bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel evolution and local differentiation in quinolone resistance in Pseudomonas aeruginosa
Authors: Wong Alex , Kassen Rees
Published: February 2011

The emergence and spread of antibiotic resistance in pathogens is a major impediment to the control of microbial disease. Here, we review mechanisms of quinolone resistance inPseudomonas aeruginosa, an important nosocomial pathogen and a major cause of morbidity in cystic fibrosis (CF) patients. In this quantitative literature review, we find that mutations in DNA gyrase A, the primary target of quinolones in Gram-negative bacteria, are the most common resistance mutations identified in clinical samples of all origins, in keeping with previous observations. However, the identities of non-gyrase resistance mutations vary systematically between samples isolated from CF patients and those isolated from acute infections. CF-derived strains tend to harbour mutations in the efflux pump regulatornfxB, while non-CF strains tend to bear mutations in the efflux regulatormexRor inparC, which encodes one of two subunits of DNA topoisomerase IV. We suggest that differences in resistance mechanisms between CF and non-CF strains result either from local adaptation to different sites of infection or from differences in mutational processes between different environments. We further discuss the therapeutic implications of local differentiation in resistance mechanisms to a common antibiotic.
Participation of CheR and CheB in the chemosensory response of Campylobacter jejuni
Authors: Kanungpean Doungjit , Kakuda Tsutomu , Takai Shinji
Published: February 2011

Campylobacter jejuniis a leading cause of bacterial gastroenteritis in humans and a commensal bacterium of the intestinal tracts of animals, especially poultry. Chemotaxis is an important determinant for chicken colonization ofC. jejuni. Adaptation has a crucial role in the gradient-sensing mechanism that underlies chemotaxis. The genome sequence ofC. jejunireveals the presence of genes encoding putative adaptation proteins, CheB and CheR. In-frame deletions ofcheB,cheRandcheBRwere constructed and the chemosensory behaviour of the resultant mutants was examined on swarm plates. CheB and CheR proteins significantly influence chemotaxis but are not essential for this behaviour to occur. Increased mobility of two methyl-accepting chemotaxis proteins (MCPs), DocC and Tlp1, during SDS-PAGE was detected in the mutants lacking functional CheB in the presence of CheR, presumably resulting from stable methylation of receptors.In vitrostudies using tissue culture revealed that deletion ofcheRresulted in hyperadherent and hyperinvasive phenotypes, while deletion ofcheBresulted in nonadherent, noninvasive phenotypes. Furthermore, the ΔcheBRmutant showed significantly reduced ability to colonize chick caeca. Our data suggest that modification of chemoreceptors by the CheBR system is involved in regulation of chemotaxis inC. jejunialthough CheB is apparently not controlled by phosphorylation.
Crosstalk between Hsp90 and Hsp70 Chaperones and Heat Stress Transcription Factors in Tomato
Authors: Hahn Alexander , Bublak Daniela , Schleiff Enrico , Scharf Klaus-Dieter
Published: February 2011

Heat stress transcription factors (Hsfs) regulate gene expression in response to environmental stress. The Hsf network in plants is controlled at the transcriptional level by cooperation of distinct Hsf members and by interaction with chaperones. We found two general mechanisms of Hsf regulation by chaperones while analyzing the three major Hsfs, A1, A2, and B1, in tomato (Solanum lycopersicum). First, Hsp70 and Hsp90 regulate Hsf function by direct interactions. Hsp70 represses the activity of HsfA1, including its DNA binding, and the coactivator function of HsfB1 in the complex with HsfA2, while the DNA binding activity of HsfB1 is stimulated by Hsp90. Second, Hsp90 affects the abundance of HsfA2 and HsfB1 by modulating hsfA2 transcript degradation involved in regulation of the timing of HsfA2 synthesis. By contrast, HsfB1 binding to Hsp90 and to DNA are prerequisites for targeting this Hsf for proteasomal degradation, which also depends on a sequence element in its carboxyl-terminal domain. Thus, HsfB1 represents an Hsp90 client protein that, by interacting with the chaperone, is targeted for, rather than protected from, degradation. Based on these findings, we propose a versatile regulatory regime involving Hsp90, Hsp70, and the three Hsfs in the control of heat stress response.
Influence of traditional tobacco use on smoking cessation among American Indians
Authors: Daley Christine M. , Faseru Babalola , Nazir Niaman , Solomon Cheree , Greiner K. Allen , Ahluwalia Jasjit S. , Choi Won S.
Published: February 2011

Aims  To examine the influence of traditional tobacco use on smoking cessation among American Indian adult smokers.

Design, setting and participants  A cross‐sectional survey of self‐identified American Indians was conducted from 2008 to 2009. A total of 998 American Indian adults (18 years and older) from the Midwest participated in the study.

Measurements  Traditional tobacco use and method of traditional use were both assessed. Commercial tobacco use (current smoking) was obtained through self‐reported information as well as the length of their most recent quit attempt. We also assessed knowledge and awareness of pharmacotherapy for current smokers.

Findings  Among participants in our study, 33.3% were current smokers and they reported smoking an average of 10 cigarettes per day. American Indian current smokers who used traditional tobacco reported a greater number of days abstinent during their last quit attempt compared to those who do not use traditional tobacco (P = 0.01). However, it appears that this protective effect of traditional tobacco use is diminished if the person smokes traditional tobacco. Finally, very few (fewer than 20% of current smokers) were aware of more recent forms of pharmacotherapy such as Chantix or bupropion.

