bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell–cell and cell–surface interactions mediated by cellulose and a novel exopolysaccharide contribute to Pseudomonas putida biofilm formation and fitness under water‐limiting conditions
Authors: Nielsen Lindsey , Li Xiaohong , Halverson Larry J.
Published: March 2011

The composition of the exopolysaccharide matrix of Pseudomonas putida mt2 biofilms is relatively undefined as well as the contributions of each polymer to ecological fitness. Here, we describe the role of two putative exopolysaccharide gene clusters, putida exopolysaccharide A (pea) and bacterial cellulose (bcs) in biofilm formation and stability, rhizosphere colonization and matrix hydration under water‐limiting conditions. Our findings suggest that pea is involved in the production of a novel glucose, galactose, and mannose‐rich polymer that contributes to cell–cell interactions necessary for pellicle and biofilm formation and stability. In contrast, Bcs plays a minor role in biofilm formation and stability, although it does contribute to rhizosphere colonization based on a competition assay. We show that pea expression is highly induced transiently under water‐limiting conditions but only slightly by high osmolarity, as determined by qRT‐PCR. In contrast, both forms of water stress highly induced bcs expression. Cells deficient in making one or more exopolysaccharide experienced greater dehydration‐mediated cell‐envelope stress, leading to increased alginate promoter activity. However, this did not lead to increased exopolysaccharide production, except in bcs or pea mutants unable to produce alginate, indicating that P. putida compensates by producing, presumably more Pea or Bcs exopolysaccharides, to facilitate biofilm hydration. Collectively, the data suggest that Pea and Bcs contribute to biofilm formation and in turn their presence contributes to fitness under water‐limiting conditions, but not to the extent of alginate.
Essential metals for nitrogen fixation in a free‐living N2‐fixing bacterium: chelation, homeostasis and high use efficiency
Authors: Bellenger J.‐P. , Wichard T. , Xu Y. , Kraepiel A. M. L.
Published: March 2011

Biological nitrogen fixation, the main source of new nitrogen to the Earth's ecosystems, is catalysed by the enzyme nitrogenase. There are three nitrogenase isoenzymes: the Mo‐nitrogenase, the V‐nitrogenase and the Fe‐only nitrogenase. All three types require iron, and two of them also require Mo or V. Metal bioavailability has been shown to limit nitrogen fixation in natural and managed ecosystems. Here, we report the results of a study on the metal (Mo, V, Fe) requirements of Azotobacter vinelandii, a common model soil diazotroph. In the growth medium of A. vinelandii, metals are bound to strong complexing agents (metallophores) excreted by the bacterium. The uptake rates of the metallophore complexes are regulated to meet the bacterial metal requirement for diazotrophy. Under metal‐replete conditions Mo, but not V or Fe, is stored intracellularly. Under conditions of metal limitation, intracellular metals are used with remarkable efficiency, with essentially all the cellular Mo and V allocated to the nitrogenase enzymes. While the Mo‐nitrogenase, which is the most efficient, is used preferentially, all three nitrogenases contribute to N2 fixation in the same culture under metal limitation. We conclude that A. vinelandii is well adapted to fix nitrogen in metal‐limited soil environments.
Acquisition and maintenance of resistance to viruses in eukaryotic phytoplankton populations
Authors: Thomas Rozenn , Grimsley Nigel , Escande Marie‐line , Subirana Lucie , Derelle Evelyne , Moreau Hervé
Published: March 2011

Viruses are known to play a key role in the regulation of eukaryotic phytoplankton population densities; however, little is known about the mechanisms of how they interact with their hosts and how phytoplankton populations mediate their regulations. Viruses are obligate parasites that depend on host cell machinery for their dissemination in the environment (most of the time through host cell lysis that liberates many new particles). But viruses also depend on a reliable host population to carry on their replication before losing their viability. How do hosts cells survive when they coexist with their viruses? We show that clonal lines of three picoeukaryotic green algae (i.e. Bathycoccus sp., Micromonas sp., Ostreococcus tauri) reproducibly acquire resistance to their specific viruses following a round of infection. Our observations show that two mechanisms of resistance may operate in O. tauri. In the first resistant type, viruses can attach to their host cells but no new particles develop. In the second one, O. tauri acquires tolerance to its virus and releases these viruses consistently. These lines maintained their resistance over a 3‐year period, irrespective of whether or not they were re‐challenged with new viral inoculations. Co‐culturing resistant and susceptible lines revealed resistance to be associated with reduced host fitness in terms of growth rate.
Exploring and quantifying fungal diversity in freshwater lake ecosystems using rDNA cloning/sequencing and SSU tag pyrosequencing
Authors: Monchy Sébastien , Sanciu Giovanna , Jobard Marlène , Rasconi Serena , Gerphagnon Mélanie , Chabé Magali , Cian Amandine , Meloni Dionigia , Niquil Nathalie , Christaki Urania , Viscogliosi Eric , Sime‐Ngando Télesphore
Published: March 2011

