bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic and Developmental Effects Resulting from Deletion of thecitAGene Encoding Citrate Synthase in Aspergillus nidulans
Authors: Murray Sandra L. , Hynes Michael J.
Published: February 2010

Citrate synthase is a central activity in carbon metabolism. It is required for the tricarboxylic acid (TCA) cycle, respiration, and the glyoxylate cycle. InSaccharomyces cerevisiaeandArabidopsis thaliana, there are mitochondrial and peroxisomal isoforms encoded by separate genes, while inAspergillus nidulans, a single gene,citA, encodes a protein with predicted mitochondrial and peroxisomal targeting sequences (PTS). Deletion ofcitAresults in poor growth on glucose but not on derepressing carbon sources, including those requiring the glyoxylate cycle. Growth on glucose is restored by a mutation in thecreAcarbon catabolite repressor gene. Methylcitrate synthase, required for propionyl-coenzyme A (CoA) metabolism, has previously been shown to have citrate synthase activity. We have been unable to construct themcsAΔcitAΔ double mutant, and the expression ofmcsAis subject to CreA-mediated carbon repression. Therefore, McsA can substitute for the loss of CitA activity. Deletion ofcitAdoes not affect conidiation or sexual development but results in delayed conidial germination as well as a complete loss of ascospores in fruiting bodies, which can be attributed to loss of meiosis. These defects are suppressed by thecreA204mutation, indicating that McsA activity can substitute for the loss of CitA. A mutation of the putative PTS1-encoding sequence incitAhad no effect on carbon source utilization or development but did result in slower colony extension arising from single conidia or ascospores. CitA-green fluorescent protein (GFP) studies showed mitochondrial localization in conidia, ascospores, and hyphae. Peroxisomal localization was not detected. However, a very low and variable detection of punctate GFP fluorescence was sometimes observed in conidia germinated for 5 h when the mitochondrial targeting sequence was deleted.
Spontaneous Excision of the
Salmonella enterica
Serovar Enteritidis-Specific Defective Prophage-Like Element φSE14
Authors: Santiviago Carlos A. , Blondel Carlos J. , Quezada Carolina P. , Silva Cecilia A. , Tobar Pia M. , Porwollik Steffen , McClelland Michael , Andrews-Polymenis Helene L. , Toro Cecilia S. , Zaldívar Mercedes , Contreras Inés
Published: February 2010

Salmonella enterica
serovar Enteritidis has emerged as a major health problem worldwide in the last few decades. DNA loci unique to
S
. Enteritidis can provide markers for detection of this pathogen and may reveal pathogenic mechanisms restricted to this serovar. An
in silico
comparison of 16
Salmonella
genomic sequences revealed the presence of an ∼12.5-kb genomic island (GEI) specific to the sequenced
S
. Enteritidis strain NCTC13349. The GEI is inserted at the 5′ end of gene
ydaO
(
SEN1377
), is flanked by 308-bp imperfect direct repeats (
attL
and
attR
), and includes 21 open reading frames (
SEN1378
to
SEN1398
), encoding primarily phage-related proteins. Accordingly, this GEI has been annotated as the defective prophage SE14 in the genome of strain NCTC13349. The genetic structure and location of φSE14 are conserved in 99 of 103 wild-type strains of
S
. Enteritidis studied here, including reference strains NCTC13349 and LK5. Notably, an extrachromosomal circular form of φSE14 was detected in every strain carrying this island. The presence of
attP
sites in the circular forms detected in NCTC13349 and LK5 was confirmed. In addition, we observed spontaneous loss of a
tetRA
-tagged version of φSE14, leaving an empty
attB
site in the genome of strain NCTC13349. Collectively, these results demonstrate that φSE14 is an unstable genetic element that undergoes spontaneous excision under standard growth conditions. An internal fragment of φSE14 designated Sdf I has been used as a serovar-specific genetic marker in PCR-based detection systems and as a tool to determine
S
. Enteritidis levels in experimental infections. The instability of this region may require a reassessment of its suitability for such applications.
The Nonmevalonate Pathway of Isoprenoid Biosynthesis in
Mycobacterium tuberculosis
Is Essential and Transcriptionally Regulated by Dxs
Authors: Brown Amanda C. , Eberl Matthias , Crick Dean C. , Jomaa Hassan , Parish Tanya
Published: February 2010

Mycobacterium tuberculosis
synthesizes isoprenoids via the nonmevalonate or DOXP pathway. Previous work demonstrated that three enzymes in the pathway (Dxr, IspD, and IspF) are all required for growth
in vitro
. We demonstrate the essentiality of the key genes
dxs1
and
gcpE
, confirming that the pathway is of central importance and that the second homolog of the synthase (
dxs2
) cannot compensate for the loss of
dxs1
. We looked at the effect of overexpression of Dxr, Dxs1, Dxs2, and GcpE on viability and on growth in
M. tuberculosis
. Overexpression of
dxs1
or
dxs2
was inhibitory to growth, whereas overexpression of
dxr
or
gcpE
was not. Toxicity is likely to be, at least partially, due to depletion of pyruvate from the cells. Overexpression of
dxs1
or
gcpE
resulted in increased flux through the pathway, as measured by accumulation of the metabolite 4-hydroxy-3-methyl-but-2-enyl pyrophosphate. We identified the functional translational start site and promoter region for
dxr
and demonstrated that it is expressed as part of a polycistronic mRNA with
gcpE
and two other genes. Increased expression of this operon was seen in cells overexpressing Dxs1, indicating that transcriptional control is effected by the first enzyme of the pathway via an unknown regulator.
In theStaphylococcus aureusTwo-Component Systemsae, the Response Regulator SaeR Binds to a Direct Repeat Sequence and DNA Binding Requires Phosphorylation by the Sensor Kinase SaeS
Authors: Sun Fei , Li Chunling , Jeong Dowon , Sohn Changmo , He Chuan , Bae Taeok
Published: February 2010