Conclusions  American Indians appear to show low levels of awareness of effective pharmacotherapies to aid smoking cessation, but those who use ‘traditional tobacco’ report somewhat longer periods of abstinence from past quit attempts.
In Salmonella enterica, the sirtuin‐dependent protein acylation/deacylation system (SDPADS) maintains energy homeostasis during growth on low concentrations of acetate
Authors: Chan Chi Ho , Garrity Jane , Crosby Heidi A. , Escalante‐Semerena Jorge C.
Published: February 2011

Acetyl‐coenzyme A synthetase (Acs) activates acetate into acetyl‐coenzyme A (Ac‐CoA) in most cells. In Salmonella enterica, acs expression and Acs activity are controlled. It is unclear why the sirtuin‐dependent protein acylation/deacylation system (SDPADS) controls the activity of Acs. Here we show that, during growth on 10 mM acetate, acs+ induction in a S. enterica strain that cannot acetylate (i.e. inactivate) Acs leads to growth arrest, a condition that correlates with a drop in energy charge (0.17) in the acetylation‐deficient strain, relative to the energy charge in the acetylation‐proficient strain (0.71). Growth arrest was caused by elevated Acs activity, a conclusion supported by the isolation of a single‐amino‐acid variant (AcsG266S), whose overproduction did not arrest growth. Acs‐dependent depletion of ATP, coupled with the rise in AMP levels, prevented the synthesis of ADP needed to replenish the pool of ATP. Consistent with this idea, overproduction of ADP‐forming Ac‐CoA‐synthesizing systems did not affect the growth behaviour of acetylation‐deficient or acetylation‐proficient strains. The AcsG266S variant was > 2 orders of magnitude less efficient than the AcsWT enzyme, but still supported growth on 10 mM acetate. This work provides the first evidence that SDPADS function helps cells maintain energy homeostasis during growth on acetate.
Biphasic control logic of HAMP domain signalling in the Escherichia coli serine chemoreceptor
Authors: Zhou Qin , Ames Peter , Parkinson John S.
Published: February 2011

HAMP domains mediate input–output communication in many bacterial signalling proteins. To explore the dynamic bundle model of HAMP signalling (Zhou et al., Mol. Microbiol. 73: 801, 2009), we characterized the signal outputs of 118 HAMP missense mutants of the serine chemoreceptor, Tsr, by flagellar rotation patterns. Receptors with proline or charged amino acid replacements at critical hydrophobic packing residues in the AS1 and AS2 HAMP helices had locked kinase‐off outputs, indicating that drastic destabilization of the Tsr‐HAMP bundle prevents kinase activation, both in the absence and presence of the sensory adaptation enzymes, CheB and CheR. Attractant‐mimic lesions that enhance the structural stability of the HAMP bundle also suppressed kinase activity, demonstrating that Tsr‐HAMP has two kinase‐off output states at opposite extremes of its stability range. HAMP mutants with locked‐on kinase outputs appeared to have intermediate bundle stabilities, implying a biphasic relationship between HAMP stability and kinase activity. Some Tsr‐HAMP mutant receptors exhibited reversed output responses to CheB and CheR action that are readily explained by a biphasic control logic. The findings of this study provide strong support for a three‐state dynamic bundle model of HAMP signalling in Tsr, and possibly in other bacterial transducers as well.
The expression and impact of antifungal grooming in ants
Authors: REBER A. , PURCELL J. , BUECHEL S. D. , BURI P. , CHAPUISAT M.
Published: February 2011

Parasites can cause extensive damage to animal societies in which many related individuals frequently interact. In response, social animals have evolved diverse individual and collective defences. Here, we measured the expression and efficiency of self‐grooming and allo‐grooming when workers of the ant Formica selysi were contaminated with spores of the fungal entomopathogen Metarhizium anisopliae. The amount of self‐grooming increased in the presence of fungal spores, which shows that the ants are able to detect the risk of infection. In contrast, the amount of allo‐grooming did not depend on fungal contamination. Workers groomed all nestmate workers that were re‐introduced into their groups. The amount of allo‐grooming towards noncontaminated individuals was higher when the group had been previously exposed to the pathogen. Allo‐grooming decreased the number of fungal spores on the surface of contaminated workers, but did not prevent infection in the conditions tested (high dose of spores and late allo‐grooming). The rate of disease transmission to groomers and other nestmates was extremely low. The systematic allo‐grooming of all individuals returning to the colony, be they contaminated or not, is probably a simple but robust prophylactic defence preventing the spread of fungal diseases in insect societies.
Genetic population structure, fitness variation and the importance of population history in remnant populations of the endangered plant Silene chlorantha (Willd.) Ehrh. (Caryophyllaceae)
Authors: Lauterbach D. , Ristow M. , Gemeinholzer B.
Published: February 2011

Habitat fragmentation can lead to a decline of genetic diversity, a potential risk for the survival of natural populations. Fragmented populations can become highly differentiated due to reduced gene flow and genetic drift. A decline in number of individuals can result in lower reproductive fitness due to inbreeding effects. We investigated genetic variation within and between 11 populations of the rare and endangered plant Silene chlorantha in northeastern Germany to support conservation strategies. Genetic diversity was evaluated using AFLP techniques and the results were correlated to fitness traits. Fitness evaluation in nature and in a common garden approach was conducted. Our analysis revealed population differentiation was high and within population genetic diversity was intermediate. A clear population structure was supported by a Bayesian approach, amova and neighbour‐joining analysis. No correlation between genetic and geographic distance was found. Our results indicate that patterns of population differentiation were mainly caused by temporal and/or spatial isolation and genetic drift. The fitness evaluation revealed that pollinator limitation and habitat quality seem, at present, to be more important to reproductive fitness than genetic diversity by itself. Populations of S. chlorantha with low genetic diversity have the potential to increase in individual number if habitat conditions improve. This was detected in a single large population in the investigation area, which was formerly affected by bottleneck effects.
Implant‐induced intraperitoneal inflammatory angiogenesis is attenuated by fluvastatin
Authors: Araújo Fernanda A , Rocha Monaliza A , Ferreira Mônica And , Campos Paula P , Capettini Luciano SA , Lemos Virginia S , Andrade Silvia P
Published: February 2011