Water samples were collected along transects from the shore to the centre of two French lakes: the deep, volcanic, oligomesotrophic and low allochthonic‐impacted Lake Pavin, and the productive and higher allochthonic‐impacted Lake Aydat. The biodiversity was analysed using two approaches: the classical approach consisting of cloning/sequencing of the 18S, ITS1, 5.8S, ITS2 and partial 28S region using primers designed for fungus sequences, and the pyrosequencing of 18S rRNA hypervariable V2, V3 and V5 regions using two primer sets (one universal for eukaryotes and one for fungi). The classical approach yielded 146 (Lake Pavin) and 143 (Lake Aydat) sequences, corresponding to 46 and 63 operational taxonomic units (OTUs) respectively. Fungi represented half of the OTUs identified in Lake Pavin and 30% in Lake Aydat, and were dominated by sequences from Chytridiomycota found throughout Lake Pavin but mostly in the central pelagic zone of Lake Aydat. The pyrosequencing approach yielded 42 064 (Pavin) and 61 371 (Aydat) reads, of which 12–15% and 9–19% reads were assigned to fungi in Lakes Pavin and Aydat respectively. Chytridiomycota members were also dominant among these reads, with OTUs displaying up to > 33‐fold overrepresentation in the centre compared with the riparian areas of Lake Aydat. Besides fungi, both approaches revealed other major eukaryote groups, with the highest diversity in the central areas of lakes. One of the major findings of our study was that the two lakes displayed contrasting spatial distributions, homogenous for Lake Pavin and heterogeneous for Lake Aydat, which may be related to their peculiarities. This study represents the first unveiling of microbial eukaryote and fungus diversity assessed with two complementary molecular methods, and is considered a major milestone towards understanding the dynamics and ecology of fungi in freshwater lake ecosystems, which are directly link to the abundance and distribution of taxa.
Replication, lies and lesser‐known truths regarding experimental design in environmental microbiology
Authors: Lennon Jay T.
Published: March 2011

A recent analysis revealed that most environmental microbiologists neglect replication in their science (Prosser, 2010). Of all peer‐reviewed papers published during 2009 in the field's leading journals, slightly more than 70% lacked replication when it came to analyzing microbial community data. The paucity of replication is viewed as an ‘endemic’ and ‘embarrassing’ problem that amounts to ‘bad science’, or worse yet, as the title suggests, lying (Prosser, 2010). Although replication is an important component of experimental design, it is possible to do good science without replication. There are various quantitative techniques – some old, some new – that, when used properly, will allow environmental microbiologists to make strong statistical conclusions from experimental and comparative data. Here, I provide examples where unreplicated data can be used to test hypotheses and yield novel information in a statistically robust manner.
Composition and dynamics of the gill microbiota of an invasive Indo‐Pacific oyster in the eastern Mediterranean Sea
Authors: Zurel Dror , Benayahu Yehuda , Or Amitai , Kovacs Amir , Gophna Uri
Published: March 2011

Gill bacterial communities of Chama pacifica, an Indo‐Pacific invasive oyster to the eastern Mediterranean Sea, were compared with those of Chama savignyi, its northern Red Sea congeneric species. Summer and winter bacterial populations were characterized and compared using 16S rDNA clone libraries, and seasonal population dynamics were monitored by automated ribosomal intergenic spacer analysis (ARISA). Clone libraries revealed a specific clade of bacteria, closely related to marine endosymbionts from the Indo‐Pacific, found in both ecosystems, of which one taxon was conserved in oysters from both sites. This taxon was dominant in summer libraries and was weakly present in winter ones, where other members of this group were dominant. ARISA results revealed significant seasonal variation in bacterial populations of Mediterranean Sea oysters, as opposed to Red Sea ones that were stable throughout the year. We suggest that this conserved association between bacteria and oyster reflects either a symbiosis between the oyster host and some of its bacteria, a co‐invasion of both parties, or both.
Screening for prostate cancer: an updated Cochrane systematic review
Authors: Ilic Dragan , O’Connor Denise , Green Sally , Wilt Timothy J.
Published: March 2011

OBJECTIVE

• To determine whether screening for prostate cancer reduces prostate cancer‐specific mortality, impact on all‐cause mortality and patient health‐related quality of life.

MATERIALS AND METHODS

• An update to our 2006 Cochrane systematic review was performed by re‐running an updated search of several databases, including MEDLINE and the Cochrane CENTRAL Register of Controlled Trials.

• Articles were included if they were a randomized controlled trial (RCT) examining screening vs no screening for prostate cancer. Data was collected and analysed according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions.

RESULTS

• Five RCTs with a total of 341 351 participants were included in this updated Cochrane systematic review. All involved PSA testing, although the interval and threshold for further evaluation varied across trials. The age of participants was 50–74 years, with durations of patient follow‐up of 7–15 years.

• The methodological quality of three of the studies was assessed as posing a high risk of bias.

• Meta‐analysis of the five included studies indicated no statistically significant difference in prostate cancer‐specific mortality between men randomized to screening and control [relative risk (RR) 0.95, 95% CI 0.85–1.07]. Sub‐group analyses indicated that prostate cancer‐specific mortality was not affected by age at which participants were screened. A pre‐planned analysis of a ‘core’ age group of men aged 55–69 years from the largest RCT (European Randomised Study of Screening for Prostate Cancer) reported a significant 20% relative reduction in prostate cancer‐specific mortality; (95% CI 0.65–0.98; absolute risk 0.71 per 1000 men). The number of men diagnosed with prostate cancer was significantly greater in men randomized to screening, compared with those randomized to control (RR 1.35, 95% CI 1.06–1.72).

• Harms of screening included high rates of false‐positive results for the PSA test, over‐diagnosis and adverse events associated with transrectal ultrasonography guided biopsies such as infection, bleeding and pain.

CONCLUSIONS

• Prostate cancer screening did not significantly decrease all‐cause or prostate cancer‐specific mortality in a combined meta‐analysis of five RCTs.

• Any benefits from prostate cancer screening may take >10 years to accrue; therefore, men who have a life expectancy of <10–15 years should be informed that screening for prostate cancer is not beneficial and has harms.
Outcomes of robot‐assisted radical prostatectomy in men with previous transurethral resection of prostate
Authors: Gupta Narmada P. , Singh Prabhjot , Nayyar Rishi
Published: March 2011

Study Type – Therapy (case series)

Level of Evidence 4

OBJECTIVE

• To critically analyze and compare surgical, oncological and functional outcomes of robot‐assisted radical prostatectomy (RARP) in patients with and without previous transurethral resection of prostate (TURP).