Staphylococcus aureususes the SaeRS two-component system to control the expression of many virulence factors such as alpha-hemolysin and coagulase; however, the molecular mechanism of this signaling has not yet been elucidated. Here, using the P1 promoter of thesaeoperon as a model target DNA, we demonstrated that the unphosphorylated response regulator SaeR does not bind to the P1 promoter DNA, while its C-terminal DNA binding domain alone does. The DNA binding activity of full-length SaeR could be restored by sensor kinase SaeS-induced phosphorylation. Phosphorylated SaeR is more resistant to digestion by trypsin, suggesting conformational changes. DNase I footprinting assays revealed that the SaeR protection region in the P1 promoter contains a direct repeat sequence (GTTAAN6GTTAA [where N is any nucleotide]). This sequence is critical to the binding of phosphorylated SaeR. Mutational changes in the repeat sequence greatly reduced both thein vitrobinding of SaeR and thein vivofunction of the P1 promoter. From these results, we concluded that SaeR recognizes the direct repeat sequence as a binding site and that binding requires phosphorylation by SaeS.
Genomic Content ofNeisseriaSpecies
Authors: Tobiason Deborah M. , Seifert H. Steven
Published: February 2010

The physical properties of most bacterial genomes are largely unexplored. We have previously demonstrated that the strict human pathogenNeisseria gonorrhoeaeis polyploid, carrying an average of three chromosome copies per cell and only maintaining one pair of replication forks per chromosome (D. M. Tobiason and H. S. Seifert, PLos Biol. 4:1069-1078, 2006). We are following up this initial report to test several predictions of the polyploidy model of gonococcal chromosome organization. We demonstrate that theN. gonorrhoeaechromosomes exist solely as monomers and not covalently linked dimers, and in agreement with the monomer status, we show that distinct nucleoid regions can be detected by electron microscopy. Two different approaches to isolate heterozygousN. gonorrhoeaeresulted in the formation of merodiploids, showing that even with more than one chromosome copy, these bacteria are genetically haploid. We show that the closely related bacteriumNeisseria meningitidisis also polyploid, while the commensal organismNeisseria lactamicamaintains chromosomes in single copy. We conclude that the pathogenicNeisseriastrains are homozygous diploids.
Modified approach for preparing (E)-stilbenes related to resveratrol, and evaluation of their potential immunobiological effects
Authors: Šmidrkal Jan , Harmatha Juraj , Buděšínský Miloš , Vokáč Karel , Zídek Zdeněk , Kmoníčková Eva , Merkl Roman , Filip Vladimír
Published: February 2010

Resveratrol and closely related stilbenoids belong to the most intensively studied biologically active compounds. This interest evoked several attempts to prepare such compounds in a convenient synthetic way. Our approach allowed obtaining largely methoxystilbenes, formed asE-isomers only (using Wittig–Horner synthesis as the key step), which were further demethylated by boron tribromide. The hydroxymethoxystilbenes (e.g. pterostilbene) were prepared using isopropyl protection, later selectively deprotected by boron trichloride. The method is suitable for preparing such compounds in a large amount. Effects of the obtained stilbene derivatives on immunobiological responses triggered by lipopolysacharide and interferon-γ were tested under in vitro conditions. Namely production of nitric oxide (NO) was investigated, and relation between the molecular structure and immunobiological activity was assessed.
NFATc4 is negatively regulated in miR-133a-mediated cardiomyocyte hypertrophic repression
Authors: Li Qi , Lin Xi , Yang Xiangsheng , Chang Jiang
Published: February 2010

Activation of NFAT (nuclear factor of activated T cells)-mediated hypertrophic signaling is a major regulatory response to hypertrophic stimuli. A recent study unveiled potential regulatory roles for microRNA-133a (miR-133a) in cardiac hypertrophy. To date, however, no connection has been made between miR-133a and NFAT signaling. In this study, we determined that NFATc4, a hypertrophy-associated mediator, is negatively regulated by miR-133a. Two conserved base-pairing sites between the NFATc4 3′-untranslated region (UTR) and miR-133a were verified. Mutation of these sites in the NFATc4 3′-UTR completely blocked the negative effect of miR-133a on NFATc4, suggesting that NFATc4 is a direct target for miR-133a regulation. Using a gain-of-function approach, we demonstrate that miR-133 significantly reduces the endogenous level of, as well as the hypertrophic stimulus-mediated increase in, NFATc4 gene expression. This latter effect of miR-133a on NFATc4 gene expression was coincided with an attenuated cardiomyocyte hypertrophy induced by an α-adrenergic receptor agonist. Conversely, cells treated with miR-133a inhibitor resulted in an increase in NFATc4 expression level. Application of miR-133a had no apparent effect on NFATc4 nuclear localization. We conclude that the negative regulation of NFATc4 expression contributes to miR-133a-mediated hypertrophic repression.
Structural inhomogeneity and fiber orientation in the inner arterial media
Authors: Timmins Lucas H. , Wu Qiaofeng , Yeh Alvin T. , Moore James E. , Greenwald Stephen E.
Published: February 2010