1. Statins, 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMG‐CoA) inhibitors, exert anti‐inflammatory, anti‐oxidant and anti‐angiogenic effects. These effects are associated with downregulation of pro‐inflammatory/pro‐angiogenic molecules and upregulation of endothelial nitric oxide synthase (e‐NOS) expression/nitric oxide (NO) production.

2. Using the murine sponge model to induce chronic intraperitoneal inflammatory response, we evaluated the inflammatory components, angiogenic and NO production of the fibrovascular tissue, and their modulation by fluvastatin.

3. Our results showed that fluvastatin (0.6 and 6 mg/kg per day) inhibited haemoglobin (Hb) content 4.9 ± 0.4 (n = 15; control) vs 2.2 ± 0.2 (n = 6; fluvastatin 0.6) and 1.8 ± 0.2 (n = 6; fluvastatin 6.0) and the number of vessels in the treated group when compared with the control group. The inflammatory component, as assessed by myeloperoxidase and N‐acetyl‐β‐d‐glucosaminidase activities and by the pro‐inflammatory cytokines, tumour necrosis factor‐α (TNF‐α) and Monocyte chemotactic protein‐1 (MCP‐1)/CCL2/JE levels, was also decreased by the compound. In the treated group, inhibition of both enzyme activities was 54% and 57%, respectively. The levels of the cytokines (TNF‐α and CCL2/JE) intra‐implant were decreased relative to the control. In these implants, fluvastatin was also able to increase NO production, as detected with an NO‐sensitive electrode.

4. The inhibitory function of fluvastatin on key components of intraperitoneal inflammatory angiogenesis shown in the present study is clearly associated with the modulatory effects of this statin on vascular endothelial growth factor, TNF‐α and NO production.
The effect of caudal vs intravenous morphine on early extubation and postoperative analgesic requirements for stage 2 and 3 single‐ventricle palliation: a double blind randomized trial
Authors: Stuth Eckehard A. E. , Berens Richard J. , Staudt Susan. R. , Robertson Frederick A. , Scott John P. , Stucke Astrid G. , Hoffman George M. , Troshynski Todd J. , Tweddell James S. T. , Zuperku Edward J.
Published: February 2011

Background:  High‐dose single‐shot caudal morphine has been postulated to facilitate early extubation and to lower initial analgesic requirements after staged single‐ventricle (SV) palliation.

Methods:  With Institutional Review Board approval and written informed parental consent, 64 SV children aged 75–1667 days were randomized to pre‐incisional caudal morphine–bupivacaine (100 μg·kg−1 morphine (concentration 0.1%), mixed with 0.25% bupivacaine with 1 : 200 000 epinephrine, total 1 ml·kg−1) and postcardiopulmonary bypass (CPB) intravenous (IV) droperidol (75 μg·kg−1) (‘active caudal group’) or pre‐incisional caudal saline (1 ml·kg−1) and post‐CPB IV morphine (150 μg·kg−1) with droperidol (75 μg·kg−1) (‘active IV group’). Assignment remained concealed from families and the care teams throughout the trial. Early extubation failure rates (primary or reintubation within 24 h), time to first postoperative rescue morphine analgesia, and 12‐h postoperative morphine requirements were assessed for extubated patients.

Results:  Thirty‐one (12 stage 2) SV patients received caudal morphine and 32 (15 stage 2) received IV morphine. Extubation failure rates were 6/31 (19%) for caudal and 5/32 (16%) for IV morphine. For successfully extubated patients (n = 54), active caudal treatment significantly delayed the need for postoperative rescue morphine in stage 3 patients (P = 0.02) but not in stage 2 patients (P = 0.189) (Kaplan–Meier survival analysis with LogRank test). The reduction in 12‐h postoperative morphine requirements with active caudal treatment did not reach significance (P = 0.085) but morphine requirements were significantly higher for stage 2 compared with stage 3 patients (P < 0.001) (two‐way anova in n = 50 extubated patients).

Conclusions:  High‐dose caudal morphine with bupivacaine delayed the need for rescue morphine analgesia in stage 3 patients. All stage 2 patients required early rescue morphine and had significantly higher postoperative 12‐h morphine requirements than stage 3 patients. Early extubation is feasible for the majority of stage 2 and 3 SV patients regardless of analgesic regimen. The study was underpowered to assess differences in extubation failure rates.
Capitalizing on Bare Life: Sovereignty, Exception, and Gender Politics
Authors: Fluri Jennifer
Published: February 2011