PATIENTS AND METHODS

• The study comprised 158 cases of RARP for clinically localized prostate cancer, including 26 cases that had undergone previous TURP (Group A).

• Surgical, oncological and functional (short‐ and intermediate‐term) outcomes of Group A were compared with 132 cases without previous TURP (Group B).

RESULTS

• Post TURP patients were found to have significantly greater blood loss (494 vs 324 mL) and a need for bladder neck reconstruction (26.7% vs 9.7%) compared to the non‐TURP group.

• Surgical time (189 vs 166 min), conversion rate, margin positivity rate and biochemical recurrence rate were also higher.

• Incontinence rates were higher both at 6 (14% vs 11.8%) and 12 (25% vs 8%) months follow‐up.

CONCLUSIONS

• RARP is feasible but challenging after TURP. It entails a longer operating time, greater operative difficulty and compromised oncological or continence outcomes.

• These cases should be handled by an experienced robotic surgeon with the appropriate expertise.
CORPORATE GOVERNANCE AND INNOVATION: A SURVEY
Authors: Belloc Filippo
Published: March 2011

AbstractThe traditional economics of innovation, inspired by Schumpeter and more recent advances on his work, seem unable to explain why firms with similar external conditions may show greatly different performance in innovation. Contrastingly, the literature on corporate governance provides some useful insights for understanding corporate innovation activity, to the extent that such literature examines the economic effects of different modes of coordination between firm members. The process through which individuals integrate their human and physical resources within the firm is central to the dynamics of corporate innovation. This paper provides the first survey of the literature on this issue. We start by discussing how various theoretical approaches to the analysis of the firm deal with technological innovation. We then describe three main channels – corporate ownership, corporate finance and labour – through which a system of corporate governance shapes a firm's innovation activity. Finally, we examine the relationship between country‐level institutional settings, national patterns of corporate governance and the aggregate innovation activity of corporations. We conclude by suggesting that future research should focus more deeply on the interrelation between the various dimensions of corporate governance and on their joint effect on firm innovation.
Partial Regulation in Vertically Differentiated Industries
Authors: BERGANTINO ANGELA S. , DE VILLEMEUR ETIENNE BILLETTE , VINELLA ANNALISA
Published: March 2011

We provide theoretical foundations for quality‐adjusted price‐cap regulation in industries where a regulated incumbent and an unregulated entrant offer vertically differentiated products competing in price and quality. We show that, whether or not the incumbent anticipates the reaction of the entrant, the optimal weights in the cap depend upon the market served by the entrant, despite the latter not being directly concerned by regulation. We further show that the cap is robust to small errors in the weights. Our findings point to the conclusion that, in partially regulated industries, regulators should use information about the whole sectors rather than on the sole regulated incumbents.
Democracy, Rule of Law, Corruption Incentives, and Growth
Authors: DE LA CROIX DAVID , DELAVALLADE CLARA
Published: March 2011

We bridge the gap between the standard theory of growth and the mostly static theory of corruption. Some public investment can be diverted from its purpose by corrupt individuals. Voters determine the level of public investment subject to an incentive constraint equalizing the returns from productive and corrupt activities. We concentrate on two exogenous institutional parameters: the “technology of corruption” is the ease with which rent‐seekers can capture a proportion of public spending. The “concentration of political power” is the extent to which rent‐seekers have more political influence than other people. One theoretical prediction is that the effects of the two institutional parameters on income growth and equilibrium corruption are different according to the constraints that are binding at equilibrium. In particular, the effect of judicial quality on growth should be stronger when political power is concentrated. We estimate a system of equations where both corruption and income growth are determined simultaneously and show that income growth is more affected by our proxies for legal and political institutions in countries where political rights and judicial institutions, respectively, are limited.
Capacity Investment with Dynamic Operation and Intertemporal Budget Balance
Authors: DANAU DANIEL
Published: March 2011

We characterize the optimal investment and production path in a project characterized by indivisible capacity and stochastic inverse demand curve. At first best (without budget requirements), the investment is made earlier the lower the price elasticity of demand, causing the trajectory of production to be below the trajectory of capacity. At second best (when the investor is required to break even), the investment delay is upward distorted, the distortion being larger the lower the price elasticity of demand. Moreover, in the particular case of constant elasticity demand, investment is delayed but production remains at its first‐best level.
A Risk‐Dominant Allocation: Maximizing Coalition Stability
Authors: McGINTY MATTHEW
Published: March 2011

This paper presents a rule to allocate a coalition’s worth for superadditive games with positive externalities. The allocation rule awards each member their outside payoff, plus an equal share of the surplus. The resulting allocation maximizes coalition stability. Stable coalitions are Strong Nash equilibria since no subset of members has an incentive to leave. Similarly, no subset of non‐members has an incentive to join a stable coalition if the game is concave in this region. The allocation is risk‐dominant. All stable coalitions are robust to the maximum probability of 50% that players’ deviate from their individual best‐responses. The paper compares the allocation to the Shapley value and the Nash bargaining solution, and illustrates why these traditional rules result in small coalitions when applied to issues such as international environmental agreements.
Regression for Compositional Data by using Distributions Defined on the Hypersphere
Authors: Scealy J. L. , Welsh A. H.
Published: March 2011