The microstructural orientation of vascular wall constituents is of interest to scientists and clinicians because alterations in their native states are associated with various cardiovascular diseases. In the arterial media, the orientation of these constituents is often described as circumferential. However, it has been noted that, just below the endothelial surface, the vascular wall constituents are oriented axially. To further study this reported change in orientation, and to resolve previous observations (which were made under conditions of no load), we used nonlinear optical microscopy to examine the orientation of collagen and elastin fibers in the inner medial region of bovine common carotid arteries. Images were obtained from this part of the arterial wall under varying degrees of mechanical strain: 0%, 10% axial, 10% circumferential, and 10% biaxial. We observed that close to the endothelium these components are aligned in the axial direction but abruptly change to a circumferential alignment at a depth of ∼20 μm from the endothelial surface. The application of mechanical strain resulted in a significantly greater degree of fiber alignment, both collagen and elastin, in the strain direction, regardless of their initial unloaded orientation. Furthermore, variations in strain conditions resulted in an increase or a decrease in the overall degree of fiber alignment in the subendothelial layer depending on the direction of the applied strain. This high-resolution investigation adds more detail to existing descriptions of complex structure-function relationships in vascular tissue, which is essential for a better understanding of the pathophysiological processes resulting from injury, disease progression, and interventional therapies.
Targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced sustained ventricular tachycardia in conscious rats
Authors: Lujan Heidi L. , Palani Gurunanthan , Zhang Lijie , DiCarlo Stephen E.
Published: February 2010

The Cardiac Arrhythmia Suppression Trial demonstrated that antiarrhythmic drugs not only fail to prevent sudden cardiac death, but actually increase overall mortality. These findings have been confirmed in additional trials. The “proarrhythmic” effects of most currently available antiarrhythmic drugs makes it essential that we investigate novel strategies for the prevention of sudden cardiac death. Targeted ablation of cardiac sympathetic neurons may become a therapeutic option by reducing sympathetic activity. Thus cholera toxin B subunit (CTB) conjugated to saporin (a ribosomal inactivating protein that binds to and inactivates ribosomes; CTB-SAP) was injected into both stellate ganglia to test the hypothesis that targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced, sustained ventricular tachycardia in conscious rats. Rats were randomly divided into three groups: 1) control (no injection); 2) bilateral stellate ganglia injection of CTB; and 3) bilateral stellate ganglia injection of CTB-SAP. CTB-SAP rats had a reduced susceptibility to ischemia-induced, sustained ventricular tachycardia. Associated with the reduced susceptibility to ventricular arrhythmias were a reduced number of stained neurons in the stellate ganglia and spinal cord (segments T1-T4), as well as a reduced left ventricular norepinephrine content and sympathetic innervation density. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing the susceptibility to ventricular arrhythmias.
Knockout of Na+/Ca2+exchanger in smooth muscle attenuates vasoconstriction and L-type Ca2+channel current and lowers blood pressure
Authors: Zhang Jin , Ren Chongyu , Chen Ling , Navedo Manuel F. , Antos Laura K. , Kinsey Stephen P. , Iwamoto Takahiro , Philipson Kenneth D. , Kotlikoff Michael I. , Santana Luis F. , Wier W. Gil , Matteson Donald R. , Blaustein Mordecai P.
Published: February 2010

Mice with smooth muscle (SM)-specific knockout of Na+/Ca2+exchanger type-1 (NCX1SM−/−) and the NCX inhibitor, SEA0400, were used to study the physiological role of NCX1 in mouse mesenteric arteries. NCX1 protein expression was greatly reduced in arteries from NCX1SM−/−mice generated with Cre recombinase. Mean blood pressure (BP) was 6–10 mmHg lower in NCX1SM−/−mice than in wild-type (WT) controls. Vasoconstriction was studied in isolated, pressurized mesenteric small arteries from WT and NCX1SM−/−mice and in heterozygotes with a global null mutation (NCX1Fx/−). Reduced NCX1 activity was manifested by a marked attenuation of responses to low extracellular Na+concentration, nanomolar ouabain, and SEA0400. Myogenic tone (MT, 70 mmHg) was reduced by ∼15% in NCX1SM−/−arteries and, to a similar extent, by SEA0400 in WT arteries. MT was normal in arteries from NCX1Fx/−mice, which had normal BP. Vasoconstrictions to phenylephrine and elevated extracellular K+concentration were significantly reduced in NCX1SM−/−arteries. Because a high extracellular K+concentration-induced vasoconstriction involves the activation of L-type voltage-gated Ca2+channels (LVGCs), we measured LVGC-mediated currents and Ca2+sparklets in isolated mesenteric artery myocytes. Both the currents and the sparklets were significantly reduced in NCX1SM−/−(vs. WT or NCX1Fx/−) myocytes, but the voltage-dependent inactivation of LVGCs was not augmented. An acute application of SEA0400 in WT myocytes had no effect on LVGC current. The LVGC agonist, Bay K 8644, eliminated the differences in LVGC currents and Ca2+sparklets between NCX1SM−/−and control myocytes, suggesting that LVGC expression was normal in NCX1SM−/−myocytes. Bay K 8644 did not, however, eliminate the difference in myogenic constriction between WT and NCX1SM−/−arteries. We conclude that, under physiological conditions, NCX1-mediated Ca2+entry contributes significantly to the maintenance of MT. In NCX1SM−/−mouse artery myocytes, the reduced Ca2+entry via NCX1 may lower cytosolic Ca2+concentration and thereby reduce MT and BP. The reduced LVGC activity may be the consequence of a low cytosolic Ca2+concentration.
Chronic AT1receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1expression within the PVN in rats with heart failure
Authors: Kleiber Allison C. , Zheng Hong , Sharma Neeru M. , Patel Kaushik P.
Published: February 2010