Abstract:  This article examines the capital value of bare life as part of aid/development in (post)Taliban Afghanistan. I argue that the political production and spatial fixity of homo sacer “as the object of aid and protection” within specific geographic locations subsequently territorializes gendered bodies as a site for capital accumulation and exchange value through aid/development allocation. This occurs through a continual discursive reduction of “full or proper” human life to the remnants of bare life. This subjective reduction subsequently elicits capitalist‐modernity as a prime method for rescuing bare life and transferring it to an image (and imaginary) of western political and economic life. Gendered multiplicities of bare life emerge from variant forms of political and economic opportunity among aid/development workers and Afghan recipients. I argue that the discursive framing of bare life is situated as a site for (re)constructing rights through “western” frameworks infused with geopolitical and economic exchange value.
Governmentality, Diaspora Assemblages and the Ongoing Challenge of “Development”
Authors: Mullings Beverley
Published: February 2011

Abstract:  Drawing on governmentality debates, I argue that skilled members of the Jamaican diaspora are becoming important actors in an ongoing development strategy to extend the rationality of the market into everyday social relations and institutions. Diaspora members are imagined by states and development institutions to be ideal development partners because of their access to potentially lucrative business, knowledge and capital networks, and their desire to direct them towards socially transformative ends. But, as I shall demonstrate, efforts to incorporate skilled émigrés into national development plans raise important questions about the entanglements between diaspora strategies, state power and enduring local patterns of uneven development. Rather than a space of social transformation, diaspora can also function as a space of stasis that reproduces rather than transforms such patterns. By examining Jamaica's emerging diaspora strategy, I examine not only the governmental role that diaspora groups are increasingly beginning to play, but also their potential to support or disrupt the class, gender and racial asymmetries that have historically governed flows of wealth, opportunity and power across the island.
Water Sector Reforms and Courts in India: Lessons from the Evolving Case Law
Authors: Cullet Philippe
Published: February 2011

This article analyses the evolving Indian case law concerning water, with a special focus on the fundamental right to water, as well as issues related to control over water, and the links between environment and water. While courts have long engaged with water law, activities in recent years have been particularly important because of the introduction of water sector reforms and water law reforms that seek to reshape the water sector. The response of courts to these developments is particularly important. However, there has been no unified response to ongoing changes as Indian courts have given varying responses to the variety of cases submitted to them.
On the New Passive
Authors: Sigurðsson Halldór Ármann
Published: February 2011

Abstract. The so‐called New Passive in Icelandic takes the form ‘it was elected us’ (or, e.g., ‘then was elected us’, without an expletive), instead of the standard passive form ‘we were elected’. It has neither A‐movement to subject noracc‐to‐nomconversion, which are otherwise diagnostic of the canonical passive in Icelandic and related languages. Some researchers have argued that “passive” is in fact a misnomer and that the construction should instead be analyzed as an active one, with a nominativepro. This paper argues instead in favor of a minimalist analysis, where the New Passive is closely related to the impersonal P passive (with a PP, type ‘then was shoutedat us’), which is highly common and productive in Icelandic. On the approach pursued,acc‐to‐nomconversion involvescase‐star deletion, absent from the New Passive (much as from so‐called psych and fate (un)accusatives in standard Icelandic). Additionally, the New Passive has a strong vP phase edge, blocking A‐movement, in contrast to the defective vP edge in the canonical passive. The paper argues that A‐grounding or “freezing” is brought about by φ‐minimality, A‐islands thus arising in a parallel fashion with A′‐islands.
Influence of sucrose, high fructose corn syrup and honey from different floral sources on growth and acid production by lactic acid bacteria and bifidobacteria
Authors: POPA DARCLEE , USTUNOL ZEYNEP
Published: February 2011

Sage, alfalfa and sourwood honey, which vary in their oligosaccharide contents, were compared with sucrose, high fructose corn syrup and inulin in their ability to support growth, activity and viability of lactic acid bacteria and bifidobacteria typically used in yoghurt manufacturing. Growth and the end products of fermentation (lactic and acetic acids) were determined. Growth and acid production by organisms studied in the presence of different sweeteners were dependent on the specific organism investigated; however, it was not influenced by sweetener type, oligosaccharide content or the floral source of the honeys. All the sweeteners studied supported the growth, activity and viability of the organisms studied.
Statistical guidelines for clinical studies of human vision
Authors: Armstrong Richard A , Davies Leon N , Dunne Mark C M , Gilmartin Bernard
Published: February 2011

Citation information:Armstrong RA, Davies LN, Dunne MCM & Gilmartin B. Statistical guidelines for clinical studies of human vision.Ophthalmic Physiol Opt2011,31, 123–136. doi: 10.1111/j.1475‐1313.2010.00815.x

Statistical analysis of data can be complex and different statisticians may disagree as to the correct approach leading to conflict between authors, editors, and reviewers. The objective of this article is to provide some statistical advice for contributors to optometric and ophthalmic journals, to provide advice specifically relevant to clinical studies of human vision, and to recommend statistical analyses that could be used in a variety of circumstances. In submitting an article, in which quantitative data are reported, authors should describe clearly the statistical procedures that they have used and to justify each stage of the analysis. This is especially important if more complex or ‘non‐standard’ analyses have been carried out. The article begins with some general comments relating to data analysis concerning sample size and ‘power’, hypothesis testing, parametric and non‐parametric variables, ‘bootstrap methods’, one and two‐tail testing, and the Bonferroni correction. More specific advice is then given with reference to particular statistical procedures that can be used on a variety of types of data. Where relevant, examples of correct statistical practice are given with reference to recently published articles in the optometric and ophthalmic literature.
A comparison of the NCT Reichert R7 with Goldmann applanation tonometry and the Reichert ocular response analyzer
Authors: Jorge Jorge , González‐Méijome José M , Queirós António , Fernandes Paulo , Diaz‐Rey José A
Published: February 2011

Citation information: Jorge J, González‐Méijome JM, Queirós A, Fernandes P & Diaz‐Rey JA. A comparison of the NCT Reichert R7 with Goldmann applanation tonometry and the Reichert ocular response analyzer. Ophthalmic Physiol Opt 2011, 31, 174–179. doi: 10.1111/j.1475‐1313.2010.00817.x

Purpose:  The aim of this study was to evaluate the accuracy of intraocular pressure (IOP) values from the new non‐contact tonometer (NCT) Reichert R7 by comparing results with those from Goldmann applanation tonometry (GAT) and the Reichert Ocular Response Analyzer (ORA). Other ocular dimensions were assessed to evaluate their potential influence on the IOP values obtained.