Compositional data can be transformed to directional data by the square-root transformation and then modelled by using distributions defined on the hypersphere. One advantage of this approach is that zero components are catered for naturally in the models. The Kent distribution for directional data is a good candidate model because it has a sufficiently general covariance structure. We propose a new regression model which models the mean direction of the Kent distribution as a function of a vector of covariates. Our estimators can be regarded as asymptotic maximum likelihood estimators. We show that these estimators perform well and are suitable for typical compositional data sets, including those with some zero components.
Non-Parametric Bayesian Inference on Bivariate Extremes
Authors: Guillotte Simon , Perron François , Segers Johan
Published: March 2011

The tail of a bivariate distribution function in the domain of attraction of a bivariate extreme value distribution may be approximated by that of its extreme value attractor. The extreme value attractor has margins that belong to a three-parameter family and a dependence structure which is characterized by a probability measure on the unit interval with mean equal to 12, which is called the spectral measure. Inference is done in a Bayesian framework using a censored likelihood approach. A prior distribution is constructed on an infinite dimensional model for this measure, the model being at the same time dense and computationally manageable. A trans-dimensional Markov chain Monte Carlo algorithm is developed and convergence to the posterior distribution is established. In simulations, the Bayes estimator for the spectral measure is shown to compare favourably with frequentist non-parametric estimators. An application to a data set of Danish fire insurance claims is provided.
Usefulness of the script concordance test in dermatology
Authors: Bursztejn A.‐C. , Cuny J.‐F. , Adam J.‐L. , Sido L. , Schmutz J.‐L. , de Korwin J.‐D. , Latarche C. , Braun M. , Barbaud A.
Published: March 2011

Background  The script concordance test (SCT) measures clinical data interpretation in the context of uncertainty. To our knowledge, its feasibility has not yet been demonstrated in dermatology.

Objectives  This study describes the feasibility, reliability and validity of the SCT for use in dermatology teaching to family medicine residents.

Methods  We designed an SCT for dermatology teaching, adapted to the level of family medicine students. The family medicine residents attending a dermatology lecture course and a reference panel of dermatologists underwent the test. Software available on the SCT‐dedicated website was used to determine the scores. The Cronbach’s α was calculated. The scores were described by means, standard deviation, and minimum and maximum scores. Mann–Whitney tests were used to compare resident and reference panel scores.

Results  The test contained 33 vignettes of four questions each. Cronbach’s α was 0.80. Mean scores were 75.6 for the reference panel and 65.0 for the residents (P = 0.0009).

Conclusions  This study confirmed the SCT’s capacity to distinguish groups on the basis of experience. This study demonstrated the feasibility and reliability of the SCT in the field of dermatology.
Comparison of pegylated interferon α‐2b plus psoralen PUVA versus standard interferon α‐2a plus PUVA in patients with cutaneous T‐cell lymphoma
Authors: Hüsken A.C. , Tsianakas A. , Hensen P. , Nashan D. , Loquai C. , Beissert S. , Luger T.A. , Sunderkötter C. , Schiller M.
Published: March 2011

Objective  The aim of this study was to evaluate the safety and efficacy profile of pegylated interferon α‐2b (PEG‐IFN α‐2b) in combination with photochemotherapy (PUVA) in the treatment of cutaneous T‐cell lymphoma (CTCL) in comparison with standard IFN α plus PUVA.

Design  Retrospective cohort study over a period of 7 years.

Patients and interventions  A total of 17 consecutive CTCL patients (stage IA–IV) were retrospectively analysed for toxicity and response rates associated with PEG‐IFN α‐2b (1.5 μg/kg weekly) plus PUVA (n = 9) or standard IFN α‐2a (9 MIU 3×/week) plus PUVA (n = 8).

Main outcome measures  Differences of response rates (complete/partial remission), progression‐free survival, discontinuation of therapy, safety and toxicity profiles according to World Health Organization – Common Terminology Criteria of Adverse Events (WHO‐CTCAE).

Results  Myelosuppression and liver toxicity occured more frequently during PEG‐IFN α‐2b plus PUVA treatment than during standard IFN α‐2a plus PUVA therapy [77.8 vs. 50% (odds ratio 1.477) and 77.8 vs. 50% (odds ratio 1.692), respectively]. By contrast, the occurence of constitutional side‐effects (mainly fatigue) [100 vs.77.8% (odds ratio 0.889)] and more adverse events leading to study discontinuation was considerably higher in the standard IFN α‐2a plus PUVA group. The overall response rate in the PEG‐IFN α‐2b plus PUVA group (89%) was significantly superior.

Conclusions  In patients with cutaneous T‐cell lymphoma PEG‐IFN α‐2b plus PUVA might become a promising treatment alternative as its higher rate of myelosuppression and liver toxicity is outweighed by its lower percentage of constitutional side‐effects, and its significantly higher overall response. Due to the small number of participants at this retrospective study, a larger prospective study is essential to verify our results.
Comparison of the time and latitude trends of melanoma incidence in anorectal region and perianal skin with those of cutaneous malignant melanoma in Norway
Authors: Micu E. , Juzeniene A. , Moan J.
Published: March 2011

Background  Melanoma incidence is increasing in many parts of the world. The main environmental risk factor is exposure to solar radiation. However, melanomas may arise also on non‐sun‐exposed areas (uveal and mucosal melanomas) and little is known about a possible relationship between sun exposure and melanoma on such locations.

Objectives  We have compared the time and latitude trends of melanoma incidence in the anorectal region and perianal skin (non‐sun‐exposed sites) with those of cutaneous malignant melanoma (CMM) (sun‐exposed skin) to gain more information about the relationship between sun exposure and melanoma on such sites.

Methods  We analysed epidemiological data from the Cancer Registry of Norway for melanomas of the anorectal mucosa, perianal skin and overall CMM for the time period 1966–2007.