Exercise training normalizes enhanced glutamatergic mechanisms within the paraventricular nucleus (PVN) concomitant with the normalization of increased plasma ANG II levels in rats with heart failure (HF). We tested whether ANG II type 1 (AT1) receptors are involved in the normalization of PVN glutamatergic mechanisms using chronic AT1receptor blockade with losartan (Los; 50 mg·kg−1·day−1in drinking water for 3 wk). Left ventricular end-diastolic pressure was increased in both HF + vehicle (Veh) and HF + Los groups compared with sham-operated animals (Sham group), although it was significantly attenuated in the HF + Los group compared with the HF + Veh group. The effect of Los on cardiac function was similar to exercise training. At the highest dose of N-methyl-d-aspartate (NMDA; 200 pmol) injected into the PVN, the increase in renal sympathetic nerve activity was 93 ± 13% in the HF + Veh group, which was significantly higher ( P < 0.05) than the increase in the Sham + Veh (45 ± 2%) and HF + Los (47 ± 2%) groups. Relative NMDA receptor subunit NR1mRNA expression within the PVN was increased 120% in the HF + Veh group compared with the Sham + Veh group ( P < 0.05) but was significantly attenuated in the HF + Los group compared with the HF + Veh group ( P < 0.05). NR1protein expression increased 87% in the HF + Veh group compared with the Sham + Veh group but was significantly attenuated in the HF + Los group compared with the HF + Veh group ( P < 0.05). Furthermore, in in vitro experiments using neuronal NG-108 cells, we found that ANG II treatment stimulated NR1protein expression and that Los significantly ameliorated the NR1expression induced by ANG II. These data are consistent with our hypothesis that chronic AT1receptor blockade normalizes glutamatergic mechanisms within the PVN in rats with HF.
Chorioamnionitis stimulates angiogenesis in saccular stage fetal lungs via CC chemokines
Authors: Miller J. Davin , Benjamin John T. , Kelly David R. , Frank David B. , Prince Lawrence S.
Published: February 2010

The fetal lung vasculature forms in tandem with developing airways. Whereas saccular airway morphogenesis is arrested in bronchopulmonary dysplasia (BPD), the potential vascular phenotype in BPD at this stage of development is less well-understood. As inflammation increases the risk of BPD and induces arrest of saccular airway morphogenesis, we tested the effects of Escherichia coli LPS on fetal mouse lung vascular development. Injecting LPS into the amniotic fluid of Tie2- lacZ endothelial reporter mice at embryonic day 15 stimulated angiogenesis in the saccular stage fetal lung mesenchyme. LPS also increased the number of endothelial cells in saccular stage fetal mouse lung explants. Inflammation appeared to directly promote vascular development, as LPS stimulated pulmonary microvascular endothelial cell angiogenesis, cell migration, and proliferation in vitro. Whereas LPS did not increase expression of VEGF, angiopoietin-1 (Ang-1), Tie2, fetal liver kinase-1 (Flk-1), fms-like tyrosine kinase-1 (Flt-1), PDGFA, PDGFB, heparin-binding EGF-like growth factor (HB-EGF), or connective tissue growth factor (CTGF), LPS did stimulate the production of the angiogenic CC chemokines macrophage inflammatory protein-1α (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1). Both MIP-1α and MCP-1 increased angiogenesis in fetal mouse lung explants. In addition, inhibitory antibodies against MIP-1α and MCP-1 blocked the effects of LPS on fetal lung vascular development, suggesting these chemokines are downstream mediators of LPS-induced angiogenesis. We speculate that an inflammation-mediated surge in angiogenesis could lead to formation of aberrant alveolar capillaries in the lungs of patients developing BPD.
Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
Authors: Marcus Frank I. , McKenna William J. , Sherrill Duane , Basso Cristina , Bauce Barbara , Bluemke David A. , Calkins Hugh , Corrado Domenico , Cox Moniek G.P.J. , Daubert James P. , Fontaine Guy , Gear Kathleen , Hauer Richard , Nava Andrea , Picard Michael H. , Protonotarios Nikos , Saffitz Jeffrey E. , Sanborn Danita M. Yoerger , Steinberg Jonathan S. , Tandri Harikrishna , Thiene Gaetano , Towbin Jeffrey A. , Tsatsopoulou Adalena , Wichter Thomas , Zareba Wojciech
Published: February 2010

Background—

In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims—the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease.