Methods:  Ninety two right eyes from 92 adults aged between 21 and 59 years (mean 34.9 ± 11.7 years) were enrolled in this study. IOP was measured with R7, ORA and GAT. All measurements were taken between 14:00 and 16:00 in the afternoon. Corneal resistance factor (CRF) and corneal hysteresis were measured with the Reichert ORA. The spherical equivalent refractive error was obtained using an open field auto‐refractor (WAM5500; Grand Seiko) and corneal curvature, anterior chamber depth, corneal diameter and axial length were assessed with an optical coherence biometer (IOL Master; Zeiss Meditec, CA, USA).

Results:  The mean values for IOP measurements were 15.20 ± 3.37 mmHg (R7), 13.49 ± 3.55 mmHg (GAT), 15.01 ± 3.38 mmHg (ORA IOPcc) and 14.44 ± 3.47 mmHg (ORA IOPg). With the exception of the CRF (ρ = 0.72 p < 0.001) the correlations between ocular parameters and IOP obtained with the R7 were neither statistically nor clinically significant.

Conclusions:  The new NCT, R7 overestimated the IOP compared with GAT in normal, healthy eyes by about 1.7 mmHg on average (95% confidence range of approximately −2 to +6mmHg). The measures provided by the R7 were significantly influenced by the stiffness of the corneal tissue as measured by the ORA CRF value but not by other dimensional parameters of the eye.
Cigarette smoke and α,β‐unsaturated aldehydes elicit VEGF release through the p38 MAPK pathway in human airway smooth muscle cells and lung fibroblasts
Authors: Volpi Giorgia , Facchinetti Fabrizio , Moretto Nadia , Civelli Maurizio , Patacchini Riccardo
Published: February 2011

BACKGROUND AND PURPOSE Vascular endothelial growth factor (VEGF) is an angiogenic factor known to be elevated in the sputum of asymptomatic smokers as well as smokers with bronchitis type of chronic obstructive pulmonary disease. The aim of this study was to investigate whether acute exposure to cigarette smoke extract altered VEGF production in lung parenchymal cells.

EXPERIMENTAL APPROACH We exposed human airway smooth muscle cells (ASMC), normal human lung fibroblasts (NHLF) and small airways epithelial cells (SAEC) to aqueous cigarette smoke extract (CSE) in order to investigate the effect of cigarette smoke on VEGF expression and release.

KEY RESULTS Vascular endothelial growth factor release was elevated by sub‐toxic concentrations of CSE in both ASMC and NHLF, but not in SAEC. CSE‐evoked VEGF release was mimicked by its component acrolein at concentrations (10–100 µM) found in CSE, and prevented by the antioxidant and α,β‐unsaturated aldehyde scavenger, N‐acetylcysteine (NAC). Both CSE and acrolein (30 µM) induced VEGF mRNA expression in ASMC cultures, suggesting an effect at transcriptional level. Crotonaldehyde and 4‐hydroxy‐2‐nonenal, an endogenous α,β‐unsaturated aldehyde, stimulated VEGF release, as did H2O2. CSE‐evoked VEGF release was accompanied by rapid and lasting phosphorylation of p38 MAPK (mitogen‐activated protein kinase), which was abolished by NAC and mimicked by acrolein. Both CSE‐ and acrolein‐evoked VEGF release were blocked by selective inhibition of p38 MAPK signalling.

CONCLUSIONS AND IMPLICATIONS α,β‐Unsaturated aldehydes and possibly reactive oxygen species contained in cigarette smoke stimulate VEGF expression and release from pulmonary cells through p38 MAPK signalling.
How can we improve our understanding of cardiovascular safety liabilities to develop safer medicines?
Authors: Laverty HG , Benson C , Cartwright EJ , Cross MJ , Garland C , Hammond T , Holloway C , McMahon N , Milligan J , Park BK , Pirmohamed M , Pollard C , Radford J , Roome N , Sager P , Singh S , Suter T , Suter W , Trafford A , Volders PGA , Wallis R , Weaver R , York M , Valentin JP
Published: February 2011

Given that cardiovascular safety liabilities remain a major cause of drug attrition during preclinical and clinical development, adverse drug reactions, and post‐approval withdrawal of medicines, the Medical Research Council Centre for Drug Safety Science hosted a workshop to discuss current challenges in determining, understanding and addressing ‘Cardiovascular Toxicity of Medicines’. This article summarizes the key discussions from the workshop that aimed to address three major questions: (i) what are the key cardiovascular safety liabilities in drug discovery, drug development and clinical practice? (ii) how good are preclinical and clinical strategies for detecting cardiovascular liabilities? and (iii) do we have a mechanistic understanding of these liabilities? It was concluded that in order to understand, address and ultimately reduce cardiovascular safety liabilities of new therapeutic agents there is an urgent need to:

Fully characterize the incidence, prevalence and impact of drug‐induced cardiovascular issues at all stages of the drug development process.