Results  We found that melanoma incidence on these shielded sites tends to decrease or remain constant over a period during which the CMM rates increase. This is true both in the North and in the South regions of Norway. Comparison of latitudinal trends of the incidence rates of CMM and melanoma on these shielded sites shows that there is no latitude gradient for melanoma of the anorectal mucosa and perianal skin, whereas there is a strong one for CMM.

Conclusions  The time and latitudinal trends are likely to support the assumption that melanomas on these shielded sites are not generated by ultraviolet radiation. Possible causes and significances of these trends are discussed.
Annual Research Review: Developmental considerations of gene by environment interactions
Authors: Lenroot Rhoshel K. , Giedd Jay N.
Published: March 2011

Biological development is driven by a complex dance between nurture and nature, determined not only by the specific features of the interacting genetic and environmental influences but also by the timing of their rendezvous. The initiation of large‐scale longitudinal studies, ever‐expanding knowledge of genetics, and increasing availability of neuroimaging data to provide endophenotypic bridges between molecules and behavior are beginning to provide some insight into interactions of developmental stage, genes, and the environment, although daunting challenges remain. Prominent amongst these challenges are difficulties in identifying and quantifying relevant environmental factors, discerning the relative contributions to multiply determined outcomes, and the likelihood that brain development is a non‐linear dynamic process in which small initial differences may yield large later effects. Age‐sensitive mechanisms include developmental changes in gene expression, epigenetic modifications, synaptic arborization/pruning, and maturational improvements in our capacity to seek out environments of our choosing. Greater understanding of how genetic and environmental factors interact differently across ages is an important step toward elucidating the mechanisms by which phenotypes are created – and how they may differ in health and disease. This knowledge may also provide clues to guide the type and timing of interventions to maximize outcomes.
Regulation of cyclooxygenase‐2 and cytosolic phospholipase A2 gene expression by lipopolysaccharide through the RNA‐binding protein HuR: involvement of NADPH oxidase, reactive oxygen species and mitogen‐activated protein kinases
Authors: Lin Wei‐Ning , Lin Chih‐Chung , Cheng Hsin‐Yi , Yang Chuen‐Mao
Published: March 2011

BACKGROUND AND PURPOSE Lipopolysaccharide (LPS)‐induced expression of cyclooxygenase‐2 (COX‐2) and cytosolic phospholipase A2 (cPLA2) has been implicated in several respiratory diseases. HuR is known to enhance the expression of genes by binding to 3′‐untranslated region (3′‐UTR) of mRNA and stabilizing mRNA. However, the exact mechanisms by which HuR affects the stability of mRNA and modulates LPS‐induced COX‐2 and cPLA2 expression in human tracheal smooth muscle cells (HTSMCs) are not known.

EXPERIMENTAL APPROACH The expression of prostaglandin E2 (PGE2) was measured by ELISA, and pro‐inflammatory proteins were determined by use of a promoter assay, PCR or Western blot analysis. Overexpression of siRNAs to knock down the target components was used to manipulate the expression of HuR. Release of reactive oxygen species (ROS) was detected by fluorescence dye. The activation of signalling components was assessed by comparing phosphorylation levels, localization of protein kinases or coimmunoprecipitation assay.

KEY RESULTS LPS induced COX‐2 and cPLA2 expression via post‐translational regulation of mRNA stabilization, which were attenuated by transfection with HuR siRNA in HTSMCs. In addition, LPS‐stimulated NADPH oxidase activation and ROS generation were attenuated by the NADPH oxidase inhibitors diphenyleneiodonium chloride (DPI) and apocynin (APO). Generation of ROS induced phosphorylation of p42/p44 mitogen‐activated protein kinase (MAPK), p38 MAPK and JNK1/2, which was attenuated by DPI and APO and the ROS scavenger N‐acetylcysteine.

CONCLUSIONS AND IMPLICATIONS These results suggested that in HTSMCs, LPS‐induced COX‐2 and cPLA2 expression is mediated through NADPH oxidase/ROS‐dependent MAPKs associated with HuR accumulation in the cytoplasm. Activated MAPKs may regulate the nucleocytoplasmic shuttling of HuR, and thus induce the cytoplasmic accumulation of HuR.
Defects in mouse nephrogenesis induced by selective and non‐selective cyclooxygenase‐2 inhibitors
Authors: Olliges Anke , Wimmer Stefanie , Nüsing Rolf M
Published: March 2011

BACKGROUND AND PURPOSE Deletion of the cyclooxygenase‐2 (COX‐2) gene causes impairment of kidney development, but the effect of selective inhibitors of COX‐2 (coxibs) or the non‐selective inhibitors of COX (the classical non‐steroidal anti‐inflammatory drugs; NSAIDs) on kidney development was less well described.

EXPERIMENTAL APPROACH We assessed the effects of equipotent analgesic doses of celecoxib, rofecoxib, valdecoxib, etoricoxib and lumiracoxib and of the NSAIDs, diclofenac and naproxen, on postpartum kidney development in mice, from postnatal day 1 (P1) to P21.

KEY RESULTS All the COX inhibitors, at the doses used, blocked COX‐2 activity by more than 80% as assayed by PGE2 synthesis in lipopolysaccharide‐stimulated mouse blood samples. Rofecoxib, etoricoxib and lumiracoxib exerted the most marked impairment of postpartum kidney development, demonstrated by attenuation of kidney growth, reduction in size of glomeruli, increase in immature superficial glomeruli, thinning of subcapsular cortical mass and reduction in size of juxtamedullary glomeruli. These defects were less severe than those in kidneys from COX‐2−/− mice. Administration of diclofenac and naproxen revealed renal defects similar to those after coxib treatment, but both NSAIDs induced greater arrest of immature superficial glomeruli in the outer cortex and increased the number of undifferentiated proliferating cell nuclear antigen‐positive cells. Treatment with celecoxib or valdecoxib caused only minimal changes in renal morphology.