Methods and Results—

Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data.

Conclusions—

The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00024505.
Engaging the Disengaged: Collective Action, Media Uses, and Sense of (Virtual) Community by Evacuees From Gush Katif
Authors: Lev-On Azi
Published: February 2010

Former residents of the evacuated Gush Katif region, once parts of closely knit and cohesive communities, have been spread across Israel in temporary settlements since the disengagement, in 2005. The goal of this study was to learn how the evacuees interacted with one another online to organize politically and retain their social capital. The study focused on Katif.net, the major Internet site in use by the former residents of Gush Katif. This is an unusual case of a virtual community that continues to thrive online even as its offline predecessor has been evacuated.
In vitro Remineralization of Severely Compromised Bonded Dentin
Authors: Mai S. , Kim Y.K. , Kim J. , Yiu C.K.Y. , Ling J. , Pashley D.H. , Tay F.R.
Published: February 2010

Biomimetic remineralization is potentially useful for the remineralization of incompletely resin-infiltrated collagen matrices created by etch-and-rinse adhesives. In this study, we tested the hypothesis that structurally altered dentin collagen cannot be remineralized to the same hierarchical order and dimension seen in structurally intact dentin collagen. The remineralization medium consisted of a set Portland cement/simulated body fluid system containing polycarboxylic acid and polyvinylphosphonic acid as biomimetic analogs. Remineralization of air-dried, collapsed hybrid layers was apparent after one month, with hybrid layers remineralized to 80–90% of their thickness after 2–4 months. A hypermineralized layer was seen on the hybrid layer surface, and tubular orifices were occluded with apatite deposits that resembled those present in non-carious cervical dentin. Structurally altered collagen is unlikely to be remineralized to the same hierarchical order and dimension as seen in intact dentin. The aggressively air-dried acid-etched dentin remineralization model also sheds light on the mechanism of sclerotic dentin formation.
Relative Accessibility Deprivation Indicators for Urban Settings: Definitions and Application to Food Deserts in Montreal
Authors: Páez Antonio , Gertes Mercado Ruben , Farber Steven , Morency Catherine , Roorda Matthew
Published: February 2010

Accessibility research, within the context of the social exclusion dimensions of transport, has provided valuable tools to understand the potential of people to reach daily life activity locations. In this paper, model-based estimates of distance travelled are used to calculate a cumulative opportunities measure of accessibility. Multivariate, spatially expanded models produce estimates of distance travelled that are specific to both geographical location and type of individual. Opportunity landscapes obtained based on these estimates are used for comparative accessibility analysis by means of what are termed relative accessibility deprivation indicators. The indicators proposed are demonstrated with a case study of food deserts in the city of Montreal, Canada. The results of the analysis illustrate the variations in accessibility between individuals in low-income households and the reference group, and the effect of vehicle ownership for accessibility to food services, thus highlighting the social exclusion implications of these factors.
Playing the Ethnic Card: Politics and Segregation in London’s East End
Authors: Glynn Sarah
Published: February 2010

This article takes a critical look at the exploitation of difference and at the impact of political forces of various kinds on ethnic segregation. It examines both external forces and forces from within ‘communities’ themselves through the case history of Bengali settlement in the East End of London. It assesses the different, though interacting, roles of immigration legislation and resource allocation, community and separatist politics, populism and multiculturalism, and brings the story up to date with an account of the incorporation of faith groups in local governance and of the wooing of the Muslim vote in the context of ‘the war on terror’. This understanding is presented as a necessary first step in combating ethnic division and focusing instead on social equality for all ethnicities.
Managing the Parameters of Visibility: The Revelations of Katrina
Authors: Rhodes James
Published: February 2010

Hurricane Katrina exposed the immobility of the Black poor, revealing the dual logics of concealment and containment on which public space throughout US cities is increasingly built. However, the force of the hurricane eroded the distinction between the private ‘ghetto’ and the public arena. The response of government and the media was guided by an interpretive framework in which poor urban Blacks are marked by their ‘criminality’. It was through this, alongside the dominant colour-blind racial ideology, that the ‘revelations’ of Katrina, its knowledge or ‘truths’, were produced and managed. Finally, the rebuilding of New Orleans will be considered, demonstrating how the Black urban poor are excluded from the imaginary of the remodelled contemporary American city.
Bioequivalence Studies of Omnitrope, the First Biosimilar/rhGH Follow‐on Protein: Two Comparative Phase 1 Randomized Studies and Population Pharmacokinetic Analysis
Authors: Stanhope Richard , Sörgel Fritz , Gravel Patricia , Schuetz Yannic B. Pannatier , Zabransky Markus , Muenzberg Michael
Published: February 2010