Ascertain the predictive value of existing non‐clinical models and assays towards the clinical outcome.

Understand the mechanistic basis of cardiovascular liabilities; by addressing areas where it is currently not possible to predict clinical outcome based on preclinical safety data.

Provide scientists in all disciplines with additional skills to enable them to better integrate preclinical and clinical data and to better understand the biological and clinical significance of observed changes.

Develop more appropriate, highly relevant and predictive tools and assays to identify and wherever feasible to eliminate cardiovascular safety liabilities from molecules and wherever appropriate to develop clinically relevant and reliable safety biomarkers.
Pharmacological relevance and potential of sphingosine 1‐phosphate in the vascular system
Authors: Schuchardt Mirjam , Tölle Markus , Prüfer Jasmin , van der Giet Markus
Published: February 2011

Sphingosine‐1‐phosphate (S1P) was identified as a crucial molecule for regulating immune responses, inflammatory processes as well as influencing the cardiovascular system. S1P mediates differentiation, proliferation and migration during vascular development and homoeostasis. S1P is a naturally occurring lipid metabolite and is present in human blood in nanomolar concentrations. S1P is not only involved in physiological but also in pathophysiological processes. Therefore, this complex signalling system is potentially interesting for pharmacological intervention. Modulation of the system might influence inflammatory, angiogenic or vasoregulatory processes. S1P activates G‐protein coupled receptors, namely S1P1–5, whereas only S1P1–3 is present in vascular cells. S1P can also act as an intracellular signalling molecule. This review highlights the pharmacological potential of S1P signalling in the vascular system by giving an overview of S1P‐mediated processes in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). After a short summary of S1P metabolism and signalling pathways, the role of S1P in EC and VSMC proliferation and migration, the cause of relaxation and constriction of arterial blood vessels, the protective functions on endothelial apoptosis, as well as the regulatory function in leukocyte adhesion and inflammatory responses are summarized. This is followed by a detailed description of currently known pharmacological agonists and antagonists as new tools for mediating S1P signalling in the vasculature. The variety of effects influenced by S1P provides plenty of therapeutic targets currently under investigation for potential pharmacological intervention.

LINKED ARTICLES This article is one of a set of reviews submitted to BJP in connection with talks given at the September 2010 meeting of the International Society of Hypertension in Vancouver, Canada. To view the other articles in this collection visit http://dx.doi.org/10.1111/j.1476‐5381.2010.01167.x, http://dx.doi.org/10.1111/j.1476‐5381.2011.01235.x and http://dx.doi.org/10.1111/j.1476‐5381.2011.01366.x
Interactions in Calcium Aluminate Cement (CAC)‐Based Castables Containing Magnesia—Part II: Hydration–Dehydration Behavior of CAC and their Mixtures with Dead‐Burned and Reactive‐Grade MgO
Authors: Durán Teresa , Pena Pilar , De Aza Salvador , Gómez‐Millán Jesus , Alvarez Margarita , De Aza Antonio H.
Published: February 2011

A priori several technological problems arise on adding MgO to castable systems, due to its high tendency to react with water and the subsequent great volumetric expansion promoted by this reaction. This is detrimental to the volume stability and accordingly, the strength of the self‐forming spinel‐containing refractory castables. Nevertheless, very few basic researches have been systematically performed related to these castables behavior during the hydration and the dehydration process. In the current work, the hydration of a neat paste of a commercial ∼70 wt% Al2O3calcium aluminate cement (CAC) with and without two varieties of MgO additions (dead burned and reactive grade) was continuously followed at 24°±2°C by monitoring the exothermic heat evolution and the changes in pH. Additionally,in situtime‐resolved laboratory X‐ray diffraction (in situ‐LXRD) was continuously registered from 0 to 62 h during the dissolution of the anhydrous pastes and subsequent precipitation of hydrates. Further, the evolution of hydration and dehydration was studied from room temperature up to 1200°C by dilatometry, thermogravimetry, and differential thermal analyses to establish volumetric changes and reaction process, respectively. Also, isothermal treatments were carried out at selected temperatures, ranging from room temperature to 1200°C, and subsequently analyzed by conventional LXRD. Finally, the change of the modulus of rupture and the Young's modulus at room temperature, of the neat paste of the CAC with and without dead‐burned MgO, was measured and analyzed as a function of temperature, employing treated samples between 110° and 1400°C.
Newman, the Church of England and the Catholic Church
Authors: Rowell Geoffrey
Published: February 2011

Newman was formed in the Church of England and all his major theological concerns were developed in an Anglican context. The rebuttal of utilitarian scepticism in the University Sermons; the ecclesial context of Christian faith and life in The Lectures on the Prophetical Office of the Church; the strong sense of mystery in Newman's epistemology and apologetic; the sacramental character of Christian truth are all significantly part of the Anglican inheritance that he took to the Roman Catholic Church. Furthermore Newman's early formation was ‘pre-Victorian’– he was engaged when writing his Essay on Scriptural Miracles with earlier debates with the Deists, as well as sharing in the rediscovery of the imagination that characterised Coleridge and the Romantic Movement. This paper explores these and other issues to show an important part of Newman's enduring Anglican inheritance.
Making the Case for Laws That Improve Health: The Work of the Public Health Law Research National Program Office
Authors: Burris Scott C. , Anderson Evan D.
Published: February 2011