CONCLUSIONS AND IMPLICATIONS Classical NSAIDs cause similar or even stronger nephrodysgenesis than the coxibs. Also, the ranking of coxibs regarding adverse effects on renal development, using equi‐analgesic doses, is rofecoxib = etoricoxib = lumiracoxib > valdecoxib > celecoxib.
Liposome‐encapsulated dexamethasone attenuates ventilator‐induced lung inflammation
Authors: Hegeman MA , Cobelens PM , Kamps JAAM , Hennus MP , Jansen NJG , Schultz MJ , van Vught AJ , Molema G , Heijnen CJ
Published: March 2011

BACKGROUND AND PURPOSE Systemic glucocorticoid therapy may effectively attenuate lung inflammation but also induce severe side‐effects. Delivery of glucocorticoids by liposomes could therefore be beneficial. We investigated if liposome‐encapsulated dexamethasone inhibited ventilator‐induced lung inflammation. Furthermore, we evaluated whether targeting of cellular Fcγ‐receptors (FcγRs) by conjugating immunoglobulin G (IgG) to liposomes, would improve the efficacy of dexamethasone‐liposomes in attenuating granulocyte infiltration, one of the hallmarks of lung inflammation.

EXPERIMENTAL APPROACH Mice were anaesthetized, tracheotomized and mechanically ventilated for 5 h with either ‘low’ tidal volumes ∼7.5 mL·kg−1 (LVT) or ‘high’ tidal volumes ∼15 mL·kg−1 (HVT). At initiation of ventilation, we intravenously administered dexamethasone encapsulated in liposomes (Dex‐liposomes), dexamethasone encapsulated in IgG‐modified liposomes (IgG‐Dex‐liposomes) or free dexamethasone. Non‐ventilated mice served as controls.

KEY RESULTS Dex‐liposomes attenuated granulocyte infiltration and IL‐6 mRNA expression after LVT‐ventilation, but not after HVT‐ventilation. Dex‐liposomes also down‐regulated mRNA expression of IL‐1β and KC, but not of CCL2 (MCP‐1) in lungs of LVT and HVT‐ventilated mice. Importantly, IgG‐Dex‐liposomes inhibited granulocyte influx caused by either LVT or HVT‐ventilation. IgG‐Dex‐liposomes diminished IL‐1β and KC mRNA expression in both ventilation groups, and IL‐6 and CCL2 mRNA expression in the LVT‐ventilated group. Free dexamethasone prevented granulocyte influx and inflammatory mediator expression induced by LVT or HVT‐ventilation.

CONCLUSIONS AND IMPLICATIONS FcγR‐targeted IgG‐Dex‐liposomes are pharmacologically more effective than Dex‐liposomes particularly in inhibiting pulmonary granulocyte infiltration. IgG‐Dex‐liposomes inhibited most parameters of ventilator‐induced lung inflammation as effectively as free dexamethasone, with the advantage that liposome‐encapsulated dexamethasone will be released locally in the lung thereby preventing systemic side‐effects.
Mass‐scale high‐throughput multiplex polymerase chain reaction for human platelet antigen single‐nucleotide polymorphisms screening of apheresis platelet donors
Authors: Shehata Nadine , Denomme Gregory A. , Hannach Barbara , Banning Nancy , Freedman John
Published: March 2011

BACKGROUND:Treatment with human platelet antigen (HPA)‐matched platelets (PLTs) is the optimal therapy for bleeding secondary to neonatal alloimmune thrombocytopenia. Recent advances in high‐throughput DNA‐based blood group and PLT antigen genotyping have made it possible to screen plateletpheresis donors for potential HPA‐matched PLT transfusion.

STUDY DESIGN AND METHODS:This prospective study evaluated genomic DNA from plateletpheresis donors for single‐nucleotide polymorphisms (SNPs) associated with HPA‐1, ‐2, ‐3, ‐4, ‐5, and ‐15 to determine whether high‐throughput multiplex genomic DNA PCR and oligonucleotide extension technology can be used for mass‐scale PLT antigen genotyping. Genotyping using SNP technology was confirmed using sequence‐specific polymerase chain reaction (SSP‐PCR).

RESULTS:Of the 748 donors screened, 277 were found to be negative for antigens implicated in alloimmune thrombocytopenia. In addition, two donors were homozygous for HPA‐1b/b and ‐2b/b, six donors for HPA‐1b/b and ‐3b/b, one for HPA‐2b/b and ‐3b/b, one for HPA‐1b/b and ‐5b/b, 10 for HPA‐1b/b and ‐15 b/b, four for HPA‐5b/b and ‐15b/b, and one for HPA‐2b/b and ‐15b/b. Retesting using SSP‐PCR was conducted for 60 donors. Discrepant results occurred between SNP and SSP‐PCR in less than 20% of samples for HPA‐1b/1b/HPA‐3b/3b, HPA‐5b/5b, and HPA‐15b/b.