This article discusses the bioequivalence of Omnitrope (Sandoz's rhGH biosimilar) and Genotropin (reference rhGH product), assessed in the first 2 clinical phase 1 studies conducted during the development of Omnitrope. Both of these phase 1 studies were randomized, double‐blind, crossover studies, each involving 24 healthy volunteers who underwent pituitary somatrope cell down‐regulation using octreotide. Three different formulations of recombinant human growth hormone (rhGH) were compared: Omnitrope lyophilisate, Omnitrope liquid and Genotropin (lyophilized powder for injection). Both pharmacokinetics (area under the curve [AUC], Cmax, tmax and t1/2) and pharmacodynamics (serum levels of insulin‐like growth factor 1, insulin‐like growth factor binding protein‐3 and non‐esterified fatty acid) were assessed after a single subcutaneous injection of 5 mg rhGH. The 3 formulations had comparable pharmacokinetics and pharmacodynamics. All the 90% confidence intervals of the ratios of the least squares means for the pharmacokinetic and pharmacodynamic parameters AUC and Cmax were within the predefined FDA and EMEA acceptance range of 80%–125% for bioequivalence. In addition, a comparative population pharmacokinetic analysis further supports that Omnitrope lyophilisate, Omnitrope liquid and Genotropin can be regarded as equivalent in terms of pharmacokinetics. Therefore, Omnitrope lyophilisate was demonstrated to be bioequivalent to both Genotropin and the Omnitrope liquid formulation.
Effect of Raltegravir on the Pharmacokinetics of Methadone
Authors: Anderson Matt S. , Luk Julie Ann Mabalot , Hanley William D. , Jin Bo , Riesenberg Robert A. , Wenning Larissa A. , Chodakewitz Jeffery A. , Wagner John A. , Iwamoto Marian
Published: February 2010

A randomized, placebo‐controlled, 2‐period crossover study in subjects on methadone maintenance therapy was conducted to assess the effect of the HIV‐1 integrase inhibitor, raltegravir, on the pharmacokinetics of methadone. Twelve HIV‐negative male and female subjects stabilized on an oral methadone program were enrolled. Subjects maintained their prescribed oral doses of methadone throughout the study and, in each of 2 periods, received either 400 mg of raltegravir or matching placebo every 12 hours on days 1 through 10 of each treatment period with a washout of 7 days between periods. Plasma samples for analysis of methadone pharmacokinetics were collected over 24 hours postdose on day 10 of each treatment period. Safety and tolerability were assessed throughout the study. The geometric mean ratio (90% confidence interval) for methadone when administered with raltegravir relative to methadone alone was 1.00 (0.93‐1.09) for area under the methadone concentration‐time curve from time 0 to 24 hours and 1.00 (0.94‐1.07) for maximal concentration. There were no serious clinical or laboratory adverse experiences. There were no discontinuations due to an adverse experience. Coadministration of raltegravir and methadone is generally well tolerated. Raltegravir has no clinically meaningful effect on methadone pharmacokinetics. No dose adjustment is required for methadone when coadministered with raltegravir.
Comparable biocompatibility of Phisio- and Bioline-coated cardiopulmonary bypass circuits indicated by the inflammatory response
Authors: Thiara AS , Andersen VY , Videm V. , Mollnes TE , Svennevig K. , Hoel TN , Fiane AE
Published: February 2010

Background: The biocompatibility of cardiopulmonary bypass surfaces has been improved by heparin and polymer surface modifications. The present study compared the effect of two such coatings on the inflammatory reactions after open heart surgery.

Methods:Thirty patients undergoing elective heart surgery were randomly assigned to receive one of two types of coated circuits: Bioline (n=15) or phosphorylcholine (Phisio, n=15). The platelet and leukocyte counts, neutrophil activation (myeloperoxidase), complement activation (C3a and TCC), concentrations of lactate dehydrogenase, 27 cytokines (including interleukins, chemokines and growth factors), thrombin-antithrombin complexes, and the endothelial cell marker syndecan-1 were analyzed at five predetermined time points until 24 hrs post operatively.

Results: Most measurements were comparable in both groups. However, myeloperoxidase was significantly higher in the Bioline group (p < 0.001). Postoperative lactate dehydrogenase concentrations were significantly higher in the Phisio group (p<0.01) and the maximal concentration of thrombin-antithrombin complexes 2 hours postoperatively tended to be higher in the Phisio group (p=0.08), consistent with a longer aortic cross-clamp and cardiopulmonary bypass time. Conclusions: The two circuits exhibited a comparable degree of in vivo biocompatibility.
Brachyspira murdochii Colitis in Pigs
Authors: Jensen T. K. , Christensen A. S. , Boye M.
Published: February 2010

The weakly beta-hemolytic porcine spirochete Brachyspira murdochii is considered a normal intestinal commensal. In the present study, however, a field case of B murdochii–associated catarrhal colitis was identified in a pig, as characterized by extensive spirochetal colonization of the surface epithelium. Experimentally, 8 weaned pigs were challenged with the B murdochii isolate, reproducing catarrhal colitis in 2 animals. By applying fluorescent in situ hybridization using a species-specific oligonucleotide probe targeting 23S rRNA, B murdochii organisms were found in high numbers and were closely associated with the surface epithelium in the pigs with catarrhal colitis. The results indicate that, when present in high numbers, B murdochii is low pathogenic for pigs.
Enhancement of Passive Fire Protection Ability of Inorganic Fire Retardants in Vinyl Ester Resin Using Glass Frit Synergists
Authors: Kandola Baljinder K. , Pornwannachai Wiwat
Published: February 2010

