mice to investigatein vivothe involvement of TIMP‐1 in neuronal death and axonal sprouting following KA. We found no differences in seizure behaviour between the wild‐type (WT) and the TIMP‐1 knock‐out (KO) mice, without any compensation by other TIMPs, at least at the mRNA level. However, the TIMP‐1 KO mice were resistant to excitotoxicity and did not undergo the typical mossy fibre sprouting observed in WT mice. The lack of TIMP‐1 paradoxically hampered the increase in the activity of MMPs observed in the seizing WT mice. In addition, we demonstrate that learning and memory are impaired in untreated KO mice. In conclusion, this study provides the firstin vivoevidence for the implication of TIMP‐1 in neuronal death and axonal sprouting in a pathological situation, but also suggests the involvement of TIMP‐1 in the synaptic mechanisms underlying learning and memory in physiological conditions. More generally, these data support the idea that the control of proteolysis is instrumental for pathological and physiological processes in the brain.
Dopamine D3 receptor‐preferring agonists induce neurotrophic effects on mesencephalic dopamine neurons
Authors: Du Fang , Li Rui , Huang Yuangui , Li Xuping , Le Weidong
Published: January 2009

Anti‐parkinsonian agents, pramipexole (PPX) and ropinirole (ROP), have been reported to possess neuroprotective properties, bothin vitroandin vivo. The mechanisms underlying neuroprotection afforded by the D3‐preferring receptor agonists remain poorly understood. The present study demonstrates that incubation of primary mesencephalic cultures with PPX and ROP or the conditioned medium from PPX‐ or ROP‐treated primary cultures induced a marked increase in the number of dopamine (DA) neurons in the cultures. Similar effects can be observed after incubating with the conditioned medium derived from PPX‐ and ROP‐treated substantia nigra astroglia. Meanwhile, PPX and ROP can protect the primary cells from insult of 1‐methyl‐4‐phenylpyridinium (MPP+), the active metabolite of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,5,6‐tetrahydropyridine (MPTP). Furthermore, the neurotrophic effects of PPX and ROP on mesencephalic dopamine neurons could be significantly blocked by D3 receptor antagonist, but not by D2 receptor antagonist. Moreover, we found that the levels of glial cell line‐derived neurotrophic factor (GDNF) and brain‐derived neurotrophic factor (BDNF) in the conditioned medium of mesencephalic cultures treated with PPX and ROP were significantly increased. Blocking GDNF and BDNF with the neutralizing antibodies, the neurotrophic effects of PPX and ROP were greatly diminished. These results suggest that D3 dopamine receptor‐preferring agonists, PPX and ROP, exert neurotrophic effects on cultured DA neurons by modulating the production of endogenous GDNF and BDNF, which may participate in their neuroprotection.
Ret deficiency in mice impairs the development of A5 and A6 neurons and the functional maturation of the respiratory rhythm
Authors: Viemari J. C. , Maussion G. , Bévengut M. , Burnet H. , Pequignot J. M. , Népote V. , Pachnis V. , Simonneau M. , Hilaire G.
Published: January 2009

Although a normal respiratory rhythm is vital at birth, little is known about the genetic factors controlling the prenatal maturation of the respiratory network in mammals. In Phox2a mutant mice, which do not express A6 neurons, we previously hypothesized that the release of endogenous norepinephrine by A6 neurons is required for a normal respiratory rhythm to occur at birth. Here we investigated the role of the Ret gene, which encodes a transmembrane tyrosine kinase receptor, in the maturation of norepinephrine and respiratory systems. As Ret‐null mutants (Ret–/–) did not survive after birth, our experiments were performed in wild‐type (wt) and Ret–/– fetuses exteriorized from pregnant heterozygous mice at gestational day 18. First, in wt fetuses, quantitative in situ hybridization revealed high levels of Ret transcripts in the pontine A5 and A6 areas. Second, in Ret–/– fetuses, high‐pressure liquid chromatography showed significantly reduced norepinephrine contents in the pons but not the medulla. Third, tyrosine hydroxylase immunocytochemistry revealed a significantly reduced number of pontine A5 and A6 neurons but not medullary norepinephrine neurons in Ret–/– fetuses. Finally, electrophysiological and pharmacological experiments performed on brainstem ‘en bloc’ preparations demonstrated impaired resting respiratory activity and abnormal responses to central hypoxia and norepinephrine application in Ret–/– fetuses. To conclude, our results show that Ret gene contributes to the prenatal maturation of A6 and A5 neurons and respiratory system. They support the hypothesis that the normal maturation of the respiratory network requires afferent activity corresponding to the A6 excitatory and A5 inhibitory input balance.
Ephrin‐A4 inhibits sensory neurite outgrowth and is regulated by neonatal skin wounding
Authors: Moss Andrew , Alvares Debie , Meredith‐Middleton Jacqueta , Robinson Michelle , Slater Rebeccah , Hunt Stephen P. , Fitzgerald Maria
Published: January 2009