DISCUSSION:High‐throughput multiplex PCR SNP and confirmatory molecular genotyping are useful for mass‐scale screening of apheresis PLT donors to provide antigen‐negative genotypes. Refinements to mass‐scale multiplex analysis technology would reduce further the confirmatory testing needed.
Isolation of Streptococcus bovis from apheresis platelets of asymptomatic donor warranted colonoscopy investigation: case report and literature review
Authors: Lin Chun‐Yu , Tseng Shih‐Bin , Lu Po‐Liang , Chen Tun‐Chieh , Lin Wei‐Ru , Chen Yen‐Hsu , Lin Kuo‐Sin
Published: March 2011

BACKGROUND: Bacterial contamination of platelet (PLT) products is one of the most serious complications of transfusion. Culturing PLT components may detect the presence of bacteria, thus reducing the risk of a septic result after transfusion. Streptococcus bovis has previously been reported as a contaminating microorganism in PLT products. Here we report an asymptomatic donor diagnosed with occult colon malignancy after positive isolation of S. bovis from his apheresis PLTs (APs). We also review previous cases.

CASE REPORT: The PLT donor was a 50‐year‐old man with more than 150 prior plateletpheresis or whole blood donations. Bacterial culture of his AP components yielded two positive results: group D Streptococcus was isolated in July 2008 and S. bovis was reported in April 2010. The donor received further testing, and colonofibroscopic examination revealed colonic neoplasm. Pathologic examination of the biopsied tissue led to a diagnosis of invasive adenocarcinoma. He underwent a left hemicolectomy in July 2010. Examination of the resection specimen confirmed adenocarcinoma, Stage III with regional lymph node metastatic adenocarcinoma.

CONCLUSION: Donated AP products positive for S. bovis should not be presumed to be due to contamination during collection. This bacteremia originating from donor factors needs to be carefully evaluated. Colonofibroscopic examination is recommended for these donors to detect colonic malignancy as early as possible.
A mild acute hemolytic transfusion reaction in a patient with alloanti‐Ge3: a case report and review of the literature
Authors: Baughn Mariah R. , Whitacre Patricia , Lo Grace S. , Pandey Suchitra , Lane Thomas A.
Published: March 2011

BACKGROUND: The clinical significance of the Gerbich antibodies has been described as variable and there are no well‐documented reports of hemolytic transfusion reactions (HTRs).

CASE REPORT: We present the case of a woman with a long history of documented anti‐Ge3 alloantibody who received multiple units of Ge+ red blood cells (RBCs) uneventfully. During the first admission to our hospital she was transfused 8 units of Ge+ RBCs and had a negative monocyte monolayer assay (MMA) before receiving the units. Within 2 weeks of the transfusions, the anti‐Ge3 became significantly stronger by indirect antiglobulin test, and the MMA increased from 2.2 to 79.5% reactivity. She returned 4.5 years later with an emergent need for blood and was transfused with 2 units of Ge+ RBCs after premedication with steroids and intravenous immunoglobulin.

RESULTS: The first unit was transfused without incident; however, she developed clinical and laboratory signs consistent with an acute HTR with the second unit.

CONCLUSION: After a comprehensive review of the literature, we believe this to be the first well‐documented case of acute HTR due to anti‐Gerbich alloantibodies.
Improvement of Carbon Nanofibers/ZrO2 Composites Properties with a Zirconia Nanocoating on Carbon Nanofibers by Sol–Gel Method
Authors: Borrell Amparo , Rocha Victoria G. , Torrecillas Ramon , Fernández Adolfo
Published: March 2011

The development of new carbon nanofibers (CNFs)–ceramic nanocomposite materials with excellent mechanical, thermal, and electrical properties is interesting for a wide range of industrial applications. Among the ceramic materials, zirconia stands out for their excellent mechanical properties. The main limitations in the preparation of this kind of nanocomposites are related with the difficulty in obtaining materials with homogeneous distribution of both phases and the dissimilar properties of CNFs and ZrO2 which causes poor interaction between them. CNFs‐reinforced zirconia nanocomposites ZrO2/xCNFs (x=1–20 vol%) were prepared by powder mixture and sintered by spark plasma sintering (SPS). ZrO2‐reinforced CNFs nanocomposites CNFs/xZrO2 (x=20 vol%) were prepared by powder mixture and a surface coating of CNFs by the wet chemical route with zirconia precursor is proposed as a very effective way to improve the interaction between CNFs and ZrO2. After SPS sintering, an improvement of 50% in fracture strength was found for similar nanocomposite compositions when the surface coating was used. The improved mechanical properties of these nanocomposites are caused by stronger interaction between the CNFs and ZrO2.
Atomic Scale Modeling of Point Defects in Zirconium Diboride
Authors: Middleburgh Simon C. , Parfitt David C. , Blair Paul R. , Grimes Robin W.
Published: March 2011

Simulations using density functional theory were carried out to investigate the defect properties of zirconium diboride (ZrB2) and also the solution and diffusion of He and Li. Schottky and Frenkel intrinsic defect processes were all high energy as were mechanisms giving rise to nonstoichiometry; this has implications for high‐temperature performance. Li and He species, formed by the transmutation of a 10B, should therefore mostly be accommodated at the resulting vacant B sites or interstitial sites. Because Li is considerably more stable at the vacant B sites, He will be accommodated interstitially. Furthermore, He was found to diffuse as an interstitial species through the lattice with a low activation energy. This would be consistent with He being lost from the ZrB2 but with Li being retained to a much greater extent.
Quality‐of‐life in wasp venom allergy – validation of the German version of the “Vespid Allergy Quality of Life Questionnaire” (VQLQ‐d)
Authors: Fischer Jörg , Feidt Alexandra , Giel Katrin Elisabeth , Martens Ute , Zipfel Stephan , Biedermann Tilo , Teufel Martin
Published: March 2011

Background: Little is known about the quality of life of patients who are allergic to insect venom. This fact is due to the lack of specific instruments assessing the interaction of type 1 allergy and its psychological burden.