Two types of glass frit samples, XF100 and XF105 (Johnson Matthey), in combination with conventional inorganic flame retardants, Ultracarb (mixture of huntite and hydromagnesite) and alumina trihydrate, were introduced into a thermoset vinyl ester resin. The methodology involved dispersing glass additives with other two flame retardants in different ratios in a vinyl ester resin and casting into plaques. Thermal stability and flammability of the samples studied by thermogravimetry, LOI and UL-94, indicated that the presence of glass frit increased the char yield and reduced the burning rate of the resin sample. The results from cone calorimetry at 50 kW/m2 heat flux showed that both glass frits, XF100 and XF105, improved the effectiveness of Ultracarb and alumina trihydrate, respectively by increasing the time-to-ignition, reducing total heat release values, and char formation, only when they were used in low amounts in the combinations. However, they did not help in reducing the respective peak of heat release rates, indicating their passive fire protection mechanism.
Effects of climatic change and bog development on Holocene tufa formation in the Lorze Valley (central Switzerland)
Authors: Wehrli Michael , Mitchell Edward A.D. , van der Knaap W.O. , Ammann Brigitta , Tinner Willy
Published: February 2010

A massive tufa complex in the lower Lorze Valley (550 m a.s.l., north-central Switzerland) formed between 9000 and 5000 cal. yr BP. In the plain 4 km southeast of the complex lies Neugrundmoor (830 m a.s.l.), a mire in the hydrologic recharge area of the springs responsible for the tufa formation. Here we address an earlier, untested hypothesis that the transition of Neugrundmoor from fen to raised bog caused the end of the tufa formation, by means of pollen and testate amoebae analyses on a peat section. The chronology of the section is based on ten AMS 14C-dates of terrestrial plant macrofossils. Our results suggest that until 7100 cal. yr BP the plain had shallow ponds, which gradually developed into fens. Starting 5350 cal. yr BP, large raised bogs developed in the fens in a few centuries. This agrees with the hypothesis that the end of tufa formation coincided with the transition from fen to raised bog. It also coincided with the end of the mid-Holocene temperature optimum, when climate became cooler and wetter. We suggest that the main factor causing the end of tufa formation at 5500—5000 cal. yr BP was declining air temperatures, which on the one hand led to diminished calcium precipitation, on the other to enhanced bog formation. Peat has a low hydraulic conductivity, so we suggest that less water became available for tufa formation because of increased thickness of peat layers, exacerbating the direct effect of cooling on calcium precipitation. Noticeable human influence in the surroundings did presumably not start before c. 3500 cal. yr BP and was then very weak, so this was not responsible for the end of the tufa formation. Extrapolation of our results suggests that climatic cooling alone is sufficient to explain the widespread termination of tufa formation after the mid Holocene.
Holocene environmental variations recorded by organic-related and carbonate-related proxies of the lacustrine sediments from Bosten Lake, northwestern China
Authors: Zhang Chengjun  , Feng Zhaodong  , Yang Qili  , Gou Xiaohui  , Sun Feifei
Published: February 2010

We reconstructed a multiproxy record of the Holocene climate changes from a 9.53 m core from Bosten Lake in the southern Xinjiang of northwestern China based on a chronology supported by nine AMS 14C dates in the hope that the previous reconstructions can be improved. Our data exhibited three timescales of variation in the water salinity of the lake. First, the upward-increasing parallel trends of major salinity proxies suggest that the salinity has been gradually increasing in the past ~8000 years. This constant increase in the salinity is most likely to have resulted from the shrinking of glacial cover in the central Tianshan Mountains where the inflowing river (i.e. Kaidu River) originated. Second, the C/S ratio and carbonate-based salinity proxies suggest that the lake was formed around ~8060 cal. yr BP and reached its maximum depth around ~7250 cal yr BP. The lake level then declined to the mid- and late-Holocene average level around ~6370 cal. yr BP and has varied drastically around a relatively constant mean during the past ~6370 years. Third, the past ~8060 yr history of the Bosten Lake can be divided into five salinity stages. That is, three high salinity intervals are separated by two low salinity intervals. The two low salinity stages occurred between ~6370 and ~5170 cal. yr BP and between ~3000 and ~2170 cal. yr BP. Each one of the three high salinity stages can be further divided into less saline and more saline substages. Specifically, less saline time intervals are: substage 2-1 (~8060—~7250 cal. yr BP), substage 4-2 (~4370—~3830 cal. yr BP) and substage 6-2 (~1250—~0 cal. yr BP). Also, saltier time intervals are: substage 2-2 (~7250—~6370 cal. yr BP), substage 4-1 (~5170—~4370 cal. yr BP), substage 4-3 (~3830—~3000 cal. yr BP) and substage 6-1 (~2170—~1250 cal. yr BP). It should be stressed that the phase relationships between the carbonate-based salinity proxy and diatom-based temperature proxy suggest that the salinity was mainly controlled by temperature. Finally, the comparison between the Bosten Lake salinity record and the high northern latitudinal climate pattern suggests that the lower salinity and cooler periods in Bosten Lake area correspond with abrupt climatic events (i.e. cooling events) in the high northern latitudes.
What can we learn from the failures of technology and innovation policies in the European periphery?
Authors: Liagouras George
Published: February 2010