The mechanisms for directing and organising sensory axons within developing skin remain largely unknown. The present study provides the first evidence that signalling occurs between A‐ephrins and Eph‐A receptors during the development of rat cutaneous sensory innervation both during normal development and following skin injury. Specifically, our data indicate that ephrin‐A4 mRNA and protein are expressed in the epidermis during late embryogenesis and the early postnatal period (E16–P3), and expression is significantly down‐regulated postnatally. In addition, Eph‐A receptors are expressed on dorsal root ganglia (DRG) cells at birth. The pattern of ephrin‐A4 expression is mirrored by epidermal innervation, so that sensory terminals are restricted to epidermal regions devoid of ephrin‐A4 but increase as ephrin‐A4 expression subsides postnatally. Neonatal skin wounding causes sensory hyperinnervation and a differential screen of wounded vs. nonwounded skin revealed down‐regulation of epidermal ephrin‐A4 following neonatal skin wounding. Expression studies showed that this down‐regulation is below the wound and coincides exactly with the onset of hyperinnervation. In vitro experiments show a function for ephrin‐A4‐Fc in inhibiting rat DRG neuronal growth and guidance when presented as either substratum‐bound stripes of ephrin‐A4‐Fc or as soluble clustered proteins. In conclusion, these observations suggest that the Eph family ligand ephrin‐A4 has an inhibitory influence on neonatal cutaneous nerve terminals from DRG sensory neurons in the hindlimb, and may serve to prevent inappropriate innervation of cutaneous regions. In addition, the absence of ephrin‐A4 following neonatal skin wounding may play a critical permissive role in the sprouting response.
The Grueneberg ganglion of the mouse projects axons to glomeruli in the olfactory bulb
Authors: Fuss Stefan H. , Omura Masayo , Mombaerts Peter
Published: January 2009

First described in 1973, the Grueneberg ganglion (GG) is an arrow‐shaped neuronal structure at the anterior end of the nasal cavity. It lines both sides of the nasal septum, within the nasal vestibule, close to the opening of the naris. The functions of the GG and the pattern of projections to the brain are not known. Here, we report that neurons of the mouse GG express olfactory marker protein, which is normally expressed in mature olfactory or vomeronasal sensory neurons. The approx. 500 cells in each GG are arranged in several densely packed cell clusters. Individual cells give rise to single axons, which fasciculate to form a nerve bundle that projects caudally. The axons terminate in glomeruli of the olfactory bulb, one or two large glomeruli associated with a semicircle of up to 10 smaller, somewhat diffusely organized glomeruli that surround the most anterior part of the accessory olfactory bulb. Development of the GG starts around embryonic day 16 and appears to be completed at birth; cell numbers then undergo a minor decrease during postnatal development. The strategic location of the GG, expression of olfactory marker protein, axonal projections to glomeruli at particular locations in the olfactory bulb and early development suggest that this neuronal structure performs specific chemosensory functions at neonatal stages.
The Black diaspora and health inequalities in the US and England: does where you go and how you get there make a difference?
Authors: Nazroo James , Jackson James , Karlsen Saffron , Torres Myriam
Published: January 2009

The relatively poor health of Black American people in the US and Black Caribbean people in England is a consistent finding in the health inequalities literature. Indeed, there are many similarities between the health, social, economic and demographic profiles of these two groups. However, there is evidence that Caribbean people in the US are faring considerably better. This paper explores differences in the social and economic position of Black American, Black Caribbean and white people in the US and Black Caribbean and white people in England, how these relate to ethnic inequalities in health, and may be underpinned by differences in patterns and contexts of migration. We use similar surveys from the US and England to explore these questions. The US data were drawn from the National Survey of American Life and the English data were drawn from the Health Survey for England and a follow up study. Findings show the advantaged health position of Caribbean American people in comparison with both Caribbean people in England and Black American people. Multivariate analyses indicate that these differences, and the differences in health between Black and white people in the two countries, are a consequence of social and economic inequalities.
Circulating beliefs, resilient metaphors and faith in biomedicine: hepatitis C patients and interferon combination therapy
Authors: Jenner Anton , Scott Anne
Published: January 2009

In this paper, we argue that circulating metaphors and beliefs can create an environment in which particular biomedical treatments make cultural sense, even if they seem to be ineffective or are associated with unpleasant side effects. We develop this argument in relation to interferon combined therapy. An innovative methodology combining the collection and deconstructive analysis of visual and narrative texts produced by people with hepatitis C is used to demonstrate links between a predisposition towards Western biomedical practice, discomfort with uncertainty, a desire to reassert control, and adoption of conflict metaphors associated with the tropes of invasion and eradication.