No one who attended the 2010 national public health law conference hosted by the Public Health Law Association (PHLA) and the American Society of Law, Medicine & Ethics (ASLME) could miss the sense of excitement and momentum. The revival of this annual public health law meeting, with the support of the Robert Wood Johnson Foundation (RWJF), the energetic leadership of the PHLA president and board, ASLME’s expert guidance, and a rousing address by Dr. Tom Frieden, Director of the Centers for Disease Control and Prevention (CDC), symbolize the continued commitment of a wide range of important individuals and institutions to the proposition that law is of substantial importance to public health. But there is more than just symbolism to be excited about. CDC’s public health law program continues to champion efforts to promote the use and understanding of law as a public health tool.
The Potential of Shared Decision Making to Reduce Health Disparities
Authors: King Jaime S. , Eckman Mark H. , Moulton Benjamin W.
Published: February 2011

Current methods of obtaining an informed consent leave much to be desired. Patients rarely read consent forms or understand all of the risks, benefits, or alternatives associated with their treatment. Evaluating the advantages and disadvantages of treatment options often presents a more significant challenge for patients with lower levels of health literacy. This article reviews the evidence of shortcomings in our informed consent system and then explores the potential for a new approach to engage patients at all levels of health literacy in their treatment decisions. Specifically, the article will examine the potential of shared decision-making (SDM) to bridge gaps in knowledge, increase patient adherence to treatment, and improve health outcomes in low health literacy patient populations. Leveling barriers to treatment information for disadvantaged populations should be a public health imperative, especially if it can be shown to improve health outcomes and reduce health disparities.
Five Legal Preparedness Challenges for Responding to Future Public Health Emergencies
Authors: Courtney Brooke
Published: February 2011

Since the anthrax attacks of 2001 and the severe acute respiratory syndrome (SARS) outbreak of 2003, significant efforts have been made to develop and revise a range of legal tools designed to strengthen public health emergency responses. The 2009 H1N1 pandemic provided an unprecedented opportunity to implement and exercise many of these mechanisms. At the global level, the World Health Organization (WHO) declared a public health emergency of international concern (PHEIC) pursuant to the revised International Health Regulations [IHR (2005)], and many governments declared national or regional emergencies. At the U.S. federal level, the Secretary of Health and Human Services (HHS) made public health emergency and Public Readiness and Emergency Preparedness (PREP) Act declarations. In addition, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) (to allow the emergency use of certain antiviral medications, diagnostic tests, and respirators during the pandemic), and President Obama declared a National Emergency (to authorize the use of temporary waivers or modifications of certain federal requirements related to health care facility responses). Select state and local governments also declared emergencies.
Generation of melanocytes from neural crest cells
Authors: Sommer Lukas
Published: February 2011

The neural crest is a transient structure in vertebrate embryos that generates multiple neural and mesenchymal cell types as well as melanocytes. Melanocytes in the skin either derive directly from neural crest cells populating the skin via a dorsolateral migratory pathway or arise by detaching from nerves innervating the skin. Several transcription factors, such as FoxD3, Sox10, Pax3, and Mitf, take part in a genetic network regulating melanocyte formation from the neural crest. The activity of these intrinsic factors is controlled and modulated by extracellular signals including canonical Wnt, Edn, Kitl, and other signals that remain to be identified. Here, we summarize the current view of how melanocytes are specified from the neural crest and put this process into the context of spatiotemporal lineage decisions in neural crest cells.
A New Gigantic Sauropod Dinosaur with the Deepest Known Body Cavity from the Cretaceous of Asia
Authors: Junchang Lü , Li XU , Xingliao ZHANG , Weiyong HU , Yanhua WU , Songhai JIA , Qiang JI
Published: February 2011

Abstract: A new species of sauropod dinosaur Huanghetitan ruyangensis is erected based on the following characters: deepest body cavity with a dorsal rib reaching at least 2.93 m long, anterior caudal vertebrae with mushroom‐shaped neural spines. Based on this new specimen of Huanghetitan found in the early Late Cretaceous Mangchuan Formation of Ruyang, Henan Province, the family Huanghetitanidae fam. nov. is proposed as a new rank to include only the genus Huanghetitan You et al. 2006. At present, Huanghetitan includes two species: H. liujiaxiaensis You et al., 2006 and H. ruyangensis sp. nov. The systematic relationships of Huanghetitan among sauropod dinosaurs are briefly discussed.
40Ar‐39 Ar Isotopic Dating of the Xianghualing Sn‐polymetallic Orefield in Southern Hunan, China and Its Geological Implications
Authors: Shunda YUAN , Jiantang PENG , Nengping SHEN , Ruizhong HU , Tongmo DAI
Published: February 2011