Patients and methods: The only established questionnaire on health‐related quality‐of‐life in patients with wasp venom allergies is the “Vespid Allergy Quality of Life Questionnaire” (VQLQ). This questionnaire was translated from Dutch into German and validated with 79 patients with wasp venom allergy, including the use of the well‐established general quality‐of‐life questionnaire WHOQOL‐BREF.

Results: In the German version VQLQ‐d we could reproduce the validity and reliability of the original Dutch version. Cronbach's alpha of the VQLQ‐d was α= 0.95. The results of the VQLQ‐d corresponded to the total score of the WHOQOL‐BREF.

Conclusion: The VQLQ‐d enables measurement of quality‐of‐life in patients with wasp venom allergy in the German‐speaking population. This economic tool makes it possible to better describe and treat affected patients. Furthermore, it can be used to advance research in this field.
The impact of oral vitamin A derivatives on lipid metabolism – What recommendations can be derived for dealing with this issue in the daily dermatological practice?
Authors: Klör Hans‐Ulrich , Weizel Achim , Augustin Matthias , Diepgen Thomas L. , Elsner Peter , Homey Bernhard , Kapp Alexander , Ruzicka Thomas , Luger Thomas
Published: March 2011

Retinoids and vitamin A derivatives have been widely used topically and systemically in the treatment of hyper‐ and parakeratotic skin diseases, genodermatoses, severe acne, autoimmune diseases (i. e. lupus erythematosus) or cutaneous T‐cell lymphoma for more than 30 years. In addition to the desired proliferation‐inhibiting, differentiation‐inducing and antiinflammatory or sebo‐suppressive effects, vitamin A derivatives also affect lipid metabolism. This is shown primarily by an increase of transaminases, triglycerides or cholesterol levels which vary in intensity from patient to patient. The degree of impact on the different parameters of lipid metabolism depends on the nature of the vitamin A derivative on the one hand due to different receptor specific binding interactions (RAR/RXR), while on the other hand posttranslational processes also play a major role.

This review paper gives a brief, concise overview of the vitamin A derivatives and possible effects on lipid metabolism that can be expected. Additionally it contains a recommendation for secure handling of abnormal laboratory values before, during and after oral therapy with vitamin A derivatives. The aim of this article is to provide practical help and confidence in dealing with vitamin A derivatives in daily clinical practice. The publication was created in cooperation with the Deutsche Dermatologische Gesellschaft (DDG) and Deutsche Gesellschaft zur Bekämpfung von Fettstoffwechselstörungen und ihren Folgeerkrankungen (DGFF [Lipid‐Liga] e. V.).
Response to atomoxetine in boys with high‐functioning autism spectrum disorders and attention deficit/hyperactivity disorder
Authors: Zeiner Pål , Gjevik Elen , Weidle Bernhard
Published: March 2011

Aim:  To study the efficacy and tolerability of atomoxetine in high‐functioning boys with autism spectrum disorders (ASD) and comorbid attention deficit/hyperactivity disorder (AD/HD).

Methods:  Fourteen boys (age 7–17) participated in a 10‐week open‐label study. Atomoxetine doses were 0.5 mg/kg/day in week 1 and 1.2–1.4 mg/kg/day in weeks 2–10. Changes in AD/HD symptoms were measured by the AD/HD Rating Scale, and global improvements by the Clinical Global Improvement Scale. Both measures were used to assess drug response. Assessments were done at baseline and at weeks 2, 4, 6 and 10. Teacher ratings were done at baseline and 10 weeks.

Results:  There were significant reductions in AD/HD symptoms rated by parents (p < 0.005) and by teachers (p < 0.05). One participant was rated as ‘Much improved’, five as ‘Moderately improved’, seven as ‘Minimally improved’, and one as ‘Unchanged or worse’. Seven subjects were classified as clinical responders. The most common adverse events were nausea and headache. Two participants discontinued treatment.

Conclusion:  Seven out of 14 boys with high‐functioning ASD and comorbid AD/HD showed significant reductions in AD/HD symptoms and were classified as responders to atomoxetine. Most children tolerated the drug well.
CONSUMER HEDONIC EVALUATION OF EIGHT FRESH SPECIALTY LEAFY GREENS AND THEIR RELATIONSHIP TO INSTRUMENTAL QUALITY ATTRIBUTES AND INDICATORS OF SECONDARY METABOLITES
Authors: FOULADKHAH ALIYAR , BUNNING MARISA , STONE MARTHA , STUSHNOFF CECIL , STONAKER FRANK , KENDALL PATRICIA
Published: March 2011

Sensory properties, quality attributes (color, texture, total soluble solids, dry weight) and indicators of secondary metabolites (total phenolic compounds, radical scavenging capacity) of eight specialty leafy greens were evaluated in this study. Because of its commercial availability and consumer familiarity, red iceberg lettuce was chosen as the control for comparison with amaranth, huauzontle, pac choi, tai sai, arugula, mizuna and komatsuna. For a majority of the greens, more than 50% of panelists reported appearance, texture and overall acceptability of the samples as highly acceptable or acceptable. Flavor, however, had lower values. There were no significant differences in overall acceptability among five taxa (amaranth, pac choi, tai sai, mizuna and komatsuna) compared with red iceberg lettuce; however, the mean appearance values of five greens (komatsuna, mizuna, arugula, tai sai and pac choi) were higher than red iceberg (P < 0.05). Panelists' flavor perceptions were strongly correlated with overall acceptability of the greens.

PRACTICAL APPLICATIONS

This study demonstrated that selected specialty leafy greens (amaranth, huauzontle, pac choi, tai sai, arugula, mizuna, komatsuna and red iceberg lettuce) have desirable sensory attributes that are comparable with traditional greens available in the market. This suggests potential for commercial production and marketing of the selected specialty leafy greens.