This paper examines the technology policy challenges facing peripheral European Union economies in their effort to catch up with the more advanced countries. It is argued that, generally, the subordinate position of peripheral economies within the EU compels them to replicate the technology policies followed in advanced countries. Yet the latter have proven more or less inappropriate for peripheral countries and regions because they usually do not properly accommodate their growth models and their corresponding production structures. On the other hand, the EU’s preoccupation with ‘high-tech’ and ‘best-practice’ policies can be attributed to the underestimation of business organization and broader economic structures by the dominant theoretical paradigm of technology and innovation.
The Assembly of European Regions’ Udine Declaration: Contradictory approaches to European and regional identities
Authors: Ivic Sanja
Published: February 2010

This paper explores whether the Udine Declaration embraces contradictory approaches to European and regional identities. It will be argued that the Udine Declaration employs two different logics that undermine its basic task of establishing a broader notion of identity.
Adolescents’ and Parents’ Experiences of Managing the Psychosocial Impact of Appearance Change During Cancer Treatment
Authors: Williamson Heidi , Harcourt Diana , Halliwell Emma , Frith Hannah , Wallace Melissa
Published: February 2010

Using combined qualitative data from multiple case study interviews and an online survey, this study explored the impact of appearance change on 22 adolescents receiving cancer treatment aged 13 to 18 years and six of their parents. Data were analyzed using template analysis. Appearance changes were a major concern. Adolescents typically struggled to adapt to new experiences and concerns related to this highly sensitive issue. Many felt anxious and self-conscious and were reluctant to reveal appearance changes in public. These feelings were compounded by the negative reactions of others (e.g., staring, teasing, and inappropriate questioning), which sometimes lead to avoidance of social activity and threats of noncompliance. Parents of these children felt ill-prepared to manage appearance-related anxieties. Adolescents wanted support to develop the practical and social skills necessary to maintain a “normal” appearance and manage the negative responses of others. However, some adolescents showed resilience and, with support from friends and family, developed strategies to manage their altered appearance and its social consequences. These strategies are explored, which can inform interventions to support adolescents and parents.
Euroscepticism and the Emergence of Political Parties in Poland
Authors: Markowski Radosław , Tucker Joshua A.
Published: February 2010

One of the most interesting features of the 2003 Polish referendum on European Union (EU) membership was the strong link between voting behaviour in the 2003 referendum and voting behaviour in the 2001 Polish parliamentary election. In this article, we test two competing mechanisms that could account for this finding: a responsible party model, whereby citizens’ attitudes towards EU membership would have been driven by their preferred party’s position on the issue, and a more Downsian model, whereby the existence of an unrepresented Polish Eurosceptic electorate could have driven the success of two new Eurosceptic parties in the 2001 parliamentary elections. Drawing upon data from the 1997, 2001 and 2005 Polish National Election Studies, we find much stronger empirical support for the Downsian approach. Far from being led to their Euroscepticism by party leaders as the 2003 referendum on Polish EU membership approached, voters for Poland’s Eurosceptic parties in 2001 already possessed healthy degrees of Euroscepticism, especially when compared to supporters of other parties and even to non-voters.
Automatic Constructive Appraisal as a Candidate Cause of Emotion
Authors: Moors Agnes
Published: February 2010

Critics of appraisal theory have difficulty accepting appraisal (with its constructive flavor) as an automatic process, and hence as a potential cause of most emotions. In response, some appraisal theorists have argued that appraisal was never meant as a causal process but as a constituent of emotional experience. Others have argued that appraisal is a causal process, but that it can be either rule-based or associative, and that the associative variant can be automatic. This article first proposes empirically investigating whether rule-based appraisal can also be automatic and then proposes investigating the automatic nature of constructive (instead of rule-based) appraisal because the distinction between rule-based and associative is problematic. Finally, it discusses experiments that support the view that constructive appraisal can be automatic.
Emotional Facial Expressions in Infancy
Authors: Camras Linda A. , Shutter Jennifer M.
Published: February 2010

In this article, we review empirical evidence regarding the relationship between facial expression and emotion during infancy. We focus on differential emotions theory’s view of this relationship because of its theoretical and methodological prominence. We conclude that current evidence fails to support its proposal regarding a set of pre-specified facial expressions that invariably reflect a corresponding set of discrete emotions in infants. Instead, the relationship between facial expression and emotion appears to be more complex. Some facial expressions may have different meanings in infants than in children and adults. In addition, nonemotion factors may sometimes lead to the production of “emotional” facial expressions. We consider alternative perspectives on the nature of emotion and emotional expression in infancy with particular focus on differentiation and dynamical systems approaches.
Fictions and Feelings: On the Place of Literature in the Study of Emotion
Authors: Colm Hogan Patrick
Published: February 2010

Explanatory accounts of emotion require, among other things, theoretically tractable representations of emotional experience. Common methods for producing such representations have well-known drawbacks, such as observer interference or lack of ecological validity. Literature offers a valuable supplement. It provides detailed instructions for simulating emotions; when successful, it induces empathic emotions. It too involves distortions, through emotion-intensifying idealization and ideological biases. But these also relate to emotion study. There are three levels at which literature bears on emotion research: (1) the individual work; (2) generic and related patterns; and (3) properties found widely across individual works and genres. Even at the third, most general level, literature suggests potentially important hypotheses about our pleasure in emotional simulation and our need to share emotional experiences.