Abstract: The Xianghualing Sn‐polymetallic orefield in Hunan Province, southern China, is a large‐size tin orefield. Although numerous studies have been undertaken on this orefield, its genesis, mineralization age, and tectonic setting are still controversial, mainly because of the lack of reliable geochronological data on tin mineralization. The 40Ar/39 Ar stepwise heating dating method was first employed on muscovite from different deposits in this orefield. The muscovite sample from the Xianghualing Sn‐polymetallic deposit defines a plateau age of 154.4±1.1 Ma and an isochron age of 151.9±3.0 Ma; muscovite from the Xianghuapu W‐polymetallic deposit yields a plateau age of 161.3±1.1 Ma and an isochron age of 160.0±3.2 Ma; muscovite from the Jianfengling greisen‐type Sn‐polymetallic deposit gives a plateau age of 158.7±1.2 Ma and an isochron age of 160.3±3.2 Ma. The tungsten‐tin mineralization ages in the Xianghualing area are therefore restricted within 150–160 Ma. The tungsten ‐tin mineralization in Xianghualing occurred at the same time as the regional tin‐tungsten mineralization including the Furong tin orefield, Shizhuyuan tungsten‐tin polymetallic deposit and Yaogangxian tungsten‐polymetallic deposit. Thus, the large‐scale tungsten‐tin metallogenesis in South China occurring at 160‐150 Ma, probably is closely related to asthenospheric upwelling and crust‐mantle interaction under a geodynamic setting of crustal extension and lithosphere thinning during the transformation of tectonic regimes during the Mid‐Late Jurassic.
Rock Deformation, Component Migration and 18O/16O Variations during Mylonitization in the Southern Tan‐Lu Fault Belt
Authors: Xiaoyong YANG , Deliang LIU , Min FENG , Qingni YU , Kuiren WANG
Published: February 2011

Abstract: This paper discusses the relationship between the volume loss, fluid flow and component variations in the ductile shear zone of the southern Tan‐Lu fault belt. The results show that there is a large amount of fluids flowing through the shear zone during mylonitization, accompanied with the loss of volume of rocks and variations of elements and oxygen isotopes. The calculated temperature for mylonitization in different mylonites ranges from 446 to 484°C, corresponding to that of 475 to 500°C for the wall rocks. The condition of differential stress during mylonization has been obtained between 99 and 210 MPa, whereas the differential stress in the wall rock gneiss is 70–78 MPa. The mylonites are enriched by factors of 1.32‐1.87 in elements such as TiO2, P2O5, MnO, Y, Zr and V and depleted in SiO2, Na2O, K2O, Al2O3, Sr, Rb and light REEs compared to their protolith gneiss. The immobile element enrichments are attributed to enrichments in residual phases such as ilmentite, zircon, apatite and epidote in mylonites and are interpreted as due to volume losses from 15% to 60% in the ductile shear zone. The largest amount of SiO2 loss is 35.76 g/100 g in the ductile shear zone, which shows the fluid infiltration. Modeling calculated results of the fluid/rock ratio for the ductile shear zone range from 196 to 1192 by assuming different degrees of fluid saturation. Oxygen isotope changes of quartz and feldspar and the calculated fluid are corresponding to the variations of differential flow stress in the ductile shear zone. With increasing differential flow stress, the mylonites show a slight decrease of δ18O in quartz, K‐feldspar and fluid.
New Nodosaurid Dinosaur from the Late Cretaceous of Lishui, Zhejiang Province, China
Authors: Junchang Lü , Xingsheng JIN , Yiming SHENG , Yihong LI , Guoping WANG , AZUMA Yoichi
Published: February 2011

Abstract: A new genus and species of nodosaurid dinosaur: Zhejiangosaurus lishuiensis gen. et sp. nov. is erected herein. It is characterized by the sacrum consisting of at least three true sacral vertebrae, 5 caudal dorsal vertebrae fused to form the presacral rod, wide divergence of long slender preacetabular process of the ilium from the middle line of the body, and the fourth trochanter located at the femoral mid‐length.
Modes of Occurrence and Geological Origin of Beryllium in Coals from the Pu'an Coalfield, Guizhou, Southwest China
Authors: Jianye YANG
Published: February 2011

Abstract: The concentration, modes of occurrence and geological origin of beryllium in five workable coal beds from the Pu'an Coalfield of Guizhou were studied using the inductively coupled‐plasma mass spectrometry (ICP‐MS), floating and sinking experiments (FSE) and sequential chemical extraction procedures (SCEP). The results show that the average concentration of beryllium in coals from the Pu'an Coalfield is 1.54 μ/g, much lower than that in most Chinese and worldwide coals. Beryllium in the Pu'an coals was not significantly enriched. However, it should be noted that the No. 8 coal bed from the study area has a high concentration of beryllium, 6.89 μg/g, three times higher than the background value of beryllium in coal. Beryllium in coal mainly occurs as organic association and has predominantly originated from coal‐forming plants when its concentration is relatively low. The concentration of beryllium occurring as organic association is close to that distributed in inorganic matter when beryllium concentration of coal is similar to its background value, and in addition to coal‐forming plants, beryllium is mainly derived from detrital materials of terrigenous origin. When beryllium is anomalously enriched in coal, it mainly occurs as organic association and is derived from volcanic tonsteins leached for a long geological time and then adsorbed by organic matter in peat mire.
Occurrences of Excess 40Ar in Hydrothermal Tourmaline: Interpretations from 40Ar‐39 Ar Dating Results by Stepwise Heating
Authors: Huaning QIU , Tongmo PU Zhiping and DAI
Published: February 2011

Abstract: The occurrences of excess 40Ar within a hydrothermal tourmaline is discussed in term of the analysis data of syngenetic muscovite and tourmaline from the Lushui hydrothermal tin‐tungsten deposit in western Yunnan, China, using the 40Ar‐39 Ar stepwise heating technique. About 80% excess 40Ar was released in the last step when the tourmaline was fused, corresponding to a release of only ∼‐3% 39Ar (K), which indicates that most excess 40Ar was held in the mineral lattice rather than in the channels parallel to the Z‐axis. This suggests that the excess 40Ar was incorporated during crystallization and not diffused into the tourmaline during the post‐crystallization history.